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Sample records for coronary atherosclerosis illness

  1. Pathway analysis of coronary atherosclerosis.

    PubMed

    King, Jennifer Y; Ferrara, Rossella; Tabibiazar, Raymond; Spin, Joshua M; Chen, Mary M; Kuchinsky, Allan; Vailaya, Aditya; Kincaid, Robert; Tsalenko, Anya; Deng, David Xing-Fei; Connolly, Andrew; Zhang, Peng; Yang, Eugene; Watt, Clifton; Yakhini, Zohar; Ben-Dor, Amir; Adler, Annette; Bruhn, Laurakay; Tsao, Philip; Quertermous, Thomas; Ashley, Euan A

    2005-09-21

    Large-scale gene expression studies provide significant insight into genes differentially regulated in disease processes such as cancer. However, these investigations offer limited understanding of multisystem, multicellular diseases such as atherosclerosis. A systems biology approach that accounts for gene interactions, incorporates nontranscriptionally regulated genes, and integrates prior knowledge offers many advantages. We performed a comprehensive gene level assessment of coronary atherosclerosis using 51 coronary artery segments isolated from the explanted hearts of 22 cardiac transplant patients. After histological grading of vascular segments according to American Heart Association guidelines, isolated RNA was hybridized onto a customized 22-K oligonucleotide microarray, and significance analysis of microarrays and gene ontology analyses were performed to identify significant gene expression profiles. Our studies revealed that loss of differentiated smooth muscle cell gene expression is the primary expression signature of disease progression in atherosclerosis. Furthermore, we provide insight into the severe form of coronary artery disease associated with diabetes, reporting an overabundance of immune and inflammatory signals in diabetics. We present a novel approach to pathway development based on connectivity, determined by language parsing of the published literature, and ranking, determined by the significance of differentially regulated genes in the network. In doing this, we identify highly connected "nexus" genes that are attractive candidates for therapeutic targeting and followup studies. Our use of pathway techniques to study atherosclerosis as an integrated network of gene interactions expands on traditional microarray analysis methods and emphasizes the significant advantages of a systems-based approach to analyzing complex disease. PMID:15942018

  2. Rapid Progression of Coronary Atherosclerosis: A Review

    PubMed Central

    Shah, Priyank; Bajaj, Sharad; Virk, Hartaj; Bikkina, Mahesh; Shamoon, Fayez

    2015-01-01

    Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis. PMID:26823982

  3. Positron emission tomography imaging of coronary atherosclerosis.

    PubMed

    Moss, Alastair J; Adamson, Philip D; Newby, David E; Dweck, Marc R

    2016-07-01

    Inflammation has a central role in the progression of coronary atherosclerosis. Recent developments in cardiovascular imaging with the advent of hybrid positron emission tomography have provided a window into the molecular pathophysiology underlying coronary plaque inflammation. Using novel radiotracers targeted at specific cellular pathways, the potential exists to observe inflammation, apoptosis, cellular hypoxia, microcalcification and angiogenesis in vivo. Several clinical studies are now underway assessing the ability of this hybrid imaging modality to inform about atherosclerotic disease activity and the prediction of future cardiovascular risk. A better understanding of the molecular mechanisms governing coronary atherosclerosis may be the first step toward offering patients a more stratified, personalized approach to treatment. PMID:27322032

  4. Infections, atherosclerosis, and coronary heart disease.

    PubMed

    Famularo, G; Trinchieri, V; Santini, G; De Simone, C

    2000-01-01

    There is growing evidence that the immune response is involved in atherosclerosis. Studies done over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia. Overall, these data have greatly renewed interest in the infectious theory of atherosclerosis and coronary heart disease. Search of bibliographic databases (from January 1991 through December 1999) and manual scanning of both peer-reviewed publications and other documents were used to identify pertinent literature. Infections and coronary heart disease were indexed as key words. A large number of studies have reported an association of human coronary heart disease and certain persistent bacterial and viral infections. The association between Chlamydia pneumoniae and coronary heart disease appears quite significant although the sequence of infection and disease is uncertain. The association between Helicobacter pylori and coronary heart disease may be accounted for by residual confounding from classic risk factors. Preliminary findings indicate that this association could be due to a higher prevalence of more virulent Helicobacter strains. Infection with Cytomegalovirus appears to be associated with a greater risk of restenosis after angioplasty rather than primary atherosclerosis. Early trials of appropriate antibiotic therapy in subjects with recent acute myocardial infarction have been encouraging. A causal relationship between infections and coronary heart disease is still elusive. Improved studies involving prospective collection of data are required to demonstrate such an association with potential implications for public health worldwide. PMID:10920505

  5. Coronary atherosclerosis -- a postmortem histopathological study.

    PubMed

    Kumar, S; Kumar, Verma A; Kumar, N; Baranwal, R K; Kumar, Verma R; Singh, M

    2012-01-01

    Cardiovascular disease in general and coronary heart disease in particular remains the leading cause of morbidity and mortality in developed countries. The aim of this study was to look at the prevalence of coronary atherosclerosis, its severity and site of involvement in postmortem hearts. The hearts of 30-60 yrs old, fifty dead victims were considered who died from various natural and unnatural deaths. After autopsy, coronary arteries were inspected grossly and microscopically. Out of all these cases, 10 cases (20 %) showed no pathological lesions. Total distribution of lesions in the coronaries are as follows; 34 (68 %) atheromatous lesions in Left Anterior Descending Artery, 25 (50 %) lesions in the Right Coronary Artery, 18 (36 %) lesions in Left Circumflex. Proximal involvement was more common except in the right coronary artery, which was involved distally. The overall prevalence of coronary atherosclerosis in the present study was comparable with that noted by other investigators in autopsy studied. There is a higher prevalence of atherosclerosis in Indians, which may be due to changes in life-styles and other risks factors (Tab. 1, Ref. 14). Full Text in PDF www.elis.sk. PMID:22502752

  6. Translational Coronary Atherosclerosis Imaging with PET.

    PubMed

    Adamson, Philip D; Newby, David E; Dweck, Marc R

    2016-02-01

    Although still in its infancy, coronary atherosclerosis imaging with PET holds promise in improving understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. Fludeoxyglucose F 18 offers the potential to measure inflammatory activity within the plaque itself whereas fluoride F 18 allows detection of microcalcification, both of which are key characteristics of plaques at risk of rupture. Further work is required to improve these imaging techniques and to assess their ability to predict cardiac events prospectively. PMID:26590788

  7. Atherosclerosis

    MedlinePlus

    Atherosclerosis is a disease in which plaque builds up inside your arteries. Plaque is a sticky substance ... flow of oxygen-rich blood to your body. Atherosclerosis can lead to serious problems, including Coronary artery ...

  8. Coronary Atherosclerosis: Pathophysiologic Basis for Diagnosis and Management.

    PubMed

    Boudoulas, Konstantinos Dean; Triposciadis, Filippos; Geleris, Paraschos; Boudoulas, Harisios

    2016-01-01

    Coronary atherosclerosis is a long lasting and continuously evolving disease with multiple clinical manifestations ranging from asymptomatic to stable angina, acute coronary syndrome (ACS), heart failure (HF) and sudden cardiac death (SCD). Genetic and environmental factors contribute to the development and progression of coronary atherosclerosis. In this review, current knowledge related to the diagnosis and management of coronary atherosclerosis based on pathophysiologic mechanisms will be discussed. In addition to providing state-of-the-art concepts related to coronary atherosclerosis, special consideration will be given on how to apply data from epidemiologic studies and randomized clinical trials to the individual patient. The greatest challenge for the clinician in the twenty-first century is not in absorbing the fast accumulating new knowledge, but rather in applying this knowledge to the individual patient. PMID:27091673

  9. SUSCEPTIBILITY TO ATHEROSCLEROSIS IN AORTAS AND CORONARY ARTERIES OF SWINE WITH VON WILLEBRAND'S DISEASE

    EPA Science Inventory

    The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis ...

  10. Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis.

    PubMed Central

    Geer, J. C.; Crago, C. A.; Little, W. C.; Gardner, L. L.; Bishop, S. P.

    1980-01-01

    Morphologic changes in the subendocardial myocardium that appeared to be caused by severe, chronic subendocardial ischemia were studied in patients with fatal ischemic heart disease admitted to the Specialized Center of Research for Ischemic Heart Disease at the University of Alabama in Birmingham in the period 1970--1977. Thirteen patients were selected for this report on the basis that they had the lesions in the subendocardial myocardium we believe to have been caused by subendocardial ischemia and had no evidence of acute or remote myocardial infarction or other conditions that may have contributed to their terminal illness or death. Clinical findings were unstable angina, congestive heart failure, usually no increase in plasma enzymes indicative of myocardial damage, and electrocardiographic changes consistent with subendocardial ischemia. All 13 patients had 75% or greater stenosis of the three major coronary arteries; none had acute thrombotic or embolic coronary artery occlusion. The left ventricle in all cases was hypertrophied. The subendocardial myocardium showed circumferential pallor, hyperemia, or focal fibrosis without perceptible loss of volume in papillary muscles or trabeculae carneae. Microscopically, acute lesions showed one to two layers of preserved myofibers adjacent to the endocardium, vacuolar change in the deeper fibers, and focal areas of coagulation necrosis of variable size in the myocardium external to the fibers with vacuolar change. Coagulation necrosis was extensive in some cases and usually was not associated with infiltration of neutrophils. The repair reaction involved removal of necrotic sarcoplasm by mononuclear phagocytes, resulting in a reticular-appearing tissue without evidence of stromal collapse. Granulation tissue was not seen. Collagen fibers appeared to be deposited within the area of previous sarcolemmal sheaths. The distribution and morphology of subendocardial myocardial lesions associated with severe coronary

  11. Thyroid Function, Prevalent Coronary Heart Disease, and Severity of Coronary Atherosclerosis in Patients Undergoing Coronary Angiography

    PubMed Central

    Ling, Yan; Jiang, Jingjing; Gui, Minghui; Liu, Lin; Aleteng, Qiqige; Wu, Bingjie; Wang, Shanshan; Liu, Xiaojing; Gao, Xin

    2015-01-01

    This study investigated if free T4 and TSH concentrations or thyroid function categories were associated with prevalent CHD and the severity of coronary atherosclerosis in a population undergoing coronary angiography. This was a cross-sectional study including 1799 patients who were consecutively admitted and underwent coronary angiography. We evaluated the severity of coronary atherosclerosis using Gensini score. In the entire study population, free T4 level was inversely associated with prevalent CHD (OR = 0.95, 95% CI 0.91–0.99, P = 0.01) and the natural log-transformed Gensini score (ln(Gensini score)) (β = −0.03, 95% CI −0.05–−0.01, P = 0.005). The odds of CHD increased gradually across hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism groups using the euthyroid group as the reference, and the trend is borderline significant (P for trend = 0.051). When comparing to the euthyroid group, ln(Gensini score) of the overt hypothyroidism group was significantly higher (P = 0.009), but the trend was not significant (P for trend = 0.08). A significant association of thyroid function with CHD or ln(Gensini score) in euthyroid patients was not observed. The present study demonstrated an association of thyroid function with prevalent CHD and the severity of coronary atherosclerosis in a population undergoing coronary angiography. However, this association was not observed in euthyroid individuals. PMID:26770196

  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. Aortic Root Calcification: A Possible Imaging Biomarker of Coronary Atherosclerosis.

    PubMed

    Nafakhi, Hussein; Al-Nafakh, Hasan A; Al-Mosawi, Abdulameer A

    2016-04-01

    It has been reported that coronary atherosclerosis risk assessment using coronary artery calcium and thoracic aorta calcium quantification may improve risk stratification as it can lead to the reclassification of persons at increased risk. The aortic root has been characterized by its close anatomical proximity to the ostial origins of the right and left coronary arteries, and it can be evaluated using multi-detector computed tomography without additional radiation exposure and the use of contrast. The correlations between aortic root calcification and coronary atherosclerotic markers as well as cardiac risk factors have been analyzed. PMID:27195236

  14. Aortic Root Calcification: A Possible Imaging Biomarker of Coronary Atherosclerosis

    PubMed Central

    Nafakhi, Hussein; Al-Nafakh, Hasan A.; Al-Mosawi, Abdulameer A.

