Sample records for accelerated coronary atherosclerosis

  1. Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

    PubMed Central

    Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

    2012-01-01

    Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

  2. Endothelial dysfunction in patients with coronary atherosclerosis.

    PubMed

    Chapidze, L; Kapanadze, S; Dolidze, N; Bakhutashvili, Z; Latsabidze, N

    2007-01-01

    It is well known that endothelial dysfunction as a nontraditional risk factor is an important early event in the pathogenesis of coronary atherosclerosis, contributing to plaque initiation and progression. In order to assess endothelial function plasma nitric oxide (NO) concentrations were determined. A total of 157 patients (119 men and 38 women, mean age 57+/-5,4 years) with coronary atherosclerosis were enrolled in the research. The study was cross-sectional in design. Most of the patients (n=127) had undergone myocardial revascularization procedures. There was statistically significant difference in mean values of plasma nitric oxide levels between patients with coronary atherosclerosis and healthy subjects (11,1+/-2,52 mkmol/L and 22,3+/-3,27 mkmol/L, respectively. p<0,01). Among all 157 patients only 17% had normal NO concentrations. In 59% cases low and in 24% cases high nitric oxide levels were found. Extent of coronary artery disease was associated with severity of endothelial dysfunction. The patients with three-vessel disease had the lowest mean plasma NO concentration. There was statistically significant negative correlation between mean plasma NO level and extent of coronary artery disease. Measurement of plasma nitric oxide concentration will give useful information for cardiologists, modification of abnormal levels of this parameter may delay progression of aggressive atherosclerotic process and thus, may prevent recurrent coronary events in patients with coronary atherosclerosis.

  3. Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

    PubMed

    Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

    2008-10-14

    This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

  4. Relationship of Hypertension to Coronary Atherosclerosis and Cardiac Events in Patients With Coronary Computed Tomographic Angiography.

    PubMed

    Nakanishi, Rine; Baskaran, Lohendran; Gransar, Heidi; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Cury, Ricardo; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Kaufmann, Philipp A; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Pontone, Gianluca; Andreini, Daniele; Rubinshtein, Ronen; Bax, Jeroen; Jones, Erica; Hindoyan, Niree; Gomez, Millie; Lin, Fay Y; Min, James K; Berman, Daniel S

    2017-08-01

    Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events. © 2017 American Heart Association, Inc.

  5. Incremental prognostic value of coronary and systemic atherosclerosis after myocardial infarction.

    PubMed

    Calais, Fredrik; Eriksson Östman, Maja; Hedberg, Pär; Rosenblad, Andreas; Leppert, Jerzy; Fröbert, Ole

    2018-06-15

    The role of systemic atherosclerosis in myocardial infarction (MI) patients is not fully understood. We investigated the incremental prognostic value of coronary and systemic atherosclerosis after acute MI by estimating extra-cardiac artery disease (ECAD) and extent of coronary atherosclerosis. The study included 544 prospective MI patients undergoing coronary angiography. For all patients, the longitudinal coronary atherosclerotic extent, expressed as Sullivan extent score (SES) was calculated. In addition, the patients underwent non-invasive screening for ECAD in the carotid, aortic, renal and lower limb. SES was found to be associated with ECAD independent of baseline clinical parameters [adjusted odds ratio (OR) 1.04 95% confidence interval (CI) 1.02-1.06, P < 0.001]. Extensive systemic atherosclerosis, defined as the combination of extensive coronary disease (SES ≥ 17) and ECAD, was associated with higher risk for all-cause mortality compared to limited systemic atherosclerosis (SES < 17 and no ECAD) (hazard ratio [HR] 2.9 95% CI 1.9-4.5, P < 0.001, adjusted for Global Registry of Acute Coronary Events risk score parameters 1.8, 95% CI 1.1-3.0, P = 0.019). The risk for the composite endpoint of cardiovascular death or hospitalization was significantly higher in patients with extensive systemic atherosclerosis compared to patients with limited systemic atherosclerosis (HR 3.1, 95% CI 2.1-4.7, P < 0.001, adjusted HR 1.9, 95% CI 1.2-3.1, P < 0.004). Visual estimation of the longitudinal coronary atherosclerotic extent at the time of MI predicts ECAD. Coexistence of extensive coronary disease and ECAD defines a group with particularly poor prognosis after MI. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Impact of Prediabetic Status on Coronary Atherosclerosis

    PubMed Central

    Kurihara, Osamu; Takano, Masamichi; Yamamoto, Masanori; Shirakabe, Akihiro; Kimata, Nakahisa; Inami, Toru; Kobayashi, Nobuaki; Munakata, Ryo; Murakami, Daisuke; Inami, Shigenobu; Okamatsu, Kentaro; Ohba, Takayoshi; Ibuki, Chikao; Hata, Noritake; Seino, Yoshihiko; Mizuno, Kyoichi

    2013-01-01

    OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. PMID:23223344

  7. Inverse association between hyperthymic affective temperament and coronary atherosclerosis: A coronary computed tomography angiography study.

    PubMed

    Nemcsik, János; Vecsey-Nagy, Milán; Szilveszter, Bálint; Kolossváry, Márton; Karády, Júlia; László, Andrea; Kőrösi, Beáta; Nemcsik-Bencze, Zsófia; Gonda, Xénia; Merkely, Béla; Rihmer, Zoltán; Maurovich-Horvat, Pál

    2017-12-01

    A bidirectional relationship exists between psychiatric disorders and cardiovascular diseases, however less is known with regards to personality traits. Accumulating data suggest that affective temperaments are both associated with psychiatric and somatic diseases. The aim of our study was to evaluate the associations between different affective temperaments and the presence of coronary atherosclerosis. 200 consecutive patients referred to coronary computed tomography angiography (CCTA) due to suspected coronary artery disease (CAD) were included in our study. Medical history and demographic parameters were recorded and all patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) and the Beck Depression Inventory (BDI). The presence of coronary artery disease was evaluated based on the CCTA images. 39 patients were free of any coronary atherosclerosis (CCTA-) and 161 had coronary atherosclerosis (CCTA+). Hyperthymic affective temperament score was higher in CCTA- subjects as compared to CCTA+ (13.1±3.0 vs 11.5±4.6, p=0.010, respectively). Hyperthymic affective temperament score showed a significant independent, inverse relationship with coronary atherosclerosis (OR: 0.91 CI: 0.82-0.99, p=0.04). Our results suggest that hyperthymic affective temperament is independently associated with the absence of CAD. It requires further research to delineate the mechanism mediating the effect of hyperthymia on better coronary artery health and establishing potential biochemical or behavioral factors, both of which could be exploited for prevention and treatment purposes. But it is plausible, that the evaluation of affective temperaments have importance both in relation with psychiatric and cardiovascular disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Predictive value of apolipoprotein for coronary atherosclerosis in asymptomatic non-diabetic population.

    PubMed

    Song, Xiang; Tian, Shu-ping; Ju, Hai-yue; Zhang, Fan; Li, Ying-na; Wu, Fang; Yang, Li

    2015-02-01

    To explore the potential correlation between apolipoprotein (Apo) levels and coronary atherosclerosis and investigate its predictive value for coronary artery lesions in asymptomatic population without diabetes. We performed a retrospective analysis of data collected from 401 asymptomatic patients who took health check-ups. They were divided into atherosclerosis group (n=224)and control group (n=177) based on the outcome of CT angiography and blood biochemical findings. The risk factors, lipid profiles, and Apo levels were compared between these two groups. The best biochemical indicators for predicting the coronary atherosclerosis were explored. The levels of ApoB, ApoC2,ApoC3,and ApoE and ApoB/ApoA1 ratio were significantly higher in the atherosclerosis group than in the control group (all P<0.01), whereas the ApoA1,ApoA2, and lipoprotein a levels showed no such significant difference (all P>0.05). Logistic regression analysis revealed that age, male, hypertension,ApoC3(OR=1.572,95%CI 1.200-2.061) and ApoB/ApoA1 ratio (OR=1.767,95% CI 1.335-2.338) were independently correlated with coronary atherosclerosis (all P<0.01). In the prediction of the presence of plaque, ApoB had the largest area under curves, and the optimal cutoff point was 1.005 g/L. ApoC3 is closely associated with subclinical coronary atherosclerosis,while the decrease of ApoA1 level is not obvious during this period. Compared with other lipid indicators, ApoB is the strongest predictor for coronary atherosclerosis in asymptomatic non-diabetic population.

  9. Reversal of coronary atherosclerosis: Role of life style and medical management.

    PubMed

    Parsons, Christine; Agasthi, Pradyumna; Mookadam, Farouk; Arsanjani, Reza

    2018-05-17

    Atherosclerotic coronary artery disease continues to be a major global health burden in developing and developed nations. Newer imaging techniques afford an accurate assessment of plaque burden and characteristics as well as the effects of treatment. Lifestyle interventions and pharmacotherapy remain the mainstay of non-interventional treatment of coronary atherosclerosis, with reversal seen in many studies. In addition, control of modifiable risk factors can be beneficial. As a better understanding of atherosclerosis pathophysiology is achieved, new therapeutic targets and combination therapies may join the armamentarium that promotes regression of atherosclerotic plaque. We present a review of the literature regarding lifestyle and medical therapies that can promote the reversal of coronary atherosclerosis. Copyright © 2018. Published by Elsevier Inc.

  10. A multicentre, randomized, double-blind placebo-controlled trial evaluating rosiglitazone for the prevention of atherosclerosis progression after coronary artery bypass graft surgery in patients with type 2 diabetes. Design and rationale of the VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) trial

    PubMed Central

    Bertrand, Olivier F; Poirier, Paul; Rodés-Cabau, Josep; Rinfret, Stéphane; Title, Lawrence; Dzavik, Vladimir; Natarajan, Madhu; Angel, Juan; Batalla, Nuria; Alméras, Natalie; Costerousse, Olivier; De Larochellière, Robert; Roy, Louis; Després, Jean-Pierre

    2009-01-01

    BACKGROUND: The number of patients with coronary artery disease and type 2 diabetes will increase dramatically over the next decade. Diabetes has been related to accelerated atherosclerosis and many patients with diabetes will require coronary artery bypass graft (CABG) surgery utilizing saphenous vein grafts. After CABG, accelerated atherosclerosis in saphenous vein grafts leads to graft failure in approximately 50% of cases over a 10-year period. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, has been shown to improve multiple metabolic parameters in patients with type 2 diabetes. However, its role in the prevention of atherosclerosis progression is uncertain. STUDY DESIGN: VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) is a cardiometabolic trial in which patients with type 2 diabetes, one to 10 years after CABG, will be randomly assigned to receive rosiglitazone (up to 8 mg/day) or a placebo after qualifying angiography and intravascular ultrasound of a segment of one vein graft with or without a native anastomosed coronary artery. A comprehensive set of athero-thrombo-inflammatory markers will be serially assessed during the 12-month follow-up period. Body fat distribution and body composition will be assessed by computed tomography and dual energy x-ray absorptiometry, respectively, at baseline, six months and 12 months follow-up. For atherosclerosis progression evaluation, repeat angiography and intravascular ultrasound will be performed after 12 months follow-up. The primary end point of the study will be the change in atherosclerotic plaque volume in a 40 mm or longer segment of one vein graft. CONCLUSIONS: The VICTORY trial is the first cardiometabolic study to evaluate the antiatherosclerotic and metabolic effects of rosiglitazone in post-CABG patients with type 2 diabetes. PMID:19746240

  11. Prediabetes is not a risk factor for subclinical coronary atherosclerosis.

    PubMed

    Park, Gyung-Min; Cho, Young-Rak; Lee, Seung-Whan; Yun, Sung-Cheol; Won, Ki-Bum; Ann, Soe Hee; Kim, Yong-Giun; Kim, Shin-Jae; Roh, Jae-Hyung; Kim, Young-Hak; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Chang Hee; Koh, Eun Hee; Lee, Woo Je; Kim, Min-Seon; Lee, Ki-Up; Park, Joong-Yeol; Kim, Hong-Kyu; Choe, Jaewon; Lee, Sang-Gon

    2017-09-15

    There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals. We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively. Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80-1.22, p=0.888), any plaque (0.96, 95% CI 0.86-1.07, p=0.483), calcified plaque (0.90, 95% CI 0.79-1.01, p=0.080), non-calcified plaque (1.02, 95% CI 0.88-1.17, p=0.803), and mixed plaque (1.00, 95% CI 0.82-1.22, p=0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34-2.19, p<0.001), any plaque (1.45, 95% CI 1.26-1.68, p<0.001), calcified plaque (1.35, 95% CI 1.15-1.57, p<0.001), non-calcified plaque (1.33, 95% CI 1.11-1.59, p=0.002), and mixed plaque (1.64, 95% CI 1.30-2.07, p<0.001) of diabetic individuals were significantly higher than those of the normal individuals. In asymptomatic individuals, diabetic individuals had a higher risk for subclinical coronary atherosclerosis, but prediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Imaging of coronary atherosclerosis and identification of the vulnerable plaque

    PubMed Central

    de Feyter, P.J.; Serruys, P. W.; Nieman, K.; Mollet, N.; Cademartiri, F.; van Geuns, R. J.; Slager, C.; van der Steen, A.F.W.; Krams, R.; Schaar, J.A.; Wielopolski, P.; Pattynama, P.M.T.; Arampatzis, A.; van der Lugt, A.; Regar, E.; Ligthart, J.; Smits, P.

    2003-01-01

    Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation. Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque. The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:25696244

  13. Elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis.

    PubMed

    Kang, Seung Joo; Kim, Donghee; Park, Hyo Eun; Chung, Goh Eun; Choi, Seung Ho; Choi, Su-Yeon; Lee, Whal; Kim, Joo Sung; Cho, Sang-Heon

    2013-10-01

    Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis. The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48-0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49-0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.

    PubMed

    Potekhina, Alexandra V; Pylaeva, Ekaterina; Provatorov, Sergey; Ruleva, Natalya; Masenko, Valery; Noeva, Elena; Krasnikova, Tatiana; Arefieva, Tatiana

    2015-01-01

    Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively. We aimed to investigate the balance of circulating Treg and Th17 in stable angina patients with different stages of coronary atherosclerosis. Methods. Treg, Th17 and Th1 cell frequencies were studied in 117 patients via direct immunofluorescence staining and flow cytometry. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone previous coronary stenting; in Group 2 no coronary atherosclerosis progression was found, in Group 3 patients had disease progression in non-invaded coronary arteries. Group 4 had severe coronary atherosclerosis. Results. The frequencies of CD4+CD25highCD127low, CD4+foxp3+, and CD4+IL10 + T cells were decreased, and CD4+IL17 + T cells frequencies were increased in group 4 vs. 1. Treg/Th17 ratios were declined in groups 3 and 4 vs. groups 1 and 2. IL-10 level was lower while hsCRP and sCD25 levels were higher in group 4 vs. 1. Conclusion. We assume that the imbalance in pro- and anti-inflammatory/atherogenic lymphocyte subpopulations is associated with atherosclerosis progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Atherosclerosis and Liver Function Tests in Coronary Angiography Patients.

    PubMed

    Doganer, Y C; Rohrer, J E; Aydogan, U; Agerter, D C; Cayci, T; Barcin, C

    2015-09-01

    Elevated aminotransferase levels indicating liver function, even in the normal range, have attracted great concern as potential novel markers of cardiovascular risk assessment. We hypothesized the possibility that liver function test variations in the normal range might be meaningfully associated to coronary artery disease (CAD). Eighty-eight patients were randomly selected from those who underwent coronary angiography from June 2010 to June 2011 after applying to the outpatient cardiology clinic in Gulhane Military Medical Academy. According to the results of angiographies, patients were classified into three groups as normal, non-critical (< 50% involvement in coronaries), and critical (≥ 50% involvement in coronaries). In addition to angiographic intervention, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, albumin and the other serum parameters were performed in all patients. The patient groups of CAD were balanced (28 critical cases, 30 non-critical cases and 30 normal cases). Mean age was 51.93 ± 9.3 (range 32-65) years and 19.3 per cent (n = 17) were females. Multiple linear regression analysis of all three liver function tests explained a significant portion of the variance, but adjusted r-squares were small (AST = 0.174, ALT = 0.242, albumin = 0.124). Albumin was significantly higher for patients with critical CAD than for patients with no CAD (beta = 3.205, p = 0.002). Non-critical CAD was not significantly different from no CAD for any of the dependent variables. Mean AST was significantly higher for patients taking aspirin (beta = 0.218, p = 0.049), as was mean ALT (beta = 0.264, p = 0.015). Alanine aminotransferase and AST may not be associated with angiographically determined coronary atherosclerosis. Albumin may be more sensitive to demonstrate the burden of atherosclerosis. These results indicate that the association between the liver function tests and coronary atherosclerosis may be more

  16. Relationship between inter-arm blood pressure difference and severity of coronary atherosclerosis.

    PubMed

    Park, Se-Jun; Son, Jung-Woo; Park, Sang-Min; Choi, Hyun-Hee; Hong, Kyung-Soon

    2017-08-01

    A greater inter-arm blood pressure difference (IABPD) is associated with atherosclerosis, but its association with coronary artery disease is unknown. We investigated the relationship between IABPD and coronary atherosclerosis. We retrospectively reviewed blood pressure (BP) data that was measured simultaneously in both arms of patients who underwent initial coronary angiography. Coronary atherosclerosis was assessed using the Gensini score, based on quantitative coronary angiography findings. To adjust for the effect of baseline BP, the percentages of systolic IABPD to higher mean BP (cIABPD sys ), diastolic IABPD to higher mean BP (cIABPD dia ), and mean IABPD to higher mean BP (cIABPD mean ) were calculated as BP-adjusted IABPDs. We examined the records of 816 patients (516 males, mean age: 65.5 ± 11.8 years). The mean Gensini score was 33.4 ± 30.4, and the median was 25. All cIAPBDs had positive correlations with the Gensini score (cIABPD sys : r = 0.208, p < 0.001; cIABPD dia : r = 0.123, p < 0.001; cIABPD mean : r = 0.120, p = 0.001). Multiple regression analysis indicated that cIABPD sys was associated with the Gensini score, independently of age, gender, smoking, diabetes, hypertension and dyslipidemia (B = 0.031, p < 0.001). The BP-adjusted IABPD parameters are related to the severity of coronary artery disease. Further studies should investigate the use of the IABPD to improve management of coronary atherosclerosis. Copyright © 2017. Published by Elsevier B.V.

  17. Epicardial fat is associated with severity of subclinical coronary atherosclerosis in familial hypercholesterolemia.

    PubMed

    Mangili, Leonardo C; Mangili, Otavio C; Bittencourt, Márcio S; Miname, Márcio H; Harada, Paulo H; Lima, Leonardo M; Rochitte, Carlos E; Santos, Raul D

    2016-11-01

    Familial hypercholesterolemia (FH) is a common genetic disorder characterized by elevated blood cholesterol, increased prevalence of subclinical atherosclerosis and high risk of premature coronary heart disease. However, this risk is not explained solely by elevated LDL-cholesterol concentrations, and other factors may influence atherosclerosis development. There is evidence that increased adiposity may predispose to atherosclerosis in FH. Epicardial fat has been associated with subclinical coronary atherosclerosis in the general population. This study evaluated the association of epicardial fat (EFV) volume with the presence and extent of subclinical coronary atherosclerosis detected by computed tomography angiography in FH patients. Ninety-seven FH subjects (35% male, mean age 45 ± 13 years, LDL-C 281 ± 56 mg/dL, 67% with proven molecular defects) underwent computed tomography angiography and coronary artery calcium (CAC) scoring. EFV was measured in non-contrast images using a semi-automated method. Segment-stenosis score (SSS) and segment-involvement score (SIS) were calculated. Multivariate Poisson regression was utilized to assess an independent association of EFV with coronary atherosclerotic burden. EFV was positively associated with age, body mass index, waist circumference, blood glucose, the presence of the metabolic syndrome components, but not with LDL-C. After adjusting for confounders and abdominal circumference, an independent association (shown as β coefficients and 95% confidence intervals) of EVF with CAC scores [β = 0.263 (0.234; 0.292), p=0.000], SIS [β = 0.304 (0.141; 0.465) p=0.000] and SSS [β = 0.296 (0.121; 0.471), p=0.001] was found. In FH, EFV was independently associated with coronary atherosclerotic presence and severity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Relation of ABO blood groups to the severity of coronary atherosclerosis: an Gensini score assessment.

    PubMed

    Gong, Ping; Luo, Song-Hui; Li, Xiao-Lin; Guo, Yuan-Lin; Zhu, Cheng-Gang; Xu, Rui-Xia; Li, Sha; Dong, Qian; Liu, Geng; Chen, Juan; Zeng, Rui-Xiang; Li, Jian-Jun

    2014-12-01

    Although the study on the relationship between ABO blood groups and coronary atherosclerosis has a long history, few data is available regarding ABO to severity of coronary atherosclerosis in a large cohort study. Therefore, the present study aimed to investigate the relation of the ABO blood groups to the severity of coronary atherosclerosis assessed by Gensini score (GS) in a large Chinese cohort undergoing coronary angiography. A total of 2919 consecutive patients undergoing coronary angiography were enrolled, and their baseline characteristics and ABO blood groups were collected. The GS was calculated as 1st tertile (0-10), 2nd tertile (11-36), 3rd tertile (>36) according to angiographic results. The relation of the ABO blood groups to GS was investigated. The frequency of blood group A was significantly higher in the upper GS tertiles (24.4% vs. 28.2% vs. 29.5%, p = 0.032). Multivariable linear regression analysis revealed that blood group A was independently associated with GS (β = 0.043, p = 0.017). Likewise, multivariable logistic regression analysis showed that group A remained significantly associated with mid-high GS (OR = 1.44, 95% CI 1.16-1.80, p = 0.001), and the group O was showed as a protective factor (OR = 0.77, 95% CI = 0.65-0.92, p = 0.004). In this large Chinese cohort study, the data indicated that there was an association between ABO blood groups and the severity of coronary atherosclerosis. Moreover, the blood group A was an independent risk factor for serious coronary atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Cardiovascular risk scores for coronary atherosclerosis.

    PubMed

    Yalcin, Murat; Kardesoglu, Ejder; Aparci, Mustafa; Isilak, Zafer; Uz, Omer; Yiginer, Omer; Ozmen, Namik; Cingozbay, Bekir Yilmaz; Uzun, Mehmet; Cebeci, Bekir Sitki

    2012-10-01

    The objective of this study was to compare frequently used cardiovascular risk scores in predicting the presence of coronary artery disease (CAD) and 3-vessel disease. In 350 consecutive patients (218 men and 132 women) who underwent coronary angiography, the cardiovascular risk level was determined using the Framingham Risk Score (FRS), the Modified Framingham Risk Score (MFRS), the Prospective Cardiovascular Münster (PROCAM) score, and the Systematic Coronary Risk Evaluation (SCORE). The area under the curve for receiver operating characteristic curves showed that FRS had more predictive value than the other scores for CAD (area under curve, 0.76, P < or = 0.001), but all scores had good specificity and positive predictive value. For 3-vessel disease, the FRS had better predictive value than the other scores (area under curve, 0.74, P < or = 0.001), but all scores had good specificity and negative predictive value. The risk scores (FRS, MFRS, PROCAM, and SCORE) may predict the presence and severity of coronary atherosclerosis.The FRS had better predictive value than the other scores.

  20. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.

    PubMed

    Reilly, Muredach P; Li, Mingyao; He, Jing; Ferguson, Jane F; Stylianou, Ioannis M; Mehta, Nehal N; Burnett, Mary Susan; Devaney, Joseph M; Knouff, Christopher W; Thompson, John R; Horne, Benjamin D; Stewart, Alexandre F R; Assimes, Themistocles L; Wild, Philipp S; Allayee, Hooman; Nitschke, Patrick Linsel; Patel, Riyaz S; Martinelli, Nicola; Girelli, Domenico; Quyyumi, Arshed A; Anderson, Jeffrey L; Erdmann, Jeanette; Hall, Alistair S; Schunkert, Heribert; Quertermous, Thomas; Blankenberg, Stefan; Hazen, Stanley L; Roberts, Robert; Kathiresan, Sekar; Samani, Nilesh J; Epstein, Stephen E; Rader, Daniel J

    2011-01-29

    We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Lasting monitoring of immune state in patients with coronary atherosclerosis

    NASA Astrophysics Data System (ADS)

    Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

    2007-02-01

    Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

  2. Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

    PubMed

    Kijani, Siavash; Vázquez, Ana Maria; Levin, Malin; Borén, Jan; Fogelstrand, Per

    2017-07-01

    Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on

  3. The association of ABO blood groups with extent of coronary atherosclerosis in Croatian patients suffering from chronic coronary artery disease.

    PubMed

    Karabuva, Svjetlana; Carević, Vedran; Radić, Mislav; Fabijanić, Damir

    2013-01-01

    The aim of study was to: 1) examine the relationship between ABO blood groups and extent of coronary atherosclerosis in patients with chronic coronary artery disease (CAD), 2) compare ABO blood groups distribution in CAD patients and general population, 3) examine possible differences in traditional risk factors frequency in CAD patients with different ABO blood groups. In the 646 chronic CAD patients (72.4% males) coronary angiograms were scored by quantitative assessment using multiple angiographic scoring system, Traditional risk factors were self reported or measured by standard methods. ABO blood distribution of patients was compared with group of 651 healthy blood donors (74.6% males). Among all ABO blood group patients there was no significant difference between the extent of coronary atherosclerosis with regard to all the three scoring systems: number of affected coronary arteries (P = 0.857), Gensini score (P = 0.818), and number of segments narrowed > 50% (P = 0.781). There was no significant difference in ABO blood group distribution between CAD patients and healthy blood donors. Among CAD patients, men with blood group AB were significantly younger than their pairs with non-AB blood groups (P = 0.008). Among CAD patients with AB blood group, males < 50 yrs were significantly overrepresented when compared with the non-AB groups (P = 0.003). No association between ABO blood groups and the extent of coronary atherosclerosis in Croatian CAD patients is observed. Observation that AB blood group might possibly identify Croatian males at risk to develop the premature CAD has to be tested in larger cohort of patients.

  4. Brazilian adult individuals with untreated isolated GH deficiency do not have accelerated subclinical atherosclerosis

    PubMed Central

    Costa, Ursula M M; Oliveira, Carla R P; Salvatori, Roberto; Barreto-Filho, José A S; Campos, Viviane C; Oliveira, Francielle T; Rocha, Ivina E S; Oliveira, Joselina L M; Silva, Wersley A; Aguiar-Oliveira, Manuel H

    2016-01-01

    GH and its principal mediator IGF1 have important effects on metabolic and cardiovascular (CV) status. While acquired GH deficiency (GHD) is often associated with increased CV risk, the consequences of congenital GHD are not known. We have described a large group of patients with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G>A) in the GH releasing hormone receptor gene, and shown that adult GH-naïve individuals have no evidence of clinically evident premature atherosclerosis. To test whether subclinical atherosclerosis is anticipated in untreated IGHD, we performed a cross-sectional study of 25 IGHD and 27 adult controls matched for age and gender. A comprehensive clinical and biochemical panel and coronary artery calcium scores were evaluated by multi-detector tomography. Height, weight, IGF1, homeostasis model assessment of insulin resistance, creatinine and creatininekinase were lower in the IGHD group. Median and interquartile range of calcium scores distribution was similar in the two groups: IGHD 0(0) and control 0(4.9). The vast majority of the calcium scores (20 of 25 IGHD (80%) and 18 of 27 controls (66.6%)) were equal to zero (difference not significant). There was no difference in the calcium scores classification. None of IGHD subjects had minimal calcification, which were present in four controls. Three IGHD and four controls had mild calcification. There were two IGHD individuals with moderate calcification and one control with severe calcification. Our study provides evidence that subjects with congenital isolated lifetime and untreated severe IGHD do not have accelerated subclinical coronary atherosclerosis. PMID:26811426

  5. Protective Effects of Hydroxychloroquine against Accelerated Atherosclerosis in Systemic Lupus Erythematosus

    PubMed Central

    Cauli, Alberto

    2018-01-01

    Cardiovascular (CV) morbidity and mortality are a challenge in management of patients with systemic lupus erythematosus (SLE). Higher risk of CV disease in SLE patients is mostly related to accelerated atherosclerosis. Nevertheless, high prevalence of traditional cardiovascular risk factors in SLE patients does not fully explain the increased CV risk. Despite the pathological bases of accelerated atherosclerosis are not fully understood, it is thought that this process is driven by the complex interplay between SLE and atherosclerosis pathogenesis. Hydroxychloroquine (HCQ) is a cornerstone in treatment of SLE patients and has been thought to exert a broad spectrum of beneficial effects on disease activity, prevention of damage accrual, and mortality. Furthermore, HCQ is thought to protect against accelerated atherosclerosis targeting toll-like receptor signaling, cytokine production, T-cell and monocyte activation, oxidative stress, and endothelial dysfunction. HCQ was also described to have beneficial effects on traditional CV risk factors, such as dyslipidemia and diabetes. In conclusion, despite lacking randomized controlled trials unambiguously proving the protection of HCQ against accelerated atherosclerosis and incidence of CV events in SLE patients, evidence analyzed in this review is in favor of its beneficial effect. PMID:29670462

  6. Regional Coronary Endothelial Function is Closely Related to Local Early Coronary Atherosclerosis in Patients with Mild Coronary Artery Disease: A Pilot Study

    PubMed Central

    Hays, Allison G.; Kelle, Sebastian; Hirsch, Glenn A.; Soleimanifard, Sahar; Yu, Jing; Agarwal, Harsh K.; Gerstenblith, Gary; Schär, Michael; Stuber, Matthias; Weiss, Robert G.

    2012-01-01

    Background Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT). Methods and Results Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008). Conclusions There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease. PMID:22492483

  7. Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies.

    PubMed

    Andrews, Jordan; Puri, Rishi; Kataoka, Yu; Nicholls, Stephen J; Psaltis, Peter J

    2016-08-01

    Despite advances in risk prediction, preventive and therapeutic strategies, atherosclerotic cardiovascular disease remains a major public health challenge worldwide, carrying considerable morbidity, mortality and health economic burden. There continues to be a need to better understand the natural history of this disease to guide the development of more effective treatment, integral to which is the rapidly evolving field of coronary artery imaging. Various imaging modalities have been refined to enable detailed visualization of the pathological substrate of atherosclerosis, providing accurate and reproducible measures of coronary plaque burden and composition, including the presence of high-risk characteristics. The serial application of such techniques, including coronary computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have uncovered important insights into the progression of coronary plaque over time in patients with stable and unstable coronary artery disease (CAD), and its responsiveness to therapeutic interventions. Here we review the use of different imaging modalities for the surveillance of coronary atherosclerosis and the lessons they have provided about the modulation of CAD by both traditional and experimental therapies.

  8. [Values of computed tomography angiogram in non-cardiac surgery planning and cardiac risk assessment of coronary atherosclerosis during perioperative period].

    PubMed

    Chang, Rui-ping; Ju, Hai-yue; Zhang, Xing-hua; Wu, Jian; Zhang, Fan; Mi, Wei-dong; Cao, Xiu-tang; Gao, Chang-qing; Yang, Li

    2013-02-19

    To explore the values of detecting coronary atherosclerosis by computed tomography angiogram (CTA) on non-cardiac surgery planning and cardiac risk assessment of coronary atherosclerosis during perioperative period. A total of 89 patients with suspected coronary heart disease (CHD) scheduled for non-cardiac surgery underwent coronary CTA to evaluate luminal stenosis and calculate calcification score. There were 56 males and 33 females with a mean age of 65.1 years. Operative sites included chests (n = 29), abdomens and pelvis (n = 26), large vessels (n = 3), bones and joints (n = 19) and other regions (n = 12). Reasons of abandoned or postponed surgery were documented to analyze the influence of CTA results on surgery planning. Cardiac events were recorded to assess the correlation with coronary atherosclerosis. Among them, 75 patients (84.27%) were diagnosed as atherosclerosis while 10 patients (11.24%) were negative; 2 patients had coronary artery bypass and another 2 had stent implantation. According to the results of CTA, 12 operations (13.48%) were canceled and 8 (8.98%) postponed after interventions. Severe stenosis of coronary lumen had significant effects on surgery planning (P = 0.003) while calcification score did not. In patients undergoing surgery as scheduled or after intervention, 1 had atrial fibrillation at post-operation. For the patients with suspected CHD scheduled for non-cardiac surgery, severity of coronary stenosis may greatly influence surgery planning. Preoperative coronary CTA may decrease the incidence of cardiac events during perioperative period.

  9. Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

    PubMed

    Gaubert, Mélanie; Marlinge, Marion; Alessandrini, Marine; Laine, Marc; Bonello, Laurent; Fromonot, Julien; Cautela, Jennifer; Thuny, Franck; Barraud, Jeremie; Mottola, Giovanna; Rossi, Pascal; Fenouillet, Emmanuel; Ruf, Jean; Guieu, Régis; Paganelli, Franck

    2018-06-01

    The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R 2  = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.

  10. Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes.

    PubMed

    Aengevaeren, Vincent L; Mosterd, Arend; Braber, Thijs L; Prakken, Niek H J; Doevendans, Pieter A; Grobbee, Diederick E; Thompson, Paul D; Eijsvogels, Thijs M H; Velthuis, Birgitta K

    2017-07-11

    Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis. Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants' activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk. A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3-145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0-60.9] versus 0 [interquartile range, 0-43.5]; P =0.02) and prevalence of CAC (68%; adjusted odds ratio [OR adjusted ]=3.2; 95% confidence interval [CI], 1.6-6.6) and plaque (77%; OR adjusted =3.3; 95% CI, 1.6-7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (OR adjusted =1.47; 95% CI, 1.14-1.91) and plaque (OR adjusted =1.56; 95% CI, 1.17-2.08). Among participants with CAC>0, there was no difference in CAC score ( P =0.20), area ( P =0.21), density ( P =0.25), and regions of interest ( P =0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; OR adjusted =0.35; 95% CI, 0.15-0.85) and more often had only calcified plaques (38% versus

  11. Effects of Bazedoxifene Alone and with Conjugated Equine Estrogens on Coronary and Peripheral Artery Atherosclerosis of Postmenopausal Monkeys

    PubMed Central

    Clarkson, Thomas B.; Ethun, Kelly F.; Chen, Haiying; Golden, Debbie; Floyd, Edison; Appt, Susan E.

    2012-01-01

    Objective The objective was to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atherosclerosis and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) in a monkey model. Methods Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and then randomized to receive no treatment, or women’s equivalent doses of BZA (20 mg/day), CEE (0.45 mg/day) or BZA+CEE. The experiment period was for 20 months (approximately equivalent to 5 years of patient experience) during which interim measures were made of cardiovascular risk factors. At the end of the experimental period, the extent and severity of coronary and iliac artery atherosclerosis was quantified. Results Body weight, adiposity, fasting glucose concentrations and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on coronary artery nor common iliac artery atherosclerosis extent or severity when compared to no-treatment. CEE, administered soon after inducing menopause, had a robust atheroprotective effect on both iliac and coronary artery extent and severity. The addition of BZA to the CEE treatment antagonized the atheroprotective effect of the CEE. Conclusions In this nonhuman primate trial, treatment with BZA alone, CEE alone and BZA and CEE in combination did not have significant effects on plasma lipid profiles. CEE markedly inhibited the progression and complication of both coronary and iliac artery atherosclerosis. BZA had no adverse effects on atherosclerosis but attenuated the atheroprotective effects of CEE. PMID:23435024

  12. Herpes simplex virus type 2 (HSV-2) as a coronary atherosclerosis risk factor in HIV-infected men: Multicenter AIDS Cohort Study

    PubMed Central

    Hechter, Rulin C.; Budoff, Matthew; Hodis, Howard N.; Rinaldo, Charles R.; Jenkins, Frank J.; Jacobson, Lisa P.; Kingsley, Lawrence A.; Taiwo, Babafemi; Post, Wendy S.; Margolick, Joseph B.; Detels, Roger

    2012-01-01

    We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2), cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT imaging. Markers for herpesviruses infection were measured in frozen specimens collected 10-12 years prior to case identification. Multivariable logistic regression models and ordinal logistic regression models were performed. HSV-2 seropositivity was associated with coronary atherosclerosis (adjusted odds ratio [AOR] =4.12, 95% confidence interval [CI] =1.58-10.85) after adjustment for age, race/ethnicity, cardiovascular risk factors, and HIV infection related factors. Infection with a greater number of herpesviruses was associated with elevated CAC levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk factor for subclinical coronary atherosclerosis in HIV-infected men. Infection with multiple herpesviruses may contribute to the increased burden of atherosclerosis. PMID:22472456

  13. Herpes simplex virus type 2 (HSV-2) as a coronary atherosclerosis risk factor in HIV-infected men: multicenter AIDS cohort study.

    PubMed

    Hechter, Rulin C; Budoff, Matthew; Hodis, Howard N; Rinaldo, Charles R; Jenkins, Frank J; Jacobson, Lisa P; Kingsley, Lawrence A; Taiwo, Babafemi; Post, Wendy S; Margolick, Joseph B; Detels, Roger

    2012-08-01

    We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2), cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT imaging. Markers for herpesviruses infection were measured in frozen specimens collected 10-12 years prior to case identification. Multivariable logistic regression models and ordinal logistic regression models were performed. HSV-2 seropositivity was associated with coronary atherosclerosis (adjusted odds ratio [AOR]=4.12, 95% confidence interval [CI]=1.58-10.85) after adjustment for age, race/ethnicity, cardiovascular risk factors, and HIV infection related factors. Infection with a greater number of herpesviruses was associated with elevated CAC levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk factor for subclinical coronary atherosclerosis in HIV-infected men. Infection with multiple herpesviruses may contribute to the increased burden of atherosclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. A comparison of postmortem coronary atherosclerosis findings in general aviation pilot fatalities.

    DOT National Transportation Integrated Search

    1985-08-01

    Autopsy reports of 710 pilots involved in fatal general aviation accidents and received by the FAA for the years 1980-82 were reviewed to appraise the age-specific prevalence of coronary atherosclerosis among the autopsied group and compare findings ...

  15. Postmortem coronary atherosclerosis findings in general aviation accident pilot fatalities : 1975 - 1977.

    DOT National Transportation Integrated Search

    1980-02-01

    Autopsy reports of 710 pilots involved in fatal general aviation accidents and received by the FAA for the years 1980-82 were reviewed to appraise the age-specific prevalence of coronary atherosclerosis among the autopsied group and compare findings ...

  16. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography

    USDA-ARS?s Scientific Manuscript database

    Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector row ...

  17. Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs.

    PubMed

    Li, Wennan; Chen, Xingjuan; Riley, Ashley M; Hiett, S Christopher; Temm, Constance J; Beli, Eleni; Long, Xin; Chakraborty, Saikat; Alloosh, Mouhamad; White, Fletcher A; Grant, Maria B; Sturek, Michael; Obukhov, Alexander G

    2017-09-01

    Coronary transient receptor potential canonical (TRPC) channel expression is elevated in metabolic syndrome (MetS). However, differential contribution of TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and determined whether long-term treatment with a mineralocorticoid receptor inhibitor, spironolactone, attenuates coronary TRPC expression and associated dysfunctions. MetS coronary arteries exhibited significant atherosclerosis, endothelial dysfunction, and increased histamine-induced contractions. Immunohistochemical studies revealed that TRPC6 immunostaining was significantly greater in the medial layer of MetS pig coronary arteries compared to that in Lean pigs, whereas little TRPC6 immunostaining was found in atheromas. Conversely, TRPC1 immunostaining was weak in the medial layer but strong in MetS atheromas, where it was predominantly localized to macrophages. Spironolactone treatment significantly decreased coronary TRPC expression and dysfunctions in MetS pigs. In vivo targeted delivery of the dominant-negative (DN)-TRPC6 cDNA to the coronary wall reduced histamine-induced calcium transients in the MetS coronary artery medial layer, implying a role for TRPC6 in mediating calcium influx in MetS coronary smooth muscles. Monocyte adhesion was increased in Lean pig coronary arteries cultured in the presence of aldosterone; and spironolactone antagonized this effect, suggesting that coronary mineralocorticoid receptor activation may regulate macrophage infiltration. TRPC1 expression in atheroma macrophages was associated with advanced atherosclerosis, whereas medial TRPC6 upregulation correlated with increased histamine-induced calcium transients and coronary contractility. We propose that long-term spironolactone treatment may be a therapeutic strategy to decrease TRPC expression and coronary pathology associated with MetS.

  18. Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

    2012-10-01

    Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke. The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline. Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively). Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.

  19. Coronary atherosclerosis and adverse outcomes in patients with recent-onset atrial fibrillation and troponin rise.

    PubMed

    Conti, Alberto; Angeli, Elena; Scorpiniti, Margherita; Alesi, Andrea; Trausi, Federica; Lazzeretti, Delia; Padeletti, Luigi; Gensini, Gian Franco

    2015-10-01

    The relationship between troponin and atrial fibrillation (AF) without acute coronary syndrome is still unclear. We sought to investigate the presence of coronary atherosclerosis and adverse outcomes in patients with AF. Consecutive patients with recent-onset AF and without severe comorbidities were enrolled between 2004 and 2013. Patients with a troponin rise or with adverse outcomes were considered for coronary angiography and revascularization when "critical" stenosis (≥70%) was recognized. Propensity score matching was performed to adjust for baseline characteristics; after matching, no differences existed between the groups of patients with or without troponin rise. The primary end point was the composite of acute coronary syndrome, revascularization, and cardiac death at 1- and 12-month follow-ups. Of 3627 patients enrolled, 3541 completed the study; 202 (6%) showed troponin rise; and 91 (3%), an adverse outcome. In the entire cohort, on multivariate analysis, the odds ratio for the occurrence of the primary end point of troponin rise was 14 (95% confidence interval [CI], 10-23; P<.001), and that of known coronary artery disease was 3 (CI, 2-5; P=.001). In the matching cohort, the odds ratio of troponin rise was 10 (CI, 4-22; P<.001), and that of TIMI score greater than 2 was 4 (CI, 2-9; P≤.001). In the entire cohort, patients with or without troponin rise achieved the primary end point in 38 (19%) and 43 (1%) patients, respectively (P<.001). Stroke occurred in 4 (2%) and 20 (1%), respectively (P=.018). Critical stenosis and revascularization account for 23 (12%) and 15 (1%), respectively (P<.001). In the matching cohort, results were confirmed, but incidence of stroke was comparable. Patients with recent-onset AF and troponin rise showed higher prevalence of coronary atherosclerosis and adverse cardiac events. Stroke per se did not succeed in justifying the high morbidity. Thus, beyond stroke, coronary atherosclerosis might have a pivotal role in poor

  20. Manifestation of Coronary Atherosclerosis in Klang Valley, Malaysia: An Autopsy Study

    PubMed Central

    Rahimi, Razuin; Singh, Mansharan Kaur Chainchel; Noor, Norizal Mohd; Omar, Effat; Noor, Shahidan Md; Mahmood, Mohd Shah; Abdullah, Nurliza; Nawawi, Hapizah Mohd

    2018-01-01

    Aims: The present study aimed to determine the epidemiological aspects of medico-legal autopsies and manifestation of coronary atherosclerosis. Methods: This was a cross sectional study involving 222 cases recruited from National Institute of Forensic Medicine (NIFM) Hospital Kuala Lumpur (HKL) and Department of Forensic Medicine Hospital Sungai Buloh (HSgB) for a period of 15 months, from December 2012 to April 2014. Sociodemographic and autopsy findings, including the cause and manner of death were documented. Results: Male and female subjects aged 18–70 years were recruited. Males contributed to 86% of the total subjects and comprised 61% of young adults. Road traffic accidents were the primary cause of death, contributing almost 50% of the subjects. One third of the cases comprised of death due to natural causes, wherein almost 75% of the subjects within this category succumbed to sudden cardiac death. Coronary artery disease (CAD) contributed to 60% of the sudden cardiac death (SCD). Single and double-vessel diseases were the most common pattern of atherosclerosis. In almost 80% of CAD cases, atherosclerosis affected the left anterior descending artery (LAD). Conclusion: Cardiovascular diseases were the most significant natural cause of sudden death with a staggering figure of 75%. CAD was the single most commonly encountered pathology within the SCD. Most cases presented with single and double-vessel diseases, observed in all subjects, as well as the young adult population. PMID:29118310

  1. Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis.

    PubMed

    López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A; Huaranga, Marco A Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A

    2017-01-06

    A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.

  2. Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

    PubMed Central

    López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A.; Huaranga, Marco A. Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J.; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J. Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

    2017-01-01

    A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA. PMID:28059143

  3. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial.

    PubMed

    Tardif, Jean-Claude; Ballantyne, Christie M; Barter, Philip; Dasseux, Jean-Louis; Fayad, Zahi A; Guertin, Marie-Claude; Kastelein, John J P; Keyserling, Constance; Klepp, Heather; Koenig, Wolfgang; L'Allier, Philippe L; Lespérance, Jacques; Lüscher, Thomas F; Paolini, John F; Tawakol, Ahmed; Waters, David D

    2014-12-07

    High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. The nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other

  4. Resveratrol, Wine, and Atherosclerosis

    PubMed Central

    Prasad, Kailash

    2012-01-01

    This review emphasizes the effects of resveratrol on factors involved in the mechanism of atherosclerosis and risk factors for atherosclerosis. The effects of wine and resveratrol on atherosclerosis are also discussed. Resveratrol is a potent antioxidant and an anti-inflammatory agent. It reduces the expression of cell adhesion molecules, monocyte colony stimulating factors, matrix metalloproteinases, and growth factors; and inhibits platelet aggregation and vascular smooth muscle cell proliferation. It reduces the serum levels of total cholesterol, triglycerides (TG), and raises high-density lipoprotein cholesterol, inhibits expression of C-reactive protein and lowers the levels of advanced glycation end products and its receptor in the vascular tissue. It lowers the risk factors for plaque rupture. Epidemiological data show that moderate consumption of alcohol has an inverse association with carotid atherosclerosis while high consumption has a positive association with carotid atherosclerosis. Wine reduces the extent of atherosclerosis in animal model. The antiatherosclerotic effect of wine is mainly due to it resveratrol content. Resveratrol reduces the extent of atherosclerosis in animal model of atherosclerosis (apolipoprotein [Apo] E-deficient and Apo E−/−/low-density lipoprotein receptor-deficient mice and macrophage). In rabbit model of atherosclerosis, both reduction and acceleration of atherosclerosis have been reported with resveratrol. There are no data for regression and slowing of progression of atherosclerosis. Robust clinical trials for suppression of atherosclerosis are lacking. In conclusion, resveratrol has potential but experimental studies in depth and robust clinical trials are lacking for this agent to be of any value in the primary and secondary prevention of coronary and peripheral artery disease. PMID:23450206

  5. Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Bakhshi, Hooman; Ambale-Venkatesh, Bharath; Yang, Xiaoying; Ostovaneh, Mohammad R; Wu, Colin O; Budoff, Matthew; Bahrami, Hossein; Wong, Nathan D; Bluemke, David A; Lima, João A C

    2017-04-20

    Although the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis is a population-based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline and follow-up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease ( P =0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P =0.03) and LV end systolic volume (β=0.12; P =0.006) after excluding participants with any coronary heart disease. CAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow-up exam independent of overt coronary heart disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. Early Menopause Predicts Future Coronary Heart Disease and Stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

    2012-01-01

    Objective Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if a self-reported early menopause (menopause at an age <46) identifies women as at risk for future coronary heart disease or stroke. Methods The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000–2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46) and future coronary heart disease and stroke was assessed in 2509 women (ages 45–84, 987 White, 331 Chinese, 641 Black, 550 Hispanic) from the Multi-Ethnic Study Atherosclerosis, who were free of cardiovascular disease at baseline. Results 693/2509 (28%) of women reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank p=<0.008 and 0.0158). In models adjusted for age, race/ethnicity, Multi-Ethnic Study Atherosclerosis site and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (HR 2.08, 95% CI 1.17, 3.70 and 2.19, 95% CI 1.11, 4.32, respectively). Conclusions Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors. PMID:22692332

  7. Coronary artery atherosclerosis associated with shift work in chemical plant workers by using coronary CT angiography.

    PubMed

    Kang, WonYang; Park, Won-Ju; Jang, Keun-Ho; Kim, Soo-Hyeon; Gwon, Do-Hyeong; Lim, Hyeong-Min; Ahn, Ji-Sung; Moon, Jai-Dong

    2016-08-01

    The aim of this study was to investigate whether shift work is related to elevated risk of coronary artery disease (CAD) by determining the coronary artery calcium (CAC) score and the presence of coronary artery stenosis by using coronary artery CT angiography (CCTA). In this study, 110 male workers participated and underwent a CCTA examination for CAC scoring, which represents coronary artery plaque, and were evaluated for luminal stenosis. All of the participants were working in the same chemical plant, of whom 70 worked day shifts and 40 worked rotating shifts. In a multivariate logistic regression analysis, including age, smoking status, alcohol consumption, regular exercise and waist circumference, shift work was associated with a 2.89-fold increase in the odds of developing coronary plaque compared with day work (OR, 2.89; 95% CI 1.07 to 7.82). The association between shift work and coronary plaque was strong after adjustment for age, low-density lipoprotein cholesterol, hypertension and diabetes mellitus (OR, 2.92; 95% CI 1.02 to 8.33). In addition, the number of years of shift work employment was associated with coronary plaque. However, no association was found between shift work and coronary artery stenosis. Shift work could induce CAD onset via the atherosclerotic process, and shift work employment duration was associated with an increased risk of atherosclerosis in male workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice.

    PubMed

    Hoving, Lisa R; de Vries, Margreet R; de Jong, Rob C M; Katiraei, Saeed; Pronk, Amanda; Quax, Paul H A; van Harmelen, Vanessa; Willems van Dijk, Ko

    2018-02-03

    The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden ( E3L ) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

  9. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

    PubMed Central

    de Jong, Rob C. M.; Katiraei, Saeed; Pronk, Amanda; van Harmelen, Vanessa

    2018-01-01

    The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol. PMID:29401645

  10. Evidence of extensive atherosclerosis, coronary artery disease and myocardial infarction in the ApoE-/-:Ins2+/Akita mouse fed a western diet.

    PubMed

    Venegas-Pino, Daniel E; Lagrotteria, Andrew; Wang, Pei-Wen; Morphet, Jaiya; Clapdorp, Cassaundra; Shi, Yuanyuan; Werstuck, Geoff H

    2018-05-23

    Diabetic patients with no history of cardiac infarction have a prevalence of coronary atherosclerosis and a risk of heart attack equivalent to euglycemic patients who have coronary atherosclerosis and have suffered a prior myocardial infarction. Although several murine models of diabetes have been established, none of these show indications of cardiac events. In an attempt to establish a diabetic mouse model with coronary atherosclerosis and myocardial injury, we have fed hyperglycemic ApoE -/- :Ins2 +/Akita mice a western diet to enhance the dyslipidemic phenotype. Five-week-old ApoE -/- :Ins2 +/Akita mice and ApoE -/- controls were fed a diet, 0.15% cholesterol and 21% anhydrous milk lipids, until 25 weeks of age. Changes in lifespan, clinical and metabolic parameters were evaluated as well as atherosclerosis and heart injury. In comparison to male ApoE -/- , male ApoE -/- :Ins2 +/Akita mice presented with chronic hyperglycemia (30.8 ± 1.2 mM vs. 9.3 ± 0.5 mM) accompanied by extremely high levels of total plasma cholesterol (49.3 ± 6.3 mM vs. 30.1 ± 1.5 mM) and triglycerides (11.6 ± 1.7 mM vs. 2.36 ± 0.18 mM). These mice have atherosclerosis at multiple vascular sites, including aortic sinus, ascending and descending aorta, brachiocephalic artery and coronary arteries. In addition, myocardial infarcts and a significant reduction of the lifespan (close to 20% of survival vs. other groups) were observed. Distinctively, both strains of female mice presented a parallel increase in plasma lipids, atherosclerosis, and no effects on mortality. We have established a diabetic mouse model, the western-diet-fed male ApoE -/- :Ins2 +/Akita mouse, with profound cardiovascular disease involving extensive atherosclerosis, coronary artery disease and myocardial infarct resulting in shortened lifespan. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Suppression of Coronary Atherosclerosis by Helix B Surface Peptide, a Nonerythropoietic, Tissue-Protective Compound Derived from Erythropoietin

    PubMed Central

    Ueba, Hiroto; Shiomi, Masashi; Brines, Michael; Yamin, Michael; Kobayashi, Tsutomu; Ako, Junya; Momomura, Shin-ichi; Cerami, Anthony; Kawakami, Masanobu

    2013-01-01

    Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. PMID:23648638

  12. [Cumulative effect of Coriolis acceleration on coronary hemodynamics].

    PubMed

    Lapaev, E V; Bednenko, V S

    1985-01-01

    Time-course variations in coronary circulation and cardiac output were measured in 29 healthy test subjects who performed tests with a continuous cumulation of Coriolis accelerations and in 12 healthy test subjects who were exposed to Coriolis accelerations combined with acute hypoxia. Adaptive changes in coronary circulation were seen. It is recommended to monitor coronary circulation during vestibulometric tests as part of medical expertise of the flying personnel.

  13. Thrombolysis in myocardial infarction frame count in coronary arteries without visible atherosclerosis in coronary angiography of patients with stable coronary artery disease.

    PubMed

    Tacoy, Gulten A; Yazici, Guliz E; Kocaman, Sinan A; Ozdemir, Murat H

    2009-06-01

    To investigate the thrombolysis in myocardial infarction (TIMI) frame count (TFC) in the coronary arteries without visible atherosclerosis in coronary angiography of patients with stable coronary artery disease (CAD). Eighty-three patients (mean age 58+/-10, 31 [37%] males), who underwent coronary angiographic evaluation for stable angina in Gazi University, Ankara, Turkey, Cardiology clinic between 2006-2007 were enrolled. Forty patients with normal coronary arteries were defined as group I. Group II consisted of 43 patients, who have one normal coronary artery in the setting of stable CAD defined as stenoses 50% or greater in at least one major coronary artery. Coronary blood flow and microvascular perfusion was evaluated by TFC. In group II, the TFC of left anterior descending artery (LAD) in 15 patients, TFC of circumflex artery (CX) in 18 patient, and TFC of right coronary artery (RCA) in 10 patients were evaluated. In group II, the TFC of LAD (37+/-12 versus 29+/-12, p=0.015) and CX (22+/-8 versus 18+/-9, p=0.035) were significantly higher than those in group I. The TFC of RCA was similar between groups (17+/-9 versus 17+/-8, p=0.990). After the adjustment of the risk factors by multivariate regression analyses, the association between TFC and clinical characteristic was statistically non-significant. The TFC decreased in angiographically normal LAD and CX arteries in the setting of stable angina pectoris. The important predictor was CAD alone, irrespective of the clinical parameters.

  14. Monocyte Chemoattractant Protein-1 as a Predictor of Coronary Atherosclerosis in Patients Receiving Coronary Angiography.

    PubMed

    Mahler, Simon A; Register, Thomas C; Riley, Robert F; D'Agostino, Ralph B; Stopyra, Jason P; Miller, Chadwick D

    2018-06-01

    Animal studies suggest that monocyte chemoattractant protein-1 (MCP-1) is a promising biomarker for coronary artery atherosclerosis (CAA), but human studies have been inconclusive. To determine potential relationships between plasma MCP-1 and CAA in patients with acute chest pain. A secondary analysis of 150 patients enrolled in emergency department chest pain risk stratification clinical investigations was conducted. Participants with stored blood and known coronary phenotypes (determined by coronary angiography) were selected using stratified randomization such that 50 patients were included into 3 groups: (1) no angiographic evidence of CAA, (2) nonobstructive CAA, and (3) obstructive CAA (stenosis ≥ 70%). Plasma MCP-1 levels were determined by enzyme-linked immunosorbent assay. The association between MCP-1 and obstructive CAA or any CAA was modeled using logistic regression. Variables in the unreduced model included age, sex, race, prior diagnosis of CAA or acute coronary syndrome, hyperlipidemia, hypertension, diabetes, smoking, and cardiac troponin I measurement. Among the 150 participants, 65.3% (98/150) had invasive coronary angiography and 34.7% (52/150) had coronary computed tomographic angiography. Myocardial infarction occurred in 27.3% (41/150) and coronary revascularization occurred in 26% (39/150) of the participants. Each 10 pg/mL increase in MCP-1 measurement was associated with an odds ratio of 1.12 (95% confidence interval, 1.06-1.19) for obstructive CAA. MCP-1 remained a significant predictor of obstructive CAA and any CAA after adjustment for age, sex, race, traditional cardiac risk factors, and cardiac troponin I. MCP-1 is independently associated with CAA among emergency department patients with chest pain.

  15. Association Between Coronary Artery Disease Genetic Variants and Subclinical Atherosclerosis: An Association Study and Meta-analysis.

    PubMed

    Zabalza, Michel; Subirana, Isaac; Lluis-Ganella, Carla; Sayols-Baixeras, Sergi; de Groot, Eric; Arnold, Roman; Cenarro, Ana; Ramos, Rafel; Marrugat, Jaume; Elosua, Roberto

    2015-10-01

    Recent studies have identified several genetic variants associated with coronary artery disease. Some of these genetic variants are not associated with classical cardiovascular risk factors and the mechanism of such associations is unclear. The aim of the study was to determine whether these genetic variants are related to subclinical atherosclerosis measured by carotid intima media thickness, carotid stiffness, and ankle brachial index. A cross-sectional study nested in the follow-up of the REGICOR cohort was undertaken. The study included 2667 individuals. Subclinical atherosclerosis measurements were performed with standardized methods. Nine genetic variants were genotyped to assess associations with subclinical atherosclerosis, individually and in a weighted genetic risk score. A systematic review and meta-analysis of previous studies that analyzed these associations was undertaken. Neither the selected genetic variants nor the genetic risk score were significantly associated with subclinical atherosclerosis. In the meta-analysis, the rs1746048 (CXCL12; n = 10581) risk allele was directly associated with carotid intima-media thickness (β = 0.008; 95% confidence interval, 0.001-0.015), whereas the rs6725887 (WDR12; n = 7801) risk allele was inversely associated with this thickness (β = -0.013; 95% confidence interval, -0.024 to -0.003). The analyzed genetic variants seem to mediate their association with coronary artery disease through different mechanisms. Our results generate the hypothesis that the CXCL12 variant appears to influence coronary artery disease risk through arterial remodeling and thickening, whereas the WDR12 risk variant could be related to higher plaque vulnerability. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population.

    PubMed

    Gómez, Miquel; Vila, Joan; Elosua, Roberto; Molina, Lluís; Bruguera, Jordi; Sala, Joan; Masià, Rafel; Covas, Maria Isabel; Marrugat, Jaume; Fitó, Montserrat

    2014-01-01

    To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis. Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02-2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Relationship between left main coronary artery plaque burden and nonleft main coronary atherosclerosis: results from the PROSPECT study.

    PubMed

    Shimizu, Takehisa; Mintz, Gary S; De Bruyne, Bernard; Farhat, Naim Z; Inaba, Shinji; Cao, Yang; Marso, Steven P; Weisz, Giora; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

    2018-05-17

    Whether the severity of left main coronary artery (LMCA) disease reflects LMCA and overall coronary atherosclerotic burden is not known. We aimed to assess nonculprit LMCA disease characteristics and the relationship with atherosclerosis in the rest of the coronary arteries as well as patient outcomes. In the PROSPECT study, 697 patients with acute coronary syndromes underwent three-vessel gray-scale and radiofrequency intravascular ultrasound after percutaneous coronary intervention. Overall, 552 patients with adequate LMCA imaging were compared according to LMCA plaque burden. The tertile with the highest plaque burden in the LMCA had the smallest LMCA minimum lumen area (17.4, 14.2, 10.5, lowest through highest tertiles, respectively, P<0.0001) and the greatest percent necrotic core volume (2.8, 5.6, 9.5%, lowest through highest tertiles, respectively, P<0.0001). Furthermore, the tertile with the highest plaque burden was also significantly associated with the highest overall non-LMCA percent atheroma volume within the major epicardial arteries (48.3, 49.2, 50.8%, lowest through highest tertiles, respectively, P<0.0001). After adjusting for patient background, the LMCA plaque burden was independently associated with non-LMCA percent atheroma volume (P=0.003). Of the three PROSPECT predictors of future nonculprit major adverse cardiac events (MACE) (minimum lumen area≤4 mm, plaque burden≥70%, and virtual histology thin-cap fibroatheroma), the tertile with the highest LMCA plaque burden had the highest number of patients with at least one of three PROSPECT predictors (P=0.03). In multivariable model, though total atheroma volume (per 1%) was an independent predictor of all MACE [hazard ratio (95% confidence interval)=1.06 (1.01-1.11), P=0.02] and strong trend for non-culprit-related MACE [hazard ratio (95% confidence interval)=1.06 (1.00-1.13), P=0.06], plaque burden at LMCA was not (all MACE, P=0.90, non-culprit-related MACE, P=0.85). The severity of

  18. Prevention and treatment of atherosclerosis with flaxseed-derived compound secoisolariciresinol diglucoside.

    PubMed

    Prasad, Kailash; Jadhav, Ashok

    2016-01-01

    Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease

  19. The Association of Pericardial Fat with Coronary Artery Plaque Index at MR Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Miao, Cuilian; Chen, Shaoguang; Ding, Jingzhong; Liu, Kiang; Li, Debiao; Macedo, Robson; Lai, Shenghan; Vogel-Claussen, Jens; Brown, Elizabeth R.; Lima, João A. C.

    2011-01-01

    Purpose: To determine the relationship of pericardial fat, which secretes proinflammatory markers that have been implicated in coronary atherosclerosis, with atherosclerotic plaque in an asymptomatic population–based cohort. Materials and Methods: In this institutional review board–approved study, all participants supplied written informed consent. One hundred eighty-three participants (89 women, 94 men; mean age, 61 years ± 9 [standard deviation]) from the community-based Multi-Ethnic Study of Atherosclerosis (MESA) were included. The coronary artery eccentricity (ratio of maximal to minimal coronary artery wall thickness) was determined by using magnetic resonance (MR) imaging and served as an index of plaque burden. The pericardial fat volume was determined by using computed tomography. Linear regression coefficient analysis was used to correlate pericardial fat volume with coronary artery wall thickness and plaque eccentricity. Results: Pericardial fat volume correlated significantly with degree of plaque eccentricity (P < .05) in both men and women. After adjustments for body mass index (BMI) and waist circumference, traditional risk factors, C-reactive protein level, and coronary artery calcium content, the relationship between pericardial fat and plaque eccentricity remained significant in men (P < .01) but not in women. BMI and waist circumference correlated with degree of plaque eccentricity in the univariate model (P < .05) but not after adjustment for pericardial fat volume or traditional risk factors. Conclusion: Pericardial fat volume, rather than BMI and waist circumference, was more strongly related to plaque eccentricity as a measure of coronary atherosclerotic plaque burden. The results support the proposed role of pericardial fat in association with atherosclerosis. © RSNA, 2011 PMID:21846753

  20. [Combination treatment with coenzyme Q10 and simvastatin in patients with coronary atherosclerosis].

    PubMed

    Chapidze G E; Kapanadze, S D; Dolidze, N K; Latsabidze, N E; Bakhutashvili, Z V

    2006-01-01

    In order to assess efficacy of one of natural antioxidants--coenzyme Q10 (90 mg daily) and its combination with simvastatin (10 mg daily) 44 outpatients with coronary atherosclerosis were examined. Twenty four patients had undergone coronary artery bypass surgery, 12--coronary angioplasty and in 8 coronary heart disease was confirmed by angiography. Duration of treatment was 12 weeks. Positive effects of coenzyme Q10 was particularly expressed in relation to antiatherogenic fraction of cholesterol which increased by 23%. Index of atherogenicity decreased by 27%. At the background of coenzyme Q10 treatment 30% reduction in plasma lipoperoxide levels occurred demonstrating potentially independent role of coenzyme Q10 in positive modification of oxidative stress. Coenzyme Q10 revealed antiaggregatory ability. It was not related to the improvement of endothelial function. Normalization of plasma nitric oxide concentrations was achieved only with combination of coenzyme Q10 and simvastatin. This fact may be explained by positive action of statins on endothelial function.

  1. Coronary calcification in SLE: comparison with the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Kiani, Adnan N; Magder, Laurence S; Post, Wendy S; Szklo, Moyses; Bathon, Joan M; Schreiner, Pam J; O'Leary, Daniel; Petri, Michelle

    2015-11-01

    Accelerated atherosclerosis is a major cause of morbidity and death in SLE. The purpose of this study was to determine whether the prevalence and extent of coronary artery calcium (CAC) is higher in female SLE patients compared with a non-SLE sample from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC was measured in 80 female SLE patients and 241 female MESA controls from the Baltimore Field Centre, ages 45-64 years, without evidence of clinical cardiovascular disease. Binary regression was used to estimate the ratio of CAC prevalence in SLE vs MESA controls, controlling for demographic and cardiovascular risk factors. To compare the groups with respect to the quantity of CAC among those with non-zero Agatston scores, we used linear models in which the outcome was a log-transformed Agatston score. The prevalence of CAC was substantially higher in SLE. The differences were most pronounced and statistically significant in those aged 45-54 years (58% vs 20%, P < 0.0001), but were still observed among those aged 55-65 years (57% vs 36%, P = 0.069). After controlling for age, ethnicity, education, income, diabetes mellitus, hypertension, hyperlipidaemia, high-density lipoprotein levels, smoking, education and BMI, SLE patients still had a significantly higher prevalence of CAC than controls. Among those with CAC, the mean log Agatston score did not differ significantly between SLE and MESA participants. Women with SLE have a higher prevalence of CAC than comparable women without SLE, even after adjusting for traditional cardiovascular risk factors, especially among those aged 45-54 years. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

  2. Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins.

    PubMed

    Chapidze, G; Kapanadze, S; Dolidze, N; Bachutashvili, Z; Latsabidze, N

    2005-01-01

    The goal of the present research was to assess the efficacy of combination treatment with antioxidant coenzyme Q10 and simvastatin as well as coenzyme Q10 without statin therapy in order to prevent coronary atherosclerosis. 42 outpatients were divided into 2 groups: receiving coenzyme Q10 (Hasco-Lek, Poland) 60mg daily and its combination with simvastatin (zocor, vasilip) 10mg daily for an 8-week period. The treatment with coenzyme Q10 demonstrated its potential independent role in positive modification of oxidative stress, antiatherogenic fraction of lipid profile, atherogenic ratio, platelet aggregability. Taking into consideration the obtained results the study supports the use of coenzyme Q10 in combination with statins. Suggested attractive approach may result in complete correction of dislipidemia, reverse of endothelial dysfunction, reduce degree of oxidative stress and platelet aggregability. Consequently such a combination may be beneficial in preventing of further development of atherosclerosis in native coronary arteries as well as in bypass grafts in all coronary heart disease patients with or without myocardial revascularization.

  3. Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

    PubMed Central

    Bruemmer, Dennis; Collins, Alan R.; Noh, Grace; Wang, Wei; Territo, Mary; Arias-Magallona, Sarah; Fishbein, Michael C.; Blaschke, Florian; Kintscher, Ulrich; Graf, Kristof; Law, Ronald E.; Hsueh, Willa A.

    2003-01-01

    Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in diabetic patients. To determine the role of OPN in atherogenesis, ApoE–/–OPN+/+, ApoE–/–OPN+/–, and ApoE–/–OPN–/– mice were infused with Ang II, inducing vascular OPN expression and accelerating atherosclerosis. Compared with ApoE–/–OPN+/+ mice, ApoE–/–OPN+/– and ApoE–/–OPN–/– mice developed less Ang II–accelerated atherosclerosis. ApoE–/– mice transplanted with bone marrow derived from ApoE–/–OPN–/– mice had less Ang II–induced atherosclerosis compared with animals receiving ApoE–/–OPN+/+ cells. Aortae from Ang II–infused ApoE–/–OPN–/– mice expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to intraperitoneal thioglycollate, recruitment of leukocytes in OPN–/– mice was impaired, and OPN–/– leukocytes exhibited decreased basal and MCP-1–directed migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang II–infused ApoE–/–OPN–/– mice was decreased. Finally, Ang II–induced abdominal aortic aneurysm formation in ApoE–/–OPN–/– mice was reduced and associated with decreased MMP-2 and MMP-9 activity. These data suggest an important role for leukocyte-derived OPN in mediating Ang II–accelerated atherosclerosis and aneurysm formation. PMID:14597759

  4. Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

    PubMed

    Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

    2015-04-01

    The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min. In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Brachial artery vasoreactivity is associated with cross-sectional and longitudinal anatomical measures of atherosclerosis in postmenopausal women with coronary artery disease

    PubMed Central

    Gatto, Nicole M.; Hodis, Howard N.; Liu, Chao-Ran; Liu, Chi-Hua; Mack, Wendy J.

    2009-01-01

    Background The diagnostic and prognostic importance of brachial artery flow-mediated dilation (BFMD) for cardiovascular disease (CVD) is not certain and associations between BFMD and recognized measures of atherosclerosis have not been well established. Methods We investigated cross-sectional and longitudinal correlations between repeated measures of BFMD and quantitative coronary artery angiographic (QCA) measurements of average percent diameter stenosis, number of lesions and minimum luminal diameter (MLD), and ultrasonographic measurement of carotid artery intima-media thickness (CIMT) in an ethnically diverse cohort of postmenopausal women (n = 132) with coronary artery disease (CAD). Subjects were participants in a 3-year randomized, placebo-controlled clinical trial, testing the efficacy of hormone therapy on atherosclerosis progression. Associations between BFMD and QCA measures, and between BFMD and CIMT were examined using measurements from the same study visit. Results BFMD was significantly inversely correlated with coronary artery stenosis at baseline (β = −1.21% [S.E.(β) = 0.38], p = 0.002). BFMD levels significantly predicted rate of change in CIMT over the trial period (β = −0.76 μm/year [S.E.(β) = 0.29], p = 0.008). Conclusions Physiological and anatomical measures of atherosclerosis are correlated among postmenopausal women with CAD, which provides some validation of BFMD as a measure of atherosclerosis in high-risk populations. PMID:17803999

  6. Methamphetamine-associated acute myocardial infarction and cardiogenic shock with normal coronary arteries: refractory global coronary microvascular spasm.

    PubMed

    Chen, Jack P

    2007-04-01

    Methamphetamine (MET) is a growing public health concern and is prevalent in, although not limited to, the youth. The drug's association with myocardial infarction is well described and is attributed to accelerated atherosclerosis, hypercoagulable state, and macrovascular epicardial coronary spasm. However, global slow-flow of all coronary systems in the absence of significant stenoses has not been previously reported. We hereby present a young patient who likely experienced severe, global microvascular coronary spasm unrelieved by intracoronary vasodilator therapy, resulting in acute myocardial infarction. The pharmacology of MET, its postulated mechanism in acute coronary syndromes, as well as the pathophysiology and treatments of microvascular coronary spasm are briefly reviewed. Readers are recommended to be vigilant of potential illicit drug use in patients with atypical presentations of acute coronary syndromes.

  7. 2013 ACC/AHA versus 2004 NECP ATP III Guidelines in the Assignment of Statin Treatment in a Korean Population with Subclinical Coronary Atherosclerosis.

    PubMed

    Jung, Chang Hee; Lee, Min Jung; Kang, Yu Mi; Yang, Dong Hyun; Kang, Joon-Won; Kim, Eun Hee; Park, Duk-Woo; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

    2015-01-01

    The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asian population remains controversial. In this study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines is better aligned with the presence of subclinical coronary atherosclerosis detected by CCTA (coronary computed tomography angiography) compared to the previously recommended 2004 NCEP ATP III guidelines. We collected the data from 5,837 asymptomatic subjects who underwent CCTA using MDCT during routine health examinations. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy according to the 2013 ACC/AHA and 2004 NCEP ATP III guidelines. We defined the presence and severity of subclinical coronary atherosclerosis detected in CCTA according to the presence of significant coronary artery stenosis (defined as >50% stenosis), plaques, and the degree of coronary calcification. As compared to the 2004 ATP III guidelines, a significantly higher proportion of subjects with significant coronary stenosis (61.8% vs. 33.8%), plaques (52.3% vs. 24.7%), and higher CACS (CACS >100, 63.6% vs. 26.5%) was assigned to statin therapy using the 2013 ACC/AHA guidelines (P < .001 for all variables). The area under the curves of the pooled cohort equation of the new guidelines in detecting significant stenosis, plaques, and higher CACS were significantly higher than those of the Framingham risk calculator. Compared to the previous ATP III guidelines, the 2013 ACC/AHA guidelines were more sensitive in identifying subjects with subclinical coronary atherosclerosis detected by CCTA in an Asian population.

  8. Atherosclerosis and leukocyte-endothelial adhesive interactions are increased following acute myocardial infarction in apolipoprotein E deficient mice.

    PubMed

    Wright, Andrew P; Öhman, Miina K; Hayasaki, Takanori; Luo, Wei; Russo, Hana M; Guo, Chiao; Eitzman, Daniel T

    2010-10-01

    To determine the effect of myocardial infarction (MI) on progression of atherosclerosis in apolipoprotein E deficient (ApoE-/-) mice. MI was induced following left anterior descending coronary artery (LAD) ligation in wild-type (WT) (n=9) and ApoE-/- (n=25) mice. Compared to sham-operated animals, MI mice demonstrated increased intravascular leukocyte rolling and firm adhesion by intravital microscopy, reflecting enhanced systemic leukocyte-endothelial interactions. To determine if MI was associated with accelerated atherogenesis, LAD ligation was performed in ApoE-/- mice. Six weeks following surgery, atherosclerosis was quantitated throughout the arterial tree by microdissection and Oil-Red-O staining. There was 1.6-fold greater atherosclerotic burden present in ApoE-/- MI mice compared to sham-operated mice. Acute MI accelerates atherogenesis in mice. These results may be related to the increased risk of recurrent ischemic coronary events following MI in humans. Published by Elsevier Ireland Ltd.

  9. [Association between IGF system and PAPP-A in coronary atherosclerosis].

    PubMed

    Fierro-Macías, Alfonso Eduardo; Floriano-Sánchez, Esaú; Mena-Burciaga, Victoria Michelle; Gutiérrez-Leonard, Hugo; Lara-Padilla, Eleazar; Abarca-Rojano, Edgar; Fierro-Almanzán, Alfonso Edmundo

    2016-01-01

    Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  10. Multi-Ethnic Study of Atherosclerosis (MESA)

    ClinicalTrials.gov

    2016-07-28

    Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Coronary Disease; Stroke; Myocardial Infarction; Heart Failure; Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

  11. Coronary atherosclerosis burden is not advanced in patients with β-thalassemia despite premature extracardiac atherosclerosis: a coronary artery calcium score and carotid intima-media thickness study.

    PubMed

    Hahalis, George; Zacharioglou, Evangelia; Xanthopoulou, Ioanna; Koniari, Ioanna; Kalogeropoulou, Chistina; Tsota, Irene; Rigopoulou, Aspasia; Diamantopoulos, Athanasios; Gkizas, Vasilios; Davlouros, Periklis; Akinosoglou, Karolina; Leopoulou, Marianna; Gogos, Charalampos; Alexopoulos, Dimitrios

    2016-02-01

    Thalassemic patients demonstrate an increased rate of extracardiac vascular complications and increased carotid wall intima-media thickness (cIMT), but very low prevalence of coronary artery disease (CAD). We investigated the atheroma burden by assessing the coronary artery calcium (CAC) and cIMT in these patients. We examined 37 patients with β-thalassemia and 150 healthy control volunteers with multi-detector computer tomography (CT) and ultrasonography to determine CAC score and cIMT, respectively. Propensity score matching (C-statistic: 0.88; 95% CI: 0.83-0.93) resulted in 27 pairs of patients; severe CAC was observed in 2 (7.4%) and 0 of β-thalassemia patients and healthy volunteers respectively (P = 0.5). Median calcium score was 0 (0-0) in β-thalassemia patients and 0 (0-4) in healthy volunteers (P = 0.8). Median intima-media thickness was higher in β-thalassemia patients compared to control group [0.45 (0.06-0.65) vs. 0.062 (0.054-0.086); P = 0.04]. Patients with β-thalassemia in comparison with healthy control subjects exhibit similar CAC score and increased cIMT. Our findings indicate a disparate rate of progression of atherosclerosis between coronary and extracardiac arteries in these patients lending support to the epidemiological evidence.

  12. 2013 ACC/AHA versus 2004 NECP ATP III Guidelines in the Assignment of Statin Treatment in a Korean Population with Subclinical Coronary Atherosclerosis

    PubMed Central

    Kang, Yu Mi; Yang, Dong Hyun; Kang, Joon-Won; Kim, Eun Hee; Park, Duk-Woo; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

    2015-01-01

    Background The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asian population remains controversial. In this study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines is better aligned with the presence of subclinical coronary atherosclerosis detected by CCTA (coronary computed tomography angiography) compared to the previously recommended 2004 NCEP ATP III guidelines. Methods We collected the data from 5,837 asymptomatic subjects who underwent CCTA using MDCT during routine health examinations. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy according to the 2013 ACC/AHA and 2004 NCEP ATP III guidelines. We defined the presence and severity of subclinical coronary atherosclerosis detected in CCTA according to the presence of significant coronary artery stenosis (defined as >50% stenosis), plaques, and the degree of coronary calcification. Results As compared to the 2004 ATP III guidelines, a significantly higher proportion of subjects with significant coronary stenosis (61.8% vs. 33.8%), plaques (52.3% vs. 24.7%), and higher CACS (CACS >100, 63.6% vs. 26.5%) was assigned to statin therapy using the 2013 ACC/AHA guidelines (P < .001 for all variables). The area under the curves of the pooled cohort equation of the new guidelines in detecting significant stenosis, plaques, and higher CACS were significantly higher than those of the Framingham risk calculator. Conclusions Compared to the previous ATP III guidelines, the 2013 ACC/AHA guidelines were more sensitive in identifying subjects with subclinical coronary atherosclerosis detected by CCTA in an Asian population. PMID:26372638

  13. A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic

    PubMed Central

    Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Z. Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Miranda, Marie Lynn; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.

    2017-01-01

    Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk. PMID:28355232

  14. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease

    PubMed Central

    Fernández-Hernando, Carlos; Ackah, Eric; Yu, Jun; Suárez, Yajaira; Murata, Takahisa; Iwakiri, Yasuko; Prendergast, Jay; Miao, Robert Q.; Birnbaum, Morris J.; Sessa, William C.

    2013-01-01

    SUMMARY The Akt signaling pathway controls several cellular functions in the cardiovascular system; however, its role in atherogenesis is unknown. Here we show that the genetic ablation of Akt1 on an apolipoprotein E knockout background (ApoE−/−Akt1−/−) increases aortic lesion expansion and promotes coronary atherosclerosis. Mechanistically, lesion formation is due to enhanced expression of pro-inflammatory genes and endothelial cell and macrophage apoptosis. Bone marrow transfer experiments suggest that macrophages from ApoE−/−Akt1−/− donors were not sufficient to worsen atherogenesis when transferred to ApoE−/− recipients suggesting that lesion expansion in the ApoE−/− Akt1−/ strain may be of vascular origin. In the vessel wall, the loss of Akt1 increases inflammatory mediators and reduces eNOS phosphorylation suggesting that Akt1 exerts vascular protection against atherogenesis. The presence of coronary lesions in ApoE−/−/Akt1−/− mice provides a new model for studying the mechanisms of acute coronary syndrome in humans. PMID:18054314

  15. Atherosclerosis in the Erythrocebus patas, an old world monkey.

    PubMed Central

    Mahley, R. W.; Johnson, D. K.; Pucak, G. J.; Fry, D. L.

    1980-01-01

    Fifty monkeys of the species Erythrocebus patas were fed a control monkey chow, a semi-synthetic diet containing 25% lard, or a semisynthetic diet containing 25% lard and 0.5% cholesterol for 2 years. The patas monkeys had naturally occurring atherosclerosis that was greatly accelerated by feeding a diet containing cholesterol. The atherosclerosis involved the aorta, predominantly the abdominal portion, the coronary arteries, and various peripheral vessels. Histologically, the atherosclerosis was characterized by intimal proliferative lesions associated with intra- and extracellular lipid deposition. Complicated lesions that developed after 2 years on the cholesterol-containing diet were associated with lipid crystals, necrosis, mineralization, and encroachment upon the media. Adventitial reactions characterized by increased vascularity and the presence of inflammatory cells were seen. All of these observations have been described as components of the human atherosclerotic disease process. The similarity of the patas monkey atherosclerosis to human atherosclerosis, the relatively large size and easy handling of the animals, and the fact that previous studies have shown the lipoproteins of both control and cholesterol-fed monkeys to resemble human lipoproteins all contribute to making the patas monkey a useful model for the study of experimental atherosclerosis. Images Figure 1-5 Figure 6 Figure 7-10 Figure 11 Figure 12 PMID:6766672

  16. PDGFRβ signaling regulates local inflammation and synergizes with hypercholesterolemia to promote atherosclerosis

    PubMed Central

    He, Chaoyong; Medley, Shayna C.; Hu, Taishan; Hinsdale, Myron E.; Lupu, Florea; Virmani, Renu; Olson, Lorin E.

    2015-01-01

    Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (VSMCs). However, the direct effects of PDGF receptor β (PDGFRβ) activation on VSMCs have not been studied in the context of atherosclerosis. Here, we present a new mouse model of atherosclerosis with an activating mutation in PDGFRβ. Increased PDGFRβ signaling induces chemokine secretion and leads to leukocyte accumulation in the adventitia and media of the aorta. Furthermore, PDGFRβD849V amplifies and accelerates atherosclerosis in hypercholesterolemic ApoE−/− or Ldlr−/− mice. Intriguingly, increased PDGFRβ signaling promotes advanced plaque formation at novel sites in the thoracic aorta and coronary arteries. However, deletion of the PDGFRβ-activated transcription factor STAT1 in VSMCs alleviates inflammation of the arterial wall and reduces plaque burden. These results demonstrate that PDGFRβ pathway activation has a profound effect on vascular disease and support the conclusion that inflammation in the outer arterial layers is a driving process for atherosclerosis. PMID:26183159

  17. Molecular intravascular imaging approaches for atherosclerosis.

    PubMed

    Press, Marcella Calfon; Jaffer, Farouc A

    2014-10-01

    Coronary artery disease (CAD) is an inflammatory process that results in buildup of atherosclerosis, typically lipid-rich plaque in the arterial wall. Progressive narrowing of the vessel wall and subsequent plaque rupture can lead to myocardial infarction and death. Recent advances in intravascular fluorescence imaging techniques have provided exciting coronary artery-targeted platforms to further characterize the molecular changes that occur within the vascular wall as a result of atherosclerosis and following coronary stent-induced vascular injury. This review will summarize exciting recent developments in catheter-based imaging of coronary arterial-sized vessels; focusing on two-dimensional near-infrared fluorescence imaging (NIRF) molecular imaging technology as an approach to specifically identify inflammation and fibrin directly within coronary artery-sized vessels. Intravascular NIRF is anticipated to provide new insights into the in vivo biology underlying high-risk plaques, as well as high-risks stents prone to stent restenosis or stent thrombosis.

  18. Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: a 3-dimensional cardiac computed tomography imaging study in Japanese subjects.

    PubMed

    Dagvasumberel, Munkhbaatar; Shimabukuro, Michio; Nishiuchi, Takeshi; Ueno, Junji; Takao, Shoichiro; Fukuda, Daiju; Hirata, Yoichiro; Kurobe, Hirotsugu; Soeki, Takeshi; Iwase, Takashi; Kusunose, Kenya; Niki, Toshiyuki; Yamaguchi, Koji; Taketani, Yoshio; Yagi, Shusuke; Tomita, Noriko; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Harada, Masafumi; Kitagawa, Tetsuya; Sata, Masataka

    2012-09-10

    Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis. The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group. EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia. Increased EATV is strongly associated with coronary atherosclerosis in men.

  19. Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: A 3-dimensional cardiac computed tomography imaging study in Japanese subjects

    PubMed Central

    2012-01-01

    Background Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis. Methods The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group. Results EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia. Conclusions Increased EATV is strongly associated with coronary atherosclerosis in men. PMID:22963346

  20. Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

    USDA-ARS?s Scientific Manuscript database

    While animal studies found vitamin K treatment reduced vascular calcification, human data are limited. Using a case-cohort design, we determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-ethnic Study of Atherosclerosis. Serum phylloquinone (v...

  1. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).

    PubMed

    Liang, C Jason; Budoff, Matthew J; Kaufman, Joel D; Kronmal, Richard A; Brown, Elizabeth R

    2012-07-02

    Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

  2. Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

    PubMed

    Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

    2017-09-01

    Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

  3. Ten-year trends in coronary calcification in individuals without clinical cardiovascular disease in the multi-ethnic study of atherosclerosis.

    PubMed

    Bild, Diane E; McClelland, Robyn; Kaufman, Joel D; Blumenthal, Roger; Burke, Gregory L; Carr, J Jeffrey; Post, Wendy S; Register, Thomas C; Shea, Steven; Szklo, Moyses

    2014-01-01

    Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known. To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55-84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000-02, 50.4% in 2003-04, 60.0% is 2005-06, 57.4% in 2007-08, and 61.3% in 2010-12 (p for trend <0.001). The trend was strongest among African Americans aged 55-64 [prevalence ratio for 2010-12 vs. 2000-02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence. There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.

  4. High-intensity statin therapy and regression of coronary atherosclerosis in patients with diabetes mellitus.

    PubMed

    Athyros, Vasilios G; Katsiki, Niki; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2015-01-01

    Recommended low-density lipoprotein cholesterol (LDL-C) levels for patients with documented cardiovascular disease (CVD) are <100mg/dL (2.6mmol/l) with further reduction to <70mg/dL (1.8mmol/l) for higher-risk patients. High-intensity statin treatment may halt the progression as well as stabilize and induce regression of coronary atheromatous plaques while lowering CVD event rates. Diabetes mellitus (DM) is a major negative determinant of coronary artery plaque regression during statin therapy. However, regression of coronary atherosclerosis in DM patients is feasible to the same degree as in those without DM when very low LDL-C values (<70mg/dL; 1.8mmol/l) are achieved with high intensity statin treatment. The recent 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults suggest to abandon specific LDL-C treatment targets. This strategy may deprive high risk patients, such as those with DM, from very high intensity statin treatment or drug combinations aiming to achieve very low LDL-C levels in order to reduce clinical events. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Coronary Artery Disease | Coronary Artery Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Coronary Artery Disease Coronary Artery Disease Past Issues / Fall 2010 Table of Contents David ... up inside your arteries. One atherosclerosis-related disease, coronary artery disease (CAD) is the most common heart disease and ...

  6. Carotid Intima-Media Thickness and Coronary Artery Calcium Score as Indications of Subclinical Atherosclerosis

    PubMed Central

    Lester, Steven J.; Eleid, Mackram F.; Khandheria, Bijoy K.; Hurst, R. Todd

    2009-01-01

    OBJECTIVE: To determine the ability of carotid intima-media thickness (CIMT) and coronary artery calcium score (CACS) to detect subclinical atherosclerosis in a young to middle-aged, low-risk, primary-prevention population. PATIENTS AND METHODS: Patients aged 36 to 59 years who underwent determination of CIMT and CACS at our institution between May 1, 2004, and April 1, 2008, were included in the study. Those with diabetes mellitus or a history of coronary, peripheral, or cerebral vascular disease were excluded. Other information, such as Framingham risk score (FRS), was obtained by a review of clinical and laboratory data. RESULTS: Of 118 patients, 89 (75%) had a CACS of zero and 94 (80%) were men; mean ± SD age was 48.9±5.7 years. The mean FRS of this group was 4.0; 86 patients (97%) were considered at low risk (<1% annualized rate) of cardiovascular events. Evidence of carotid atherosclerosis was found in 42 (47%; 95% confidence interval, 37%-58%) of these 89 patients; carotid plaque was found in 30 (34%); and CIMT above the 75th percentile was found in 12 (13%) of age-, sex-, and race-matched control patients. Of the 40 patients with low-risk CIMT (below the 50th percentile), 4 (10%) had a CACS at or above the 50th percentile. CONCLUSION: Subclinical vascular disease can be detected by CIMT evaluation in young to middle-aged patients with a low FRS and a CACS of zero. These findings have important implications for vascular disease screening and the implementation of primary-prevention strategies. PMID:19252109

  7. Plaque Burden Influences Accurate Classification of Fibrous Cap Atheroma by In-Vivo Optical Coherence Tomography in a Porcine Model of Advanced Coronary Atherosclerosis.

    PubMed

    Poulsen, Christian B; Pedrigi, Ryan M; Pareek, Nilesh; Kilic, Ismail D; Holm, Niels Ramsing; Bentzon, Jacob F; Bøtker, Hans Erik; Falk, Erling; Krams, Rob; de Silva, Ranil

    2018-04-03

    In-vivo validation of coronary optical coherence tomography (OCT) against histology and the effects of plaque burden (PB) on plaque classification remain unreported. We investigated this in a porcine model with human-like coronary atherosclerosis. Five female Yucatan D374Y-PCSK9 transgenic hypercholesterolemic mini-pigs were implanted with a coronary shear-modifying stent to induce advanced atherosclerosis. OCT frames (n=201) were obtained 34 weeks after implantation. Coronary arteries were perfusion-fixed, serially sectioned and co-registered with OCT using a validated algorithm. Lesions were adjudicated using the Virmani classification and PB assessed from histology. OCT had a high sensitivity, but modest specificity (92.9% and 74.6%), for identifying fibrous cap atheroma (FCA). The reduced specificity for OCT was due to misclassification of plaques with histologically defined pathological intimal thickening (PIT) as FCA (46.1% of the frames with histological PIT were misclassified). PIT lesions misclassified as FCA by OCT had a statistically higher PB than in other OCT frames (median 32.0% versus 13.4%; p<0.0001). Misclassification of PIT lesions by OCT occurred when PB exceeded approximately 20%. Compared with histology, in-vivo OCT classification of FCA had high sensitivity but reduced specificity due to misclassification of PITs with high PB.

  8. Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study

    ClinicalTrials.gov

    2016-02-05

    Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial Infarction; Heart Diseases; Diabetes Mellitus, Non-insulin Dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus

  9. Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study: rationale and design.

    PubMed

    Nakanishi, Rine; Post, Wendy S; Osawa, Kazuhiro; Jayawardena, Eranthi; Kim, Michael; Sheidaee, Nasim; Nezarat, Negin; Rahmani, Sina; Kim, Nicholas; Hathiramani, Nicolai; Susarla, Shriraj; Palella, Frank; Witt, Mallory; Blaha, Michael J; Brown, Todd T; Kingsley, Lawrence; Haberlen, Sabina A; Dailing, Christopher; Budoff, Matthew J

    2018-01-01

    The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

  10. Relation of ABO Blood Groups to the Plaque Characteristic of Coronary Atherosclerosis.

    PubMed

    Huang, Xingtao; Zou, Yongpeng; Li, Lulu; Chen, Shuyuan; Hou, Jingbo; Yu, Bo

    2017-01-01

    The ABO blood types related to morphological characteristics of atherosclerosis plaque are not clear. We aimed to evaluate the relationship between ABO blood groups and the coronary plaque characteristic. We retrospectively identified the target lesions in 392 acute coronary syndrome patients who underwent optical coherence tomography examination before stenting. Subjects were divided into different groups according to different blood types. The fibrous cap thickness was significantly thicker in O type compared with non-O type (0.075 ± 0.033 mm versus 0.061 ± 0.024, p < 0.001). Meanwhile, the incidence of thin-cap fibroatheroma was also significantly higher in O type compared with non-O type (51.0% versus 71.5%, p < 0.001). The O type showed a significantly larger minimum lumen area [1.26 (0.82, 2.13) versus 1.05 (0.67, 1.82), p = 0.020] and minimum lumen diameter [1.03 (0.74, 1.31) versus 0.95 (0.66, 1.25), p = 0.039] compared with non-O type. There were no differences found in incidence of lipid plaque, plaque rupture, and thrombus between different blood type groups even between O type and non-O type group ( p > 0.05). The plaques of O type blood group were exhibited more stably compared with non-O type blood group. Moreover, the non-O type blood group have more serious coronary artery stenosis than O type blood group.

  11. Atherosclerosis in ancient Egyptian mummies: the Horus study.

    PubMed

    Allam, Adel H; Thompson, Randall C; Wann, L Samuel; Miyamoto, Michael I; Nur El-Din, Abd El-Halim; El-Maksoud, Gomaa Abd; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; El-Rahman Amer, Hany Abd; Sutherland, M Linda; Sutherland, James D; Thomas, Gregory S

    2011-04-01

    The purpose of this study was to determine whether ancient Egyptians had atherosclerosis. The worldwide burden of atherosclerotic disease continues to rise and parallels the spread of diet, lifestyles, and environmental risk factors associated with the developed world. It is tempting to conclude that atherosclerotic cardiovascular disease is exclusively a disease of modern society and did not affect our ancient ancestors. We performed whole body, multislice computed tomography scanning on 52 ancient Egyptian mummies from the Middle Kingdom to the Greco-Roman period to identify cardiovascular structures and arterial calcifications. We interpreted images by consensus reading of 7 imaging physicians, and collected demographic data from historical and museum records. We estimated age at the time of death from the computed tomography skeletal evaluation. Forty-four of 52 mummies had identifiable cardiovascular (CV) structures, and 20 of these had either definite atherosclerosis (defined as calcification within the wall of an identifiable artery, n = 12) or probable atherosclerosis (defined as calcifications along the expected course of an artery, n = 8). Calcifications were found in the aorta as well as the coronary, carotid, iliac, femoral, and peripheral leg arteries. The 20 mummies with definite or probable atherosclerosis were older at time of death (mean age 45.1 ± 9.2 years) than the mummies with CV tissue but no atherosclerosis (mean age 34.5 ± 11.8 years, p < 0.002). Two mummies had evidence of severe arterial atherosclerosis with calcifications in virtually every arterial bed. Definite coronary atherosclerosis was present in 2 mummies, including a princess who lived between 1550 and 1580 BCE. This finding represents the earliest documentation of coronary atherosclerosis in a human. Definite or probable atherosclerosis was present in mummies who lived during virtually every era of ancient Egypt represented in this study, a time span of >2,000 years

  12. Increased Th9 cells and IL-9 levels accelerate disease progression in experimental atherosclerosis.

    PubMed

    Li, Qing; Ming, Tingting; Wang, Yuanmin; Ding, Shaowei; Hu, Chaojie; Zhang, Cuiping; Cao, Qi; Wang, Yiping

    2017-01-01

    Atherosclerosis (AS) is the number one killer in developed countries, and currently considered a chronic inflammatory disease. The central role of T cells in the pathogenesis of atherosclerosis is well documented. However, little is known about the newly described T cell subset-Th9 cells and their role in AS pathogenesis. Here, the amounts of Th9 cells as well as their key transcription factors and relevant cytokines during atherosclerosis were assessed in ApoE -/- mice and age-matched C57BL/6J mice. Significantly increased Th9 cell number, Th9 related cytokine (IL-9), and key transcription factor (PU.1) were found in ApoE -/- mice compared with age-matched C57BL/6J mice. Additionally, treatment with rIL-9 accelerated atherosclerotic development, which was attenuated by anti-IL-9 antibodies. These data suggested that both Th9 cells and related IL-9 play key roles in the pathogenesis of atherosclerosis, and antibodies against these antigens offer a novel therapeutic approach in AS treatment.

  13. Activities of red blood cell anti-oxidative enzymes (SOD, GPx) and total anti-oxidative capacity of serum (TAS) in men with coronary atherosclerosis and in healthy pilots.

    PubMed

    Zawadzka-Bartczak, Ewelina

    2005-09-01

    Reactive oxygen species (ROS) have been proposed to play important pathogenic roles, especially in harmful oxidative modifications of low-density cholesterol. Redox balance within the organism is largely determined by the activities of anti-oxidative enzymes of red blood cells and by the total anti-oxidative capacity of the serum (TAS). SOD and GPx activities and TAS in 13 men aged 42-65 years with coronary atherosclerosis (group I) were compared with those of both 15 clinically healthy pilots matched for age and lipid abnormalities (cholesterol and triglycerides) (group II) and 14 age-matched pilots without lipid abnormalities (group III). There were statistically significant differences in SOD and GPx activities and in TAS between the groups. 1. SOD and GPx activities and TAS were lower in men with advanced coronary atherosclerosis that in age-matched clinically healthy men with similar dyslipidemia and were even further decreased compared with clinically healthy men without dyslipidemia. 2. The decrease in SOD and GPx activities and TAS in men with advanced coronary atherosclerosis was more pronounced than the degree of hypercholesterolemia or hypertriglyceridemia. 3. If hyperlipidemia and the activity of antioxidative enzymes and TAS were considered without reference to other risk factors of atherosclerosis, it appeared that the decreases in SOD, GPx, and TAS may play a more important role in the development of the atherosclerotic process than isolated increases in free cholesterol or triglyceride levels.

  14. Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.

    PubMed

    Tyynelä, Petri; Goebeler, Sirkka; Ilveskoski, Erkki; Mikkelsson, Jussi; Perola, Markus; Lehtimäki, Terho; Karhunen, Pekka J

    2013-05-01

    Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis. APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area. Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively. Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.

  15. Healthy Lifestyle Change and Subclinical Atherosclerosis in Young Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study

    PubMed Central

    Spring, Bonnie; Moller, Arlen C.; Colangelo, Laura A.; Siddique, Juned; Roehrig, Megan; Daviglus, Martha L.; Polak, Joseph F.; Reis, Jared P.; Sidney, Stephen; Liu, Kiang

    2015-01-01

    Background The benefits of healthy habits are well-established, but it is unclear whether making health behavior changes as an adult can still alter coronary artery disease risk. Methods and Results The Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study (n = 3538) assessed 5 healthy lifestyle factors (HLFs) among young adults between ages 18–30 (Year 0 baseline) and 20 years later (Year 20): not overweight/obese, low alcohol intake, healthy diet, physically active, nonsmoker. We tested whether change from Year 0 to 20 in a continuous composite HLF score (HLF change; range: −5 to +5) is associated with subclinical atherosclerosis [coronary artery calcification (CAC) and carotid intima-media thickness (IMT)] at Year 20, after adjustment for demographics, medications, and baseline HLFs. By Year 20, 25·3% of the sample improved (HLF change ≥ +1); 40·4% deteriorated (had fewer HLFs); 34·4% stayed the same; 19·2% had CAC (>0). Each increase in HLFs was associated with reduced odds of detectable CAC (OR = .85, 95% CI: .74 – .98) and lower IMT (carotid bulb β = −.024, p = 0.001), and each decrease in HLFs was predictive to a similar degree of greater odds of CAC (OR = 1.17, 95% CI: 1.02 – 1.33) and greater IMT (β = +.020, p < 0.01). Conclusions Healthy lifestyle changes during young adulthood are associated with decreased, and unhealthy lifestyle changes with increased risk for subclinical atherosclerosis in middle age. PMID:24982115

  16. Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study.

    PubMed

    Nozue, Tsuyoshi; Fukui, Kazuki; Koyama, Yutaka; Fujii, Hiroyuki; Kunishima, Tomoyuki; Hikita, Hiroyuki; Hibi, Kiyoshi; Miyazawa, Akiyoshi; Michishita, Ichiro

    2016-05-01

    Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48 weeks' treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.

  17. Novel anti-inflammatory therapies for the treatment of atherosclerosis.

    PubMed

    Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L

    2015-06-01

    The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Coronary atherosclerosis: Significance of autophagic armour.

    PubMed

    Arora, Mansi; Kaul, Deepak

    2012-09-26

    Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.

  19. Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia

    PubMed Central

    Romanelli, Filippo; Corbo, AnthonyMarco; Salehi, Maryam; Yadav, Manisha C.; Salman, Soha; Petrosian, David; Rashidbaigi, Omid J.; Chait, Jesse; Kuruvilla, Jes; Plummer, Maria; Radichev, Ilian; Margulies, Kenneth B.; Gerdes, A. Martin; Pinkerton, Anthony B.; Millán, José Luis; Savinov, Alexei Y.

    2017-01-01

    Objective Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium. Approach and results A vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study. Endothelial overexpression of TNAP was achieved in mice harboring a homozygous recessive mutation in the low density lipoprotein receptor (whc allele) utilizing a Tie2-cre recombinase (WHC-eTNAP mice). WHC-eTNAP developed significant coronary artery calcification at baseline compared WHC controls (4312 vs 0μm2 alizarin red area, p<0.001). Eight weeks after induction of atherosclerosis, lipid deposition in the coronary arteries of WHC-eTNAP was increased compared to WHC controls (121633 vs 9330μm2 oil red O area, p<0.05). Coronary lesions in WHC-eTNAP mice exhibited intimal thickening, calcifications, foam cells, and necrotic cores. This was accompanied by the reduction in body weight and left ventricular ejection fraction (19.5 vs. 23.6g, p<0.01; 35% vs. 47%, p<0.05). In a placebo-controlled experiment under atherogenic conditions, pharmacological inhibition of TNAP in WHC-eTNAP mice by a specific inhibitor SBI-425 (30mg*kg-1*d-1, for 5 weeks) reduced coronary calcium (78838 vs.144622μm2) and lipids (30754 vs. 77317μm2); improved body weight (22.4 vs.18.8g) and ejection fraction (59 vs. 47%). The effects of SBI-425 were significant in the direct comparisons with placebo but disappeared after TNAP-negative placebo-treated group was included in the models as healthy controls. Conclusions Endogenous TNAP activity is present in human cardiac tissues. TNAP overexpression in vascular endothelium in mice leads to an unusual course of coronary

  20. Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

    PubMed

    Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

    2017-09-18

    Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

  1. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    NASA Technical Reports Server (NTRS)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  2. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Ding, Jingzhong; Hsu, Fang-Chi; Harris, Tamara B; Liu, Yongmei; Kritchevsky, Stephen B; Szklo, Moyses; Ouyang, Pamela; Espeland, Mark A; Lohman, Kurt K; Criqui, Michael H; Allison, Matthew; Bluemke, David A; Carr, J Jeffrey

    2009-09-01

    Pericardial fat (ie, fat around the heart) may have a direct role in the atherosclerotic process in coronary arteries through local release of inflammation-related cytokines. Cross-sectional studies suggest that pericardial fat is positively associated with coronary artery disease independent of total body fat. We investigated whether pericardial fat predicts future coronary heart disease events. We conducted a case-cohort study in 998 individuals, who were randomly selected from 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants and 147 MESA participants (26 from those 998 individuals) who developed incident coronary heart disease from 2000 to 2005. The volume of pericardial fat was determined from cardiac computed tomography at baseline. The age range of the subjects was 45-84 y (42% men, 45% white, 10% Asian American, 22% African American, and 23% Hispanic). Pericardial fat was positively correlated with both body mass index (correlation coefficient = 0.45, P < 0.0001) and waist circumference (correlation coefficient = 0.57, P < 0.0001). In unadjusted analyses, pericardial fat (relative hazard per 1-SD increment: 1.33; 95% CI: 1.15, 1.54), but not body mass index (1.00; 0.84, 1.18), was associated with the risk of coronary heart disease. Waist circumference (1.14; 0.97, 1.34; P = 0.1) was marginally associated with the risk of coronary heart disease. The relation between pericardial fat and coronary heart disease remained significant after further adjustment for body mass index and other cardiovascular disease risk factors (1.26; 1.01, 1.59). The relation did not differ by sex. Pericardial fat predicts incident coronary heart disease independent of conventional risk factors, including body mass index.

  3. Cocaine and coronary calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    PubMed

    Pletcher, Mark J; Kiefe, Catarina I; Sidney, Steve; Carr, J Jeffrey; Lewis, Cora E; Hulley, Stephen B

    2005-11-01

    Cocaine use is associated with myocardial ischemia and infarction, but it is unclear whether this is only because of the acute effects of cocaine on heart rate, blood pressure, and vasomotor tone or whether accelerated atherosclerosis from long-term exposure to cocaine also contributes. We sought to measure the association between cocaine exposure and coronary calcification, a marker for atherosclerosis, among participants in the CARDIA Study who received computed tomography scanning and answered questions about illicit drug use at the year 15 examination in 2000-2001. Among 3038 CARDIA participants (age 33-45 years, 55% women and 45% black), past cocaine exposure was reported by 35% and was more common among men, smokers, drinkers, and participants with less education. Powdered cocaine exposure was more common among whites, crack cocaine among blacks. Before adjustment, cocaine exposure was strongly associated with coronary calcification. After adjusting for age, sex, ethnicity, socioeconomic status, family history, and habits, however, these associations disappeared: adjusted odds ratios for coronary calcification were 0.9 (95% CI 0.6-1.3) for 1 to 10, 1.2 (95% CI 0.8-1.7) for 11 to 99, and 1.0 (95% CI 0.6-1.6) for > or =100 lifetime episodes of cocaine use, in comparison with none. Sex, tobacco, and alcohol use appeared to be primarily responsible for the confounding we observed in unadjusted models. We found no evidence of a causal relationship between long-term exposure to cocaine and coronary calcification and conclude that acute nonatherogenic mechanisms probably explain most cocaine-associated myocardial infarction.

  4. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

    PubMed

    Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

    2017-02-01

    The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

  5. Significance of a positive family history for coronary heart disease in patients with a zero coronary artery calcium score (from the Multi-Ethnic Study of Atherosclerosis).

    PubMed

    Cohen, Randy; Budoff, Matthew; McClelland, Robyn L; Sillau, Stefan; Burke, Gregory; Blaha, Michael; Szklo, Moyses; Uretsky, Seth; Rozanski, Alan; Shea, Steven

    2014-10-15

    Although a coronary artery calcium (CAC) score of 0 is associated with a very low 10-year risk for cardiac events, this risk is nonzero. Subjects with a family history of coronary heart disease (CHD) has been associated with more subclinical atherosclerosis than subjects without a family history of CHD. The purpose of this study was to assess the significance of a family history for CHD in subjects with a CAC score of 0. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical cardiovascular disease (CVD) at baseline. Positive family history was defined as reporting a parent, sibling, or child who had a heart attack. Time to incident CHD or CVD event was modeled using the multivariable Cox regression; 3,185 subjects were identified from the original Multi-Ethnic Study of Atherosclerosis cohort as having a baseline CAC score of 0 (mean age 58 years, 37% men). Over a median follow-up of 10 years, 101 participants (3.2%) had CVD events and 56 (1.8%) had CHD events. In age- and gender-adjusted analyses, a family history of CHD was associated with an ∼70% increase in CVD (hazard ratio 1.73, 95% confidence interval 1.17 to 2.56) and CHD (hazard ratio 1.72, 95% confidence interval 1.01 to 2.91) events. CVD events remained significant after further adjustment for ethnicity, risk factors, and baseline medication use. In conclusion, asymptomatic subjects with a 0 CAC score and a positive family history of CHD are at increased risk for CVD and CHD events compared with those without a family history of CHD, although absolute event rates remain low. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. A Genome-wide Trans-ethnic Interaction Study Links the PIGR-FCAMR Locus to Coronary Atherosclerosis Via Interactions Between Genetic Variants and Residential Exposure to Traffic

    EPA Science Inventory

    Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic air pollution is a ubiquitous source of air pollution in developed nations, and is associated with multiple cardiovascular outcomes such as: coronary atherosclerosis, peripheral ar...

  7. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

    PubMed Central

    Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

    2018-01-01

    Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

  8. Subclinical atherosclerosis detected by coronary computed tomographic angiography in Qatar: a comparison between Qataris and south Asian migrants.

    PubMed

    Schulman-Marcus, Joshua; Heo, Ran; Gransar, Heidi; Suwaidi, Jassim Al; Alkuwari, Maryam; Elmore, Kimberly; Gomez, Mille J; Jayyousi, Amin; Zirie, Mahmoud; Min, James K; Peña, Jessica M

    2017-06-01

    There are limited data regarding subclinical atherosclerosis in Middle Eastern countries. We aimed to describe and compare coronary computed tomographic angiography (CCTA) findings in Qatari native and South Asian migrants at increased risk of coronary artery disease (CAD). We performed CCTA in 251 consecutive volunteers (126 South Asian, 125 Qatari, mean age 50.0 ± 7.3 years, 27.1% female) at increased risk of cardiovascular disease. Given differences in baseline risk factors, we employed propensity score matching to create a cohort of 162 subjects for comparative analyses. We compared CAD severity, extent, plaque morphology, adverse plaque characteristics, and quantitative measures of atherosclerotic burden in both subgroups. After matching, no CAD was seen in 58.0% of South Asians and 49.4% of Qataris (p = 0.3), while obstructive CAD (≥50% luminal stenosis) was present in 40.7% of South Asians and 49.4% of Qataris (p = 0.3). There was a high prevalence of adverse plaque characteristics in both ethnicities, particularly positive remodeling. South Asians had significantly smaller vessel and lumen volumes, but the percent aggregate plaque volumes were not significantly different (2.9 ± 6.3% vs. 3.8 ± 8.0%, p = 0.4). In this first study of CCTA findings performed in a Middle Eastern country, we observed a high prevalence of obstructive CAD in a middle-aged cohort. There were no significant differences in CCTA findings between Qataris and South Asians after adjustment for clinical risk factors. Future studies are needed to identify patterns of coronary atherosclerosis by CCTA in non-European populations where cardiovascular disease is increasingly prevalent.

  9. [Relationship between coronary tortuosity and coronary microvascular disease].

    PubMed

    Wang, Z Y; Wang, Y B; Hao, G Z; Jiang, Y F; Gu, X S; Fan, W Z; Gong, Q; Wang, Q; Fu, X H

    2018-05-24

    Objective: To explore the relationship between coronary tortuosity and coronary microvascular disease (CMVD). Methods: Patients with typical angina symptoms and without serious coronary artery stenosis by coronary angiography were enrolled from June 2014 to December 2016, and CMVD was diagnosed by single photon emission tomography (SPECT). According to the SPECT results, patients were divided to the CMVD group and non-CMVD group. The baseline clinical characteristics, results of coronary angiography were compared between the two groups. The logistic analysis was used to analyze the relationship between coronary tortuosity and CMVD. Result: A total of 117 cases were enrolled, with 69 cases in the CMVD group and 48 cases in the non-CMVD group. No differences were found in gender distribution, age, hypertension, lipid abnormality, hyperuricemia and uses of statins between the two groups (all P >0.05). Incidence of diabetes (78.26%(54/69) vs. 35.42% (17/48) , P <0.05), hs-CRP ((4.29±2.15)mmol/L vs. (2.63±1.20)mmol/L, P <0.001), LDL-C ((2.98±0.96)mmol/L vs. (2.52±0.83)mmol/L, P= 0.008) and homocysteine ((13.7±5.61)mmol/L vs. (11.5±4.38)mmol/L, P= 0.025) levels were higher in the CMVD group than in the non-CMVD group. The data derived from echocardiographic examination were similar between the two groups. The Corrected TIMI frame counts were higher in the CMVD group than in non-CMVD group (LAD: 31.56±4.92 vs. 27.31±3.75, LCX: 29.47±4.18 vs. 26.62±3.19, RCA: 29.09±5.05 vs. 26.24±3.28, all P <0.001). The incidences of coronary atherosclerosis (76.81% (53/69) vs. 27.08% (13/48) , P <0.001) and coronary tortuosity ( (60.87% (42/69) vs. 33.33% (16/48) , P= 0.035) were also higher in the CMVD group than in non-CMVD group. Logistic analysis found that coronary tortuosity ( OR= 6.111, 95% CI 2.707-13.794, P <0.001), diabetes ( OR= 6.565, 95% CI 2.883-14.948, P <0.001) and coronary atherosclerosis ( OR= 8.918, 95% CI 3.822-20.808, P <0.001) were independent risk

  10. Annexin A5 prevents post-interventional accelerated atherosclerosis development in a dose-dependent fashion in mice.

    PubMed

    Ewing, M M; Karper, J C; Sampietro, M L; de Vries, M R; Pettersson, K; Jukema, J W; Quax, P H A

    2012-04-01

    Activated cells in atherosclerotic lesions expose phosphatidylserine (PS) on their surface. Annexin A5 (AnxA5) binds to PS and is used for imaging atherosclerotic lesions. Recently, AnxA5 was shown to inhibit vascular inflammatory processes after vein grafting. Here, we report a therapeutic role for AnxA5 in post-interventional vascular remodeling in a mouse model mimicking percutaneous coronary intervention (PCI). Associations between the rs4833229 (OR = 1.29 (CI 95%), p(allelic) = 0.011) and rs6830321 (OR = 1.35 (CI 95%), p(allelic) = 0.003) SNPs in the AnxA5 gene and increased restenosis-risk in patients undergoing PCI were found in the GENDER study. To evaluate AnxA5 effects on post-interventional vascular remodeling and accelerated atherosclerosis development in vivo, hypercholesterolemic ApoE(-/-) mice underwent femoral arterial cuff placement to induce intimal thickening. Dose-dependent effects were investigated after 3 days (effects on inflammation and leukocyte recruitment) or 14 days (effects on remodeling) after cuff placement. Systemically administered AnxA5 in doses of 0.1, 0.3 and 1.0mg/kg compared to vehicle reduced early leukocyte and macrophage adherence up to 48.3% (p = 0.001) and diminished atherosclerosis development by 71.2% (p = 0.012) with a reduction in macrophage/foam cell presence. Moreover, it reduced the expression of the endoplasmic reticulum stress marker GRP78/BiP, indicating lower inflammatory activity of the cells present. AnxA5 SNPs could serve as markers for restenosis after PCI and AnxA5 therapeutically prevents vascular remodeling in a dose-dependent fashion, together indicating clinical potential for AnxA5 against post-interventional remodeling. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice

    PubMed Central

    Yamamoto, Suguru; Zuo, Yiqin; Ma, Ji; Yancey, Patricia G.; Hunley, Tracy E.; Motojima, Masaru; Fogo, Agnes B.; Linton, MacRae F.; Fazio, Sergio; Ichikawa, Iekuni

    2011-01-01

    Background. Accelerated atherosclerosis and increased cardiovascular events are not only more common in chronic kidney disease (CKD) but are more resistant to therapeutic interventions effective in the general population. The oral charcoal adsorbent, AST-120, currently used to delay start of dialysis, reduces circulating and tissue uremic toxins, which may contribute to vasculopathy, including atherosclerosis. We, therefore, investigated whether AST-120 affects CKD-induced atherosclerosis. Methods. Apolipoprotein E-deficient mice, a model of atherosclerosis, underwent uninephrectomy, subtotal nephrectomy or sham operation at 8 weeks of age and were treated with AST-120 after renal ablation. Atherosclerosis and its characteristics were assessed at 25 weeks of age. Results. Uninephrectomy and subtotal nephrectomised mice had significantly increased acceleration of atherosclerosis. AST-120 treatment dramatically reduced the atherosclerotic burden in mice with kidney damage, while there was no beneficial effect in sham-operated mice. The benefit was independent of blood pressure, serum total cholesterol or creatinine clearance. AST-120 significantly decreased necrotic areas and lessened aortic deposition of the uremic toxin indoxyl sulfate without affecting lesional macrophage or collagen content. Furthermore, AST-120 lessened aortic expression of monocyte chemoattractant protein-1, tumor necrosis factor-α and interleukin-1β messenger RNA. Conclusions. AST-120 lessens the extent of atherosclerosis induced by kidney injury and alters lesion characteristics in apolipoprotein E-deficient mice, resulting in plaques with a more stable phenotype with less necrosis and reduced inflammation. PMID:21245127

  12. N-acetylcysteine improves coronary and peripheral vascular function.

    PubMed

    Andrews, N P; Prasad, A; Quyyumi, A A

    2001-01-01

    We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

  13. Elevated Adiponectin Antibody Levels in Sera of Patients with Atherosclerosis-Related Coronary Artery Disease, Cerebral Infarction and Diabetes Mellitus

    PubMed Central

    Hiwasa, Takaki; Zhang, Xiao-Meng; Kimura, Risa; Ohno, Mikiko; Chen, Po-Min; Nishi, Eiichiro; Ono, Koh; Kimura, Takeshi; Kamitsukasa, Ikuo; Wada, Takeshi; Aotsuka, Akiyo; Mine, Seiichiro; Takizawa, Hirotaka; Kashiwado, Koichi; Takemoto, Minoru; Kobayashi, Kazuki; Kawamura, Harukiyo; Ishibashi, Ryoichi; Yokote, Koutaro; Nakamura, Rika; Tomiyoshi, Go; Shinmen, Natsuko; Kuroda, Hideyuki

    2016-01-01

    Adiponectin secreted from the adipocytes plays pleiotropic, anti-atherosclerotic roles, such as enhancement of insulin secretion and an increase in energy expenditure. The measurement of levels of circulating adiponectin is useful to evaluate the progression of atherosclerosis-related diseases, such as coronary artery disease (CAD), cerebral infarction (CI) and diabetes mellitus (DM). We examined the serum antibody levels against recombinant adiponectin protein via the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method. The results revealed that the antibody levels were significantly higher in patients with CAD, CI and type 2 DM, than in healthy donors. Receiver operating curve analysis showed that the sensitivity was in a range of 41–48% for CAD, CI and DM. Thus, the serum anti-adiponectin antibody levels could be a common marker for atherosclerosis-related diseases. PMID:28936256

  14. A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

    PubMed

    Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

    2017-12-15

    Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

  15. Association of tobacco use and cessation with coronary atherosclerosis.

    PubMed

    Cheezum, Michael K; Kim, Alexander; Bittencourt, Marcio S; Kassop, David; Nissen, Alexander; Thomas, Dustin M; Nguyen, Binh; Glynn, Robert J; Shah, Nishant R; Villines, Todd C

    2017-02-01

    The impact of tobacco use and cessation on atherogenesis remains unclear. We aimed to study the association of tobacco use and prior cessation with the presence, extent and severity of atherosclerosis on coronary computed tomographic angiography (CTA). We examined 1798 consecutive symptomatic patients without known coronary artery disease (CAD) referred for CTA, stratified by smoking status (never, current [within 30 days], or former [>30 days before CTA]). Plaque severity (none, <50%, ≥50% stenosis), composition (non-calcified [NCP], partially calcified [PCP], or calcified plaque [CP]), and segment involvement score (SIS) were visually graded. Multivariate analysis was performed, adjusting for CAD risk factors and cholesterol lowering medication use. The median age of patients was 50 years [IQR:42-58] (61% male), with 74% never smokers, 12% current smokers, and 14% former smokers (median quit duration = 12 years [IQR:3-26]). Smoking exposure in former versus current smokers was 11 [IQR:5-25] and 10 [IQR:2-20] pack-years, respectively (p = 0.01). Compared to never smokers, current smokers demonstrated an increased odds ratio of all plaque types (adjusted OR: any NCP = 1.55 [95% CI 1.04-2.32], p = 0.03; any PCP = 1.61 [1.10-2.37], p = 0.02; any CP = 1.93 [1.32-2.81], p = 0.001), non-obstructive CAD (aOR = 1.47 [1.04, 2.07], p = 0.03), obstructive CAD (aOR = 1.81 [1.01-3.24], p = 0.047), and SIS > 4 (aOR = 1.60 [1.04-2.46], p = 0.03). Compared to current smoking, prior smoking cessation (≥12 years) was associated with a decreased odds ratio of any NCP (aOR = 0.42 [0.19-0.90], p = 0.03), CP (aOR = 0.43 [0.22-0.84], p = 0.02), and obstructive CAD (aOR = 0.40, [0.15-0.98], p = 0.048). Current smoking is independently associated with the presence and extent of coronary plaque, and a higher risk of non-obstructive and obstructive CAD compared to never smoking. Prior smoking cessation correlated with improvements in CTA

  16. Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Bell, Elizabeth J; Decker, Paul A; Tsai, Michael Y; Pankow, James S; Hanson, Naomi Q; Wassel, Christina L; Larson, Nicholas B; Cohoon, Kevin P; Budoff, Matthew J; Polak, Joseph F; Stein, James H; Bielinski, Suzette J

    2018-05-01

    Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater progression of measures of atherosclerosis: coronary artery calcium (CAC) and carotid plaque. Participants aged 45-84 years from the prospective cohort study Multi-Ethnic Study of Atherosclerosis had HGF measured at baseline (between 2000 and 2002) and were followed for progression of atherosclerosis for up to 12 years. CAC was measured at all five exams using the Agatston method. Mixed-effects models were used to examine the association of HGF and CAC progression among 6695 participants with available data. Relative risk regression was used to assess the association between HGF and new or additional carotid plaque between exams 1 and 5 in 3400 participants with available data. All point estimates were adjusted for potential confounding variables. Each standard deviation higher HGF at baseline was associated with 2.9 Agatston units/year greater CAC progression (95% CI: 1.6-4.2, p < 0.0001), and the magnitude of this association differed by race/ethnicity (p value for interaction by race = 0.003). Each standard deviation higher HGF at baseline was associated with a 4% higher risk of new or additional carotid plaque (95% CI: 1.01-1.08, p = 0.005). Higher levels of HGF were significantly associated with greater progression of atherosclerosis in this large and diverse population. Circulating HGF continues to show promise as a potential clinical biomarker for cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. 56Fe accelerates development of atherosclerosis in apoE -/-mice

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has

  18. A comparison of outcomes with coronary artery calcium scanning in unselected populations: the Multi-Ethnic Study of Atherosclerosis (MESA) and Heinz Nixdorf RECALL study (HNR).

    PubMed

    Budoff, Matthew J; Möhlenkamp, Stefan; McClelland, Robyn; Delaney, Joseph A; Bauer, Marcus; Jöckel, Heinz Karl; Kälsch, Hagen; Kronmal, Richard; Nasir, Khurram; Lehmann, Nils; Moebus, Susanne; Mukamal, Ken; Erbel, Raimund

    2013-01-01

    The Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf RECALL (Risk factors, Evaluation of Coronary Calcium and Lifestyle Factors) study (HNR) differed in regard to informing physicians and patients of the results of their subclinical atherosclerosis. This study investigates whether the association of the presence of coronary calcium with incident nonfatal and fatal cardiovascular events is different among these 2 large, population-based observational studies. All white subjects aged 45 to 75 years, free of baseline cardiovascular disease were included (n = 2232 in MESA; n = 3119 HNR participants). We studied the association between coronary calcium and event rates at 5 years, including hard cardiac events (myocardial infarction, cardiac death, resuscitated cardiac arrest), and separately added revascularizations and strokes (fatal and nonfatal) to determine adjusted hazard ratios. Both cohorts showed low coronary heart disease (including revascularization) rates with zero coronary calcium (1.13% and 1.16% over 5 years in MESA and HNR, respectively) and increasing significantly in both groups with Agatston score 100 to 399 (6.71% and 4.52% in MESA and HNR, respectively) and Agatston score > 400 (12.5% and 13.54% in MESA and HNR, respectively) and showing strong independent predictive values for Agatston scores of 100 to 399 and >400, despite multivariable adjustment for risk factors. Risk factor-adjusted 5-year revascularization rates were nearly identical for HNR and MESA and were generally low for both studies (1.4% [45 of 3119] for HNR and 1.9% [43 of 2232] for MESA) over 5 years. Across 2 culturally diverse populations, Agatston score >400 is a strong predictor of events. High Agatston score did not statistically result in revascularization, and knowledge of the presence of coronary calcium did not increase revascularizations. Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  19. Cyanotic congenital heart disease and atherosclerosis.

    PubMed

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

    2017-06-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. PKM2-dependent metabolic reprogramming in CD4+ T cells is crucial for hyperhomocysteinemia-accelerated atherosclerosis.

    PubMed

    Lü, Silin; Deng, Jiacheng; Liu, Huiying; Liu, Bo; Yang, Juan; Miao, Yutong; Li, Jing; Wang, Nan; Jiang, Changtao; Xu, Qingbo; Wang, Xian; Feng, Juan

    2018-06-01

    Inflammation mediated by activated T cells plays an important role in the initiation and progression of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis in ApoE -/- mice. Homocysteine (Hcy) activates T cells to secrete proinflammatory cytokines, especially interferon (IFN)-γ; however, the precise mechanisms remain unclear. Metabolic reprogramming is critical for T cell inflammatory activation and effector functions. Our previous study demonstrated that Hcy regulates T cell mitochondrial reprogramming by enhancing endoplasmic reticulum (ER)-mitochondria coupling. In this study, we further explored the important role of glycolysis-mediated metabolic reprogramming in Hcy-activated CD4 + T cells. Mechanistically, Hcy-activated CD4 + T cell increased the protein expression and activity of pyruvate kinase muscle isozyme 2 (PKM2), the final rate-limiting enzyme in glycolysis, via the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin signaling pathway. Knockdown of PKM2 by small interfering RNA reduced Hcy-induced CD4 + T cell IFN-γ secretion. Furthermore, we generated T cell-specific PKM2 knockout mice by crossing LckCre transgenic mice with PKM2 fl/fl mice and observed that Hcy-induced glycolysis and oxidative phosphorylation were both diminished in PKM2-deficient CD4 + T cells with reduced glucose and lipid metabolites, and subsequently reduced IFN-γ secretion. T cell-depleted apolipoprotein E-deficient (ApoE -/- ) mice adoptively transferred with PKM2-deficient CD4 + T cells, compared to mice transferred with control cells, showed significantly decreased HHcy-accelerated early atherosclerotic lesion formation. In conclusion, this work indicates that the PKM2-dependent glycolytic-lipogenic axis, a novel mechanism of metabolic regulation, is crucial for HHcy-induced CD4 + T cell activation to accelerate early atherosclerosis in ApoE -/- mice. Metabolic reprogramming is crucial for Hcy-induced CD4 + T cell inflammatory activation. Hcy activates

  1. BAFF Neutralization Aggravates Atherosclerosis.

    PubMed

    Tsiantoulas, Dimitrios; Sage, Andrew P; Göderle, Laura; Ozsvar-Kozma, Maria; Murphy, Deirdre; Porsch, Florentina; Pasterkamp, Gerard; Menche, Jörg; Schneider, Pascal; Mallat, Ziad; Binder, Christoph J

    2018-06-01

    Background -Atherosclerotic cardiovascular disease (heart attacks and strokes) is the major cause of death globally and is caused by the buildup of a plaque in the arterial wall. Genomic data showed that the B cell activating factor receptor (BAFFR) pathway, which is specifically essential for the survival of conventional B lymphocytes (B-2 cells), is a key driver of coronary heart disease. Deletion or antibody-mediated blockade of BAFFR ablates B-2 cells and decreases experimental atherosclerosis. Anti-BAFF immunotherapy is approved for treatment of autoimmune systemic lupus erythematosus and can therefore be expected to limit their associated cardiovascular risk. However, direct effects of anti-BAFF immunotherapy on atherosclerosis remain unknown. Methods -To investigate the effect of BAFF neutralization in atherosclerosis, we treated Apoe -/- and Ldlr -/- mice with a well-characterized blocking anti-BAFF antibody. Moreover, to investigate the mechanism by which BAFF impacts atherosclerosis, we studied atherosclerosis-prone mice that lack the alternative receptor for BAFF, transmembrane activator and CAML interactor (TACI). Results -We demonstrate here that anti-BAFF antibody treatment increased atherosclerosis in mice, despite efficient depletion of mature B-2 cells, suggesting a unique mechanism of action. Indeed, myeloid cell specific deletion TACI, also results in increased atherosclerosis, while B cell-specific TACI deletion had no effect. Mechanistically, BAFF-TACI signaling represses macrophage IRF7-dependent (but not NF-kB dependent) TLR9 responses including proatherogenic CXCL10 production. Conclusions -These data identify a novel B cell independent anti-inflammatory role for BAFF in atherosclerosis and may have important clinical implications.

  2. Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

    PubMed

    Dotsenko, O; Chaturvedi, N; Thom, S A McG; Wright, A R; Mayet, J; Shore, A; Schalkwijk, C; Hughes, A D

    2007-10-01

    Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

  3. [Atherosclerosis in inflammatory diseases].

    PubMed

    Páramo, José A; Rodríguez, José A; Orbe, Josune

    2007-05-19

    The recognition that inflammation is a hallmark of atherosclerotic disease and its complications has led to a series of studies reporting high prevalence of atherosclerosis in chronic inflammatory diseases. Indeed, chronic immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, are associated with proinflammation, accelerated atherosclerosis and increased incidence of cardiovascular disease. Since the susceptibility towards cardiovascular events cannot be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors, potentially important for future prevention and treatment of atherosclerosis associated with chronic inflammatory diseases.

  4. Coronary artery screening by electron beam computed tomography. Facts, controversy, and future.

    PubMed

    Wong, N D; Detrano, R C; Abrahamson, D; Tobis, J M; Gardin, J M

    1995-08-01

    Coronary calcium as detected by electron beam computed tomography always signifies at least some atherosclerosis, appears to be correlated with coronary risk factors, cardiac history, and overall angiographic severity of disease, but is inconsistently related to degree of atherosclerotic lesion stenosis in a given artery. Increasing evidence, however, suggests an association between coronary artery calcium, atherosclerosis, and coronary risk. But atherosclerosis is a very common condition, its prevalence increasing with age. No fully validated method for determining the quantity of coronary calcium is available, and we do not know whether the amount of calcium is a consistently accurate reflection of the amount of atherosclerosis or whether the amount of atherosclerosis reflects the degree of risk. Furthermore, the prognostic significance of coronary calcium in any given atherosclerotic lesion is not yet established. What is clear from cohort studies, however, is that at least three quarters of asymptomatic individuals, at least half of whom would have "positive" coronary calcium electron beam computed tomographic scans, will live for at least 10 years without cardiac problems of any kind. Investigation is needed to determine whether medical intervention may impact the clinical outcome of the rest of those identified with a positive scan but destined to suffer future clinical events. Despite lack of validation, this test has widespread appeal, both to the public as a means of being able to find out the condition of their coronary arteries "without injections or dye" and to hospitals and private medical groups who view this both as an innovation in cardiovascular diagnosis and as a potentially profitable diagnostic procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Vitamin D and conjugated equine estrogen: the association with coronary artery atherosclerosis in cynomolgus monkeys.

    PubMed

    McCurdy, Rebekah; Jiang, Xuezhi; Clarkson, Thomas B; Nudy, Matthew; Schnatz, Peter F

    2016-05-01

    To analyze vitamin D3 plasma concentrations among monkeys randomized to oral conjugated equine estrogen (CEE) versus control and the association with coronary artery atherosclerosis (CAA). Surgically postmenopausal monkeys (N = 50) were fed an atherogenic diet containing a woman's equivalent of 1000 IU/day of vitamin D3. The monkeys were randomized at baseline to receive CEE (equivalent of 0.45 mg/d, n = 25) or placebo (n = 25). 25-hydroxyvitamin D3 (25OHD3) was measured at baseline and 20 months later. At 20 months, CAA evidence of coronary artery remodeling, and American Heart Association (AHA) severity scores were assessed. The percent change in 25OHD3 concentrations from baseline to 20 months postrandomization was inversely correlated with plaque area of the right coronary artery (P = 0.048), left circumflex artery (P = 0.039), left anterior descending artery (P = 0.017), and AHA severity score (AHA LADmax) (P = 0.016). Those with increased 25OHD3 concentrations who were taking CEE also had significantly lower AHA scores compared with those who were not taking CEE and did not have an increase in 25OHD3 (P = 0.01). Monkeys with increases in 25OHD3 concentrations had significantly less severe CAA. Those with increases in 25OHD3 with CEE were associated with significantly decreased AHA lesion scores, decreased plaque, and greater coronary artery remodeling. If these findings are present in women, achieving higher 25OHD3 concentrations (or being a vitamin D supplementation "responder") may be associated with cardioprotection, and further studies to evaluate a synergistic effect with CEE and vitamin D on cardiovascular health are needed.

  6. Porphyromonas gingivalis Accelerates Inflammatory Atherosclerosis in the Innominate Artery of ApoE Deficient Mice

    PubMed Central

    Hayashi, Chie; Viereck, Jason; Hua, Ning; Phinikaridou, Alkystis; Madrigal, Andres G.; Gibson, Frank C.; Hamilton, James A.; Genco, Caroline A.

    2011-01-01

    Objective Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. Methods and Results Apolipoprotein E-deficient (ApoE−/−) mice were orally infected with P. gingivalis, and Magnetic Resonance Imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. Conclusions These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in-vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization. PMID:21251656

  7. Genetic Basis of Atherosclerosis: Insights from Mice and Humans

    PubMed Central

    Stylianou, Ioannis M.; Bauer, Robert C.; Reilly, Muredach P.; Rader, Daniel J.

    2012-01-01

    Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have in part been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease (CAD). Here we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human CAD. Furthermore, we discuss in greater detail some of these novel human CAD loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches. PMID:22267839

  8. Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study.

    PubMed

    Kaufman, Joel D; Adar, Sara D; Barr, R Graham; Budoff, Matthew; Burke, Gregory L; Curl, Cynthia L; Daviglus, Martha L; Diez Roux, Ana V; Gassett, Amanda J; Jacobs, David R; Kronmal, Richard; Larson, Timothy V; Navas-Acien, Ana; Olives, Casey; Sampson, Paul D; Sheppard, Lianne; Siscovick, David S; Stein, James H; Szpiro, Adam A; Watson, Karol E

    2016-08-13

    g PM2.5/m(3) and 7.2-139.2 parts per billion (ppb) NOX. For each 5 μg PM2.5/m(3) increase, coronary calcium progressed by 4.1 Agatston units per year (95% CI 1.4-6.8) and for each 40 ppb NOX coronary calcium progressed by 4.8 Agatston units per year (0.9-8.7). Pollutant exposures were not associated with intima-media thickness change. The estimate for the effect of a 5 μg/m(3) higher long-term exposure to PM2.5 in intima-media thickness was -0.9 μm per year (95% CI -3.0 to 1.3). For 40 ppb higher NOX, the estimate was 0.2 μm per year (-1.9 to 2.4). Increased concentrations of PM2.5 and traffic-related air pollution within metropolitan areas, in ranges commonly encountered worldwide, are associated with progression in coronary calcification, consistent with acceleration of atherosclerosis. This study supports the case for global efforts of pollution reduction in prevention of cardiovascular diseases. US Environmental Protection Agency and US National Institutes of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Hemoglobin A1c Level Is Not Related to the Severity of Atherosclerosis in Patients with Acute Coronary Syndrome.

    PubMed

    Wang, Xinhong; Han, Zhenhua; Hao, Guanghua; Li, Yongqin; Dong, Xin; Wang, Congxia

    2015-01-01

    The relationship between hemoglobin A1c (HbA1c) levels and the extent of coronary artery stenosis in patients with acute coronary syndrome (ACS) remains uncertain. The present study aimed to assess the correlation of HbA1c level with angiographic coronary atherosclerosis. 292 consecutive ACS patients were enrolled and stratified into three groups according to HbA1c levels (group 1: < 6.0%, n = 137; group 2: 6.0-6.4%, n = 67; group 3: ≥ 6.5%, n = 88). The severity of coronary arteriosclerosis was assessed by Gensini score. The relationship between HbA1c and Gensini score was analyzed by multiple variables analysis. HbA1c level was not associated with the severity of CAD assessed by Gensini score in patients with ACS, even after the adjustment for other risk factors. However, NT-proBNP, ApoA1 and LVEF levels were independent predictors for CAD severity. Moreover, HbA1c level was not associated with the risk of high Gensini score (> 40) by logistic regression analysis. Diabetes mellitus (DM) and LVEF levels were two independent risk factors for high Gensini score. HbA1c level is not a significant and independent marker for the severity of angiography in ACS patients, even in high-risk patients.

  10. Low protein Z plasma level is a risk factor for acute myocardial infarction in coronary atherosclerosis disease patients.

    PubMed

    Liu, Baoxin; Li, Yong; Luo, Jiachen; Dai, Liming; Zhao, Jinlong; Li, Hongqiang; Jie, Qiqiang; Wang, Dongzhi; Huang, Xin; Wei, Yidong

    2016-12-01

    To examine plasma protein Z (PZ) levels in acute myocardial infarction (AMI) and chronic coronary atherosclerosis disease (CCAD) patients without history of AMI and explore its potential clinical significance. Plasma PZ concentrations were measured in 90 AMI patients (Group A), 87 CCAD patients without AMI history who remained free of major clinical events at least one year (Group B), and 88 clinically healthy controls (Group C). PZ was found to be significantly lower (P<0.001) in Group A (1508.5±486.2ng/mL) compared with Group B (1823.0±607.8ng/mL) and C (2001.7±733.0ng/mL) and in Group A+B compared with Group C (Group A+B 1663.1±570.0 ng/mL, P<0.001). No statistically significant difference was reached between Group B and C (P=0.081). PZ level was significantly correlated with concentration of creatine kinase MB, high sensitive-cardiac troponin T, high sensitive C reactive protein, D-dimer and coagulation factor II and may be a useful predictor for AMI (OR: 1.38, 95% CI: 1.13-1.77, P=0.03). Subgroup analysis showed PZ concentration below the lowest tertile (<1398ng/mL) had a significantly increased risk for AMI and CCAD (OR: 3.39; 95% CI: 1.12-10.31; P=0.03 and OR: 7.39; 95% CI: 2.62-20.79; P<0.001 respectively). PZ deficiency is found in AMI patients and could potentially reflect the myocardium injury, local coagulation activation and inflammation response during the acute phase of coronary atherosclerosis disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Low protein Z plasma level is a risk factor for acute myocardial infarction in coronary atherosclerosis disease patients

    PubMed Central

    Liu, Baoxin; Li, Yong; Luo, Jiachen; Dai, Liming; Zhao, Jinlong; Li, Hongqiang; Jie, Qiqiang; Wang, Dongzhi; Huang, Xin; Wei, Yidong

    2016-01-01

    Objectives To examine plasma protein Z (PZ) levels in acute myocardial infarction (AMI) and chronic coronary atherosclerosis disease (CCAD) patients without history of AMI and explore its potential clinical significance. Methods Plasma PZ concentrations were measured in 90 AMI patients (Group A), 87 CCAD patients without AMI history who remained free of major clinical events at least one year (Group B), and 88 clinically healthy controls (Group C). Results PZ was found to be significantly lower (P<0.001) in A (1508.5 ± 486.2 ng/mL) compared with B (1823.0 ± 607.8 ng/mL) and C (2001.7 ± 733.0 ng/mL) groups and in A+B compared with C Group (A+B 1663.1±570.0, P<0.001). No statistically significant difference was reached between B and C groups (P=0.081). PZ level was significantly correlated with concentration of creatine kinase MB, high sensitive-cardiac troponin T, high sensitive C reactive protein, D-dimer and coagulation factor II and may be a useful predictor for AMI (OR: 1.38, 95% CI: 1.13-1.77, P=0.03). Subgroup analysis showed PZ concentration below the lowest tertile (< 1398 ng/mL) had a significantly increased risk for AMI and CCAD (OR: 3.39; 95% CI: 1.12-10.31; P=0.03 and OR: 7.39; 95% CI: 2.62-20.79; P<0.001 respectively). Conclusions PZ deficiency is found in AMI patients and could potentially reflect the myocardium injury, local coagulation activation and inflammation response during the acute phase of coronary atherosclerosis disease. PMID:27770663

  12. Gender differences in coronary plaque composition by coronary computed tomography angiography.

    PubMed

    Blaha, Michael J; Nasir, Khurram; Rivera, Juan J; Choi, Eue-Keun; Chang, Sung-A; Yoon, Yeonyee E; Chun, Eun Ju; Choi, Sang-il; Agatston, Arthur; Blumenthal, Roger S; Chang, Hyuk-Jae

    2009-12-01

    Coronary computed tomography angiography allows the differentiation of non-calcified (NCAP), calcified (CAP), and mixed coronary artery plaques (MCAP). Although males are thought to have a higher prevalence of atherosclerosis for a given age, there are currently few data regarding age-adjusted sex differences in plaque morphology and composition. We studied 1015 consecutive asymptomatic South Korean patients (49+/-10 years, 64% men) who underwent 64-slice coronary computed tomography angiography during a routine health evaluation. Coronary plaque characteristics were analyzed on a per-segment basis according to the modified AHA classification. Plaques with more than 50% calcified tissue were classified as CAP, plaques with less than 50% calcified tissue were classified as MCAP, and plaques without calcium were classified as NCAP. Multiple regression analysis was used to describe the cross-sectional association between sex and plaque-type burden (>or=2 affected segments) after adjustment for age and other cardiovascular risk factors. There was a greater prevalence of coronary plaque among men (13 vs. 4%, P<0.001). Males were more likely to have an increased burden of CAP (4 vs. 1%, P = 0.01) and MCAP (5 vs. 1%, P<0.001), whereas the burden of NCAP was similar across sex (2 vs. 1%, P = 0.28). After multivariable adjustment, men have six to seven times greater odds of having an increased burden of CAP and MCAP, whereas no sex difference was observed in the burden of NCAP. In this population of asymptomatic middle-aged Korean individuals, males had a significantly greater burden of MCAP and CAP. Future studies will determine whether these differences contribute to the accelerated cardiovascular risk observed in men.