    2016-01-01

    It has been reported that coronary atherosclerosis risk assessment using coronary artery calcium and thoracic aorta calcium quantification may improve risk stratification as it can lead to the reclassification of persons at increased risk. The aortic root has been characterized by its close anatomical proximity to the ostial origins of the right and left coronary arteries, and it can be evaluated using multi-detector computed tomography without additional radiation exposure and the use of contrast. The correlations between aortic root calcification and coronary atherosclerotic markers as well as cardiac risk factors have been analyzed. PMID:27195236

  15. Prediction of cardiovascular outcomes by imaging coronary atherosclerosis

    PubMed Central

    Pathan, Faraz

    2016-01-01

    Over the last two decades, several invasive and non-invasive coronary atherosclerosis imaging modalities have emerged as predictors of cardiovascular outcomes in at-risk population. These modalities have demonstrated independent or incremental prognostic information over existing/standard risk stratification schemes, such as the Framingham risk score (FRS), by identifying characteristics of coronary artery diseases (CADs). In this review, we begin with discussing the importance of pre-test probability and quality of outcome measure, followed by specific findings of each modality in relation to prognosis. We focused on both short and long term prognostic aspects of coronary computed tomography (CT) (including coronary calcium score and coronary angiography) and magnetic resonance imaging as non-invasive tools, as well as invasive modalities including intravascular ultrasound (IVUS), optical coherence tomography (OCT), near infrared spectroscopy and Angioscopy. PMID:27500091

  16. Adropin is associated with hyperhomocysteine and coronary atherosclerosis

    PubMed Central

    ZHAO, LIANG-PING; YOU, TAO; CHAN, SIEW-PANG; CHEN, JIAN-CHANG; XU, WEI-TING

    2016-01-01

    Homocysteine has been recognized as a risk factor for atherosclerosis and cardiovascular diseases. Adropin is a newly-identified energy homeostasis protein with a potential protective effect against coronary artery disease (CAD). This study attempted to measure the correlation between serum homocysteine and adropin levels in patients with CAD, and to ascertain how the two hormones could affect the severity of coronary atherosclerosis. A cohort of CAD patients who had undergone coronary angiography was prospectively recruited. The serum homocysteine and adropin levels of the patients were measured and the severity of coronary atherosclerosis was quantified with the SYNTAX score. The data were analyzed with a generalized structural equation model. In total, 170 consecutive patients were recruited with a mean serum homocysteine level of 15.9±8.3 µmol/l, and 76 (44.7%) patients were identified as hyperhomocysteinemic with a serum homocysteine level >15 µmol/l. Serum homocysteine level was found to be significantly negatively correlated with serum adropin level (r=−0.169, P=0.028). Patients with hyperhomocysteinemia had lower serum adropin levels and higher SYNTAX scores than patients without hyperhomocysteinemia. Further analysis with a generalized structural equation model showed that adropin was significantly associated with hyperhomocysteinemia (adjusted odds ratio: 0.95, 95% confidence interval: 0.93 to 0.98; P=0.002), which in turn was significantly associated with the SYNTAX score (coefficient: 4.71, 95% confidence interval: 1.39 to 8.03; P=0.005). In conclusion, the serum homocysteine level was inversely correlated with the serum adropin level in patients with CAD. A low serum adropin level was associated with hyperhomocysteinemia and more severe coronary atherosclerosis, as reflected by a higher SYNTAX score. PMID:26998038

  17. Pathology of coronary atherosclerosis and thrombosis.

    PubMed

    Otsuka, Fumiyuki; Yasuda, Satoshi; Noguchi, Teruo; Ishibashi-Ueda, Hatsue

    2016-08-01

    The process of early atherosclerotic plaque progression is characterized by the development of pathologic intimal thickening (PIT) with lipid pool that may transform into the necrotic core to form fibroatheroma, where infiltration of foamy macrophages plays a crucial role. The expansion of the necrotic core is also attributable to intraplaque hemorrhage. Thin-cap fibroatheroma (TCFA) is characterized by a relatively large necrotic core with an overlying thin fibrous cap measuring <65 µm typically containing numerous macrophages, and is considered to be the precursor lesion of plaque rupture which is the most common cause of coronary thrombosis. The second common cause of acute thrombosis is plaque erosion, while calcified nodules is known to be the least frequent cause of coronary thrombosis. Coronary thrombosis can occur without symptoms to form healed lesions, which contributes to an increase in plaque burden and luminal narrowing. The process of plaque progression is generally accompanied by the progression of calcification. An understanding of the histomorphological characteristics of coronary plaques should provide important insights into the pathogenesis, diagnosis, and treatment of atherosclerotic coronary disease for both basic and clinical researchers as well as for clinicians. PMID:27500096

  18. Pathology of coronary atherosclerosis and thrombosis

    PubMed Central

    Yasuda, Satoshi; Noguchi, Teruo; Ishibashi-Ueda, Hatsue

    2016-01-01

    The process of early atherosclerotic plaque progression is characterized by the development of pathologic intimal thickening (PIT) with lipid pool that may transform into the necrotic core to form fibroatheroma, where infiltration of foamy macrophages plays a crucial role. The expansion of the necrotic core is also attributable to intraplaque hemorrhage. Thin-cap fibroatheroma (TCFA) is characterized by a relatively large necrotic core with an overlying thin fibrous cap measuring <65 µm typically containing numerous macrophages, and is considered to be the precursor lesion of plaque rupture which is the most common cause of coronary thrombosis. The second common cause of acute thrombosis is plaque erosion, while calcified nodules is known to be the least frequent cause of coronary thrombosis. Coronary thrombosis can occur without symptoms to form healed lesions, which contributes to an increase in plaque burden and luminal narrowing. The process of plaque progression is generally accompanied by the progression of calcification. An understanding of the histomorphological characteristics of coronary plaques should provide important insights into the pathogenesis, diagnosis, and treatment of atherosclerotic coronary disease for both basic and clinical researchers as well as for clinicians. PMID:27500096

  19. 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.

  20. Intravascular photoacoustic imaging of human coronary atherosclerosis

    NASA Astrophysics Data System (ADS)

    Jansen, Krista; van der Steen, Antonius F. W.; Springeling, Geert; van Beusekom, Heleen M. M.; Oosterhuis, J. Wolter; van Soest, Gijs

    2011-03-01

    We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. We specifically imaged lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction. An integrated intravascular photoacoustics (IVPA) and ultrasound (IVUS) catheter with an outer diameter of 1.25 mm was developed. The catheter comprises an angle-polished optical fiber adjacent to a 30 MHz single-element transducer. The ultrasonic transducer was optically isolated to eliminate artifacts in the PA image. We performed measurements on a cylindrical vessel phantom and isolated point targets to demonstrate its imaging performance. Axial and lateral point spread function widths were 110 μm and 550 μm, respectively, for PA and 89 μm and 420 μm for US. We imaged two fresh human coronary arteries, showing different stages of disease, ex vivo. Specific photoacoustic imaging of lipid content, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm.

  1. Imaging of coronary atherosclerosis in various susceptible groups

    PubMed Central

    Nerlekar, Nitesh; Wong, Dennis T. L.

    2016-01-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Atherosclerosis, which is the primary pathophysiologic mechanism for the development of plaque leading to CAD, is a multifactorial process resulting from a complex interplay between genetic susceptibility and various risk factors such as hypertension (HT), dyslipidaemia, diabetes mellitus (DM) and smoking. In addition, influences from other disease states such as chronic kidney disease (CKD), obesity and the metabolic syndrome as well as gender and ethnic diversity also contribute to the disease process. Insights from pathological observations and advances in cellular and molecular biology have helped us understand the process of plaque formation, progression and rupture leading to events. Several intravascular imaging techniques such as intravascular ultrasound (IVUS), Virtual histology IVUS (VH-IVUS) and optical coherence tomography (OCT) allow in vivo assessment of plaque burden, plaque morphology and response to therapy. In addition, non invasive assessment using coronary artery calcium (CAC) score allows risk stratification and plaque burden assessment whilst computed tomography coronary angiography (CTCA) allows evaluation of luminal stenosis, plaque characterisation and quantification. This review aims to summarise the results of invasive and non-invasive imaging studies of coronary atherosclerosis seen in various high-risk populations including DM, metabolic syndrome, obesity, CKD and, gender differences and ethnicity. Understanding the phenotype of plaques in various susceptible groups may allow potential development of personalised therapies. PMID:27500095

  2. Imaging of coronary atherosclerosis in various susceptible groups.

    PubMed

    Munnur, Ravi Kiran; Nerlekar, Nitesh; Wong, Dennis T L

    2016-08-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Atherosclerosis, which is the primary pathophysiologic mechanism for the development of plaque leading to CAD, is a multifactorial process resulting from a complex interplay between genetic susceptibility and various risk factors such as hypertension (HT), dyslipidaemia, diabetes mellitus (DM) and smoking. In addition, influences from other disease states such as chronic kidney disease (CKD), obesity and the metabolic syndrome as well as gender and ethnic diversity also contribute to the disease process. Insights from pathological observations and advances in cellular and molecular biology have helped us understand the process of plaque formation, progression and rupture leading to events. Several intravascular imaging techniques such as intravascular ultrasound (IVUS), Virtual histology IVUS (VH-IVUS) and optical coherence tomography (OCT) allow in vivo assessment of plaque burden, plaque morphology and response to therapy. In addition, non invasive assessment using coronary artery calcium (CAC) score allows risk stratification and plaque burden assessment whilst computed tomography coronary angiography (CTCA) allows evaluation of luminal stenosis, plaque characterisation and quantification. This review aims to summarise the results of invasive and non-invasive imaging studies of coronary atherosclerosis seen in various high-risk populations including DM, metabolic syndrome, obesity, CKD and, gender differences and ethnicity. Understanding the phenotype of plaques in various susceptible groups may allow potential development of personalised therapies. PMID:27500095

  3. Idiopathic hypertrophic subaortic stenosis and coronary atherosclerosis. Results of coronary artery bypass alone and myectomy combined with coronary artery bypass.

    PubMed

    Gill, C C; Duda, A M; Kitazume, H; Kramer, J R; Loop, F D

    1982-12-01

    Twenty-one patients with combined coronary artery disease and idiopathic hypertrophic subaortic stenosis (IHSS) have had coronary artery bypass grafting alone (Group I, n = 7) or in combination with left ventricular septal myectomy (Group II, n = 14). Patients ranged in age from 46 to 73 years (mean 59 years). There were no operative deaths, but one Group I patient died 16 months after operation. Patients in Group I have had continuing symptoms after the operation, whereas Group II patients have had consistent relief of symptoms. Patients with documented IHSS and coronary atherosclerosis should undergo combined coronary bypass and septal myectomy if symptoms recur with medical management. PMID:6983006

  4. Imaging of coronary atherosclerosis - evolution towards new treatment strategies.

    PubMed

    Dweck, Marc R; Doris, Mhairi K; Motwani, Manish; Adamson, Philip D; Slomka, Piotr; Dey, Damini; Fayad, Zahi A; Newby, David E; Berman, Daniel

    2016-09-01

    Coronary atherosclerosis and the precipitation of acute myocardial infarction are highly complex processes, which makes accurate risk prediction challenging. Rapid developments in invasive and noninvasive imaging technologies now provide us with detailed, exquisite images of the coronary vasculature that allow direct investigation of a wide range of these processes. These modalities include sophisticated assessments of luminal stenoses and myocardial perfusion, complemented by novel measures of the atherosclerotic plaque burden, adverse plaque characteristics, and disease activity. Together, they can provide comprehensive, individualized assessments of coronary atherosclerosis as it occurs in patients. Not only can this information provide important pathological insights, but it can also potentially be used to guide personalized treatment decisions. In this Review, we describe the latest advances in both established and emerging imaging techniques, focusing on the strengths and weakness of each approach. Moreover, we discuss how these technological advances might be translated from attractive images into novel imaging strategies and definite improvements in clinical risk prediction and patient outcomes. This process will not be easy, and the many potential barriers and difficulties are also reviewed. PMID:27226154

  5. Progression of coronary atherosclerosis. Clues to pathogenesis from serial coronary arteriography.

    PubMed Central

    Singh, R N

    1984-01-01

    Fifty two patients with coronary artery disease underwent repeat coronary arteriographic studies separated by 2-108 (mean 51) months of medical treatment. The results were compared and correlated with symptoms to determine the nature of the progression of coronary atherosclerosis. The condition appeared to progress episodically in the proximal segments of the coronary arteries and in relation to the abrupt development of new symptoms or acute coronary events such as unstable angina or myocardial infarction. Thirty four of 105 (33%) of the pre-existing stenoses showed evidence of progression. Progression to total occlusion was uncommon (13) except for stenoses greater than 90% (six out of 18). New lesions frequently occurred (37) in previously normal segments of the arteries; most of these were stenoses greater than 90% (13) or total occlusions (12). Rapid progression of a mild lesion and new lesions occurred in the form of smooth intimal protrusions into the arterial lumen. Intimal haemorrhages are the likely explanation for these intimal encroachments and also for the episodic nature of the progression of coronary artery disease. Coronary atherosclerosis does not progress gradually in a linear fashion, and local anatomical factors appear to play a dominant role in the natural history. Images PMID:6477785

  6. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography.

    PubMed

    Scherer, Daniel J; Psaltis, Peter J

    2016-08-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of (18)Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of (18)Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF). PMID:27500093

  7. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

    PubMed Central

    Psaltis, Peter J.

    2016-01-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of 18Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of 18Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) and sodium 18F-fluoride (18F-NaF). PMID:27500093

  8. Tissue Factor Pathway Inhibitor-2 Gene Polymorphisms Associate With Coronary Atherosclerosis in Chinese Population

    PubMed Central

    Yu, Jia; Liu, Rong-Le; Luo, Xin-Ping; Shi, Hai-ming; Ma, Duan; Pan, Jun-Jie; Ni, Huan-Chun

    2015-01-01

    Abstract Tissue factor pathway inhibitor-2 (TFPI-2) may play critical roles in the pathogenesis of atherosclerosis. In this study, we aimed to investigate the association between TFPI-2 gene polymorphisms and coronary atherosclerosis. Four hundred and seven patients with coronary atherosclerosis and 306 individuals with normal coronary artery were enrolled in the present study. Nine single-nucleotide polymorphisms (SNPs) (rs3763473, rs59805398, rs60215632, rs59999573, rs59740167, rs34489123, rs4517, rs4264, and rs4271) were detected with polymerase chain reaction-direct sequencing method. Severity of coronary atherosclerosis was assessed by Gensini score. After the baseline investigation, patients with coronary atherosclerosis were followed up for incidence of cardiovascular events (CVEs). Eight SNPs were in accordance with the Hardy–Weinberg equilibrium, and 8 haplotypes were constructed based on rs59999573, rs59740167, and rs34489123 after linkage disequilibrium and haplotype analysis. Two SNPs (rs59805398 and rs34489123) and 5 haplotypes correlated with coronary atherosclerosis even after adjustment by Gensini score. At follow-up (median 53 months, range 1–60 months), 85 patients experienced CVE. However, there was no strong association between the gene polymorphisms and the occurrence of CVE. Tissue factor pathway inhibitor-2 gene polymorphisms were associated with coronary atherosclerosis in the Chinese population, suggesting that the information about TFPI-2 gene polymorphisms was useful for assessing the risk of developing coronary atherosclerosis, but there was not enough evidence showing it could predict occurrence of CVE. PMID:26496276