  13. Race-Specific Associations of Myeloperoxidase with Atherosclerosis in a Population-Based Sample: The Dallas Heart Study

    PubMed Central

    Chen, Lu; Rohatgi, Anand; Ayers, Colby R.; Das, Sandeep R.; Khera, Amit; Berry, Jarett D.; McGuire, Darren K.; de Lemos, James A.

    2011-01-01

    Objective Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. Methods and Results Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p=0.02), and AWT (beta coefficient 0.04, p=0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (pinteraction=0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44). Conclusion Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease. PMID:21917261

  14. The roles of salusins in atherosclerosis and related cardiovascular diseases.

    PubMed

    Watanabe, Takuya; Sato, Kengo; Itoh, Fumiko; Iso, Yoshitaka; Nagashima, Masaharu; Hirano, Tsutomu; Shichiri, Masayoshi

    2011-01-01

    Human salusin-α and -β are related peptides of 28 and 20 amino acids, respectively, produced from the same precursor, prosalusin. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-α. Human macrophage foam cell formation is significantly stimulated by salusin-β, but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-knockout mice enhances atherosclerotic lesions, paralleling increases in foam cell formation and upregulation of scavenger receptors and of acyl-CoA:cholesterol acyltransferase-1 (ACAT1) in macrophages. In contrast, chronic salusin-α infusion reduces atherosclerotic lesions accompanied by significant suppression of foam cell formation owing to ACAT1 downregulation. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and -β immunoreactivity has been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Serum salusin-α levels are markedly decreased in patients with angiographically proven coronary artery disease compared with patients with mild hypertension and healthy volunteers. Furthermore, among patients with acute coronary syndrome, serum salusin-α levels are decreased in accordance with the severity of coronary atherosclerotic lesions. These findings suggest that salusin-β may contribute to the pathogenesis of atherosclerosis. Decreased levels of salusin-α in circulating blood and vascular tissue are closely linked with human atherosclerosis. Therefore, salusin-α could be a candidate biomarker for atherosclerosis and may be therapeutically useful for prevention of atherosclerotic cardiovascular diseases. Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  15. Effectiveness of atrial fibrillation as an independent predictor of death and coronary events in patients having coronary angiography.

    PubMed

    Marte, Thomas; Saely, Christoph H; Schmid, Fabian; Koch, Lorena; Drexel, Heinz

    2009-01-01

    The impact of atrial fibrillation (AF) on future coronary events is uncertain. In particular, the prognostic impact of AF in the clinically important population of coronary patients who undergo angiography is unknown. The aim of this study was to investigate (1) the prevalence of AF, (2) its association with coronary atherosclerosis, and (3) its impact on future coronary events in patients who undergo angiography. Electrocardiograms were evaluated in a consecutive series of 613 patients who underwent coronary angiography. Prospectively, death and cardiovascular events were recorded over 4.0 +/- 0.6 years. Among these patients, 37 (6%) at baseline had AF, and 576 (94%) were in sinus rhythm. The presence of AF was associated with a lower prevalence of coronary artery disease and of coronary diameter narrowing >or=50% on baseline angiography. However, prospectively, patients with AF were at a strongly increased risk for all-cause mortality (adjusted hazard ratio 5.15, 95% confidence interval 2.36 to 11.26, p <0.001), coronary death (hazard ratio 8.16, 95% confidence interval 2.89 to 23.09, p <0.001), and major coronary events (hazard ratio 3.80, 95% confidence interval 1.45 to 9.94, p = 0.007). In conclusion, although inversely associated with the presence of angiographically determined coronary atherosclerosis, AF is a strong predictor of death and future coronary events in patients with coronary artery disease who undergo coronary angiography.

  16. Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

    PubMed Central

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

  17. Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland.

    PubMed

    Salonen, J T; Seppänen, K; Lakka, T A; Salonen, R; Kaplan, G A

    2000-02-01

    Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42-60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P2.81 microg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.

  18. Coronary atherosclerosis evaluation among Iranian patients with zero coronary calcium score in computed tomography coronary angiography.

    PubMed

    Moradi, Maryam; Varasteh, Elham

    2016-01-01

    Coronary artery calcification (CAC) is a specific indicator of and a sensitive marker for the atherosclerotic disease process. However, calcium scoring may miss noncalcified plaques with clinical importance. The present study aimed to identify the presence and extent of coronary plaques in computed tomography coronary angiography (CTCA) in patients with a zero CAC score and the secondary endpoint was to evaluate the association between coronary risk factors and the presence of noncalcified plaques. In a retrospective descriptive-analytic study, a total of 2000 consecutive patients who undergone CTCA between September 2012 and September 2014 at Alzahra Hospital in Isfahan, Iran were analyzed. Three hundred and eighty-five patients with a zero calcium score were included in the study. The demographic information and coronary artery disease (CAD), risk factors including diabetes mellitus (DM), hypertension, hyperlipidemia, smoking, and family history of CAD, were obtained from the questionnaire. Furthermore, the presence of plaques and extent of stenosis were evaluated in patients with zero CAC score. Of the 385 patients with a zero calcium score, 16 (4.2%) had atherosclerotic plaques. Among them, 6 (1.6%) had significant (>50%) coronary stenosis, and 10 (2.6%) had no significant (<50%) coronary stenosis. Hyperlipidemia, DM, and smoking were significantly associated with obstructive CAD. Furthermore, in patients with zero calcium score, DM, hyperlipidemia, and smoking had odds ratios of 5.9, 14, and 32.5 for the development of coronary artery plaques, respectively. Although, CAC scoring is a noninvasive and valuable method to evaluate CAD; but zero CAC score does not absolutely exclude the CAD, especially in the presence of risk factors such as diabetes, hyperlipidemia, and smoking.

  19. G Protein-coupled Estrogen Receptor Protects from Atherosclerosis

    PubMed Central

    Meyer, Matthias R.; Fredette, Natalie C.; Howard, Tamara A.; Hu, Chelin; Ramesh, Chinnasamy; Daniel, Christoph; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

    2014-01-01

    Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity. PMID:25532911

  20. S100A12 and the S100/Calgranulins - Emerging Biomarkers for Atherosclerosis and Possibly Therapeutic Targets

    PubMed Central

    Oesterle, Adam; Hofmann Bowman, Marion A

    2016-01-01

    Atherosclerosis is mediated by local and systematic inflammation. The multi-ligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans, and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell targeted expression of S100A12 demonstrate increased coronary and aortic calcification as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis susceptible Apolipoprotein E (ApoE) null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the Quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 ApoE null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis. PMID:26515415

  1. Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children with Kawasaki Disease and Transient Coronary Abnormalities.

    PubMed

    Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar

    2017-08-01

    There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis

  2. Effect of Red Blood Cell Storage on Cardiac Performance. Improved Myocardial Oxygen Delivery and Function during Constant Flow Coronary Perfusion with Low Oxy-Hemoglobin Affinity Human Red Blood Cells in Normothermic and Hypothermic Rabbit Hearts.

    DTIC Science & Technology

    1983-02-01

    with an isovolumic left ven- tricular balloon. Coronary flow was held constant to simulate the physiolog of coronary atherosclerosis and other...erythrocyte DPG content can potentially benefit patients with coronary atherosclerosis , or other states with a limited coronary vasodilator reserve, who...Coronary flow was held constant to simulate the physiology of coronary atherosclerosis and other conditions of limited coronary vasodilator reserve

  3. Dark chocolate improves coronary vasomotion and reduces platelet reactivity.

    PubMed

    Flammer, Andreas J; Hermann, Frank; Sudano, Isabella; Spieker, Lukas; Hermann, Matthias; Cooper, Karen A; Serafini, Mauro; Lüscher, Thomas F; Ruschitzka, Frank; Noll, Georg; Corti, Roberto

    2007-11-20

    Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.

  4. Agonistic antibody to angiotensin II type 1 receptor accelerates atherosclerosis in ApoE-/- mice

    PubMed Central

    Li, Weijuan; Chen, Yaoqi; Li, Songhai; Guo, Xiaopeng; Zhou, Wenping; Zeng, Qiutang; Liao, Yuhua; Wei, Yumiao

    2014-01-01

    This study aimed to investigate the effects of agonistic antibody to angiotensin II type 1 receptor (AT1-AA) on atherosclerosis in male ApoE-/- mice which were employed to establish the animal models of AT1-AA in two ways. In the first group, mice were injected subcutaneously with conjugated AT1 peptide at multiple sites; in the second group, mice were infused with AT1-AA prepared from rabbits that were treated with AT1 peptide intraperitoneally. Mice in each group were further randomly divided into five subgroups and treated with AT1 peptide/AT1-AA, AT1 peptide/AT1-AA plus valsartan, AT1 peptide/AT1-AA plus fenofibrate, AT1 peptide/ AT1-AA plus pyrrolidine dithiocarbamate (PDTC) and control vehicle, respectively. Antibodies were detected in mice (except for mice in control group). Aortic atherosclerotic lesions were assessed by oil red O staining, while plasma CRP, TNF-α, nuclear factor-kappa B (NF-κB) and H2O2 were determined by ELISA. CCR2 (the receptor of MCP-1), macrophages, and smooth muscle cells were detected by immunohistochemistry. P47phox, MCP-1 and eNOS were detected by RT-PCR, while P47phox, NF-κB and MCP-1 were detected by Western blot assay. The aortic atherosclerotic lesions were significantly increased in AT1 peptide/AT1-AA treated mice, along with simultaneous increases in inflammatory parameters. However, mice treated with valsartan, fenofibrate or PDTC showed alleviated progression of atherosclerosis and reductions in inflammatory parameters. Thus, AT1-AA may accelerate aortic atherosclerosis in ApoE-/- mice, which is mediated, at least in part, by the inflammatory reaction involving nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species, and NF-κB. In addition, valsartan, fenofibrate and PDTC may inhibit the AT1-AA induced atherosclerosis. PMID:25628779

  5. Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

    PubMed Central

    Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

    2011-01-01

    Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

  6. Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis.

    PubMed

    Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy, Patrick F; Turner, Stephen T; Chu, Julia S; Peyser, Patricia A

    2011-12-01

    Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. 877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P = 0.001) and -1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024). Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study

    PubMed Central

    Kaufman, Joel D; Adar, Sara D; Barr, R Graham; Budoff, Matthew; Burke, Gregory L; Curl, Cynthia L; Daviglus, Martha L; Roux, Ana V Diez; Gassett, Amanda J; Jacobs, David R; Kronmal, Richard; Larson, Timothy V; Navas-Acien, Ana; Olives, Casey; Sampson, Paul D; Sheppard, Lianne; Siscovick, David S; Stein, James H; Szpiro, Adam A; Watson, Karol E

    2016-01-01

    the years 2000–10 ranged from 9·2–22·6 μg PM2·5/m3 and 7·2–139·2 parts per billion (ppb) NOX. For each 5 μg PM2·5/m3 increase, coronary calcium progressed by 4·1 Agatston units per year (95% CI 1·4–6·8) and for each 40 ppb NOX coronary calcium progressed by 4·8 Agatston units per year (0·9–8·7). Pollutant exposures were not associated with intima-media thickness change. The estimate for the effect of a 5 μg/m3 higher long-term exposure to PM2·5 in intima-media thickness was −0·9 μm per year (95% CI −3·0 to 1·3). For 40 ppb higher NOX, the estimate was 0·2 μm per year (−1·9 to 2·4). Interpretation Increased concentrations of PM2·5 and traffc-related air pollution within metropolitan areas, in ranges commonly encountered worldwide, are associated with progression in coronary calcification, consistent with acceleration of atherosclerosis. This study supports the case for global efforts of pollution reduction in prevention of cardiovascular diseases. Funding US Environmental Protection Agency and US National Institutes of Health. PMID:27233746

  8. Predictors of coronary heart disease events among asymptomatic persons with low low-density lipoprotein cholesterol MESA (Multi-Ethnic Study of Atherosclerosis).

    PubMed

    Blankstein, Ron; Budoff, Matthew J; Shaw, Leslee J; Goff, David C; Polak, Joseph F; Lima, Joao; Blumenthal, Roger S; Nasir, Khurram

    2011-07-19

    Our aim was to identify risk factors for coronary heart disease (CHD) events among asymptomatic persons with low (≤ 130 mg/dl) low-density lipoprotein cholesterol (LDL-C). Even among persons with low LDL-C, some will still experience CHD events and may benefit from more aggressive pharmacologic and lifestyle therapies. The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort of 6,814 participants free of clinical cardiovascular disease. Of 5,627 participants who were not receiving any baseline lipid-lowering therapies, 3,714 (66%) had LDL-C ≤ 130 mg/dl and were included in the present study. Unadjusted and adjusted hazard ratios were calculated to assess the association of traditional risk factors and biomarkers with CHD events. To determine if subclinical atherosclerosis markers provided additional information beyond traditional risk factors, coronary artery calcium (CAC) and carotid intima media thickness were each separately added to the multivariable model. During a median follow-up of 5.4 years, 120 (3.2%) CHD events were observed. In unadjusted analysis, age, male sex, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and subclinical atherosclerosis markers (CAC >0; carotid intima media thickness ≥1 mm) predicted CHD events. Independent predictors of CHD events included age, male sex, hypertension, diabetes, and low HDL-C. After accounting for all traditional risk factors, the predictive value of CAC was attenuated but remained highly significant. The relationship of all independent clinical predictors remained robust even after accounting for elevated CAC. Among persons with low LDL-C, older age, male sex, hypertension, diabetes, and low HDL-C are associated with adverse CHD events. Even after accounting for all such variables, the presence of CAC provided incremental prognostic value. These results may serve as a basis for deciding which patients with low LDL-C may be considered for

  9. Prevention of Coronary Atherosclerosis: The Role of a College Health Service.

    ERIC Educational Resources Information Center

    Manchester, Ralph A.; Greenland, Philip

    1987-01-01

    This paper reviews the concept of behavioral risk factors for atherosclerosis which become entrenched in adolescence or young adulthood. Evidence favoring intervention in the adolescent years and a screening program at the University of Rochester Health Service are described. A preliminary strategy for prevention of atherosclerosis on campus is…

  10. Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study.

    PubMed

    Andrews, Jordan; Janssan, Alex; Nguyen, Tracy; Pisaniello, Anthony D; Scherer, Daniel J; Kastelein, John J P; Merkely, Bela; Nissen, Steven E; Ray, Kausik; Schwartz, Gregory G; Worthley, Stephen G; Keyserling, Connie; Dasseux, Jean-Louis; Butters, Julie; Girardi, Jacinta; Miller, Rosemary; Nicholls, Stephen J

    2017-02-01

    High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS). The CARAT is a phase 2, multicenter trial in which 292 patients with an ACS undergoing intracoronary ultrasonography and showing percent atheroma volume (PAV) greater than 30% are randomly assigned to treatment with ten infusions of CER-001 3 mg/kg or matching placebo, administered at weekly intervals. Intracoronary ultrasonography is repeated at the end of the treatment period. The primary endpoint is the nominal change in PAV. Safety and tolerability will also be evaluated. CARAT will establish whether serial 3 mg/kg infusions of an engineered pre-beta HDL mimetic containing SM and dipalmitoyl phosphatidlyglycerol (CER-001) will regress atherosclerotic plaque in patients with a recent ACS.

  11. Prevalence and Correlates of Subclinical Atherosclerosis in Alaskan Eskimos

    PubMed Central

    Cutchins, Alexis; Roman, Mary J.; Devereux, Richard B.; Ebbesson, Sven O.E.; Umans, Jason G.; Zhu, Jianhui; Weissman, Neil J.; Howard, Barbara V.

    2009-01-01

    Background and Purpose The recent increase in clinical cardiovascular disease in Alaska Eskimos suggests that changes in traditional lifestyle may have adverse public health consequences. This study examines the prevalence of subclinical vascular disease and its relation to risk factors in Alaska Eskimos. Methods Participants in the population-based Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study underwent evaluation of cardiovascular disease risk factors and carotid ultrasound. Outcome variables were carotid intimal-medial thickness and presence and extent of atherosclerosis. Results In multivariate analyses, intimal-medial thickness and presence and extent of atherosclerosis were all associated with traditional cardiovascular disease risk factors but not dietary intake of omega-3 fatty acids. Rates of carotid atherosclerosis were higher than those reported in 2 large population-based US studies. Conclusions Alaska Eskimos have similar traditional risk factors for carotid atherosclerosis as other ethnic and racial populations but have higher prevalences of atherosclerosis, possibly attributable to higher rates of smoking. PMID:18617652

  12. Alloxan-induced diabetes exacerbates coronary atherosclerosis and calcification in Ossabaw miniature swine with metabolic syndrome.

    PubMed

    Badin, Jill K; Kole, Ayeeshik; Stivers, Benjamin; Progar, Victor; Pareddy, Anisha; Alloosh, Mouhamad; Sturek, Michael

    2018-03-09

    There is a preponderance of evidence implicating diabetes with increased coronary artery disease (CAD) and calcification (CAC) in human patients with metabolic syndrome (MetS), but the effect of diabetes on CAD severity in animal models remains controversial. We investigated whether diabetes exacerbates CAD/CAC and intracellular free calcium ([Ca 2+ ] i ) dysregulation in the clinically relevant Ossabaw miniature swine model of MetS. Sixteen swine, eight with alloxan-induced diabetes, were fed a hypercaloric, atherogenic diet for 6 months. Alloxan-induced pancreatic beta cell damage was examined by immunohistochemical staining of insulin. The metabolic profile was confirmed by body weight, complete blood panel, intravenous glucose tolerance test (IVGTT), and meal tolerance test. CAD severity was assessed with intravascular ultrasound and histology. [Ca 2+ ] i handling in coronary smooth muscle (CSM) cells was assessed with fura-2 ratiometric imaging. Fasting and post-prandial blood glucose, total cholesterol, and serum triglycerides were elevated in MetS-diabetic swine. This group also exhibited hypoinsulinemia during IVGTT and less pancreatic beta cell mass when compared to lean and MetS-nondiabetic swine. IVUS analysis revealed that MetS-diabetic swine had greater percent wall coverage, percent plaque burden, and calcium index when compared to lean and MetS-nondiabetic swine. Fura-2 imaging of CSM [Ca 2+ ] i revealed that MetS-nondiabetic swine exhibited increased sarcoplasmic reticulum Ca 2+ store release and Ca 2+ influx through voltage-gated Ca 2+ channels compared to lean swine. MetS-diabetic swine exhibited impaired Ca 2+ efflux. Diabetes exacerbates coronary atherosclerosis and calcification in Ossabaw miniature swine with MetS, accompanied by progression of [Ca 2+ ] i dysregulation in advanced CAD/CAC. These results recapitulate increased CAD in humans with diabetes and establish Ossabaw miniature swine as an animal model for future Met

  13. Sarcopenia, but not excess weight or increased caloric intake, is associated with coronary subclinical atherosclerosis in the very elderly.

    PubMed

    Campos, Alessandra M; Moura, Filipe A; Santos, Simone N; Freitas, Wladimir M; Sposito, Andrei C

    2017-03-01

    Excess weight is a widespread condition related to increased risk of coronary heart disease (CHD). Sarcopenia is a catabolic pathway common of the aging process and also associated with CHD. In the elderly, both changes occur concurrently and it remains unclear the relative contribution on CHD risk. We aimed to investigate whether sarcopenia, excess weight, or both are associated with subclinical atherosclerosis and/or endothelial dysfunction in very elderly individuals. We performed a cross-sectional study of cohort enrolled individuals, aged 80 years or older (n = 208), who had never manifested cardiovascular diseases. Blood tests, medical and nutritional evaluations, cardiac computed tomography, flow-mediated dilation (FMD) and physical performance tests were obtained at the study admission. Odds ratio (OR) was calculated by multivariate regression models using coronary calcium score (CCS) categories and FMD as dependent variables. Adjustment for potential confounders was done. Muscle mass, but not fatty mass, was inversely associated with CCS categories [OR:2.54(1.06-6.06); p = 0.018]. The lowering of gait speed was negatively related to CCS>100 [OR:2.36 (1.10-5.06); p = 0.028] and skeletal muscle index was directly associated with FMD [OR:5.44 (1.22-24.24); p = 0.026]. Total caloric intake was positively related to fatty mass [OR:2.71 (1.09-6.72); p = 0.031], but was not related to CCS. This study reveals that sarcopenia - comprised by reduction of muscle mass and its strength - is associated with subclinical atherosclerosis and endothelial dysfunction. Surprisingly, the excess of fatty mass seems not to be related to atherosclerotic burden in very elderly individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Lipoprotein-associated phospholipase A(2) and atherosclerosis.

    PubMed

    Wilensky, Robert L; Macphee, Colin H

    2009-10-01

    There is substantial data from over 50 000 patients that increased lipoprotein-associated phospholipase A2 (Lp-PLA2) mass or activity is associated with an increased risk of cardiac death, myocardial infarction, acute coronary syndromes and ischemic stroke. However, only recently have data emerged demonstrating a role of Lp-PLA2 in development of advanced coronary artery disease. Indeed, Lp-PLA2 may be an important link between lipid homeostasis and the vascular inflammatory response. Lp-PLA2, also known as platelet-activating factor acetylhydrolase, rapidly cleaves oxidized phosphatidylcholine molecules produced during the oxidation of LDL and atherogenic lipoprotein Lp(a), generating the soluble proinflammatory and proapoptotic lipid mediators, lyso-phosphatidylcholine and oxidized nonesterified fatty acids. These proinflammatory lipids play an important role in the development of atherosclerotic necrotic cores, the substrate for acute unstable coronary disease by recruiting and activating leukocytes/macrophages, inducing apoptosis and impairing the subsequent removal of dead cells. Selective inhibition of Lp-PLA2 reduces development of necrotic cores and may result in stabilization of atherosclerotic plaques. Recent data have shown that immune pathways play a major role in the development and progression of high-risk atherosclerosis, which leads to ischemic sudden death, myocardial infarction, acute coronary syndromes and ischemic strokes. Persistent and sustained macrophage apoptosis appears to play a major role in the resulting local inflammatory response in part by effects elicited by Lp-PLA2. Selective inhibition of Lp-PLA2 has been postulated to reduce necrotic core progression and the clinical sequelae of advanced, unstable atherosclerosis.

  15. Hopelessness and 4-year progression of carotid atherosclerosis. The Kuopio Ischemic Heart Disease Risk Factor Study.

    PubMed

    Everson, S A; Kaplan, G A; Goldberg, D E; Salonen, R; Salonen, J T

    1997-08-01

    The importance of hope has long been recognized, whereas a lack of hope, or "giving up," is generally believed to have a negative impact on psychological well-being and physical health. Recently, hopelessness has been identified as a strong, independent predictor of cardiovascular disease morbidity and mortality in both American and Finnish populations. In this study we examined the association between high levels of hopelessness and progression of carotid atherosclerosis in participants (n = 942) in the Kuopio Ischemic Heart Disease Study, a population-based study of middle-aged men from eastern Finland who underwent carotid ultrasonography at baseline and 4 years later. Men reporting high levels of hopelessness at baseline had faster progression of carotid atherosclerosis, assessed by four measures of intima-media thickening (IMT), than men reporting low to moderate levels of hopelessness. Further analyses revealed significant interactions between hopelessness and initial level of atherosclerosis, such that the effects of high hopelessness on progression were greatest among men who had baseline mean IMT values at or above the median. Moreover, progression was greatest among men reporting high levels of hopelessness at both baseline and follow-up. Traditional coronary risk factors and use of cholesterol-lowering and antihypertensive medications did not account for much variance in the observed relationships. These findings indicate that hopelessness contributes to accelerated progression of carotid atherosclerosis, particularly among men with early evidence of atherosclerosis, and that chronically high levels of hopelessness may be especially detrimental. Additional research is needed to identify the contributory pathways and/or mechanisms underlying these relationships.

  16. Sleep duration and subclinical atherosclerosis: The Aragon Workers' Health Study.

    PubMed

    Blasco-Colmenares, Elena; Moreno-Franco, Belén; Latre, Montserrat León; Mur-Vispe, Eusebio; Pocovi, Miguel; Jarauta, Estíbaliz; Civeira, Fernando; Laclaustra, Martín; Casasnovas, José A; Guallar, Eliseo

    2018-05-03

    Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, and with heterogeneous findings. We evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities. We performed a cross-sectional analysis of 1968 men, 40-60 years of age, participating in the Aragon Workers' Health Study (AWHS). Duration of sleep during a typical work week was assessed by questionnaire. Coronary artery calcium scores (CACS) was assessed by computed tomography and the presence of carotid plaque and femoral plaque by ultrasound. In fully adjusted models, the odds ratios (95% CI) for CACS >0 comparing sleep durations of ≤5, 6, and ≥8 h with 7 h were 1.34 (0.98-1.85), 1.35 (1.08-1.69) and 1.21 (0.90-1.62), respectively (p = 0.04). A similar U-shaped association was observed for CACS ≥100 and for CACS. The corresponding odds ratios for the presence of at least one carotid plaque were ≤5, 6, and ≥8 h with 7 h were 1.23 (0.88-1.72), 1.09 (0.86-1.38), and 0.86 (0.63-1.17), respectively (p = 0.31), and for the presence of at least one femoral plaque were 1.25 (0.87-1.80), 1.19 (0.93-1.51) and 1.17 (0.86-1.61), respectively (p = 0.39). Middle-aged men reporting 7 h of sleep duration had the lowest prevalence of subclinical coronary atherosclerosis as assessed by CACs. Our results support that men with very short or very long sleep durations are at increased risk of atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans.

    PubMed

    Castillo-Richmond, A; Schneider, R H; Alexander, C N; Cook, R; Myers, H; Nidich, S; Haney, C; Rainforth, M; Salerno, J

    2000-03-01

    African Americans suffer disproportionately higher cardiovascular disease mortality rates than do whites. Psychosocial stress influences the development and progression of atherosclerosis. Carotid intima-media thickness (IMT) is a valid surrogate measure for coronary atherosclerosis, is a predictor of coronary outcomes and stroke, and is associated with psychosocial stress factors. Stress reduction with the Transcendental Meditation (TM) program decreases coronary heart disease risk factors and cardiovascular mortality in African Americans. B-mode ultrasound is useful for the noninvasive evaluation of carotid atherosclerosis. This randomized controlled clinical trial evaluated the effects of the TM program on carotid IMT in hypertensive African American men and women, aged >20 years, over a 6- to 9-month period. From the initially enrolled 138 volunteers, 60 subjects completed pretest and posttest carotid IMT data. The assigned interventions were either the TM program or a health education group. By use of B-mode ultrasound, mean maximum IMT from 6 carotid segments was used to determine pretest and posttest IMT values. Regression analysis and ANCOVA were performed. Age and pretest IMT were found to be predictors of posttest IMT values and were used as covariates. The TM group showed a significant decrease of -0.098 mm (95% CI -0. 198 to 0.003 mm) compared with an increase of 0.054 mm (95% CI -0.05 to 0.158 mm) in the control group (P=0.038, 2-tailed). Stress reduction with the TM program is associated with reduced carotid atherosclerosis compared with health education in hypertensive African Americans. Further research with this stress-reduction technique is warranted to confirm these preliminary findings.

  18. Atherosclerosis in epilepsy: its causes and implications.

    PubMed

    Hamed, Sherifa A

    2014-12-01

    Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Coronary artery disease (image)

    MedlinePlus

    ... through these arteries is critical for the heart. Coronary artery disease usually results from the build-up of fatty material and plaque, a condition called atherosclerosis. As the ... blood to the heart can slow or stop, causing chest pain (stable ...

  20. Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

    PubMed

    Mainous, Arch G; Everett, Charles J; Diaz, Vanessa A; Player, Marty S; Gebregziabher, Mulugeta; Smith, Daniel W

    2010-01-01

    To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45-84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80-1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

  1. Angiographic findings and clinical outcomes in asymptomatic patients with severe obstructive atherosclerosis on computed tomography angiography.

    PubMed

    Kornowski, Ran; Bachar, Gil N; Dvir, Danny; Fuchs, Shmuel; Atar, Eli

    2008-01-01

    Cardiac computed tomography angiography is a relatively new imaging modality to detect coronary atherosclerosis. To explore the diagnostic value of CTA in assessing coronary artery disease among asymptomatic patients. In this retrospective single-centered analysis, 622 consecutive patients underwent CTA of coronary arteries between November 2004 and May 2006 at the Mor Institute for Cardiovascular Imaging in Bnei Brak, Israel. All patients were asymptomatic but had at least one risk factor for atherosclerotic CAD. The initial 244 patients were examined with the 16-slice Brilliance CT scanner (Philips, Cleveland, OH, U.S.A.), and in the remaining 378 patients the 64-slice scanner (GE Healthcare, The Netherlands) with dedicated cardiac reconstruction software and electrocardiography triggering was used. Scanning was performed in the cranio-caudal direction. Images reconstructed in different phases of the cardiac cycle using a retrospective ECG-gated reconstruction algorithm were transferred to a dedicated workstation for review by experienced CT radiologists and cardiologists. Of 622 patients, 52 (8.4%) had severe obstructive atherosclerosis (suspected > or = 75% stenosis) according to CTA interpretation. Invasive coronary angiography was performed in 48 patients while 4 patients had no further procedure. A non-significant CAD (e.g., diameter stenosis < 70%) was identified in 6 of 48 patients (12%) by selective coronary angiography. Forty-two patients showed severe CAD with at least one lesion of 70% stenosis. Percutaneous coronary intervention was performed in 35 patients and coronary artery bypass grafting surgery in the other 4 patients. Angioplasty procedures were successful in all 35 patients and stents were utilized in all cases without complications. No further complications occurred among the study cohort undergoing either PCI or surgery. The 6 month survival rate in these patients was 100%. Non-invasive coronary CTA appears to be a reliable technique, with

  2. Coronary artery calcium before and after hospitalization with pneumonia: The MESA study.

    PubMed

    Corrales-Medina, Vicente F; Dwivedi, Girish; Taljaard, Monica; Petrcich, William; Lima, Joao A; Yende, Sachin; Kronmal, Richard A; Chirinos, Julio A

    2018-01-01

    Epidemiological analyses demonstrate that pneumonia survivors have a higher risk of myocardial infarction than people with similar load of risk factors for atherosclerotic cardiovascular disease (ASCVD) but without pneumonia. This may be due to a higher baseline burden of ASCVD in patients with pneumonia that is not captured by the accounting of known ASCVD risk factors in epidemiological analyses or to unfavorable accelerating effects of pneumonia on atherosclerosis. We analyzed data from the Multi-Ethnic Study of Atherosclerosis. We identified 54 participants that were hospitalized for pneumonia during study follow-up and that also had assessment of coronary artery calcium (CAC, an objective marker of coronary atherosclerotic burden) before and after this hospitalization. We matched them to 54 participants who were not hospitalized for pneumonia but that had CAC assessments at the same study visits as the pneumonia cases. We compared baseline CAC scores and their progression between groups. Baseline CAC scores were similar in both groups (median [IQR]; 6.3 [0-356.8] in pneumonia participants vs. 10.8 [0-178.3] in controls; p = 0.25). After a median of 4.8 years, the direction and magnitude of CAC score change, and the slope of CAC score progression between groups was also similar (median change [IQR], 21.8 [0 to 287.29] in participants with pneumonia versus 15.8 [0 to 140.94] in controls, p = 0.28; difference in slope, 7.7, 95% CI -9.0 to 24.6, p = 0.18). However, among participants with high baseline ASCVD risk (i.e. ACC/AHA 10-year risk estimate ≥7.5%), participants with pneumonia showed a larger increase in CAC scores (median change [IQR]; 159.10 [38.55-407.34] versus 48.72 [0.97-246.99] in controls; p = 0.02) and a trend towards a steeper slope of CAC score progression (difference in slope, 19.7, 95% CI -6.6 to 45.6, p = 0.07). Pneumonia may accelerate the progression of atherosclerosis in people with high baseline ASCVD risk.

  3. Macrophage Polarization by Angiotensin II-type 1 Receptor Aggravates Renal Injury-acceleration of Atherosclerosis

    PubMed Central

    Yamamoto, Suguru; Yancey, Patricia G.; Zuo, Yiqin; Ma, Li-Jun; Kaseda, Ryohei; Fogo, Agnes B.; Ichikawa, Iekuni; Linton, MacRae F.; Fazio, Sergio; Kon, Valentina

    2011-01-01

    Background Angiotensin II (AII) is a major determinant of atherosclerosis. Although macrophages are the most abundant cells in atherosclerotic plaques and express AII type 1 receptor (AT1), the pathophysiologic role of macrophage AT1 in atherogenesis remains uncertain. We examined the contribution of macrophage AT1 to accelerated atherosclerosis in an AII-responsive setting induced by uninephrectomy (UNx). Methods and Results AT1−/− or AT1+/+ marrow from apolipoprotein E deficient (apoE−/−) mice was transplanted into recipient apoE−/− mice with subsequent UNx or sham operation: apoE−/−/AT1+/+→apoE−/− + Sham; apoE−/−/AT1+/+→apoE−/− + UNx; apoE−/−/AT1−/−→apoE−/− + Sham; apoE−/−/AT1−/−→apoE−/− + UNx. No differences in body weight, blood pressure, lipid profile, and serum creatinine were observed between the two UNx groups. ApoE−/−/AT1+/+→apoE−/− + UNx had significantly more atherosclerosis (16907 ± 21473 vs 116071 ± 8180 μm2, p<0.05). By contrast, loss of macrophage AT1 which reduced local AT1 expression, prevented any effect of UNx on atherosclerosis (77174 ± 9947 vs 75714 ± 11333 μm2, p=NS). Although UNx did not affect total macrophage content in the atheroma, lesions in apoE−/−/AT1−/−→apoE−/− + UNx had fewer classically activated macrophage phenotype (M1) and more alternatively activated phenotype (M2). Further, UNx did not affect plaque necrosis or apoptosis in apoE−/−/AT1−/−→apoE−/− whereas it significantly increased both (by 2- and 6-fold, respectively) in apoE−/−/AT1+/+→apoE−/− mice. Instead, apoE−/−/AT1−/−→apoE−/− had 5-fold-increase in macrophage-associated apoptotic bodies, indicating enhanced efferocytosis. In vitro studies confirmed blunted susceptibility to apoptosis, especially in M2 macrophages, and a more efficient phagocytic function of AT1−/− macrophages vs AT1+/+. Conclusions AT1 receptor of bone marrow

  4. Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population.

    PubMed

    Owens, David S; Budoff, Matthew J; Katz, Ronit; Takasu, Junichiro; Shavelle, David M; Carr, J Jeffrey; Heckbert, Susan R; Otto, Catherine M; Probstfield, Jeffrey L; Kronmal, Richard A; O'Brien, Kevin D

    2012-06-01

    This study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population. Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals. We performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis. Over a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21). In this MESA cohort, free of clinical cardiovascular disease, AVC predicts

  5. Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions.

    PubMed

    Shiomi, M; Yamada, S; Amano, Y; Nishimoto, T; Ito, T

    2008-07-01

    Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions.

  6. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis.

    PubMed

    Shimabukuro, Michio; Hirata, Yoichiro; Tabata, Minoru; Dagvasumberel, Munkhbaatar; Sato, Hiromi; Kurobe, Hirotsugu; Fukuda, Daiju; Soeki, Takeshi; Kitagawa, Tetsuya; Takanashi, Shuichiro; Sata, Masataka

    2013-05-01

    The impact of epicardial adipose tissue (EAT) over abdominal or overall adiposity on coronary artery disease (CAD) is currently unknown. We compared the association among EAT volume (EATV), cytokine/adipocytokine profiles in EAT and subcutaneous fat, and atherogenic CAD. Paired samples were obtained from EAT and subcutaneous adipose tissue during elective cardiac surgery for CAD (n=50) or non-CAD (n=50). EATV was the sum of cross-sectional EAT areas, and visceral and subcutaneous fat areas were determined at the umbilicus level on computed tomography scans. CD68(+), CD11c(+), and CD206(+) cells were counted using immunohistochemical staining. Cytokine/adipocytokine expression was evaluated using quantitative real-time polymerase chain reaction. Multivariate analysis indicated that male sex, age, diabetes mellitus, high triglycerides, and low high-density lipoprotein cholesterol, and EATV index (EATV/body surface area, cm(3)/m(2)) were significant CAD predictors (corrected R(2)=0.401; P<0.001); visceral fat area, hypertension, smoking, low-density lipoprotein cholesterol (140 mg/dL [3.63 mmol/L]) or statin use were not predictors. The EATV index positively correlated with the CD68(+) and CD11c(+) cell numbers and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), interleukin-1β, and interleukin-1R expression; and negatively correlated with adiponectin expression in EAT. A multivariate analysis model, including CD68(+) cells and interleukin-1β, and adiponectin expression in EAT strongly predicted CAD (corrected R(2)=0.756; P<0.001). EATV and macrophage and cytokine/adipocytokine signals in EAT strongly correlated with CAD. Our findings suggest that EATV and adipocytokine imbalance are strongly linked to human coronary atherosclerosis.

  7. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications

    PubMed Central

    Kratz, Jeremy D.; Chaddha, Ashish; Bhattacharjee, Somnath

    2016-01-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID:26809711

  8. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    PubMed

    Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

    2016-02-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

  9. Hydroxychloroquine, a promising choice for coronary artery disease?

    PubMed

    Sun, Lizhe; Liu, Mengping; Li, Ruifeng; Zhao, Qiang; Liu, Junhui; Yang, Yanjie; Zhang, Lisha; Bai, Xiaofang; Wei, Yuanyuan; Ma, Qiangqiang; Zhou, Juan; Yuan, Zuyi; Wu, Yue

    2016-08-01

    Coronary artery disease is a common disease that seriously threaten the health of more than 150 million people per year. Atherosclerosis is considered to be the main cause of coronary artery disease which begins with damage or injury to the inner layer of a coronary artery, sometimes as early as childhood. The damage may be caused by various factors, including: smoking, high blood pressure, hypercholesterolemia, sedentary lifestyle, diabetes and insulin resistance. Once a coronary artery disease has developed, all patients need to be treated with long term standard treatment, including heart-healthy lifestyle changes, medicines, and medical procedures or surgery. Hydroxychloroquine, an original antimalarial drug, prevents inflammation caused by lupus erythematosus and rheumatoid arthritis. It is relatively safe and well-tolerated during the treatment. Since atherosclerosis and rheumatoid arthritis have resemble mechanism and increasing clinical researches confirm that hydroxychloroquine has an important role in both anti-rheumatoid arthritis and cardiovascular protection (such as anti-platelet, anti-thrombotic, lipid-regulating, anti-hypertension, hypoglycemia, and so on), we hypothesize that hydroxychloroquine might be a promising choice to coronary artery disease patients for its multiple benefits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Relationship of aortic valve calcification with coronary artery calcium severity: the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Nasir, Khurram; Katz, Ronit; Al-Mallah, Mouaz; Takasu, Junichiro; Shavelle, David M; Carr, Jeffery J; Kronmal, Richard; Blumenthal, Roger S; O'Brien, Kevin; Budoff, Matthew J

    2010-01-01

    Aortic valve calcification (AVC) and atherosclerosis share causative and pathologic features. We evaluated the relationship between AVC and coronary artery calcium (CAC) severity in the Multi-Ethnic Study of Atherosclerosis (MESA). Men and women aged 45-84 years (n=6809; mean age, 62 years) were studied. The presence and burden of AVC and CAC were determined by noncontrast cardiac computed tomography. Relative risk regression was used to model the probability of AVC as a function of CAC > 0 as well as CAC categories (0, 1-99, 100-399, and > or = 400) with the reference group being CAC=0. The prevalence of AVC and CAC was 13% and 50%, respectively. Among those without CAC, the prevalence of AVC was 5% and increased across levels of CAC severity such that 14%, 25%, and 38% had AVC with increasing CAC scores of 1-99, 100-399, and > or = 400, respectively (P for trend<0.0001). After controlling for patient demographic factors and cardiovascular risk factors, the prevalence ratio of AVC among those with mild CAC (1-99) was 1.83 (95% CI, 1.45-2.31) and increased to 3.36 (95% CI, 2.56-4.42) for CAC > or = 400. Similar statistically significant increased risk of AVC was found when CAC was assessed as a continuous variable. Our study shows that AVC is independently associated with increasing severity of CAC. 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  11. Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions

    PubMed Central

    Shiomi, M; Yamada, S; Amano, Y; Nishimoto, T; Ito, T

    2008-01-01

    Background and purpose: Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). Experimental approach: Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. Key results: Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. Conclusion and implications: Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions. PMID:18587443

  12. Serum neutrophil gelatinase-associated lipocalin levels are correlated with the complexity and the severity of atherosclerosis in acute coronary syndrome

    PubMed Central

    Soylu, Korhan; Aksan, Gökhan; Nar, Gökay; Özdemir, Metin; Gülel, Okan; İnci, Sinan; Aksakal, Aytekin; İdil Soylu, Ayşegül; Yılmaz, Özcan

    2015-01-01

    Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is a novel inflammatory marker that is released from neutrophils. In this study, we evaluated the correlation between serum NGAL level and clinical and angiographic risk scores in patients diagnosed with non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: Forty-seven random NSTE-ACS patients and 45 patients with normal coronary arteries (NCA) who underwent coronary angiography were enrolled in the study. GRACE risk score and SYNTAX and Gensini risk scores were used, respectively, for the purpose of clinical risk assessment and angiographic risk scoring. Serum NGAL level was measured via ELISA in peripheral blood samples obtained from the patients at the time of admission. Results: Serum NGAL level was significantly higher in the NSTE-ACS group compared to the control group (112.3±49.6 ng/mL vs. 58.1±24.3 ng/mL, p<0.001). There was a significant positive correlation between serum NGAL levels and the GRACE (r=0.533 and p<0.001), SYNTAX (r=0.395 and p=0.006), and Gensini risk scores (r=0.575 and p<0.001). The intermediate-high SYNTAX (>22) group had statistically significantly higher serum NGAL levels compared to the low SYNTAX (≤22) group (143±29.5 ng/mL vs. 98.7±43.2 ng/mL, p=0.001). Conclusion: NGAL level was positively correlated with lesion complexity and severity of coronary artery disease in patients with NSTE-ACS. Serum NGAL levels on admission are associated with increased burden of atherosclerosis in patients with NSTE-ACS. PMID:25430410

  13. Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration

    NASA Technical Reports Server (NTRS)

    Lin, S. S.; Lauer, M. S.; Asher, C. R.; Cosgrove, D. M.; Blackstone, E.; Thomas, J. D.; Garcia, M. J.

    2001-01-01

    OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (< or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

  14. Intravascular ultrasound in coronary atherosclerosis: a new approach to clinical assessment.

    PubMed

    Liebson, P R; Klein, L W

    1992-06-01

    Intravascular ultrasound evaluation of the coronary arteries by means of a selective coronary catheter attached to an ultrasound unit has afforded precise depiction of coronary lumen diameter and area at the level of the catheter tip. The arterial wall at this level can be evaluated for lipid, fibrous tissue, calcification, wall dissections, and intraluminal thrombi. The technique has the advantage over coronary angioscopy and angiography in that it does not require infusions or injections to allow visualization, and it has the ability to depict the inside of the arterial wall. The current disadvantages include the inability to visualize the vessel segments distal to the catheter tip. Three-dimensional reconstruction techniques allow depiction of the segment of the artery traversed by the catheter tip. The use of Doppler ultrasound imaging provides information on coronary flow velocities through coronary obstructions. Intravascular ultrasound images may provide information that complements the coronary arteriogram and may have an impact on patient care and clinical investigation strategies.

  15. Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics.

    PubMed

    Ratner, Robert E; Cannon, Christopher P; Gerstein, Hertzel C; Nesto, Richard W; Serruys, Patrick W; Van Es, Gerrit-Anne; Kolatkar, Nikheel S; Kravitz, Barbara G; Zalewski, Andrew; Fitzgerald, Peter J

    2008-12-01

    Rosiglitazone, a thiazolidinedione, has effects on insulin sensitivity and cardiovascular risk factors that may favorably impact the progression of coronary atherosclerosis. APPROACH is a double-blind randomized clinical trial comparing the effects of the insulin sensitizer rosiglitazone with the insulin secretagogue glipizide on the progression of coronary atherosclerosis. Patients with type 2 diabetes and coronary artery disease undergoing clinically indicated coronary angiography or percutaneous coronary intervention are randomized to receive rosiglitazone or glipizide for 18 months using a titration algorithm designed to provide comparable glycemic control between treatment groups. The primary end point is change in percent atheroma volume from baseline to study completion in a nonintervened coronary artery, as measured by intravascular ultrasound. Cardiovascular events are adjudicated by an end point committee. A total of 672 patients were randomized. The mean age was 61 years, hemoglobin A(1c) (HbA(1c)) 7.2%, body mass index 29.5 kg/m(2), and median duration of diabetes 4.8 years. At baseline, approximately half of the participants were receiving oral antidiabetic monotherapy (53.9%) with 27.5% receiving dual combination therapy and 17.9% treated with diet and exercise alone. Approximately two thirds of the participants (68%) had dyslipidemia, 79.9% hypertension, and 24% prior myocardial infarction. APPROACH has fully enrolled a high-risk patient population and will compare the glucose-independent effects of rosiglitazone and glipizide on the progression of coronary atherosclerosis, as well as provide additional data on the cardiovascular safety of rosiglitazone in patients with type 2 diabetes and coronary artery disease.

  16. Aneurysmal coronary artery disease: An overview

    PubMed Central

    ElGuindy, Mohamed S.

    Aneurysmal coronary artery disease (ACAD) comprises both coronary artery aneurysms (CAA) and coronary artery ectasia (CAE). The reported prevalence of ACAD varies widely from 0.2 to 10%, with male predominance and a predilection for the right coronary artery (RCA). Atherosclerosis is the commonest cause of ACAD in adults, while Kawasaki disease is the commonest cause in children and adolescents, as well as in the Far East. Most patients are asymptomatic, but when symptoms do exist, they are usually related to myocardial ischemia. Coronary angiography is the mainstay of diagnosis, but follow up is best achieved using noninvasive imaging that does not involve exposure to radiation. The optimal management strategy in patients with ACAD remains controversial. Medical therapy is indicated for the vast majority of patients and includes antiplatelets and/or anticoagulants. Covered stents effectively limit further expansion of the affected coronary segments. Surgical ligation, resection, and coronary artery bypass grafting are appropriate for large lesions and for associated obstructive coronary artery disease. PMID:29564347

  17. Association between green tea intake and coronary artery disease in a Chinese population.

    PubMed

    Wang, Qi-Ming; Gong, Qing-Yue; Yan, Jian-Jun; Zhu, Jun; Tang, Jian-Jin; Wang, Ming-Wei; Yang, Zhi-Jian; Wang, Lian-Sheng

    2010-02-01

    There is still conflicting evidence that green tea may protect against coronary atherosclerosis therefore the present study investigated the association between green tea consumption and arteriographically determined coronary atherosclerosis in a Chinese population. The study population consisted of 520 consecutive patients (379 men and 141 women) who underwent coronary arteriography for the first time. Patients were divided into 2 groups (Non-coronary artery disease [CAD] and CAD groups) according to the results of coronary arteriography. After adjusting the established and potential confounders, green tea consumption was associated with a reduced risk of CAD in male patients, with an adjusted odds ratio (OR) of 0.62 (95% confidence interval, 0.38-1.01) compared with those who did not drink green tea. Compared to non-tea drinkers, the adjusted ORs were 1.09 (0.61-1.96) in male patients consuming less than 125 g of dried green tea leaves per month, 0.36 (0.19-0.71) for 125-249 g per month and 0.36 (0.17-0.73) for > or =250 g per month, with a statistically significant test for trend (P<0.001). Similar dose-response relationships were also observed for frequency, duration, concentration and starting age of green tea drinking in male patients. In female patients, no inverse association was found between green tea consumption and CAD. Green tea consumption can protect against the development of coronary atherosclerosis in Chinese male patients.

  18. Fluorescence multispectral imaging-based diagnostic system for atherosclerosis.

    PubMed

    Ho, Cassandra Su Lyn; Horiuchi, Toshikatsu; Taniguchi, Hiroaki; Umetsu, Araya; Hagisawa, Kohsuke; Iwaya, Keiichi; Nakai, Kanji; Azmi, Amalina; Zulaziz, Natasha; Azhim, Azran; Shinomiya, Nariyoshi; Morimoto, Yuji

    2016-08-20

    Composition of atherosclerotic arterial walls is rich in lipids such as cholesterol, unlike normal arterial walls. In this study, we aimed to utilize this difference to diagnose atherosclerosis via multispectral fluorescence imaging, which allows for identification of fluorescence originating from the substance in the arterial wall. The inner surface of extracted arteries (rabbit abdominal aorta, human coronary artery) was illuminated by 405 nm excitation light and multispectral fluorescence images were obtained. Pathological examination of human coronary artery samples were carried out and thickness of arteries were calculated by measuring combined media and intima thickness. The fluorescence spectra in atherosclerotic sites were different from those in normal sites. Multiple regions of interest (ROI) were selected within each sample and a ratio between two fluorescence intensity differences (where each intensity difference is calculated between an identifier wavelength and a base wavelength) from each ROI was determined, allowing for discrimination of atherosclerotic sites. Fluorescence intensity and thickness of artery were found to be significantly correlated. These results indicate that multispectral fluorescence imaging provides qualitative and quantitative evaluations of atherosclerosis and is therefore a viable method of diagnosing the disease.

  19. [Myocardial bridge as the only cause of acute coronary syndrome among the young patients].

    PubMed

    Miakinkova, Liudmila O; Teslenko, Yurii V; Tsyhanenko, Irina V

    2018-01-01

    Introduction: Myocardial bridge is an inborn anomaly of coronary artery development, when a part of it is submerged in a myocard, which is pressing the coronary artery to a systola and restrains coronary blood circulation. Generally this feature of coronary blood circulation does not cause any clinical symptoms because the 85% of coronary blood stream of the left ventricle is provided by diastolic filling. Hemodynamic changes in atherosclerosis, tahicardie, hypertrophie of myocard are leading to the manifestation of clinical symptoms of ischemia. The aim: The purpose of the investigation was to discover the features of clinical development of acute coronary syndrome caused by myocardial bridge of young patients without the features of atherosclerotical harm of coronary arteries. Materials and methods: Eight causes of acute coronary syndrome among patients of 28±8,5 years with myocardial bridge which was revealed during coronary angiography, were investigated. Standardized examination and conservative treatment of patients was held, except for three who have got interventional therapy. Results: According to our investigation, myocardial bridge of all investigated patients was located in the middle of the third front interventricular branch of the left coronary artery. Causes of acute coronary syndrome manifestation were tahicardia, spasms of coronary artery, inducted by iatrogenic factors hypertrophie of myocard, hypertrophic cardiomyopatie. Connection between the manifestation of clinical symptoms and length of tunneled segment which did not depend on the level of systolic compres was discovered. The results of conservative and interventional treatment were analyzed. Conclusions: Myocardial bridge can be the cause of myocardial ischemia among patients without signs of coronary atherosclerosis with additional hemodynamic risk facts such as tahicardia, spasms of coronary artery, hypertrophie of myocard. Clinical symptomatology of the acute coronary syndrome is more

  20. Coronary heart disease risk stratification: pitfalls and possibilities.

    PubMed

    Negi, Smita; Nambi, Vijay

    Atherosclerosis of the coronary arteries, or coronary heart disease (CHD), is the most common cause of mortality in U.S. adults. The pathobiology of atherosclerosis and its complications is a continuum. At one end of the spectrum are young individuals without atherosclerotic disease who have not yet been exposed to lifestyle or other risk factors, and at the other end are patients with manifest atherosclerosis - myocardial infarction, stroke, and disabling peripheral arterial disease - where risk of recurrent disease and death is driven by the same factors initially responsible for the emergence of disease. However, it is clear that while risk factors are important in the development of CHD, not everyone with risk factors develops the disease and not everyone with CHD has risk factors. Furthermore, even similar degrees of exposure to a risk factor leads to disease in some individuals and not in others. Risk prediction, which is crucial in predicting and hence preventing disease, therefore becomes very challenging. In this article we review the currently available risk stratification tools for predicting CHD risk and discuss potential ways to improve risk prediction.

  1. Single nucleotide polymorphisms associated with coronary heart disease predict incident ischemic stroke in the atherosclerosis risk in communities study.

    PubMed

    Morrison, Alanna C; Bare, Lance A; Luke, May M; Pankow, James S; Mosley, Thomas H; Devlin, James J; Willerson, James T; Boerwinkle, Eric

    2008-01-01

    Ischemic stroke and coronary heart disease (CHD) may share genetic factors contributing to a common etiology. This study investigates whether 51 single nucleotide polymorphisms (SNPs) associated with CHD in multiple antecedent studies are associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. From the multiethnic ARIC cohort of 14,215 individuals, 495 validated ischemic strokes were identified. Cox proportional hazards models, adjusted for age and gender, identified three SNPs in Whites and two SNPs in Blacks associated with incident stroke (p

  2. HIV-1-Associated Atherosclerosis: Unraveling the Missing Link.

    PubMed

    Kearns, Alison; Gordon, Jennifer; Burdo, Tricia H; Qin, Xuebin

    2017-06-27

    Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation. There is a pressing need to experimentally unravel the missing link between HIV and atherosclerosis. Understanding these mechanisms will help to better develop and design novel therapeutic interventions for the treatment of HIV-associated cardiovascular disease. HIV mainly infects T cells and macrophages resulting in the induction of oxidative and endoplasmic reticulum stress, the formation of the inflammasome, and the dysregulation of autophagy. These mechanisms may contribute to HIV-associated atherogenesis. In this review, we will summarize our current understanding and propose potential mechanisms of HIV-associated atherosclerosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat.

    PubMed

    Company, Joseph M; Booth, Frank W; Laughlin, M Harold; Arce-Esquivel, Arturo A; Sacks, Harold S; Bahouth, Suleiman W; Fain, John N

    2010-12-01

    Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies.

  4. Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat

    PubMed Central

    Booth, Frank W.; Laughlin, M. Harold; Arce-Esquivel, Arturo A.; Sacks, Harold S.; Bahouth, Suleiman W.; Fain, John N.

    2010-01-01

    Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies. PMID:20947714

  5. Endothelium-specific insulin resistance leads to accelerated atherosclerosis in areas with disturbed flow patterns: a role for reactive oxygen species.

    PubMed

    Gage, Matthew C; Yuldasheva, Nadira Y; Viswambharan, Hema; Sukumar, Piruthivi; Cubbon, Richard M; Galloway, Stacey; Imrie, Helen; Skromna, Anna; Smith, Jessica; Jackson, Christopher L; Kearney, Mark T; Wheatcroft, Stephen B

    2013-09-01

    Systemic insulin resistance is associated with a portfolio of risk factors for atherosclerosis development. We sought to determine whether insulin resistance specifically at the level of the endothelium promotes atherosclerosis and to examine the potential involvement of reactive oxygen species. We cross-bred mice expressing a dominant negative mutant human insulin receptor specifically in the endothelium (ESMIRO) with ApoE(-/-) mice to examine the effect of endothelium-specific insulin resistance on atherosclerosis. ApoE(-/-)/ESMIRO mice had similar blood pressure, plasma lipids and whole-body glucose tolerance, but blunted endothelial insulin signalling, in comparison to ApoE(-/-) mice. Atherosclerosis was significantly increased in ApoE(-/-)/ESMIRO mice at the aortic sinus (226 ± 16 versus 149 ± 24 × 10(3) μm(2), P = 0.01) and lesser curvature of the aortic arch (12.4 ± 1.2% versus 9.4 ± 0.9%, P = 0.035). Relaxation to acetylcholine was blunted in aorta from ApoE(-/-)/ESMIRO mice (Emax 65 ± 41% versus 103 ± 6%, P = 0.02) and was restored by the superoxide dismutase mimetic MnTMPyP (Emax 112 ± 15% versus 65 ± 41%, P = 0.048). Basal generation of superoxide was increased 1.55 fold (P = 0.01) in endothelial cells from ApoE(-/-)/ESMIRO mice and was inhibited by the NADPH oxidase inhibitor gp91ds-tat (-12 ± 0.04%, P = 0.04), the NO synthase inhibitor L-NMMA (-8 ± 0.02%, P = 0.001) and the mitochondrial specific inhibitor rotenone (-23 ± 0.04%, P = 0.006). Insulin resistance specifically at the level of the endothelium leads to acceleration of atherosclerosis in areas with disturbed flow patterns such as the aortic sinus and the lesser curvature of the aorta. We have identified a potential role for increased generation of reactive oxygen species from multiple enzymatic sources in promoting atherosclerosis in this setting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Computational fluid dynamics tools can be used to predict the progression of coronary artery disease

    NASA Astrophysics Data System (ADS)

    Coşkun, A. Ümit; Chen, Caixia; Stone, Peter H.; Feldman, Charles L.

    2006-03-01

    Atherosclerosis is focal and individual plaques evolve in an independent manner. The endothelium regulates arterial behavior by responding to its local shear stress. In vitro studies indicate that low endothelial shear stress (ESS) upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic ESS is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High ESS promotes platelet aggregation. ESS and vascular wall morphology along the course of human coronary arteries can now be characterized in vivo, and may predict the focal areas in which atherosclerosis progression occurs. Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic factors likely responsible for progression of coronary disease in man. These new diagnostic modalities allow for identification of plaque progression. Accurate identification of arterial segments at high-risk for progression may permit pre-emptive intervention strategies to avoid adverse coronary events.

  7. Dark-field imaging in coronary atherosclerosis.

    PubMed

    Hetterich, Holger; Webber, Nicole; Willner, Marian; Herzen, Julia; Birnbacher, Lorenz; Auweter, Sigrid; Schüller, Ulrich; Bamberg, Fabian; Notohamiprodjo, Susan; Bartsch, Harald; Wolf, Johannes; Marschner, Mathias; Pfeiffer, Franz; Reiser, Maximilian; Saam, Tobias

    2017-09-01

    Dark-field imaging based on small angle X-ray scattering has been shown to be highly sensitive for microcalcifications, e.g. in breast tissue. We hypothesized (i) that high signal areas in dark-field imaging of atherosclerotic plaque are associated with microcalcifications and (ii) that dark-field imaging is more sensitive for microcalcifications than attenuation-based imaging. Fifteen coronary artery specimens were examined at an experimental set-up consisting of X-ray tube (40kV), grating-interferometer and detector. Tomographic dark-field-, attenuation-, and phase-contrast data were simultaneously acquired. Histopathology served as standard of reference. To explore the potential of dark field imaging in a full-body CT system, simulations were carried out with spherical calcifications of different sizes to simulate small and intermediate microcalcifications. Microcalcifications were present in 10/10 (100%) cross-sections with high dark-field signal and without evidence of calcifications in attenuation- or phase contrast. In positive controls with high signal areas in all three modalities, 10/10 (100%) cross-sections showed macrocalcifications. In negative controls without high signal areas, no calcifications were detected. Simulations showed that the microcalcifications generate substantially higher dark-field than attenuation signal. Dark-field imaging is highly sensitive for microcalcifications in coronary atherosclerotic plaque and might provide complementary information in the assessment of plaque instability. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Migraine and subclinical atherosclerosis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    PubMed

    Goulart, Alessandra C; Santos, Itamar S; Bittencourt, Márcio S; Lotufo, Paulo A; Benseñor, Isabela M

    2016-08-01

    The relationship between migraine and coronary heart disease (CHD) remains controversial. We aimed to investigate the association of subclinical atherosclerosis and migraine with or without aura compared to a non-migraine subgroup (reference) in a large Brazilian multicentric cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Migraine diagnostic was based on International Headache Society criteria, and aura symptoms were validated by a medical doctor in a sub-sample of the ELSA-Brasil, who also underwent coronary artery calcium score (CAC) and carotid intima-media thickness (C-IMT) evaluations. Subclinical atherosclerosis indexes (CAC and C-IMT) were analyzed as dependent variables and migraine (all, with aura, without aura) as an independent variable in the linear and multinomial logistic regression models adjusted for possible confounders. Of 3217 ELSA participants free from CVD at baseline, we found a migraine frequency of 11.9% (5.1% with aura and 6.8% without aura). Overall, migraineurs were mostly women, younger and had lower frequency of CV risk factors, such as hypertension, diabetes and low HDL-cholesterol, compared to non-migraineurs. The strongest inverse correlation between migraine and subclinical atherosclerosis was verified with CAC score. However, all associations lost their significance after multivariate adjustment. In this cross-sectional evaluation of the ELSA study, migraine was not associated with subclinical atherosclerosis, regardless of aura symptoms. © International Headache Society 2015.

  9. A Cylindrical, Inner Volume Selecting 2D-T2-Prep Improves GRAPPA-Accelerated Image Quality in MRA of the Right Coronary Artery

    PubMed Central

    Coristine, Andrew J.; Yerly, Jerome; Stuber, Matthias

    2016-01-01

    Background Two-dimensional (2D) spatially selective radiofrequency (RF) pulses may be used to excite restricted volumes. By incorporating a "pencil beam" 2D pulse into a T2-Prep, one may create a "2D-T2-Prep" that combines T2-weighting with an intrinsic outer volume suppression. This may particularly benefit parallel imaging techniques, where artefacts typically originate from residual foldover signal. By suppressing foldover signal with a 2D-T2-Prep, image quality may therefore improve. We present numerical simulations, phantom and in vivo validations to address this hypothesis. Methods A 2D-T2-Prep and a conventional T2-Prep were used with GRAPPA-accelerated MRI (R = 1.6). The techniques were first compared in numerical phantoms, where per pixel maps of SNR (SNRmulti), noise, and g-factor were predicted for idealized sequences. Physical phantoms, with compartments doped to mimic blood, myocardium, fat, and coronary vasculature, were scanned with both T2-Preparation techniques to determine the actual SNRmulti and vessel sharpness. For in vivo experiments, the right coronary artery (RCA) was imaged in 10 healthy adults, using accelerations of R = 1,3, and 6, and vessel sharpness was measured for each. Results In both simulations and phantom experiments, the 2D-T2-Prep improved SNR relative to the conventional T2-Prep, by an amount that depended on both the acceleration factor and the degree of outer volume suppression. For in vivo images of the RCA, vessel sharpness improved most at higher acceleration factors, demonstrating that the 2D-T2-Prep especially benefits accelerated coronary MRA. Conclusion Suppressing outer volume signal with a 2D-T2-Prep improves image quality particularly well in GRAPPA-accelerated acquisitions in simulations, phantoms, and volunteers, demonstrating that it should be considered when performing accelerated coronary MRA. PMID:27736866

  10. Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma.

    PubMed

    Tsukahara, Tamotsu; Tsukahara, Ryoko; Haniu, Hisao; Matsuda, Yoshikazu; Murakami-Murofushi, Kimiko

    2015-09-05

    Atherosclerosis is a disease characterized by building up plaques formation and leads to a potentially serious condition in which arteries are clogged by fatty substances such as cholesterol. Increasing evidence suggests that atherosclerosis is accelerated in type 2 diabetes. Recent study reported that high level of alkyl glycerophosphate (AGP) was accumulated in atherosclerotic lesions. The presence of this phospholipid in mildly oxidized low-density lipoprotein (LDL) is likely to be involved in atherogenesis. It has been reported that the activation of peroxisome proliferator-activated receptor gamma plays a key role in developing atherosclerosis. Our previous result indicates that cyclic phosphatidic acid (cPA), one of bioactive lipids, potently suppresses neointima formation by inhibiting the activation of peroxisome proliferator-activated receptor gamma (PPARγ). However, the detailed mechanism is still unclear. In this study, to elucidate the mechanism of the cPA-PPARγ axis in the coronary artery endothelium, especially in patients with type 2 diabetes, we investigated the proliferation, migration, and secretion of VEGF in human coronary artery endothelial cells from diabetes patients (D-HCAECs). AGP induced cell growth and migration; however, cPA suppressed the AGP-elicited growth and migration in D-HCAECs. Moreover, AGP increased VEGF secretion from D-HCAECs, and this event was attenuated by cPA. Taken together, these results suggest that cPA suppresses VEGF-stimulated growth and migration in D-HCAECs. These findings could be important for regulatory roles of PPARγ and VEGF in the vascular processes associated with diabetes and atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Gene expression variation between African Americans and whites is associated with coronary artery calcification: the multiethnic study of atherosclerosis

    PubMed Central

    Lloyd-Jones, Donald M.; Guo, Xiuqing; Rajamannan, Nalini M.; Lin, Simon; Du, Pan; Huang, Qiquan; Hou, Lifang; Liu, Kiang

    2011-01-01

    Coronary artery calcium (CAC) is a strong indicator of total atherosclerosis burden. Epidemiological data have shown substantial differences in CAC prevalence and severity between African Americans and whites. However, little is known about the molecular mechanisms underlying initiation and progression of CAC. Microarray gene expression profiling of peripheral blood leucocytes was performed from 119 healthy women aged 50 yr or above in the Multi-Ethnic Study of Atherosclerosis cohort; 48 women had CAC score >100 and carotid intima-media thickness (IMT) >1 mm, while 71 had CAC <10 and IMT <0.65 mm. When 17 African Americans were compared with 41 whites in the low-CAC group, 409 differentially expressed genes (false discovery rate <5%)were identified. In addition, 316 differentially expressed genes were identified between the high- and low-CAC groups. A substantial overlap between these two gene lists was observed (148 genes, P < 10−6). Furthermore, genes expressed lower in African Americans also tend to express lower in individuals with low CAC (correlation 0.69, P = 0.002). Ontology analysis of the 409 race-associated genes revealed significant enrichment in mobilization of calcium and immune/inflammatory response (P < 10−9). Of note, 25 of 30 calcium mobilization genes were involved in immune/inflammatory response (P < 10−10). Our data suggest a connection between immune response and vascular calcification and the result provides a potential mechanistic explanation for the lower prevalence and severity of CAC in African Americans compared with whites. PMID:21521779

  12. Subclinical atherosclerosis and subsequent cognitive function

    PubMed Central

    Rossetti, Heidi C.; Weiner, Myron; Hynan, Linda S.; Cullum, C. Munro; Khera, Amit; Lacritz, Laura H.

    2016-01-01

    Objective To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Method Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8–65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. Results A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥.052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥.455). Conclusion In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. PMID:25957568

  13. Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis

    PubMed Central

    Aikawa, Elena; Newby, David E.; Tarkin, Jason M.; Rudd, James H.F.; Narula, Jagat; Fayad, Zahi A.

    2016-01-01

    Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques. PMID:27390335

  14. Predict value of adiponectin for coronary atherosclerosis plaques according to computed tomography angiography in an asymptomatic population.

    PubMed

    Gan, Lu; Yang, Li; Yan, Guangtao

    2018-05-25

    The association between serum adiponectin levels and coronary atherosclerosis plaque characteristics in asymptomatic populations is unclear. To examine the predictive value of serum adiponectin levels for coronary high risk plaques as detected by computed tomography angiography (CTA). This was a cross-sectional study. All patients were divided into high risk plaque group and non high risk plaque group. The FRS was calculated for each patient. CTA was performed for each patient. Adiponectin levels were measured by flow fluorescence immunmicrobead assay (FFIA). Receiver-operating characteristic (ROC) curves and multivariate analysis was used to determine the predictive value of adiponectin for high risk plaques. The high risk plaque group showed lower adiponectin levels than non high risk plaque group (median, 7.27 vs. 8.51 μg/ml, P = 0.003). The multivariate analysis showed that age (OR = 2.62, 95%CI: 1.51-4.56, P = 0.001), hyperlipidemia (OR = 1.89, 95%CI: 1.07-3.36, P = 0.029), high-density lipoprotein cholesterol (HDL-C) (OR = 0.46, 95%CI: 0.24-0.87, P = 0.02), the ratio of total cholesterol to high-density lipoproteincholesterol (TC/HDL-C) (OR = 0.69, 95%CI: 0.50-0.94, P = 0.02), apolipoprotein B (apoB) (OR = 3.08, 95%CI: 1.50-6.32, P = 0.002), and adiponectin (OR = 0.37, 95%CI: 0.19-0.74, P = 0.005) were independently associated with the presence of high risk plaques. AUC of the multivariate model for high-risk plaques was 0.728 (95%CI: 0.627-0.783). Sensitivity was 74.9%, specificity was 60.2%, the positive predictive value was 65.3%, and the negative predictive value was 70.6%. Decreased adiponectin levels were associated with the presence of high-risk plaques in asymptomatic populations at low to intermediate FRS. Adiponectin can play an important role in plaque screening before coronary CTA. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden.

    PubMed

    Kataoka, Yu; Andrews, Jordan; Duong, MyNgan; Nguyen, Tracy; Schwarz, Nisha; Fendler, Jessica; Puri, Rishi; Butters, Julie; Keyserling, Constance; Paolini, John F; Dasseux, Jean-Louis; Nicholls, Stephen J

    2017-06-01

    CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001. CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group. A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV <30% (-0.45%±2.65% vs. +0.34%±1.69%, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV <30% (3 mg/kg; +0.41%±0.32%, P=0.39; 6 mg/kg; +0.27%±0.36%, P=0.76; 12 mg/kg; +0.32%±0.37%, P=0.97). Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

  16. Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden

    PubMed Central

    Kataoka, Yu; Andrews, Jordan; Duong, MyNgan; Nguyen, Tracy; Schwarz, Nisha; Fendler, Jessica; Puri, Rishi; Butters, Julie; Keyserling, Constance; Paolini, John F.; Dasseux, Jean-Louis

    2017-01-01

    Background CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001. Methods CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group. Results A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV <30% (−0.45%±2.65% vs. +0.34%±1.69%, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30% (−0.96%±0.34% vs. −0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV <30% (3 mg/kg; +0.41%±0.32%, P=0.39; 6 mg/kg; +0.27%±0.36%, P=0.76; 12 mg/kg; +0.32%±0.37%, P=0.97). Conclusions Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy. PMID:28567351

  17. Rapid emergence of atherosclerosis in Asia: a systematic review of coronary atherosclerotic heart disease epidemiology and implications for prevention and control strategies.

    PubMed

    Wong, Martin C S; Zhang, De Xing; Wang, Harry H X

    2015-08-01

    There is a global epidemic of coronary heart disease (CHD) caused by atherosclerosis. We discussed its emergence, underlying reasons, and implications for prevention and control strategies in Asia. Most countries in Asia are experiencing the challenges from CHD, with the mortality rate varying from 103 to 366 per 100 000 adult populations, reported by recently published studies. Raised population cholesterol levels played a pivotal role. Men, older adults, and those with dyslipidemia, hypertension, and diabetes were high-risk individuals. During the past decade, there was a marked rising trend of atherosclerosis-related burden particularly in Eastern Asia where an alarming increase of 117.2 and 115.3% of total deaths and disability adjusted life-years, respectively, were observed. The rise of CHD could be attributed to unhealthy lifestyles, clinical-risk factors, psychosocial factors, and public health transitions. Ageing, urbanization, and increase in prosperity may serve as underlying key drivers. The burden of CHD is substantial, whereas contributors are multifactorial. This grand challenge should be a top priority for injecting healthcare resources. The formulation of public health measures will need to adopt an integrated and life-course approach, based on the need and risks of different population subgroups in Asia.

  18. Mitral annular calcification associated with impaired coronary microvascular function.

    PubMed

    Bozbas, Huseyin; Pirat, Bahar; Yildirir, Aylin; Simşek, Vahide; Sade, Elif; Altin, Cihan; Muderrisoglu, Haldun

    2008-05-01

    Mitral annular calcification (MAC) has been shown to be associated with atherosclerosis, and is a predictor of cardiovascular events. Coronary flow reserve (CFR) determined by transthoracic echocardiography has been introduced as a reliable indicator for coronary microvascular function. In this study we sought to investigate CFR in patients with and without MAC. Seventy patients (mean age, 68.2+/-6.6 years) who were free of coronary artery disease or diabetes mellitus were involved; 35 patients with MAC constituted the experimental group while 35 patients without MAC served as controls. Using transthoracic Doppler echocardiography coronary peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities. The clinical and demographic characteristics including age, sex, and traditional coronary risk factors did not differ between the groups (P>.05). The mean value of CFR was significantly lower in participants with mitral annular calcification than it was in controls (2.25+/-0.41 vs. 2.64+/-0.57; P<.0001). Multivariable regression analysis identified MAC (beta=-0.40, P=.004), smoking (beta=-0.36, P=.007), and C-reactive protein levels (beta=-0.28, P=.04) as the independent variables significantly associated with CFR. Our results demonstrate that CFR is impaired in patients with mitral annular calcification suggesting that coronary microvascular-endothelial dysfunction, an early finding of atherosclerosis, is present in these patients.

  19. Family history does not predict angiographic localization or severity of coronary artery disease.

    PubMed

    Banerjee, Amitava; Lim, Chris C S; Silver, Louise E; Heneghan, Carl; Welch, Sarah J V; Mehta, Ziyah; Banning, Adrian P; Rothwell, Peter M

    2012-04-01

    Family history of MI is an established risk factor for coronary artery disease and subclinical atherosclerosis. Maternal MI and maternal stroke are more common in females than males presenting with acute coronary syndromes (ACS), suggesting sex-specific heritability, but the effects of family history on location and extent of coronary artery disease are unknown. In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS, family history data for stroke and MI were analysed by sex of proband and affected first degree relatives (FDRs), and coronary angiograms were reviewed, where available. Of 835 probands with one or more ACS, 623 (420 males) had incident events and complete family history data. 351 patients with incident events (56.3%; 266 males) underwent coronary angiography. Neither angiographic disease localization nor severity were associated with sex-of-parent/sex-of-offspring in men or women. Sex-specific family history data do not predict angiographic localization of coronary disease in patients presenting with ACS. Maternal stroke and maternal MI probably affect ACS in females by a mechanism unrelated to atherosclerosis or coronary anatomy. However, family history data may still be useful in risk prediction and prognosis of ACS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    PubMed

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  1. Cyanotic congenital heart disease and coronary artery atherogenesis.

    PubMed

    Fyfe, Alistair; Perloff, Joseph K; Niwa, Koichiro; Child, John S; Miner, Pamela D

    2005-07-15

    Hypoxemic erythrocytotic residents of high altitudes lack coronary atherosclerosis and have low cholesterol levels. It was postulated that hypoxemic erythrocytotic adults with cyanotic congenital heart disease (CCHD) might be analogous. The incidence of coronary atherosclerosis in this patient population has not been established, and hypocholesterolemia has not previously been recognized. Accordingly, 279 patients were divided into 4 groups: group A: 143 cyanotic patients not operated on (54 men and 89 women, aged 18 to 69 years); group B: 47 cyanotic patients (28 men and 19 women rendered acyanotic by operation at age 22 to 69 years); group C: 41 acyanotic patients not operated on (22 men and 19 women, aged 22 to 75 years); and group D: 48 patients acyanotic before and after operation (24 men and 24 women, aged 21 to 70 years). Coronary arteries were studied angiographically in 59 patients and at necropsy in 5 subjects aged 37 to 56 years. Total cholesterol was <160 mg/dl in 58% of group A, 52% of group B, 10% of group C, and 12% of group D (p <0.000001, chi-square analysis). Angiograms disclosed dilated coronary arteries without obstruction. Necropsy disclosed ectatic coronary arteries with structural abnormalities of the media. In conclusion, this study provides the first quantitative and qualitative data on antiatherogenic changes in lipoproteins in adults with CCHD. The coronary arteries are atheroma free because hypocholesterolemia acts in concert with the antiatherogenic properties of upregulated nitric oxide, hyperbilirubinemia, hypoxemia, and low platelet counts. The persistence of hypocholesterolemia after the surgical elimination of cyanosis suggests a genetic determinant.

  2. [EVALUATION OF ARTERIAL STIFFNESS AND POSSIBILITY TO PREDICT CAROTID ATHEROSCLEROSIS IN PATIENTS WITH ESSENTIAL HYPERTENSION BASED ON AN OUTPATIENT FACILITY].

    PubMed

    Polipanov, A G; Mamasaidov, Zh A; Geleskhanova, Yu N; Cheskidova, N B; Romanova, T A; Dzhumagulova, A S

    2016-01-01

    To estimate the possibility of predicting the presence and severity of coronary atherosclerosis from arterial stiffness characteristics and augmentation index (AIx) in patients with essential hypertension (EH) obtained under outpatient conditions. The general clinical examination of 15 patients aged 30-70 yr with EH was supplemented by measuring blood glucose and creatinine levels, the lipid status (LWLP, HDLP, TG), duplex scanning of carotid arteries, and evaluation of arterial stiffness by pulsed wave contour analysis. AIx and age were independent risk factors of coronary atherosclerosis in patients with EH and severity of its manifestations. AIx values over 25% were with high specificity (over 85%) associated with atherosclerotic lesions.

  3. Intensive lifestyle changes for reversal of coronary heart disease.

    PubMed

    Ornish, D; Scherwitz, L W; Billings, J H; Brown, S E; Gould, K L; Merritt, T A; Sparler, S; Armstrong, W T; Ports, T A; Kirkeeide, R L; Hogeboom, C; Brand, R J

    1998-12-16

    The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. Two tertiary care university medical centers. Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). More regression

  4. Functional Constituents of a Local Serotonergic System, Intrinsic to the Human Coronary Artery Smooth Muscle Cells

    PubMed Central

    Baskar, Kannan; Sur, Swastika; Selvaraj, Vithyalakashmi; Agrawal, Devendra K.

    2015-01-01

    Human coronary artery smooth muscle cells (HCASMCs) play an important role in the pathogenesis of coronary atherosclerosis and coronary artery diseases (CAD). Serotonin is a mediator known to produce vascular smooth muscle cell (VSMC) mitogenesis and contribute to coronary atherosclerosis. We hypothesize that the human coronary artery smooth muscle cell possesses certain functional constituents of the serotonergic system such as: tryptophan hydroxylase and serotonin transporter. Our aim was to examine the presence of functional tryptophan hydroxylase-1 (TPH1) and serotonin transporter (SERT) in HCASMCs. The mRNA transcripts by qPCR and protein expression by Western blot of TPH1 and SERT were examined. The specificity and accuracy of the primers were verified using DNA gel electrophoresis and sequencing of qPCR products. The functionality of SERT was examined using a fluorescence dye-based serotonin transporter assay. The enzymatic activity of TPH was evaluated using UPLC. The HCASMCs expressed both mRNA transcripts and protein of SERT and TPH. The qPCR showed a single melt curve peak for both transcripts and in sequence analysis the amplicons were aligned with the respective genes. SERT and TPH enzymatic activity was present in the HCASMCs. Taken together, both TPH and SERT are functionally expressed in HCASMCs. These findings are novel and represent an initial step in examining the clinical relevance of the serotonergic system in HCASMCs and its role in the pathogenesis of coronary atherosclerosis and CAD. PMID:25861735

  5. Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese

    PubMed Central

    Nang, Ei Ei Khaing; van Dam, Rob M.; Tan, Chuen Seng; Mueller-Riemenschneider, Falk; Lim, Yi Ting; Ong, Kai Zhi; Ee, Siqing; Lee, Jeannette; Tai, E. Shyong

    2015-01-01

    Objective Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed. Methods This was a cross-sectional study of 398 Chinese participants (192 men and 206 women) from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman’s correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis. Results In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day) was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93) but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31) after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations. Conclusions Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation

  6. Computer assessment of atherosclerosis from angiographic images

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Blankenhorn, D. H.; Brooks, S. H.; Crawford, D. W.; Cashin, W. L.

    1982-01-01

    A computer method for detection and quantification of atherosclerosis from angiograms has been developed and used to measure lesion change in human clinical trials. The technique involves tracking the vessel edges and measuring individual lesions as well as the overall irregularity of the arterial image. Application of the technique to conventional arterial-injection femoral and coronary angiograms is outlined and an experimental study to extend the technique to analysis of intravenous angiograms of the carotid and cornary arteries is described.

  7. Subclinical coronary artery disease in Swiss HIV-positive and HIV-negative persons.

    PubMed

    Tarr, Philip E; Ledergerber, Bruno; Calmy, Alexandra; Doco-Lecompte, Thanh; Marzel, Alex; Weber, Rainer; Kaufmann, Philipp A; Nkoulou, René; Buechel, Ronny R; Kovari, Helen

    2018-03-24

    HIV-positive persons have increased cardiovascular event rates but data on the prevalence of subclinical atherosclerosis compared with HIV-negative persons are not uniform. We assessed subclinical atherosclerosis utilizing coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) in 428 HIV-positive participants of the Swiss HIV Cohort Study and 276 HIV-negative controls concurrently referred for clinically indicated CCTA. We assessed the association of HIV infection, cardiovascular risk profile, and HIV-related factors with subclinical atherosclerosis in univariable and multivariable analyses. HIV-positive participants (median duration of HIV infection, 15 years) were younger than HIV-negative participants (median age 52 vs. 56 years; P < 0.01) but had similar median 10-year Framingham risk scores (9.0% vs. 9.7%; P = 0.40). The prevalence of CAC score >0 (53% vs. 56.2%; P = 0.42) and median CAC scores (47 vs. 47; P = 0.80) were similar, as was the prevalence of any, non-calcified/mixed, and high-risk plaque. In multivariable adjusted analysis, HIV-positive participants had a lower prevalence of calcified plaque than HIV-negative participants [36.9% vs. 48.6%, P < 0.01; adjusted odds ratio (aOR) 0.57; 95% confidence interval (CI) 0.40-0.82; P < 0.01], lower coronary segment severity score (aOR 0.72; 95% CI 0.53-0.99; P = 0.04), and lower segment involvement score (aOR 0.71, 95% CI 0.52-0.97; P = 0.03). Advanced immunosuppression was associated with non-calcified/mixed plaque (aOR 1.97; 95% CI 1.09-3.56; P = 0.02). HIV-positive persons in Switzerland had a similar degree of non-calcified/mixed plaque and high-risk plaque, and may have less calcified coronary plaque, and lower coronary atherosclerosis involvement and severity scores than HIV-negative persons with similar Framingham risk scores.

  8. Subclinical atherosclerosis and subsequent cognitive function.

    PubMed

    Rossetti, Heidi C; Weiner, Myron; Hynan, Linda S; Cullum, C Munro; Khera, Amit; Lacritz, Laura H

    2015-07-01

    To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8-65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥ .052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥ .455). In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Heart transplant coronary artery disease: Multimodality approach in percutaneous intervention.

    PubMed

    Leite, Luís; Matos, Vítor; Gonçalves, Lino; Silva Marques, João; Jorge, Elisabete; Calisto, João; Antunes, Manuel; Pego, Mariano

    2016-06-01

    Coronary artery disease is the most important cause of late morbidity and mortality after heart transplantation. It is usually an immunologic phenomenon termed cardiac allograft vasculopathy, but can also be the result of donor-transmitted atherosclerosis. Routine surveillance by coronary angiography should be complemented by intracoronary imaging, in order to determine the nature of the coronary lesions, and also by assessment of their functional significance to guide the decision whether to perform percutaneous coronary intervention. We report a case of coronary angiography at five-year follow-up after transplantation, using optical coherence tomography and fractional flow reserve to assess and optimize treatment of coronary disease in this challenging population. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  10. Targeted disruption of LDLR causes hypercholesterolemia and atherosclerosis in Yucatan miniature pigs.

    PubMed

    Davis, Bryan T; Wang, Xiao-Jun; Rohret, Judy A; Struzynski, Jason T; Merricks, Elizabeth P; Bellinger, Dwight A; Rohret, Frank A; Nichols, Timothy C; Rogers, Christopher S

    2014-01-01

    Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR) gene in an effort to provide an improved large animal model of familial hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models because of similarities to humans in physiology, anatomy, genetics, and size. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, male and female LDLR+/- pigs were generated. Subsequent breeding of heterozygotes produced LDLR-/- pigs. When fed a standard swine diet (low fat, no cholesterol), LDLR+/- pigs exhibited a moderate, but consistent increase in total and LDL cholesterol, while LDLR-/- pigs had considerably elevated levels. This severe hypercholesterolemia in homozygote animals resulted in atherosclerotic lesions in the coronary arteries and abdominal aorta that resemble human atherosclerosis. These phenotypes were more severe and developed over a shorter time when fed a diet containing natural sources of fat and cholesterol. LDLR-targeted Yucatan miniature pigs offer several advantages over existing large animal models including size, consistency, availability, and versatility. This new model of cardiovascular disease could be an important resource for developing and testing novel detection and treatment strategies for coronary and aortic atherosclerosis and its complications.

  11. Facilitatory effects of fetuin-A on atherosclerosis.

    PubMed

    Naito, Chisato; Hashimoto, Mio; Watanabe, Kaho; Shirai, Remina; Takahashi, Yui; Kojima, Miho; Watanabe, Rena; Sato, Kengo; Iso, Yoshitaka; Matsuyama, Taka-Aki; Suzuki, Hiroshi; Ishibashi-Ueda, Hatsue; Watanabe, Takuya

    2016-03-01

    Fetuin-A is a circulating glycoprotein that is produced by liver and adipose tissue. Fetuin-A is known to induce insulin resistance and suppress vascular calcification. There are conflicting reports that show increased or decreased serum fetuin-A levels in patients with coronary artery disease (CAD). Since the role of fetuin-A in atherosclerosis remains still controversial, we aimed to clarify it in this study. We investigated the expression of fetuin-A in atheromatous plaques in CAD patients and restenosis lesions in balloon-injured rat carotid arteries in vivo. We also assessed in vitro effects of fetuin-A on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), oxidized low-density lipoprotein-induced foam cell formation in human monocyte-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs) in a serum-free culture system. Fetuin-A was abundantly expressed in cultured human monocytes, macrophages, fibroblasts, HASMCs, and human coronary artery SMCs, atheromatous plaques in human coronary arteries, and restenosis lesions in rat carotid arteries. In vitro experiments showed that fetuin-A stimulated interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and E-selectin expression in HUVECs. Fetuin-A enhanced macrophage foam cell formation associated with scavenger receptors (CD36 and SR-A) and acyl-CoA:cholesterol acyltransferase-1 down-regulation and ATP-binding cassette transporter A1 up-regulation, and increased cell proliferation and collagen-1 and -3 expression via PI3K/AKT/c-Src/NF-κB/ERK1/2 pathways in HASMCs. Our results indicate that fetuin-A exerts the stimulatory effects on inflammatory responses in HUVECs, macrophage foam cell formation, and proliferation and collagen production in HASMCs, leading to the development of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

    PubMed

    Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2014-01-01

    It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

  13. Increased interarm blood pressure difference is associated with autonomic dysfunction and atherosclerosis in patients with chest pain and no history of coronary artery disease.

    PubMed

    Hwang, Hui-Jeong; Sohn, Il Suk; Kim, Dong-Hee; Park, Chang-Bum; Cho, Jin-Man; Kim, Chong-Jin

    2017-08-15

    Interarm blood pressure (BP) difference has been reported to be associated with atherosclerosis and increased cardiovascular death. We were to investigate associations of interarm systolic blood pressure (SBP) difference with heart rate recovery (HRR) after exercise, an index of autonomic function, and carotid atherosclerotic markers, and to evaluate the association of interarm SBP difference with concurrent coronary artery disease (CAD). A total of 995 consecutive patients who underwent treadmill stress echocardiography with chest pain but no history of CAD were enrolled. Interarm SBP difference, carotid intima-media thickness (IMT) and plaque were measured before exercise, and HRR 2min following exercise was assessed. Suspected CAD was defined as newly developed wall motion abnormalities after treadmill exercise. Patients with an interarm SBP difference≥10mmHg had higher prevalence of hypertension, increased right and left SBP, right diastolic BP, mean arterial pressure, body mass index and carotid IMT, existent carotid plaque, lower metabolic equivalents and slower HRR. Interarm SBP difference≥10mmHg was independently associated with slower HRR and existent carotid plaque. Suspected CAD was associated with existent carotid plaque or slower HRR, but not with an interarm SBP difference≥10mmHg. Increased interarm SBP difference was associated with lower autonomic modulation and carotid atherosclerosis in patients with chest pain and no history of CAD, but not with suspected CAD. Observed adverse prognosis in patients with increased interarm BP difference might result from long-term persistent autonomic dysfunction and atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Dual-energy computed tomography for detection of coronary artery disease

    PubMed Central

    Danad, Ibrahim; Ó Hartaigh, Bríain; Min, James K.

    2016-01-01

    Recent technological advances in computed tomography (CT) technology have fulfilled the prerequisites for the cardiac application of dual-energy CT (DECT) imaging. By exploiting the unique characteristics of materials when exposed to two different x-ray energies, DECT holds great promise for the diagnosis and management of coronary artery disease. It allows for the assessment of myocardial perfusion to discern the hemodynamic significance of coronary disease and possesses high accuracy for the detection and characterization of coronary plaques, while facilitating reductions in radiation dose. As such, DECT enabled cardiac CT to advance beyond the mere detection of coronary stenosis expanding its role in the evaluation and management of coronary atherosclerosis. PMID:26549789

  15. Epicardial adipose tissue as a predictor of coronary artery disease in asymptomatic subjects.

    PubMed

    Bachar, Gil N; Dicker, Dror; Kornowski, Ran; Atar, Eli

    2012-08-15

    This study sought to elucidate the relation between epicardial adipose tissue (EAT) thickness measured by multidetector computed tomography and presence of coronary artery atherosclerosis. Recent studies have suggested that fat disposition in visceral organs and epicardial tissue could serve as a predictor of coronary artery disease (CAD). The sample included 190 asymptomatic subjects with ≥ 1 cardiovascular risk factor who were referred for cardiac computed tomographic angiography. Body mass index, blood pressure, fasting glucose level, and lipid profile were measured. Multidetector computed tomographic results were analyzed for atherosclerosis burden, calcium Agatston score, and EAT thickness: mean EAT values were 3.54 ± 1.59 mm in patients with atherosclerosis and 1.85 ± 1.28 mm in patients without atherosclerosis (p <0.001). On receiver operating characteristic analysis, an EAT value ≥ 2.4 mm predicted the presence of significant (>50% diameter) coronary artery stenosis. There was a significant difference in EAT values between patients with and without metabolic syndrome (2.58 ± 1.63 vs 2.04 ± 1.46 mm, p <0.05) and between patients with a calcium score >400 and <400 (3.38 ± 1.58 vs 2.02 ± 1.42 mm, p <0.0001). In conclusion, asymptomatic patients with CAD have significantly more EAT than patients without CAD. An EAT thickness of 2.4 mm is the optimal cutoff for prediction of presence of significant CAD. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Association of Apolipoprotein B/Apolipoprotein A1 Ratio and Coronary Artery Stenosis and Plaques Detected by Multi-Detector Computed Tomography in Healthy Population

    PubMed Central

    Jung, Chang Hee; Hwang, Jenie Yoonoo; Shin, Mi Seon; Yu, Ji Hee; Kim, Eun Hee; Bae, Sung Jin; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu

    2013-01-01

    Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT. PMID:23678262

  17. Association of apolipoprotein b/apolipoprotein A1 ratio and coronary artery stenosis and plaques detected by multi-detector computed tomography in healthy population.

    PubMed

    Jung, Chang Hee; Hwang, Jenie Yoonoo; Shin, Mi Seon; Yu, Ji Hee; Kim, Eun Hee; Bae, Sung Jin; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

    2013-05-01

    Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

  18. Sex Differences in Nonculprit Coronary Plaque Microstructures on Frequency-Domain Optical Coherence Tomography in Acute Coronary Syndromes and Stable Coronary Artery Disease.

    PubMed

    Kataoka, Yu; Puri, Rishi; Hammadah, Muhammad; Duggal, Bhanu; Uno, Kiyoko; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; King, Peta; Nicholls, Stephen J

    2016-08-01

    Numerous reports suggest sex-related differences in atherosclerosis. Frequency-domain optical coherence tomography has enabled visualization of plaque microstructures associated with disease instability. The prevalence of plaque microstructures between sexes has not been characterized. We investigated sex differences in plaque features in patients with coronary artery disease. Nonculprit plaques on frequency-domain optical coherence tomography imaging were compared between men and women with either stable coronary artery disease (n=320) or acute coronary syndromes (n=115). A greater prevalence of cardiovascular risk factors was observed in women. Nonculprit plaques in women with stable coronary artery disease were more likely to exhibit plaque erosion (8.6% versus 0.3%; P=0.03) and a smaller lipid arc (163.1±71.4° versus 211.2±71.2°; P=0.03), and less likely to harbor cholesterol crystals (17.2% versus 27.5%; P=0.01) and calcification (15.4% versus 34.4%; P=0.008), whereas fibrous cap thickness (105.2±62.1 versus 96.1±40.4 µm; P=0.57), the prevalence of thin-cap fibroatheroma (26.5% versus 25.2%; P=0.85), and microchannels (19.2% versus 20.5%; P=0.95) were comparable. In women with acute coronary syndrome, a smaller lipid arc (171.6±53.2° versus 235.8±86.4°; P=0.03), a higher frequency of plaque erosion (11.4% versus 0.6%; P=0.04), and a lower prevalence of cholesterol crystal (28.6% versus 38.2%; P=0.03) and calcification (10.0% versus 23.7%; P=0.01) were observed. These differences persisted after adjusting clinical demographics. Although thin-cap fibroatheromas in men clustered within proximal arterial segments, thin-cap fibroatheromas were evenly distributed in women. Despite more comorbid risk factors in women, their nonculprit plaques exhibited more plaque erosion, and less cholesterol and calcium content. This distinct phenotype suggests sex-related differences in the pathophysiology of atherosclerosis. © 2016 American Heart Association, Inc.

  19. Hepatic JAK2 protects against atherosclerosis through circulating IGF-1

    PubMed Central

    Sivasubramaniyam, Tharini; Schroer, Stephanie A.; Li, Angela; Luk, Cynthia T.; Shi, Sally Yu; Besla, Rickvinder; Metherel, Adam H.; Kitson, Alex P.; Brunt, Jara J.; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P.; Bendeck, Michelle P.; Robbins, Clinton S.

    2017-01-01

    Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2’s essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection. PMID:28724798

  20. Dietary cod-liver oil improves endothelium-dependent responses in hypercholesterolemic and atherosclerotic porcine coronary arteries.

    PubMed

    Shimokawa, H; Vanhoutte, P M

    1988-12-01

    This study examined the effects of dietary supplementation with cod-liver oil on impaired endothelium-dependent relaxations in hypercholesterolemia and in atherosclerosis in porcine coronary arteries. Sixteen male Yorkshire pigs underwent balloon endothelium removal of the left coronary arteries and were fed a 2% high-cholesterol diet for 10 weeks, with or without dietary supplementation of cod-liver oil (30 ml/day) (oil-fed and cholesterol-fed groups, respectively). This model allowed the simultaneous examination of the effects of dietary cod-liver oil on vascular reactivity in hypercholesterolemia alone (right coronary artery) and in atherosclerosis (left coronary artery). After 10 weeks of feeding, the dietary treatment with cod-liver oil caused an increase in plasma levels of eicosapentaenoic acid and a decrease in the plasma levels of arachidonic acid, whereas the treatment had no significant effect on the increases in plasma lipid levels induced by the high-cholesterol feeding. Morphometric analysis showed significant inhibition of coronary atherosclerosis by the treatment. Endothelium-dependent responses were examined in vitro in ring preparations and in bioassay experiments. Endothelium-dependent relaxations to bradykinin, serotonin, and adenosine 5'-diphosphate were larger in both right and left coronary arteries from oil-fed than from cholesterol-fed animals. Aggregating platelets from cholesterol-fed and oil-fed pigs induced comparable, larger endothelium-dependent relaxations in rings from oil-fed than from cholesterol-fed pigs. The contractions induced by serotonin or aggregating platelets were significantly inhibited in rings with endothelium from oil-fed pigs, whereas they were comparable in rings without endothelium in both groups. Relaxations to sodium nitroprusside and contractions to potassium chloride or serotonin were comparable in rings without endothelium in both groups. The bioassay experiments revealed that the release of endothelium

  1. Why did ancient people have atherosclerosis?: from autopsies to computed tomography to potential causes.

    PubMed

    Thomas, Gregory S; Wann, L Samuel; Allam, Adel H; Thompson, Randall C; Michalik, David E; Sutherland, M Linda; Sutherland, James D; Lombardi, Guido P; Watson, Lucia; Cox, Samantha L; Valladolid, Clide M; Abd El-Maksoud, Gomaa; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; el-Halim Nur el-Din, Abd; Clarke, Emily M; Thomas, Ian G; Miyamoto, Michael I; Kaplan, Hillard S; Frohlich, Bruno; Narula, Jagat; Stewart, Alexandre F R; Zink, Albert; Finch, Caleb E

    2014-06-01

    Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors. Copyright © 2014 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

  2. Pleiotropic effects of cardilopin (secondary coronary prevention).

    PubMed

    Kapanadze, S; Dolidze, N; Bakhutashvili, Z; Chapidze, L; Shengelia, E

    2005-02-01

    In order to evaluate some pleiotropic effects of cardilopin (Amlodipine, EGIS Pharmaceuticals) 33 ambulatory patients were examined. During the 2-month study period on the background of cardilopin treatment there were positive changes in some parameters of coronary atherosclerosis. Pleiotropic effects of cardilopin were particularly expressed in restoring of endothelial function and inhibition of platelet aggregation. There was found tendency to reduce the degree of hyperlipoperoxidemia related to oxidative stress. Obtained results of the present trial support the use of cardilopin in all coronary heart disease patients with or without myocardial revascularization and arterial hypertension.

  3. Resistant Atherosclerosis: The Need for Monitoring of Plaque Burden.

    PubMed

    Spence, J David; Solo, Karla

    2017-06-01

    Recent studies indicate that patients with lower levels of low-density lipoprotein cholesterol (LDL-C) have greater regression of coronary plaque. In 2002, we found that carotid plaque progression doubled cardiovascular risk. In 2003, we therefore implemented a new approach, treating arteries instead of risk factors. Since then, we have seen many patients with carotid plaque progression despite very low levels of LDL-C, suggesting other causes of atherosclerosis. We studied the relationship of achieved LDL-C and change in LDL-C to progression/regression of atherosclerosis, before and after 2003. All 4512 patients in our clinic database with at least 2 measurements of LDL-C and carotid total plaque area approximately a year apart and complete data for analyses (n=2025 before and 2487 after December 31, 2003) were included in the study. Baseline total plaque area was significantly higher after 2003 (129.56±134.32 versus 113.33±121.52 mm 2 ; P <0.0001), and plaque progression was significantly less after 2003 (2.94±37.11 versus 12.62±43.24 mm 2 ; P <0.0001). Many patients with LDL-C <1.8 mm had plaque progression (47.5%), and change in LDL-C was not correlated with plaque progression/regression. Increasing age and serum creatinine contributed to resistant atherosclerosis. Many patients have Resistant Atherosclerosis, failing to achieve regression of atherosclerosis despite low levels of LDL-C. Instead of relying on LDL-C, measuring plaque burden may be a more useful way of assessing individual response to therapy, particularly in resistant atherosclerosis. © 2017 American Heart Association, Inc.

  4. Time-dependent expression of ICAM-1 & VCAM-1 on coronaries of the heterotopically transplanted mouse heart.

    PubMed Central

    Lee, J. R.; Huh, J. H.; Seo, J. W.; Suk, C. J.; Jeong, H. M.; Kim, E. K.

    1999-01-01

    To investigate the pathogenesis of accelerated graft atherosclerosis after cardiac transplantation, a genetically well-defined and reproducible animal model is required. We performed heterotopic intraabdominal heart transplantation between the two inbred strains of mice. Forty hearts from B10.A mice were transplanted into B10.BR mice. Recipients were sacrificed at 1, 3, 5, 7, 14, 28, and 42 days after implantation. The specimens from both donor and recipient were examined with fluorescent immunohistochemistry and the serial histopathologic changes were evaluated. In the donor hearts, ICAM-1 and VCAM-1 expressions were minimal at day 1 and they gradually increased, reaching their peaks on day 5 or 7 and remained unchanged by day 42. However, there were very little expressions in the recipients' hearts. Mean percent areas of intima in the donor coronaries revealed progressive increase by day 42. However, those in the recipients occupied consistently less than 5% of the lumen. In conclusion, we demonstrated that a heterotopic murine heart transplantation model was a useful tool to produce transplantation coronary artery disease and that adhesion molecules on the cardiac allografts were activated very early and remained elevated at all time-points, nonetheless the arterial lesion was detected after day 28 and its progression was accelerated thereafter. PMID:10402165

  5. Estimation of shear stress by using a myocardial bridge-mural coronary artery simulating device.

    PubMed

    Ding, Hao; Yang, Qian; Shang, Kun; Lan, Hailian; Lv, Jie; Liu, Zhilin; Liu, Yang; Sheng, Lixing; Zeng, Yanjun

    2017-01-01

    This study was aimed at developing a myocardial bridge-mural coronary artery simulative device and analyzing the relationship between shear stress on the mural coronary artery and atherosclerosis. A myocardial bridge-mural coronary artery simulative device was used to simulate experiments in vitro. In the condition of maintaining any related parameters such as system temperature, average flow rate, and heart rate, we calculated and observed changes in proximal and distal mean values, and oscillatory value of shear stress on the mural coronary artery by regulating the compression level of the myocardial bridge to the mural coronary artery. Under 0% compression, no significant differences were observed in distal and proximal mean values and oscillatory value of the shear stress on the mural coronary artery. With the increase in the degree of compression, the mean shear stress at the distal end was greater than that at the proximal end, but the oscillatory value of the shear stress at the proximal end was greater than that at the distal end. The experimental results of this study indicate that myocardial bridge compression leads to abnormal hemodynamics at the proximal end of the mural coronary artery. This abnormal phenomenon is of great significance in the study of atherosclerosis hemodynamic pathogenesis, which has potential clinical value for pathological effects and treatments of myocardial bridge.

  6. Polymer-Based Therapeutics: Nanoassemblies and Nanoparticles for Management of Atherosclerosis

    PubMed Central

    Lewis, Daniel R.; Kamisoglu, Kubra; York, Adam; Moghe, Prabhas V.

    2012-01-01

    Coronary arterial disease, one of the leading causes of adult mortality, is triggered by atherosclerosis. A disease with complex etiology, atherosclerosis results from the progressive long-term combination of atherogenesis, the accumulation of modified lipoproteins within blood vessel walls, along with vascular and systemic inflammatory processes. The management of atherosclerosis is challenged by the localized flare-up of several multipronged signaling interactions between activated monocytes, atherogenic macrophages and inflamed or dysfunctional endothelial cells. A new generation of approaches is now emerging founded on multifocal, targeted therapies that seek to reverse or ameliorate the athero-inflammatory cascade within the vascular intima. This article reviews the various classes and primary examples of bioactive configurations of nanoscale assemblies. Of specific interest are polymer-based or polymer-lipid micellar assemblies designed as multimodal receptor-targeted blockers or drug carriers whose activity can be tuned by variations in polymer hydrophobicity, charge, and architecture. Also reviewed are emerging reports on multifunctional nanoassemblies and nanoparticles for improved circulation and enhanced targeting to athero-inflammatory lesions and atherosclerotic plaques. PMID:21523920

  7. Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis

    PubMed Central

    Mortensen, Martin B.; Kjolby, Mads; Gunnersen, Stine; Larsen, Jakob V.; Palmfeldt, Johan; Falk, Erling; Nykjaer, Anders; Bentzon, Jacob F.

    2014-01-01

    Genome-wide association studies have identified a link between genetic variation at the human chromosomal locus 1p13.3 and coronary artery disease. The gene encoding sortilin (SORT1) has been implicated as the causative gene within the locus, as sortilin regulates hepatic lipoprotein metabolism. Here we demonstrated that sortilin also directly affects atherogenesis, independent of its regulatory role in lipoprotein metabolism. In a mouse model of atherosclerosis, deletion of Sort1 did not alter plasma cholesterol levels, but reduced the development of both early and late atherosclerotic lesions. We determined that sortilin is a high-affinity receptor for the proinflammatory cytokines IL-6 and IFN-γ. Moreover, macrophages and Th1 cells (both of which mediate atherosclerotic plaque formation) lacking sortilin had reduced secretion of IL-6 and IFN-γ, but not of other measured cytokines. Transfer of sortilin-deficient BM into irradiated atherosclerotic mice reduced atherosclerosis and systemic markers of inflammation. Together, these data demonstrate that sortilin influences cytokine secretion and that targeting sortilin in immune cells attenuates inflammation and reduces atherosclerosis. PMID:25401472

  8. Macrophage Sortilin Promotes LDL Uptake, Foam Cell Formation, and Atherosclerosis

    PubMed Central

    Patel, Kevin M.; Strong, Alanna; Tohyama, Junichiro; Jin, Xueting; Morales, Carlos R.; Billheimer, Jeffery; Millar, John; Kruth, Howard; Rader, Daniel J.

    2015-01-01

    Rationale Non-coding gene variants at the SORT1 locus are strongly associated with LDL-C levels as well as with coronary artery disease (CAD). SORT1 encodes a protein called sortilin, and hepatic sortilin modulates LDL metabolism by targeting apoB-containing lipoproteins to the lysosome. Sortilin is also expressed in macrophages, but its role in macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C levels is unknown. Objective To determine the effect of macrophage sortilin expression on LDL uptake, foam cell formation, and atherosclerosis. Methods and Results We crossed Sort1−/− mice onto a ‘humanized’ Apobec1−/−; hAPOB Tg background and determined that Sort1 deficiency on this background had no effect on plasma LDL-C levels but dramatically reduced atherosclerosis in the aorta and aortic root. In order to test whether this effect was a result of macrophage sortilin deficiency, we transplanted Sort1−/−;LDLR−/− or Sort1+/+;LDLR−/− bone marrow into Ldlr−/− mice and observed a similar reduction in atherosclerosis in mice lacking hematopoetic sortilin without an effect on plasma LDL-C levels. In an effort to determine the mechanism by which hematopoetic sortilin deficiency reduced atherosclerosis, we found no effect of sortilin deficiency on macrophage recruitment or LPS-induced cytokine release in vivo. In contrast, sortilin deficient macrophages had significantly reduced uptake of native LDL ex vivo and reduced foam cell formation in vivo, whereas sortilin overexpression in macrophages resulted in increased LDL uptake and foam cell formation. Conclusions Macrophage sortilin deficiency protects against atherosclerosis by reducing macrophage uptake of LDL. Sortilin-mediated uptake of native LDL into macrophages may be an important mechanism of foam cell formation and contributor to atherosclerosis development. PMID:25593281

  9. Nitric Oxide-Mediated Coronary Flow Regulation in Patients with Coronary Artery Disease: Recent Advances

    PubMed Central

    Toda, Noboru; Tanabe, Shinichi; Nakanishi, Sadanobu

    2011-01-01

    Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance, and in inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. Endothelial function is impaired by several pathogenic factors including smoking, chronic alcohol intake, hypercholesterolemia, obesity, hyperglycemia, and hypertension. The mechanisms underlying endothelial dysfunction include reduced NO synthase (NOS) expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. Atrial fibrillation appears to be a risk factor for endothelial dysfunction. Endothelial dysfunction is an important predictor of coronary artery disease (CAD) in humans. Penile erectile dysfunction, associated with impaired bioavailability of NO produced by eNOS and neuronal NOS, is also considered to be highly predictive of ischemic heart disease. There is evidence suggesting an important role of nitrergic innervation in coronary blood flow regulation. Prophylactic and therapeutic measures to eliminate pathogenic factors inducing endothelial and nitrergic nerve dysfunction would be quite important in preventing the genesis and development of CAD. PMID:22942627

  10. Contrasting patterns of coronary atherosclerosis in normocholesterolaemic smokers and patients with familial hypercholesterolaemia.

    PubMed Central

    Sugrue, D D; Thompson, G R; Oakley, C M; Trayner, I M; Steiner, R E

    1981-01-01

    An angiographic comparison was made of the extent and severity of coronary artery disease in 25 patients with heterozygous familial hypercholesterolaemia and 25 normocholesterolaemic patients with coronary artery disease in whom heavy cigarette consumption was the chief risk factor. The patients with familial hypercholesterolaemia were younger and included a much higher proportion of women than the smokers. Significantly more patients with familial hypercholesterolaemia had disease of the main stem of the left coronary artery (eight v none, p less than 0.05) and triple-vessel disease (18 v four, p less than 0.05). Disease affecting only distal vessels occurred in five smokers, whereas all the patients with familial hypercholesterolaemia showed a combination of proximal and distal lesions. These findings suggest that cigarette smoking and familial hypercholesterolaemia predispose to different patterns of coronary atheroma. Early coronary angiography with a view to coronary artery bypass surgery seems desirable in symptomatic patients with familial hypercholesterolaemia because of the common association of this disorder with life-threatening left main-stem disease. PMID:6797539

  11. 2013 Russell Ross memorial lecture in vascular biology: cellular and molecular mechanisms of diabetes mellitus-accelerated atherosclerosis.

    PubMed

    Bornfeldt, Karin E

    2014-04-01

    Adults with diabetes mellitus are much more likely to have cardiovascular disease than those without diabetes mellitus. Genetically engineered mouse models have started to provide important insight into the mechanisms whereby diabetes mellitus promotes atherosclerosis. Such models have demonstrated that diabetes mellitus promotes formation of atherosclerotic lesions, progression of lesions into advanced hemorrhaged lesions, and that it prevents lesion regression. The proatherosclerotic effects of diabetes mellitus are driven in part by the altered function of myeloid cells. The protein S100A9 and the receptor for advanced glycation end-products are important modulators of the effect of diabetes mellitus on myelopoiesis, which might promote monocyte accumulation in lesions. Furthermore, myeloid cell expression of the enzyme acyl-CoA synthetase 1 (ACSL1), which converts long-chain fatty acids into their acyl-CoA derivatives, has emerged as causal to diabetes mellitus-induced lesion initiation. The protective effects of myeloid ACSL1-deficiency in diabetic mice, but not in nondiabetic mice, indicate that myeloid cells are activated by diabetes mellitus through mechanisms that play minor roles in the absence of diabetes mellitus. The roles of reactive oxygen species and insulin resistance in diabetes mellitus-accelerated atherosclerosis are also discussed, primarily in relation to endothelial cells. Translational studies addressing whether the mechanisms identified in mouse models are equally important in humans with diabetes mellitus will be paramount.

  12. [Valvular heart disease associated with coronary artery disease].

    PubMed

    Yildirir, Aylin

    2009-07-01

    Nowadays, age-related degenerative etiologies have largely replaced the rheumatic ones and as a natural result of this etiologic change, coronary artery disease has become associated with valvular heart disease to a greater extent. Degenerative aortic valve disease has an important pathophysiological similarity to atherosclerosis and is the leader in this association. There is a general consensus that severely stenotic aortic valve should be replaced during bypass surgery for severe coronary artery disease. For moderate degree aortic stenosis, aortic valve replacement is usually performed during coronary bypass surgery. Ischemic mitral regurgitation has recently received great attention from both diagnostic and therapeutic points of view. Ischemic mitral regurgitation significantly alters the prognosis of the patient with coronary artery disease. Severe ischemic mitral regurgitation should be corrected during coronary bypass surgery and mitral valve repair should be preferred to valve replacement. For moderate degree ischemic mitral regurgitation, many authors prefer valve surgery with coronary bypass surgery. In this review, the main characteristics of patients with coronary artery disease accompanying valvular heart disease and the therapeutic options based on individual valve pathology are discussed.

  13. Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan

    PubMed Central

    Fujiyoshi, Akira; Miura, Katsuyuki; Ohkubo, Takayoshi; Kadowaki, Takashi; Kadowaki, Sayaka; Zaid, Maryam; Hisamatsu, Takashi; Sekikawa, Akira; Budoff, Matthew J.; Liu, Kiang; Ueshima, Hirotsugu; Fujiyoshi, Akira; Miura, Katsuyuki; Ohkubo, Takayoshi; Kadowaki, Takashi; Kadowaki, Sayaka; Zaid, Maryam; Hisamatsu, Takashi; Ueshima, Hirotsugu; Miura, Katsuyuki; Hisamatsu, Takashi; Ueshima, Hirotsugu; Ohkubo, Takayoshi; Sekikawa, Akira; Budoff, Matthew J.; Liu, Kiang

    2014-01-01

    The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45–54, 55–64, or 65–74 years). We used community-based samples of Caucasian men in the United States (2000–2002; n = 1,067) and Japanese men in Japan (2006–2008; n = 832) aged 45–74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45–54, 55–64, and 65–74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. PMID:25125689

  14. Innate immune cell activation and epigenetic remodeling in symptomatic and asymptomatic atherosclerosis in humans in vivo.

    PubMed

    Bekkering, Siroon; van den Munckhof, Inge; Nielen, Tim; Lamfers, Evert; Dinarello, Charles; Rutten, Joost; de Graaf, Jacqueline; Joosten, Leo A B; Netea, Mihai G; Gomes, Marc E R; Riksen, Niels P

    2016-11-01

    We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis. Monocytes were isolated from 20 patients with severe symptomatic coronary atherosclerosis (total plaque score >4 on coronary computed tomography angiography) and 17 patients with asymptomatic carotid atherosclerosis and matched controls for both groups. Ex vivo stimulation, RNA analysis and chromatin immunoprecipitation were performed. Monocytes from patients with symptomatic atherosclerosis have a higher production of pro-inflammatory cytokines upon LPS stimulation than healthy controls (TNFα 499 ± 102 vs. 267 ± 45 pg/ml, p = 0.01). This was associated with lower histone 3 lysine 4 trimethylation (H3K4me3) (19% vs. 33%, p = 0.002), and lower H3K27me3 (0.005% vs. 0.8%, p < 0.0001) on the TNFα promoter. Furthermore, relative mRNA expression of the glycolytic rate limiting enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 was higher in patients (0.7 ± 0.2 vs. 0.3 ± 0.1 resp. 1.7 ± 0.2 vs. 1.0 ± 0.1, p = 0.007 resp. 0.003) compared to control individuals. Interestingly, this pro-inflammatory phenotype was only present in patients with symptomatic atherosclerosis, and not in patients with asymptomatic carotid atherosclerosis. Circulating monocytes of patients with symptomatic, but not asymptomatic, atherosclerosis have a pro-inflammatory phenotype and increased expression of glycolytic enzymes, associated with epigenetic remodeling at

  15. Acute coronary disease Athero-Inflammation: Therapeutic approach

    PubMed Central

    Altman, Raul

    2003-01-01

    Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events. Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease. PMID:12904261

  16. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome.

    PubMed

    Christian, Rose C; Dumesic, Daniel A; Behrenbeck, Thomas; Oberg, Ann L; Sheedy, Patrick F; Fitzpatrick, Lorraine A

    2003-06-01

    Polycystic ovary syndrome (PCOS), a common endocrine disorder of reproductive-aged women, is associated with multiple risk factors for coronary heart disease (CHD), such as diabetes mellitus, dyslipidemia, visceral obesity, and hypertension. However, premature coronary atherosclerosis has not been demonstrated in PCOS women. Electron beam computed tomography (EBCT) noninvasively measures coronary artery calcium (CAC), a marker for coronary atherosclerosis. We measured CAC by EBCT in 30- to 45-yr-old premenopausal PCOS women and compared the results to CAC in 1) recruited normal ovulatory volunteers matched for age and weight to the PCOS cohort, and 2) community-dwelling women of similar age in an extant coronary calcium database. Healthy, community-dwelling, ovulatory controls (n = 71) were matched by age and body mass index (BMI) to PCOS women (n = 36). Women with diabetes or known CHD were excluded. Subjects underwent EBCT scanning, oral glucose tolerance testing, and CHD risk factor assessment. PCOS women had significantly higher levels of serum total and low density lipoprotein cholesterol and testosterone levels than matched controls. PCOS and control women were obese and had a greater mean BMI than community-dwelling women (33 kg/m(2) for PCOS vs. 31 kg/m(2) for control; P < 0.001). CAC was more prevalent in PCOS women (39%) than in matched controls (21%; odds ratio, 2.4; P = 0.05) or community-dwelling women (9.9%; odds ratio, 5.9; P < 0.001). BMI, waist circumference, and total and low density lipoprotein cholesterol levels predicted CAC prevalence after adjustment for BMI. CAC is more prevalent in PCOS women than in obese or nonobese women of similar age. PCOS women are at increased risk for atherosclerosis and should be targeted for primary prevention of CHD.

  17. [The role of subclinical inflammation in progression of multifocal atherosclerosis during one year after myocardial infarction].

    PubMed

    Barbarash, O L; Usol'tseva, E N; Kashtalap, V V; Kolomytseva, I S; Sizova, I N; Volykova, M A; Shibanova, I A

    2014-01-01

    To elucidate role of subclinical inflammation in progression of atherosclerotic process in magistral noncoronary arteries in patients during one year after ST-elevation myocardial infarction (MI). We examined 168 men with MI (mean age 59.5 years). All patients during hospitalization underwent coronary angiography and color duplex scanning of brachiocephalic arteries. In a year ultrasound study of noncoronary vessels was repeated and progression of atherosclerosis assessed. Parameters of inflammation in blood serum were measured on days 10-14 of MI and after one year. At repeat study most patients demonstrated progression of noncoronary atherosclerosis. Some biomarkers measured during inhospital phase of MI (low concentration of anti-inflammatory interleukin 10 - IL-10, elevated N-terminal pro brain natriuretic peptide) allowed to distinguish group of patients with subsequent progression of noncoronary atherosclerosis. Elevated concentrations of C-reactive protein and 11-10 registered in a year after MI were also associated with more severe progression of atherosclerosis. Serum levels of neopterin and IL-12 remained stable in patients with and decreased in patients without pronounced progression of atherosclerosis.

  18. Acute Loss of Apolipoprotein E Triggers an Autoimmune Response That Accelerates Atherosclerosis.

    PubMed

    Centa, Monica; Prokopec, Kajsa E; Garimella, Manasa G; Habir, Katrin; Hofste, Lisa; Stark, Julian M; Dahdah, Albert; Tibbit, Chris A; Polyzos, Konstantinos A; Gisterå, Anton; Johansson, Daniel K; Maeda, Nobuyo N; Hansson, Göran K; Ketelhuth, Daniel F J; Coquet, Jonathan M; Binder, Christoph J; Karlsson, Mikael C I; Malin, Stephen

    2018-06-07

    Dyslipidemia is a component of the metabolic syndrome, an established risk factor for atherosclerotic cardiovascular disease, and is also observed in various autoimmune and chronic inflammatory conditions. However, there are limited opportunities to study the impact of acquired dyslipidemia on cardiovascular and immune pathology. We designed a model system that allows for the conversion to a state of acute hyperlipidemia in adult life, so that the consequences of such a transition could be observed, through conditionally deleting APOE (apolipoprotein E) in the adult mouse. The transition to hypercholesterolemia was accompanied by adaptive immune responses, including the expansion of T lymphocyte helper cell 1, T follicular helper cell, and T regulatory subsets and the formation of germinal centers. Unlike steady-state Apoe -deficientmice, abrupt loss of APOE induced rapid production of antibodies recognizing rheumatoid disease autoantigens. Genetic ablation of the germinal center reduced both autoimmunity and atherosclerosis, indicating that the immune response that follows loss of APOE is independent of atherosclerosis but nevertheless promotes plaque development. Our findings suggest that immune activation in response to hyperlipidemia could contribute to a wide range of inflammatory autoimmune diseases, including atherosclerosis. © 2018 American Heart Association, Inc.

  19. Improved animal models for testing gene therapy for atherosclerosis.

    PubMed

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  20. Scaling laws of coronary circulation in health and disease.

    PubMed

    Huo, Yunlong; Kassab, Ghassan S

    2016-08-16

    The heterogeneity and complexity of coronary vasculature (structure) and myocardial flow (function) have fractal-like characteristics and can be described by scaling laws with remarkable simplicity. In contrast with allometric (interspecific) scaling law, intraspecific scaling laws describe the design rules of vascular trees within a species. This paper provides an overview of intraspecific scaling laws of vascular trees and the physiological and clinical implications thereof. The significance and shortcomings of these scaling laws are discussed in relation to diffuse coronary artery disease, Glagov's positive remodeling in early stages of coronary atherosclerosis, treatment guidelines of complex bifurcation lesions, and for estimation of outlet resistance values for computation of blood flow in epicardial coronary arteries. Finally, we summarize the highlights of scaling relations and suggest some future directions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

    PubMed Central

    Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

    2014-01-01

    Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr−/−Apob 100/100 Mttp flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

  2. Feasibility and Safety of Evaluating Patients with Prior Coronary Artery Disease Using an Accelerated Diagnostic Algorithm in a Chest Pain Unit

    PubMed Central

    Goldkorn, Ronen; Goitein, Orly; Ben-Zekery, Sagit; Shlomo, Nir; Narodetsky, Michael; Livne, Moran; Sabbag, Avi; Asher, Elad; Matetzky, Shlomi

    2016-01-01

    An accelerated diagnostic protocol for evaluating low-risk patients with acute chest pain in a cardiologist-based chest pain unit (CPU) is widely employed today. However, limited data exist regarding the feasibility of such an algorithm for patients with a history of prior coronary artery disease (CAD). The aim of the current study was to assess the feasibility and safety of evaluating patients with a history of prior CAD using an accelerated diagnostic protocol. We evaluated 1,220 consecutive patients presenting with acute chest pain and hospitalized in our CPU. Patients were stratified according to whether they had a history of prior CAD or not. The primary composite outcome was defined as a composite of readmission due to chest pain, acute coronary syndrome, coronary revascularization, or death during a 60-day follow-up period. Overall, 268 (22%) patients had a history of prior CAD. Non-invasive evaluation was performed in 1,112 (91%) patients. While patients with a history of prior CAD had more comorbidities, the two study groups were similar regarding hospitalization rates (9% vs. 13%, p = 0.08), coronary angiography (13% vs. 11%, p = 0.41), and revascularization (6.5% vs. 5.7%, p = 0.8) performed during CPU evaluation. At 60-days the primary endpoint was observed in 12 (1.6%) and 6 (3.2%) patients without and with a history of prior CAD, respectively (p = 0.836). No mortalities were recorded. To conclude, Patients with a history of prior CAD can be expeditiously and safely evaluated using an accelerated diagnostic protocol in a CPU with outcomes not differing from patients without such a history. PMID:27669521

  3. Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis).

    PubMed

    Budoff, Matthew J; Nasir, Khurram; McClelland, Robyn L; Detrano, Robert; Wong, Nathan; Blumenthal, Roger S; Kondos, George; Kronmal, Richard A

    2009-01-27

    In this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score. The presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units). There were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank. Using absolute CAC in standard groups performed

  4. Evaluation of the biomechanics of atherosclerosis by acoustic microscopy

    NASA Astrophysics Data System (ADS)

    Saijo, Yoshifumi; Nitta, Shin-ichi; Schiott Jorgensen, Claus; Falk, Erling

    2001-07-01

    Acoustic microscopy provides not only the morphology, but also the biomechanical properties of the biological soft tissues. The biomechanics of atherosclerosis is important because the pathophysiology of atherosclerosis is closely related with mechanical properties and mechanical stress. Rupture of the fibrous cap of atheromatous plaque is the initial event in acute coronary syndrome such as acute myocardial infarction or unstable angina. In addition to extrinsic physical stresses to the plaque, the intrinsic biomechanical property of the plaque is important for assessing the mechanism of the rupture. Two sets of SAMs operating in 100 to 200 MHz and in 800 MHz to 1.3 GHz were equipped to measure the acoustic properties of atherosclerosis of human or mouse arteries. The values of attenuation and sound speed in the tissue components of atherosclerosis were measured by analyzing the frequency dependent characteristics of the amplitude and phase signals. Both values were highest in calcification and lowest in lipid pool. Although attenuation and sound speed were relatively high in intimal fibrosis, the inhomogeneity of acoustic parameters was found within the fibrous cap. Polarized microscopy for the collagen stained with Picrosirius red showed that the attenuation of ultrasound was significantly higher in type I collagen with orange polarized color compared to type III collagen with green color. SAM has shown the possibility to detect the plaque vulnerability and it might improve our understanding of the sudden rupture from micro-mechanical point of view.

  5. A relative difference in systolic blood pressure between arms by synchronal measurement and conventional cardiovascular risk factors are associated with the severity of coronary atherosclerosis.

    PubMed

    Yamamoto, Tomohiko; Miura, Shin-Ichiro; Suematsu, Yasunori; Kuwano, Takashi; Sugihara, Makoto; Ike, Amane; Iwata, Atsushi; Nishikawa, Hiroaki; Saku, Keijiro

    2016-06-01

    It is not known the relationships between a difference in systolic blood pressure (SBP) or diastolic BP (DBP) between arms by synchronal measurement and the presence of coronary artery disease (CAD), and between a difference in BP between arms and the severity of coronary atherosclerosis. We enrolled 425 consecutive patients (M/F = 286/139, 67 ± 13 year) who were admitted to our University Hospital and in whom we could measure the absolute (|rt. BP - lt. BP|) and relative (rt. BP - lt. BP) differences in SBP and DBP using a nico PS-501(®) (Parama-Tech). We divided all patients into those who did and did not have CAD. The relative differences in SBP between arms in patients with CAD were significantly lower than those in patients without CAD. However, the relative difference in SBP between arms was not a predictor of the presence of CAD. We also divided 267 patients who underwent coronary angiography into tertiles according to the Gensini score (low, middle, and high score groups). Interestingly, the middle + high score groups showed significantly lower relative differences in SBP between arms than the low score group. The mean Korotkoff sound graph in the middle + high Gensini score group was significantly higher than that in the low Gensini score group. Among conventional cardiovascular risk factors and nico parameters, the relative difference in SBP between arms in addition to the risk factors (age, gender, body mass index, hypertension, dyslipidemia, and diabetes mellitus) was associated with the score by a logistic regression analysis. In conclusion, the relative difference in SBP between arms as well as conventional risk factors may be associated with the severity of coronary arteriosclerosis.

  6. Silent myocardial ischemia in patients with symptomatic intracranial atherosclerosis: associated factors.

    PubMed

    Arenillas, Juan F; Candell-Riera, Jaume; Romero-Farina, Guillermo; Molina, Carlos A; Chacón, Pilar; Aguadé-Bruix, Santiago; Montaner, Joan; de León, Gustavo; Castell-Conesa, Joan; Alvarez-Sabín, José

    2005-06-01

    Optimization of coronary risk evaluation in stroke patients has been encouraged. The relationship between symptomatic intracranial atherosclerosis and occult coronary artery disease (CAD) has not been evaluated sufficiently. We aimed to investigate the prevalence of silent myocardial ischemia in patients with symptomatic intracranial atherosclerosis and to identify factors associated with its presence. From 186 first-ever transient ischemic attack or ischemic stroke patients with intracranial stenoses, 65 fulfilled selection criteria, including angiographic confirmation of a symptomatic atherosclerotic stenosis and absence of known CAD. All patients underwent a maximal-stress myocardial perfusion single-photon emission computed tomography (SPECT). Lipoprotein(a) [Lp(a)], C-reactive protein, and homocysteine (Hcy) levels were determined before SPECT. Stress-rest SPECT detected reversible myocardial perfusion defects in 34 (52%) patients. Vascular risk factors associated with a pathologic SPECT were hypercholesterolemia (P=0.045), presence of >2 risk factors (P=0.004) and high Lp(a) (P=0.023) and Hcy levels (P=0.018). Ninety percent of patients with high Lp(a) and Hcy levels had a positive SPECT. Existence of a stenosed intracranial internal carotid artery (ICA; odds ratio [OR], 7.22, 2.07 to 25.23; P=0.002) and location of the symptomatic stenosis in vertebrobasilar arteries (OR, 4.89, 1.19 to 20.12; P=0.027) were independently associated with silent myocardial ischemia after adjustment by age, sex, and risk factors. More than 50% of the patients with symptomatic intracranial atherosclerosis and not overt CAD show myocardial perfusion defects on stress-rest SPECT. Stenosed intracranial ICA, symptomatic vertebrobasilar stenosis and presence of high Lp(a) and Hcy levels may characterize the patients at a higher risk for occult CAD.

  7. Association between gamma-glutamyltransferase and coronary artery calcification.

    PubMed

    Atar, Asli I; Yilmaz, Omer C; Akin, Kayihan; Selcoki, Yusuf; Er, Okan; Eryonucu, Beyhan

    2013-08-20

    The exact mechanisms behind the association between atherosclerosis and gamma-glutamyltransferase (GGT) are unclear. Coronary artery calcification (CAC) detected by computerized tomography is an important marker of atherosclerosis and its severity correlates with coronary plaque burden. The aim of this study was to investigate if serum GGT levels are associated with CAC in patients without known coronary heart disease (CHD) who had low-intermediate risk for CHD. Two hundred and seventy two patients who had low-intermediate risk for coronary artery disease were included in the study. Serum GGT levels were measured spectrophotometrically. CACS (Agatston method) were performed using a 64-slice computerized tomography scanner. The patients were grouped according to their GGT values in four quartiles. Patients in higher GGT quartiles had elevated CAC score (P<0.001). Patients in higher GGT quartiles were predominantly males (P<0.001) and were more likely to be smoking (P=0.004), and have elevated uric acid (P<0.001), fasting blood glucose (P<0.001), CRP levels (P=0.003) and 10-year total cardiovascular risk (P=0.007) and low HDL levels (P<0.001). Positive correlations were found between log GGT and CAC (r=0.233, P<0.001). In the multivariate analysis GGT, age, smoking and serum uric acid levels appeared as independent factors predictive of presence of CAC. We demonstrated a significant correlation between serum GGT levels and CAC and CHD risk factors. Serum GGT level was an independent marker of CAC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Influence of acquired obesity on coronary vessel wall late gadolinium enhancement in discordant monozygote twins.

    PubMed

    Makowski, Marcus R; Jansen, Christian H P; Ebersberger, Ullrich; Schaeffter, Tobias; Razavi, Reza; Mangino, Massimo; Spector, Tim D; Botnar, Rene M; Greil, Gerald F

    2017-11-01

    The aim of this study was to investigate the impact of BMI on late gadolinium enhancement (LGE) of the coronary artery wall in identical monozygous twins discordant for BMI. Coronary LGE represents a useful parameter for the detection and quantification of atherosclerotic coronary vessel wall disease. Thirteen monozygote female twin pairs (n = 26) with significantly different BMIs (>1.6 kg/m2) were recruited out of >10,000 twin pairs (TwinsUK Registry). A coronary 3D-T2prep-TFE MR angiogram and 3D-IR-TFE vessel wall scan were performed prior to and following the administration of 0.2 mmol/kg of Gd-DTPA on a 1.5 T MR scanner. The number of enhancing coronary segments and contrast to noise ratios (CNRs) of the coronary wall were quantified. An increase in BMI was associated with an increased number of enhancing coronary segments (5.3 ± 1.5 vs. 3.5 ± 1.6, p < 0.0001) and increased coronary wall enhancement (6.1 ± 1.1 vs. 4.8 ± 0.9, p = 0.0027) compared to matched twins with lower BMI. This study in monozygous twins indicates that acquired factors predisposing to obesity, including lifestyle and environmental factors, result in increased LGE of the coronary arteries, potentially reflecting an increase in coronary atherosclerosis in this female study population. • BMI-discordant twins allow the investigation of the influence of lifestyle factors independent from genetic confounders. • Only thirteen obesity-discordant twins were identified underlining the strong genetic component of BMI. • In female twins, a BMI increase is associated with increased coronary late gadolinium enhancement. • Increased late gadolinium enhancement in the coronary vessel wall potentially reflects increased atherosclerosis.

  9. Inflammatory Obesity Phenotypes, Gender Effects, and Subclinical Atherosclerosis in African Americans: The Jackson Heart Study.

    PubMed

    Lin, Albert; Lacy, Mary E; Eaton, Charles; Correa, Adolfo; Wu, Wen-Chih

    2016-12-01

    Reasons for variations in atherosclerotic burden among individuals with similar levels of obesity are poorly understood, especially in African Americans. This study examines whether high-sensitivity C-reactive protein (hsCRP) is useful for discriminating between benign and high-risk obesity phenotypes for subclinical atherosclerosis in African Americans. Participants from the Jackson Heart Study (n=4682) were stratified into 4 phenotypes based on the presence of National Heart and Lung and Blood Institute definition of obesity or obesity-equivalent (body mass index ≥30 or body mass index 25-30 with waist circumference >102 cm in men and >88 cm in women) and inflammation by hsCRP ≥2 mg/L. Using multivariate regression models, we conducted cross-sectional analyses of the association between inflammatory obesity phenotypes and subclinical atherosclerosis determined by carotid intima-media thickness or coronary artery calcium scores. Sex-specific analyses were conducted given significant interaction for gender (P=0.03). The prevalence of obesity or equivalent was 65%, of which 30% did not have inflammation. Conversely, 37% of nonobese individuals had inflammation. Among nonobese men, hsCRP ≥2 mg/L identified a subset of individuals with higher carotid intima-media thickness (adjusted mean difference =0.05, 95% confidence interval 0.02, 0.08 mm) compared with their noninflammatory counterparts. Among obese men, hsCRP <2 mg/L identified a subset of individuals with lower coronary artery calcium compared with their inflammatory counterparts. Among women, associations between hsCRP and carotid intima-media thickness or coronary artery calcium were not found. In the largest African American population-based cohort to date, hsCRP was useful in identifying a subset of nonobese men with higher carotid intima-media thickness, but not in women. hsCRP did not identify a subset of obese individuals with less subclinical atherosclerosis. © 2016 American Heart Association

  10. Polymorphisms in IL-10 and INF-γ genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults.

    PubMed

    Esperança, José Carlos P; Miranda, William R R; Netto, José B; Lima, Fabiane S; Baumworcel, Leonardo; Chimelli, Leila; Silva, Rosane; Ürményi, Turán P; Cabello, Pedro H; Rondinelli, Edson; Faffe, Débora S

    2015-06-01

    Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n = 103) and carotid arteries (CA, n = 66) of autopsied young adults (< 30 years old). Histological sections (H-E) were classified according to the American Heart Association. Polymorphisms in ACE, TNF-α (- 308G/A and - 238 G/A), IFN-γ (+ 874 A/T), MMP-9 (- 1562 C/T), IL-10 (- 1082 A/G and - 819 C/T), NOS3 (894 G/T), ApoA1 (rs964184), ApoE (E2E3E4 isoforms), and TGF-β (codons 25 and 10) genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69%) and CA (39%) arteries, while severe type IV and V lesions were observed in 14% (DA) and 33% (CA). Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-γ and IL-10 (- 1082 A/G) were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-γ (p < 0.001) and IL-10 (p = 0.013) genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification.

  11. Neck circumference is not associated with subclinical atherosclerosis in retired National Football League players.

    PubMed

    Pokharel, Yashashwi; Macedo, Francisco Y; Nambi, Vijay; Martin, Seth S; Nasir, Khurram; Wong, Nathan D; Boone, Jeffrey; Roberts, Arthur J; Ballantyne, Christie M; Virani, Salim S

    2014-07-01

    Neck circumference (NC) is associated with metabolic syndrome (MetS) in the general population. It is not known if NC is associated with MetS and subclinical atherosclerosis in retired National Football League (NFL) players. We hypothesized that NC is associated with MetS and subclinical atherosclerosis (assessed as coronary artery calcium [CAC] and carotid artery plaque [CAP]) in retired NFL players. NC was measured midway between the midcervical spine and midanterior neck in 845 retired NFL players. CAC presence was defined as total CAC score >0. CAP was defined as carotid plaque of at least 50% greater than that of the surrounding vessel wall, with a minimal thickness of at least 1.2 mm on carotid ultrasound. Logistic regression analysis was used for the association of NC with CAC or CAP. Of the participants, 21% had MetS. CAC and CAP were present in 62% and 56%, respectively. Those with MetS had a higher median NC than those without MetS (17 vs 16 inches, P < 0.0001). NC was not associated with the presence of CAC or CAP in an unadjusted model and after adjusting for age, race, and cardiometabolic risk factors (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.94-1.31 for CAC; OR: 0.96, 95% CI: 0.82-1.12 for CAP per 1-standard deviation increase in NC [3.8 inches]). The results were similar when the predictor variable was NC indexed to body mass index. In retired NFL players with a high prevalence of CAC and CAP, NC was not associated with coronary or carotid subclinical atherosclerosis. NC may not be the most appropriate risk marker for atherosclerosis. © 2014 Wiley Periodicals, Inc.

  12. The association of coronary artery calcium with non-cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Dardari, Zeina A.; Al-Mallah, Mouaz H.; Miedema, Michael D.; Ouyang, Pamela; Budoff, Matthew J.; Blumenthal, Roger S.; Nasir, Khurram; Blaha, Michael J.

    2016-01-01

    Objective To determine if coronary artery calcium (CAC) is associated with incident non-cardiovascular disease (CVD). Background CAC is considered a measure of vascular aging, associated with increased risk of cardiovascular and all-cause mortality. The relationship with non-CVD is not well defined. Methods 6,814 participants from 6 MESA (Multi-ethnic Study of Atherosclerosis) field centers, followed for a median of 10.2 years. Modified Cox proportional hazard ratios accounting for the competing risk of fatal coronary heart disease (CHD) were calculated for new diagnoses of cancer, pneumonia, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), deep vein thrombosis (DVT)/pulmonary embolism (PE), hip fracture and dementia. Analyses were adjusted for age, gender, race, socioeconomic status, health insurance status, body mass index, physical activity, diet, tobacco use, number of medications used, systolic and diastolic blood pressure, total and HDL-C cholesterol, antihypertensive, aspirin and cholesterol medication and diabetes. The outcome was first incident non-CVD diagnosis. Results Compared to those with CAC=0, those with CAC >400 had an increased hazard of cancer (1.53, 1.18-1.99), CKD (1.70, 1.21-2.39), pneumonia (1.97, 1.37-2.82), COPD (2.71, 1.60-4.57) and hip fracture (4.29, 1.47-12.50). CAC>400 was not associated with dementia or DVT/PE. Those with CAC=0 had decreased risk of cancer (0.76, 0.63-0.92), CKD (0.77, 0.60-0.98), COPD (0.61, 0.40- 0.91) and hip fracture (0.31, 0.14 - 0.70) compared to those with CAC>0. CAC=0 was not associated with less pneumonia, dementia or DVT/PE. The results were attenuated, but remained significant, after removing participants with non-fatal CHD. Conclusion Participants with elevated CAC were at increased risk of cancer, CKD, COPD and hip fractures. Those with CAC=0 are less likely to develop common age related comorbid conditions, and represent a unique population of “healthy agers”. PMID:26970999

  13. Cyanotic Congenital Heart Disease The Coronary Arterial Circulation

    PubMed Central

    Perloff, Joseph K

    2012-01-01

    Background: The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. Methods: Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. Results: Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens. Conclusions: Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia. PMID:22845810

  14. Cyanotic congenital heart disease the coronary arterial circulation.

    PubMed

    Perloff, Joseph K

    2012-02-01

    The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens. Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia.

  15. Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

    PubMed

    Salmazo, Péricles Sidnei; Bazan, Silméia Garcia Zanati; Shiraishi, Flávio Gobbis; Bazan, Rodrigo; Okoshi, Katashi; Hueb, João Carlos

    2018-04-09

    AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p < 0.05. Plaques were found in 37% of the HIV group and 4% of controls (p < 0.001). Furthermore, carotid intima-media thickness was higher in the HIV group than in controls (p < 0.001). Patients with carotid plaque had higher fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides than those without plaques. The presence of HIV, adjusted for age, overweight/obesity, and smoking increased by almost fivefold the risk of atherosclerotic carotid plaque (OR: 4.9; 95%CI: 2.5-9.9; p < 0.001). Exposure to protease inhibitors did not influence carotid intima-media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of

  16. Epicardial adipose tissue density and volume are related to subclinical atherosclerosis, inflammation and major adverse cardiac events in asymptomatic subjects.