  9. Coronary Atherosclerosis The Implications of Being a Woman.

    PubMed

    Morales-Villegas, E

    2014-07-01

    The profile of ischemic heart disease by coronary atherosclerosis has been developed based on clinical, paraclinical and angiographic grounds inherent to the male gender. A man in his 40s - 50s with "classical" cardiovascular risk factors, angina pectoris and hemodynamically significant myocardial ischemia associated with angiographic stenosis (≥ 50% endovascular diameter reduction equivalent to ≥ 75% endovascular area reduction and determining a trans-stenotic pressure gradient) is the prototype over which guidelines for prevention, diagnosis and treatment of this disease are structured. However, this "male" pattern of coronary atherosclerosis is not the rule in female gender. Therefore, in women, the frequent lack of a clinical, paraclinical and angiographic profile, classically masculine, results in a suboptimal medical approach, characterized by low implementation of the guidelines for prevention, diagnosis and treatment of ischemic heart disease. The final consequence of this cycle, favored by other gender, social and environmental circumstances, is a high morbidity and mortality caused by this pathology in the female gender. In this chapter, which concludes with a review of the state-of-the-art knowledge of atheroma in females, the current concepts on the physiological level of c-LDL, oxidized c-LDL "a mimicked pathogen" and atherogenesis will be reviewed in sequence for didactic purposes. PMID:24993280

  10. Decreased bone mineral density is associated with coronary atherosclerosis in healthy postmenopausal women

    PubMed Central

    Seo, Seok Kyo; Yun, Bo Hyon; Noe, Eun Bee; Suh, Jong Wook; Choi, Young Sik

    2015-01-01

    Objective This study aimed to assess the association between bone mineral density (BMD) and coronary atherosclerosis in healthy postmenopausal women. Methods We performed a retrospective review of 252 postmenopausal women who had visited a health promotion center for a routine checkup. BMD of the lumbar spine (L1-L4) and femoral neck was evaluated using dual-energy X-ray absorptiometry, and coronary atherosclerosis was assessed using 64-row multidetector computed tomography. Participants were divided into normal BMD and osteopenia-osteoporosis groups, according to the T-scores of their lumbar spine or femoral neck. Results Participants with osteopenia-osteoporosis had a significantly higher proportion of coronary atherosclerosis than did those with normal BMD at the lumbar spine (P=0.003) and femoral neck (P=0.004). Osteopenia-osteoporosis at the lumbar spine (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.12 to 7.27) or femoral neck (OR, 3.35; 95% CI, 1.07 to 10.57) was associated with coronary atherosclerosis, after controlling for age and cardiovascular risk factors. Conclusion Decreased BMD is associated with coronary atherosclerosis in healthy postmenopausal women, independent of age and cardiovascular risk factors. Postmenopausal women with decreased BMD may have a higher risk of developing coronary atherosclerosis. PMID:25798428

  11. [Risk factors for coronary atherosclerosis. Comparison between two Argentine regions].

    PubMed

    Coniglio, R I; Castillo, S; Dahinten, E; Doubnia, M I; Vasquez, L A; Colombo, O; Estevez, S; Duffard, M C; Lopez Torres, J; Rodriguez, M D

    1994-01-01

    The prevalence of risk factors for coronary atherosclerosis were studied in two population samples, Northeast (Posadas, n = 498) and South (Viedma, C. Rivadavia and Cipolletti, n = 652) of 20 years and older, males and females. The diet in the Northeast (n = 102) contained more monounsaturated acids and polyunsaturated acids than the one in the South (n = 62), 9.5 +/- 4.1 vs. 8.1 +/- 3.5% TCV (Total Caloric Value) (P < 0.02) and 8.1 +/- 4.1 vs. 6.2 +/- 3.0% TCV (P < 0.001) respectively. The P/S relationship was greater in the Northeast, 1.02 +/- 0.44 vs. 0.85 +/- 0.50 (P < 0.001). Total cholesterol (TC) in the Northeast was less than in the South, in males 176 +/- 41 vs. 213 +/- 43 mg/dl (P < 0.001); CLDL (LDL cholesterol) 109 +/- 37 vs. 141 +/- 41 mg/dl (P < 0.001). The most frequent risk factors in the South vs. Northeast (males) were: TC > or = 240 mg/dl, 26.7% vs. 9.5% (P < 0.001); LDL-C > or = 160 mg/dl, 30.3% vs. 10.9% (P < 0.001); Cig > or = 10/d (equal or more than 10 cigarettes per day), 30.0% vs. 16.4% (P < 0.001). The hypertension prevalence (HTA, 160/95), in males, was higher in the Northeast than in the South, 23.7% vs. 11.5% (P < 0.001). BMI > 27 Kg/m2 was higher in the women of Northeast than in the South, 38.4% vs. 24.2% (P < 0.001). In the males of the Northeast, the combination Cig > or = 10/d and HTA, 4.1 vs 0.9% was more common; in the South Cig > or = 10/d and LDL-C > or = 160 mg/d, 8.2% vs. 1.8% (P < 0.001) was more common. The differences in the prevalence of the risk factors between the population samples indicate the need to plan the prevention of coronary atherosclerosis locally. PMID:7997127

  12. Insight into the Spectrum of Coronary Atherosclerosis in Asymptomatic Urban Han Chinese Population by Coronary Computed Tomography Angiography

    PubMed Central

    Li, Jiangbing; Liu, Ruihong; Ji, Xiaokang; Xue, Hao; Zhang, Guang; Wang, Chunxia; Chen, Qicai; Xue, Fuzhong; Cui, Lianqun

    2015-01-01

    Objectives Highlighted the spectrum of coronary atherosclerosis in asymptomatic population by Computed Tomography Angiography (CTA) and developed a surrogation of expensive CTA to early detect coronary atherosclerosis. Methods Three hundred and seven self-referred urban Han Chinese asymptomatic individuals underwent coronary CTA were consecutively enrolled. Total plaque score (TPS), Segment stenosis score (SSS) and Coronary Artery Disease severity (CADS) were used to measure and illustrate the spectrum of atherosclerosis burden by mapping their incidence and proportion onto coronary artery tree. Logistic regression model was further used to explore the association between lipid biomarkers and TPS (SSS) for developing a surrogation of CTA to early detect coronary atherosclerosis. Results We found that the incidence of TPS, SSS and CADS were up to 71.34%, 68.08%, and 71.34%; and high-risk individuals reached up to 11.07%, 15.31% and 16.29% respectively. All TPS, SSS and CADS were much higher in male than female, and have trend of increasing with age. The most lesion segment emerged on proximal LAD, followed by proximal RCA, mid LAD, proximal LCX, and mid RCA with mixed plaque as dominant. HDL-C was a predictor to both TPS [OR: 0.12 (0.02–0.82)] and SSS [OR: 0.15 (0.03–0.76)], and could identify the serious atherosclerosis subjects of TPS or SSS score >5 (AUC 0.73 and 0.70). Conclusions The atherosclerosis plaque burden was about one in ten as high-risk individuals in this specific urban Han Chinese population. As potential surrogation of CTA, HDL-C was recognized as a significant predictor to atherosclerosis burden and revealed a good performance for identifying high-risk individuals. PMID:26151132

  13. Endothelial dysfunction and progressive coronary atherosclerosis: sequential invasive studies in a patient with multiple cardiac risk factors.

    PubMed

    Chander, R; Kuhner, P A; Laws Houghton, J

    2001-08-01

    This manuscript describes sequential angiographic, endothelial and vasoreactivity characteristics of the coronary arterial circulation in a middle-aged patient with multiple cardiac risk factors who developed hemodynamically significant coronary atherosclerosis over a 6-year period. A 56-year-old woman demonstrated marked angiographic progression of coronary atherosclerosis over time beginning with minor luminal irregularities in the setting of severe endothelial dysfunction. The association of endothelial dysfunction, ineffective cardiac risk factor management and progressive atherosclerosis is discussed. PMID:11481511

  14. Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in acute coronary syndrome patients.

    PubMed

    Afrasyab, Altaf; Qu, Peng; Zhao, Yang; Peng, Kuang; Wang, Hongyan; Lou, Dayuan; Niu, Nan; Yuan, Dajun

    2016-08-01

    We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE. PMID:26290166

  15. Effects of gender and social behavior on the development of coronary artery atherosclerosis in cynomolgus macaques.

    PubMed

    Hamm, T E; Kaplan, J R; Clarkson, T B; Bullock, B C

    1983-09-01

    This experiment involved examination of the effects of gender and social status ('competitive dominance') on the coronary artery atherosclerosis of cynomolgus monkeys. Thirty-two adult Macaca fascicularis (16 males, 16 females) were fed a diet containing a moderate amount of cholesterol (0.56 mg/cal) for 16 months. The monkeys were housed in groups of 4 animals of the same sex, and all groups were stable in composition for the entire experiment. After 1 year a'competitive dominance' score was determined for each monkey, based on feeding order in 9 trials involving a preferred food as incentive. At necropsy the coronary arteries were pressure perfused; 5 sections each were then taken from the left anterior descending, left circumflex and right coronary arteries. For each animal, the mean percent lumen stenosis calculated from theses 15 sections was used as the index of extent of coronary artery atherosclerosis. Males had significantly more extensive coronary artery atherosclerosis than did females. Further, among both males and females, submissive animals (low in competitiveness) had more extensive coronary artery stenosis than did their dominant (highly competitive) counterparts. A similar pattern was observed in the thoracic and abdominal portions of the aorta with respect to competitiveness, but not gender. In the iliac artery, females had less atherosclerosis than males but there was no competitiveness effect. The gender and social status effects on atherosclerosis were each statistically independent of variability in clinical-pathological measures (serum lipid concentrations and heart weight). The results indicated that: (a) gender and psychosocial stress independently affect the development of coronary artery atherosclerosis; (b) the mechanisms mediating these effects remain unknown; and (c) the cynomolgus macaque is a good model for the study of such phenomena. PMID:6685520

  16. Grade-response relationship between blood pressure and severity of coronary atherosclerosis in asymptomatic adults: assessment with coronary CT angiography.

    PubMed

    Im, Tae Seong; Chun, Eun Ju; Lee, Min Su; Adla, Theodor; Kim, Jeong A; Choi, Sang Il

    2014-12-01

    Hypertension is known to be a strong risk factor for coronary atherosclerosis. We aimed to investigate the prevalence, severity, and plaque characteristics of coronary atherosclerosis according to grade of blood pressure (BP) using coronary CT angiography (CCTA) in asymptomatic adults. We enrolled 8,238 asymptomatic subjects who underwent coronary artery calcium scoring (CACS) and CCTA for health screening purposes. Subjects were classified according to JNC 7 guidelines (normal, systolic BP/diastolic BP < 120/80; pre-hypertension [PH], 120-139/80-89; hypertension stage 1 [H1], 140-159/90-99; hypertension stage 2 [H2], >160/100). Isolated systolic hypertension (ISH; systolic BP > 140, diastolic BP < 80) was additionally categorized. With CCTA, the presence of plaques, severity of stenosis, and plaque types were assessed. Using multiple logistic regression analysis, the adjusted odds ratios (AORs) for plaque, obstructive coronary artery disease (CAD) (luminal stenosis ≥50 %), non-calcified plaque (NCP), and CACS > 100 were assessed according to BP grade. After adjustment for clinical risk factors, the risk of subclinical atherosclerosis, NCP, and CACS > 100 gradually increased from PH stage (all P values for trend <0.05), while the risk of obstructive CAD increased from the H1 stage (AORs of H1 and H2: 1.70 and 2.33, respectively). In the ISH group, the AOR of subclinical atherosclerosis (1.64) was higher than in the H1 group (1.55), while the AOR of obstructive CAD (2.58) was higher than in the H2 group (2.33). Therefore, our study strongly suggests that coronary atherosclerosis in asymptomatic adults shows a grade-response relationship according to hypertension grade. PMID:25178841

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

    PubMed Central

    Moradi, Maryam; Varasteh, Elham

    2016-01-01

    Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:26962526

  18. Intracoronary imaging of coronary atherosclerosis: validation for diagnosis, prognosis and treatment.

    PubMed

    Koskinas, Konstantinos C; Ughi, Giovanni J; Windecker, Stephan; Tearney, Guillermo J; Räber, Lorenz

    2016-02-01

    While coronary atherosclerosis is a leading cause of mortality, evaluation of coronary lesions was previously limited to either indirect angiographic assessment of the lumen silhouette or post mortem investigations. Intracoronary (IC) imaging modalities have been developed that allow for visualization and characterization of coronary atheroma in living patients. Used alone or in combination, these modalities have enhanced our understanding of pathobiological mechanisms of atherosclerosis, identified factors responsible for disease progression, and documented the ability of various medications to reverse the processes of plaque growth and destabilization. These methodologies have established a link between in vivo plaque characteristics and subsequent coronary events, thereby improving individual risk stratification, paving the way for risk-tailored systemic therapies and raising the option for pre-emptive interventions. Moreover, IC imaging is increasingly used during coronary interventions to support therapeutic decision-making in angiographically inconclusive disease, guide and optimize procedural results in selected lesion and patient subsets, and unravel mechanisms underlying stent failure. This review aims to summarize current evidence regarding the role of IC imaging for diagnosis and risk stratification of coronary atherosclerosis, and to describe its clinical role for guiding percutaneous coronary interventions. Future perspectives for in-depth plaque characterization using novel techniques and multimodality imaging approaches are also discussed. PMID:26655874

  19. Atherosclerosis

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Atherosclerosis? Español Atherosclerosis is a disease in which plaque ... problems, including heart attack , stroke , or even death. Atherosclerosis Figure A shows a normal artery with normal ...

  20. The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes.

    PubMed

    Idzkowska, E; Eljaszewicz, A; Miklasz, P; Musial, W J; Tycinska, A M; Moniuszko, M

    2015-09-01

    The inflammation underlying both atherosclerosis and acute coronary syndromes is strongly related to monocyte-related actions. However, different monocyte subsets can play differential roles in the formation and destabilization of atherosclerotic plaque as well as healing of damaged myocardial tissue. Monocytes are currently being divided into three functionally distinct subsets with different levels of CD14 (cluster of differentiation 14) and CD16 expression. Thus, there are classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. Here, we summarize the current knowledge on complex activities of different monocyte subsets in atherosclerosis and acute coronary syndromes. Moreover, we discuss which monocyte subsets can serve either as predictive biomarkers of cardiovascular risk or as potential targets used in atherosclerosis and its complications. PMID:25997925

  1. Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation.

    PubMed

    Alie, Nadia; Eldib, Mootaz; Fayad, Zahi A; Mani, Venkatesh

    2014-01-01

    Atherosclerosis is a prevalent cardiovascular disease marked by inflammation and the formation of plaque within arterial walls. As the disease progresses, there is an increased risk of major cardiovascular events. Owing to the nature of atherosclerosis, it is imperative to develop methods to further understand the physiological implications and progression of the disease. The combination of positron emission tomography (PET)/computed tomography (CT) has proven to be promising for the evaluation of atherosclerotic plaques and inflammation within the vessel walls. The utilization of the radiopharmaceutical tracer, 18F-fluorodeoxyglucose ((18)F-FDG), with PET/CT is invaluable in understanding the pathophysiological state involved in atherosclerosis. In this review, we will discuss the use of (18)F-FDG-PET/CT imaging for the evaluation of atherosclerosis and inflammation both in preclinical and clinical studies. The potential of more specific novel tracers will be discussed. Finally, we will touch on the potential benefits of using the newly introduced combined PET/magnetic resonance imaging (MRI) for non-invasive imaging of atherosclerosis. PMID:25674025

  2. Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation

    PubMed Central

    Alie, Nadia; Eldib, Mootaz; Fayad, Zahi A; Mani, Venkatesh

    2014-01-01

    Atherosclerosis is a prevalent cardiovascular disease marked by inflammation and the formation of plaque within arterial walls. As the disease progresses, there is an increased risk of major cardiovascular events. Owing to the nature of atherosclerosis, it is imperative to develop methods to further understand the physiological implications and progression of the disease. The combination of positron emission tomography (PET)/computed tomography (CT) has proven to be promising for the evaluation of atherosclerotic plaques and inflammation within the vessel walls. The utilization of the radiopharmaceutical tracer, 18F-fluorodeoxyglucose (18F-FDG), with PET/CT is invaluable in understanding the pathophysiological state involved in atherosclerosis. In this review, we will discuss the use of 18F-FDG-PET/CT imaging for the evaluation of atherosclerosis and inflammation both in preclinical and clinical studies. The potential of more specific novel tracers will be discussed. Finally, we will touch on the potential benefits of using the newly introduced combined PET/magnetic resonance imaging (MRI) for non-invasive imaging of atherosclerosis. PMID:25674025

  3. Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis

    PubMed Central

    Chen, Suet Nee; Cilingiroglu, Mehmet; Todd, Josh; Lombardi, Raffaella; Willerson, James T; Gotto, Antonio M; Ballantyne, Christie M; Marian, AJ

    2009-01-01

    Background Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis. Methods We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR). Results Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in APOA5, APOC2, CETP, LPL and LIPC (each q ≤0.01). Likewise, plasma apo A-I levels, available in the LCAS subset, were associated with SNPs in CETP, APOA5, and APOC2 as well as with BMI, sex and age (all q values ≤0.03). The APOA5 variant S19W was also associated with minimal lumen diameter (MLD) of coronary atherosclerotic lesions, a quantitative index of severity of coronary atherosclerosis (q = 0.018); mean number of coronary artery occlusions (p = 0.034) at the baseline and progression of coronary atherosclerosis, as indicated by the loss of MLD. Conclusion Putatively functional variants of APOA2, APOA5, APOC2, CETP, LPL, LIPC and SOAT2 are independent genetic determinants of plasma HDL-C levels. The non-synonymous S19W SNP in APOA5 is also an independent determinant of plasma

  4. Pokkuri Death Syndrome; sudden cardiac death cases without coronary atherosclerosis in South Asian young males.

    PubMed

    Nakajima, Katsuyuki; Takeichi, Sanae; Nakajima, Yasuhiro; Fujita, Masaki Q

    2011-04-15

    Sudden death is one of the major concerns in forensic medicine. Especially when the deceased is a young subject without significant history, the case will be of major interest to the authorities. Sudden unexplained cardiac death has been known as "Pokkuri Death Syndrome" (PDS) in Japan, "Lai Tai" in Thailand, "Bangungut" in the Philippines, "Dream Disease" in Hawaii, and "Sudden Unexpected Nocturnal Death Syndrome" among South Asian immigrants in the USA. However, the clinical and pathological features of these sudden death cases, especially the characteristics of no coronary atherosclerosis, are surprisingly similar and mainly occur among Southeast Asian young males during sleep in the midnight. In this manuscript, we have reviewed the pathological characteristics and the possible mechanism of death in PDS cases, which were associated with significantly elevated remnant lipoproteins in plasma as revealed from our studies during the past 15 years in Japan. Although elevated plasma remnant lipoproteins have been known to be strongly atherogenic, coronary atherosclerosis was not observed in PDS cases. PDS cases were shown to be an interesting cardiovascular disease death discovered in forensic medicine research, which may suggest the difference between the occurrence of cardiovascular events and the severity of coronary atherosclerosis as separate factors. These observations in PDS cases suggest the possibility that the intervention could be more targeted to suppress the cardiovascular events rather than to slow down the progression of atherosclerosis, which is now most extensively targeted for the therapy of cardiovascular disease in Western countries. PMID:21084168

  5. Atherosclerosis

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atherosclerosis Updated:Jul 6,2015 View an animation of ... the arteries as you get older. How does atherosclerosis start and progress? It's a complex process. Exactly ...

  6. Coronary, aortic and cerebral atherosclerosis in swine of 3 age-groups: implications*

    PubMed Central

    Ratcliffe, H. L.; Luginbühl, H.; Pivnik, L.

    1970-01-01

    Coronary, aortic and intercranial atherosclerosis has been compared in swine maintained under the following conditions: (1) adequate food and housing but animals held in test social situations for 1 year; postmortem examination at ages of 13 to 15 months; (2) food and management designed for high productivity; postmortem examination at ages of 6 to 9 years; (3) an outdoor system of husbandry and a cooked garbage diet; postmortem examination at ages of 8 to 14 years. Extramural coronary, aortic and intracranial atherosclerosis was most advanced in swine that were fed garbage. Cerebral infarction (cerebromalacia) also was most advanced in these swine but developed in swine of the younger groups in which it was associated with atherosclerosis of small intracranial extracerebral arteries rather than with stenosis of the larger intracranial extracerebral arteries as in the oldest swine. The lesions of atherosclerosis in swine of these 3 age-groups form a continuous series and are morphologically identical with corresponding stages of atherosclerosis of man. It is concluded that swine can replace non-human primates as subjects for studies of atherosclerotic vascular disease, and that experimental designs must allow for age and behaviour patterns of the species. ImagesFIG. 4-7FIG. 1FIG. 2FIG. 3 PMID:5310139

  7. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease.

    PubMed

    Mehta, J L; Saldeen, T G; Rand, K

    1998-05-01

    Although first suggested at the turn of the 20th century, there is a renewed interest in the infectious theory of atherosclerosis. Studies done in many laboratories around the world over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia, particularly in the early stages of reperfusion. It is also being recognized that the traditional risk factors, such as smoking, dyslipidemia, hypertension and diabetes mellitus, do not explain the presence of coronary atherosclerosis in a large proportion of patients. We believe that in certain genetically susceptible people, infection with very common organisms, such as Chlamydia pneumoniae or cytomegalovirus, may lead to a localized infection and a chronic inflammatory reaction. Persistence of infection may relate to the degree of inflammation and severity of atherosclerosis. Early trials with appropriate antibiotic agents in some patients with a recent history of acute myocardial infarction have led to very salutary results. If patients with an infectious basis of atherosclerosis can be identified, a therapy directed at eradication of the offending organism may be appropriate. PMID:9581711

  8. Monocytes in coronary artery disease and atherosclerosis: where are we now?

    PubMed

    Ghattas, Angie; Griffiths, Helen R; Devitt, Andrew; Lip, Gregory Y H; Shantsila, Eduard

    2013-10-22

    Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function. PMID:23973684

  9. Atherosclerosis in coronary artery and aorta in a semi-urban population by applying modified American Heart Association classification of atherosclerosis: An autopsy study

    PubMed Central

    Thej, Mothakapalli Jagadish; Kalyani, Raju; Kiran, Jayaramaiah

    2012-01-01

    Background: Ischemic heart disease (IHD) following atherosclerosis is a giant killer and the incidence of atherosclerosis in coronary arteries is rapidly increasing among Indians. The study was formulated to assess the histomorphological atherosclerotic changes in aorta and coronary arteries at autopsy by applying the modified American Heart Association classification of atherosclerosis based on morphological descriptions to find out the age and sex related prevalence of atherosclerosis in the semi-urban population of Kolar, a district in Southern India. Materials and Methods: Autopsy was conducted on 113 cases whose age ranged from 8-85 years. Autopsy was conducted by the conventional technique; heart and the aorta were removed and fixed in 10% formalin. The heart was dissected along the direction of flow of blood and aorta along the posterior surface. Microscopic assessment of the three main coronary arteries and aorta was done using the modified American Heart Association classification of atherosclerosis. Proportions were analyzed using Chi-square test. Results: The number of males was 78 (69%) and number of females was 35 (31%). Mean age was 37.11 ± 15.69 years. Increased incidence of intermediate lesions was noted in young individuals (15-34 yrs). Atherosclerotic lesions were more in left anterior descending artery compared to other coronary arteries and in abdominal aorta compared to thoracic and ascending aorta. Vulnerable plaques were more in right coronary artery. Conclusion: With cardiovascular disease attaining pandemic proportions, the study of subclinical atherosclerosis is the need of the hour to estimate the disease burden in the asymptomatic population. The increased amount of atherosclerosis (advanced and intermediate lesions) found in the young population in this study gives an indication that anti-atherogenic preventive measures need to be implemented in young individuals, so as to prevent coronary artery disease from causing premature death

  10. Effect of n-3 Polyunsaturated Fatty Acids on Regression of Coronary Atherosclerosis in Statin Treated Patients Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Ahn, Jinhee; Park, Seo Kwang; Park, Tae Sik; Kim, Jin Hee; Yun, Eunyoung; Kim, Sang-Pil; Lee, Hye Won; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Lee, Sang Yeoup

    2016-01-01

    Background and Objectives Statins remain the mainstay of secondary coronary artery disease (CAD) prevention, but n-3 polyunsaturated fatty acids (ω-3 PUFA) display biological effects that may also reduce the risk of atherosclerosis and CAD. However, data on the possible antiatherosclerotic benefits of adding ω-3 PUFA to statin therapy are limited. This study aimed to investigate the potential additive effects of ω-3 PUFA on regression of atherosclerosis in CAD patients receiving statin therapy and stent implantation. Subjects and Methods Seventy-four CAD patients undergoing percutaneous coronary intervention (PCI) with stent implantation were enrolled, prescribed statins, and randomly assigned to two groups: n-3 group (ω-3 PUFA 3 g/day, n=38) or placebo group (placebo, n=36). All patients completed the study follow-up consisting of an intravascular ultrasound at baseline and at 12 months. Results There was no difference in the baseline characteristics and distribution of other medications. No significant differences were observed in primary endpoints, including changes in atheroma volume index (−12.65% vs. −8.51%, p=0.768) and percent atheroma volume (−4.36% vs. −9.98%, p=0.526), and in secondary endpoints including a change in neointimal volume index (7.84 vs. 4.94 mm3/mm, p=0.087). Conclusion ω-3 PUFA had no definite additional effect on the regression of coronary atherosclerosis when added to statin in CAD patients undergoing PCI. PMID:27482256

  11. "State-of-Art" paper of the Italian Working Group on Atherosclerosis: Preclinical assessment of early coronary atherosclerosis.

    PubMed

    Madonna, Rosalinda; Selvaggio, Stefano; Selvaggio, Giancarlo; Coronelli, Maurizio; Cocco, Nino

    2016-07-01

    Although the early diagnosis and treatment for acute myocardial infarction have improved over the past decades, the morbidity and mortality from coronary artery disease (CAD) remain significant in Europe and worldwide. It is estimated that the majority of people in the developed countries who die suddenly from CAD, have no prior manifestation of disease, and the majority of these individuals are not considered to be at high risk. Accurate identification of individuals at risk of such events before the clinical manifestations is therefore required. This "State-of-Art" paper of the Italian Working Group on Atherosclerosis aims to i. provide an overview of both the traditional and emerging non-invasive imaging techniques used to detect early atherosclerosis in the general population with moderate cardiovascular risk; ii. identify the rationale for screening asymptomatic patients with preclinical atherosclerotic lesions and the optimal algorithm that should be used to detect them; iii. discuss the future directions of atherosclerosis research, with special focus on nanotechnology, aimed at early identification and treatment of low- and intermediate-risk patients. PMID:27093681

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

    PubMed Central

    Andrews, Jordan; Puri, Rishi; Kataoka, Yu; Nicholls, Stephen J.