    PubMed

    Goeller, Markus; Achenbach, Stephan; Marwan, Mohamed; Doris, Mhairi K; Cadet, Sebastien; Commandeur, Frederic; Chen, Xi; Slomka, Piotr J; Gransar, Heidi; Cao, J Jane; Wong, Nathan D; Albrecht, Moritz H; Rozanski, Alan; Tamarappoo, Balaji K; Berman, Daniel S; Dey, Damini

    We investigated whether epicardial adipose tissue (EAT) volume and density are related to early atherosclerosis, plaque inflammation and major adverse cardiac events (MACE, cardiac death and myocardial infarction) in asymptomatic subjects. EAT volume and density were quantified from non-contrast cardiac CT in 456 asymptomatic individuals (age 60.3 ± 8.3; 68% with CCS>0) from the prospective EISNER trial. EAT volume and density were examined in relation to coronary calcium score (CCS), inflammatory biomarkers and MACE. EAT volume was higher and EAT density lower in subjects with coronary calcium compared to subjects without [89 vs 74 cm 3 , p < 0.001] [-76.9 vs -75.7 HU,p = 0.024]. EAT volume was lowest in individuals with no coronary calcium and was significant higher in subjects with early atherosclerosis (CCS 1-99) [74 vs 87 cm 3 ,p = 0.016] and in subjects with more advanced atherosclerosis (CCS≥100) [89 cm 3 ,p = 0.002]). EAT volume was independently related to serum levels of PAI-1, and MCP-1 and inversely related to adiponectin and HDL-cholesterol (p < 0.05). EAT density was inversely related to PAI-1 and LDL-cholesterol and positively associated to adiponectin, sICAM-1 and HDL-cholesterol (p < 0.05). EAT density was more significantly associated with MACE [(HR 0.8, 95%CI:0.7-0.98), p = 0.029] than EAT volume or CCS. EAT volume was higher and density lower in subjects with coronary calcium compared to subjects with CCS = 0, with similar EAT volume in CCS<100 and CCS≥100. Lower EAT density and increased EAT volume were associated with coronary calcification, serum levels of plaque inflammatory markers and MACE, suggesting that dysfunctional EAT may be linked to early plaque formation and inflammation. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  17. Are Elevated Levels of IGF-1 Caused by Coronary Arteriesoclerosis?: Molecular and Clinical Analysis

    PubMed Central

    Gozdzicka-Jozefiak, Anna; Zurawski, Jakub; Nowak, Witold; Durzynska, Julia; Link, Rafał; Grotowski, Tomasz; Siminiak, Tomasz

    2010-01-01

    The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with “3 vessel disease” and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2–4) nor in internal domain (exon 16–21). The effect of increased IGF-1 serum level in our study was probably

  18. Are elevated levels of IGF-1 caused by coronary arteriesoclerosis?: Molecular and clinical analysis.

    PubMed

    Burchardt, Pawel; Gozdzicka-Jozefiak, Anna; Zurawski, Jakub; Nowak, Witold; Durzynska, Julia; Link, Rafał; Grotowski, Tomasz; Siminiak, Tomasz

    2010-11-01

    The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with "3 vessel disease" and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2-4) nor in internal domain (exon 16-21). The effect of increased IGF-1 serum level in our study was probably independent

  19. [Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy].

    PubMed

    Hanefeld, Markolf; Metzler, Wolfgang; Köhler, Carsta; Schaper, Frank

    2006-05-01

    Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.

  20. Translational atherosclerosis research: From experimental models to coronary artery disease in humans.

    PubMed

    Gleissner, Christian A

    2016-05-01

    Atherosclerosis is the leading cause of death worldwide. Research on the pathophysiological mechanisms of atherogenesis has made tremendous progress over the past two decades. However, despite great advances there is still a lack of therapies that reduce adverse cardiovascular events to an acceptable degree. This review addresses successes, but also questions, challenges, and chances regarding the translation of basic science results into clinical practice, i.e. the capability to apply the results of basic and/or clinical research in order to design therapies suitable to improve patient outcome. Specifically, it discusses problems in translating findings from the most broadly used murine models of atherosclerosis into clinically feasible therapies and strategies potentially improving the results of clinical trials. Most likely, the key to success will be a multimodal approach employing novel imaging methods as well as large scale screening tools-summarized as "omics" approach. Using individually tailored therapies, plaque stabilization and regression could prevent adverse cardiovascular events thereby improving outcome of a large number of patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

    PubMed

    Thompson, Randall C; Allam, Adel H; Lombardi, Guido P; Wann, L Samuel; Sutherland, M Linda; Sutherland, James D; Soliman, Muhammad Al-Tohamy; Frohlich, Bruno; Mininberg, David T; Monge, Janet M; Vallodolid, Clide M; Cox, Samantha L; Abd el-Maksoud, Gomaa; Badr, Ibrahim; Miyamoto, Michael I; el-Halim Nur el-Din, Abd; Narula, Jagat; Finch, Caleb E; Thomas, Gregory S

    2013-04-06

    Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in

  2. Regulation of coronary blood flow

    PubMed Central

    Gorlin, Richard

    1971-01-01

    Coronary blood flow is dependent upon arterial pressure, diastolic time, and small vessel resistance. The system is regulated to achieve a low flow high oxygen extraction and low myocardial Po2. This setting is sensitive to change in oxygen needs. Regulation of blood flow occurs primarily through local intrinsic regulation, most likely through production of vasodilating metabolites in response to minimal degrees of ischaemia. Local regulation appears to dominate over remote regulation in most circumstances. Blood flow distribution to the myocardium is depth dependent as well as regional in variation. Both types of distribution of blood flow are profoundly disturbed in the presence of obstructive coronary atherosclerosis. This results in either concentric myocardial shells or patchy transmural zones of selective ischaemia with clear-cut but local abnormalities in metabolism and performance. Images PMID:4929442

  3. Relationship Between Central and Peripheral Atherosclerosis and Left Ventricular Dysfunction in a Community Population

    PubMed Central

    Tsao, Connie W.; Gona, Philimon; Salton, Carol; Murabito, Joanne M.; Oyama, Noriko; Danias, Peter G.; O’Donnell, Christopher J.; Manning, Warren J.; Yeon, Susan B.

    2011-01-01

    We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and PAD in a community cohort. 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65±9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional LV systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at Examination 7. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p<0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p<0.001) and volume of aortic plaque were associated with decreased ABI (p<0.001). After multivariable adjustment, ABI≤0.9 or prior revascularization was associated with a three-fold odds of aortic plaque (p=0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p<0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment suggesting shared mechanisms beyond those captured by traditional risk factors. PMID:21708875

  4. Revascularization with percutaneous coronary intervention does not affect androgen status in males with chronic stable angina pectoris.

    PubMed

    Gosai, J N; Charalampidis, P; Nikolaidou, T; Parviz, Y; Morris, P D; Channer, K S; Jones, T H; Grech, E D

    2016-05-01

    There is a clear association between low serum testosterone and coronary artery disease (CAD) in men. Hypotestosteronaemia is associated with accelerated atherosclerosis and a quarter of men with CAD are biochemically hypogonadal. Amongst those with CAD, hypotestosteronaemia is associated with increased mortality. Testosterone vasodilates coronary arteries, and exogenous testosterone reduces ischaemia. Whether hypotestosteronaemia is a cause or a consequence of CAD remains unanswered. The aim of this prospective observational study was to investigate whether coronary revascularization affected androgen status in men with stable angina pectoris. Twenty five men (mean age 62.7, SD 9.18) with angiographically significant CAD and symptomatic angina underwent full coronary revascularization by percutaneous coronary intervention. Androgen status and symptoms of angina, stress, depression and sexual function were assessed before, and at one and 6 months after the coronary revascularization. All patients underwent complete revascularization which was associated with a significant reduction in angina symptoms and ischaemia. No significant difference was seen in total testosterone (11.33 nmol/L baseline; 12.56, 1 month post; 13.04 at 6 months; p = 0.08). A significant and sustained rise in sex hormone-binding globulin was seen (33.99 nm/L baseline; 36.11 nm/L 1 month post PCI; 37.94 nm/L at 6 months; p = 0.03) Overall, there was no significant alteration in any other marker of androgen status including free testosterone or bioavailable testosterone. There was no change in symptoms of anxiety, depression or sexual function. Coronary revascularization has no sustained effect on androgen status. This supports the hypothesis that hypotestosteronaemia is not a consequence of angina pectoris or myocardial ischaemia. © 2016 American Society of Andrology and European Academy of Andrology.

  5. Hematocrit is associated with carotid atherosclerosis in men but not in women.

    PubMed

    Irace, Concetta; Ciamei, Monica; Crivaro, Andrea; Fiaschi, Elio; Madia, Angela; Cortese, Claudio; Gnasso, Agostino

    2003-06-01

    It is known that blood and plasma viscosities are associated with clinical manifestations of atherosclerosis, though evidence is not conclusive particularly in women. To verify whether hematocrit and blood and plasma viscosities are independently associated with carotid atherosclerosis and whether their measurement can improve the definition of the global coronary heart disease (CHD) risk. Eight hundred and ninety-two participants in a cardiovascular disease prevention campaign were examined with regard to conventional CHD risk factors (age, blood pressure, lipids, glucose, body mass index, waist/hip ratio, cigarette smoking and diabetes), hematocrit and blood and plasma viscosities. According to the degree of carotid atherosclerosis, investigated by echo-Doppler, participants were divided in three groups: those without atherosclerosis, those with a low degree of atherosclerosis and those with a high degree of atherosclerosis. In men, age, blood pressure, intima-media thickness (IMT), hematocrit (47.4+/-3.7%, 47.8+/-3.7%, 48.4+/-3.7%, P<0.05) and blood viscosity (4.69+/-0.51 cP, 4.77+/-0.55 cP, 4.82+/-0.51 cP, P=0.05) increased with increasing degree of carotid atherosclerosis. In women, age, blood pressure, total cholesterol and low-density lipoprotein-cholesterol, IMT and plasma viscosity (1.42+/-0.12 cP, 1.44+/-0.11 cP, 1.46+/-0.13 cP, P<0.05) increased with increasing carotid score. Analysis of covariance (ANCOVA) showed that after adjusting for hematocrit, blood viscosity was no longer different in the three groups. In discriminant analysis, hematocrit, among the hemorheological variables investigated, was independently associated with carotid score in men (F=3.66, P<0.05). Neither hematocrit nor blood and plasma viscosities were significantly associated with carotid score in women. These findings suggest that in men, both hematocrit and blood viscosity are related to carotid atherosclerosis but hematocrit would appear to have an independent effect over and

  6. Role of Animal Models in Coronary Stenting.

    PubMed

    Iqbal, Javaid; Chamberlain, Janet; Francis, Sheila E; Gunn, Julian

    2016-02-01

    Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

  7. Childhood Antecedents to Adult Coronary Artery Diseases. Special Reference Briefs.

    ERIC Educational Resources Information Center

    Winick, Myron

    This reference brief deals with the childhood antecedents to atherosclerosis and hypertension. While diet is related to the development of coronary artery diseases, there is some disagreement about what dietary changes are necessary or desirable in children to prevent their development, and at what age such changes should be made. Fifty-five…

  8. A dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages of diabetic mice: evaluation of the diabetes-accelerated atherosclerosis risk.

    PubMed

    Huang, Qilin; An, Yarui; Tang, Linlin; Jiang, Xiaoli; Chen, Hua; Bi, Wenji; Wang, Zhongchuan; Zhang, Wen

    2011-11-30

    In this paper, a novel dual enzymatic-biosensor is described for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages (PMs) of diabetic mice to evaluate the risk of diabetes-accelerated atherosclerosis. The biosensor was constructed by a three-step method. First, a poly-thionine (PTH) film was assembled on the surface of glassy carbon electrode by cyclic voltammetric electropolymerization of thionine, which serves as an electron transfer mediator (ETM). Second, gold nanoparticles (GNPs) were covered on the surface of PTH facilitating the electron transfer between glucose oxidase (GOx), cholesterol oxidase (ChOx) and electrode. Finally, the enzymes, GOx, cholesterol esterase (ChE), and ChOx, were covalently attached to the PTH layer through a chitosan (CH) linker. The PTH coupled with GNPs provides good selectivity, high sensitivity and little crosstalk for the dual enzymatic-biosensor. The developed biosensor had good electrocatalytic activity toward the oxidations of glucose and cholesterol, exhibiting a linear range from 0.008 mM to 6.0 mM for glucose with a detection limit of 2.0 μM, and a linear range from 0.002 mM to 1.0 mM for cholesterol with a detection limit of 0.6 μM. The results of the diabetic mice demonstrated that the cholesterol level did not change obviously with the increase of glucose level in serum, while the cholesterol level was induced with the increase of the glucose level in PMs. Previous studies have shown that the large accumulation of cholesterol in macrophage could lead to macrophage foam cell formation, which is the hallmark of early atherosclerosis. This study provides useful further evidences for the development of diabetes-accelerated atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. From Lipid Retention to Immune-Mediate Inflammation and Associated Angiogenesis in the Pathogenesis of Atherosclerosis.

    PubMed

    Usman, Ammara; Ribatti, Domenico; Sadat, Umar; Gillard, Jonathan H

    2015-08-26

    Atherosclerosis is a leading cause of mortality and long-term morbidity worldwide. It is a lipoprotein-driven disease that leads to plaque formation at focal areas in the arterial blood vessels through intimal inflammation, necrosis, fibrosis, and calcification. Adventitial and intimal angiogenesis contributes to the progression of intimal hyperplasia and the development of a necrotic core. The volatile nature of an atheromatous plaque is responsible for approximately 60% of symptomatic carotid artery diseases and about 75% of acute coronary events. In this review the pathogenesis of atherosclerosis is discussed from the initial step of lipid retention to advanced stages of immune-mediate inflammation and associated angiogenesis. Mechanisms of plaque rupture are also discussed.

  10. Local factors modify the dose dependence of 56Fe-induced atherosclerosis.

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Gupta, Kiran; Wu, Xing; Yu, Tao; Chang, Polly; Kabarowski, Janusz; Yu, Shaohua

    2012-07-01

    Radiation exposure from a number of terrestrial sources is associated with an increased risk of cardiovascular disease, but evidence establishing whether high-LET radiation has similar effects has been lacking. We recently demonstrated that 600 MeV/n 56Fe induces atherosclerosis as well. Ten-week old male apolipoprotein-E deficient mice, a well-characterized atherosclerosis animal model, were exposed to 0 (control) 2, or 5Gy 56Fe targeted to the chest and neck. In these mice, 56Fe-induced atherosclerosis was similar in character to that induced by X-rays in the same mouse model and to that resulting from therapeutic radiation in cancer patients. Atherosclerosis was exacerbated by 56Fe only in targeted areas, however, suggesting a direct effect of the radiation on the arteries themselves. This is in contrast to some other risk factors, such as high cholesterol or tobacco use, which have systemic effects. The radiation dose required to accelerate development of atherosclerotic plaques, however, differed depending on the vessel that was irradiated and even the location within the vessel. For example, atherosclerosis in the aortic arch was accelerated only by the highest dose (5 Gy), while the carotid arteries and the aortic root showed effects at 2 Gy (a dose four- to eight-fold lower than the dose of X-rays that produces similar effects in this model). Since shear stress is disrupted in the area of the aortic root, it is likely that at least part of the site-specificity is due to additive or synergistic effects of radiation and local hydrodynamics. Other factors, such as local oxidative stress or gene expression may also have been involved. Since the pro-atherogenic effects of 56Fe depend on additional local factors, this suggests that radiation exposure, when unavoidable, might be mitigated by modification of factors unrelated to the radiation itself.

  11. Precision phenotyping, panomics, and system-level bioinformatics to delineate complex biologies of atherosclerosis: rationale and design of the "Genetic Loci and the Burden of Atherosclerotic Lesions" study.

    PubMed

    Voros, Szilard; Maurovich-Horvat, Pal; Marvasty, Idean B; Bansal, Aruna T; Barnes, Michael R; Vazquez, Gustavo; Murray, Sarah S; Voros, Viktor; Merkely, Bela; Brown, Bradley O; Warnick, G Russell

    2014-01-01

    Complex biological networks of atherosclerosis are largely unknown. The main objective of the Genetic Loci and the Burden of Atherosclerotic Lesions study is to assemble comprehensive biological networks of atherosclerosis using advanced cardiovascular imaging for phenotyping, a panomic approach to identify underlying genomic, proteomic, metabolomic, and lipidomic underpinnings, analyzed by systems biology-driven bioinformatics. By design, this is a hypothesis-free unbiased discovery study collecting a large number of biologically related factors to examine biological associations between genomic, proteomic, metabolomic, lipidomic, and phenotypic factors of atherosclerosis. The Genetic Loci and the Burden of Atherosclerotic Lesions study (NCT01738828) is a prospective, multicenter, international observational study of atherosclerotic coronary artery disease. Approximately 7500 patients are enrolled and undergo non-contrast-enhanced coronary calcium scanning by CT for the detection and quantification of coronary artery calcium, as well as coronary artery CT angiography for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. In addition, patients undergo whole genome sequencing, DNA methylation, whole blood-based transcriptome sequencing, unbiased proteomics based on mass spectrometry, as well as metabolomics and lipidomics on a mass spectrometry platform. The study is analyzed in 3 subsequent phases, and each phase consists of a discovery cohort and an independent validation cohort. For the primary analysis, the primary phenotype will be the presence of any atherosclerotic plaque, as detected by cardiac CT. Additional phenotypic analyses will include per patient maximal luminal stenosis defined as 50% and 70% diameter stenosis. Single-omic and multi-omic associations will be examined for each phenotype; putative biomarkers will be assessed for association, calibration, discrimination, and reclassification. Copyright

  12. Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

    PubMed

    Arnold, Roman; Villa, Adolfo; Gutiérrez, Hipólito; Sánchez, Pedro L; Gimeno, Federico; Fernández, Maria E; Gutiérrez, Oliver; Mota, Pedro; Sánchez, Ana; García-Frade, Javier; Fernández-Avilés, Francisco; San Román, Jose A

    2010-06-01

    We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy. Copyright 2010 Mosby, Inc. All rights reserved.

  13. Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

    PubMed Central

    von Scheidt, Moritz; Zhao, Yuqi; Kurt, Zeyneb; Pan, Calvin; Zeng, Lingyao; Yang, Xia; Schunkert, Heribert; Lusis, Aldons J.

    2017-01-01

    Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWAS) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWAS. In particular, of the 46 genes with strong association signals in CAD-GWAS that were studied in mouse models all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWAS with 263 from mouse studies and observed that over 50% were consistent between both species. PMID:27916529

  14. Coronary artery calcification in obese youth: What are the phenotypic and metabolic determinants?

    USDA-ARS?s Scientific Manuscript database

    Obesity in adolescence has been associated with increased risk for coronary heart disease in adulthood. This study evaluated subclinical atherosclerosis in obese youth and the underlying risk factors. Ninety obese adolescents (37 normal glucose tolerant, 27 prediabetes, and 26 type 2 diabetes) under...

  15. The identification of the variation of atherosclerosis plaques by invasive and non-invasive methods

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Blankenhorn, D. H.

    1982-01-01

    Computer-enhanced visualization of coronary arteries and lesions within them is discussed, comparing invasive and noninvasive methods. Trial design factors in computer lesions assessment are briefly discussed, and the use of the computer edge-tracking technique in that assessment is described. The results of a small pilot study conducted on serial cineangiograms of men with premature atherosclerosis are presented. A canine study to determine the feasibility of quantifying atherosclerosis from intravenous carotid angiograms is discussed. Comparative error for arterial and venous injection in the canines is determined, and the mode of processing the films to achieve better visualization is described. The application of the computer edge-tracking technique to an ultrasound image of the human carotid artery is also shown and briefly discussed.

  16. Quantitative micro-CT based coronary artery profiling using interactive local thresholding and cylindrical coordinates.

    PubMed

    Panetta, Daniele; Pelosi, Gualtiero; Viglione, Federica; Kusmic, Claudia; Terreni, Marianna; Belcari, Nicola; Guerra, Alberto Del; Athanasiou, Lambros; Exarchos, Themistoklis; Fotiadis, Dimitrios I; Filipovic, Nenad; Trivella, Maria Giovanna; Salvadori, Piero A; Parodi, Oberdan

    2015-01-01

    Micro-CT is an established imaging technique for high-resolution non-destructive assessment of vascular samples, which is gaining growing interest for investigations of atherosclerotic arteries both in humans and in animal models. However, there is still a lack in the definition of micro-CT image metrics suitable for comprehensive evaluation and quantification of features of interest in the field of experimental atherosclerosis (ATS). A novel approach to micro-CT image processing for profiling of coronary ATS is described, providing comprehensive visualization and quantification of contrast agent-free 3D high-resolution reconstruction of full-length artery walls. Accelerated coronary ATS has been induced by high fat cholesterol-enriched diet in swine and left coronary artery (LCA) harvested en bloc for micro-CT scanning and histologic processing. A cylindrical coordinate system has been defined on the image space after curved multiplanar reformation of the coronary vessel for the comprehensive visualization of the main vessel features such as wall thickening and calcium content. A novel semi-automatic segmentation procedure based on 2D histograms has been implemented and the quantitative results validated by histology. The potentiality of attenuation-based micro-CT at low kV to reliably separate arterial wall layers from adjacent tissue as well as identify wall and plaque contours and major tissue components has been validated by histology. Morphometric indexes from histological data corresponding to several micro-CT slices have been derived (double observer evaluation at different coronary ATS stages) and highly significant correlations (R2 > 0.90) evidenced. Semi-automatic morphometry has been validated by double observer manual morphometry of micro-CT slices and highly significant correlations were found (R2 > 0.92). The micro-CT methodology described represents a handy and reliable tool for quantitative high resolution and contrast agent free full length

  17. Topographic association of angioscopic yellow plaques with coronary atherosclerotic plaque: assessment with quantitative colorimetry in human coronary artery autopsy specimens.

    PubMed

    Ishibashi, Fumiyuki; Lisauskas, Jennifer B; Kawamura, Akio; Waxman, Sergio

    2008-01-01

    Yellow plaques seen during coronary angioscopy are thought to be the surrogates for superficial intimal lipids in coronary plaque. Given diffuse and heterogeneous nature of atherosclerosis, yellow plaques in coronaries may be seen as several yellow spots on diffuse coronary plaque. We examined the topographic association of yellow plaques with coronary plaque. In 40 non-severely stenotic ex-vivo coronary segments (average length: 52.2 +/- 3.1 mm), yellow plaques were examined by angioscopy with quantitative colorimetry. The segments were cut perpendicular to the long axis of the vessel at 2 mm intervals, and 1045 slides with 5 microm thick tissue for whole segments were prepared. To construct the plaque surface, each tissue slice was considered to be representative of the adjacent 2 mm. The circumference of the lumen and the lumen border of plaque were measured in each slide, and the plaque surface region was constructed. Coronary plaque was in 37 (93%) of 40 segments, and consisted of a single mass [39.9 +/- 3.9 (0-100) mm, 311.3 +/- 47.4 (0.0-1336.2) mm2]. In 30 (75%) segments, multiple (2-9) yellow plaques were detected on a mass of coronary plaque. The number of yellow plaques correlated positively with coronary plaque surface area (r = 0.77, P < 0.0001). Yellow plaques in coronaries detected by angioscopy with quantitative colorimetry, some of them are associated with lipid cores underneath thin fibrous caps, may be used to assess the extent of coronary plaque. Further research using angioscopy could be of value to study the association of high-risk coronaries with acute coronary syndromes.

  18. Heparin Cofactor II in Atherosclerotic Lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study

    PubMed Central

    Rau, Jill C.; Deans, Carolyn; Hoffman, Maureane R.; Thomas, David B.; Malcom, Gray T.; Zieske, Arthur W.; Strong, Jack P.; Koch, Gary G.; Church, Frank C.

    2009-01-01

    Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and α1-protease inhibitor) in the same localized region of the atheroma. PMID:19747479

  19. A greater reduction in high-frequency heart rate variability to a psychological stressor is associated with subclinical coronary and aortic calcification in postmenopausal women.

    PubMed

    Gianaros, Peter J; Salomon, Kristen; Zhou, Fan; Owens, Jane F; Edmundowicz, Daniel; Kuller, Lewis H; Matthews, Karen A

    2005-01-01

    Reduced cardiac parasympathetic activity, as indicated by a reduced level of clinic or ambulatory high-frequency heart rate variability (HF-HRV), is associated with an increased risk for atherosclerosis and coronary artery disease. We tested whether the reduction in HF-HRV to a psychological stressor relative to a baseline level is also associated with subclinical coronary or aortic atherosclerosis, as assessed by calcification in these vascular regions. Spectral estimates of 0.15 to 0.40 Hz HF-HRV were obtained from 94 postmenopausal women (61-69 years) who engaged in a 3-minute speech-preparation stressor after a 6-minute resting baseline. A median of 282 days later, electron beam tomography (EBT) was used to measure the extent of coronary and aortic calcification. In univariate analyses, a greater reduction in HF-HRV from baseline to speech preparation was associated with having more extensive calcification in the coronary arteries (rho = -0.29, p = .03) and in the aorta (rho = -0.22, p = .06). In multivariate analyses that controlled for age, education level, smoking status, hormone therapy use, fasting glucose, high-density lipoproteins, baseline HF-HRV, and the stressor-induced change in respiration rate, a greater stressor-induced reduction in HF-HRV was associated with more calcification in the coronary arteries (B = -1.21, p < .05), and it was marginally associated with more calcification in the aorta (B = -0.92, p = .09). In postmenopausal women, a greater reduction in cardiac parasympathetic activity to a psychological stressor from baseline may be an independent correlate of subclinical atherosclerosis, particularly in the coronary arteries.

  20. The results of modipin monotherapy in coronary heart disease patients with arterial hypertension (secondary coronary prevention).

    PubMed

    Kapanadze, S; Dolidze, N; Bakhutashvili, Z; Latsabidze, N; Chapidze, L

    2005-01-01

    The goal of the present study was to evaluate the safety and efficacy of the third generation calcium antagonist -- modipin (amlodipin, Asfarma, Turkey) in 29 patients with coronary atherosclerosis and arterial hypertension. In addition, some pleiotropic actions were examined. On the background of 5-10 mg/day modipin monotherapy during the 3-month study period the target systolic and diastolic blood pressure were achieved in 64 and 51% of cases. Modipin revealed some antiatherogenic efficacy as well. Pleiotropic effects of the drug were particularly expressed in restoring endothelial function reducing degree of hyperlipoperoxidemia and inhibition of platelet aggregation. There were positive changes in functional class of angina. Clinical safety was good. Consequently the present trial supports the use of modipine in all coronary artery disease patients with moderate or severe arterial hypertension.

  1. Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.

    PubMed

    Grainger, Andrew T; Jones, Michael B; Li, Jing; Chen, Mei-Hua; Manichaikul, Ani; Shi, Weibin

    2016-11-01

    Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe -/- and BALB/cJ-Apoe -/- mice in atherosclerotic lesion formation. 206 female F 2 mice generated from an intercross between the two Apoe -/- strains were fed 12 weeks of western diet. Atherosclerotic lesion sizes in the aortic root were measured and 149 genetic markers genotyped across the entire genome. A significant locus, named Ath49 (LOD score: 4.18), for atherosclerosis was mapped to the H2 complex [mouse major histocompatibility complex (MHC)] on chromosome 17. Bioinformatic analysis identified 12 probable candidate genes, including Tnfrsf21, Adgrf1, Adgrf5, Mep1a, and Pla2g7. Corresponding human genomic regions of Ath49 showed significant association with coronary heart disease. Five suggestive loci on chromosomes 1, 4, 5, and 8 for atherosclerosis were also identified. Atherosclerotic lesion sizes were significantly correlated with HDL but not with non-HDL cholesterol, triglyceride or glucose levels in the F 2 cohort. We have identified the MHC as a major genetic determinant of atherosclerosis, highlighting the importance of inflammation in atherogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Coronary involvement in Churg-Strauss syndrome.

    PubMed

    Dendramis, Gregory; Paleologo, Claudia; Piraino, Davide; Arrotti, Salvatore; Assennato, Pasquale

    2015-01-01

    Systemic autoimmune diseases are themselves a relevant and independent risk factor for atherosclerosis and coronary ectasia. We describe a case of a 58-year-old Caucasian man who was admitted to our department for unstable angina. History of asthma, paranasal sinus abnormality, and peripheral eosinophilia given a high suspicion of Churg-Strauss syndrome (CSS). Diagnosis was performed with 5 of the 6 American College of Rheumatology criteria. The knowledge that CSS is often associated with significant coronary artery involvement and the persistence of chest pain led us to performing immediately a coronary angiography. Coronary angiography showed diffuse ectasic lesions, chronic occlusion of left anterior descending artery with homocoronary collateral circulation from left circumflex artery and subocclusive stenosis in the proximal tract of posterior descending artery. The early recognition of CSS, an aggressive invasive diagnostic approach, and an early appropriate therapy are important to prevent the progressive and permanent cardiac damage in these patients. In the setting of a multidisciplinary approach, careful cardiac assessment is an essential step in CSS, even in mildly symptomatic patients. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  3. Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association.

    PubMed

    Goldstein, Benjamin I; Carnethon, Mercedes R; Matthews, Karen A; McIntyre, Roger S; Miller, Gregory E; Raghuveer, Geetha; Stoney, Catherine M; Wasiak, Hank; McCrindle, Brian W

    2015-09-08

    In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications. © 2015 American Heart Association, Inc.

  4. Hereditary hemochromatosis, iron, hepcidin, and coronary heart disease.

    PubMed

    Mascitelli, Luca; Goldstein, Mark R

    2014-03-01

    Mounting evidence suggests that a state of sustained iron depletion may exert a primary protective action against coronary heart disease. A persistent criticism of the iron hypothesis has been that atherosclerosis may not be a prominent feature of hereditary hemochromatosis. The essence of this criticism is that iron cannot be a significant factor in atherogenesis in those unaffected by inherited iron overload unless an increase in atherosclerosis is observed in hereditary hemochromatosis. However, the emerging details of the physiology of hepcidin, the key hormone in iron recycling, suggest a resolution of the apparent paradox of an important role for iron in atherogenesis in the possible absence of increased plaque burden in most types of hereditary hemochromatosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Airflow obstruction, atherosclerosis and cardiovascular risk factors in the AGES Reykjavik study.

    PubMed

    Gudmundsson, Gunnar; Margretardottir, Olof Birna; Sigurdsson, Martin Ingi; Harris, Tamara B; Launer, Lenore J; Sigurdsson, Sigurdur; Olafsson, Orn; Aspelund, Thor; Gudnason, Vilmundur

    2016-09-01

    Airflow limitation, i.e. reduced forced expiratory volume in 1-s (FEV1), is associated with increased prevalence of atherosclerosis, however, causal mechanisms remain elusive. The objective of the study was to determine if the association between airflow obstruction and markers of atherosclerosis is mediated by systemic inflammation. 1154 subjects from the longitudinal AGES Reykjavik study were included. Population characteristics, systemic inflammation markers from blood (white blood cell counts (WBC) and level of C-reactive protein (CRP)) were compared between patients with and without airflow limitation defined by reduced FEV1 on spirometry. Atherosclerosis burden was quantified by measurements of coronary artery calcium, aortic arch and distal aortic calcification in addition to carotid intimal media thickness (CIMT). Subjects were split into four groups according to smoking status and whether airflow limitation was present. There was a higher overall burden of atherosclerosis in ever-smokers compared to never-smokers, and in individuals with airflow obstruction compared to individuals without airflow obstruction. After adjusting for population characteristics, Framingham cardiovascular risk factors and markers of systemic inflammation (WBC and CRP), there was a significantly increased aortic arch and distal aorta calcification and higher CIMT measurement in individuals with airflow obstruction compared to individuals without airflow obstruction. After adjusting for population characteristics, Framingham cardiovascular risk factors and markers of systemic inflammation (WBC and CRP), there was a significantly increased aortic arch and distal aorta calcification and higher CIMT measurement in individuals with airflow obstruction compared to individuals without airflow obstruction. Systemic inflammation (WBC and CRP) does not appear to mediate the association between airflow limitation and atherosclerosis. Only airflow limitation and not systemic inflammation (WBC

  6. Association between lipoprotein associated phospholipase A2 mass and subclinical coronary and carotid atherosclerosis in Retired National Football League players.

    PubMed

    Pokharel, Yashashwi; Nambi, Vijay; Martin, Seth S; Hoogeveen, Ron C; Nasir, Khurram; Khera, Amit; Wong, Nathan D; Jones, Peter H; Boone, Jeffrey; Roberts, Arthur J; Ballantyne, Christie M; Virani, Salim S

    2014-10-01

    Retired National Football League (NFL) players were reported to have high prevalence of cardiovascular risk factors. Lipoprotein Associated Phospholipase A2 (LpPLA2) has shown to be associated with cardiovascular disease in the general population, but it is unknown whether such an association exists in retired NFL players. Our objective was to assess whether LpPLA2 mass was associated with coronary artery calcium (CAC) and carotid artery plaque (CAP) in retired NFL players. LpPLA2 mass was assessed using a dual monoclonal antibody immunoassay. CAC presence was defined as CAC score>0. CAP was defined as focal thickening ≥50% than that of the surrounding vessel wall with a minimal thickness of 1.2 mm on carotid ultrasound. In 832 NFL players, the median (IQR) age and LpPLA2 levels were 54 (45-63) years and 142 (109-181) ng/mL respectively. LpPLA2 mass was positively correlated with low-density lipoprotein (LDL) cholesterol and high-density lipoprotein cholesterol; negatively correlated with LDL particle concentration and body mass index; and not correlated with high-sensitivity C-reactive protein. CAC was present in 659 (79%) and CAP in 544 (65%) players. In a fully adjusted model, LpPLA2 was not associated with CAC (OR per 1-SD increase, 0.85; 95% CI 0.71-1.02) or CAP (0.90, 0.75-1.08). LpPLA2 was also not associated with CAC burden in those with CAC>0. Results were similar when highest and lowest LpPLA2 tertiles were compared, and also in various subgroups. LpPLA2 mass was not associated with coronary or carotid subclinical atherosclerosis in retired NFL players. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis.

    PubMed

    Song, Chun-Li; Wang, Jin-Peng; Xue, Xin; Liu, Ning; Zhang, Xiao-Hao; Zhao, Zhuo; Liu, Jian-Gen; Zhang, Chun-Peng; Piao, Zhe-Hao; Liu, Yang; Yang, Yi-Bo

    2017-01-01

    This study aims to investigate the role of circular antisense non-coding RNA at the INK4 locus (cANRIL) in the inflammatory response of vascular endothelial cells (ECs) in a rat model of coronary atherosclerosis (AS). A rat model of AS was established with rats that were injected with a large dose of vitamin D3 and fed a high-fat diet. Sixty Wistar rats were randomly assigned into control, model, empty vector, over-expressed cANRIL and low-expressed cANRIL groups (12 rats in each group). Sixteen weeks later, the ultrastructure of their coronary arteries was observed via transmission electron microscopy. Rat serum lipid levels were analyzed using an automatic biochemical analyzer, and their atherogenic index (AI) values were calculated. Hematoxylin and eosin staining was used to observe the endothelial morphology of rats. Additionally, rat EC apoptosis was tested via a TUNEL assay. Enzyme-linked immunosorbent assays (ELISAs) were applied to measure serum levels of interleukin-1 (IL-1), IL-6, matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP). The cANRIL, Bax, bcl-2 and caspase-3 mRNA expression levels were measured with a quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Bax, bcl-2 and caspase-3 were detected using immunohistochemistry. In the control group, ECs were closely arranged with normal structures, and there was no proliferation. In the model, empty vector and over-expressed cANRIL groups, some cells were not present, and atherosclerotic plaques and thrombi appeared. However, in the under-expressed cANRIL group, the cells had a normal structure. Compared with the model and empty vector groups, the levels of total cholesterol (CHOL), triglycerides (TGs), low density lipoprotein (LDL), IL-1, IL-6, MMP-9, CRP, cANRIL, Bax, and caspase-3, AI values, and rates of EC apoptosis decreased in the low-expressed cANRIL group, while HDL (high density lipoprotein) levels and mRNA and protein expression levels of

  8. Relationship between central and peripheral atherosclerosis and left ventricular dysfunction in a community population.

    PubMed

    Tsao, Connie W; Gona, Philimon; Salton, Carol; Murabito, Joanne M; Oyama, Noriko; Danias, Peter G; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

    2011-08-01

    We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 ± 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI ≤ 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.

  9. Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction☆

    PubMed Central

    Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

    2010-01-01

    Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

  10. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.

    PubMed

    Fuster, José J; MacLauchlan, Susan; Zuriaga, María A; Polackal, Maya N; Ostriker, Allison C; Chakraborty, Raja; Wu, Chia-Ling; Sano, Soichi; Muralidharan, Sujatha; Rius, Cristina; Vuong, Jacqueline; Jacob, Sophia; Muralidhar, Varsha; Robertson, Avril A B; Cooper, Matthew A; Andrés, Vicente; Hirschi, Karen K; Martin, Kathleen A; Walsh, Kenneth

    2017-02-24

    Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This clonal hematopoiesis correlates with an increased risk of atherosclerotic cardiovascular disease. We studied the effects of the expansion of Tet2 -mutant cells in atherosclerosis-prone, low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice. We found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome-mediated interleukin-1β secretion. An NLRP3 inhibitor showed greater atheroprotective activity in chimeric mice reconstituted with TET2-deficient cells than in nonchimeric mice. These results support the hypothesis that somatic TET2 mutations in blood cells play a causal role in atherosclerosis. Copyright © 2017, American Association for the Advancement of Science.

  11. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice

    PubMed Central

    Fuster, José J.; MacLauchlan, Susan; Zuriaga, María A.; Polackal, Maya N.; Ostriker, Allison C.; Chakraborty, Raja; Wu, Chia-Ling; Sano, Soichi; Muralidharan, Sujatha; Rius, Cristina; Vuong, Jacqueline; Jacob, Sophia; Muralidhar, Varsha; Robertson, Avril A. B.; Cooper, Matthew A.; Andrés, Vicente; Hirschi, Karen K.; Martin, Kathleen A.; Walsh, Kenneth

    2017-01-01

    Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This clonal hematopoiesis correlates with an increased risk of atherosclerotic cardiovascular disease. We studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr−/−) mice. We found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome–mediated interleukin-1β secretion. An NLRP3 inhibitor showed greater atheroprotective activity in chimeric mice reconstituted with TET2-deficient cells than in nonchimeric mice. These results support the hypothesis that somatic TET2 mutations in blood cells play a causal role in atherosclerosis. PMID:28104796

  12. Association of Scavenger Receptor Class B Type I Polymorphisms with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Naj, Adam C.; West, Michael; Rich, Stephen S.; Post, Wendy; Kao, W.H. Linda; Wasserman, Bruce A.; Herrington, David M.; Rodriguez, Annabelle

    2012-01-01

    Background Little is known regarding the association of scavenger receptor class B type I (SCARB1) single nucleotide polymorphisms (SNPs) and subclinical atherosclerosis (SCA), particularly in subjects of different racial/ethnic backgrounds. We examined this relationship in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results Forty-three SCARB1 tagging SNPs were genotyped. Baseline examinations included fasting lipids and SCA phenotypes (coronary artery calcium [CAC], and common and internal carotid artery thickness [CCIMT and ICIMT]). Examining SNP associations with different SCA phenotypes across multiple racial/ethnic groups with adjustment for multiple covariates, we found the C allele of SNP rs10846744 was associated with higher CCIMT in African American (P=0.03), Chinese (P=0.02), European American (P=0.05), and Hispanic participants (P=0.03), and was strongly associated in pooled analyses (P=0.0002). The results also showed that the association of this SNP with CCIMT was independent of lipids and other well-established cardiovascular risk factors. Stratifying by sex, there appeared to be a strong association of rs10846744 with CCIMT in females, but no genotype-sex interactions were observed. Conclusions Variation in SCARB1 at rs10846744 was significantly associated with CCIMT across racial/ethnic groups in MESA. PMID:20160195

  13. Induction of atherosclerosis in mice and hamsters without germline genetic engineering.

    PubMed

    Bjørklund, Martin Maeng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup; Dagnaes-Hansen, Frederik; Christoffersen, Christina; Mikkelsen, Jacob Giehm; Bentzon, Jacob Fog

    2014-05-23

    Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. To develop a method for induction of atherosclerosis without germline genetic engineering. Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions to the fibroatheromatous stage. To demonstrate the applicability of this method for rapid analysis of the atherosclerosis susceptibility of a mouse strain and for providing temporal control over disease induction, we demonstrated the accelerated atherosclerosis of mature diabetic Akita mice. Furthermore, the versatility of this approach for creating atherosclerosis models also in nonmurine species was demonstrated by inducing hypercholesterolemia and early atherosclerosis in Golden Syrian hamsters. Single injections of proprotein convertase subtilisin/kexin type 9-encoding recombinant adeno-associated viral vectors are a rapid and versatile method to induce atherosclerosis in animals. This method should prove useful for experiments that are high-throughput or involve genetic techniques, strains, or species that do not combine well with current genetically engineered models. © 2014 American Heart Association, Inc.

  14. Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis.

    PubMed

    Wang, Pei; Xu, Tian-Ying; Guan, Yun-Feng; Zhao, Yan; Li, Zhi-Yong; Lan, Xiao-Hong; Wang, Xia; Yang, Peng-Yuan; Kang, Zhi-Min; Vanhoutte, Paul M; Miao, Chao-Yu

    2014-06-01

    Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  15. [THE INFLUENCE OF MONO- AND MULTIVASCULAR LESIONS OF CORONARY ARTERIES ON THE COURSE OF CORONARY HEART DISEASE IN PATIENTS WITH DIABETES MELLITUS TYPE 2].

    PubMed

    Sypalo, A; Kravchun, P; Kadykova, O

    2017-03-01

    The article assesses the influence of mono- and multivascular lesions of coronary arteries on the course of coronary heart disease at patients with diabetes mellitus type 2. For this purpose, a comprehensive survey of 75 patients with coronary heart disease and diabetes mellitus type 2 was arranged. Depending on the number of vascular lesions of the coronary arteries, according to the data of coronary arteries computer tomography, all patients were divided into two subgroups. The first subgroup included 27 patients with coronary heart disease and diabetes mellitus type 2 with monovascular lesions of coronary arteries. To the second subgroup were included 48 patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries. During the analysis of carbohydrate metabolism in cases of coronary heart disease and diabetes mellitus type 2 the HOMA index increase by 25.40% and insulin level increase by 17.05% were revealed at patients with multivascular lesions of coronary arteries in comparison with patients with monovascular lesions of coronary arteries, respectively. The combination of coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries was associated with an increase of sortilin level (233,47±47,85 ng/l). A significant increase in triglycerides, lipoprotein cholesterol of very low density influences greatly on the progression of coronary atherosclerosis with lesions of greater number of coronary arteries at patients surveyed. At patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries the left ventricle myocardial re-modeling occurred through the increase of left ventricle's size and cavity.

  16. Resting and Activated Natural Tregs Decrease in the Peripheral Blood of Patients with Atherosclerosis.

    PubMed

    Yazdani, Mohammadreza; Khosropanah, Shahdad; Hosseini, Ahmad; Doroudchi, Mehrnoosh

    2016-12-01

    Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography. Lipid profiles of the patients and controls were measured at the time of sampling. Mononuclear cells were used for both RNA extraction and immunophenotyping by real-time PCR and flowcytometry techniques, respectively. In natural Treg subsets, the frequency of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated nTregs) was significantly higher in controls compared with patients (p=0.02). However, the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory T-cell) increased in patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3 were higher in control group than in patients (p=0.015 and p=0.017, respectively). Moreover, the TGF-β gene expression showed a decrease in the peripheral blood mononuclear cells of patients compared with controls (p=0.03). Decrease in both subsets of resting and activated nTregs along with a decrease in the expression of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes in these subsets, which may as well be correlated with a more inflammatory profile in their lymphocytes.

  17. Radiographic evidence of atherosclerosis of the descending aorta in a grey-cheeked parakeet (Brotogeris pyrrhopterus).

    PubMed

    Mans, Christoph; Brown, Cynthia J

    2007-03-01

    A 16-year-old male grey-cheeked parakeet (Brotogeris pyrrhopterus) was presented for dyspnea and decreased activity. The bird's diet was primarily table food, with a large proportion of animal products. Radiographs revealed a linear mineralized structure in the plane of the aorta and an enlarged hepatocardiac silhouette. Left atrial and left ventricular enlargement and a left ventricular systolic dysfunction were diagnosed by echocardiography. The bird's condition progressively declined, and it died 5 days after presentation. A postmortem examination revealed marked atherosclerosis of the aorta, great vessels of the heart, and coronary arteries with myocardial degeneration, pulmonary congestion, and ascites. Little is known about the risk factors of atherosclerosis in psittacine birds, and dietary influence, if any, is not understood.

  18. Racial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Feinstein, Matthew; Ning, Hongyan; Kang, Joseph; Bertoni, Alain; Carnethon, Mercedes; Lloyd-Jones, Donald M

    2012-07-03

    No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously. We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute-sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95% CI, 0.60, 1.00). CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.

  19. Pulmonary Exposure to Combustion Particulate Matter Induces Myocardial Mitochondrial injury and impaired tolerance to ischemia reoxygenation

    EPA Science Inventory

    Background and aim: Air pollution is associated with increased morbidity and mortality of acute and chronic coronary heart disease. This effect has been attributed to oxidative stress, thrombogenesis, elevation of blood pressure, inflammation and accelerated atherosclerosis. H...

  20. [Surgical angioplasty of the left main coronary artery].

    PubMed

    Vranes, Mile; Velinović, Milos; Kocica, Mladen; Mikić, Aleksandar; Velimirović, Dusan; Djukić, Petar

    2010-01-01

    The conventional treatment for isolated stenosis of the left main coronary artery is bypass surgery (myocardial revascularization). However, the process of atherosclerosis is not arrested by myocardial revascularization and it will lead to the occlusion of the left main coronary artery. Revascularization will establish retrograde perfusion for 50-70% of the myocardium of the left ventricle. Direct surgical angioplasty of the left main coronary artery enables normal physiological perfusion of the whole myocardium and better myocardial function. The aim of our study is to point out a new surgical approach of treating left main coronary artery stenosis. Between October 2002 and October 2003, direct surgical angioplasty of the main left coronary artery was performed on three patients with isolated stenosis of the left main coronary artery using the anterior approach and the pericardium as a patch. The procedure was performed under total endotracheal anaesthesia and standard cardiopulmonary circulation, moderate hypothermia, anterograde St. Tomas cardioplegia and local cooling. Patients were followed clinically, echocardiographically and by load-tests. All three patients were without complications. In postoperative follow-up (54-68 months) neither angina pectoris nor electrocardiographically registered ischaemic changes were found. Load-tests performed every six months on all three patients were negative. Surgical angioplasty of isolated stenosis of the left main coronary artery is a preferred method for treating this type of coronary disease. Contraindications for this type of treatment are stenosis of the left main coronary artery with bifurcation and advanced calcification of the left main coronary artery.

  1. Early accelerated senescence of circulating endothelial progenitor cells in premature coronary artery disease patients in a developing country - a case control study.

    PubMed

    Vemparala, Kranthi; Roy, Ambuj; Bahl, Vinay Kumar; Prabhakaran, Dorairaj; Nath, Neera; Sinha, Subrata; Nandi, Pradipta; Pandey, Ravindra Mohan; Reddy, Kolli Srinath; Manhapra, Ajay; Lakshmy, Ramakrishnan

    2013-11-19

    The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR- ELISA respectively. The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD patients compared to controls. These differences persisted after adjustment for age, sex, BMI, smoking and medications. EPC-TA was reduced in PCAD patients, but was statistically significant only after adjustment for confounding factors (1.81 Vs. 2.20 IU/cell, unadjusted p = 0.057, adjusted p = 0.044). We observed an association between increased vascular cell senescence with PCAD in a sample of young patients from India. This suggests that early accelerated vascular cell senescence may play an important mechanistic role in CAD epidemic in developing countries like India where PCAD burden is markedly higher compared to developed countries.

  2. Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy.

    PubMed

    Nielsen, Signe H; Mygind, Naja D; Michelsen, Marie M; Bechsgaard, Daria F; Suhrs, Hannah E; Genovese, Federica; Nielsen, Henning B; Brix, Susanne; Karsdal, Morten; Prescott, Eva; Kastrup, Jens

    2018-05-01

    Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001-0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001-0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

  3. An integrated approach to coronary heart disease diagnosis and clinical management.

    PubMed

    Infante, Teresa; Forte, Ernesto; Schiano, Concetta; Cavaliere, Carlo; Tedeschi, Carlo; Soricelli, Andrea; Salvatore, Marco; Napoli, Claudio

    2017-01-01

    The major issue in coronary heart disease (CHD) diagnosis and management is that symptoms onset in an advanced state of disease. Despite the availability of several clinical risk scores, the prediction of cardiovascular events is lacking, and many patients at risk are not well stratified according to the canonical risk factors alone. Therefore, adequate risk assessment remains the most challenging issue. Recently, the integration of imaging data with biochemical markers in a radiogenomic framework has been proposed in many fields of medicine as well as in cardiology. Multimodal imaging and advanced processing techniques can provide both direct (e.g., remodeling index, calcium score, total plaque volume, plaque burden) and indirect (e.g., myocardial perfusion index, coronary flow reserve) imaging features of CHD. Furthermore, the identification of novel non-invasive biochemical markers, mainly focused on plasma and/or serum samples, has increased the specificity of findings, reflecting several pathophysiological pathways of atherosclerosis, the principal actor in CHD. In this context, a multifaced approach, derived from the strengths of all these modalities, appears promising for finer risk stratification and treatment strategies, facilitating the decision-making and clinical management of patients. This review underlines the role of different imaging modalities in the quantification of coronary atherosclerosis and describes novel blood-based markers that could improve diagnosis and have a better predictive value in CHD.

  4. Diet and the role of lipoproteins, lipases, and thyroid hormones in coronary lesion growth

    NASA Technical Reports Server (NTRS)

    Barth, Jacques D.; Jansen, Hans; Reiber, Johan H. C.; Birkenhager, Jan C.; Kromhout, Daan

    1987-01-01

    The relationships between the coronary lesion growth and the blood contents of lipoprotein fractions, thyroic hormones, and the lipoprotein lipase activity were investigated in male patients with severe coronary atherosclerosis, who participated in a lipid-lowering dietary intervention program. A quantitative computer-assisted image-processing technique was used to assess the severity of coronary obstructions at the beginning of the program and at its termination two years later. Based on absolute coronary scores, patients were divided into a no-lesion growth group (14 patients) and a progression group (21 paients). At the end of the trial, the very-low-density lipoprotein cholesterol and triglycerides were found to be significantly higher, while the high-density lipoprotein cholesterol and hepatic lipase (HL) were lower in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions.

  5. Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

    PubMed

    Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Benavente, Oscar; Zweifler, Richard M; Callahan, Alfred; Hennerici, Michael G; Zivin, Justin A; Welch, K Michael A

    2010-03-01

    Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients. A total of 4731 patients (mean age, 63 years) was randomized to 80 mg/day atorvastatin placebo. The rates of major coronary event, any CHD event, and any revascularization procedure were evaluated. After 4.9 years of follow-up, the risks of a major coronary event and of any CHD end point in the placebo group were 5.1% and 8.6%, respectively. The rate of outcome of stroke decreased over time, whereas the major coronary event rate was stable. Relative to those having a large vessel-related stroke at baseline, those having a transient ischemic attack, hemorrhagic stroke, small vessel stroke, or a stroke of unknown cause had similar absolute rates for a first major coronary event and for any CHD event; transient ischemic attack, small vessel, and unknown cause groups had lower absolute revascularization procedure rates. Major coronary event, any CHD event, and any revascularization procedure rates were similarly reduced in all baseline stroke subtypes in the atorvastatin arm compared with placebo with no heterogeneity between groups. CHD risk can be substantially reduced by atorvastatin therapy in patients with recent stroke or transient ischemic attack regardless of stroke subtype.

  6. Polycystic ovarian syndrome and subclinical atherosclerosis among women of reproductive age in the Dallas heart study.

    PubMed

    Chang, Alice Y; Ayers, Colby; Minhajuddin, Abu; Jain, Tulika; Nurenberg, Pamela; de Lemos, James A; Wild, Robert A; Auchus, Richard J

    2011-01-01

    Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of young women, is characterized by androgen excess and is frequently associated with cardiovascular risk factors. However, it is unclear whether PCOS is a risk factor for atherosclerosis. We sought to determine in a multiethnic population-based sample whether women with PCOS have greater measures of subclinical atherosclerosis than women without PCOS. Cross-sectional study of a nested cohort from the Dallas Heart Study (2000-2002). Women between the ages of 35 and 49 (n = 827). PCOS was defined by Rotterdam criteria. The normal control group had regular menses, total testosterone <2·78 nmol/l, no signs of hirsutism and no polycystic ovarian morphology by magnetic resonance imaging (MRI). Subclinical atherosclerosis defined as coronary artery calcium (CAC) by computed tomography and abdominal aortic plaque by MRI. The prevalence of PCOS in Dallas County was 19·6% (n = 144), and 8·0% (n = 56) had both oligomenorrhea and hyperandrogenism. Women with PCOS had higher body mass index, blood pressure, insulin and leptin than regularly cycling controls. Despite a greater prevalence of cardiovascular risk factors, women with PCOS did not have a greater prevalence of CAC > 10 Agatston units (PCOS 5%, controls 6·3%, P = 0·74) or abdominal aortic plaque (PCOS 25·8%, controls 34·4%, P = 0·13) than controls. In a large, multiethnic, population-based sample of premenopausal women, PCOS, defined by Rotterdam criteria, was not associated with a higher prevalence of coronary artery calcium or abdominal aortic plaque. © 2010 Blackwell Publishing Ltd.

  7. Prospective Study of Particulate Air Pollution Exposures, Subclinical Atherosclerosis, and Clinical Cardiovascular Disease

    PubMed Central

    Kaufman, Joel D.; Adar, Sara D.; Allen, Ryan W.; Barr, R. Graham; Budoff, Matthew J.; Burke, Gregory L.; Casillas, Adrian M.; Cohen, Martin A.; Curl, Cynthia L.; Daviglus, Martha L.; Roux, Ana V. Diez; Jacobs, David R.; Kronmal, Richard A.; Larson, Timothy V.; Liu, Sally Lee-Jane; Lumley, Thomas; Navas-Acien, Ana; O'Leary, Daniel H.; Rotter, Jerome I.; Sampson, Paul D.; Sheppard, Lianne; Siscovick, David S.; Stein, James H.; Szpiro, Adam A.; Tracy, Russell P.

    2012-01-01

    The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45–84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD. PMID:23043127

  8. Emerging Roles of GPER in Diabetes and Atherosclerosis

    PubMed Central

    Barton, Matthias; Prossnitz, Eric R.

    2015-01-01

    G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor implicated in rapid estrogen signaling. Originally cloned from vascular endothelial cells, GPER plays a central role in the regulation of vascular tone and cell growth, as well as lipid and glucose homeostasis. This review highlights our knowledge of the physiological and pathophysiological functions of GPER in the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent findings of its roles in obesity, diabetes, and atherosclerosis, including the GPER-dependent regulation of lipid metabolism and inflammation, are presented. The therapeutic potential of targeting GPER-dependent pathways in chronic diseases such as coronary artery disease and diabetes and in the context of menopause is also discussed. PMID:25767029

  9. Atherosclerosis (image)

    MedlinePlus

    Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

  10. Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis

    PubMed Central

    Linton, MacRae F.; Babaev, Vladimir R.; Huang, Jiansheng; Linton, Edward F.; Tao, Huan; Yancey, Patricia G.

    2017-01-01

    Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes. Akt displays isoform-specific effects on atherogenesis, which vary with different vascular cell types. Loss of macrophage Akt2 promotes the anti-inflammatory M2 phenotype and reduces atherosclerosis. However, Akt isoforms are redundant with regard to apoptosis. c-Jun NH2-terminal kinase (JNK) is a pro-apoptotic effector of the UPR, and the JNK1 isoform opposes anti-apoptotic Akt signaling. Loss of JNK1 in hematopoietic cells protects macrophages from apoptosis and accelerates early atherosclerosis. IκB kinase α (IKKα, a member of the serine/threonine protein kinase family) plays an important role in mTORC2-mediated Akt signaling in macrophages, and IKKα deficiency reduces macrophage survival and suppresses early atherosclerosis. Efferocytosis involves the interaction of receptors, bridging molecules, and apoptotic cell ligands. Scavenger receptor class B type I is a critical mediator of macrophage efferocytosis via the Src/PI3K/Rac1 pathway in atherosclerosis. Agonists that resolve inflammation offer promising therapeutic potential to promote efferocytosis and prevent atherosclerotic clinical events. PMID:27725526

  11. Coronary calcium in systemic lupus erythematosus is associated with traditional cardiovascular risk factors, but not with disease activity.

    PubMed

    Kiani, Adnan N; Magder, Laurence; Petri, Michelle

    2008-07-01

    Cardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). The frequency of both subclinical and clinically evident atherosclerosis is greatly increased over healthy controls. We assessed cardiovascular risk factors present in patients with SLE at the baseline visit in a statin intervention trial and their correlation with coronary calcium. Coronary calcium was measured by helical computed tomography (continuous volumetric data acquisition in a single breath-hold) in 200 patients with SLE enrolled in the Lupus Atherosclerosis Prevention Study. Patients had a mean age of 44.3 +/- 11.4 years and were 92% women, 61% Caucasian, 34% African American, 2% Asian, and 2% Hispanic. Coronary calcium was found in 43%. In univariate analysis, coronary calcification was associated with age (p = 0.0001), hypertension (p = 0.0008), body mass index (BMI; p = 0.03), erythrocyte sedimentation rate (ESR; p = 0.03), anti-dsDNA (p = 0.067), and lipoprotein(a) (p = 0.03). Homocysteine (p = 0.050), high-sensitivity C-reactive protein (hsCRP; p = 0.053), and LDL (p = 0.048) had a stronger association when considered as quantitative predictors. In a multiple logistic regression model, only age (p coronary calcium. We also examined variables independently predictive of a coronary calcium score > 100. Based on a multiple logistic regression model, only age (p = 0.0017) and diabetes mellitus (p = 0.019) remained significant independent predictors of coronary calcium > 100. Inflammation, measured as ESR or hsCRP, is associated with coronary calcium only in univariate analyses. Age, BMI, and diabetes mellitus are more important associates of coronary calcium in SLE than inflammatory markers and SLE clinical activity.

  12. Invasion of Human Coronary Artery Cells by Periodontal Pathogens

    PubMed Central

    Dorn, Brian R.; Dunn, William A.; Progulske-Fox, Ann

    1999-01-01

    There is an emerging paradigm shift from coronary heart disease having a purely hereditary and nutritional causation to possibly having an infectious etiology. Recent epidemiological studies have shown a correlation between periodontal disease and coronary heart disease. However, to date, there is minimal information as to the possible disease mechanisms of this association. It is our hypothesis that invasion of the coronary artery cells by oral bacteria may start and/or exacerbate the inflammatory response in atherosclerosis. Since a few periodontal pathogens have been reported to invade oral epithelial tissues, we tested the ability of three putative periodontal pathogens—Eikenella corrodens, Porphyromonas gingivalis, and Prevotella intermedia—to invade human coronary artery endothelial cells and coronary artery smooth muscle cells. In this study we demonstrate by an antibiotic protection assay and electron microscopy that specific species and strains invade coronary artery cells at a significant level. Actin polymerization and eukaryotic protein synthesis in metabolically active cells were required since the corresponding inhibitors nearly abrogated invasion. Many intracellular P. gingivalis organisms were seen to be present in multimembranous vacuoles resembling autophagosomes by morphological analysis. This is the first report of oral microorganisms invading human primary cell cultures of the vasculature. PMID:10531230

  13. The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis

    PubMed Central

    2016-01-01

    Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms. TLR4 is expressed in lipid-rich and atherosclerotic plaques. In TLR2−/− and TLR4−/− mice, atherosclerosis-associated inflammation was diminished. Moreover, TLR2 and TLR4 may induce expression of Wnt5a in advanced staged atheromatous plaque leading to activation of the inflammatory processes. TLR9 is activated by CpG motifs in nucleic acids and have been implicated in macrophage activation and the uptake of oxLDL from the circulation. Furthermore, TLR9 also stimulates interferon-α (INF-α) secretion and increases cytotoxic activity of CD4+ T-cells towards coronary artery tunica media smooth muscle cells. This review outlines the pathophysiological role of TLR2, TLR4, and TLR9 in atherosclerosis, focusing on evidence from animal models of the disease. PMID:27795867

  14. Rate of atherosclerosis progression in ApoE-/- mice long after discontinuation of cola beverage drinking.

    PubMed

    Otero-Losada, Matilde; Cao, Gabriel; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Ottaviano, Graciela; Milei, José

    2014-01-01

    This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE-/- C57BL/6J mice (8 week-old) were randomized in 3 groups (n = 20 each) according to free accessto water (W), sucrose sweetened carbonated cola drink(C) or aspartame-acesulfame K sweetened carbonated 'light' cola drink (L)for the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8 weeks-old), at the end of treatment (16 weeks-old) and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice). Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04) and mice age (F4,54 = 5.009, p<0.03) and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks). Natural evolution of atherosclerosis in ApoE-/- mice (W group) evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8-16 weeks of age accelerated atherosclerosis progression in ApoE-/- mice favoring aortic plaque enlargement (inward remodeling) over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE-/- mice.

  15. Immune function of peripheral T cells in patients with venous thromboembolism or coronary artery atherosclerosis.

    PubMed

    Zhou, Lin; Song, Haoming; Xu, Wenjun; Xu, Jiahong; Jiang, Jinfa; Gong, Zhu; Liu, Yang; Yan, Wenwen; Wang, Lemin

    2014-06-01

    Recent studies have shown that the major risk factors for arterial thrombotic diseases are closely associated with venous thromboembolism (VTE). This study aimed to investigate the expression of CD3, CD4 and CD8 in T lymphocytes, the CD4/CD8 ratio and high-sensitivity C-reactive protein (hs-CRP) levels in patients with VTE, coronary artery atherosclerosis (CAA) and healthy subjects. A total of 82 healthy subjects, 51 VTE patients and 114 CAA patients were recruited, and the expression of CD3, CD4 and CD8 in T lymphocytes and the CD4/CD8 ratio were determined. Serum hs-CRP was also measured. Compared to healthy subjects, VTE patients had significantly reduced CD3 expression (p=0.019), comparable CD4 expression (p=0.868), significantly reduced CD8 expression (p<0.001) and increased CD4/CD8 ratio (p=0.044). However, VTE patients had comparable expression of CD3, CD4 and CD8 and CD4/CD8 ratio to CAA patients. In addition, among patients with VTE or CAA, the proportion of patients with reduced CD3+ and CD8+ T lymphocytes or increased CD4/CD8 ratio was significantly higher than in healthy subjects. In addition, hs-CRP in both VTE and CAA groups was significantly higher than in healthy subjects. The antigen recognition and signal transduction activation of T cells is significantly reduced in patients with VTE or CAA, and the killing effect of T cells on pathogens, including viruses, is also significantly compromised. In addition, inflammatory and immune mechanisms are involved in the occurrence and development of venous and arterial thrombosis. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  16. Psychosocial predictors of coronary artery calcification progression in postmenopausal women.

    PubMed

    Low, Carissa A; Matthews, Karen A; Kuller, Lewis H; Edmundowicz, Daniel

    2011-01-01

    Coronary artery calcification (CAC) has been associated with psychosocial factors in some but not all cross-sectional analyses. The goal of this study was to determine whether positive and negative psychosocial factors prospectively predict CAC progression in postmenopausal women. Participants from the Healthy Women Study who also participated in the Pittsburgh Mind-Body Center protocol (n = 149) completed self-report psychosocial measures before two electron beam computed tomographic scans of CAC separated by an average of 3.3 years. Results of exploratory factor analysis were used to create aggregate psychosocial indices: psychological risk (depressive symptoms, perceived stress, cynicism, and anger-in) and psychosocial resources (optimism, purpose in life, mastery, self-esteem, and social support). The psychological risk index predicted significantly greater CAC progression over 3 years (β = 0.16, p = .035, ΔR(2) = 0.03), whereas the psychosocial resources index was not predictive of CAC progression (β = -0.08, p = .30, ΔR(2) = 0.01). On individual scales, higher scores on cynicism emerged as a significant predictor of CAC progression, along with a trend linking anger-in to atherosclerosis progression. A post hoc analysis showed a significant interaction between cynicism and anger-in (β = 0.20, p = .01, ΔR(2) = 0.03), such that women reporting high levels of both cynicism and anger suppression exhibited the most CAC progression. These findings highlight psychosocial risk factors that may accelerate the progression of subclinical atherosclerosis in older women, suggest the potential importance of examining combinations of psychosocial risk factors, and identify potential targets for psychological interventions to reduce cardiovascular risk.

  17. Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study

    PubMed Central

    Agarwala, Anandita; Virani, Salim; Couper, David; Chambless, Lloyd; Boerwinkle, Eric; Astor, Brad C.; Hoogeveen, Ron C.; Coresh, Joe; Sharrett, A. Richey; Folsom, Aaron R; Mosley, Tom; Ballantyne, Christie M.; Nambi, Vijay

    2016-01-01

    Background and aims Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort. Methods 8,127 participants from the ARIC study (4th visit, 1996–1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein-associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis. Results While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis. Conclusions These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD. PMID:27665201

  18. Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study.

    PubMed

    Agarwala, Anandita; Virani, Salim; Couper, David; Chambless, Lloyd; Boerwinkle, Eric; Astor, Brad C; Hoogeveen, Ron C; Coresh, Joe; Sharrett, A Richey; Folsom, Aaron R; Mosley, Tom; Ballantyne, Christie M; Nambi, Vijay

    2016-10-01

    Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort. 8127 participants from the ARIC study (4th visit, 1996-1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein-associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis. While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis. These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD. Published by Elsevier Ireland Ltd.

  19. High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS).

    PubMed

    Daida, Hiroyuki; Takayama, Tadateru; Hiro, Takafumi; Yamagishi, Masakazu; Hirayama, Atsushi; Saito, Satoshi; Yamaguchi, Tetsu; Matsuzaki, Masunori

    2012-07-25

    The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl). In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group). In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm(3)) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm(3)). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c. Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease. ClinicalTrials.gov, Identifier NCT00329160.

  20. High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: Results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS)

    PubMed Central

    2012-01-01

    Background The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl). Methods In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group). Results In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs −0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c. Conclusions Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease. Trial registration ClinicalTrials.gov, Identifier NCT00329160 PMID:22831708

  1. The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice

    PubMed Central

    Mihailovic, Peter M.; Lio, Wai Man; Yano, Juliana; Zhao, Xiaoning; Zhou, Jianchang; Chyu, Kuang-Yuh; Shah, Prediman K.; Cercek, Bojan

    2017-01-01

    Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/-) with different doses of the shortened peptide (Cramp) resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs), whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/-) mouse model. PMID:29091929

  2. Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice

    PubMed Central

    Chung, Rosanna W. S.; Wang, Zeneng; Bursill, Christina A.; Wu, Ben J.; Barter, Philip J.

    2017-01-01

    Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice. PMID:29240800

  3. Comparison of left anterior descending coronary artery hemodynamics before and after angioplasty.

    PubMed

    Ramaswamy, S D; Vigmostad, S C; Wahle, A; Lai, Y G; Olszewski, M E; Braddy, K C; Brennan, T M H; Rossen, J D; Sonka, M; Chandran, K B

    2006-02-01

    Coronary artery disease (CAD) is characterized by the progression of atherosclerosis, a complex pathological process involving the initiation, deposition, development, and breakdown of the plaque. The blood flow mechanics in arteries play a critical role in the targeted locations and progression of atherosclerotic plaque. In coronary arteries with motion during the cardiac contraction and relaxation, the hemodynamic flow field is substantially different from the other arterial sites with predilection of atherosclerosis. In this study, our efforts focused on the effects of arterial motion and local geometry on the hemodynamics of a left anterior descending (LAD) coronary artery before and after clinical intervention to treat the disease. Three-dimensional (3D) arterial segments were reconstructed at 10 phases of the cardiac cycle for both pre- and postintervention based on the fusion of intravascular ultrasound (IVUS) and biplane angiographic images. An arbitrary Lagrangian-Eulerian formulation was used for the computational fluid dynamic analysis. The measured arterial translation was observed to be larger during systole after intervention and more out-of-plane motion was observed before intervention, indicating substantial alterations in the cardiac contraction after angioplasty. The time averaged axial wall shear stress ranged from -0.2 to 9.5 Pa before intervention compared to -0.02 to 3.53 Pa after intervention. Substantial oscillatory shear stress was present in the preintervention flow dynamics compared to that in the postintervention case.

  4. CAD-RADS - a new clinical decision support tool for coronary computed tomography angiography.

    PubMed

    Foldyna, Borek; Szilveszter, Bálint; Scholtz, Jan-Erik; Banerji, Dahlia; Maurovich-Horvat, Pál; Hoffmann, Udo

    2018-04-01

    Coronary computed tomography angiography (CTA) has been established as an accurate method to non-invasively assess coronary artery disease (CAD). The proposed 'Coronary Artery Disease Reporting and Data System' (CAD-RADS) may enable standardised reporting of the broad spectrum of coronary CTA findings related to the presence, extent and composition of coronary atherosclerosis. The CAD-RADS classification is a comprehensive tool for summarising findings on a per-patient-basis dependent on the highest-grade coronary artery lesion, ranging from CAD-RADS 0 (absence of CAD) to CAD-RADS 5 (total occlusion of a coronary artery). In addition, it provides suggestions for clinical management for each classification, including further testing and therapeutic options. Despite some limitations, CAD-RADS may facilitate improved communication between imagers and patient caregivers. As such, CAD-RADS may enable a more efficient use of coronary CTA leading to more accurate utilisation of invasive coronary angiograms. Furthermore, widespread use of CAD-RADS may facilitate registry-based research of diagnostic and prognostic aspects of CTA. • CAD-RADS is a tool for standardising coronary CTA reports. • CAD-RADS includes clinical treatment recommendations based on CTA findings. • CAD-RADS has the potential to reduce variability of CTA reports.

  5. High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial.

    PubMed

    Hodis, Howard N; Mack, Wendy J; Dustin, Laurie; Mahrer, Peter R; Azen, Stanley P; Detrano, Robert; Selhub, Jacob; Alaupovic, Petar; Liu, Chao-ran; Liu, Ci-hua; Hwang, Juliana; Wilcox, Alison G; Selzer, Robert H

    2009-03-01

    Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression. In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 micromol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B(12)+50 mg vitamin B(6)) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome). Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy >or=9.1 micromol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 micromol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups. High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin "replete" individuals at low risk for cardiovascular disease with a fasting tHcy >or=9.1 micromol/L.