    2016-01-01

    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. PMID:27500089

  13. Comparison of Non-Invasive Methods for the Detection of Coronary Atherosclerosis

    PubMed Central

    Bampi, Angela Bacelar Albuquerque; Rochitte, Carlos Eduardo; Favarato, Desiderio; Lemos, Pedro Alves; da Luz, Protásio Lemos

    2009-01-01

    BACKGROUND: Non-invasive detection of atherosclerosis is critical for its prevention. Objective: To correlate non-invasively detectable indicators of coronary atherosclerosis, or Coronary Artery Disease (i.e., classical risk factors, hs-CRP test results, carotid intima-media thickness, endothelial function, ankle-brachial index and calcium score by computed tomography) with the extent of coronary disease assessed by the Friesinger index from conventional coronary angiography. METHODS: We conducted a prospective study of 100 consecutive patients, mean age 55.1 ± 10.7 years, 55% men and 45% women. Patients with acute coronary syndrome, renal dialytic insufficiency, collagen disease and cancer were not included. All patients were subjected to clinical evaluation and laboratory tests. Endothelial function of the brachial artery and carotid artery were evaluated by high-resolution ultrasound; ankle-brachial index and computed tomography for coronary determination of calcium score were also performed, and non-HDL cholesterol and TG/HDL-c ratio were calculated. All patients were subjected to coronary angiography at the request of the assistant physician. We considered patients without an obstructive lesion (< 29% stenosis) demonstrated by coronary angiography to be normal. RESULTS: Univariate analysis showed that calcium score, HDL-c, TG/HDL ratio and IMT were significantly correlated with the Friesinger index. However, multivariate analysis indicated that only calcium score and low HDL-c levels correlated significantly with the extension of CAD. On the other hand, hs-CRP, LDL-c, flow-mediated dilation, and Framingham score did not correlate with the Friesinger index. ROC analysis showed that calcium score, HDL-c and TG-HDL ratio accurately predicted extensive CAD in a statistically significant manner. CONCLUSION: It is possible to approximately determine the presence and extent of CAD by non-invasive methods, especially by calcium score, HDL-c and TG/HDL-c ratio assays

  14. Carotid Atherosclerosis Does Not Predict Coronary, Vertebral, or Aortic Atherosclerosis in Patients with Acute Stroke Symptoms

    PubMed Central

    2010-01-01

    PURPOSE The purpose of this study was to determine whether significant atherosclerotic disease in the carotid arteries predicts significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. METHODS Atherosclerotic disease was imaged using computed tomography angiography (CTA) in a prospective study of 120 consecutive patients undergoing emergent CT evaluation for symptoms of stroke. Using a comprehensive CTA protocol that captured the carotid arteries, coronary arteries, vertebral arteries, and aorta, we evaluated these arteries for the presence and severity of atherosclerotic disease. Significant atherosclerotic disease was defined as > 50% stenosis in the carotid, coronary, and vertebral arteries, or ≥ 4mm thickness and encroaching in the aorta. Presence of any and significant atherosclerotic disease were compared in the different types of arteries assessed. RESULTS Of these 120 patients, 79 had CTA exams of adequate image quality and were evaluated in this study. Of these 79 patients, 33 had significant atherosclerotic disease. In 26 of these 33 patients (79%), significant disease was isolated to one type of artery, most often to the coronary arteries (N = 14; 54%). Non-significant atherosclerotic disease was more systemic and involved multiple arteries. CONCLUSIONS Significant atherosclerotic disease in the carotid arteries does not predict significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. Significant atherosclerotic disease is most often isolated to one type of artery in these patients, while non-significant atherosclerotic disease tends to be more systemic. PMID:20595672

  15. Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis

    PubMed Central

    Horn, Patrick; Erkilet, Gülsüm; Veulemans, Verena; Kröpil, Patric; Schurgers, Leon; Zeus, Tobias; Heiss, Christian; Kelm, Malte; Westenfeld, Ralf

    2016-01-01

    Background Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification. Methods In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation. Results Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation. Conclusion In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification. PMID:27010400

  16. Role of biomechanical forces in the natural history of coronary atherosclerosis.

    PubMed

    Brown, Adam J; Teng, Zhongzhao; Evans, Paul C; Gillard, Jonathan H; Samady, Habib; Bennett, Martin R

    2016-04-01

    Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events. PMID:26822720

  17. Characterization of coronary atherosclerosis by intravascular imaging modalities.

    PubMed

    Honda, Satoshi; Kataoka, Yu; Kanaya, Tomoaki; Noguchi, Teruo; Ogawa, Hisao; Yasuda, Satoshi

    2016-08-01

    Coronary artery disease (CAD) is highly prevalent in Western countries and is associated with morbidity, mortality, and a significant economic burden. Despite the development of anti-atherosclerotic medical therapies, many patients still continue to suffer from coronary events. This residual risk indicates the need for better risk stratification and additional therapies to achieve more reductions in cardiovascular risk. Recent advances in imaging modalities have contributed to visualizing atherosclerotic plaques and defining lesion characteristics in vivo. This innovation has been applied to refining revascularization procedure, assessment of anti-atherosclerotic drug efficacy and the detection of high-risk plaques. As such, intravascular imaging plays an important role in further improvement of cardiovascular outcomes in patients with CAD. The current article reviews available intravascular imaging modalities with regard to its method, advantage and disadvantage. PMID:27500094

  18. Characterization of coronary atherosclerosis by intravascular imaging modalities

    PubMed Central

    Honda, Satoshi; Kanaya, Tomoaki; Noguchi, Teruo; Ogawa, Hisao; Yasuda, Satoshi

    2016-01-01

    Coronary artery disease (CAD) is highly prevalent in Western countries and is associated with morbidity, mortality, and a significant economic burden. Despite the development of anti-atherosclerotic medical therapies, many patients still continue to suffer from coronary events. This residual risk indicates the need for better risk stratification and additional therapies to achieve more reductions in cardiovascular risk. Recent advances in imaging modalities have contributed to visualizing atherosclerotic plaques and defining lesion characteristics in vivo. This innovation has been applied to refining revascularization procedure, assessment of anti-atherosclerotic drug efficacy and the detection of high-risk plaques. As such, intravascular imaging plays an important role in further improvement of cardiovascular outcomes in patients with CAD. The current article reviews available intravascular imaging modalities with regard to its method, advantage and disadvantage. PMID:27500094

  19. Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden/composition in young adult population

    PubMed Central

    Satilmis, Seckin; Celik, Omer; Biyik, Ismail; Ozturk, Derya; Celik, Kubra Asik; Akın, Fatih; Ayca, Burak; Yalcin, Burce; Dagdelen, Sinan

    2015-01-01

    Evidence suggests that low 25-OH vitamin D 25(OH)D concentrations may increase the risk of several cardiovascular diseases such as hypertension, peripheral vascular disease, diabetes mellitus, obesity, myocardial infarction, heart failure and cardiovascular mortality. Recent studies suggested a possible relationship between vitamin D deficiency and increased carotid intima-media wall thickness and vascular calcification. We hypothesized that low 25(OH)D may be associated with coronary atherosclerosis and coronary plaque burden and composition, and investigated the relationship between serum vitamin D levels and coronary atherosclerosis, plaque burden or structure, in young adult patients by using dual-source 128x2 slice coronary computed tomography angiography (CCTA). We included 98 patients with coronary atherosclerosis and 110, age and gender matched, subjects with normal findings on CCTA examinations. Patients with subclinical atherosclerosis had significantly higher serum total cholesterol, triglycerides, hs-CRP, uric acid, HbA1c and creatinine levels and lower serum 25(OH)D levels in comparison with controls. There was no significant correlation between 25(OH)D and plaque morphology. There was also a positive relationship between 25(OH)D and plaque burden of coronary atherosclerosis. In multivariate analysis, coronary atherosclerosis was associated high hs-CRP (adjusted OR: 2.832), uric acid (adjusted OR: 3.671) and low 25(OH)D (adjusted OR: 0.689). Low levels of 25(OH)D were associated with coronary atherosclerosis and plaque burden, but there was no significant correlation between 25(OH)D and plaque morphology. PMID:25725147

  20. Imaging Coronary Atherosclerosis and Vulnerable Plaques with Optical Coherence Tomography

    NASA Astrophysics Data System (ADS)

    Tearney, Guillermo J.; Jang, Ik-Kyung; Kashiwagi, Manubu; Bouma, Brett E.

    Intracoronary optical coherence tomography (OCT) is an invasive microscopic imaging technology that has been developed for the identification of vulnerable plaque. OCT acquires cross-sectional images of tissue reflectance and, since it may be implemented through an optical fiber probe, it is readily adaptable to coronary catheters for insertion into coronary arteries and circumferential imaging of arterial pathology. The first investigation of vascular optical coherence tomography ex vivo demonstrated the potential of this technique to identify arterial microstructure. Subsequent development of OCT technology enabled image acquisition at rates sufficient for intracoronary imaging in human patients. In this chapter, we review studies conducted with this technology at the Massachusetts General Hospital (MGH). Results from these studies show that a wide variety of microscopic features, including those associated with TCFAs, can be identified by OCT imaging both ex vivo and in living human patients. These findings suggest that this technology will play an important role in improving our understanding of coronary artery disease, guiding local therapy, and decreasing themortality of AMI.

  1. Effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model

    PubMed Central

    Li, Xiaolong; Lu, Yan; Sun, Yi; Zhang, Qi

    2015-01-01

    Objective: Our objective is to explore the effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. Methods: 45 healthy male Wistar rats of clean grade were selected and divided into treatment group, model control group and blank control group. The rats in the treatment group and model control group received high-fat diet for 12 weeks and intraperitoneal injection of VD3 to establish rat coronary atherosclerosis heart disease model. After modeling, the rats in the treatment group received gavage of 100 mg/(kg·d) curcimin, and the rats in the model control group and blank control group received gavage of 5 ml/(kg·d) distilled water, the intervention time was 4 weeks. After intervention, the rats were killed, and the hearts were dissected to obtain the samples of coronary artery. After embedding and frozen section, immunofluorescence method was used to detect the change of endarterium permeability in 3 groups, Western blot was used to detect matrix metalloproteinase-9 (MMP-9) and CD40L in coronary artery tissue, and enzyme linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α) and C reaction protein (CRP). Results: After modeling, compared with the blank control group, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-c) in the treatment group and model control group were significantly higher (P<0.05), however, high density lipoprotein cholesterin (HDL-c) was significantly lower. The pathological sections showed that there was lipidosis in rat coronary artery in treatment group and model control group, indicating that the modeling was successful. Immunofluorescence showed that there was only a little fluorochrome permeability in artery in blank control group, there was some fluorochrome permeability in artery in the treatment group and there was a lot of fluorochrome permeability in artery in the model

  2. Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis.

    PubMed

    Kretowski, Adam; McFann, Kim; Hokanson, John E; Maahs, David; Kinney, Gregory; Snell-Bergeon, Janet K; Wadwa, R Paul; Eckel, Robert H; Ogden, Lorraine; Garg, Satish; Li, Jia; Cheng, Suzanne; Erlich, Henry A; Rewers, Marian

    2007-03-01

    Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6-388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes. PMID:17327458

  3. 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 Central

    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

    2016-01-01

    Background 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. Methods 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. Results 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]. Conclusions 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. PMID:27168742

  4. Cardiovascular Risk Factors and Coronary Atherosclerosis in Retired National Football League Players

    PubMed Central

    Chang, Alice Y.; FitzGerald, Shannon J.; Cannaday, John; Zhang, Song; Patel, Amit; Palmer, M. Dean; Reddy, Gautham P.; Ordovas, Karen G.; Stillman, Arthur E; Janowitz, Warren; Radford, Nina B.; Roberts, Arthur J.; Levine, Benjamin D.

    2013-01-01

    A high prevalence of obesity exists among National Football League (NFL) players as determined by body mass index (BMI). It is not established whether elevated BMI is associated with a greater prevalence of CV risk factors or coronary atherosclerosis in former NFL players as in non-athletes. This study compared cardiovascular (CV) risk factors and coronary atherosclerosis among retired NFL players and two groups of community controls, the population-based Dallas Heart Study and the preventive medicine cohort, the Aerobics Center Longitudinal Study. Retired NFL players (n=201) were matched for ethnicity, age and BMI (Aerobics Center Longitudinal Study, age only). CV risk factors were assessed by survey and screening visit. Coronary atherosclerosis was measured by computed tomography as coronary artery calcium (CAC). Compared to population-based controls, retired NFL players had a significantly lower prevalence of diabetes, hypertension, sedentary lifestyle and the metabolic syndrome, yet a higher prevalence of impaired fasting glucose and hyperlipidemia. However, there was no significant difference in the prevalence of detectable CAC (46 v 48.3%, p=0.69) or distribution of CAC (0-10, 10-100, 100-400, 400+, p=0.11). Comparing retired NFL players to the physically active preventive medicine controls, there was no difference in the amount of CAC. Among retired NFL players, age and hyperlipidemia, not body size, were the most significant predictors of CAC. In conclusion, despite their large body size, retired NFL players do not have a greater prevalence of CV risk factors or amount of CAC than community controls. PMID:19733715

  5. [Obstructive sleep apnea syndrome, endothelial dysfunction and coronary atherosclerosis].

    PubMed

    Dursunoğlu, Neşe; Dursunoğlu, Dursun

    2005-01-01

    In obstructive sleep apnea syndrome (OSAS), repetitive episodes of apnea cause increased sympathetic nerve activity, increased surges in arterial blood pressure, swings in intrathoracic pressure, oxidative stres, hypoxia and hypercapnia. The association of OSAS with some diseases, having endothelial dysfunction in their physiopathology, such as hypertension, diabetes mellitus, obesity, coronary artery diseases, stroke and heart failure is common. Increased sympathetic nerve activity and also endothelial dysfunction which are the results of hypoxia, have important roles in vascular complications of OSAS. When compared with healthy population, an important endothelial dysfunction in OSAS patients and relationship between OSAS severity and endothelial dysfunction have been shown. In this review, the relationship between OSAS and endothelial dysfunction was overviewed. PMID:16258893

  6. Atherosclerosis

    MedlinePlus Videos and Cool Tools

    ... are smooth, allowing blood to flow unimpeded. Atherosclerosis is when harmful material collects on the wall of ... Eventually, the material builds up and a plaque is formed, narrowing the artery. When the build-up ...

  7. Preliminary report: genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis.

    PubMed Central

    Ye, S.; Watts, G. F.; Mandalia, S.; Humphries, S. E.; Henney, A. M.