  6. Egg consumption and coronary artery calcification in asymptomatic men and women.

    PubMed

    Choi, Yuni; Chang, Yoosoo; Lee, Jung Eun; Chun, Sohyun; Cho, Juhee; Sung, Eunju; Suh, Byung-Seong; Rampal, Sanjay; Zhao, Di; Zhang, Yiyi; Pastor-Barriuso, Roberto; Lima, Joao A C; Shin, Hocheol; Ryu, Seungho; Guallar, Eliseo

    2015-08-01

    The association of egg consumption with subclinical coronary atherosclerosis remains unknown. Our aim was to examine the association between egg consumption and prevalence of coronary artery calcium (CAC). Cross-sectional study of 23,417 asymptomatic adult men and women without a history of cardiovascular disease (CVD) or hypercholesterolemia, who underwent a health screening examination including cardiac computed tomography for CAC scoring and completed a validated food frequency questionnaire at the Kangbuk Samsung Hospital Total Healthcare Centers, South Korea (March 2011-April 2013). The prevalence of detectable CAC (CAC score > 0) was 11.2%. In multivariable-adjusted models, CAC score ratio (95% confidence interval [CI]) comparing participants eating ≥ 7 eggs/wk to those eating < 1 egg/wk was 1.80 (1.14-2.83; P for trend = 0.003). The multivariable CAC score ratio (95% CI) associated with an increase in consumption of 1 egg/day was 1.54 (1.11-2.14). The positive association seemed to be more pronounced among participants with low vegetable intake (P for interaction = 0.02) and those with high BMI (P for interaction = 0.05). The association was attenuated and no longer significant after further adjustment for dietary cholesterol. Egg consumption was associated with an increased prevalence of subclinical coronary atherosclerosis and with a greater degree of coronary calcification in asymptomatic Korean adults, which may be mediated by dietary cholesterol. The association was particularly pronounced among individuals with low vegetable intake and those with high BMI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Atherosclerotic involvement in patients with left or right dominant coronary circulation.

    PubMed

    Balci, Bahattin; Yilmaz, Ozcan

    2004-06-01

    There are variations in the anatomy of the coronary arteries in patients with left dominant circulation. The influence of anatomical variations in patients with left dominant circulation on coronary arteriosclerosis is not clear. We investigated whether atherosclerotic involvement in patients with left dominant circulation differs from that in patients with right dominant circulation. We retrospectively compared 38 consecutive angiograms with left coronary dominance with 459 consecutive angiograms with right coronary dominance. By using the 29-segment coding system of the American College of Cardiology/American Heart Association, numerical values were given to each segment, according to the percentage of the decrease in luminary diameter. Using, the sum of numerical values in each coronary artery, LAD score, LCx score, RCA score, and left main coronary artery (LMCA) score were obtained. Using the sum of these 4 vessel scores, the coronary artery disease (CAD) score was calculated. Total LAD score (49+/-48 vs 47+/-57), total LCx score (29+/-45 vs 41+/-58), total RCA score (32+/-68 vs 30+/-51), total LMCA score (1.8+/-11.3 vs 2.9+/-13.6) and total CAD score (108+/-108 vs 108+/-123) were similar in patients with left and right dominant circulation (all differences NS). The extent of coronary atherosclerosis does not depend on the type of dominant coronary circulation.

  8. A default normal chest CT structured reporting field for coronary calcifications does not cause excessive false-negative reporting.

    PubMed

    Walter, William R; Goldberg-Stein, Shlomit; Levsky, Jeffrey M; Cohen, Hillel W; Scheinfeld, Meir H

    2015-08-01

    The aim of this study was to compare the accuracy of coronary atherosclerosis reporting before and after the implementation of a structured reporting chest CT template. A noncardiac, noncontrast chest CT structured reporting template was developed and mandated for department-wide use at a large academic center. The template included the statement "There are no coronary artery calcifications." All noncardiac, noncontrast chest CT examinations reported over 3 days, 1 month after template implementation (structured template group), and from a 3-day period 1 year prior (control group) were retrospectively collected. Final radiology reports were reviewed and designated positive or negative for coronary calcifications. CT images were reviewed in consensus by 2 radiologists, who scored each case for the presence or absence of coronary calcifications, blinded to the original report. Statistical analysis was performed using Pearson χ(2) and Fisher exact tests. Sixty-five percent (69 of 106) of structured template group and 58% (62 of 106) of control group cases had coronary calcifications. Reports from the structured template group were more likely to correctly state the presence or absence of coronary atherosclerosis compared with those from the control group (96.2% vs 85.8%; odds ratio, 4.2; 95% confidence interval, 1.3-13.1; P = .008). Structured template group reports were less likely to be falsely negative compared with control group reports (3.8% vs 11.7%; odds ratio, 3.4; 95% confidence interval, 1.0-10.8; P = .03). Implementing a structured reporting template improves reporting accuracy of coronary calcifications. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  9. Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

    PubMed

    Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

    2015-01-14

    In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

  10. Acute myocardial infarction in a young bodybuilder taking anabolic androgenic steroids: A case report and critical review of the literature.

    PubMed

    Christou, Georgios A; Christou, Konstantinos A; Nikas, Dimitrios N; Goudevenos, John A

    2016-11-01

    We describe a case report of a 30-year-old bodybuilder suffering acute myocardial infarction (AMI). He had been taking stanozolol and testosterone for two months. The coronary angiogram showed high thrombotic burden in the left anterior descending artery without underlying atherosclerosis. Few case reports of AMI in athletes taking anabolic androgenic steroids (AASs) have been reported so far. AAS-related AMI is possibly underreported in the medical literature due to the desire of the affected individuals to hide AAS use. Physicians should always consider the possibility of AAS abuse in the context of a young athlete suffering AMI. AASs can predispose to AMI through the acceleration of coronary atherosclerosis. Additionally, thrombosis without underlying atherosclerosis or vasospasm is highly possible to cause AMI in AAS users. Complications after AMI may be more frequent in AAS users. © The European Society of Cardiology 2016.

  11. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study.

    PubMed

    Reis, Jared P; Loria, Catherine M; Steffen, Lyn M; Zhou, Xia; van Horn, Linda; Siscovick, David S; Jacobs, David R; Carr, J Jeffrey

    2010-10-01

    To determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness later in life. The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a cohort of 5115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC (score, >0 Agatston units at year 15 or 20), CAC progression (incident CAC at year 20 or increase in CAC score by ≥20 Agatston units), or high carotid intima-media thickness (>80th percentile, year 20). However, tea consumption displayed a nonsignificant trend for an inverse association with CAC (P=0.08 for trend) and an inverse association with CAC progression (P=0.04 for trend) but no association with high carotid intima-media thickness (P>0.20 for trend). Stratification of the coffee analyses by sex, race, or smoking yielded similar nonsignificant patterns. We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC but not carotid atherosclerosis.

  12. Early changes in coronary artery wall structure detected by microcomputed tomography in experimental hypercholesterolemia.

    PubMed

    Zhu, Xiang-Yang; Bentley, Michael D; Chade, Alejandro R; Ritman, Erik L; Lerman, Amir; Lerman, Lilach O

    2007-09-01

    Changes in the structure of the artery wall commence shortly after exposure to cardiovascular risk factors, such as hypercholesterolemia (HC), but may be difficult to detect. The ability to study vascular wall structure could be helpful in evaluation of the factors that instigate atherosclerosis and its pathomechanisms. The present study tested the hypothesis that early morphological changes in coronary arteries of hypercholesterolemic (HC) pigs can be detected using the novel X-ray contrast agent OsO(4) and three-dimensional micro-computed tomography (CT). Two groups of pigs were studied after they were fed a normal or an HC (2% cholesterol) diet for 12 wk. Hearts were harvested, coronary arteries were injected with 1% OsO(4) solution, and cardiac samples (6-mum-thick) were scanned by micro-CT. Layers of the epicardial coronary artery wall, early lesions, and perivascular OsO(4) accumulation were determined. Leakage of OsO(4) from myocardial microvessels was used to assess vascular permeability, which was correlated with immunoreactivity of vascular endothelial growth factor in corresponding histological cross sections. OsO(4) enhanced the visualization of coronary artery wall layers and facilitated detection of early lesions in HC in longitudinal tomographic sections of vascular segments. Increased density of perivascular OsO(4) in HC was correlated with increased vascular endothelial growth factor expression and suggested increased microvascular permeability. The use of OsO(4) as a contrast agent in micro-CT allows three-dimensional visualization of coronary artery wall structure, early lesion formation, and changes in vascular permeability. Therefore, this technique can be a useful tool in atherosclerosis research.

  13. Femoral and carotid subclinical atherosclerosis association with risk factors and coronary calcium: the AWHS study

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Early subclinical atherosclerosis has been mainly researched in carotid arteries. The potential value of femoral arteries for improving the predictive capacity of traditional risk factors is an understudied area. OBJECTIVES: This study sought to evaluate the association of subclinical ca...

  14. The additive effect of adherence to multiple healthy lifestyles on subclinical atherosclerosis: Insights from the AWHS.

    PubMed

    Uzhova, Irina; Mateo-Gallego, Rocio; Moreno-Franco, Belén; Molina-Montes, Esther; Leon-Latre, Montserrat; Casasnovas Lenguas, José A; Civeira, Fernando; Peñalvo, José L

    2018-03-28

    Public health strategies targeting multiple healthy behaviors, rather than individual factors, have been proposed as more efficient strategies to promote cardiovascular health. However, the additive effect of multiple targets on primary prevention has not been fully characterized. To examine how adherence to multiple healthy behaviors is associated with the presence of subclinical atherosclerosis, a measure of early cardiovascular disease. Analysis of a baseline data from 1798 middle-aged men from the Aragon Workers Health Study conducted between 2009 and 2010. Healthy behaviors were defined according to American Heart Association recommendations, aligned with Spanish Nutritional recommendations and included moderate alcohol consumption, smoking abstinence, no abdominal adiposity, decreased sedentarism, and adherence to Alternate Mediterranean Dietary Index. Presence of coronary artery calcium and plaques in femoral and carotid was quantified by a 16-slice computed tomography scanner and 2D ultrasound. Moderate alcohol consumption, as well as adherence to Mediterranean diet is independently associated with a 6% lower risk of having subclinical atherosclerosis. Smoking abstinence is associated with a 11% lower risk of subclinical atherosclerosis. Those who follow 3 lifestyle behaviors (Mediterranean diet, nonsmoking, and moderate alcohol intake) have 18% lower odds of presenting subclinical atherosclerosis compared with those who do not follow these protective lifestyle habits. Adoption of multiple healthy lifestyle behaviors early in life could be a key strategy to tackle the onset of atherosclerosis and reduce cardiovascular disease burden. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  15. Computational fluid dynamics comparisons of wall shear stress in patient-specific coronary artery bifurcation using coronary angiography and optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Poon, Eric; Thondapu, Vikas; Chin, Cheng; Scheerlinck, Cedric; Zahtila, Tony; Mamon, Chris; Nguyen, Wilson; Ooi, Andrew; Barlis, Peter

    2016-11-01

    Blood flow dynamics directly influence biology of the arterial wall, and are closely linked with the development of coronary artery disease. Computational fluid dynamics (CFD) solvers may be employed to analyze the hemodynamic environment in patient-specific reconstructions of coronary arteries. Although coronary X-ray angiography (CA) is the most common medical imaging modality for 3D arterial reconstruction, models reconstructed from CA assume a circular or elliptical cross-sectional area. This limitation can be overcome with a reconstruction technique fusing CA with intravascular optical coherence tomography (OCT). OCT scans the interior of an artery using near-infrared light, achieving a 10-micron resolution and providing unprecedented detail of vessel geometry. We compared 3D coronary artery bifurcation models generated using CA alone versus OCT-angiography fusion. The model reconstructed from CA alone is unable to identify the detailed geometrical variations of diseased arteries, and also under-estimates the cross-sectional vessel area compared to OCT-angiography fusion. CFD was performed in both models under pulsatile flow in order to identify and compare regions of low wall shear stress, a hemodynamic parameter directly linked with progression of atherosclerosis. Supported by ARC LP150100233 and VLSCI VR0210.

  16. Rate of Atherosclerosis Progression in ApoE−/− Mice Long After Discontinuation of Cola Beverage Drinking

    PubMed Central

    Otero-Losada, Matilde; Cao, Gabriel; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Ottaviano, Graciela; Milei, José

    2014-01-01

    This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE−/− C57BL/6J mice (8 week-old) were randomized in 3 groups (n = 20 each) according to free accessto water (W), sucrose sweetened carbonated cola drink(C) or aspartame-acesulfame K sweetened carbonated ‘light’ cola drink (L)for the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8weeks-old), at the end of treatment (16 weeks-old) and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice). Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04) and mice age (F4,54 = 5.009, p<0.03) and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks). Natural evolution of atherosclerosis in ApoE−/− mice (W group) evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8–16 weeks of age accelerated atherosclerosis progression in ApoE−/− mice favoring aortic plaque enlargement (inward remodeling) over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE−/− mice

  17. Emerging roles of GPER in diabetes and atherosclerosis.

    PubMed

    Barton, Matthias; Prossnitz, Eric R

    2015-04-01

    The G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor implicated in rapid estrogen signaling. Originally cloned from vascular endothelial cells, GPER plays a central role in the regulation of vascular tone and cell growth as well as lipid and glucose homeostasis. This review highlights our knowledge of the physiological and pathophysiological functions of GPER in the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent findings on its roles in obesity, diabetes, and atherosclerosis, including GPER-dependent regulation of lipid metabolism and inflammation, are presented. The therapeutic potential of targeting GPER-dependent pathways in chronic diseases such as coronary artery disease and diabetes and in the context of menopause is also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Relationship between serum visfatin levels and coronary slow-flow phenomenon.

    PubMed

    Cakmak, Huseyin Altug; Aslan, Serkan; Yalcin, Ahmet Arif; Akturk, Ibrahim Faruk; Yalcin, Burce; Uzun, Fatih; Ozturk, Derya; Erturk, Mehmet; Gul, Mehmet

    2015-09-01

    Increased levels of visfatin, a novel adipocytokine, are reported in atherosclerosis, obesity, and type 2 diabetes. The aim of the present study was to investigate the relationship between coronary slow flow (CSF) and visfatin in patients undergoing elective coronary angiography for suspected coronary artery disease. A total of 140 recruited participants (90 patients with CSF and 50 controls) were divided into two groups according to their coronary flow rates. Coronary flow was quantified by thrombolysis in myocardial infarction (TIMI) frame count (TFC). Serum visfatin levels were higher in the CSF group than in the control group (3.29 ± 1.11 vs. 2.70 ± 1.08 ng/ml, p = 0.003). A significant correlation was found between TFC and visfatin (r = 0.535, p < 0.001). The area under the receiver operating characteristic curve was 0.720 (95 % confidence interval, 0.622-0.817, p < 0.001) for visfatin in the diagnosis of CSF. If a cut-off value of 2.59 ng/ml was used, higher levels of visfatin could predict the presence of CSF with 78.9 % sensitivity and 64.0 % specificity. Visfatin levels might be a useful biomarker for predicting CSF in patients undergoing diagnostic coronary angiography.

  19. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

    PubMed Central

    Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

    2015-01-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  20. Structural and functional changes of the coronary arteries in elderly senile patients with essential hypertension.

    PubMed

    Hu, Jun; Zhu, Fu; Xie, Jun; Cheng, Xinhai; Chen, Guiyu; Tai, Haifen; Fan, Shaohua

    2013-11-01

    The aim of this study was to evaluate the effect of aging on the changes to the structure and function of coronary arteries in senile elderly patients with essential hypertension. Patients (aged 60-80 years) were divided into three groups. The 195 hypertensive patients were divided into four sub-groups according to the duration of hypertension. The changes to the coronary arteries (left and right) of all those patients were tested using the following index by 64 coronary computed tomography (CT) scans. The 24 h systolic blood pressure (SBP) and other blood biochemical parameters were assayed for all patients. We found that the value of the body mass index (BMI), total cholesterol (TC) and low density lipoproteins (LDL) were lower, but age and high density lipoproteins (HDL) were higher in the group of very elderly patients with hypertension (Group I; P<0.05) compared with those of a group of elderly patients with hypertension (Group III). The left anterior descending branch calcification score (CSLAD), total calcification score (CST), pulse pressure (PP), the left main branch calcification score (CSLM), the left circumflex branch calcification score (CSLCX) were significantly increased in Group I compared with Group III (P<0.01 and P<0.05, respectively). In addition, the 24 h SBP value for Group I was higher than in the 'very elderly without hypertension' group (Group II). Hence, in elderly patients, a decrease in the levels of BMI, HDL, TC and LDL accompanies aging. Furthermore, the decline of arterial compliance and increase in arterial stiffness develops with age. Aging is more likely to lead to atherosclerosis in the coronary arteries, particularly in the left main coronary artery and its main branches. Aging is an uncontrollable risk factor, which plays a crucial role in coronary artery atherosclerosis.

  1. Cardiovascular magnetic resonance profiling of coronary atherosclerosis: vessel wall remodelling and related myocardial blood flow alterations.

    PubMed

    Jahnke, Cosima; Manka, Robert; Kozerke, Sebastian; Schnackenburg, Bernhard; Gebker, Rolf; Marx, Nikolaus; Paetsch, Ingo

    2014-12-01

    To determine the association between coronary vessel wall morphology and haemodynamic consequences to the myocardium using a combined cardiovascular magnetic resonance (CMR) imaging protocol. Non-invasive CMR profiling of coronary atherosclerotic wall changes and related myocardial blood flow impairment has not been established yet. Sixty-three patients (45 men, 61.5 ± 10.7 years) with suspected or known coronary artery disease underwent 3.0 Tesla CMR imaging. The combined CMR protocol consisted of the following imaging modules at rest: 3D vessel wall imaging and flow measurement of the proximal right coronary artery (RCA), myocardial T2*, and first-pass perfusion imaging. During adenosine stress coronary flow, T2* and first-pass perfusion imaging were repeated. Coronary X-ray angiography classified patient groups: (i) all-smooth (n = 19); (ii) luminal irregular (diameter reduction < 30%; n = 35); and (iii) stenosed RCA (diameter reduction ≥ 50%; n = 9). The ratio of CMR-derived vessel wall area-to-lumen area significantly increased stepwise for the comparison of all-smooth vs. luminal irregular vs. stenosed RCA (1.9 ± 0.6 vs. 2.6 ± 0.6 vs. 3.6 ± 0.9, P < 0.01). Epicardial coronary flow reserve exhibited a stepwise significant decrease (3.4 ± 0.5 vs. 2.9 ± 0.7 vs. 1.7 ± 0.3, P < 0.01). On the myocardial level, stress-induced percentage gain of T2* values (ΔT2*) was significantly decreased between groups (29.2 ± 10.6 vs. 9.0 ± 9.8 vs. 2.2 ± 11.8%, P < 0.01) while perfusion reserve index decreased in the presence of stenosed RCA only (2.2 ± 0.6 vs. 2.0 ± 0.4 vs. 1.3 ± 0.3, P = ns and P < 0.01, respectively). The proposed comprehensive CMR imaging protocol provided a non-invasive approach for direct assessment of coronary vessel wall remodelling and resultant pathophysiological consequences on the level of epicardial coronary and myocardial blood flow in patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The

  2. The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

    PubMed Central

    She, Zhi-Gang; Chen, Hou-Zao; Yan, Yunfei; Li, Hongliang

    2012-01-01

    Abstract The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar β propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence. Clinical observations focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Many other conditions, such as diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The abundance and/or activity of PONs can be regulated by lipoproteins and their metabolites, biological macromolecules, pharmacological treatments, dietary factors, and lifestyle. In conclusion, both previous results and ongoing studies provide evidence, making the PON cluster a prospective target for the treatment of atherosclerosis. Antioxid. Redox Signal. 16, 597–632. PMID:21867409

  3. Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease.

    PubMed

    Vrtovec, Matjaz; Anzic, Ajda; Zupan, Irena Preloznik; Zaletel, Katja; Blinc, Ales

    2017-06-01

    Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], β- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p < 0.01]. No significant differences between groups were found in carotid artery morphology and function, digital endothelial function or overall coronary calcium score. Significantly more ET patients had an elevated coronary calcium score of >160, indicating high cardiovascular risk, not predicted by the Framingham equation.

  4. Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a new acute coronary event.

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Medina-Gil, José María; Garay-Sánchez, Paloma; Tugores, Antonio

    Paraoxonase 1 (PON1) plays a major role in the oxidation of low density lipoprotein and in the prevention of coronary atherogenesis. In this context, coding region polymorphisms of PON1 gene, responsible for the enzyme activity, has become of interest as a marker for atherogenesis. A study and follow-up was conducted on 529 patients with an acute coronary event in order to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the type of acute coronary syndrome, cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and severity of coronary atherosclerosis, and the medium-term clinical follow-up. The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%) patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No significant differences were found between the QQ and QR/RR genotypes as regards the clinical characteristics, the analytical data, and the angiographic variables. Similarly, Kaplan-Meier survival analysis showed no significant differences in presenting with a new acute coronary event (p=0.598), cardiac mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598) between QQ and QR/RR genotypes during the follow-up period (3.3±2.2 years). In patients with an acute coronary syndrome, the PON1 Q192R genotypes did not influence the risk of suffering a new acute coronary event during the medium-term follow-up. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Comparative gene expression analysis between coronary arteries and internal mammary arteries identifies a role for the TES gene in endothelial cell functions relevant to coronary artery disease.

    PubMed

    Archacki, Stephen R; Angheloiu, George; Moravec, Christine S; Liu, Hui; Topol, Eric J; Wang, Qing Kenneth

    2012-03-15

    Coronary artery disease (CAD) is the leading cause of death worldwide. It has been established that internal mammary arteries (IMA) are resistant to the development of atherosclerosis, whereas left anterior descending (LAD) coronary arteries are athero-prone. The contrasting properties of these two arteries provide an innovative strategy to identify the genes that play important roles in the development of atherosclerosis. We carried out microarray analysis to identify genes differentially expressed between IMA and LAD. Twenty-nine genes showed significant differences in their expression levels between IMA and LAD, which included the TES gene encoding Testin. The role of TES in the cardiovascular system is unknown. Here we show that TES is involved in endothelial cell (EC) functions relevant to atherosclerosis. Western blot analysis showed higher TES expression in IMA than in LAD. Reverse transcription polymerase chain reaction and western blot analyses showed that TES was consistently and markedly down-regulated by more than 6-fold at both mRNA and protein levels in patients with CAD compared with controls without CAD (P= 0.000049). The data suggest that reduced TES expression is associated with the development of CAD. Knockdown of TES expression by small-interfering RNA promoted oxidized-LDL-mediated monocyte adhesion to ECs, EC migration and the transendothelial migration of monocytes, while the over-expression of TES in ECs blunted these processes. These results demonstrate association between reduced TES expression and CAD, establish a novel role for TES in EC functions and raise the possibility that reduced TES expression increases susceptibility to the development of CAD.

  6. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

    PubMed Central

    Corcoran, David

    2018-01-01

    The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

  7. The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol <70 mg/dL: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    PubMed

    Al Rifai, Mahmoud; Martin, Seth S; McEvoy, John W; Nasir, Khurram; Blankstein, Ron; Yeboah, Joseph; Miedema, Michael; Shea, Steven J; Polak, Joseph F; Ouyang, Pamela; Blumenthal, Roger S; Bittencourt, Marcio; Bensenor, Isabela; Santos, Raul D; Duncan, Bruce B; Santos, Itamar S; Lotufo, Paulo A; Blaha, Michael J

    2018-07-01

    The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C <70 mg/dL. We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4 th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis. Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C <70 mg/dL (MESA: 206, ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively). Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study.

    PubMed

    Haque, Sahena; Gordon, Caroline; Isenberg, David; Rahman, Anisur; Lanyon, Peter; Bell, Aubrey; Emery, Paul; McHugh, Neil; Teh, Lee Suan; Scott, David G I; Akil, Mohamed; Naz, Sophia; Andrews, Jacqueline; Griffiths, Bridget; Harris, Helen; Youssef, Hazem; McLaren, John; Toescu, Veronica; Devakumar, Vinodh; Teir, Jamal; Bruce, Ian N

    2010-02-01

    Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and

  9. Box-Cox transformation of left-censored data with application to the analysis of coronary artery calcification and pharmacokinetic data.

    PubMed

    Han, Cong; Kronmal, Richard

    2004-12-15

    Box-Cox transformation is investigated for regression models for left-censored data. Examples are provided using coronary calcification data from the Multi-Ethnic Study of Atherosclerosis and pharmacokinetic data of a nicotine nasal spray. Copyright 2004 John Wiley & Sons, Ltd.

  10. Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Vargas, Jose D; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Rotter, Jerome I; Post, Wendy S; Polak, Joseph F; Budoff, Matthew J; Bluemke, David A

    2016-02-01

    Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds. The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66). In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN. Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations. Published by Elsevier Ireland Ltd.

  11. Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.

    PubMed

    Zhang, Jifeng; Niimi, Manabu; Yang, Dongshan; Liang, Jingyan; Xu, Jie; Kimura, Tokuhide; Mathew, Anna V; Guo, Yanhong; Fan, Yanbo; Zhu, Tianqing; Song, Jun; Ackermann, Rose; Koike, Yui; Schwendeman, Anna; Lai, Liangxue; Pennathur, Subramaniam; Garcia-Barrio, Minerva; Fan, Jianglin; Chen, Y Eugene

    2017-06-01

    CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only had higher HDL cholesterol levels but also lower total cholesterol levels than WT rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total cholesterol in KO rabbits was attributable to decreased apolipoprotein B-containing particles, while HDLs remained higher than that in WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. Apolipoprotein B-depleted plasma isolated from CETP KO rabbits showed significantly higher capacity for cholesterol efflux from macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO rabbits suppressed tumor necrosis factor-α-induced vascular cell adhesion molecule 1 and E-selectin expression in cultured endothelial cells. These results provide evidence that genetic ablation of CETP activity protects against cholesterol diet-induced atherosclerosis in rabbits. © 2017 American Heart Association, Inc.

  12. Fluorescence spectroscopic detection of virus-induced atherosclerosis

    NASA Astrophysics Data System (ADS)

    Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

    1994-07-01

    Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

  13. Simultaneous Increases in Proliferation and Apoptosis of Vascular Smooth Muscle Cells Accelerate Diabetic Mouse Venous Atherosclerosis

    PubMed Central

    Liu, Shuying; Zhang, Zhengyu; Wang, Jingjing; Zhou, Yuhuan; Liu, Kefeng; Huang, Jintao; Chen, Dadi; Wang, Junmei; Li, Chaohong

    2015-01-01

    Aims This study was designed to demonstrate simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) leading to accelerated vein graft remodeling and to explore the underlying mechanisms. Methods Vein grafts were performed in non-diabetic and diabetic mice. The cultured quiescent VSMCs were subjected to mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs). Harvested vein grafts and treated VSMCs were used to detect cell proliferation, apoptosis, mitogen-activated protein kinases (MAPKs) activation and SM-α-actin expression. Results Significantly thicker vessel walls and greater increases in proliferation and apoptosis were observed in diabetic vein grafts than those in non-diabetic. Both SS and AGEs were found to induce different activation of three members of MAPKs and simultaneous increases in proliferation and apoptosis of VSMCs, and combined treatment with both had a synergistic effect. VSMCs with strong SM-α-actin expression represented more activated JNKs or p38MAPK, and cell apoptosis, while the cells with weak SM-α-actin expression demonstrated preferential activation of ERKs and cell proliferation. In contrast, inhibition of MAPKs signals triggered significant decreases in VSMC proliferation, and apoptosis. Treatment of the cells with RNA interference of receptor of AGEs (RAGE) also resulted in significant decreases in both proliferation and apoptosis. Conclusions Increased pressure-induced SS triggers simultaneous increases in proliferation and apoptosis of VSMCs in the vein grafts leading to vein arterializations, which can be synergistically accelerated by high glucose-induced AGEs resulting in vein graft atherosclerosis. Either SS or AGEs and their combination induce simultaneous increases in proliferation and apoptosis of VSMCs via different activation of three members of MAPKs resulting from different VSMC subtypes classified by SM-α-actin expression levels. PMID:26488175

  14. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?

    PubMed

    Gotsman, Israel; Stabholz, Ayala; Planer, David; Pugatsch, Thea; Lapidus, Ludmila; Novikov, Yelena; Masrawa, Siham; Soskolne, Aubrey; Lotan, Chaim

    2008-07-01

    Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease. To determine the relationship between inflammatory markers and the angiographic severity of CAD. We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay. There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05). TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

  15. Thyroid hormones and coronary artery calcification in euthyroid men and women.

    PubMed

    Zhang, Yiyi; Kim, Bo-Kyoung; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Rampal, Sanjay; Zhao, Di; Pastor-Barriuso, Roberto; Lima, Joao A; Shin, Hocheol; Guallar, Eliseo

    2014-09-01

    Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone. In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification. © 2014 American Heart Association, Inc.

  16. P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation

    PubMed Central

    PENG, KUANG; LIU, LUSHAN; WEI, DANGHENG; LV, YUNCHENG; WANG, GANG; XIONG, WENHAO; WANG, XIAOQING; ALTAF, AFRASYAB; WANG, LILI; HE, DAN; WANG, HONGYAN; QU, PENG

    2015-01-01

    Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation. PMID:25761252

  17. Elevated lipoprotein(a) levels are associated with coronary artery calcium scores in asymptomatic individuals with a family history of premature atherosclerotic cardiovascular disease.

    PubMed

    Verweij, Simone L; de Ronde, Maurice W J; Verbeek, Rutger; Boekholdt, S Matthijs; Planken, R Nils; Stroes, Erik S G; Pinto-Sietsma, Sara-Joan

    2018-02-16

    Elevated lipoprotein(a) (Lp(a)) levels are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Individuals with a family history of premature ASCVD are at increased cardiovascular risk with concomitantly a higher burden of (subclinical) atherosclerosis. However, whether Lp(a) contributes to the increased atherosclerotic burden in these individuals remains to be established. In this study, we evaluated the association between Lp(a) levels and coronary atherosclerotic burden, assessed by coronary arterty calcium (CAC) scores, in asymptomatic individuals with a family history of premature ASCVD. Lp(a) levels and other ASCVD risk factors were assessed in 432 individuals with premature ASCVD and in 937 healthy asymptomatic family members. CAC scores were only measured in asymptomatic family members. In this cohort, 16% had elevated Lp(a) levels, defined as ≥ 50 mg/dL. Among healthy family members, elevated Lp(a) levels were associated with both absolute CAC scores of ≥ 100 (odds ratio [OR] 1.79 [95% confidence interval {CI} 1.13-2.83]) as well as with age- and gender-corrected CAC scores ≥ 80th percentile (OR 1.69 [95% CI 1.14-2.50]). This coincides with a higher prevalence of cardiovascular events (OR 1.48 [95% CI 1.11-2.01]) in the whole cohort. Elevated Lp(a) levels were associated with higher CAC scores, both absolute as well as age- and gender-corrected percentiles, in individuals with a family history of premature ASCVD. These data imply that Lp(a) accelerates progression of atherosclerosis in these individuals, thereby contributing to their increased ASCVD risk. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  18. Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease

    PubMed Central

    Vrtovec, Matjaz; Anzic, Ajda; Zupan, Irena Preloznik; Zaletel, Katja

    2017-01-01

    Abstract Background Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. Patients and methods 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. Results No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], β- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p < 0.01]. Conclusions No significant differences between groups were found in carotid artery morphology and function, digital endothelial function or overall coronary calcium score. Significantly more ET patients had an elevated coronary calcium score of >160, indicating high cardiovascular risk, not predicted by the Framingham equation. PMID:28740456

  19. Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1-Mediated Protein Kinase A/Uncoupling Protein 2 Pathway.

    PubMed

    Xiong, Shiqiang; Wang, Peijian; Ma, Liqun; Gao, Peng; Gong, Liuping; Li, Li; Li, Qiang; Sun, Fang; Zhou, Xunmei; He, Hongbo; Chen, Jing; Yan, Zhencheng; Liu, Daoyan; Zhu, Zhiming

    2016-02-01

    Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide. Mitochondria are the principal source of reactive oxygen species (ROS), and defective oxidative phosphorylation by the mitochondrial respiratory chain contributes to ROS generation. Uncoupling protein 2 (UCP2), an adaptive antioxidant defense factor, protects against mitochondrial ROS-induced endothelial dysfunction in atherosclerosis. The activation of transient receptor potential vanilloid 1 (TRPV1) attenuates vascular dysfunction. Therefore, whether TRPV1 activation antagonizes coronary lesions by alleviating endothelial mitochondrial dysfunction and enhancing the activity of the protein kinase A/UCP2 pathway warrants examination. ApoE(-/-), ApoE(-/-)/TRPV1(-/-), and ApoE(-/-)/UCP2(-/-) mice were fed standard chow, a high-fat diet (HFD), or the HFD plus 0.01% capsaicin. HFD intake profoundly impaired coronary vasodilatation and myocardial perfusion and shortened the survival duration of ApoE(-/-) mice. TRPV1 or UCP2 deficiency exacerbated HFD-induced coronary dysfunction and was associated with increased ROS generation and reduced nitric oxide production in the endothelium. The activation of TRPV1 by capsaicin upregulated UCP2 expression via protein kinase A phosphorylation, thereby alleviating endothelial mitochondrial dysfunction and inhibiting mitochondrial ROS generation. In vivo, dietary capsaicin supplementation enhanced coronary relaxation and prolonged the survival duration of HFD-fed ApoE(-/-) mice. These effects were not observed in ApoE(-/-) mice lacking the TRPV1 or UCP2 gene. The upregulation of protein kinase A /UCP2 via TRPV1 activation ameliorates coronary dysfunction and prolongs the lifespan of atherosclerotic mice by ameliorating endothelial mitochondrial dysfunction. Dietary capsaicin supplementation may represent a promising intervention for the primary prevention of coronary heart disease. © 2015 American Heart Association, Inc.

  20. Bioresorbable scaffolds for percutaneous coronary interventions

    PubMed Central

    Gogas, Bill D.

    2014-01-01

    Innovations in drug-eluting stents (DES) have substantially reduced rates of in-segment restenosis and early stent thrombosis, improving clinical outcomes following percutaneous coronary interventions (PCI). However a fixed metallic implant in a vessel wall with restored patency and residual disease remains a precipitating factor for sustained local inflammation, in-stent neo-atherosclerosis and impaired vasomotor function increasing the risk for late complications attributed to late or very late stent thrombosis and late target lesion revascularization (TLR) (late catch-up). The quest for optimal coronary stenting continues by further innovations in stent design and by using biocompatible materials other than cobalt chromium, platinum chromium or stainless steel for engineering coronary implants. Bioresorbable scaffolds made of biodegradable polymers or biocorrodible metals with properties of transient vessel scaffolding, local drug-elution and future restoration of vessel anatomy, physiology and local hemodynamics have been recently developed. These devices have been utilized in selected clinical applications so far providing preliminary evidence of safety showing comparable performance with current generation drug-eluting stents (DES). Herein we provide a comprehensive overview of the current status of these technologies, we elaborate on the potential benefits of transient coronary scaffolds over permanent stents in the context of vascular reparation therapy, and we further focus on the evolving challenges these devices have to overcome to compete with current generation DES. Condensed Abstract:: The quest for optimizing percutaneous coronary interventions continues by iterative innovations in device materials beyond cobalt chromium, platinum chromium or stainless steel for engineering coronary implants. Bioresorbable scaffolds made of biodegradable polymers or biocorrodible metals with properties of transient vessel scaffolding; local drug-elution and future

  1. Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

    PubMed

    Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

    2015-08-01

    Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma

  2. Correlation between calcium and phosphate levels to calculus accumulation on coronary heart disease patients

    NASA Astrophysics Data System (ADS)

    Cahaya, Cindy; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni

    2017-02-01

    Coronary Artery Disease (CAD) or Coronary Heart Disease (CHD) is a disease that happened because of blood flow being blocked by atherosclerosis. Atherosclerosis is a process of hardening of the arteries which characterized by thickening and loss of elasticity of the intimal layer of vascular wall, by lipid deposit. Periodontitis is a chronic multifactorial inflammatory disease caused by microorganism and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss. Many studies use saliva as a valuable source for clinically information, as an asset for early diagnosis, prognostic and reviewer for pascatherapy status. Dental calculus had happened as a consequence of saliva supersaturation by calcium and phosphate. Salivary flow rate and its composition influence the formation of calculus. Increasing salivary calcium levels is characteristic of periodontitis patients. An important hipotesis in Cardiology is chronic infections contribute in atherosclerosis. Objective: To analyse the correlation between calcium and phosphate levels in saliva to calculus accumulation on CHD patients. Result: Correlation analysis between salivary calcium levels with calculus accumulation in patients with CHD and non-CHD showed no significant p value, p=0.59 and p=0.518. Correlation analysis between salivary phosphate levels and calculus accumulation showed no significant p value, p=0.836 for CHD patients and p=0.484 for non-CHD patients. Conclusion: There are no correlation between calcium levels and phosphate levels with calculus accumulation in CHD patients. Further research need to be done.

  3. Relation between playing position and coronary artery calcium scores in retired National Football League players.

    PubMed

    Basra, Sukhdeep Singh; Pokharel, Yashashwi; Hira, Ravi S; Bandeali, Salman J; Nambi, Vijay; Deswal, Anita; Nasir, Khurram; Martin, Seth S; Vogel, Robert A; Roberts, Arthur J; Ballantyne, Christie M; Virani, Salim S

    2014-12-15

    Retired National Football League (NFL) linemen have an increased prevalence of risk factors for atherosclerosis and have an increased risk of cardiovascular death compared with nonlinemen and the general population. We evaluated whether playing in lineman position is independently associated with an increased risk of the presence and severity of subclinical atherosclerosis. Players were categorized as linemen if they reported playing on the offensive or defensive line during their careers. Subclinical atherosclerosis was assessed using coronary artery calcium (CAC) scores in 931 retired NFL players (310 linemen, 621 nonlinemen). CAC scores were evaluated for absence of subclinical atherosclerosis (CAC = 0), presence of mild subclinical atherosclerosis (CAC 1 to 100), and moderate to severe subclinical atherosclerosis (CAC ≥100). We performed multivariate logistic regression to determine whether the lineman position is independently associated with the presence and severity of subclinical atherosclerosis. Linemen were noted to have a lesser likelihood of absence of subclinical atherosclerosis (CAC = 0, 33.8% vs 41.7%, p = 0.02), a similar likelihood of mild subclinical atherosclerosis (CAC 1 to 100, 33.2% vs 31.8%, p = 0.7), and a greater likelihood of moderate to severe subclinical atherosclerosis (CAC >100, 32.9% vs 26.4%, p = 0.04) compared with nonlinemen. Adjusting for demographic and metabolic covariates, lineman status remained independently associated with mild subclinical atherosclerosis (CAC 1 to 100, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.05 to 2.2, p = 0.04) and moderate to severe subclinical atherosclerosis (CAC ≥100, OR 1.67, 95% CI 1.05 to 2.2). The association was attenuated after adjustment for race (CAC 1 to 100, OR 1.24, 95% CI 0.82 to 1.8; CAC >100, OR 1.59, 95% CI 1.01 to 2.49). In conclusion, lineman status in retired NFL players is associated with presence and severity of subclinical atherosclerosis, which is partly

  4. Association of heart rate profile during exercise with the severity of coronary artery disease.

    PubMed

    Cay, Serkan; Ozturk, Sezgin; Biyikoglu, Funda; Yildiz, Abdulkadir; Cimen, Tolga; Uygur, Belma; Tuna, Funda

    2009-05-01

    Coronary artery disease is the leading cause of morbidity and mortality around the world. Autonomic nervous system abnormalities are associated with coronary artery disease and its complications. Exercise stress tests are routinely used for the detection of the presence of coronary artery disease. In this study, we observed the association between heart rate profile during exercise and the severity of coronary artery disease. One hundred and sixty patients with abnormal exercise treadmill test (> or =1 mm horizontal or downsloping ST-segment depression; 119 men, 41 women; mean age = 57 +/- 9 years) were included in the study. Use of any drug affecting heart rate was not permitted. Resting heart rate before exercise, maximum heart rate during exercise, and resting heart rate after exercise (5 min later) were measured and two parameters were calculated: heart rate increment (maximum heart rate - resting heart rate before exercise) and heart rate decrement (maximum heart rate - resting heart rate after exercise). All patients underwent selective coronary angiography and subclassified into two groups according to stenotic lesion severity. Group 1 had at least 50% of stenotic lesion and group 2 had less than 50%. Patients in the first group had increased resting heart rate, decreased maximum heart rate, decreased heart rate increment, and decreased heart rate decrement compared with second group. All patients were classified into tertiles of resting heart rate, heart rate increment, and heart rate decrement level to evaluate whether these parameters were associated with severity of coronary artery stenosis in the study. The multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 21.888 (95% confidence interval 6.983-68.606) for the highest tertile of resting heart rate level compared with the lowest tertile. In addition, the multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 20.987 (95% confidence interval 6

  5. Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus.

    PubMed

    Oh, Tae Jung; Ahn, Chang Ho; Kim, Bo-Rahm; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Lim, Cheong; Jang, HakChul; Choi, Sung Hee

    2017-07-20

    A previous genome-wide association study showed that a genetic variant of sortilin was associated with the risk of coronary artery disease (CAD). However, the role of circulating sortilin is still unknown. We investigated the potential role of plasma sortilin as a biomarker for CAD and diabetes mellitus. We enrolled statin-naïve subjects with CAD (n = 31) who underwent coronary artery bypass surgery and control subjects (n = 116) who were free from CAD as evaluated by coronary CT angiography. The presence of diabetes mellitus was evaluated and plasma sortilin levels were measured with a commercial ELISA kit. Plasma sortilin levels were higher in subjects with CAD and subjects with diabetes mellitus than in those without CAD or diabetes mellitus. Subjects in the highest sortilin tertile group were older and had higher glucose and HbA1c levels, but lipid profiles in the three tertile groups were comparable. Multivariable logistic regression analysis revealed that sortilin levels were independently associated with CAD. In addition, the receiver operating characteristic curve analysis showed that plasma sortilin levels could identify the presence of CAD or diabetes mellitus. Elevated circulating sortilin levels are associated with CAD and diabetes mellitus and can be used as a biomarker of both diseases in statin-naïve subjects.

  6. Diet, atherosclerosis, and fish oil.

    PubMed

    Connor, W E; Connor, S L

    1990-01-01

    The principal goal of dietary prevention and treatment of atherosclerotic coronary heart disease is the achievement of physiological levels of the plasma total and LDL cholesterol, triglyceride, and VLDL. These goals have been well delineated by the National Cholesterol Education Program of the National Heart, Lung and Blood Institute and the American Heart Association. Dietary treatment is first accomplished by enhancing LDL receptor activity and at the same time depressing liver synthesis of cholesterol and triglyceride. Both dietary cholesterol and saturated fat decrease LDL receptor activity and inhibit the removal of LDL from the plasma by the liver. Saturated fat decreases LDL receptor activity, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is of importance also. The greater the flux of chylomicron remnants is into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect VLDL and LDL synthesis could be important. These include excessive calories (obesity), which enhance triglyceride and VLDL and hence LDL synthesis. Weight loss and omega-3 fatty acids from fish oil depress synthesis of both VLDL and triglyceride in the liver. The optimal diet for the treatment of children and adults to prevent coronary disease has the following characteristics: cholesterol (100 mg/day), total fat (20% of calories, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% of calories, two thirds from starch including 11 to 15 gm of soluble fiber), and protein (15% of calories). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18% to 21%. This diet is also an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Dietary therapy is the mainstay of the prevention and treatment of coronary heart disease through the control of plasma lipid and lipoprotein levels. The

  7. Association of Big Endothelin-1 with Coronary Artery Calcification.

    PubMed

    Qing, Ping; Li, Xiao-Lin; Zhang, Yan; Li, Yi-Lin; Xu, Rui-Xia; Guo, Yuan-Lin; Li, Sha; Wu, Na-Qiong; Li, Jian-Jun

    2015-01-01

    The coronary artery calcification (CAC) is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1) plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC. A total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS). The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5 ± 0.4 vs. 0.2 ± 0.2, P<0.001). In the multivariate analysis, big ET-1 (Tertile 2, HR = 3.09, 95% CI 1.66-5.74, P <0.001, Tertile3 HR = 10.42, 95% CI 3.62-29.99, P<0.001) appeared as an independent predictive factor of the presence of CAC. There was a positive correlation of the big ET-1 level with CACS (r = 0.567, p<0.001). The 10-year Framingham risk (%) was higher in the group with CACS>0 and the highest tertile of big ET-1 (P<0.01). The area under the receiver operating characteristic curve for the big ET-1 level in predicting CAC was 0.83 (95% CI 0.79-0.87, p<0.001), with a sensitivity of 70.6% and specificity of 87.7%. The data firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study.

  8. Associations between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary Artery and the Aorta.

    PubMed

    Salfati, Elias L; Herrington, David M; Assimes, Themistocles L

    2016-01-01

    The correlation between the extent of fatty streaks, more advanced atherosclerotic lesions, and community rates of coronary artery disease (CAD) is substantially higher for the coronary artery compared to the aorta. We sought to determine whether a genetic basis contributes to these differences. We conducted a cluster analysis of 6 subclinical atherosclerosis phenotypes documented in 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study including the extent of fatty streaks and raised lesions in the coronary artery (CF and CR), thoracic aorta (TF and TR), and abdominal aorta (AF and AR) followed by a genetic association analysis of the same phenotypes. Our cluster analysis grouped all raised lesions and fatty streaks in the coronary into one cluster (CF, CR, TR, and AR) and the fatty streaks in the aorta into a second cluster (TF and AF). We found a genetic risk score of high-risk alleles at 57 susceptibility loci for CAD to be variably associated with the phenotypes in the first cluster (OR: 1.30 p = 0.009 for being in top quartile of degree of involvement of CF, 1.34 p = 0.005 for CR, 1.25: p = 0.11 for TR, and 1.19 p = 0.08 for AR) but not at all with the phenotypes in the second cluster (OR: 1.01, p = 0.95 for TF and 0.98, p = 0.82 for AF). The genetic determinants of fatty streaks in the aorta do not appear to overlap substantially with the genetic determinants of fatty streaks in the coronary as well as raised lesions in both the coronary and the aorta. These findings may explain why a larger fraction of fatty streaks in the aorta are less likely to progress to raised lesions compared to the coronary artery.

  9. Associations between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary Artery and the Aorta

    PubMed Central

    Herrington, David M.

    2016-01-01

    Objective The correlation between the extent of fatty streaks, more advanced atherosclerotic lesions, and community rates of coronary artery disease (CAD) is substantially higher for the coronary artery compared to the aorta. We sought to determine whether a genetic basis contributes to these differences. Approach and Results We conducted a cluster analysis of 6 subclinical atherosclerosis phenotypes documented in 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study including the extent of fatty streaks and raised lesions in the coronary artery (CF and CR), thoracic aorta (TF and TR), and abdominal aorta (AF and AR) followed by a genetic association analysis of the same phenotypes. Our cluster analysis grouped all raised lesions and fatty streaks in the coronary into one cluster (CF, CR, TR, and AR) and the fatty streaks in the aorta into a second cluster (TF and AF). We found a genetic risk score of high-risk alleles at 57 susceptibility loci for CAD to be variably associated with the phenotypes in the first cluster (OR: 1.30 p = 0.009 for being in top quartile of degree of involvement of CF, 1.34 p = 0.005 for CR, 1.25: p = 0.11 for TR, and 1.19 p = 0.08 for AR) but not at all with the phenotypes in the second cluster (OR: 1.01, p = 0.95 for TF and 0.98, p = 0.82 for AF). Conclusions The genetic determinants of fatty streaks in the aorta do not appear to overlap substantially with the genetic determinants of fatty streaks in the coronary as well as raised lesions in both the coronary and the aorta. These findings may explain why a larger fraction of fatty streaks in the aorta are less likely to progress to raised lesions compared to the coronary artery. PMID:27861582

  10. Reconstitution of coronary vasculature by an active fraction of Geum japonicum in ischemic hearts

    NASA Astrophysics Data System (ADS)

    Chen, Hao; Cheng, Lei; Lin, Xiaoli; Zhou, Xiaping; Cai, Zhiming; Li, Ming

    2014-02-01

    Chronic coronary heart disease (cCHD) is characterized by atherosclerosis, which progressively narrows the coronary artery lumen and impairs myocardial blood flow. Restoration of occluded coronary vessels with newly formed collaterals remains an ideal therapeutic approach due to the need for redirecting blood flow into the ischemic heart. In this study, we investigated the effect of an active fraction isolated from Geum joponicum (AFGJ) on angiogenesis in cCHD hearts. Our results demonstrated that AFGJ not only enhanced capillary tube formation of endothelial cells, but also promoted the growth of new coronary collaterals (at the diameter 0.021-0.21 mm) in the ischemic region of hearts in rat cCHD model. Our study also indicated that the growth of new collaterals in ischemic hearts resulted in improved functional recovery of the cCHD hearts as demonstrated by ECG and echocardiography analyses. These data suggest that AFGJ may provide a novel therapeutic method for effective treatment of cCHD.

  11. Noncalcified coronary plaque in systemic lupus erythematosus.

    PubMed

    Kiani, Adnan N; Vogel-Claussen, Jens; Magder, Laurence S; Petri, Michelle

    2010-03-01

    To study noncalcified coronary plaque (NCP) in systemic lupus erythematosus (SLE). Sixty-four-slice coronary multidetector computed tomography (MDCT) was performed in 39 consecutive patients with SLE. MDCT scans were evaluated semiquantitatively by a radiologist using dedicated software. The presence or absence of NCP in each coronary artery was assessed. Patients with mixed plaque (calcified and noncalcified portions) were included in the NCP group. The patient group was 90% women, 64% Caucasian, 31% African American, 5% other; mean age 50.5 +/- 9.6 years. Fifty-four percent (21/39) had NCP. Seventy-six percent (16/21) of those with NCP also had coronary calcium (range 0.7 to 1264.1 Agatston units). In univariate analysis, NCP was associated with age (p = 0.01), current nonsteroidal antiinflammatory drug (NSAID) use (p = 0.04), hormone replacement therapy (p = 0.02), current use of immunosuppressive drugs (p = 0.02), current low serum C3 level (p = 0.07), current physician's global assessment of activity (PGA; p = 0.05), and low-density lipoprotein cholesterol (p = 0.04). NCP was not associated with other risk factors for atherosclerosis, including total serum cholesterol, high sensitivity C-reactive protein, and lipoprotein(a). Unlike coronary calcium, which is not associated with SLE activity measures or with active serologies, NCP is more common in patients with SLE with current, 3-, and 6-month activity by PGA. NCP was also associated with the need for current NSAID or immunosuppressive therapy. NCP is an important part of the total atherosclerotic burden in SLE.

  12. Effects of intra-abdominal sepsis on atherosclerosis in mice.

    PubMed

    Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

    2014-09-03

    Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

  13. The Clinical Significance of Separate Measurements of Carotid Arterial Wall to Assess the Risk Factor for Atherosclerosis.

    PubMed

    Kim, Ji-Hoon; Youn, Ho-Joong; Kim, Gee-Hee; Moon, Keon-Woong; Yoo, Ki-Dong; Kim, Chul-Min

    2016-03-01

    Carotid intima-media thickness (CIMT) is associated with several risk factors for atherosclerosis and has been consistently linked to cardiovascular and cerebrovascular disease. The clinical significance of separate measurements of CIMT, which is the sum of the intima (IT) and media thickness (MT), to use as an assessment of risk for atherosclerosis has not yet been fully established. Among 3377 patients who underwent B-mode ultrasound of carotid arteries and coronary angiography in the Medical Department of St. Mary's Hospital from September 2003 to March 2009, 1146 subjects (M:F = 616:530; mean age, 57.7 ± 12.1 years) who were diagnosed with normal coronary arteries were enrolled in this study. IT, MT, and CIMT of the enrolled patients were manually measured using high-frequency ultrasonography (15 MHz linear array transducer). In multivariate logistic regression analysis, age (β = 0.063, p < 0.0001), body mass index (BMI) (β = 0.028, p = 0.018), and hypertension (HTN) (β = 0.046, p = 0.0002) were associated with MT (R(2) = 0.256) and the IT/MT ratio (R(2) = 0.209). Age (β = 0.065, p < 0.0001), BMI (β = 0.025, p = 0.038), hemoglobin A1c (β = 0.045, p = 0.045), and HTN (β = 0.043, p = 0.0006) correlated with mean CIMT (R(2) = 0.230). Age (β = -0.071, p < 0.0001) and BMI (β = -0.046, p = 0.002) were associated with the IT/MT ratio (R(2) = 0.219) on the left side. Age (β = 0.093, p < 0.0001) was related to MT (R(2) = 0.265) and mean CIMT (R(2) = 0.243) on the left side. We noted different atherosclerotic risk factors were related to measurements of the arterial wall in different ways. Therefore, separate measurements of CIMT might be a useful method to assess the risk for atherosclerosis.

  14. Associations of cortisol/testosterone and cortisol/sex hormone-binding globulin ratios with atherosclerosis in middle-age women.

    PubMed

    Lee, Ju-Mi; Colangelo, Laura A; Schwartz, Joseph E; Yano, Yuichiro; Siscovick, David S; Seeman, Teresa; Schreiner, Pamela J; Liu, Kiang J; Lloyd-Jones, Donald M; Greenland, Philip

    2016-05-01

    The cortisol/testosterone (C/T) ratio has been hypothesized to be a better predictor of atherosclerosis than cortisol alone. No study has assessed whether the C/T and C/sex hormone-binding globulin (SHBG) ratios are associated with atherosclerosis in a U.S. population sample. This substudy included 367 women who had both cortisol from year 15 and testosterone and SHBG at year 16 of the Coronary Artery Risk Development in Young Adults study, an ongoing observational cohort in the United States. Of these, intima-media thickness (IMT) was available at follow-up year 20 in 339 (n = 332 with measurement at carotid bulb), and 303 were free of prevalent coronary artery calcium (CAC) at year 15. Area under the curve (AUC) of salivary cortisol was available in 302 individuals. Ratios of AUCs of cortisol to total testosterone, free testosterone, and SHBG were categorized into tertiles. Associations with CAC and IMT were assessed by regression models adjusted for age, race, body mass index, systolic blood pressure, menopause, oral contraceptive use, diabetes, alcohol, and smoking. Only the highest tertile of the AUC/free testosterone ratio was positively associated with carotid bulb IMT (β = 0.088, P = 0.006). This tertile was also positively associated with new onset CAC between year 15 and 25 (OR 3.45, 95% CI 1.18-10.06). Tertiles of cortisol or testosterone alone were not associated with new onset CAC. AUC/Free testosterone ratio may be more associated with atherosclerosis in women than either indicator alone. The ratio may serve as a suitable biomarker of cortisol-linked stress. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus

    PubMed Central

    Carlucci, Philip M.; Purmalek, Monica M.; Dey, Amit K.; Temesgen-Oyelakin, Yenealem; Sakhardande, Simantini; Joshi, Aditya A.; Lerman, Joseph B.; Fike, Alice; Davis, Michael; Chung, Jonathan H.; Playford, Martin P.; Naqi, Mohammad; Mistry, Pragnesh; Gutierrez-Cruz, Gustavo; Dell’Orso, Stefania; Naz, Faiza; Salahuddin, Taufiq; Natarajan, Balaji; Tsai, Wanxia L.; Gupta, Sarthak; Grayson, Peter; Chen, Marcus Y.; Sun, Hong-Wei; Hasni, Sarfaraz; Mehta, Nehal N.

    2018-01-01

    BACKGROUND. Systemic lupus erythematosus (SLE) is associated with enhanced risk of atherosclerotic cardiovascular disease not explained by Framingham risk score (FRS). Immune dysregulation associated to a distinct subset of lupus proinflammatory neutrophils (low density granulocytes; LDGs) may play key roles in conferring enhanced CV risk. This study assessed if lupus LDGs are associated with in vivo vascular dysfunction and inflammation and coronary plaque. METHODS. SLE subjects and healthy controls underwent multimodal phenotyping of vascular disease by quantifying vascular inflammation (18F-fluorodeoxyglucose–PET/CT [18F-FDG–PET/CT]), arterial dysfunction (EndoPAT and cardio-ankle vascular index), and coronary plaque burden (coronary CT angiography). LDGs were quantified by flow cytometry. Cholesterol efflux capacity was measured in high-density lipoprotein–exposed (HDL-exposed) radioactively labeled cell lines. Whole blood RNA sequencing was performed to assess associations between transcriptomic profiles and vascular phenotype. RESULTS. Vascular inflammation, arterial stiffness, and noncalcified plaque burden (NCB) were increased in SLE compared with controls even after adjustment for traditional risk factors. In SLE, NCB directly associated with LDGs and associated negatively with cholesterol efflux capacity in fully adjusted models. A neutrophil gene signature reflective of the most upregulated genes in lupus LDGs associated with vascular inflammation and NCB. CONCLUSION. Individuals with SLE demonstrate vascular inflammation, arterial dysfunction, and NCB, which may explain the higher reported risk for acute coronary syndromes. The association of LDGs and neutrophil genes with vascular disease supports the hypothesis that distinct neutrophil subsets contribute to vascular damage and unstable coronary plaque in SLE. Results also support previous observations that neutrophils may disrupt HDL function and thereby promote atherogenesis. TRIAL REGISTRATION

  16. [Epigenetics in atherosclerosis].

    PubMed

    Guardiola, Montse; Vallvé, Joan C; Zaina, Silvio; Ribalta, Josep

    2016-01-01

    The association studies based on candidate genes carried on for decades have helped in visualizing the influence of the genetic component in complex diseases such as atherosclerosis, also showing the interaction between different genes and environmental factors. Even with all the knowledge accumulated, there is still some way to go to decipher the individual predisposition to disease, and if we consider the great influence that environmental factors play in the development and progression of atherosclerosis, epigenetics is presented as a key element in trying to expand our knowledge on individual predisposition to atherosclerosis and cardiovascular disease. Epigenetics can be described as the discipline that studies the mechanisms of transcriptional regulation, independent of changes in the sequence of DNA, and mostly induced by environmental factors. This review aims to describe what epigenetics is and how epigenetic mechanisms are involved in atherosclerosis. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  17. Coronary Artery Calcium Volume and Density: Potential Interactions and Overall Predictive Value: The Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Criqui, Michael H; Knox, Jessica B; Denenberg, Julie O; Forbang, Nketi I; McClelland, Robyn L; Novotny, Thomas E; Sandfort, Veit; Waalen, Jill; Blaha, Michael J; Allison, Matthew A

    2017-08-01

    This study sought to determine the possibility of interactions between coronary artery calcium (CAC) volume or CAC density with each other, and with age, sex, ethnicity, the new atherosclerotic cardiovascular disease (ASCVD) risk score, diabetes status, and renal function by estimated glomerular filtration rate, and, using differing CAC scores, to determine the improvement over the ASCVD risk score in risk prediction and reclassification. In MESA (Multi-Ethnic Study of Atherosclerosis), CAC volume was positively and CAC density inversely associated with cardiovascular disease (CVD) events. A total of 3,398 MESA participants free of clinical CVD but with prevalent CAC at baseline were followed for incident CVD events. During a median 11.0 years of follow-up, there were 390 CVD events, 264 of which were coronary heart disease (CHD). With each SD increase of ln CAC volume (1.62), risk of CHD increased 73% (p < 0.001) and risk of CVD increased 61% (p < 0.001). Conversely, each SD increase of CAC density (0.69) was associated with 28% lower risk of CHD (p < 0.001) and 25% lower risk of CVD (p < 0.001). CAC density was inversely associated with risk at all levels of CAC volume (i.e., no interaction was present). In multivariable Cox models, significant interactions were present for CAC volume with age and ASCVD risk score for both CHD and CVD, and CAC density with ASCVD risk score for CVD. Hazard ratios were generally stronger in the lower risk groups. Receiver-operating characteristic area under the curve and Net Reclassification Index analyses showed better prediction by CAC volume than by Agatston, and the addition of CAC density to CAC volume further significantly improved prediction. The inverse association between CAC density and incident CHD and CVD events is robust across strata of other CVD risk factors. Added to the ASCVD risk score, CAC volume and density provided the strongest prediction for CHD and CVD events, and the highest correct reclassification

  18. Activity of antioxidant enzymes in children from families at high risk of premature coronary heart disease.

    PubMed

    Siemianowicz, K; Gmiński, J; Francuz, T; Wójcik, A; Posielezna, B

    2003-01-01

    A positive family history of coronary heart disease (CHD) is one of the most predictive risk factors of CHD. Many children with increased risk of CHD because of their positive family history of CHD do not present other risk factors, such as altered serum lipid profile. Oxidative stress plays an important part in the pathogenesis of atherosclerosis. Serum antioxidants and intracellular enzymatic antioxidants composed mainly of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase counterbalance oxidative stress. Diminished activity of this system may lead to accelerated progression of atherosclerosis. The aim of this study was to assess the activity of CAT, GSH-Px, SOD and glutathione reductase in children with a family history of premature CHD who did not present any other major risk factors of CHD (diabetes, obesity, dyslipidaemia or hypertension). Twenty-two healthy children from high-risk families, selected according to the National Cholesterol Education Program definition, were enrolled in the study. The control group comprised 18 children without a family history of CHD. All the children were healthy and had been screened for hyperlipidaemia, diabetes, hypertension and obesity prior to the study. The erythrocyte activity of CAT, GSH-Px, SOD and glutathione reductase was assessed. Children at high risk of CHD had a statistically significant lower level of GSH-Px and CAT activity than the children in the control group. There were no statistically significant differences in the activity of SOD and glutathione reductase.

  19. Clinical characteristics and in-hospital outcome of patients with acute coronary syndromes and systemic lupus erythematosus.

    PubMed

    de Matos Soeiro, Alexandre; de Almeida Soeiro, Maria Carolina Feres; de Oliveira, Mucio Tavares; Serrano, Carlos Viente

    2014-11-01

    Due to the chronic inflammation associated with systemic lupus erythematosus (SLE), patients develop premature atherosclerosis and the disease is a risk factor for acute myocardial infarction. The best interventional treatment for acute coronary syndrome (ACS) in these patients is unclear. The objective of this study is to describe the baseline characteristics, clinical manifestations, treatment and in-hospital outcome of patients with SLE and ACS. Eleven SLE patients with ACS were analyzed retrospectively between 2004 and 2011. The following data were obtained: age, gender, clinical and electrocardiographic characteristics, Killip class, risk factors for ACS, myocardial necrosis markers (CK-MB and troponin), creatinine clearance, left ventricular ejection fraction, inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), drugs used during hospital stay, treatment (medical, percutaneous or surgical) and in-hospital outcome. The statistical analysis is presented in percentages and absolute values. Ten of the patients (91%) were women. The median age was 47 years. Typical precordial pain was present in 91%. Around 73% had positive erythrocyte sedimentation rate. The vessel most often affected was the anterior descending artery, in 73%. One patient underwent coronary artery bypass grafting, seven underwent percutaneous coronary intervention with bare-metal stents and three were treated medically. In-hospital mortality was 18%. Despite the small number of patients, our findings were similar to those in the literature, showing coronary artery disease in young people with SLE due to premature atherosclerosis and a high mortality rate. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  20. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

    PubMed Central

    Bossaller, C; Habib, G B; Yamamoto, H; Williams, C; Wells, S; Henry, P D

    1987-01-01

    The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it. PMID:2432088

  1. [Pathophysiological role of tissue renin-angiotensin-aldosterone system (RAAS) in human atherosclerosis].

    PubMed

    Fukui, Kensuke; Yamada, Hiroyuki; Matsubara, Hiroaki

    2012-09-01

    Renin-angiotensin-aldosterone system (RAAS) has been demonstrated to play an important role in the pathogenesis of atherosclerosis development both in animal experiments and in clinical studies. Numerous clinical studies have shown that blockade of RAAS exerts beneficial effects to restore the impaired endothelial function and to reduce the mortality and morbidity of cardiovascular diseases beyond their blood pressure lowering effect. However, the underlying mechanisms of stabilizing vulnerable plaque and inhibiting plaque rupture associated with acute coronary syndrome have not yet been fully elucidated. Here, we summarized the characteristics of tissue RAAS expressions in human atherosclerotic lesions and assessed their therapeutic relevance in the prevention of atherosclerotic cardiovascular diseases.

  2. Association of vascular fluoride uptake with vascular calcification and coronary artery disease.

    PubMed

    Li, Yuxin; Berenji, Gholam R; Shaba, Wisam F; Tafti, Bashir; Yevdayev, Ella; Dadparvar, Simin

    2012-01-01

    The feasibility of a fluoride positron emission tomography/computed tomography (PET/CT) scan for imaging atherosclerosis has not been well documented. The purpose of this study was to assess fluoride uptake of vascular calcification in various major arteries, including coronary arteries. We retrospectively reviewed the imaging data and cardiovascular history of 61 patients who received whole-body sodium [¹⁸F]fluoride PET/CT studies at our institution from 2009 to 2010. Fluoride uptake and calcification in major arteries, including coronary arteries, were analyzed by both visual assessment and standardized uptake value measurement. Fluoride uptake in vascular walls was demonstrated in 361 sites of 54 (96%) patients, whereas calcification was observed in 317 sites of 49 (88%) patients. Significant correlation between fluoride uptake and calcification was observed in most of the arterial walls, except in those of the abdominal aorta. Fluoride uptake in coronary arteries was demonstrated in 28 (46%) patients and coronary calcifications were observed in 34 (56%) patients. There was significant correlation between history of cardiovascular events and presence of fluoride uptake in coronary arteries. The coronary fluoride uptake value in patients with cardiovascular events was significantly higher than in patients without cardiovascular events. sodium [¹⁸F]fluoride PET/CT might be useful in the evaluation of the atherosclerotic process in major arteries, including coronary arteries. An increased fluoride uptake in coronary arteries may be associated with an increased cardiovascular risk.

  3. Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Bidulescu, Aurelian; Chambless, Lloyd E; Siega-Riz, Anna Maria; Zeisel, Steven H; Heiss, Gerardo

    2007-01-01

    Background Low dietary intake of the essential nutrient choline and its metabolite betaine may increase atherogenesis both through effects on homocysteine methylation pathways as well as through choline's antioxidants properties. Nutrient values for many common foods for choline and betaine have recently become available in the U.S. nutrient composition database. Our objective was to assess the association of dietary intake of choline and betaine with incident coronary heart disease (CHD), adjusting for dietary intake measurement error. Methods We conducted a prospective investigation of the relation between usual intake of choline and betaine with the risk of CHD in 14,430 middle-aged men and women of the biethnic Atherosclerosis Risk in Communities study. A semi-quantitative food frequency questionnaire was used to assess nutrient intake. Proportional hazard regression models were used to calculate the risk of incident CHD. A regression calibration method was used to adjust for measurement error. Results During an average 14 years of follow-up (1987–2002), 1,072 incident CHD events were documented. Compared with the lowest quartile of intake, incident CHD risk was slightly and non-significantly higher in the highest quartile of choline and choline plus betaine, HR = 1.22 (0.91, 1.64) and HR = 1.14 (0.85, 1.53), controlling for age, sex, education, total energy intake, dietary intakes of folate, methionine and vitamin B6. No association was found between dietary choline intake and incident CHD when correcting for measurement error. Conclusion Higher intakes of choline and betaine were not protective for incident CHD. Similar investigations in other populations are of interest. PMID:17629908

  4. Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis.

    PubMed

    Brown, J Mark; Chung, Soonkyu; Sawyer, Janet K; Degirolamo, Chiara; Alger, Heather M; Nguyen, Tam M; Zhu, Xuewei; Duong, My-Ngan; Brown, Amanda L; Lord, Caleb; Shah, Ramesh; Davis, Matthew A; Kelley, Kathryn; Wilson, Martha D; Madenspacher, Jennifer; Fessler, Michael B; Parks, John S; Rudel, Lawrence L

    2010-01-01

    Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of energy metabolism and inflammation. We have previously reported that inhibition of SCD1 in hyperlipidemic mice fed a saturated fatty acid (SFA)-enriched diet prevented development of the metabolic syndrome, yet surprisingly promoted severe atherosclerosis. In this study we tested whether dietary fish oil supplementation could prevent the accelerated atherosclerosis caused by SCD1 inhibition. LDLr(-/-), ApoB(100/100) mice were fed diets enriched in saturated fat or fish oil in conjunction with antisense oligonucleotide (ASO) treatment to inhibit SCD1. As previously reported, in SFA-fed mice, SCD1 inhibition dramatically protected against development of the metabolic syndrome, yet promoted atherosclerosis. In contrast, in mice fed fish oil, SCD1 inhibition did not result in augmented macrophage inflammatory response or severe atherosclerosis. In fact, the combined therapy of dietary fish oil and SCD1 ASO treatment effectively prevented both the metabolic syndrome and atherosclerosis. SCD1 ASO treatment in conjunction with dietary fish oil supplementation is an effective combination therapy to comprehensively combat the metabolic syndrome and atherosclerosis in mice.

  5. Roles of Perivascular Adipose Tissue in the Pathogenesis of Atherosclerosis

    PubMed Central

    Tanaka, Kimie; Sata, Masataka

    2018-01-01

    Traditionally, it is believed that white adipose tissues serve as energy storage, heat insulation, and mechanical cushion, whereas non-shivering thermogenesis occurs in brown adipose tissue. Recent evidence revealed that adipose tissue secretes many types of cytokines, called as adipocytokines, which modulate glucose metabolism, lipid profile, appetite, fibrinolysis, blood pressure, and inflammation. Most of the arteries are surrounded by perivascular adipose tissue (PVAT). PVAT has been thought to be simply a structurally supportive tissue for vasculature. However, recent studies showed that PVAT influences vasodilation and vasocontraction, suggesting that PVAT regulates vascular tone and diameter. Adipocytokines secreted from PVAT appear to have direct access to the adjacent arterial wall by diffusion or via vasa vasorum. In fact, PVAT around atherosclerotic lesions and mechanically-injured arteries displayed inflammatory cytokine profiles, suggesting that PVAT functions to promote vascular lesion formation. Many clinical studies revealed that increased accumulation of epicardial adipose tissue (EAT), which surrounds coronary arteries, is associated with coronary artery disease. In this review article, we will summarize recent findings about potential roles of PVAT in the pathogenesis of atherosclerosis, particularly focusing on a series of basic and clinical studies from our laboratory. PMID:29487532

  6. The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine.

    PubMed

    Houghton, Jan L; Philbin, Edward F; Strogatz, David S; Torosoff, Mikhail T; Fein, Steven A; Kuhner, Patricia A; Smith, Vivienne E; Carr, Albert A

    2002-04-17

    The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary

  7. Work schedules and 11-year progression of carotid atherosclerosis in middle-aged Finnish men.

    PubMed

    Wang, Aolin; Arah, Onyebuchi A; Kauhanen, Jussi; Krause, Niklas

    2015-01-01

    This study investigated the relationship between different work schedules and progression of carotid atherosclerosis, an early indicator of cardiovascular disease (CVD). We studied 621 men, aged 42-60 years, in the prospective Kuopio Ischemic Heart Disease Risk Factor Study cohort. Using multivariable regressions adjusting for 22 covariates including total time worked during follow-up, we evaluated the associations of baseline work schedules with 11-year progression of ultrasonographically assessed carotid intima-media thickness (IMT), and their variation by preexisting CVD. Standard daytime work, weekend shifts, and evening/night/rotating shifts were associated with 31%, 37%, and 33% increases in IMT, respectively. Compared to daytime workers, weekend workers experienced a faster progression of carotid atherosclerosis [relative change ratio (RCR) = 1.05, 95% CI: 1.00-1.09)]. This ratio was higher among men who had preexisting CVD. Weekend shifts, more than standard daytime work, appear to accelerate carotid atherosclerosis progression among middle-aged Finnish men, especially those with pre-existing CVD. © 2014 Wiley Periodicals, Inc.