    1995-01-01

    Stromelysin is a member of the family of metalloproteinases that degrade extracellular matrix. In situ hybridisation and histopathological studies suggest that stromelysin activity may be important in the connective tissue remodelling processes associated with atherogenesis and plaque rupture. Single strand conformation polymorphism analysis identified a common polymorphism in the stromelysin gene promoter located 1171 bp upstream from the start of transcription in which one allele has a run of six adenosines (6A) and another has five adenosines (5A). 72 men with coronary heart disease, were genotyped. They were participants in the St Thomas' Atherosclerosis Regression Study who were randomised to receive usual care (UC), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 months. In these patients the frequency of the 5A allele was 0.49 (95% CI from 0.41 to 0.57) and was not significantly different from that in a sample of 354 healthy UK men. In the UC group, patients who were homozygous for the 6A allele showed greater progression of angiographic disease than those with other genotypes: the minimum absolute width of coronary segments decreased by 0.04 (SEM 0.10) mm for 5A5A, 0.20 (0.07) mm for 5A6A, and 0.67 (0.19) mm for 6A6A (P < 0.01). The findings were similar but slightly less significant for the change in mean absolute width of coronary segments (P < 0.05). No significant associations were seen in patients in the D or DC groups. In data pooled from the three treatment groups, the 6A6A genotype was significantly associated with greater progression of coronary atherosclerosis than other genotypes in patients with baseline percentage diameter stenosis less than 20% (P < 0.05), but not in those with baseline percentage diameter stenosis greater than or equal to 20%. These results provide the first evidence of a link between genetic variation in stromelysin and progression of coronary atherosclerosis and support the

  8. [Effect of a vascular event on drug regimen compliance in patients with coronary atherosclerosis].

    PubMed

    Bunova, S S; Usacheva, E V; Ivanov, A Yu

    2015-01-01

    In order to assess the effect of a vascular event on adherence to treatment we examined a total of 68 patients presenting with coronary atherosclerosis. The patients' age varied from 31 to 84 years (mean 57.1±8.7). There were 55 (81.1%) men and 13 (18.9%) women. Drug regimen compliance was evaluated by means of the Morisky-Green Medication Adherence Questionnaire before and after the vascular event. Of the 68 examined patients, 15 (22.1%) had not taken any therapeutic agents before the vascular event occurred, despite existing arterial hypertension. Drug regimen compliance prior to the vascular event was low in 82.4% of cases. The number of patients with coronary atherosclerosis and low compliance to treatment before the vascular event decreased significantly thereafter (p=0.0012). After the vascular event, the number of patients adhering to the doctor's recommendations on medicamentous therapy increases considerably. At the same time, a sufficiently great number of patients [about 30% of patients after endured myocardial infarction (MI) and 18% after transcutaneous coronary intervention (TCI)] still remain in the category of those "having low drug regimen compliance" and, accordingly, have high risk for the development of recurrent vascular events. Endured TCI increases patient compliance more significantly than MI, which requires additional study of a psychological component of the given fact. PMID:26035560

  9. Accelerated coronary atherosclerosis after execution of percutaneous coronary intervention in patient with HIV/HCV coinfection: case report and review of the literature.

    PubMed

    Ceccarelli, Giancarlo; d'Ettorre, Gabriella; Mancone, Massimo; Francone, Marco; Vullo, Vincenzo

    2011-01-01

    Highly active antiretroviral therapy has greatly reduced AIDS-related morbidity and mortality; however, its widespread use has been associated with a marked rise in the frequency of cardiovascular diseases in patients with HIV. Moreover, HIV infection is associated with accelerated coronary atherosclerosis and vasculopathy, although the mechanisms underlying these findings have not been determined. We describe the case of a 45-year-old woman with HIV/HCV coinfection, irritable bowel syndrome, and accelerated progression of coronary atherosclerosis after execution of percutaneous coronary intervention (PCI). In this case, the rapidity of progression of atherosclerosis seems linked principally to chronic inflammation and excess immune activation that can depend by a concourse of factors (chronic C hepatitis, irritable bowel syndrome, PCI execution) not directly associated with traditional risk factors. Caregivers following HIV-infected patients should be aware of the increased risk of accelerated atherogenesis in these subjects, principally in case of presence of causes of intense immune activation. PMID:21273145

  10. Effects of Long Term Sertraline Treatment and Depression on Coronary Artery Atherosclerosis in Premenopausal Female Primates

    PubMed Central

    Shively, Carol A.; Register, Thomas C.; Appt, Susan E.; Clarkson, Thomas B.

    2015-01-01

    Objectives Major depressive disorder and coronary heart disease (CHD) often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on CHD risk remain unclear. We determined the effects of a SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA. Methods 42 adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase, and assigned to SSRI (sertraline HCl 20 mg/kg, po, once/day) or Placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months CAA extent was measured using histomorphometry. Results Before and during treatment depressed monkeys had lower BW, body mass index (BMI), and plasma high density lipoprotein cholesterol, and higher heart rates during the pretreatment (p<0.01) but not the treatment phase (p=0.17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, BMI, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (Depressed, Nondepressed) × 2 (Placebo, Sertraline) × 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than nondepressed monkeys (p<0.036), and in sertraline than placebo-treated monkeys (p=0.040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than in untreated depressed monkeys, and 6.5 times higher than in non-depressed monkeys, on average. Conclusions Depressed animals develop more CAA, and that longterm treatment with sertraline promotes CAA. PMID:25829239

  11. Nonalcoholic Fatty Liver Disease Is Associated with the Presence and Morphology of Subclinical Coronary Atherosclerosis

    PubMed Central

    Kang, Min Kyoung; Kang, Byeong Hun

    2015-01-01

    Purpose In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease. Materials and Methods We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques. Results Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis. Conclusion Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis. PMID:26256971

  12. Non-invasive Detection of Aortic and Coronary Atherosclerosis in Homozygous Familial Hypercholesterolemia by 64 Slice Multi-detector Row Computed Tomography Angiography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  14. Serum Uric Acid Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals Without Renal Disease

    PubMed Central

    Rodrigues, Ticiana C.; Maahs, David M.; Johnson, Richard J.; Jalal, Diana I.; Kinney, Gregory L.; Rivard, Christopher; Rewers, Marian; Snell-Bergeon, Janet K.

    2010-01-01

    OBJECTIVE To examine uric acid (UA) as a possible predictor of the progression of coronary artery calcification (CAC) using data from the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. RESEARCH DESIGN AND METHODS CAC was measured by electron beam tomography at the baseline and at a follow-up 6.0 ± 0.5 years later. The study population included 443 participants with type 1 diabetes and 526 control subjects who were free of diagnosed coronary artery disease at baseline. The presence of renal disease was defined by the presence of albuminuria and/or low glomerular filtration rate. RESULTS In subjects without renal disease, serum UA predicted CAC progression (odds ratio 1.30 [95% CI 1.07–1.58], P = 0.007) independent of conventional cardiovascular risk factors including diabetes and the presence of metabolic syndrome. CONCLUSIONS Serum UA levels predict the progression of coronary atherosclerosis and may be useful in identifying who is at risk for vascular disease in the absence of significant chronic kidney disease. PMID:20798338

  15. [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. PMID:26906607

  16. Lipoprotein-Associated Phospholipase A2 Activity Predicts Progression of Subclinical Coronary Atherosclerosis

    PubMed Central

    Kinney, Gregory L.; Snell-Bergeon, Janet K.; Maahs, David M.; Eckel, Robert H.; Ehrlich, James; Rewers, Marian

    2011-01-01

    Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA2 is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events. In type 1 diabetes there is an increase in coronary calcium and CVD despite a favorable lipid profile. Levels of Lp-PLA2 in type 1 diabetes are not known, nor is the relationship between Lp-PLA2 and progression of coronary calcification. Methods The Coronary Artery Calcification in Type 1 Diabetes study measured coronary calcium by electron-beam computed tomography twice over a 2.6 ± 0.3-year interval. Lp-PLA2 mass and activity were measured at baseline (n = 1,097 subjects, 506 with and 591 without type 1 diabetes). Results In type 1 diabetes Lp-PLA2 mass was marginally higher (285 ± 79 vs. 278 ± 78 ng/mL, P = 0.1), and Lp-PLA2 activity was significantly lower (137 ± 30 vs. 146 ± 36 nmol/min/mL, P < 0.0001) than in those without diabetes. There was a greater proportion of those with progression of coronary calcification in type 1 diabetes compared with those without diabetes (24% vs. 10%, P < 0.0001). Lp-PLA2 activity was independently associated with progression of coronary calcification in multivariate analysis (4th quartile verses bottom three quartiles, odds ratio = 1.77 [1.08–2.91], P = 0.02). LpPLA2 mass was not significantly associated with progression of coronary calcification in this cohort (P = 0.09). Conclusions Lp-PLA2 activity predicts progression of subclinical atherosclerosis in individuals with and without type 1 diabetes. PMID:21291330

  17. Osteogenic Monocytes within the Coronary Circulation and their Association with Plaque Vulnerability in Patients with Early Atherosclerosis

    PubMed Central

    Collin, Julia; Gössl, Mario; Matsuo, Yoshiki; Cilluffo, Rebecca R.; Flammer, Andreas J.; Loeffler, Darrell; Lennon, Ryan J.; Simari, Robert D.; Spoon, Daniel B.; Erbel, Raimund; Lerman, Lilach O.; Khosla, Sundeep; Lerman, Amir

    2014-01-01

    Objectives This study tests the hypothesis that circulating mononuclear cells expressing osteocalcin (OCN) and bone alkaline phosphatase (BAP) are associated with distinct plaque tissue components in patients with early coronary atherosclerosis. Background Plaque characteristics implying vulnerability develop at the earliest stage of coronary atherosclerosis. Increasing evidence indicates that cells from the myeloid lineage might serve as important mediators of destabilization. Plaque burden and its components were assessed regarding their relationship to monocytes carrying both pro-inflammatory (CD14) and osteogenic surface markers OCN and BAP. Methods Twenty-three patients with angiographically non-obstructive coronary artery disease underwent coronary endothelial function assessment and virtual histology-intravascular ultrasound of the left coronary artery. Plaque composition was characterized in the total segment (TS) and in the target lesion (TL) containing the highest amount of plaque burden. Blood samples were collected simultaneously from the aorta and the coronary sinus. Circulating cell counts were then identified from each sample and a gradient across the coronary circulation was determined. Results Circulating CD14+/BAP+/OCN+ monocytes correlate with the extent of necrotic core and calcification (r=0.53, p=0.010; r=0.55, p=0.006, respectively). Importantly, coronary retention of CD14+/OCN+ cells also correlate with the amount of necrotic core and calcification (r=0.61, p=0.003; r=0.61, p=0.003) respectively. Conclusions Our study links CD14+/BAP+/OCN+ monocytes to the pathologic remodeling of the coronary circulation and therefore associates these cells with plaque destabilization in patients with early coronary atherosclerosis. PMID:25482280

  18. Influence of phenotype conversion of epicardial adipocytes on the coronary atherosclerosis and its potential molecular mechanism

    PubMed Central

    Wang, Jing; Chen, Dong; Cheng, Xun-Min; Zhang, Qi-Gao; Peng, Yong-Ping; Wang, Li-Jun; He, Song-Qing; Gong, Jian-Bin

    2015-01-01

    Objective: To investigate the phenotype conversion of epicardial adipocytes and its potential molecular mechanism during the occurrence and development of coronary atherosclerosis. Methods: A total of 30 health male New Zealand white rabbits were used. In experiment group (n=15), rabbits were fed with high fat food to establish atherosclerosis animal model; rabbits in control group (n=15) were fed with normal food. Results: At week 0, UCP-1 and PPARγ mRNA expressions in EAT and sBAT were significantly higher than in eWAT, and leptin mRNA expression lower than (P<0.05). In experiment group, the mRNA expressions of UCP-1 and PPARγ reduced gradually, but leptin mRNA increased progressively in EAT (P<0.05). UCP-1 expression reduced gradually, the newly generated blood vessels reduced significantly, but leptin and RAM11 increased gradually (P<0.05). The adipocyte volume in EAT increased gradually, but the adipocyte number reduced progressively (P<0.05). The number of mitochondria with multiple crests reduced gradually in EAT; IL-6 reduced the mRNA expressions of UCP-1 and PPARγ in adipocytes of BAT in a dose dependent manner, but it increased the mRNA expressions of leptin and STAT3 (P<0.05). In the presence of IL-6, JSI-124 increased the mRNA expressions of UCP-1 and PPAR-γ in adipocytes of BAT in a dose dependent manner, but it reduced the mRNA expressions of leptin and STAT3 (P<0.05). Conclusion: During the progression of atherosclerosis, there is a phenotype conversion of EAT from BAT to WAT, which further promotes the focal occurrence and development of atherosclerosis; IL-6 may activate JAK-STAT3 pathway to induce this conversion. PMID:26692919

  19. Adipocytokines in Systemic Lupus Erythematosus: Relationship to Inflammation, Insulin Resistance and Coronary Atherosclerosis

    PubMed Central

    Chung, Cecilia P.; Long, Ashley G.; Solus, Joseph F.; Rho, Young Hee; Oeser, Annette; Raggi, Paolo; Stein, C. Michael

    2009-01-01

    We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin, and visfatin were measured in 109 patients with SLE and in 78 control subjects. Coronary calcification was measured by electron beam computed tomography and insulin resistance was defined by the homeostasis (HOMA) index. Concentrations of adiponectin (28.7+/−17.9 vs. 22.0+/−15.3 µg/mL, p=0.003), leptin (41.1+/−49.9 vs. 19.8+/−24.6 ng/mL, p<0.001) and visfatin (7.5+/−10.5 vs. 4.5+/−2.8 ng/mL, p<0.001) were higher in patients with SLE than controls. These differences remained significant after adjustment for age, race, sex and BMI, (all p-values<0.02). Concentrations of resistin (10.7+/−7.6 vs. 9.1+/−5.1 ng/mL, p=0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho=0.80, p<0.001), insulin resistance (rho=0.46, p<0.001), and CRP (rho=0.30, p=0.002), while adiponectin was negatively associated with the same factors (rho= −0.40, p<0.001; rho= −0.38, p<0.001, rho=− 0.22, p=0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE. PMID:19578104

  20. Higher Plasma Docosahexaenoic Acid is Associated with Reduced Progression of Coronary-Artery Atherosclerosis in Women with Established Coronary Artery Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish intake, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and in some cases alpha-linolenic acid (ALA), have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and progression of coronary-artery atherosclerosi...

  1. Associations between HIV Infection and Subclinical Coronary Atherosclerosis: The Multicenter AIDS Cohort Study (MACS)

    PubMed Central

    Post, Wendy S; Budoff, Matthew; Kingsley, Lawrence; Palella, Frank J; Witt, Mallory D; Li, Xiuhong; George, Richard T; Brown, Todd; Jacobson, Lisa P.

    2014-01-01

    Background Coronary artery disease (CAD) has been associated with HIV infection; however data are not consistent. Objective We performed cardiac CT to determine whether HIV-infected men have more coronary atherosclerosis than uninfected men. Design Cross-sectional study within the Multicenter AIDS Cohort Study(MACS). Participants HIV-infected (n=618) and –uninfected (n=383) men who have sex with men (MSM) had non-contrast and contrast enhanced cardiac CT if they were between 40–70 years, weighed <300 pounds, and had no history of coronary revascularization. Measurements Presence and extent, for those with plaque, of coronary artery calcium (CAC) on non-contrast CT, and of any plaque, non-calcified, mixed or calcified plaque and stenosis on CT angiography. Results 1001 men underwent non-contrast CT of whom 759 had coronary CT angiography. After adjusting for age, race, center, and cohort, HIV-infected men had a greater prevalence of CAC [Prevalence ratio(PR)=1.21, 95% confidence interval (CI) 1.08–1.35, p=0.001], and any plaque [PR=1.14(1.05–1.24),p=0.001], including non-calcified plaque [PR=1.28(1.13–1.45),p<0.001) and mixed plaque [PR=1.35(1.10–1.65),p=0.004] than HIV-uninfected men. Associations between HIV-infection and any plaque and non-calcified plaque remained significant (p<0.005) after CAD risk factor adjustment. HIV-infected men also had a greater extent of non-calcified plaque after CAD risk factor adjustment (p=0.026). HIV-infected men had a greater prevalence of coronary artery stenosis>50% than HIV-uninfected men [PR=1.48(1.06–2.07),p=0.020), but not after CAD risk factor adjustment. Longer duration of highly active antiretroviral therapy [PR=1.09(1.02–1.17), p=0.007,per year] and lower nadir CD4+ T-cell count [PR=0.80(0.69–0.94),p=0.005, per 100 cells] were associated with coronary stenosis>50%. Conclusions Coronary artery plaque, especially non-calcified plaque, is more prevalent and extensive in HIV-infected men, independent of

  2. Osteoprotegerin is Associated With Endothelial Function and Predicts Early Carotid Atherosclerosis in Patients With Coronary Artery Disease.

    PubMed

    Morisawa, Taichirou; Nakagomi, Akihiro; Kohashi, Keiichi; Kosugi, Munenori; Kusama, Yoshiki; Atarashi, Hirotsugu; Shimizu, Wataru

    2015-01-01

    Osteoprotegerin (OPG) is a soluble glycoprotein belonging to the tumor necrosis factor receptor superfamily and is linked to vascular atherosclerosis and calcification. The carotid intima-media thickness (CIMT) correlates with carotid atherosclerosis and is a significant predictor of cardiovascular events. The OPG levels are associated with the CIMT in coronary artery disease (CAD) patients. However, the pathophysiological mechanisms underlying this pathway remain unclear. We investigated 114 CAD patients (89 men, 25 women; mean age: 68.7 ± 10.3 years) and measured the Gensini score (a marker of the extent of coronary atherosclerosis), the mean CIMT and the plasma levels of OPG and asymmetric dimethylarginine (ADMA; a marker of endothelial function). Early carotid atherosclerosis was defined as a mean CIMT > 1.0 mm. Only 33 of the 114 patients (28.9%) had early carotid atherosclerosis. Patients with early carotid atherosclerosis had higher OPG levels than those without. The OPG levels were found to be significantly associated with ADMA (r = 0.191, P = 0.046) and the mean CIMT (r = 0.319, P = 0.001), but not with the Gensini score. A receiver operating curve analysis revealed the optimal cut-off value of the OPG levels for predicting early carotid atherosclerosis to be 100 pmol/L. A multivariate logistic regression analysis showed OPG ≥ 100 pmol/L to be significantly and independently associated with early carotid atherosclerosis (odds ratio: 2.98, 95% confidence interval: 1.22-7.20, P = 0.017). These data indicate that OPG is significantly associated with endothelial function and predicts early carotid atherosclerosis in patients with CAD. PMID:26549398

  3. Association between the Polymorphisms in Intercellular Adhesion Molecule-1 and the Risk of Coronary Atherosclerosis: A Case-Controlled Study

    PubMed Central

    Zhang, Qingjiang; Xin, Yu; Chen, Yanjun; Tian, Ye

    2014-01-01

    Intercellular adhesion molecule-1 (ICAM-1), an important immune adhesion molecule, is related to the atherosclerosis. We explored the association between the polymorphisms of the ICAM-1 gene and coronary atherosclerotic stenosis to determine whether any risk factors correlate with genetic polymorphisms in Chinese patients with coronary atherosclerosis. Using the SNaPshot assay, we examined six SNPs of rs5491, rs281428, rs281432, rs5496, rs5498 and rs281437 in 604 patients diagnosed with coronary atherosclerotic stenosis by angiography and in 468 controls. We found that AG genotype of rs5498 had higher frequency in the coronary atherosclerotic stenosis patients (41.56% to 34.19%, P = 0.017, OR = 1.368,95%CI 1.057–1.770) and that the haplotype Ars5491Crs281428Grs281432 had higher frequency in patients (13.8% to 12.1%, P = 0.048). When analyzing the clinical risk factors for coronary atherosclerosis, we found that the rs5498 locus was associated with the levels of apolipoprotein A (APOA) (P = 0.0002) and triglycerides (TG) (P = 0.002). Furthermore, the levels of triglycerides (TG) were also associated with rs281432 (P = 0.040). Additionally, the TT genotype of rs281437 was associated with a higher level of apolipoprotein A (APOA) (P = 0.039) and apolipoprotein B (APOB) (P = 0.003). Finally, among those with coronary atherosclerosis, we found no differences in the haplotype analysis of polymorphisms of the ICAM-1 gene from individuals with hypertension or those who smoked. According to our results, the ICAM-1 polymorphisms were associated with risk of coronary atherosclerotic stenosis in Chinese individuals. PMID:25310099

  4. NALP3-Inflammasome-Related Gene Polymorphisms in Patients with Prehypertension and Coronary Atherosclerosis

    PubMed Central

    Zhao, Xin; Gu, Chonghuai; Yan, Chenghui; Zhang, Xiaolin; Li, Yi; Wang, Li; Ren, Lili; Zhang, Yan; Peng, Junyin; Zhu, Zhiming

    2016-01-01

    Objectives. Prehypertension is an early stage of hypertension that is characterized by inflammatory factors. Inflammation also plays an essential role in the development of coronary atherosclerosis (CAS). The present study evaluated the NALP3-inflammasome and its related genes, NLRP3, NOD2, and CARD8, using SNP linkage and gene haplotypes in prehypertensive patients. Methods. A total of 576 patients with prehypertension and suspected coronary heart disease (CHD) were enrolled. According to coronary angiography, patients were divided into two groups: arterial stenosis <50% of the diameter (control) and arterial stenosis >50% of the diameter (case). Fifteen polymorphisms in the NOD2, NLRP3, and CARD8 genes were analyzed, and serum levels of C-reactive protein (CRP) were measured. Results. When comparing allele frequencies, none of these 15 SNPs in NOD2, CARD8, and NLPR3 genes showed a significant difference using multiple logistic regression. However, the CTACATAA (p = 0.0064) and CCACATAG (p = 0.0126) haplotypes of the NOD2 gene SNPs were significantly different between cases and controls. Conclusions. Although our study excludes a significant association of selected SNPs in these genes with CHD in prehypertension patients, this work suggests that the CTACATAA and CCACATAG haplotypes were associated with CHD in the NOD2 locus. This work suggests that the CTACATAA and CCACATAG haplotypes were associated with CHD in prehypertension patients in the NOD2 locus. PMID:27446957

  5. Progression of coronary artery calcification at the crossroads: sign of progression or stabilization of coronary atherosclerosis?

    PubMed Central

    Carrascosa, Patricia; Bruining, Nico

    2016-01-01

    Coronary artery calcification (CAC) has been strongly established as an independent predictor of adverse events, with a significant incremental prognostic value over traditional risk stratification algorithms. CAC progression has been associated with a higher rate of events. In parallel, several randomized studies and meta-analysis have shown the effectiveness of statins to slow progression and even promote plaque regression. However, evidence regarding the effect of routine medical therapy on CAC has yielded conflicting results, with initial studies showing significant CAC regression, and contemporaneous data showing rather the opposite. Accordingly, there is currently a great controversy on whether progression of CAC is a sign of progression or stabilization of coronary artery disease (CAD). The finding of inexorable CAC progression despite the implementation of intensive contemporaneous medical therapy suggests that further understanding of this phenomenon should be undertaken before the implementation of CAC as a surrogate endpoint for longitudinal studies, or for prospective follow-up of patients under routine medical treatment. PMID:27280088

  6. Endothelial Lipase Concentrations Are Increased in Metabolic Syndrome and Associated with Coronary Atherosclerosis

    PubMed Central

    Badellino, Karen O; Wolfe, Megan L; Reilly, Muredach P; Rader, Daniel J

    2006-01-01

    Background Endothelial lipase (EL), a new member of the lipase family, has been shown to modulate high-density lipoprotein (HDL-C) metabolism and atherosclerosis in mouse models. We hypothesized that EL concentrations would be associated with decreased HDL-C and increased atherosclerosis in humans. Methods and Findings Healthy individuals with a family history of premature coronary heart disease (n = 858) were recruited as part of the Study of the Inherited Risk of Atherosclerosis. Blood was drawn in the fasting state before and, in a subgroup (n = 510), after administration of a single dose of intravenous heparin. Plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (CAC) was quantified by electron beam computed tomography. Plasma EL mass was measured using a newly developed enzyme-linked immunosorbent assay. Median EL mass in pre-heparin plasma was 442 (interquartile range = 324–617) ng/ml. Median post-heparin mass was approximately 3-fold higher, 1,313 (888–1,927) ng/ml. The correlation between pre-heparin EL mass and post-heparin EL mass was 0.46 (p < 0.001). EL mass concentrations in both pre- and post-heparin plasma significantly correlated with all NCEP ATPIII-defined metabolic syndrome factors: waist circumference (r = 0.28 and 0.22, respectively, p < 0.001 for each), blood pressure (r = 0.18 and 0.24, p < 0.001 for each), triglycerides (r = 0.22, p < 0.001; and 0.13, p = 0.004), HDL cholesterol (r = –0.11, p = 0.002; and –0.18, p < 0.001), and fasting glucose (r = 0.11 and 0.16, p = 0.001 for both). EL mass in both routine (odds ratio [OR] = 1.67, p = 0.01) and post-heparin (OR = 2.42, p = 0.003) plasma was associated with CAC as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women), and established cardiovascular risk factors. Conclusions We report, to our

  7. Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.

    PubMed

    Chambless, Lloyd E; Folsom, Aaron R; Sharrett, A Richey; Sorlie, Paul; Couper, David; Szklo, Moyses; Nieto, F Javier

    2003-09-01

    Risk prediction functions for incident coronary heart disease (CHD) were estimated using data from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of CHD in 15,792 persons recruited in 1987-1989 from four U.S. communities, with follow-up through 1998. Predictivity of which individuals had incident CHD was assessed by increase in area under ROC curves resulting from adding nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors. We also assessed the increase in population attributable risk. The additional factors were body mass index; waist-hip ratio; sport activity index; forced expiratory volume; plasma fibrinogen, factor VIII, von Willebrand factor, and Lp(a); heart rate; Keys score; pack-years smoking; and subclinical disease marker carotid intima-media thickness. These factors substantially improved prediction of future CHD for men, less for women, and also increased attributable risks. PMID:14505774

  8. Lysosomal cholesterol accumulation in macrophages leading to coronary atherosclerosis in CD38(-/-) mice.

    PubMed

    Xu, Xiaoyang; Yuan, Xinxu; Li, Ningjun; Dewey, William L; Li, Pin-Lan; Zhang, Fan

    2016-06-01

    The disruption in transportation of oxLDL-derived cholesterol and the subsequent lipid accumulation in macrophages are the hallmark events in atherogenesis. Our recent studies demonstrated that lysosomal Ca(2+) messenger of nicotinic acid adenine dinucleotide phosphate (NAADP), an enzymatic product of CD38 ADP-ribosylcyclase (CD38), promoted lipid endocytic trafficking in human fibroblast cells. The current studies are designed to examine the functional role of CD38/NAADP pathway in the regulation of lysosomal cholesterol efflux in atherosclerosis. Oil red O staining showed that oxLDL concentration-dependently increased lipid buildup in bone marrow-derived macrophages from both wild type and CD38(-/-) , but to a significant higher extent with CD38 gene deletion. Bodipy 493/503 fluorescence staining found that the deposited lipid in macrophages was mainly enclosed in lysosomal organelles and largely enhanced with the blockade of CD38/NAADP pathway. Filipin staining and direct measurement of lysosome fraction further revealed that the free cholesterol constituted a major portion of the total cholesterol segregated in lysosomes. Moreover, in situ assay disclosed that both lysosomal lumen acidity and the acid lipase activity were reduced upon cholesterol buildup in lysosomes. In CD38(-/-) mice, treatment with Western diet (12 weeks) produced atherosclerotic damage in coronary artery with striking lysosomal cholesterol sequestration in macrophages. These data provide the first experimental evidence that the proper function of CD38/NAADP pathway plays an essential role in promoting free cholesterol efflux from lysosomes and that a defection of this signalling leads to lysosomal cholesterol accumulation in macrophages and results in coronary atherosclerosis in CD38(-/-) mice. PMID:26818887