  8. Urinary Bisphenol A Concentration and Angiography-Defined Coronary Artery Stenosis

    PubMed Central

    Melzer, David; Gates, Phil; Osborn, Nicholas J.; Henley, William E.; Cipelli, Ricardo; Young, Anita; Money, Cathryn; McCormack, Paul; Schofield, Peter; Mosedale, David; Grainger, David; Galloway, Tamara S.

    2012-01-01

    Background Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses. Methodology/Principal Findings To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n = 86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD = 5.96 ng/ml OR = 1.43, CI 1.03 to 1.98, p = 0.033), and near significant for intermediate disease (OR = 1.69, CI 0.98 to 2.94, p = 0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined. Conclusions/Significance BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established. PMID:22916252

  9. Atherosclerosis in chronic kidney disease: the role of macrophages

    PubMed Central

    Kon, Valentina; Linton, MacRae F.; Fazio, Sergio

    2013-01-01

    Patients with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates atherosclerosis in animal models. Macrophages are central to atherogenesis because they regulate cholesterol traffic and inflammation in the arterial wall. CKD influences macrophage behavior at multiple levels, rendering them proatherogenic. Even at normal creatinine levels, macrophages from uninephrectomized Apoe−/− mice are enriched in cholesterol owing to downregulation of cholesterol transporter ATP-binding cassette subfamily A member 1 levels and activation of nuclear factor κB, which leads to impaired cholesterol efflux. Interestingly, treatment with an angiotensin-II-receptor blocker (ARB) improves these effects. Moreover, atherosclerotic aortas from Apoe−/− mice transplanted into renal-ablated normocholesterolemic recipients show plaque progression and increased macrophage content instead of the substantial regression seen in recipient mice with intact kidneys. ARBs reduce atherosclerosis development in mice with partial renal ablation. These results, combined with the clinical benefits of angiotensin-converting-enzyme (ACE) inhibitors and ARBs in patients with CKD, suggest an important role for the angiotensin system in the enhanced susceptibility to atherosclerosis seen across the spectrum of CKD. The role of macrophages could explain why these therapies may be effective in end-stage renal disease, one of the few conditions in which statins show no clinical benefit. PMID:21102540

  10. Ex-vivo Assessment of Coronary Artery Atherosclerosis by Magnetic Resonance Imaging: Correlation with Histopathology

    PubMed Central

    Gomes, Everli P. S. Gonçalves; Rochitte, Carlos Eduardo; Azevedo, Clerio F.; Lemos, Pedro A.; Gutierrez, Paulo Sampaio; César, Luiz Antonio M.

    2014-01-01

    Introduction: In recent years, high-resolution magnetic resonance imaging (MRI) has emerged as a very promising technique for studying atherosclerotic disease in humans. Aim: In the present study we sought to determine whether MRI allowed for the morphological characterization of the coronary vessel wall and atherosclerotic plaques using histopathological assessment as the reference standard. Methods: The study population consisted of 13 patients who died of acute myocardial infarction and underwent autopsy. The proximal portions of the coronary arteries were excised and were evaluated both by MRI and by histopathology. For each arterial segment, the following parameters were calculated through manual planimetry: 1. total vessel area (TVA); 2. luminal area (LA) and 3. plaque area (PA). Results: A total of 207 coronary artery cross-sections were found to be suitable for analysis by both MRI and histopathology and were included in the final analyses. Both methods demonstrated moderate to good agreement for the quantification of TVA (mean difference = 2.4±2.4 mm2, 95‰ limits of agreement from -2.4 to +7.2 mm2; CCC = 0.69, 95‰ CI from 0.63 to 0.75), LA (mean difference = 0.0±1.7 mm2, 95‰ limits of agreement from -3.3 to + 3.3 mm2; CCC = 0.84, 95‰ CI from 0.80 to 0.88) and PA (mean difference = 2.4±2.4 mm2, 95‰ limits of agreement from -2.3 to + 7.1 mm2; CCC = 0.64, 95‰ CI from 0.58 to 0.71). Conclusion: In this ex vivo experimental model we demonstrated good agreement between coronary artery morphometrical measurements obtained by high-resolution MRI and by histopathology. PMID:24847387

  11. Coronary Calcium Scores 6 Years After Bariatric Surgery

    PubMed Central

    Priester, Tiffany; Ault, Travis G.; Davidson, Lance; Gress, Richard; Adams, Ted D.; Hunt, Steven C.; Litwin, Sheldon E.

    2014-01-01

    Background Obesity is associated with elevated coronary artery calcium (CAC), a marker of coronary atherosclerosis that is strongly predictive of cardiovascular events. we evaluated the effects of marked weight loss achieved through roux-en-Y gastric bypass surgery (GBS) on CAC scores. Methods We performed echocardiography and computed tomography of the heart in 149 subjects 6 years after enrollment in a prospective registry evaluating the cardiovascular effects of GBS. coronary calcium scores, left ventricular ejection fraction and left ventricular mass were measured. Results At baseline most coronary risk factors were similar between the GBS and nonsurgical groups including current smoking, systolic blood pressure, LDL-C, HDL-C, and TG. However, GBS patients were younger (4.7 years), less likely to be diabetic and less likely to be postmenopausal. At 6 years after enrollment, CAC score was significantly lower in patients who underwent GBS than those without surgery (p<0.01). GBS subjects had a lower likelihood of having measureable coronary calcium (odds ratio of CAC > zero = 0.39; 95% CI of (0.17, 0.90)). Significant predictors of zero CAC were GBS, female gender, younger age, baseline BMI, and baseline LDL-C. Substituting change in BMI for group status as a predictor variable showed that BMI change also predicted CAC (p=0.045). Changes in LDL-C did not predict the CAC differences between groups (p=0.67). Conclusions Sustained weight loss achieved through bariatric surgery is associated with less coronary calcification. This effect, which appears to be independent of changes in LDL-C, may contribute to lower cardiac mortality in patients with successful GBS. PMID:24927692

  12. Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients

    PubMed Central

    Heidari, Mohammad Mehdi; Khatami, Mehri; Hadadzadeh, Mehdi; Kazemi, Mahbobeh; Mahamed, Sahar; Malekzadeh, Pegah; Mirjalili, Massomeh

    2015-01-01

    Background: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. Objectives: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. Patients and Methods: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. Conclusions: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population. PMID:26878010

  13. Relationship between Calcium Score and Myocardial Scintigraphy in the Diagnosis of Coronary Disease

    PubMed Central

    Siqueira, Fabio Paiva Rossini; Mesquita, Claudio Tinoco; dos Santos, Alair Augusto Sarmet M. Damas; Nacif, Marcelo Souto

    2016-01-01

    Half the patients with coronary artery disease present with sudden death - or acute infarction as first symptom, making early diagnosis pivotal. Myocardial perfusion scintigraphy is frequently used in the assessment of these patients, but it does not detect the disease without flow restriction, exposes the patient to high levels of radiation and is costly. On the other hand, with less radiological exposure, calcium score is directly correlated to the presence and extension of coronary atherosclerosis, and also to the risk of cardiovascular events. Even though calcium score is a tried-and-true method for stratification of asymptomatic patients, its use is still reduced in this context, since current guidelines are contradictory to its use on symptomatic diseases. The aim of this review is to identify, on patients under investigation for coronary artery disease, the main evidence of the use of calcium score associated with functional evaluation and scintigraphy. PMID:27437867

  14. [Immediate and Long-term Results of the First in Russia of IntrocoronaryMetal Stent in the Coronary Artery].

    PubMed

    Babunashvili, A M; Navtsishvili, Z G; Konstantinov, B A

    2016-02-01

    The authors present immediate and long term results of the first in Russia implantation in coronary artery of Palmaz-Shatz metal stent. Indications for stenting were urgent after complicated dissection as a result of balloon dilation of discrete bifurcational stenosis of anterior interventricular artery (IVA). Immediate angiographic and clinical result was good. At control angiography after 13 years their was no restenosis in stented IVA. However novel narrowing was found in left main coronary artery (LMCA) in which drug eluting stent was implanted. Coronary angiography carried out after 7.5 years after stenting of LMCA and in 20 years after stent implantation in IVA revealed good patency of both stented segments without signs of restenosis. This case report demonstrates possibility of long term preservation of angiographic and clinical effect of staged endovascular treatment of coronary atherosclerosis.

  15. Serum IgE levels are associated with coronary artery disease severity.

    PubMed

    Guo, Xiaoxiao; Yuan, Su; Liu, Yongtai; Zeng, Yong; Xie, Hongzhi; Liu, Zhenyu; Zhang, Shuyang; Fang, Quan; Wang, Jing; Shen, Zhujun

    2016-08-01

    Immunoglobulin E (IgE), a key element of allergic reactions, was considered to be involved in the development of atherosclerosis and the pathogenesis of myocardial ischemia. This study was designed to test whether total serum IgE levels were associated with the atherosclerosis severity of coronary artery disease (CAD). Total serum IgE concentrations were measured in 708 consecutive patients who were presented to our center for coronary angiography. Atherosclerosis severity of CAD was assessed by the number of diseased vessels showing ≥50% diameter stenosis and quantified by Gensini score. Patients with CAD (N = 562) had higher serum IgE levels than those without CAD (N = 146) [55.90 (19.10-156.00) vs. 26.90 (11.80-62.10) KU/L, p = 0.003]. Furthermore, the serum IgE levels were significantly increased in patients with multivessel disease (MVD) compared to those with single-vessel disease [61.80 (23.20-159.00) vs. 32.45(14.15-94.38) KU/L, p = 0.003]. After adjustment for traditional cardiovascular risk factors, a high serum IgE level was an independent predictor for an increased risk of MVD (OR 1.003; 95% CI 1.001-1.004; p = 0.041). Receiver-operating characteristic curve analysis demonstrated that serum IgE levels improved the predictive capability of traditional risk factors for MVD (area under the curve with and without IgE: 0.734 and 0.713, respectively, p < 0.001). Meanwhile, there was a significant linear relationship between Gensini score and the serum IgE level quartiles (p for linear trend <0.001). Increased total serum IgE levels are associated with MVD and contribute to discriminating CAD severity independently of traditional cardiovascular risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. A novel ultrasound-based vascular calcification score (CALCS) to detect subclinical atherosclerosis.

    PubMed

    Flore, R; Zocco, M A; Ainora, M E; Fonnesu, C; Nesci, A; Gasbarrini, A; Ponziani, F R

    2018-02-01

    To quantify non-coronary vascular calcifications (VC) in asymptomatic patients at low-intermediate cardiovascular risk by a new color Doppler ultrasound (DUS)-based score (the carotid, aortic, lower limbs calcium score, CALCs), and to correlate this score with classical parameters associated with cardiovascular risk [carotid intima media thickness (IMT), and arterial stiffness (AS)]. All consecutive asymptomatic patients who underwent a screening DUS of non-coronary circulation were evaluated and patients at low-intermediate cardiovascular risk were selected according to Framingham risk score (FRS). Among them, we enrolled 70 patients with US evidence of VC and 71 age, sex and FRS matched controls. The presence of VC was correlated with classical markers of cardiovascular risk, such as AS and intima-media thickness (IMT). AS, expressed as pulse wave velocity (PWV) and arterial distensibility, carotid IMT and CALCs were measured for both groups. AS and c-IMT were assessed by a new Radio-Frequency (RF) DUS-based method. CALCs was generated by our previously described B-mode DUS-based method according to number/size of VC in 11 non-coronary segments (range 0-33). Patients with VC presented higher AS and IMT values than controls (PWV 8.34±0.98 m/s vs. 6.74±0.68 m/s, p<0.0001; arterial distensibility 267±12 mm vs. 315±65 mm, p=0.001; IMT 687±132 mm vs. 572±91 mm, p<0.0001). Mean CALCs of patients with VC was 8.41±7.78. CALCs were significantly correlated with c-IMT (p<0.0001; r=0.3), PWV (p<0.0001; r=0.4) and arterial distensibility (p=0.002; r=-0.1). DUS-based CALCs is highly correlated with other validated markers of subclinical atherosclerosis, such as c-IMT and AS. Our results demonstrated the ability of CALCs to identify individual predictive factors beyond the traditional risk factors by quantifying an interesting and novel step of the atherogenic process. Future studies on larger series and with adequate follow up are necessary to confirm these results and

  17. Coronary artery endothelial dysfunction is present in HIV positive individuals without significant coronary artery disease

    PubMed Central

    IANTORNO, Micaela; SCHÄR, Michael; SOLEIMANIFARD, Sahar; BROWN, Todd T.; MOORE, Richard; BARDITCH-CROVO, Patricia; STUBER, Matthias; LAI, Shenghan; GERSTENBLITH, Gary; WEISS, Robert G.; HAYS, Allison G.

    2017-01-01

    Objective HIV+ individuals experience an increased burden of coronary artery disease (CAD) not adequately accounted for by traditional CAD risk factors. Coronary endothelial function (CEF), a barometer of vascular health, is depressed early in atherosclerosis and predicts future events but has not been studied in HIV+ individuals. We tested whether CEF is impaired in HIV+ subjects without CAD as compared to an HIV- population matched for cardiac risk factors. Design/Methods In this observational study, CEF was measured noninvasively by quantifying isometric handgrip exercise (IHE)-induced changes in coronary vasoreactivity with MRI in 18 participants with HIV but no CAD (HIV+CAD-, based on prior imaging), 36 age- and cardiac risk factor-matched healthy participants with neither HIV nor CAD (HIV-CAD-), 41 subjects with no HIV but with known CAD (HIV-CAD+) and 17 subjects with both HIV and CAD (HIV+CAD+). Results CEF was significantly depressed in HIV+CAD- subjects as compared to that of risk-factor-matched HIV-CAD- subjects (p<0.0001), and was depressed to the level of that in HIV- participants with established CAD. Mean IL-6 levels were higher in HIV+ participants (p<0.0001), and inversely related to CEF in the HIV+ subjects (p=0.007). Conclusions Marked coronary endothelial dysfunction is present in HIV+ subjects without significant CAD and is as severe as that in clinical CAD patients. Furthermore, endothelial dysfunction appears inversely related to the degree of inflammation in HIV+ subjects, as measured by IL-6. CEF testing in HIV+ patients may be useful for assessing cardiovascular risk and testing new CAD treatment strategies, including those targeting inflammation. PMID:28353539

  18. Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine.

    PubMed

    Fields, Jeremy Z; Walton, Kenneth G; Schneider, Robert H; Nidich, Sanford; Pomerantz, Rhoda; Suchdev, Parmi; Castillo-Richmond, Amparo; Payne, Kathleen; Clark, Elizabeth T; Rainforth, Maxwell

    2002-04-15

    Although the onset and progression of coronary heart disease (CHD) involve multiple risk factors, few intervention studies have attempted to modify these factors simultaneously. This pilot study tested the effect of a multimodality intervention involving dietary, exercise, herbal food supplement, and stress reduction approaches from a traditional system of natural medicine, Maharishi Vedic Medicine (MVM). The primary outcome measure was carotid intima-media thickness (IMT), a noninvasive measure of peripheral atherosclerosis and surrogate measure of coronary atherosclerosis. Comparison groups included modern medicine (conventional dietary, exercise, and multivitamin approaches) and usual care (no added intervention). Of 57 healthy seniors (mean age 74 years) randomized to the 3 treatment groups, 46 completed IMT post-testing. Carotid IMT was determined by B-mode ultrasound before and after 1 year of treatment. IMT decreased in a larger fraction of MVM subjects (16 of 20) than in the modern (5 of 9) and usual care (7 of 14) groups combined (i.e., 12 of 23; odds ratio 3.7, p = 0.05). For subjects with multiple CHD risk factors ("high-risk" subjects, n = 15), IMT decreased more in the MVM (-0.32 +/- 0.23 mm, mean +/- SD) than in the usual care (+0.022 +/- 0.085; p = 0.009) or modern (-0.082 +/- 0.095, p = 0.10) groups. Within-group reductions in IMT were significant for all MVM subjects (-0.15 +/- 0.21, n = 20, p = 0.004) and for high-risk MVM subjects (n = 6, p = 0.01). These results show that this multimodality traditional approach can attenuate atherosclerosis in older subjects, particularly those with marked CHD risk.

  19. Recent Advances in Fluorescent Angioscopy for Molecular Imaging of Human Atherosclerotic Coronary Plaque

    PubMed Central

    2017-01-01

    Purpose of Review: In vivo imaging of the native substances, including lipoproteins, that comprise human atherosclerotic plaques is currently beyond the scope of any available imaging techniques. Color and near-infrared fluorescent angioscopy (CFA and NIRFA, respectively) systems have been recently developed for molecular imaging of lipoproteins within the human coronary arterial wall ex vivo and/or in vivo. The author reviews recent findings on lipoprotein deposition in human coronary plaques obtained by these imaging techniques. Recent Findings: Using specific biomarkers, native pro-atherogenic substances such as oxidized low-density lipoprotein (ox-LDL), LDL, triglycerides (TG), apolipoprotein B-100 (ApoB-100), and lysophosphatidylcholine (LPC), and the anti-atherogenic substance such as high-density lipoprotein (HDL) were visualized by CFA, and LDL and cholesterol by NIRFA, in coronary plaques obtained from autopsy subjects. The relationship between incidence and plaque morphology differed for each substance. The incidence of ox-LDL and LDL on color fluorescence microscopy correlated well with that observed using immunohistochemical techniques. During coronary catheterization in patients, ox-LDL, LDL, and HDL in coronary plaques were visualized by CFA or NIRFA. Conclusions: Using CFA or NIRFA, the distribution of the major native pro-atherogenic and antiatherogenic lipoproteins and their components within human coronary plaques can be evaluated ex vivo and/or in vivo. Fluorescent angioscopy could help our understanding of the molecular mechanisms of coronary atherosclerosis and in the evaluation of the effects of therapy targeting the substances comprising atherosclerotic coronary plaques. PMID:28381766

  20. Lack of association of oral calcium supplementation with coronary artery calcification in rheumatoid arthritis.

    PubMed

    Geraldino-Pardilla, Laura; Dhaduvai, Shanthi; Giles, Jon T; Bathon, Joan M

    2015-06-01

    To investigate the association between oral calcium supplementation and coronary artery calcification among rheumatoid arthritis (RA) patients without known cardiovascular disease (CVD). This study was conducted as a nested, prospective cohort study of RA patients without known CVD. The daily supplemental calcium dose was ascertained from each patients' list of prescription and over-the-counter medications at baseline and at visit 2 (median 20 months postbaseline). The coronary artery calcium (CAC) score, a measure of coronary atherosclerosis, was assessed by cardiac multidetector row computed tomography at baseline and at visit 3 (median 39 months postbaseline). The association between calcium supplementation and CAC was explored. Among the 145 RA patients studied, 42 (28%) were taking ≥1,000 mg/day of supplemental calcium at baseline. A CAC score of >100 units was seen in 44 patients (30%) at baseline and 50 patients (34%) at followup. Baseline CAC scores of >100 units were significantly less frequent in patients receiving the higher dosage (≥1,000 mg/day) of supplemental calcium than in those receiving the lower dosage (<1,000 mg/day) (odds ratio [OR] 0.28, 95% confidence interval [95% CI] 0.11-0.74); this association remained significant after adjustment for relevant confounders (adjusted OR 0.30, 95% CI 0.09-0.93). Similarly, at the third study visit, CAC scores of >100 units were less frequent in the higher supplemental calcium dose group compared to the lower dose group (OR 0.41, 95% CI 0.18-0.95); however, after adjustment for relevant confounders, the statistical significance of this association was lost (adjusted OR 0.39, 95% CI 0.14-1.12). No effect of sex heterogeneity was seen in the association of calcium supplementation with coronary artery calcification, and no change in the CAC score over time was observed. Higher levels of oral calcium supplementation were not associated with an increased risk of coronary atherosclerosis, as measured by the

  1. Lack of Association of Oral Calcium Supplementation with Coronary Artery Calcification in Rheumatoid Arthritis

    PubMed Central

    Giles, Jon T.; Bathon, Joan M.

    2015-01-01

    Objectives To investigate the association between oral calcium supplementation and coronary arterial calcification among rheumatoid arthritis (RA) patients without known cardiovascular disease (CVD). Methods This study was nested in a prospective cohort study of RA patients without known CVD. Daily supplemental calcium dose was ascertained from prescription and over-the-counter medications at baseline and visit 2 (median 20 months post-baseline). Coronary artery calcium (CAC), a measure of coronary atherosclerosis, was assessed by cardiac multi-detector row computed tomography at baseline and visit 3 (median 39 months post-baseline). The association of calcium supplementation with CAC was explored. Results Among the 145 RA patients studied, 42 (28%) took ≥1000mg/day of supplemental calcium at baseline. Forty-four (30%) and 50 (34%) had a CAC score >100 units at baseline and follow-up, respectively. Baseline CAC scores >100 units were significantly less frequent in the higher (≥1000mg/day) supplemental calcium group than in the lower dosed group (<1000mg/day) [OR 0.28 (95% CI 0.11-0.74)]; this remained significant after adjusting for relevant confounders [OR 0.30 (95% CI 0.09-0.93)]. Similarly, at the third study visit, CAC scores >100 units were less frequent in the higher vs. the lower supplemental calcium group [OR 0.41 (95% CI 0.18-0.95)]. When adjusted for relevant confounders, statistical significance was lost [OR 0.39 (95% CI 0.14-1.12)]. No gender interaction and no change in CAC score over time were appreciated. Conclusion Higher levels of oral calcium supplementation were not associated with an increased risk of coronary atherosclerosis as measured by CAC score in this RA cohort. PMID:25808397

  2. Reflection magnitude as a predictor of mortality: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Zamani, Payman; Jacobs, David R; Segers, Patrick; Duprez, Daniel A; Brumback, Lyndia; Kronmal, Richard A; Lilly, Scott M; Townsend, Raymond R; Budoff, Matthew; Lima, Joao A; Hannan, Peter; Chirinos, Julio A

    2014-11-01

    Arterial wave reflections have been associated with mortality in an ethnically homogenous Asian population. It is unknown whether this association is present in a multiethnic population or whether it is independent of subclinical atherosclerosis. We hypothesized that reflection magnitude (defined as the ratio of the amplitude of the backward wave [Pb] to that of the forward wave [Pf]) is associated with all-cause mortality in a large multiethnic adult community-based sample. We studied 5984 participants enrolled in the Multi-Ethnic Study of Atherosclerosis who had analyzable arterial tonometry waveforms. During 9.8±1.7 years of follow-up, 617 deaths occurred, of which 134 (22%) were adjudicated cardiovascular deaths. In Cox proportional hazards models, each 10% increase in reflection magnitude was associated with a 31% increased risk for all-cause mortality (hazard ratio [HR]=1.31; 95% confidence interval [CI]=1.11-1.55; P=0.001). This relationship persisted after adjustment for various confounders and for markers of subclinical atherosclerosis (HR=1.23; 95% CI=1.01-1.51; P=0.04), including the coronary calcium score, ankle-brachial index, common carotid intima-media thickness, and ascending thoracic aortic Agatston score. Pb was independently associated with all-cause mortality in a similarly adjusted model (HR per 10 mm Hg increase in P(b)=2.18; 95% CI=1.21-3.92; P=0.009). Reflection magnitude (HR=1.71; 95% CI=1.06-2.77; P=0.03) and P(b) (HR=5.02; 95% CI=1.29-19.42; P=0.02) were mainly associated with cardiovascular mortality. In conclusion, reflection magnitude is independently associated with all-cause mortality in a multiethnic population initially free of clinically evident cardiovascular disease. This relationship persists after adjustment for a comprehensive set of markers of subclinical atherosclerosis. © 2014 American Heart Association, Inc.

  3. Aortic root, not valve, calcification correlates with coronary artery calcification in patients with severe aortic stenosis: A two-center study.

    PubMed

    Henein, Michael; Hällgren, Peter; Holmgren, Anders; Sörensen, Karen; Ibrahimi, Pranvera; Kofoed, Klaus Fuglsang; Larsen, Linnea Hornbech; Hassager, Christian

    2015-12-01

    The underlying pathology in aortic stenosis (AS) and coronary artery stenosis (CAS) is similar including atherosclerosis and calcification. We hypothesize that coronary artery calcification (CAC) is likely to correlate with aortic root calcification (ARC) rather than with aortic valve calcification (AVC), due to tissue similarity between the two types of vessel rather than with the valve leaflet tissue. We studied 212 consecutive patients (age 72.5 ± 7.9 years, 91 females) with AS requiring aortic valve replacement (AVR) in two Heart Centers, who underwent multidetector cardiac CT preoperatively. CAC, AVC and ARC were quantified using Agatston scoring. Correlations were tested by Spearman's test and Mann-Whitney U-test was used for comparing different subgroups; bicuspid (BAV) vs tricuspid (TAV) aortic valve. CAC was present in 92%, AVC in 100% and ARC in 82% of patients. CAC correlated with ARC (rho = 0.51, p < 0.001) but not with AVC. The number of calcified coronary arteries correlated with ARC (rho = 0.45, p < 0.001) but not with AVC. 29/152 patients had echocardiographic evidence of BAV and 123 TAV, who were older (p < 0.001) but CAC was associated with TAV even after adjusting for age (p = 0.01). AVC score was associated with BAV after adjusting for age (p = 0.03) but ARC was not. Of the total cohort, 82 patients (39%) had significant coronary stenosis (>50%), but these were not different in the pattern of calcification from those without CAS. CAC was consistently higher in patients with risk factors for atherosclerosis compared to those without. The observed relationship between coronary and aortic root calcification suggests a diffuse arterial disease. The lack of relationship between coronary and aortic valve calcification suggests a different pathology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis in systemic lupus erythematosus.

    PubMed

    Kiani, Adnan N; Fang, Hong; Akhter, Ehtisham; Quiroga, Carmen; Simpson, Nancy; Alaupovic, Petar; Magder, Laurence S; Petri, Michelle

    2015-03-01

    Traditional classification of hyperlipidemia using high-density lipoprotein, low-density lipoprotein (LDL), and very low-density lipoprotein does not provide information on lipoprotein function. Apolipoproteins (Apos), which are protein components of plasma lipoproteins (including A, B, C, D, E) with their different composition, metabolic, and atherogenic properties, provide insight on lipoprotein functioning. In particular, the Apo B/A-I ratio is associated with atherogenic LDL and development of cardiovascular disease. We explored the baseline association between these nontraditional risk factors with subclinical measures of atherosclerosis (coronary artery calcification [CAC] and carotid intima-media thickness [IMT]) in systemic lupus erythematosus (SLE). A total of 58 SLE patients (97% women, 58% white, 40% African American, and 2% other, mean ± SD age 44 ± 11 years) had measurement of Apo and lipoproteins by immunoturbidimetric procedures, electroimmunoassays, and immunoprecipitation. CAC was measured by helical computed tomography and carotid IMT by carotid duplex. This study was based on the baseline assessment of subclinical atherosclerosis in the Lupus Atherosclerosis Prevention Study. The measurement of the lipoproteins was made on sera collected at the same time. There was no association between cardioprotective Apos (Apo A-I, LpA-I, LpA-I:A-II) and CAC (P < 0.15, P < 0.41, and P < 0.39, respectively) or carotid IMT (P < 0.97, P < 0.53, and P < 0.76, respectively). CAC and carotid IMT did not associate with atherogenic Apos either, including LpB:E+LpB:C:E, Apo B, LpB, LpB:C, Apo C-III, Apo C-III-HS, Apo C-III-HP, Apo C-III-R, LpA-II:B:C:D:E, and Apo B/Apo A-I. Measures of disease activity, including physician's global assessment and Systemic Lupus Erythematosus Disease Activity Index, were not associated with CAC or carotid IMT. Neither cardioprotective nor atherogenic lipoproteins were associated with measures of subclinical atherosclerosis in this

  5. Long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis: a prospective cohort study

    PubMed Central

    Gan, Wen Qi; Allen, Ryan W; Brauer, Michael; Davies, Hugh W; Mancini, G B John; Lear, Scott A

    2014-01-01

    Objectives Epidemiological studies have demonstrated associations between long-term exposure to traffic-related air pollution and coronary heart disease (CHD). Atherosclerosis is the principal pathological process responsible for CHD events, but effects of traffic-related air pollution on progression of atherosclerosis are not clear. This study aimed to investigate associations between long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis. Setting Healthy volunteers in metropolitan Vancouver, Canada. Participants and outcome measures 509 participants aged 30–65 years were recruited and followed for approximately 5 years. At baseline and end of follow-up, participants underwent carotid artery ultrasound examinations to assess atherosclerosis severity, including carotid intima-media thickness, plaque area, plaque number and total area. Annual change of each atherosclerosis marker during the follow-up period was calculated as the difference between these two measurements divided by years of follow-up. Living close to major roads was defined as ≤150 m from a highway or ≤50 m from a major road. Residential exposures to traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide were estimated using high-resolution land-use regression models. The data were analysed using general linear models adjusting for various covariates. Results At baseline, there were no significant differences in any atherosclerosis markers between participants living close to and those living away from major roads. After follow-up, the differences in annual changes of these markers between these two groups were small and not statistically significant. Also, no significant associations were observed with concentrations of traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide. Conclusions This study did not find significant associations

  6. Impact of intensive lipid lowering on lipid profiles over time and tolerability in stable coronary artery disease: insights from a subanalysis of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS).

    PubMed

    Kawashiri, Masa-Aki; Yamagishi, Masakazu; Sakamoto, Tomohiro; Takayama, Tadateru; Hiro, Takafumi; Daida, Hiroyuki; Hirayama, Atsushi; Saito, Satoshi; Yamaguchi, Tetsu; Matsuzaki, Masunori

    2013-12-01

    Previous studies have demonstrated that intensive lipid lowering using rosuvastatin results in regression of coronary plaques. However, few data exist regarding lipid profiles over time, drug tolerability, and the effects of prior use of lipid lowering agents in patients on rosuvastatin treatment. Therefore, we studied these matters in a subanalysis of the Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS). Rosuvastatin was titrated for 76 weeks to attain LDL-C < 80 mg/dL in 213 Japanese dyslipidemic patients with CAD. Clinic visits were scheduled for every 4 weeks during the 76-week study period. Changes over time in lipid parameters, changes in those according to prior lipid-lowering therapy, and changes in those according to baseline lipid levels were evaluated in this subanalysis. Overall, 126 patients completed the study. The mean rosuvastatin dose at the last observation carried forward was 16.9 mg (range, 2.5-20 mg). Rosuvastatin significantly increased HDL-C, lowered LDL-C, and improved the LDL-C/HDL-C ratio (all, P < 0.0001). Increases in serum HDL-C levels were significantly greater in patients with HDL-C < 40 mg/dL than in those with HDL-C ≥ 40 mg/dL at baseline (P = 0.0005). The estimated glomerular filtration rate increased significantly by 2.84 ± 9.01 mL/min/1.73 m(2) (P < 0.0001). Of 166 adverse events in 74 patients, 113 events in 54 patients were laboratory values beyond the normal range. Rosuvastatin significantly improved lipid profiles, with an acceptable safety profile, contributing to plaque regression in Japanese patients with CAD. © 2013 John Wiley & Sons Ltd.

  7. Scavenger Receptor Class B Type 1 Deletion Led to Coronary Atherosclerosis and Ischemic Heart Disease in Low-density Lipoprotein Receptor Knockout Mice on Modified Western-type Diet

    PubMed Central

    Liao, Jiawei; Guo, Xin; Wang, Mengyu; Dong, Chengyan; Gao, Mingming; Wang, Huan; Kayoumu, Abudurexiti; Shen, Qiang; Wang, Yuhui; Wang, Fan; Liu, George

    2017-01-01

    Aim: Atherosclerosis-prone apolipoprotein E (apoE) or low-density lipoprotein receptor (LDL-R) knockout (KO) mice are generally resistant to developing coronary atherosclerosis (CA) and ischemic heart disease (IHD). However, studies have demonstrated the occurrence of spontaneous CA and IHD in scavenger receptor class B type 1 (SR-BI)/apoE double KO (dKO) mice, which suggests that SR-BI could be a potential target for the prevention and therapy of CA and IHD. This possibility was later investigated in SR-BI/LDL-R dKO mice, but no signs of CA or IHD was identified when mice were fed a normal western-type diet. Here we explored whether SR-BI deletion could result in CA and IHD in LDL-R KO mice when fed a modified western-type diet containing higher (0.5%) cholesterol. Methods: Cardiac functions were detected by electrocardiography, single photon emission computed tomography (SPECT), echocardiography (Echo) and 2,3,5-triphenyltetrazolium chloride staining. CA was visualized by hematoxylin-eosin staining. Results: After 12 weeks on the modified diet, SR-BI/LDL-R dKO mice developed cardiac ischemia/infarction, together with systolic dysfunction and left ventricular dilatation. CA was most severe at the aortic sinus level to an extent that no dKO mice survived to 20 weeks on the modified diet. None of control mice, however, developed CA or IHD. Conclusions: SR-BI deletion led to CA and IHD in LDL-R KO mice when fed the modified western-type diet. We established SR-BI/LDL-R dKO mice as a diet-induced murine model of human IHD and developed detection methods, using a combination of SPECT and Echo, for effective in vivo evaluation of cardiac functions. PMID:27373983

  8. Coronary hemodynamic regulation by nitric oxide in experimental animals: recent advances.

    PubMed

    Toda, Noboru; Toda, Hiroshi

    2011-09-30

    Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance and in the inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. NO restrains myocardial oxygen consumption, when coronary perfusion is restricted. Endothelial function is impaired by pathogenic factors including smoking, excess salt intake, obesity, aging, hypercholesterolemia, hyperglycemia, and hypertension. The mechanisms involved in endothelial dysfunction are reduced NOS expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. NADPH oxidase, xanthine oxidase, and NOS uncoupling are involved in increased superoxide generation. Plasma levels of asymmetric dimethylarginine, the endogenous NOS inhibitor, are increased by an impairment of enzymatic degradation by dimethylarginine dimethylaminohydrolase and alanine-glyoxylate aminotransferase 2. Impairment of coronary arteriolar dilatation induced by perivascular nitrergic nerve activation is involved in decreased coronary blood flow. NO derived from nNOS singly or in combination with eNOS protects against serious myocardial injury through ischemic insults. Ischemia-induced iNOS upregulation contributes to myocardial contractile dysfunction. Preventive and therapeutic measures, such as improvement of life-style and treatment with therapeutic agents, to eliminate pathogenic factors for endothelial dysfunction or nNOS-derived NO deprivation would be quite important for the prophylaxis and minimizing the development of coronary artery disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. The relationship between self-reported history of endodontic therapy and coronary heart disease in the Atherosclerosis Risk in Communities Study

    PubMed Central

    Caplan, Daniel J.; Pankow, James S.; Cai, Jianwen; Offenbacher, Steven; Beck, James D.

    2009-01-01

    Background Results from numerous studies have suggested links between periodontal disease and coronary heart disease (CHD), but endodontic disease has not been studied extensively in this regard. Methods The authors evaluated the relationship between self-reported history of endodontic therapy (ET) and prevalent CHD in the Atherosclerosis Risk in Communities (ARIC) Study, aprospective epidemiologic study sponsored by the National Heart, Lung, and Blood Institute. The authors used multivariable logistic regres-sionto analyze data obtained from oral health questionnaires, medical evaluations and clinical dental examinations. Results Of 6,651 participants analyzed, 50.4 percent reported never having had ET; 21.5 percent reported having had ET one time; and 28.0 percent reported having had ET two or more times. Final multivariable regression models indicated that among participants with 25 or more teeth, those reporting having had ET two or more times had 1.62 (95 percent confidence interval [CI], 1.04–2.53) times the odds of prevalent CHD compared with those reporting never having had ET. Among participants with 24 or fewer teeth, no significant differences in CHD prevalence were observed among groups regardless of their history of ET. Conclusions Among participants with 25 or more teeth, those with a greater self-reported history of ET were more likely to have CHD than were those reporting no history of ET. Clinical Implications More accurate epidemiologic quantification of endodontic infection and inflammation is required before definitive conclusions can be made about potential relationships between endodontic disease and CHD. PMID:19654253

  10. [Coronary artery disease and cardiac ischemic disease: two different pathologies with different diagnostic procedures].

    PubMed

    Vallejo, Enrique

    2009-01-01

    Coronary artery disease (CAD) remains the leading cause of death in the Western world, and early detection of CAD allows optimal therapeutic management. The gold standard has always been invasive coronary angiography, but over the years various non-invasive techniques have been developed to detect CAD, including cardiac SPECT and cardiac computed tomography (Cardiac CT). Cardiac SPECT permitted visualization of myocardial perfusion and have focused on the assessment of the hemodynamic consequences of obstructive coronary lesions as a marker of CAD. Cardiac CT focuses on the detection of atherosclerosis rather than ischemia, and permit detection of CAD at an earlier stage. Objectives of this manuscript are to discuss the clinical experience with both modalities and to provide a critical review of the strengths and limitations of Cardiac SPECT and Cardiac CT for the diagnostic and management of patients with suspected CAD or cardiac ischemic disease.

  11. Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women

    PubMed Central

    Sara, Jaskanwal D; Zhang, Ming; Gharib, Hossein; Lerman, Lilach O; Lerman, Amir

    2015-01-01

    Background Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and Results In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3

  12. Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women.

    PubMed

    Sara, Jaskanwal D; Zhang, Ming; Gharib, Hossein; Lerman, Lilach O; Lerman, Amir

    2015-07-29

    Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3

  13. Interaction between allergic asthma and atherosclerosis

    PubMed Central

    Liu, Conglin; Zhang, Jingying; Shi, Guo-Ping

    2015-01-01

    Prior studies have established an essential role of mast cells in allergic asthma and atherosclerosis. Mast cell deficiency or inactivation protects mice from allergen-induced airway hyper-responsiveness and diet-induced atherosclerosis, suggesting that mast cells share pathologic activities in both diseases. Allergic asthma and atherosclerosis are inflammatory diseases that contain similar sets of elevated numbers of inflammatory cells in addition to mast cells in the airway and arterial wall, such as macrophages, monocytes, T cells, eosinophils, and smooth muscle cells. Emerging evidence from experimental models and human studies points to a potential interaction between the two seemingly unrelated diseases. Patients or mice with allergic asthma have a high risk of developing atherosclerosis or vice versa, despite the fact that asthma is a Th2-oriented disease, whereas Th1 immunity promotes atherosclerosis. In addition to the preferred Th1/Th2 responses that may differentiate the two diseases, mast cells and many other inflammatory cells also contribute to their pathogenesis by much more than just T cell immunity. Here we summarize the different roles of airway and arterial wall inflammatory cells and vascular cells in asthma and atherosclerosis, and propose an interaction between the two diseases, although limited investigations are available to delineate the molecular and cellular mechanisms by which one disease increases the risk of the other. Results from mouse allergic asthma and atherosclerosis models and from human population studies lead to the hypothesis that patients with atherosclerosis may benefit from anti-asthmatic medications, or that the therapeutic regimens targeting atherosclerosis may also alleviate allergic asthma. PMID:26608212

  14. Effect of Long-Term Metformin and Lifestyle in the Diabetes Prevention Program and Its Outcome Study on Coronary Artery Calcium.

    PubMed

    Goldberg, Ronald B; Aroda, Vanita R; Bluemke, David A; Barrett-Connor, Elizabeth; Budoff, Matthew; Crandall, Jill P; Dabelea, Dana; Horton, Edward S; Mather, Kieren J; Orchard, Trevor J; Schade, David; Watson, Karol; Temprosa, Marinella

    2017-07-04

    Despite the reduced incidence of coronary heart disease with intensive risk factor management, people with diabetes mellitus and prediabetes remain at increased coronary heart disease risk. Diabetes prevention interventions may be needed to reduce coronary heart disease risk. This approach was examined in the DPP (Diabetes Prevention Program) and the DPPOS (Diabetes Prevention Program Outcome Study), a long-term intervention study in 3234 subjects with prediabetes (mean±SD age, 64±10 years) that showed reduced diabetes risk with lifestyle and metformin compared with placebo over 3.2 years. The DPPOS offered periodic group lifestyle sessions to all participants and continued metformin in the originally randomized metformin group. Subclinical atherosclerosis was assessed in 2029 participants with coronary artery calcium (CAC) measurements after an average of 14 years of follow-up. The CAC scores were analyzed continuously as CAC severity and categorically as CAC presence (CAC score >0) and reported separately in men and women. There were no CAC differences between lifestyle and placebo intervention groups in either sex. CAC severity and presence were significantly lower among men in the metformin versus the placebo group (age-adjusted mean CAC severity, 39.5 versus 66.9 Agatston units, P =0.04; CAC presence, 75% versus 84%, P =0.02), but no metformin effect was seen in women. In multivariate analysis, the metformin effect in men was not influenced by demographic, anthropometric, or metabolic factors; by the development of diabetes mellitus; or by use/nonuse of statin therapy. Metformin may protect against coronary atherosclerosis in prediabetes and early diabetes mellitus among men. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00038727. © 2017 American Heart Association, Inc.

  15. Porphyromonas gingivalis-dendritic cell interactions: consequences for coronary artery disease.

    PubMed

    Zeituni, Amir E; Carrion, Julio; Cutler, Christopher W

    2010-12-21

    An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

  16. Coronary Artery Calcification in Japanese Men in Japan and Hawaii

    PubMed Central

    Abbott, Robert D.; Ueshima, Hirotsugu; Rodriguez, Beatriz L.; Kadowaki, Takashi; Masaki, Kamal H.; Willcox, Bradley J.; Sekikawa, Akira; Kuller, Lewis H.; Edmundowicz, Daniel; Shin, Chol; Kashiwagi, Atsunori; Nakamura, Yasuyuki; El-Saed, Aiman; Okamura, Tomonori; White, Roger; Curb, J. David

    2013-01-01

    Explanations for the low prevalence of atherosclerosis in Japan versus United States are often confounded with genetic variation. To help remove such confounding, coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was compared between Japanese men in Japan and Japanese men in Hawaii. Findings are based on risk factor and CAC measurements that were made from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40 to 50 years and without cardiovascular disease. After age-adjustment, there was a 3-fold excess in the odds of prevalent CAC scores ≥10 in Hawaii versus Japan (relative odds [RO] = 3.2; 95% confidence interval [CI] = 2.1,4.9). While men in Hawaii had a generally poorer risk factor profile, men in Japan were 4-times more likely to smoke cigarettes (49.5 vs. 12.7%, p<0.001). In spite of marked risk factor differences between the samples, none of the risk factors provided an explanation for the low amounts of CAC in Japan. After risk factor adjustment, the RO of CAC scores ≥10 in Hawaii versus Japan was 4.0 (95% CI = 2.2,7.4). Further studies are needed to identify factors that offer protection against atherosclerosis in Japanese men in Japan. PMID:17728270

  17. Serum urate and the risk of major coronary heart disease events.

    PubMed Central

    Wannamethee, S. G.; Shaper, A. G.; Whincup, P. H.

    1997-01-01

    OBJECTIVE: To examine the relation between serum urate and the risk of major coronary heart disease events. DESIGN: A prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7688 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: Fatal and non-fatal coronary heart disease events. RESULTS: There were 1085 major coronary heart disease events during the average follow up period of 16.8 years. Serum urate was significantly associated with a wide range of cardiovascular risk factors including body mass index, alcohol intake, antihypertensive treatment, pre-existing coronary heart disease, serum triglycerides, cholesterol, and diastolic blood pressure. There was a significant positive association between serum urate and risk of coronary heart disease after adjustment for lifestyle factors and disease indicators. This relation was attenuated to non-significance upon additional adjustment for diastolic blood pressure and serum total cholesterol: cholesterol appeared to be the critical factor in attenuating this relation. When the association between serum urate and risk of coronary heart disease was examined by presence and grade of pre-existing coronary heart disease, a positive association was seen only in men with previous definite myocardial infarction, even after full adjustment (P = 0.07). CONCLUSIONS: The relation between serum urate and the risk of coronary heart disease depends heavily upon the presence of pre-existing myocardial infarction and widespread underlying atherosclerosis as well as the clustering of risk factors. Thus serum urate is not a truly independent risk factor for coronary heart disease. Raised serum urate appears to be an integral part of the cluster of risk factors associated with the insulin resistance syndrome that include obesity, raised serum triglycerides, and serum cholesterol. PMID:9326988

  18. Increased carotid wall thickness measured by computed tomography is associated with the presence and severity of coronary artery calcium.

    PubMed

    Nabavi, Vahid; Ahmadi, Naser; Bhatia, Harpreet S; Flores, Ferdinand; Ebrahimi, Ramin; Karlsberg, Ronald P; Budoff, Matthew J

    2011-03-01

    Previous studies have shown that increase in carotid wall thickness (CWT) is associated with cardiovascular risk factors. However, simultaneous systemic and local involvement of atherosclerosis in subjects with high risk of coronary atherosclerosis is not well studied. This study investigates the relation of carotid subclinical atherosclerosis assessed by CWT with the presence and severity of coronary artery calcium(CAC). One hundred and twenty nine subjects (age of 69±10 years, 72% male) underwent CAC, carotid CT angiography, and their metabolic status was evaluated. CAC was defined as 0, 1-100, 101-400, 401-1000 and 1000+. CWT (mm) was calculated as: [mean of both right and left CT-measured CWT 10-mm below the common carotid bifurcation]. Modest correlation between CWT and CAC was noted (r=0.48, p=0.0001). CWT increased substantially with the severity of CAC from CAC 0 to CAC 1000+ (p<0.05). Increased CWT (1.0 mm+) was more prevalent in subjects with significant CAC (100+) as compared to CAC 0 (44.7% vs. 3.3%, p<0.05). Increase in CWT was associated with increased rates of metabolic syndrome and diabetes mellitus. After adjustment for cardiovascular risk factors, the risk of metabolic syndrome and DM was 1.7 and 2.3 respectively for each standard deviation (SD) increase in CWT. Similarly, the risk for each SD increase in CWT increased with severity of CAC as compared to CAC 0 (RR:CAC 1-100:1.2, CAC 101-400:1.5, CAC 400-1000:2.1, and CAC 1000+:3.4, respectively). Increased CWT is associated with the presence and severity of CAC, metabolic syndrome and DM independent of conventional cardiovascular risk factors; highlighting the important role of comprehensive carotid and coronary atherosclerotic assessment to identify at-risk individuals. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Impacts of fresh lime juice and peel on atherosclerosis progression in an animal model.

    PubMed

    Boshtam, Maryam; Asgary, Sedigheh; Moshtaghian, Jamal; Naderi, Gholamali; Jafari-Dinani, Narges

    2013-11-01

    The main protective role of antioxidants in the progression of atherosclerosis has been shown in some studies. Therefore, this project evaluated the effects of Citrus aurantifolia (Christm) juice and peel on antioxidant activity and atherosclerosis progression in rabbits receiving a hypercholesterolemic diet. Forty white New Zealand male rabbits were randomly allocated to four groups. All groups were on hypercholesterolemic diet for two months. While the first group was considered as the hypercholesterolemic control, groups 2 and 3 (intervention groups) received 5 ml/day lime juice and 1 g/day dried lime peel powder, respectively. Group 4 was fed a normal diet (normal control). Before and after the study, weight was measured and a fasting blood specimen was taken from the rabbits. Serum lipids analyses and antioxidant activity evaluations were then performed. The rabbits' aorta and coronary arteries were separated and the presence of fatty streaks was studied. Comparing to the hypercholesterolemic control group (-25.2 ± 7.0), only the plasma total antioxidant capacity change was significantly more in rabbits supplemented with lime juice (16.3 ± 14.7) and peel (8.6 ± 7.1) (P = 0.008). The presence of fatty streaks in coronary arteries and aorta of the intervention groups [juice (0.2 ± 0.01); peel (0.0 ± 0.00)] was significantly decreased compared to the hypercholesterolemic control group (1.2 ± 0.4) (P < 0.001). Based on our findings, Citrus aurantifolia peel and juice increase plasma antioxidant capacity in rabbits, and can thus prevent or decelerate the process of atherogenesis. However, lime peel is more effective than lime juice.

  20. The Role of a Coronary Artery Calcium Scan in Type 1 Diabetes

    PubMed Central

    Eaton, R. Philip; Schade, David S.

    2016-01-01

    Abstract The coronary artery calcium (CAC) scan has recently emerged as a reproducible noninvasive test to detect asymptomatic atherosclerotic coronary artery disease. It has several advantages over the traditional cardiac stress testing modalities, including lower cost, greater sensitivity for nonobstructing coronary artery lesions, and excellent prognostic value when combined with the Framingham risk parameters. Its chief disadvantage is that it does not identify obstructing coronary artery lesions or noncalcified coronary artery plaque. A CAC scan utilizes a chest computed tomogram and computer software to calculate the amount of calcium in the four main coronary vessels. Calcium is deposited in coronary plaques so that the greater the calcium score, the greater the plaque burden. This, in turn, is the basis for predicting a 10–15-year risk of a cardiovascular event. Individuals with a zero calcium score have a very low 10-year risk of a cardiovascular event. Obtaining a calcium score in a diabetic patient permits rational decisions for prescribing statin therapy. In patients with a zero score, the initiation of statin therapy is not recommended because the 5-year incidence of atherosclerotic cardiovascular disease is so low. In patients with diabetes, it is recommended to repeat the calcium scan in 4–5 years to permit timely therapy in the event that the score becomes positive. Since statins mildly increase coronary calcium as part of the stabilization of plaque, a reduction in the calcium score should not be anticipated. However, progression of the calcium score by more than 15%/year (calculated from a repeat CAC scan) provides additional prognostic information of an indication of progression of atherosclerosis. In summary, the coronary calcium score is a major clinical advance for noninvasively detecting coronary artery disease and managing antiatherosclerotic therapy in type 1 diabetes. PMID:27585206

  1. Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

    PubMed Central

    Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

    2013-01-01

    Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

  2. Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis.

    PubMed

    Xu, Gang; Watanabe, Takuya; Iso, Yoshitaka; Koba, Shinji; Sakai, Tetsuo; Nagashima, Masaharu; Arita, Shigeko; Hongo, Shigeki; Ota, Hidekazu; Kobayashi, Youichi; Miyazaki, Akira; Hirano, Tsutomu

    2009-08-28

    Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR-A), acyl-coenzyme A:cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1. The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis. Plasma heregulin-beta(1) levels were significantly decreased in 31 patients with acute coronary syndrome and 33 patients with effort angina pectoris compared with 34 patients with mild hypertension and 40 healthy volunteers (1.3+/-0.3, 2.0+/-0.4 versus 7.6+/-1.4, 8.2+/-1.2 ng/mL; P<0.01). Among all patients with acute coronary syndrome and effort angina pectoris, plasma heregulin-beta(1) levels were further decreased in accordance with the severity of coronary artery lesions. Expression of heregulin-beta(1) was observed at trace levels in intracoronary atherothrombosis obtained by aspiration thrombectomy from acute coronary syndrome patients. Heregulin-beta(1), but not heregulin-alpha, significantly reduced acetylated low-density lipoprotein-induced cholesterol ester accumulation in primary cultured human monocyte-derived macrophages by reducing SR-A and ACAT1 expression and by increasing ABCA1 expression at both mRNA and protein levels. Heregulin-beta(1) significantly decreased endocytic uptake of [(125)I]acetylated low-density lipoprotein and ACAT activity, and increased cholesterol efflux to apolipoprotein (Apo)A-I from human macrophages. Chronic infusion of heregulin-beta(1) into ApoE(-/-) mice significantly suppressed the development of atherosclerotic lesions. This study provided the first evidence that heregulin-beta(1) inhibits atherogenesis and suppresses macrophage foam cell formation via SR

  3. Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice.

    PubMed

    Rasmiena, Aliki A; Barlow, Christopher K; Stefanovic, Nada; Huynh, Kevin; Tan, Ricardo; Sharma, Arpeeta; Tull, Dedreia; de Haan, Judy B; Meikle, Peter J

    2015-12-01

    We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. AIBP reduces atherosclerosis by promoting reverse cholesterol transport and ameliorating inflammation in apoE-/- mice.

    PubMed

    Zhang, Min; Zhao, Guo-Jun; Yao, Feng; Xia, Xiao-Dan; Gong, Duo; Zhao, Zhen-Wang; Chen, Ling-Yan; Zheng, Xi-Long; Tang, Xiao-Er; Tang, Chao-Ke

    2018-06-01

    ApoA-1 binding protein (AIBP) is a secreted protein that interacts with apoA-I and accelerates cholesterol efflux from cells. We have recently reported that AIBP promotes apoA-1 binding to ABCA1 in the macrophage cell membrane, partially through 115-123 amino acids. However, the effects of AIBP on the development of atherosclerosis in vivo remain unknown. ApoE -/- mice with established atherosclerotic plaques were infected with rAAV-AIBP or rAAV-AIBP(Δ115-123), respectively. AIBP-treated mice showed reduction of atherosclerotic lesion formation, increase in circulating HDL levels and enhancement of reverse cholesterol transport to the plasma, liver, and feces. AIBP increased ABCA1 protein levels in aorta and peritoneal macrophages. Furthermore, AIBP could diminish atherosclerotic plaque macrophage content and the expression of chemotaxis-related factors. In addition, AIBP prevented macrophage inflammation by inactivating NF-κB and promoted the expression of M2 markers like Mrc-1 and Arg-1. However, lack of 115-123 amino acids of AIBP(Δ115-123) had no such preventive effects on the progression of atherosclerosis. Our observations demonstrate that AIBP inhibits atherosclerosis progression and suggest that it may be an effective target for prevention of atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Association between increased epicardial adipose tissue volume and coronary plaque composition.

    PubMed

    Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

    2014-09-01

    To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or calcified tissue, based on the radiofrequency spectrum. Epicardial adipose tissue was measured as the tissue ranging from -190 to -30 Hounsfield units. EATV, calculated as the sum of the fat areas on short-axis images, was 85.0 ± 34.0 cm(3). There was a positive correlation between EATV and the percentage of necrotic plaque tissue (R (2) = 0.34, P < 0.01), while there was a negative correlation between EATV and the percentage of fibrous tissue (R (2) = 0.24, P < 0.01). Multivariate analysis revealed that an increased low-density lipoprotein cholesterol level (β = 0.15, P = 0.03) and EATV (β = 0.14, P = 0.02) were independently associated with the percentage of necrotic plaque tissue. An increase in EATV was associated with the development of coronary atherosclerosis and, potentially, with the most dangerous type of plaque.

  6. Ultrasound Imaging for Risk Assessment in Atherosclerosis

    PubMed Central

    Steinl, David C.; Kaufmann, Beat A.

    2015-01-01

    Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; (c) assessing plaque neovascularization and (d) imaging the expression of disease-relevant molecules using molecular imaging. PMID:25938969

  7. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiang, Jin; Wang, Ying; Su, Ke

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist formore » E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.« less

  8. Histone deacetylases and atherosclerosis.

    PubMed

    Zheng, Xia-xia; Zhou, Tian; Wang, Xin-An; Tong, Xiao-hong; Ding, Jia-wang

    2015-06-01

    Atherosclerosis is the most common pathological process that leads to cardiovascular diseases, a disease of large- and medium-sized arteries that is characterized by a formation of atherosclerotic plaques consisting of necrotic cores, calcified regions, accumulated modified lipids, smooth muscle cells (SMCs), endothelial cells, leukocytes, and foam cells. Recently, the question about how to suppress the occurrence of atherosclerosis and alleviate the progress of cardiovascular disease becomes the hot topic. Accumulating evidence suggests that histone deacetylases(HDACs) play crucial roles in arteriosclerosis. This review summarizes the effect of HDACs and HDAC inhibitors(HDACi) on the progress of atherosclerosis. Copyright © 2015. Published by Elsevier Ireland Ltd.

  9. The role of urotensin II and atherosclerotic risk factors in patients with slow coronary flow

    PubMed Central

    Şatıroğlu, Ömer; Emre Durakoğlugil, Murtaza; Çetin, Mustafa; Çiçek, Yüksel; Erdoğan, Turan; Duman, Hakan

    2016-01-01

    Background Slow coronary flow (SCF) is an angiographic finding characterized with delayed opacification of epicardial coronary arteries without obstructive coronary disease. Urotensin II (UII) is an important vascular peptide, which has an important role in hypertension, coronary artery disease, and vascular remodeling in addition to potent vasoconstrictor effect. Objectives We investigated UII levels, hypertension, and other atherosclerotic risk factors in patients with SCF, a variety of coronary artery disease. Methods We enrolled 14 patients with SCF and 29 subjects with normal coronary arteries without SCF. We compared the UII levels and the atherosclerotic risk factors between patients with SCF and control subjects with normal coronary flow. Results UII concentrations were significantly higher in patients with SCF compared to controls (711.0 ± 19.4 vs. 701.5 ± 27.2 ng/mL, p = 0.006). We detected a positive correlation between SCF and age (r = 0.476, p = 0.001), BMI (r = 0.404, p = .002), UII concentrations (r = 0.422, p = 0.006), and hypertension (r = 0.594, p = 0.001). Conclusion We identified increased UII levels in patients with SCF. We think that UII concentrations may be informative on SCF pathogenesis due to relationship with inflammation, atherosclerosis, and vascular remodeling. PMID:28180005

  10. Detection of Human Cytomegalovirus and Epstein-Barr Virus in Coronary Atherosclerotic Tissue

    PubMed Central

    Imbronito, Ana Vitória; Marcelino, Silvia Linardi; Grande, Sabrina Rosa; Nunes, Fabio Daumas; Romito, Giuseppe Alexandre

    2010-01-01

    Previous studies indicated that patients with atherosclerosis are predominantly infected by human cytomegalovirus (HCMV), but rarely infected by type 1 Epstein-Barr virus (EBV-1). In this study, atheromas of 30 patients who underwent aortocoronary bypass surgery with coronary endartherectomy were tested for the presence of these two viruses. HCMV occurred in 93.3% of the samples and EBV-1 was present in 50% of them. Concurrent presence of both pathogens was detected in 43.3% of the samples. PMID:24031529

  11. Mediators of Atherosclerosis in South Asians Living in America (MASALA) study: Objectives, Methods, and Cohort Description

    PubMed Central

    2013-01-01

    Background South Asians (individuals from India, Pakistani, Bangladesh, Nepal, and Sri Lanka) have high rates of cardiovascular disease which cannot be explained by traditional risk factors. There are no prospective cohort studies investigating antecedents of cardiovascular disease in South Asians. Methods The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is investigating the prevalence, correlates and outcomes associated with subclinical cardiovascular disease (CVD) in a population-based sample of South Asian men and women between ages 40 – 79 years from two U.S. clinical field centers. This cohort is similar in methods and measures to the Multi-Ethnic Study of Atherosclerosis to allow for efficient cross-ethnic comparisons. Measurements obtained at the baseline examination include sociodemographic information, lifestyle and psychosocial factors, standard CVD risk factors, oral glucose tolerance testing, electrocardiogram, assessment of microalbuminuria, ankle and brachial blood pressures, carotid intima media wall thickness using ultrasonagraphy, coronary artery calcium measurement and abdominal visceral fat using computed tomography. Blood samples will be assayed for biochemical risk factors. Results Between October 2010 and March 2013 we enrolled 906 South Asians with mean age of 55±9 years, 46% women, 98% immigrants who have lived 27±11 years in the US. Conclusions The sociodemographic characteristics of this cohort are representative of US South Asians. Participants are being followed with annual telephone calls for identification of CVD events including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, congestive heart failure, therapeutic interventions for CVD, and mortality. PMID:24194499

  12. CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology

    PubMed Central

    Erbel, Christian; Korosoglou, Grigorios; Ler, Pearlyn; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O.; Buss, Sebastian J.; Giannitsis, Evangelos; Katus, Hugo A.; Gleissner, Christian A.

    2015-01-01

    Background CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. Methods and Results CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. Conclusions While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis. PMID:26524462

  13. CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology.

    PubMed

    Erbel, Christian; Korosoglou, Grigorios; Ler, Pearlyn; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O; Buss, Sebastian J; Giannitsis, Evangelos; Katus, Hugo A; Gleissner, Christian A

    2015-01-01

    CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.

  14. High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice.

    PubMed

    Yang, An-Ning; Zhang, Hui-Ping; Sun, Yue; Yang, Xiao-Ling; Wang, Nan; Zhu, Guangrong; Zhang, Hui; Xu, Hua; Ma, Sheng-Chao; Zhang, Yue; Li, Gui-Zhong; Jia, Yue-Xia; Cao, Jun; Jiang, Yi-Deng

    2015-12-21

    Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. [Role of serum leptin in the severity of coronary artery disease in patients with stable angina].

    PubMed

    Jerez-Valero, Miguel; Meliveo-García, Ana; Jordán-Martínez, Laura; Carrasco-Chinchilla, Fernando; Moreno-Santos, Inmaculada; Ordóñez, Antonio; Sánchez-Fernández, Pedro L; Vázquez, Rafael; Hernández-García, José M; Gómez-Doblas, Juan J; Pérez-Belmonte, Luis M; de Teresa-Galván, Eduardo; Jiménez-Navarro, Manuel

    2016-07-01

    Leptin is a plasmatic peptide hormone that has been related to cardiovascular homeostasis and atherosclerosis but much is still unknown about its relationship with coronary artery disease. The aim of this study was to evaluate the value of serum leptin in patients with stable angina and its relationship with the severity of coronary disease. 204 patients, 152 with stable angina (coronary artery disease group) and 52 without coronary disease excluded by cardiac computerized tomography (control group) were included. The coronary artery disease group was divided into 2 subgroups according to severity of coronary disease (single or multivessel disease, 46 and 106 patients, respectively). Serum leptin levels were determined by Enzyme-Linked InmunoSorbent Assay. Leptin levels were significantly higher in patients with multivessel disease and were independently associated with a greater severity of coronary artery disease when compared with controls (OR 1.14; 95%CI: 1.03-1.27; p=0.014) and with patients with single vessel disease (OR 1.12; 95%CI: 1.01-1.25; p=0.036). Serum leptin was tested as a diagnostic marker of multivessel disease with an area under the curve obtained from Receiver Operating Characteristics of 0.6764 (95%CI 0.5765-0.7657). Serum leptin levels were associated in patients with stable angina with the severity of coronary artery disease, suggesting its value in the development of coronary disease and as a future therapeutic target. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. Impact of Intercellular Adhesion Molecule-1 Genetic Polymorphisms on Coronary Artery Disease Susceptibility in Taiwanese Subjects.

    PubMed

    Chou, Chi-Hung; Ueng, Kwo-Chang; Liu, Yu-Fan; Wu, Chih-Hsien; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The principal pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease of the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammation reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491, rs5498, rs281432 and rs3093030 with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography in Taiwan Chung Shan Medical University Hospital, were recruited to determine four ICAM-1 SNPs by real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic and characteristics and CAD were analyzed. This study showed that rs281432 (C8823G) was the only ICAM-1 SNP which affect the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects.

  17. Ex vivo catheter-based imaging of coronary atherosclerosis using multimodality OCT and NIRAF excited at 633 nm

    PubMed Central

    Wang, Hao; Gardecki, Joseph A.; Ughi, Giovanni J.; Jacques, Paulino Vacas; Hamidi, Ehsan; Tearney, Guillermo J.

    2015-01-01

    While optical coherence tomography (OCT) has been shown to be capable of imaging coronary plaque microstructure, additional chemical/molecular information may be needed in order to determine which lesions are at risk of causing an acute coronary event. In this study, we used a recently developed imaging system and double-clad fiber (DCF) catheter capable of simultaneously acquiring both OCT and red excited near-infrared autofluorescence (NIRAF) images (excitation: 633 nm, emission: 680nm to 900nm). We found that NIRAF is elevated in lesions that contain necrotic core – a feature that is critical for vulnerable plaque diagnosis and that is not readily discriminated by OCT alone. We first utilized a DCF ball lens probe and a bench top setup to acquire en face NIRAF images of aortic plaques ex vivo (n = 20). In addition, we used the OCT-NIRAF system and fully assembled catheters to acquire multimodality images from human coronary arteries (n = 15) prosected from human cadaver hearts (n = 5). Comparison of these images with corresponding histology demonstrated that necrotic core plaques exhibited significantly higher NIRAF intensity than other plaque types. These results suggest that multimodality intracoronary OCT-NIRAF imaging technology may be used in the future to provide improved characterization of coronary artery disease in human patients. PMID:25909020

  18. 10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study).

    PubMed

    McClelland, Robyn L; Jorgensen, Neal W; Budoff, Matthew; Blaha, Michael J; Post, Wendy S; Kronmal, Richard A; Bild, Diane E; Shea, Steven; Liu, Kiang; Watson, Karol E; Folsom, Aaron R; Khera, Amit; Ayers, Colby; Mahabadi, Amir-Abbas; Lehmann, Nils; Jöckel, Karl-Heinz; Moebus, Susanne; Carr, J Jeffrey; Erbel, Raimund; Burke, Gregory L

    2015-10-13

    Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Atherosclerosis affecting vision: therapy.

    PubMed

    Eggers, H

    1966-05-01

    The visual consequences and the pathogenesis and therapy of atherosclerosis are discussed. Atherosclerosis apparently is the result of hepatic failure to produce a stable suspension of cholesterol esters in the plasma. In some instances this represents an inherent metabolic defect. Usually it represents improper diet, namely, the excessive intake of saturated fatty acids and the inadequate intake of polyunsaturated fatty acids. Excessive ingestion of carbohydrates, insufficient physical exercise and reduced thyroid function are contributing causes. The final common denominators leading to tissue injury and destruction are vascular insufficiency and hypoxia. Hypertension is a separate disease, often concurrent with atherosclerosis. In diabetes, also a separate disease, atherosclerosis is one of the sequelae. Therapy primarily consists of the reduction or elimination of meat and milk fats from the diet, and the inclusion or increase of marine fats and vegetable oils. Simultaneously, carbohydrate intake is restricted. Adequate thyroid function, a normal hemoglobin level, and sufficient physical exercise are important. A supplementary intake of vitamins B6 and E, and of lipotropic substances is recommended.

  20. Differential Association of Psychosocial Comorbidities With Subclinical Atherosclerosis in Rheumatoid Arthritis.

    PubMed

    Liu, Ying L; Szklo, Moyses; Davidson, Karina W; Bathon, Joan M; Giles, Jon T

    2015-10-01

    Rheumatoid arthritis (RA) is associated with an elevated risk of cardiovascular disease (CVD) events and subclinical atherosclerosis, but the reasons for the excess risk are unclear. We explored whether psychosocial comorbidities, which may be associated with CVD in the general population, are differentially associated with subclinical atherosclerosis in RA compared to controls. Data were from a longitudinal cohort study of 195 RA patients and 1,073 non-RA controls. Using validated scales, heterogeneity in the associations of psychosocial measures (depression, stress, anxiety/anger, support, discrimination/hassles) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and carotid intima-media thickness [IMT]/plaque) were compared in RA and non-RA groups using multivariable generalized linear models. Computed tomography and ultrasound were used to identify CAC and IMT/plaque, respectively. CAC >100 units was used to define moderate/severe CAC. In RA, per-unit higher anxiety scores (odds ratio [OR] 1.10, P = 0.029), anger scores (OR 1.14, P = 0.037), depressive symptoms (OR 3.41, P = 0.032), and caregiver stress (OR 2.86, P = 0.014) were associated with increased odds of CAC >100 units after adjustment for relevant covariates. These findings persisted despite adjustment for markers of inflammation (C-reactive protein and interleukin-6 levels) and were seen only in RA, not in controls (adjusted multiplicative interaction P = 0.001-0.077). In RA, job stress was associated with an increased risk of carotid plaque (adjusted OR = 3.21, P = 0.019), and increasing social support was associated with lower internal carotid IMT (adjusted P = 0.024). Depressive symptoms, stress, anger/anxiety, and social support may preferentially affect CVD risk in RA, and screening/treatment for psychosocial morbidities in RA may help ameliorate the additional CVD burden. © 2015, American College of Rheumatology.

  1. Regulation of programmed cell death or apoptosis in atherosclerosis.

    PubMed

    Geng, Y J

    1997-01-01

    Intimal thickening caused by accumulation of cells, lipids, and connective tissue characterizes atherosclerosis, an arterial disease that leads to cardiac and cerebral infarction. Apoptosis, or genetically programmed cell death, is important for the development and morphogenesis of organs and tissues. As in other tissues, cells of cardiovascular tissues can undergo apoptosis. Increased apoptosis has been found in both human and animal atherosclerotic lesions, mediating tissue turnover and lesion development. In addition to vascular cells, many activated immune cells, mainly macrophages and T cells, are present in atherosclerotic lesions, where these cells produce biologically active substances such as the proinflammatory cytokines tumor necrosis factor, interleukin-1 (IL-1), and interferon-gamma. Simultaneous exposure to these cytokines may trigger apoptosis of vascular smooth muscle cells. The products of death-regulating genes including Fas/Fas ligand, members of IL-1 beta cysteinyl protease (caspase) family, the tumor suppressive gene p53, and the protooncogene c-myc have been found in vascular cells and may participate in the regulation of vascular apoptosis during the development of atherosclerosis. Abnormal occurrence of apoptosis may take place in atherosclerotic lesions, including attenuation or acceleration of the apoptotic death process. The former may cause an increase in the cellularity of the lesions, and the latter can reduce cellular components important for maintaining the integrity and stability of the plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of patients with atherosclerosis and its major complications, heart attack and stroke.

  2. Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography.

    PubMed

    Utsunomiya, Hiroto; Yamamoto, Hideya; Kunita, Eiji; Kitagawa, Toshiro; Ohashi, Norihiko; Oka, Toshiharu; Yamazato, Ryo; Horiguchi, Jun; Kihara, Yasuki

    2010-11-01

    We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (p<0.001 for both). Multivariate analyses revealed that a combined presence of AVC and MAC was independently associated with the presence (odds ratio [OR] 9.36, 95% confidence interval [95%CI] 1.55-56.53, p=0.015) and extent (β-estimate 1.86, p<0.001) of overall coronary plaque. When stratified by plaque composition, it was associated with the extent of CAP (β-estimate 1.77, p<0.001) and MCAP (β-estimate 1.04, p<0.001), but not with NCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and ofmore » key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.« less

  4. A comparison of three apolipoprotein B methods and their associations with incident coronary heart disease risk over a 12-year follow-up period: The Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Cao, Jing; Steffen, Brian T; Guan, Weihua; Remaley, Alan T; McConnell, Joseph P; Palamalai, Vikram; Tsai, Michael Y

    Apolipoprotein B-100 (ApoB) is a well-researched lipoprotein marker used in assessing the risk of coronary heart disease (CHD) development. Despite its continued use at the bedside, ApoB methodologies have not been thoroughly compared and may differentially discriminate CHD risk, resulting in patient misclassification. This study compared 3 ApoB immunoassays and their associations with incident CHD risk over a 12-year follow-up period in the Multi-Ethnic Study of Atherosclerosis. Plasma ApoB concentrations were measured in 4679 participants of Multi-Ethnic Study of Atherosclerosis at baseline, using 3 immunoturbidimetric methods. Roche and Kamiya reagent-based methods were analyzed on a Roche modular P analyzer, and the Diazyme reagent-based method was analyzed on a Siemens Dimension analyzer. Cox proportional analysis estimated ApoB-related risk of incident CHD over a median follow-up period of 12.5 years with adjustments for nonlipid CHD risk factors. ApoB concentrations were examined as continuous variables but were also dichotomized based on clinical designations of borderline (100 mg/dL), high (120 mg/dL), and very high ApoB levels (140 mg/dL). Moderate to strong correlations among ApoB methods were observed (r = 0.79-0.98). ApoB concentrations (per standard deviation) were similarly associated with CHD risk and hazard ratio (95% confidence interval): Roche: 1.16 (1.03-1.30); Kamiya: 1.14 (1.02-1.28); and Diazyme: 1.14 (1.02-1.28). Although all 3 ApoB were similarly associated with risk of incident CHD over the study period regardless of the reagent type, the bias between methods suggests that these reagents are not fungible, and assay harmonization may be warranted. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. Cannabis-associated myocardial infarction in a young man with normal coronary arteries.

    PubMed

    Hodcroft, Christopher J; Rossiter, Melissa C; Buch, Ashesh N

    2014-09-01

    The use of cannabis is not usually regarded as a risk factor for acute coronary syndrome. However, several cases of myocardial infarction (MI) associated with cannabis use have been reported in the scientific literature. The etiology of this phenomenon is not known. To present a case of cannabis-associated MI in which atherosclerotic coronary disease was excluded as a potential etiology by intravascular ultrasound examination, and briefly review the other possible mechanisms by which this effect may be mediated. We present the case of a previously healthy 21-year-old man who regularly smoked cannabis and presented to the Emergency Department with ST-elevation myocardial infarction after participating in a sport. He was also a cigarette smoker, but had no other conventional cardiovascular risk factors. At coronary angiography, a large amount of thrombus was found in the left anterior descending coronary artery. He recovered with medical treatment, and subsequent intravascular ultrasound examination showed no evidence of atherosclerosis at the site of the thrombus. Cannabis-associated MI is increasingly recognized. The etiology is unclear, but we believe this is the first report of the phenomenon where atherosclerotic plaque rupture has been excluded as the cause with a high degree of confidence. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Intravascular laser speckle imaging for the mechanical analysis of coronary plaques (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hosoda, Masaki; Wang, Jing; Tsikudi, Diane; Nadkarni, Seemantini

    2016-02-01

    Acute myocardial infarction is frequently caused by the rupture of coronary plaques with severely compromised viscoelastic properties. We have developed a new optical technology termed intravascular laser speckle imaging (ILSI) that evaluates plaque viscoelastic properties, by measuring the time scale (time constant, τ) of temporally evolving laser speckle fluctuations. To enable coronary evaluation in vivo, an optical ILSI catheter has been developed that accomplishes omni-directional illumination and viewing of the entire coronary circumference without the need for mechanical rotation. Here, we describe the capability of ILSI for evaluating human coronary atherosclerosis in cadaveric hearts. ILSI was conducted in conjunction with optical coherence tomography (OCT) imaging in five human cadaveric hearts. The left coronary artery (LCA), left anterior descending (LAD), left circumflex artery (LCx), and right coronary artery (RCA) segments were resected and secured on custom-developed coronary holders to enable accurate co-registration between ILSI, OCT, and histopathology. Speckle time constants, τ, calculated from each ILSI section were compared with lipid and collagen content measured from quantitative Histopathological analysis of the corresponding Oil Red O and Picrosirius Red stained sections. Because the presence of low viscosity lipid elicits rapid speckle fluctuations, we observed an inverse correlation between τ measured by ILSI and lipid content (R= -0.64, p< 0.05). In contrast, the higher viscoelastic modulus of fibrous regions resulted in a positive correlation between τ and collagen content (R= 0.54, p< 0.05). These results demonstrate the feasibility of conducting ILSI evaluation of arterial mechanical properties using a miniaturized omni-directional catheter.

  7. Selective estrogen receptor modulators and risk for coronary heart disease.

    PubMed

    Cano, A; Hermenegildo, C; Oviedo, P; Tarín, J J

    2007-04-01

    Coronary heart disease (CHD) is the leading cause of death in women in most countries. Atherosclerosis is the main biological process determining CHD. Clinical data support the notion that CHD is sensitive to estrogens, but debate exists concerning the effects of the hormone on atherosclerosis and its complications. Selective estrogen receptor modulators (SERMs) are compounds capable of binding the estrogen receptor to induce a functional profile distinct from estrogens. The possibility that SERMs may shift the estrogenic balance on cardiovascular risk towards a more beneficial profile has generated interest in recent years. There is considerable information on the effects of SERMs on distinct areas that are crucial in atherogenesis. The complexity derived from the diversity of variables affecting their mechanism of action plus the differences between compounds make it difficult to delineate one uniform trend for SERMs. The present picture, nonetheless, is one where SERMs seem less powerful than estrogens in atherosclerosis protection, but more gentle with advanced forms of the disease. The recent publication of the Raloxifene Use for The Heart (RUTH) study has confirmed a neutral effect for raloxifene. Prothrombotic states may favor occlusive thrombi at sites occupied by atheromatous plaques. Platelet activation has received attention as an important determinant of arterial thrombogenesis. Although still sparse, available evidence globally suggests neutral or beneficial effects for SERMs.

  8. Carotid intima-media thickness and plaque in apparently healthy Japanese individuals with an estimated 10-year absolute risk of CAD death according to the Japan Atherosclerosis Society (JAS) guidelines 2012: the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

    PubMed

    Kadota, Aya; Miura, Katsuyuki; Okamura, Tomonori; Fujiyoshi, Akira; Ohkubo, Takayoshi; Kadowaki, Takashi; Takashima, Naoyuki; Hisamatsu, Takashi; Nakamura, Yasuyuki; Kasagi, Fumiyoshi; Maegawa, Hiroshi; Kashiwagi, Atsunori; Ueshima, Hirotsugu

    2013-01-01

    To examine whether subclinical atherosclerosis of the carotid arteries is concordant with the categories in the 2012 atherosclerosis prevention guidelines proposed by the Japan Atherosclerosis Society (JAS guidelines 2012), which adopted the estimated 10-year absolute risk of coronary artery disease (CAD) death in the NIPPON DATA80 Risk Assessment Chart. Between 2006 and 2008, 868 Japanese men 40 to 74 years of age without a history of cardiovascular disease were randomly selected from Kusatsu City, Japan. The intima media thickness (IMT) and plaque number from the common to internal carotid arteries were investigated using ultrasonography. The absolute risk of CAD death was estimated based on the individual risk factor data, and the mean IMT and plaque number in Categories Ⅰ, Ⅱ and Ⅲ of the guidelines were examined. The estimated 10-year absolute risk of CAD was directly related to the IMT (mean IMT (mean ± SD) (mm) for a 10-year absolute risk of ≥ 2.0% and ≥ 5.0%: 0.88 ± 0.18 and 0.95 ± 0.19, respectively) and the plaque number. These results are compatible with the categories described by the guidelines (mean IMT (mean ± SD) (mm) for Categories Ⅰ, Ⅱ, and Ⅲ: 0.70 ± 0.11, 0.81 ± 0.16 and 0.88 ± 0.18, respectively; mean plaque number: 0.9, 2.1 and 3, respectively). These findings were similar for Category Ⅲ participants with or without DM and CKD. Subclinical atherosclerosis of the carotid arteries is concordant with the 10-year absolute risk of CAD and the categories in the JAS guidelines 2012.

  9. Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype

    PubMed Central

    Cardilo-Reis, Larissa; Gruber, Sabrina; Schreier, Sabine M; Drechsler, Maik; Papac-Milicevic, Nikolina; Weber, Christian; Wagner, Oswald; Stangl, Herbert; Soehnlein, Oliver; Binder, Christoph J

    2012-01-01

    Atherosclerotic lesions are characterized by the accumulation of oxidized LDL (OxLDL) and the infiltration of macrophages and T cells. Cytokine expression in the microenvironment of evolving lesions can profoundly contribute to plaque development. While the pro-atherogenic effect of T helper (Th) 1 cytokines, such as IFN-γ, is well established, the role of Th2 cytokines is less clear. Therefore, we characterized the role of the Th2 cytokine interleukin (IL)-13 in murine atherosclerosis. Here, we report that IL-13 administration favourably modulated the morphology of already established atherosclerotic lesions by increasing lesional collagen content and reducing vascular cell adhesion molecule-1 (VCAM-1)-dependent monocyte recruitment, resulting in decreased plaque macrophage content. This was accompanied by the induction of alternatively activated (M2) macrophages, which exhibited increased clearance of OxLDL compared to IFN-γ-activated (M1) macrophages in vitro. Importantly, deficiency of IL-13 results in accelerated atherosclerosis in LDLR−/− mice without affecting plasma cholesterol levels. Thus, IL-13 protects from atherosclerosis and promotes a favourable plaque morphology, in part through the induction of alternatively activated macrophages. PMID:23027612

  10. Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: Evidence for a protective role for glucosamine in atherosclerosis

    PubMed Central

    Duan, Wenlan; Paka, Latha; Pillarisetti, Sivaram

    2005-01-01

    Accelerated atherosclerosis is one of the major vascular complications of diabetes. Factors including hyperglycemia and hyperinsulinemia may contribute to accelerated vascular disease. Among the several mechanisms proposed to explain the link between hyperglycemia and vascular dysfunction is the hexosamine pathway, where glucose is converted to glucosamine. Although some animal experiments suggest that glucosamine may mediate insulin resistance, it is not clear whether glucosamine is the mediator of vascular complications associated with hyperglycemia. Several processes may contribute to diabetic atherosclerosis including decreased vascular heparin sulfate proteoglycans (HSPG), increased endothelial permeability and increased smooth muscle cell (SMC) proliferation. In this study, we determined the effects of glucose and glucosamine on endothelial cells and SMCs in vitro and on atherosclerosis in apoE null mice. Incubation of endothelial cells with glucosamine, but not glucose, significantly increased matrix HSPG (perlecan) containing heparin-like sequences. Increased HSPG in endothelial cells was associated with decreased protein transport across endothelial cell monolayers and decreased monocyte binding to subendothelial matrix. Glucose increased SMC proliferation, whereas glucosamine significantly inhibited SMC growth. The antiproliferative effect of glucosamine was mediated via induction of perlecan HSPG. We tested if glucosamine affects atherosclerosis development in apoE-null mice. Glucosamine significantly reduced the atherosclerotic lesion in aortic root. (P < 0.05) These data suggest that macrovascular disease associated with hyperglycemia is unlikely due to glucosamine. In fact, glucosamine by increasing HSPG showed atheroprotective effects. PMID:16207378

  11. Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

    PubMed

    Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

    2017-10-01

    Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS

  12. Lumen and calcium characteristics within calcified coronary lesions. Comparison of computed tomography coronary angiography versus intravascular ultrasound.

    PubMed

    Noll, Dariusz; Kruk, Mariusz; Pręgowski, Jerzy; Kaczmarska, Edyta; Kryczka, Karolina; Pracoń, Radosław; Skwarek, Mirosław; Dzielińska, Zofia; Petryka, Joanna; Spiewak, Mateusz; Lubiszewska, Barbara; Norwa-Otto, Bożena; Opolski, Maksymilian; Witkowski, Adam; Demkow, Marcin; Rużyłło, Witold; Kępka, Cezary

    2013-01-01

    Computed tomography coronary angiography (CTCA) is a diagnostic method used for exclusion of coronary artery disease. However, lower accuracy of CTCA in assessment of calcified lesions is a significant factor impeding applicability of CTCA for assessment of coronary atherosclerosis. To provide insight into lumen and calcium characteristics assessed with CTCA, we compared these parameters to the reference of intravascular ultrasound (IVUS). Two hundred and fifty-two calcified lesions within 97 arteries of 60 patients (19 women, age 63 ±10 years) underwent assessment with both 2 × 64 slice CT (Somatom Definition, Siemens) and IVUS (s5, Volcano Corp.). Coronary lumen and calcium dimensions within calcified lesions were assessed with CTCA and compared to the reference measurements made with IVUS. On average CTCA underestimated mean lumen diameter (2.8 ±0.7 mm vs. 2.9 ±0.8 mm for IVUS), lumen area (6.4 ±3.4 mm(2) vs. 7.0 ±3.7 mm(2) for IVUS, p < 0.001) and total calcium arc (52 ±35° vs. 83 ±54°). However, analysis of tertiles of the examined parameters revealed that the mean lumen diameter, lumen area and calcium arc did not significantly differ between CTCA and IVUS within the smallest lumens (1(st) tertile of mean lumen diameter at 2.1 mm, and 1(st) tertile of lumen area at 3.7 mm(2)) and lowest calcium arc (mean of 40°). Although, on average, CTCA underestimates lumen diameter and area as well as calcium arc within calcified lesions, the differences are not significant within the smallest vessels and calcium arcs. The low diagnostic accuracy of CTCA within calcified lesions may be attributed to high variance and not to systematic error of measurements.

  13. Imaging Atherosclerosis

    PubMed Central

    Tarkin, Jason M.; Dweck, Marc R.; Evans, Nicholas R.; Takx, Richard A.P.; Brown, Adam J.; Tawakol, Ahmed; Fayad, Zahi A.

    2016-01-01

    Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID:26892971

  14. Is the presence of AA amyloidosis associated with impaired coronary flow reserve?

    PubMed

    Bulut, Mustafa; Keles, Nursen; Caliskan, Zuhal; Kostek, Osman; Aksu, Feyza; Ozdil, Kamil; Akcakoyun, Mustafa; Demircioglu, Kenan; Yilmaz, Yusuf; Kanbay, Mehmet; Caliskan, Mustafa

    2016-08-01

    Systemic amyloid A protein (AA) amyloidosis may occur as a complication of many chronic inflammatory disorders. Patients receiving inadequate anti-inflammatory and immunosuppressive therapies have an increased risk of developing systemic AA amyloidosis. Inflammation plays a role in all stages and the thrombotic complications of atherosclerosis. In the absence of epicardial coronary stenosis, coronary flow reserve (CFR) reflects coronary microvascular dysfunction. In the present study, we hypothesized that amyloid advanced subclinical inflammation in chronic inflammatory diseases (CID) patients may further affect coronary microcirculation. Thirty-two patients with biopsy-diagnosed renal AA, 73 patients with non-amyloid CID, and a group of healthy volunteers were included in the study. The measurements of coronary flow velocity were performed by a single investigator with expertise in transthoracic Doppler harmonic echocardiography (TTDE). The AA amyloidosis subgroup had significantly lower CFR values than other non-amyloid CID patients and the control individuals (1.8 (1.5-2.1) vs. 2.1 (2.0-2.4) and 3.0 (2.8-3.2), p < 0.001). Multivariate logistic regression analysis indicated that the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR (p < 0.05). The presence of AA amyloidosis is related to decreased CFR values and the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR. Therefore, patients with AA amyloidosis may have an increased risk of developing coronary artery diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Oral microbiota in patients with atherosclerosis.

    PubMed

    Fåk, Frida; Tremaroli, Valentina; Bergström, Göran; Bäckhed, Fredrik

    2015-12-01

    Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. The Investigation of Serum Vaspin Level in Atherosclerotic Coronary Artery Disease

    PubMed Central

    Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

    2012-01-01

    Background It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Methods Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 oC by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Results Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Conclusion Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Keywords Coronary artery disease; Vaspin; Adipokine PMID:22505983

  17. The investigation of serum vaspin level in atherosclerotic coronary artery disease.

    PubMed

    Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

    2012-04-01

    It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 (o)C by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Coronary artery disease; Vaspin; Adipokine.

  18. Diagnostic Accuracy of a New High-Sensitivity Troponin I Assay and Five Accelerated Diagnostic Pathways for Ruling Out Acute Myocardial Infarction and Acute Coronary Syndrome.

    PubMed

    Greenslade, Jaimi H; Carlton, Edward W; Van Hise, Christopher; Cho, Elizabeth; Hawkins, Tracey; Parsonage, William A; Tate, Jillian; Ungerer, Jacobus; Cullen, Louise

    2018-04-01

    This diagnostic accuracy study describes the performance of 5 accelerated chest pain pathways, calculated with the new Beckman's Access high-sensitivity troponin I assay. High-sensitivity troponin I was measured with presentation and 2-hour blood samples in 1,811 patients who presented to an emergency department (ED) in Australia. Patients were classified as being at low risk according to 5 rules: modified accelerated diagnostic protocol to assess patients with chest pain symptoms using troponin as the only biomarker (m-ADAPT), the Emergency Department Assessment of Chest Pain Score (EDACS) pathway, the History, ECG, Age, Risk Factors, and Troponin (HEART) pathway, the No Objective Testing Rule, and the new Vancouver Chest Pain Rule. Endpoints were 30-day acute myocardial infarction and acute coronary syndrome. Measures of diagnostic accuracy for each rule were calculated. Data included 96 patients (5.3%) with acute myocardial infarction and 139 (7.7%) with acute coronary syndrome. The new Vancouver Chest Pain Rule and No Objective Testing Rule had high sensitivity for acute myocardial infarction (100%; 95% confidence interval [CI] 96.2% to 100% for both) and acute coronary syndrome (98.6% [95% CI 94.9% to 99.8%] and 99.3% [95% CI 96.1% to 100%]). The m-ADAPT, EDACS, and HEART pathways also yielded high sensitivity for acute myocardial infarction (96.9% [95% CI 91.1% to 99.4%] for m-ADAPT and 97.9% [95% CI 92.7% to 99.7%] for EDACS and HEART), but lower sensitivity for acute coronary syndrome (≤95.0% for all). The m-ADAPT, EDACS, and HEART rules classified more patients as being at low risk (64.3%, 62.5%, and 49.8%, respectively) than the new Vancouver Chest Pain Rule and No Objective Testing Rule (28.2% and 34.5%, respectively). In this cohort with a low prevalence of acute myocardial infarction and acute coronary syndrome, using the Beckman's Access high-sensitivity troponin I assay with the new Vancouver Chest Pain Rule or No Objective Testing Rule enabled

  19. Effect of simulated hyperemia on the flow field in a mildly atherosclerotic coronary artery casting of man

    NASA Technical Reports Server (NTRS)

    Cho, Y. I.; Back, L. H.; Crawford, D. W.

    1985-01-01

    Changes in an arterial flow field due to mild atherosclerosis were determined using a main coronary artery casting with a maximum obstruction of about 50 percent by area. Local pressure changes were measured using six pressure tap holes along the wall of the casting. The test-fluid was a 33 percent sugar-water solution of approximately the same viscosity as human blood. Flow visualization results were obtained by injecting blue-dye through the pressure tap holes. Measurement of local pressure demonstrated a significant Reynolds number effect. At Reynolds numbers of 80-710, a local pressure rise was observed downstream of the mild atherosclerotic constriction due to momentum changes. The Reynolds number necessary for flow separation in the divergent region of the coronary casting was about 330. The experimental results can be used to obtain a quantitative relation between coronary morphology and the fluid dynamic consequences of mild diffuse disease under conditions of maximum cardiac demand i.e., higher coronary flow rates and Reynolds numbers associated with space and atmospheric flight.

  20. [Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

    PubMed

    Kohara, Katsuhiko

    2014-10-01

    Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

  1. Increased risk of subclinical atherosclerosis associated with high visceral adiposity index in apparently healthy Korean adults: the Kangbuk Samsung Health Study.

    PubMed

    Park, Hye-Jeong; Kim, Jihyun; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

    2016-09-01

    The visceral adiposity index (VAI) is a mathematical tool that reflects a patient's visceral adiposity and insulin resistance. Recent studies have noted an association between VAI and cardiovascular event. We analyzed the association between VAI and coronary artery calcium score (CACS) in Korean adults. For 33,468 participants (mean age 42 yrs) in a health screening program, VAI was calculated using the following formulae: [waist circumference (WC)/{39.68 + (1.88 * body mass index (BMI))}] * (triglyceride/1.03) * {1.31/high-density lipoprotein cholesterol (HDL-C)} for men and [WC/{36.58 + (1.89 * BMI)}] * (triglyceride/0.81) * (1.52/HDL-C) for women. Coronary artery calcium scores were measured with multi-detector computed tomography. CACS was positively correlated with VAI (r = 0.027, p < 0.001). Subjects with 0 < CACS <100 and CACS ≥ 100 had significantly higher VAI compared to those with CACS = 0 (2.04 ± 1.97, 2.08 ± 1.67 vs. 1.68 ± 1.50, p < 0.001). In logistic regression analyses with CACS >0 as the dependent variable, subjects in the highest tertile of VAI (>1.777) had significantly increased odds ratio for CACS >0 compared to subjects in the lowest tertile (<0.967), even after adjusting for confounding variables, including BMI (OR 1.26, 95% CI 1.147-1.381). Subjects with high VAI had increased risk for subclinical atherosclerosis, as assessed by CACS. Key messages Recent studies have noted an association between visceral adiposity index (VAI) and cardiovascular event. Subjects with coronary artery calcification (CAC) showed significantly higher VAI compared to those without CAC. The subjects with high VAI showed increased odds ratio for CAC as compared to subjects with low VAI, suggesting high VAI reflects increased risk for subclinical atherosclerosis.

  2. Serum Carotenoids Reduce Progression of Early Atherosclerosis in the Carotid Artery Wall among Eastern Finnish Men

    PubMed Central

    Karppi, Jouni; Kurl, Sudhir; Ronkainen, Kimmo; Kauhanen, Jussi; Laukkanen, Jari A.

    2013-01-01

    Background Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids. Methods We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between concentrations of serum carotenoids, and intima-media thickness of the common carotid artery wall was explored in 840 middle-aged men (aged 46–65 years) from Eastern Finland. Ultrasonography of the common carotid arteries were performed at baseline and 7-year follow-up. Serum levels of carotenoids were analyzed at baseline. Changes in mean and maximum intima media thickness of carotid artery wall were related to baseline serum carotenoid levels in covariance analyses adjusted for covariates. Results In a covariance analysis with adjustment for age, ultrasound sonographer, maximum intima media thickness, examination year, body mass index, systolic blood pressure, smoking, physical activity, serum LDL cholesterol, family history of coronary heart disease, antihypertensive medication and serum high sensitivity C-reactive protein, 7-year change in maximum intima media thickness was inversely associated with lycopene (p = 0.005), α-carotene (p = 0.002) and β-carotene (p = 0.019), respectively. Conclusions The present study shows that high serum concentrations of carotenoids may be protective against early atherosclerosis. PMID:23700460

  3. Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.

    PubMed

    Verjans, Johan W; Osborn, Eric A; Ughi, Giovanni J; Calfon Press, Marcella A; Hamidi, Ehsan; Antoniadis, Antonios P; Papafaklis, Michail I; Conrad, Mark F; Libby, Peter; Stone, Peter H; Cambria, Richard P; Tearney, Guillermo J; Jaffer, Farouc A

    2016-09-01

    This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and

  4. Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Opdahl, Anders; Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.; Wu, Colin O.; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Carvalho, Benilton; Edvardsen, Thor; Bluemke, David A.; Lima, Joao A. C.

    2014-01-01

    OBJECTIVE To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model. CONCLUSION Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. PMID:24412444

  5. Matrix metalloproteinases in acute coronary syndromes: current perspectives.

    PubMed

    Kampoli, Anna-Maria; Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Androulakis, Emmanuel; Tsiamis, Eleftherios; Latsios, George; Stefanadis, Christodoulos

    2012-01-01

    Matrix metalloproteinases (MMPs) are a family of zinc metallo-endopeptidases secreted by cells and are responsible for much of the turnover of matrix components. Several studies have shown that MMPs are involved in all stages of the atherosclerotic process, from the initial lesion to plaque rupture. Recent evidence suggests that MMP activity may facilitate atherosclerosis, plaque destabilization, and platelet aggregation. In the heart, matrix metalloproteinases participate in vascular remodeling, plaque instability, and ventricular remodelling after cardiac injury. The aim of the present article is to review the structure, function, regulation of MMPs and to discuss their potential role in the pathogenesis of acute coronary syndromes, as well as their contribution and usefullness in the setting of the disease.

  6. Compensatory enlargement of the left main coronary artery: insights from the PROSPECT study.

    PubMed

    Inaba, Shinji; Mintz, Gary S; Shimizu, Takehisa; Weisz, Giora; Mehran, Roxana; Marso, Steven P; Xu, Ke; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

    2014-03-01

    Glagov proposed that remodeling delayed development of significant coronary artery stenoses until plaque occupied, on average, 40% of arterial area (40% plaque burden). The aim of the current study was to confirm the previously proposed concept of coronary remodeling as first described by Glagov who studied postmortem left main coronary arteries (LMCAs). Using the in-vivo intravascular ultrasound data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, we evaluated 552 LMCAs in 552 patients. External elastic membrane cross-sectional areas (CSAs) increased in proportion to the increase in plaque and media CSAs (r=0.61, P<0.0001), especially when the plaque burden was 20% or lower (r=0.88, P<0.0001). For more advanced atherosclerosis (>40% plaque burden), there was an inverse relationship between lumen CSA and plaque burden (r=-0.57, P<0.0001), whereas this relationship was weak in the presence of less than 40% plaque burden. The frequency of virtual histology derived thin-cap fibroatheroma increased with increasing plaque burden. In contrast, the frequency of pathological intimal thickening decreased. The previously proposed remodeling concept of Glagov was validated in vivo in the PROSPECT study patients. In addition, the present study suggested that plaque phenotype worsened with increasing LMCA plaque growth.

  7. TRIGLYCERIDES, ATHEROSCLEROSIS, AND CARDIOVASCULAR OUTCOME STUDIES: FOCUS ON OMEGA-3 FATTY ACIDS.

    PubMed

    Handelsman, Yehuda; Shapiro, Michael D

    2017-01-01

    To provide an overview of the roles of triglycerides and triglyceride-lowering agents in atherosclerosis in the context of cardiovascular outcomes studies. We reviewed the published literature as well as ClinicalTrials.gov entries for ongoing studies. Despite improved atherosclerotic cardiovascular disease (ASCVD) outcomes with statin therapy, residual risk remains. Epidemiologic data and recent genetic insights provide compelling evidence that triglycerides are in the causal pathway for the development of atherosclerosis, thereby renewing interest in targeting triglycerides to improve ASCVD outcomes. Fibrates, niacin, and omega-3 fatty acids (OM3FAs) are three classes of triglyceride-lowering drugs. Outcome studies with triglyceride-lowering agents have been inconsistent. With regard to OM3FAs, the JELIS study showed that eicosapentaenoic acid (EPA) significantly reduced major coronary events in statin-treated hypercholesterolemic patients. Regarding other agents, extended-release niacin and fenofibrate are no longer recommended as statin add-on therapy (by some guidelines, though not all) because of the lack of convincing evidence from outcome studies. Notably, subgroup analyses from the outcome studies have generated the hypothesis that triglyceride lowering may provide benefit in statin-treated patients with persistent hypertriglyceridemia. Two ongoing OM3FA outcome studies (REDUCE-IT and STRENGTH) are testing this hypothesis in high-risk, statin-treated patients with triglyceride levels of 200 to 500 mg/dL. There is consistent evidence that triglycerides are in the causal pathway of atherosclerosis but inconsistent evidence from cardiovascular outcomes studies as to whether triglyceride-lowering agents reduce cardiovascular risk. Ongoing outcomes studies will determine the role of triglyceride lowering in statin-treated patients with high-dose prescription OM3FAs in terms of improved ASCVD outcomes. AACE = American Association of Clinical Endocrinologists

  8. Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events.

    PubMed

    Miller, P Elliott; Zhao, Di; Frazier-Wood, Alexis C; Michos, Erin D; Averill, Michelle; Sandfort, Veit; Burke, Gregory L; Polak, Joseph F; Lima, Joao A C; Post, Wendy S; Blumenthal, Roger S; Guallar, Eliseo; Martin, Seth S

    2017-02-01

    Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup per day), and regular (≥1 cup per day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome, with coefficients exponentiated to reflect coronary artery calcium progression ratio versus the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup per day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup per day tea drinkers (adjusted hazard ratio 0.71; 95% confidence interval 0.53-0.95). Compared with never coffee drinkers, regular coffee intake (≥1 cup per day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted hazard ratio 0.97; 95% confidence interval 0.78-1.20). Caffeine intake was marginally inversely associated with coronary artery calcium progression. Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake. Published by Elsevier Inc.

  9. Associations between Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events

    PubMed Central

    Miller, P. Elliott; Zhao, Di; Frazier-Wood, Alexis C.; Michos, Erin D.; Averill, Michelle; Sandfort, Veit; Burke, Gregory L.; Polak, Joseph F.; Lima, Joao A.C.; Post, Wendy S.; Blumenthal, Roger S.; Guallar, Eliseo; Martin, Seth S.

    2016-01-01

    Background Coffee and tea are two of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. Methods We examined 6,508 ethnically-diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup/day), and regular (≥1 cup/day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome with coefficients exponentiated to reflect coronary artery calcium progression ratio vs. the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. Results Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup/day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup/day tea drinkers (adjusted HR 0.71; 95% CI 0.53–0.95). Compared to never coffee drinkers, regular coffee intake (≥1 cup/day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted HR 0.97 [0.78, 1.20]). Caffeine intake was marginally inversely associated with coronary artery calcium progression. Conclusions Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake. PMID:27640739

  10. Associations between markers of subclinical atherosclerosis and dietary patterns derived by principal components analysis and reduced rank regression in the Multi-Ethnic Study of Atherosclerosis (MESA)1–3

    PubMed Central

    Nettleton, Jennifer A; Steffen, Lyn M; Schulze, Matthias B; Jenny, Nancy S; Barr, R Graham; Bertoni, Alain G; Jacobs, David R

    2010-01-01

    Background The association between diet and cardiovascular disease (CVD) may be mediated partly through inflammatory processes and reflected by markers of subclinical atherosclerosis. Objective We investigated whether empirically derived dietary patterns are associated with coronary artery calcium (CAC) and common and internal carotid artery intima media thickness (IMT) and whether prior information about inflammatory processes would increase the strength of the associations. Design At baseline, dietary patterns were derived with the use of a food-frequency questionnaire, and inflammatory biomarkers, CAC, and IMT were measured in 5089 participants aged 45–84 y, who had no clinical CVD or diabetes, in the Multi-Ethnic Study of Atherosclerosis. Dietary patterns based on variations in C-reactive protein, interleukin-6, homocysteine, and fibrinogen concentrations were created with reduced rank regression (RRR). Dietary patterns based on variations in food group intake were created with principal components analysis (PCA). Results The primary RRR(RRR 1) and PCA(PCA factor 1) dietary patterns were high in total and saturated fat and low in fiber and micronutrients. However, the food sources of these nutrients differed between the dietary patterns. RRR 1 was positively associated with CAC [Agatston score >0: OR(95% CI) for quartile 5 compared with quartile 1 = 1.34 (1.05, 1.71); ln(Agatston score = 1): P for trend = 0.023] and with common carotid IMT [≥1.0 mm: OR (95% CI) for quartile 5 compared with quartile 1 = 1.33 (0.99, 1.79); ln(common carotid IMT): P for trend = 0.006]. PCA 1 was not associated with CAC or IMT. Conclusion The results suggest that subtle differences in dietary pattern composition, realized by incorporating measures of inflammatory processes, affect associations with markers of subclinical atherosclerosis. PMID:17556701

  11. Receptor activator of nuclear factor kappa β ligand (RANKL) and its relationship to coronary atherosclerosis in HIV patients

    PubMed Central

    Hwang, Janice J.; Wei, Jeffrey; Abbara, Suhny; Grinspoon, Steven K.; Lo, Janet

    2013-01-01

    HIV-infected individuals have an increased prevalence of coronary artery disease (CAD). Receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) have been postulated as mediators of vascular calcification. 78 HIV-infected men and 32 healthy controls without history of CAD were prospectively recruited to undergo cardiac computed tomography (CT) and CT angiography to assess coronary artery calcium and plaque burden. sRANKL was lower in HIV-infected individuals than controls (2.52 [1.08, 3.98] vs. 3.33 [2.44, 4.64] pg/ml, P=0.01, median [IQR] respectively). sRANKL was negatively associated with the number of coronary segments with plaque (Spearman ρ=−0.41, P<0.001) and Agatston calcium score (ρ=−0.30, P<0.01) in HIV-infected individuals even after adjusting for traditional cardiovascular risk factors. PMID:22842843

  12. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study.

    PubMed

    Hoogeveen, Ron C; Gaubatz, John W; Sun, Wensheng; Dodge, Rhiannon C; Crosby, Jacy R; Jiang, Jennifer; Couper, David; Virani, Salim S; Kathiresan, Sekar; Boerwinkle, Eric; Ballantyne, Christie M

    2014-05-01

    To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non-diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21-1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04-2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.

  13. Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep

    PubMed Central

    Volk, Kenneth A.; Roghair, Robert D.; Jung, Felicia; Scholz, Thomas D.; Lamb, Fred S.

    2010-01-01

    Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg·kg−1·day−1 for 48 h) was administered to pregnant ewes at 27–28-day gestation (term 145 days). Coronary arteries were isolated from 1- to 2-wk-old dex-exposed offspring and aged-matched controls. Compared with controls, coronary arteries from dex-exposed lambs demonstrated enhanced vasoconstriction to endothelin-1 and ACh that was abolished by endothelial removal or preincubation with the nitric oxide synthase inhibitor l-NNA, membrane-permeable superoxide dismutase + catalase, or apamin + charybdotoxin, but not indomethacin. The rate of coronary vascular smooth muscle cell (VSMC) proliferation was also significantly greater in dex-exposed lambs. Protein levels of the proliferating cell nuclear antigen were increased and α-smooth muscle actin decreased in dex-exposed coronary VSMC, consistent with a proliferative state. Finally, expression of the NADPH oxidase Nox 4, but not Nox 1, mRNA was also decreased in coronary VSMC from dex-exposed lambs. These findings suggest an important interaction exists between early-gestation glucocorticoid exposure and reactive oxygen species that is associated with alterations in endothelial function and coronary VSMC proliferation. These changes in coronary physiology are consistent with those associated with the development of atherosclerosis and may provide an important link between an adverse intrauterine environment and increased risk for coronary artery disease. PMID:20335378

  14. Animal Models of Atherosclerosis

    PubMed Central

    Getz, Godfrey S.; Reardon, Catherine A.

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

  15. Coronary changes in the Atlantic salmon Salmo salar L: characterization and impact of dietary fatty acid compositions.

    PubMed

    Dalum, A; Tangen, R; Falk, K; Hordvik, I; Rosenlund, G; Torstensen, B; Koppang, E O

    2016-01-01

    Consumption of fatty acids from fishes is widely regarded as beneficial for preventing cardiovascular disorders. Nevertheless, salmonids themselves are victims of vascular diseases. As the pathogenesis and nature of these changes are elusive, they are here addressed using novel morphological and transcriptional approaches. Coronary arteries of wild Atlantic salmon Salmo salar L., (n = 12) were investigated using histological and immunohistochemical techniques, and RT-qPCR was employed to investigate expression of stretch-induced genes. In an experimental trial, fish were fed diets with different fatty acids composition, and histological features of the coronary arteries (n = 36) were investigated. In addition, the heart fatty acid profile (n = 60) was analysed. There were no differences in morphological or immunological features between wild fish and groups of experimental fish. Arteriosclerotic lesions consisted of smooth muscle cells in dissimilar differential stages embedded in considerable amounts of extracellular matrix in a similar fashion to what is seen in early stages of human atherosclerosis. No fat accumulations were observed, and very few inflammatory cells were present. In affected arteries, there was an induction of stretch-related genes, pointing to a stress-related response. We suggest that salmon may have a natural resistance to developing atherosclerosis, which corresponds well with their high investment in lipid metabolism. © 2014 John Wiley & Sons Ltd.

  16. Associations of Job Strain and Occupation with Subclinical Atherosclerosis: the CARDIA Study

    PubMed Central

    Greenlund, Kurt J.; Kiefe, Catarina I.; Giles, Wayne H.; Liu, Kiang

    2010-01-01

    Purpose Although occupational factors have been associated with symptomatic ischemic heart disease, associations between job strain (low decision latitude and high psychological demands) and risk for subclinical atherosclerosis measured by coronary artery calcium (CAC) has not been assessed. Methods CAC was measured in 3,695 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study in 2000-01 and 2005-06. Job characteristics measured by the demand-control model (psychological demands and decision latitude) were assessed in 1987-88 and in 1995-96. Associations between non-zero CAC and prior job characteristics and occupation were assessed, adjusting for potential covariates. Results Low decision latitude, high psychological demands, and job strain at either earlier exam were not associated with a positive CAC, nor were changes in the status of these job characteristics between 1987/1988 and 1995/1996. However, participants whose jobs were classified as managerial or professional in 1995/1996 were less likely to have a positive CAC than those in laborer occupations. Conclusions Job strain measured at two earlier time points was not related to the presence of CAC at follow-up 5 to 18 years later. The association between earlier occupation and CAC may reflect socioeconomic differences or other occupational, industrial, or labor market characteristics. PMID:20382332

  17. Associations of job strain and occupation with subclinical atherosclerosis: The CARDIA Study.

    PubMed

    Greenlund, Kurt J; Kiefe, Catarina I; Giles, Wayne H; Liu, Kiang

    2010-05-01

    Although occupational factors have been associated with symptomatic ischemic heart disease, associations between job strain (low decision latitude and high psychological demands) and risk for subclinical atherosclerosis measured by coronary artery calcium (CAC) have not been assessed. CAC was measured in 3695 participants in the Coronary Artery Risk Development in Young Adults study in 2000 to 2001 and 2005 to 2006. Job characteristics measured by the demand-control model (psychological demands and decision latitude) were assessed in 1987 to 1988 and in 1995 to 1996. Associations between non-zero CAC and previous job characteristics and occupation were assessed, adjusting for potential covariates. Low decision latitude, high psychological demands, and job strain at either earlier examination were not associated with a positive CAC, nor were changes in the status of these job characteristics between 1987/1988 and 1995/1996. However, participants whose jobs were classified as managerial or professional in 1995/1996 were less likely to have a positive CAC than those in laborer occupations. Job strain measured at two earlier time points was not related to the presence of CAC at follow-up 5 to 18 years later. The association between earlier occupation and CAC may reflect socioeconomic differences or other occupational, industrial, or labor market characteristics. Published by Elsevier Inc.

  18. The metabolic syndrome, diabetes, and subclinical atherosclerosis assessed by coronary calcium.

    PubMed

    Wong, Nathan D; Sciammarella, Maria G; Polk, Donna; Gallagher, Amy; Miranda-Peats, Lisa; Whitcomb, Brian; Hachamovitch, Rory; Friedman, John D; Hayes, Sean; Berman, Daniel S

    2003-05-07

    We compared the prevalence and extent of coronary artery calcium (CAC) among persons with the metabolic syndrome (MetS), diabetes, and neither condition. The prevalence and extent of CAC has not been compared among those with MetS, diabetes, or neither condition. Of 1,823 persons (36% female) age 20 to 79 years who had screening for CAC by computed tomography, 279 had MetS, 150 had diabetes, and the remainder (n = 1,394) had neither condition. Metabolic syndrome was defined with >or=3 of the following: body mass index >or=30 kg/m(2); high-density lipoprotein cholesterol <40 mg/dl if male or <50 mg/dl if female; triglycerides >or=150 mg/dl; blood pressure >or=130/85 mm Hg or on treatment; or fasting glucose 110 to 125 mg/dl. The prevalence and odds of any and significant (>or=75th percentile) CAC among these groups and by number of MetS risk factors were determined. Those with neither MetS nor diabetes, MetS, or diabetes had a prevalence of CAC of 53.5%, 58.8%, and 75.3% (p < 0.001), respectively, among men and 37.6%, 50.8%, and 52.6% (p < 0.001), respectively, among women. Coronary artery calcium increased by the number (0 to 5) of MetS risk factors (from 34.0% to 58.3%) (p < 0.001). Forty-one percent of subjects with MetS had either a >20% 10-year risk of CHD or CAC >or=75th percentile for age and gender. Risk factor-adjusted odds for the presence of CAC were 1.40 (95% confidence interval [CI] 1.05 to 1.87) among those with MetS and 1.67 (95% CI 1.12 to 2.50) among those with diabetes, versus those with neither condition. Those with MetS or diabetes have an increased likelihood of CAC compared with those having neither condition.

  19. Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

    PubMed

    Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

    2009-02-01

    Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

  20. Vasostatin-2 inhibits cell proliferation and adhesion in vascular smooth muscle cells, which are associated with the progression of atherosclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hou, Jianghong, E-mail: jianghonghou@163.com; Xue, Xiaolin; Li, Junnong

    2016-01-22

    Recently, the serum expression level of vasostatin-2 was found to be reduced and is being studied as an important indicator to assess the presence and severity of coronary artery disease; the functional properties of vasostatin-2 and its relationship with the development of atherosclerosis remains unclear. In this study, we attempted to detect the expression of vasostatin-2 and its impact on human vascular smooth muscle cells (VSMCs). Quantitative real-time PCR (qRT-PCR) and western blot were used to assess the expression level of vasostatin-2 in VSMCs between those from atherosclerosis and disease-free donors; we found that vasostatin-2 was significantly down-regulated in atherosclerosismore » patient tissues and cell lines. In addition, the over-expression of vasostatin-2 apparently inhibits cell proliferation and migration in VSMCs. Gain-of-function in vitro experiments further show that vasostatin-2 over-expression significantly inhibits inflammatory cytokines release in VSMCs. In addition, cell adhesion experimental analysis showed that soluble adhesion molecules (sICAM-1, sVCAM-1) had decreased expression when vasostatin-2 was over-expressed in VSMCs. Therefore, our results indicate that vasostatin-2 is an atherosclerosis-related factor that can inhibit cell proliferation, inflammatory response and cell adhesion in VSMCs. Taken together, our results indicate that vasostatin-2 could serve as a potential diagnostic biomarker and therapeutic option for human atherosclerosis in the near future. - Highlights: • Vasostatin-2 levels were down-regulated in atherosclerosis patient tissues and VSMCs. • Ectopic expression of vasostatin-2 directly affects cell proliferation and migration in vitro. • Ectopic expression of vasostatin-2 protein affects pro-inflammatory cytokines release in VSMCs. • Ectopic expression of vasostatin-2 protein affects cell adhesion in VSMCs.« less

  1. Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard.

    PubMed

    Firoozabadi, Mehdi Dehghani; Sheikhi, Mohammad Ali; Rahmani, Hossein; Ebadi, Ahmad; Heidari, Amanollah; Gholizadeh, Behnam; Sharifi, Khosrow

    2017-10-01

    Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

  2. Predicting risk of coronary events and all-cause mortality: role of B-type natriuretic peptide above traditional risk factors and coronary artery calcium scoring in the general population: the Heinz Nixdorf Recall Study.

    PubMed

    Kara, Kaffer; Mahabadi, Amir A; Berg, Marie H; Lehmann, Nils; Möhlenkamp, Stefan; Kälsch, Hagen; Bauer, Marcus; Moebus, Susanne; Dragano, Nico; Jöckel, Karl-Heinz; Neumann, Till; Erbel, Raimund

    2014-09-01

    Several biomarkers including B-type natriuretic peptide (BNP) have been suggested to improve prediction of coronary events and all-cause mortality. Moreover, coronary artery calcium (CAC) as marker of subclinical atherosclerosis is a strong predictor for cardiovascular mortality and morbidity. We aimed to evaluate the predictive ability of BNP and CAC for all-cause mortality and coronary events above traditional cardiovascular risk factors (TRF) in the general population. We followed 3782 participants of the population-based Heinz Nixdorf Recall cohort study without coronary artery disease at baseline for 7.3 ± 1.3 years. Associations of BNP and CAC with incident coronary events and all-cause mortality were assessed using Cox regression, Harrell's c, and time-dependent integrated discrimination improvement (IDI(t), increase in explained variance). Subjects with high BNP levels had increased frequency of coronary events and death (coronary events/mortality: 14.1/28.2% for BNP ≥100 pg/ml vs. 2.7/5.5% for BNP < 100 pg/ml, respectively). Subjects with a BNP ≥100 pg/ml had increased incidence of hard endpoints sustaining adjustment for CAC and TRF (for coronary events: hazard ratio (HR) (95% confidence interval (CI)) 3.41(1.78-6.53); for all-cause mortality: HR 3.35(2.15-5.23)). Adding BNP to TRF and CAC increased measures of predictive ability: coronary events (Harrell's c, for coronary events, 0.775-0.784, p = 0.09; for all-cause mortality 0.733-0.740, p = 0.04; and IDI(t) (95% CI), for coronary events: 2.79% (0.33-5.65%) and for all-cause mortality 1.78% (0.73-3.10%). Elevated levels of BNP are associated with excess incident coronary events and all-cause mortality rates, with BNP and CAC significantly and complementary improving prediction of risk in the general population above TRF. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. Possible roles of platelet-derived microparticles in atherosclerosis.

    PubMed

    Wang, Zhi-Ting; Wang, Zi; Hu, Yan-Wei

    2016-05-01

    Platelets and platelet-derived microparticles (PMPs) play important roles in cardiovascular diseases, especially atherosclerosis. Continued research has revealed that PMPs have numerous functions in atherosclerosis, not only in thrombosis formation, but also by induction of inflammation. PMPs also induce formation of foam cells. Recent evidence strongly indicates a significant role of PMPs in atherosclerosis. Here, current research on the function of PMPs in atherosclerosis is reviewed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Effect of rosuvastatin on coronary atheroma in stable coronary artery disease: multicenter coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS).

    PubMed

    Takayama, Tadateru; Hiro, Takafumi; Yamagishi, Masakazu; Daida, Hiroyuki; Hirayama, Atsushi; Saito, Satoshi; Yamaguchi, Tetsu; Matsuzaki, Masunori

    2009-11-01

    It has been suggested that intensive lipid-lowering therapy using statins significantly decreases atheromatous plaque volume. The effect of rosuvastatin on plaque volume in patients with stable coronary artery disease (CAD), including those receiving prior lipid-lowering therapy, was examined in the present study. A 76-week open-label trial was performed at 37 centers in Japan. Eligible patients began treatment with rosuvastatin 2.5 mg/day, which could be increased at 4-week intervals to coronary plaque volume in Japanese patients with stable CAD, including those who had previously used other lipid-lowering drugs. Rosuvastatin might be useful in the setting of secondary prevention in patients with stable CAD.

  5. Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2.

    PubMed

    Zhang, Tao; Tian, Feng; Wang, Jing; Jing, Jing; Zhou, Shan-Shan; Chen, Yun-Dai

    2015-01-01

    Endothelial cell injury and subsequent apoptosis play a key role in the development and pathogenesis of atherosclerosis, which is hallmarked by dysregulated lipid homeostasis, aberrant immunity and inflammation, and plaque-instability-associated coronary occlusion. Nevertheless, our understanding of the mechanisms underlying endothelial cell apoptosis is still limited. MicroRNA-429 (miR-29) is a known cancer suppressor that promotes cancer cell apoptosis. However, it is unknown whether miR-429 may be involved in the development of atherosclerosis through similar mechanisms. We addressed these questions in the current study. We examined the levels of endothelial cell apoptosis in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of anti-apoptotic protein Bcl-2 and the levels of miR-429 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-429 and 3'-UTR of Bcl-2 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-429 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. HFD mice had significantly lower percentage of endothelial cells and significantly higher percentage of mesenchymal cells in the aorta than NOR mice. Significantly higher levels of endothelial cell apoptosis were detected in HFD mice, resulting from decreases in Bcl-2 protein, but not mRNA. The decreases in Bcl-2 in endothelial cells were due to increased levels of miR-429, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Atherosclerosis-associated endothelial cell apoptosis may result from down

  6. Coffee Consumption and Coronary Artery Calcium Score: Cross-Sectional Results of ELSA-Brasil (Brazilian Longitudinal Study of Adult Health).

    PubMed

    Miranda, Andreia M; Steluti, Josiane; Goulart, Alessandra C; Benseñor, Isabela M; Lotufo, Paulo A; Marchioni, Dirce M

    2018-03-24

    Available evidence for the relationship between coffee intake and subclinical atherosclerosis is limited and inconsistent. This study aimed to evaluate the association between coffee consumption and coronary artery calcium (CAC) in ELSA-Brasil (Brazilian Longitudinal Study of Adult Health). This cross-sectional study is based on baseline data from participants of the ELSA-Brasil cohort. Only participants living in São Paulo, Brazil, who underwent a CAC measurement (n=4426) were included. Coffee consumption was collected using a food frequency questionnaire. CAC was detected with computed tomography and expressed as Agatston units. CAC was further categorized as an Agatson score ≥100 (CAC ≥100). In multiple logistic regression analysis considering intake of coffee and smoking status interaction, significant inverse associations were observed between coffee consumption (>3 cups/d) and CAC≥100 (odds ratio [OR]: 0.85 [95% confidence interval, 0.58-1.24] for ≤1 cup/d; OR: 0.73 [95% confidence interval, 0.51-1.05] for 1-3 cups/d; OR: 0.33 [95% confidence interval, 0.17-0.65] for >3 cups/d). Moreover, there was a statistically significant interaction effect for coffee consumption and smoking status ( P =0.028 for interaction). After stratification by smoking status, the analysis revealed a lower OR of coronary calcification in never smokers drinking >3 cups/d (OR: 0.37 [95% confidence interval, 0.15-0.91]), whereas among current and former smokers, the intake of coffee was not significantly associated with coronary calcification. Habitual consumption of >3 cups/d of coffee decreased odds of subclinical atherosclerosis among never smokers. The consumption of coffee could exert a potential beneficial effect against coronary calcification, particularly in nonsmokers. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. High prevalence of subclinical atherosclerosis in Brazilian postmenopausal women with low and intermediate risk by Framingham score.

    PubMed

    Petisco, Ana Claudia Gomes Pereira; Assef, Jorge Eduardo; de Jesus, Carlos Alberto; Saleh, Mohamed Hassan; Barbosa, Jose Eduardo Martins; Costa de Souza Le Bihan, David; Pinto, Ibraim Masciarelli França; Rolim Fernandes Fontes Pedra, Simone; Barretto, Rodrigo Bellio de Mattos; Sousa, Amanda Guerra de Moraes Rego

    2017-03-01

    Cardiovascular diseases are the leading cause of mortality among women in several countries. Early detection of subclinical atherosclerosis (SA) could enable the adoption of preventive measures to avoid cardiovascular events. This study aimed to determine the prevalence of SA in Brazilian asymptomatic postmenopausal women in Framingham Risk Score (FRS) low and intermediate groups. Computed tomography (CT) and ultrasound (US) scans were performed in 138 asymptomatic postmenopausal women (56.1 ± 4.9 years of age) to survey for coronary artery and aortic calcification (CT scan) and assess carotid intima-media thickness (CIMT) and identify carotid plaques (US). The mean FRS was 2.64 ± 2.13 %. The prevalence of increased CIMT, carotid plaques, increased CIMT and/or plaques, coronary artery calcification (CAC) >0 and aortic calcification (AC) were, respectively, 45.7, 37.7, 62.3, 23.9 and 45.7 %. Normal imaging tests were found in 22.4 %. SA, defined as at least one abnormal imaging test, was associated with age, FRS, waist-to-rip ratio, systolic and diastolic blood pressure, HDL-c and ApoA1 levels, and ApoA1/ApoB ratio. In logistic regression, SA was associated with higher age (OR 1.108, 95 % CI 1.010-1.215, p = 0.029) and lower ApoA1 levels (OR 0.979, 95 % CI 0.960-0.998, p = 0.029). SA was prevalent in Brazilian postmenopausal women with low and intermediate risk groups (FRS) and was associated with higher age and lower levels of ApoA1. Carotid atherosclerosis was the most common presentation of SA in this group.

  8. Ca2+ regulatory mechanisms of exercise protection against coronary artery disease in metabolic syndrome and diabetes.

    PubMed

    Sturek, Michael

    2011-08-01

    Chronic exercise attenuates coronary artery disease (CAD) in humans largely independent of reductions in risk factors; thus major protective mechanisms of exercise are directly within the coronary vasculature. Further, tight control of diabetes, e.g., blood glucose, can be detrimental. Accordingly, knowledge of mechanisms by which exercise attenuates diabetic CAD could catalyze development of molecular therapies. Exercise attenuates CAD (atherosclerosis) and restenosis in miniature swine models, which enable precise control of exercise parameters (intensity, duration, and frequency) and characterization of the metabolic syndrome (MetS) and diabetic milieu. Intracellular Ca(2+) is a pivotal second messenger for coronary smooth muscle (CSM) excitation-contraction and excitation-transcription coupling that modulates CSM proliferation, migration, and calcification. CSM of diabetic dyslipidemic Yucatan swine have impaired Ca(2+) extrusion via the plasmalemma Ca(2+) ATPase (PMCA), downregulation of L-type voltage-gated Ca(2+) channels (VGCC), increased Ca(2+) sequestration by the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA), increased nuclear Ca(2+) localization, and greater activation of K channels by Ca(2+) release from the SR. Endurance exercise training prevents Ca(2+) transport changes with virtually no effect on the diabetic milieu (glucose, lipids). In MetS Ossabaw swine transient receptor potential canonical (TRPC) channels are upregulated and exercise training reverses expression and TRPC-mediated Ca(2+) influx with almost no change in the MetS milieu. Overall, exercise effects on Ca(2+) signaling modulate CSM phenotype. Future studies should 1) selectively target key Ca(2+) transporters to determine definitively their causal role in atherosclerosis and 2) combine mechanistic studies with clinical outcomes, e.g., reduction of myocardial infarction.

  9. Impaired coronary flow reserve in patients with metabolic syndrome.

    PubMed

    Pirat, Bahar; Bozbas, Huseyin; Simsek, Vahide; Yildirir, Aylin; Sade, L Elif; Gursoy, Yusuf; Altin, Cihan; Atar, Ilyas; Muderrisoglu, Haldun

    2008-11-01

    Metabolic syndrome (MetS) is a strong predictor of cardiovascular events. Coronary flow reserve (CFR), as determined by transthoracic echocardiography, is an indicator of microvascular function. In this study, we sought to determine whether CFR is impaired in patients with MetS without clinical coronary heart disease. Thirty-three patients with MetS (mean age, 67+/-8 years) and 35 age- and sex-matched controls were studied prospectively. Transthoracic two-dimensional and Doppler echocardiography was performed on all patients. Baseline and hyperemic (after dipyridamole infusion) coronary flow rates were measured using pulsed Doppler echocardiography. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. There was no difference with regard to baseline systolic and diastolic coronary flow rates in patients with MetS compared with control subjects (19.9+/-3.1cm/s vs. 19.7+/-2.9cm/s, P>.05; and 27.7+/-4.2cm/s vs. 27.1+/-3.6cm/s, P>.05, respectively). Hyperemic diastolic flow and CFR were significantly lower in patients with MetS than in controls (61.7+/-9.4cm/s vs. 70.2+/-9.2cm/s, P<.0001; and 2.2+/-0.5 vs. 2.6+/-0.4, P=.001, respectively). In a logistic regression analysis that included age, sex, body mass index, hypertension, and dyslipidemia and MetS, MetS was the only predictor of a CFR<2.5 (P=.007, OR=6.1, 95% CI: 1.6-23.3). In conclusion, CFR is impaired in patients with MetS suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is present in this patient population. Metabolic syndrome is associated with a CFR<2.5.

  10. Combining OCT and a fluorescence intensity imaging method for atherosclerosis detection

    NASA Astrophysics Data System (ADS)

    Liang, Shanshan; Saidi, Arya; Jing, Joe; Liu, Gangjun; Yin, Jiechen; Narula, Jagat; Chen, Zhongping

    2012-02-01

    Coronary heart disease (like myocardial infarction) is caused by atherosclerosis. It cause over 30% of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. To diagnose this atherosclerosis before it gets rupture is the most effect way to increase the chance of survival for patients who suffer from this disease. The crucial tusk is how to find out vulnerable plaques. In resent years optical coherence tomography (OCT) has become a very useful tool for intravascular imaging, since it has high axial and transverse resolution. OCT can tell the detail structure inside the plaque like the thickness of plaque cap which is an important factor to identify vulnerable plaques. But we still need to find out the biochemical characteristics that is unique for vulnerable plaques (like inflammation). Fluorescence molecular imaging is a standard way to exam the biochemical property of biological samples. So we integrate these two techniques together into one probe. Our probe is comprised of a double-clad fiber (DCF) and a grin lens, and rotates with a micro mirror in front. The single-mode inner core of the DCF transmits both OCT and fluorescence excitation light, and the multimode inner cladding is used to detect fluorescence signal. In vitro result shows that this is a possible way for more accurate diagnose of vulnerable plaques.

  11. IQ in childhood and atherosclerosis in middle-age: 40 Year follow-up of the Newcastle Thousand Families Cohort Study.

    PubMed

    Roberts, Beverly A; Batty, G David; Gale, Catharine R; Deary, Ian J; Parker, Louise; Pearce, Mark S

    2013-12-01

    Carotid intima-media thickness (IMT) is a known precursor to coronary heart disease (CHD) and other relevant health outcomes such as stroke and cognitive impairment. In addition, higher childhood intelligence has been associated with lower risk of coronary heart disease events in later life, although the mechanisms of effect are unclear. We therefore examined the association between childhood intelligence and atherosclerosis using carotid IMT as a marker of the atherosclerotic process. Participants were 412 members of the Newcastle Thousand Families Study, a prospective cohort study of all 1142 births in the city of Newcastle in May and June 1947, who took an IQ test and English and arithmetic tests at age 11 years. Study members participated in a medical examination and lifestyle assessment at age 49-51 years during which IMT was measured using ultrasound techniques. Individuals with higher childhood IQ score had a lower mean IMT in middle-age. A standard deviation higher score in childhood overall IQ was associated with a 0.053 mm (95% CI -0.102, -0.004) lower IMT in men and a 0.039 mm (95% CI -0.080, -0.002) lower IMT in women. Similar levels of association were found for the English and arithmetic tests. After adjustment for a range of covariates including education, the size of effect was undiminished in men but increased in women. In the present study, higher childhood IQ scores were associated with a lower degree of atherosclerosis by middle-age. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

    PubMed Central

    Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

    2007-01-01

    Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

  13. Non-calcified coronary plaque volume inversely related to CD4 count in HIV infection

    PubMed Central

    Duarte, Horacio; Matta, Jatin R.; Muldoon, Nancy; Masur, Henry; Hadigan, Colleen; Gharib, Ahmed M.

    2013-01-01

    Background Non-calcified coronary artery plaque (NCAP) may be an important predictor of cardiovascular events, however, few studies have directly measured NCAP in HIV-infected individuals. Methods We completed a prospective cross-sectional evaluation of NCAP and coronary calcium scores using CT angiography in HIV-infected subjects (n=26) without known coronary artery disease (CAD), but who had one or more CAD risk factor and compared them to controls matched on age, race, sex, body mass index and Framingham risk score (n=26). Results There was no difference in coronary calcium scores (114 ± 218 vs. 124 ± 298 p=0.89) or NCAP volume (65 ± 86 mm3 vs. 63 ± 82 mm3, p=0.38) between HIV-infected subjects and controls, respectively. Among HIV-infected subjects, lower CD4 count was associated with increased NCAP volume (r=-0.52, p=0.006). CD4 count remained a significant predictor of NCAP in a multivariate analysis that adjusted for age and duration of antiretroviral therapy. Conclusion Plaque burden is similar between HIV-infected and uninfected individuals when matched on traditional CAD risk factors, however immune function may mediate the development of atherosclerosis in HIV infection. PMID:22293714

  14. Computational modelling of atherosclerosis.

    PubMed

    Parton, Andrew; McGilligan, Victoria; O'Kane, Maurice; Baldrick, Francina R; Watterson, Steven

    2016-07-01

    Atherosclerosis is one of the principle pathologies of cardiovascular disease with blood cholesterol a significant risk factor. The World Health Organization estimates that approximately 2.5 million deaths occur annually because of the risk from elevated cholesterol, with 39% of adults worldwide at future risk. Atherosclerosis emerges from the combination of many dynamical factors, including haemodynamics, endothelial damage, innate immunity and sterol biochemistry. Despite its significance to public health, the dynamics that drive atherosclerosis remain poorly understood. As a disease that depends on multiple factors operating on different length scales, the natural framework to apply to atherosclerosis is mathematical and computational modelling. A computational model provides an integrated description of the disease and serves as an in silico experimental system from which we can learn about the disease and develop therapeutic hypotheses. Although the work completed in this area to date has been limited, there are clear signs that interest is growing and that a nascent field is establishing itself. This article discusses the current state of modelling in this area, bringing together many recent results for the first time. We review the work that has been done, discuss its scope and highlight the gaps in our understanding that could yield future opportunities. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Sex differences in the combined effect of chronic stress with impaired vascular endothelium functioning and the development of early atherosclerosis: The Cardiovascular Risk in Young Finns study

    PubMed Central

    2010-01-01

    Background The syndrome of vital exhaustion (VE), characterized by fatigue and irritability, may contribute to an increased risk of atherosclerosis. The aim of the study was to explore sex differences in the interactions of VE with endothelial dysfunction and VE with reduced carotid elasticity, the important contributors to the development of early atherosclerosis, on preclinical atherosclerosis. Methods The participants were 1002 women and 719 men aged 24-39 examined in the Cardiovascular Risk in Young Finns study. Vital exhaustion was measured using the Maastricht Questionnaire. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT), endothelial function was measured by brachial flow-mediated dilatation (FMD), and arterial elasticity by carotid artery compliance (CAC) using ultrasound techniques. Results We found a significant CAC x VE interaction for IMT only for the men. Our results imply that high VE level significantly related to high IMT levels among the men with low CAC, but not among the women with low CAC or among the women or men with high CAC. No significant FMD x VE interactions for IMT for the women or men were found. Conclusions High VE may exert an effect on IMT for men with impaired arterial elasticity. The results suggest that high vitally exhausted men with reduced arterial elasticity are at increased risk of atherosclerosis in early life and imply men's decreased stress coping in relation to stressful psychological coronary risk factors. PMID:20624297

  16. Optimal ECG (Electrocardiogram) Electrode Sites and Criteria for Detection of Asymptomatic Coronary Artery Disease at Rest and with Exercise.

    DTIC Science & Technology

    1985-12-01

    a healthy coronary artery can increase flow ninefold by dilating during peak workloads. By preventing dilation , circum- ferential atherosclerosis...Ischemic Canine Myocardium, J. Electrocardiol. 15(4):335, 1982. 127. Burgess, M.J., Green, L.S., Millar, K., Wyatt, R., and Abildskov, J.A.: The...Refractory Periods of Ischemic Canine Ventricular Myocardium, J. Electrocardiol. 15(1):I, 1982. 129. Burgess, M.J., Lux, R.L., Wyatt, R.F., and Abildskov, J.A

  17. Relationship of pericardial fat with lipoprotein distribution: The Multi-Ethnic study of atherosclerosis.

    PubMed

    Ong, Kwok-Leung; Ding, Jingzhong; McClelland, Robyn L; Cheung, Bernard M Y; Criqui, Michael H; Barter, Philip J; Rye, Kerry-Anne; Allison, Matthew A

    2015-08-01

    Pericardial fat and lipoprotein abnormalities contribute to increased risk of cardiovascular disease (CVD). We investigated the relationship between pericardial fat volume and lipoprotein distribution, and whether the association of pericardial fat volume with subclinical atherosclerosis and incident CVD events differs according to lipoprotein distribution. We analyzed data from 5407 participants from the Multi-Ethnic Study of Atherosclerosis who had measurements of pericardial fat volume, lipoprotein distribution, carotid intima-media thickness (IMT), and coronary artery calcium (CAC). All participants were free of clinically apparent CVD at baseline. Incident CVD was defined as any adjudicated CVD event. After adjusting for demographic factors, traditional risk factors, and biomarkers of inflammation and hemostasis, a larger pericardial fat volume was associated with higher large VLDL particle (VLDL-P) concentration and small HDL particle (HDL-P) concentration, and smaller HDL-P size (regression coefficients = 0.585 nmol/L, 0.366 μmol/L, and -0.025 nm per SD increase in pericardial fat volume respectively, all P < 0.05). The association of pericardial fat volume with large VLDL-P concentration and HDL-P size, but not small HDL-P concentration, remained significant after further adjusting for each other as well as LDL cholesterol, HDL cholesterol, and triglycerides. The relationship of pericardial fat volume with incident CVD events, carotid IMT, and prevalence and severity of CAC did not differ by quartiles of large VLDL-P concentration, small HDL-P concentration, or HDL-P size (P for interaction>0.05). Pericardial fat is associated with atherogenic lipoprotein abnormalities. However, its relationship with subclinical atherosclerosis and incident CVD events does not differ according to lipoprotein distribution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Computed tomography-based diagnosis of diffuse compensatory enlargement of coronary arteries using scaling power laws.

    PubMed

    Huo, Yunlong; Choy, Jenny Susana; Wischgoll, Thomas; Luo, Tong; Teague, Shawn D; Bhatt, Deepak L; Kassab, Ghassan S

    2013-04-06

    Glagov's positive remodelling in the early stages of coronary atherosclerosis often results in plaque rupture and acute events. Because positive remodelling is generally diffused along the epicardial coronary arterial tree, it is difficult to diagnose non-invasively. Hence, the objective of the study is to assess the use of scaling power law for the diagnosis of positive remodelling of coronary arteries based on computed tomography (CT) images. Epicardial coronary arterial trees were reconstructed from CT scans of six Ossabaw pigs fed on a high-fat, high-cholesterol, atherogenic diet for eight months as well as the same number of body-weight-matched farm pigs fed on a lean chow (101.9±16.1 versus 91.5±13.1 kg). The high-fat diet Ossabaw pig model showed diffuse positive remodelling of epicardial coronary arteries. Good fit of measured coronary data to the length-volume scaling power law ( where L(c) and V(c) are crown length and volume) were found for both the high-fat and control groups (R(2) = 0.95±0.04 and 0.99±0.01, respectively). The coefficient, K(LV), decreased significantly in the high-fat diet group when compared with the control (14.6±2.6 versus 40.9±5.6). The flow-length scaling power law, however, was nearly unaffected by the positive remodelling. The length-volume and flow-length scaling power laws were preserved in epicardial coronary arterial trees after positive remodelling. K(LV) < 18 in the length-volume scaling relation is a good index of positive remodelling of coronary arteries. These findings provide a clinical rationale for simple, accurate and non-invasive diagnosis of positive remodelling of coronary arteries, using conventional CT scans.

  19. Coronary Computed Tomography Angiography for Screening in Patients with Diabetes: Can Enhanced Detection of Subclinical Coronary Atherosclerosis Improve Outcome?

    PubMed

    Muhlestein, Joseph Brent; Moreno, Fidela Ll

    2016-11-01

    It is well known that there is a very high risk of cardiovascular complications among diabetic patients. In spite of all efforts at aggressive control of diabetes and its complications, the incidence of cardiovascular morbidity and mortality remains high, including in patients with no prior symptoms, underscoring a possible advantage for appropriate screening of asymptomatic patients for the presence of obstructive coronary artery disease (CAD). In this article, we sought primarily to review the results of studies designed to evaluate a possible role of coronary computed tomography angiography (CCTA) in the screening of asymptomatic diabetic patients for possible obstructive CAD. Our review of current literature indicates that there is still no method of CAD screening identified that has been shown to reduce the cardiovascular risk of asymptomatic diabetic patients. Therefore, the utility and value of screening for CAD in asymptomatic diabetic patients remains controversial. CCTA screening has shown promise and has been demonstrated to predict future risk, but as yet has not demonstrated improvement in the outcomes of these high-risk patients. At our present state of knowledge, aggressive risk factor reduction appears to be the most important primary prevention strategy for all asymptomatic high-risk diabetic patients. However, there remains a great need for better and more sensitive and specific screening methods, as well as more effective treatments that may allow us to more accurately target diabetic patients who really are at high risk. Further large randomized and well-controlled clinical trials may be necessary to determine whether screening for CAD can reduce cardiovascular event rates in patients with diabetes.

  20. Pediatric Origins of Nephrolithiasis-Associated Atherosclerosis.

    PubMed

    Kusumi, Kirsten; Smith, Sally; Barr-Beare, Evan; Saxena, Vijay; Schober, Megan S; Moore-Clingenpeel, Melissa; Schwaderer, Andrew L

    2015-11-01

    To determine if nephrolithiasis-associated atherosclerosis has pediatric origins and to consider possible association between kidney stones and atherosclerosis-related proteins. We matched children aged 12-17 years with kidney stones and without kidney stones. Carotid artery intima-media thickness (cIMT) was measured by ultrasound. Participants' urine was investigated by enzyme-linked immunosorbent assay for the atherosclerosis-related proteins fibronectin 1, macrophage scavenger receptor 1, osteopontin, and vascular cell adhesion molecule 1 levels, and normalized to urine creatinine levels. Subjects with nephrolithiasis had higher cIMT in the right common carotid artery and overall mean measurement. Urine osteopontin and fibronectin 1 were significant predictors of cIMT. We have provided initial preliminary evidence that nephrolithiasis-associated atherosclerosis has pediatric origins and performed studies that begin to identify potential reasons for the association of nephrolithiasis and vascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.