  9. Pericoronary adipose tissue: a novel therapeutic target in obesity-related coronary atherosclerosis.

    PubMed

    Mazurek, Tomasz; Opolski, Grzegorz

    2015-01-01

    Inflammation plays a crucial role in the development and destabilization of atherosclerotic plaques in coronary vessels. Adipose tissue is considered to act in paracrine manner, which modulates a number of physiological and pathophysiological processes. Perivascular adipose tissue has developed specific properties that distinguish it from the fat in other locations. Interestingly, its activity depends on several metabolic conditions associated with insulin resistance and weight gain. Particularly in obesity perivascular fat seems to change its character from a protective to a detrimental one. The present review analyzes literature in terms of the pathophysiology of atherosclerosis, with particular emphasis on inflammatory processes. Additionally, the authors summarize data about confirmed paracrine activity of visceral adipose tissue and especially about pericoronary fat influence on the vascular wall. The contribution of adiponectin, leptin and resistin is addressed. Experimental and clinical data supporting the thesis of outside-to-inside signaling in the pericoronary milieu are further outlined. Clinical implications of epicardial and pericoronary adipose tissue activity are also evaluated. The role of pericoronary adipose tissue in obesity-related atherosclerosis is highlighted. In conclusion, the authors discuss potential therapeutical implications of these novel phenomena, including adipokine imbalance in pericoronary adipose tissue in the setting of obesity, the influence of lifestyle and diet modification, pharmaceutical interventions and the growing role of microRNAs in adipogenesis, insulin resistance and obesity. Key teaching points: • adipose tissue as a source of inflammatory mediators • changes in the vascular wall as a result of outside-to-inside signaling • anatomy, physiology, and clinical implications of epicardial and pericoronary adipose tissue activity • adipokines and their role in obesity-related atherosclerosis • therapeutic

  10. Cytomegalovirus Infection and Atherosclerosis in Candidate of Coronary Artery Bypass Graft

    PubMed Central

    Heybar, Habib; Alavi, Seyed Mohammad; Farashahi Nejad, Mehdi; Latifi, Mahmood

    2015-01-01

    Background: Although there is enough evidence that infectious agents such as Chlamydia pneumonia and Helicobacter pylori may play a pathogenic role in atherosclerosis, this role for cytomegalovirus (CMV) is yet controversial. Objectives: The aim of the present study was to detect CMV-DNA in atherosclerotic plaques in patients who underwent coronary artery bypass graft (CABG). Patients and Methods: In this case-control study, candidates for CABG (cases) and patients with valvular or congenital malformation but without atherosclerotic plaques (controls) were studied from 2012 to 2013 at Golestan hospital, Ahvaz, IR Iran. Demographic and laboratory data were collected. Atherosclerotic and histological samples were obtained from visible plaques and from aorta by the surgeon. All the samples were examined for the presence of CMV-DNA by polymerase chain reaction (PCR) method using a commercial kit (SinaClon, Tehran, IR Iran). Results: The mean ages in case and control groups were 60.8 ± 6.8 and 57.5 ± 11.5 years, respectively, with no significant difference (P = 0.09). Thirty patients (54.5%) in case and 32 (58.2%) in control groups were male with no significant difference (P = 0.7). CMV-DNA was present in 8 (14.5%) of the cases and 2 (4%) of the controls. CMV-DNA was associated with higher risk of atherosclerosis (OR: 7.7, 95% CI = 1.1-51.4, P = 0.03). Of the total normal aortic samples (55 in cases and 55 in controls), there was no individual with simultaneous positive CMV-DNA among aortic atherosclerotic and normal tissue samples. Conclusions: The presence of CMV-DNA in aortic plaques is associated with increased risk of atherosclerosis. CMV infection may be considered as an independent risk factor for this event. PMID:25834719

  11. Progression of Coronary Calcium and Incident Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Budoff, Matthew J.; Young, Rebekah; Lopez, Victor A.; Kronmal, Richard A.; Nasir, Khurram; Blumenthal, Roger S.; Detrano, Robert C.; Bild, Diane E.; Guerci, Alan D.; Liu, Kiang; Shea, Steven; Szklo, Moyses; Post, Wendy; Lima, Joao; Bertoni, Alain; Wong, Nathan D.

    2014-01-01

    Background Coronary artery calcium (CAC) predicts coronary heart disease (CHD) events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. We examined whether progression of CAC is a predictor of future CHD events. Methods and Results We studied 6,778 persons (52.8% female) aged 45–84 years from the Multi-Ethnic Study of Atherosclerosis. 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n=1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max=9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HR) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. 343 total and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 units. Among persons without CAC at baseline (n=3,396), a 5 unit annual change in CAC was associated with an adjusted HR of 1.4 (1.0–1.9) for total and 1.5 (1.1–2.1) for hard CHD. Among those with CAC>0 at baseline HR’s (per 100 unit annual change) were 1.2 (1.1–1.4) and 1.3 (1.1–1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HR’s of 3.8 (1.5–9.6) for total and 6.3 (1.9–21.5) for hard CHD compared to those without progression. Conclusions Progression of CAC is associated with an increased risk for future hard and total CHD events. PMID:23500326

  12. [Clinical study of the month: ASTEROID: regression of coronary atherosclerosis with rosuvastatin at a maximal daily dose of 40 mg].

    PubMed

    Scheen, A J

    2006-04-01

    ASTEROID is a prospective, open-label blinded end-points trial aiming to assess whether very intensive statin therapy with rosuvastatin 40 mg/day could regress coronary atherosclerosis as determined by intravascular ultrasound (IVUS). This multinational study included 507 patients, among whom 349 had evaluable serial IVUS examinations at 24 months. Rosuvastatin decreased LDL cholesterol level from 130 mg/dl to 61 mg/dl (- 53.2%) and increased HDL cholesterol from 43 to 49 mg/dl (+ 14.7%). The three prespecified IVUS efficacy parameters were positively altered by rosuvastatin, demonstrating regression of coronary atherosclerosis : the mean change in percent atheroma volume (- 0.98%), the change in atheroma volume in the most diseased 10-mm subsegment me (- 6.1 mm3) and the change in total atheroma volume (- 6.8%) were all significant (p < 0,001). Adverse events were infrequent and similar to other statin trials. The present study demonstrates that a 2-year treatment with a high dose of rosuvastatin 40 mg/day is able to induce significant regression of coronary atherosclerosis as determined by IVU imaging. Further ongoing studies in the GALAXY clinical investigation programme should now demonstrate that rosuvastatin, the most potent statin to reduce LDL and increase HDL cholesterol, is also able to diminish the incidence of clinical outcomes, cardiovascular events in general and major coronary events in particular. PMID:16789616

  13. Coronary Artery Calcium Score and Risk Classification for Coronary Heart Disease Prediction: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Polonsky, Tamar S.; McClelland, Robyn L.; Jorgensen, Neal W.; Bild, Diane E.; Burke, Gregory L.; Guerci, Alan D.; Greenland, Philip

    2010-01-01

    Context Coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. Objective To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. Design, Setting and Participants CACS was measured by computed tomography on 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded for the primary analysis. Five-year risk estimates for incident CHD were categorized as 0-<3%, 3-<10%, and ≥10% using Cox proportional hazards models. Model 1 used age, gender, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement (NRI) and compared the distribution of risk using Model 2 versus Model 1. Main Outcome Measures Incident CHD events Results Over 5.8 years median follow-up, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared to Model 1 (NRI=0.25, 95% confidence interval 0.16-0.34, P<0.001). With Model 1, 69% of the cohort was classified in the highest or lowest risk categories, compared to 77% with Model 2. An additional 23% of those who experienced events were reclassified to high risk, and an additional 13% without events were reclassified to low risk using Model 2. Conclusions In the MESA cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in

  14. Relationship Between Cystatin C and Coronary Artery Atherosclerosis Progression Differs by Type 1 Diabetes

    PubMed Central

    Snell-Bergeon, Janet K.; Hokanson, John E.; Kinney, Gregory L.; Berl, Tomas; Rewers, Marian; Ogden, Lorraine G.

    2010-01-01

    Abstract Background Cystatin C has been proposed to better estimate renal function and predict cardiovascular disease (CVD) than serum creatinine. To expand on our previous report, we investigated whether the relationship of cystatin C to progression of coronary artery atherosclerosis (CA) differed between individuals with type 1 diabetes (T1D) and persons without diabetes. Methods Coronary artery calcium was measured twice over 2.4 ± 0.4 years (n = 1,123, age = 39 ± 9 years, 47% male, 45% T1D). Significant CA progression was defined as a ≥2.5 increase in square root calcium volume score or development of clinical coronary artery disease. Stepwise multiple logistic regression was performed to investigate whether the association of cystatin C to CA progression differed by T1D status. Results The main finding and novelty of this article is that while the univariate association of cystatin C to CA progression was similar in T1D patients and persons without diabetes mellitus and in the expected direction (increased cystatin C as a biomarker of worsening renal function associated with CA progression), the association of cystatin C to progression of CA differed by T1D status (P = 0.01) after adjustment for other CVD risk factors. Unexpectedly, in persons without diabetes mellitus having relatively normal renal function, increased cystatin C was associated with decreased CA progression (odd ratio [OR] = 0.65, 95% confidence interval 0.44–0.96, P = 0.029) after adjustment, primarily due to adjustment for body mass index (BMI). Removal of BMI from this model resulted in a 49% change in the OR. Conclusions Our hypothesis-generating data suggest a complex relationship among cystatin C, BMI, and CA progression that requires further study. PMID:20082582

  15. Leptin Receptor Gene Polymorphisms and the Risk of Non-Alcoholic Fatty Liver Disease and Coronary Atherosclerosis in the Chinese Han Population

    PubMed Central

    An, Bai-Quan; Lu, Lin-Lin; Yuan, Chen; Xin, Yong-Ning; Xuan, Shi-Ying

    2016-01-01

    Background Leptin receptor (LEPR) polymorphisms have been reported to be associated with lipid metabolism and insulin resistance in various populations. However, whether LEPR polymorphisms are associated with the risks of non-alcoholic fatty liver disease (NAFLD) and coronary atherosclerosis in the Chinese Han population remains unknown. Objectives To investigate the association of LEPR polymorphisms at Q223R and K109R with the risks of NAFLD and coronary atherosclerosis in the Chinese Han population. Patients and Methods Genotypes of LEPR Q223R and K109R were determined by polymerase chain reaction followed by sequencing in patients with NAFLD (n = 554), coronary atherosclerosis (n = 421), and healthy controls (n = 550). Serum lipid profiles were determined using biochemical methods. Pearson’s χ2 test was used to check for Hardy-Weinberg equilibrium and to analyze the distributions of genotypes’ alleles between groups. Baseline characteristics were analyzed using student’s t-test, paired-samples t-test, or the χ2 test where appropriate. Results The LEPR Q223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR = 0.683, 95% CI: 0.527 - 0.884, P = 0.004 and OR = 0.724, 95% CI: 0.548 - 0.955, P = 0.022, respectively). Compared to controls, no significant differences in the genotype and allele frequencies of K109R were found in the NAFLD and coronary atherosclerosis populations, respectively. However, there was a significantly increased risk of coronary atherosclerosis in NAFLD patients who carried the K109R A allele (OR = 2.283, 95% CI: 1.556 - 3.348, P < 0.001). Conclusions LEPR Q223R polymorphisms may confer a significant risk of NAFLD and coronary atherosclerosis. The A allele in the K109R polymorphism might be considered an independent risk factor for coronary atherosclerosis in NAFLD patients. PMID:27257426

  16. Epicardial Fat is Associated with Duration of Antiretroviral Therapy and Coronary Atherosclerosis: The Multicenter AIDS Cohort Study

    PubMed Central

    Brener, Michael; Ketlogetswe, Kerunne; Budoff, Matthew; Jacobson, Lisa P.; Li, Xiuhong; Rezaeian, Panteha; Razipour, Aryabod; Palella, Frank J; Kingsley, Lawrence; Witt, Mallory D; George, Richard T; Post, Wendy S

    2014-01-01

    Objective Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and anti-retroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine if HIV infection is associated with greater epicardial fat and if epicardial fat is associated with subclinical coronary atherosclerosis. Design We studied 579 HIV-infected and 353 HIV-uninfected men age 40 to 70 years with non-contrast computed tomography (CT) to measure epicardial adipose tissue volume (EAT) and coronary artery calcium (CAC). Total plaque score (TPS), and plaque subtypes (non-calcified, calcified and mixed) were measured by coronary CT angiography in 706 men. Methods We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race and serostatus and with additional cardiovascular (CV) risk factors and tested for modifying effects of HIV serostatus. Results HIV-infected men had greater EAT than HIV-uninfected men (p=0.001). EAT was positively associated with duration of antiretroviral therapy (p=0.02), specifically AZT (p<0.05). EAT was associated with presence of any coronary artery plaque (p=0.006) and non-calcified plaque (p=0.001), adjusting for age, race, serostatus and CV risk factors. Among men with CAC, EAT was associated with CAC extent (p=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. Conclusions Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV. PMID:24809732

  17. Suppression of coronary atherosclerosis by helix B surface Peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin.

    PubMed

    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

  18. Do Cardiovascular Risk Factors and Severity and Complexity of Coronary Atherosclerosis Predict Aortic Pulse Pressure during Cardiac Catheterization?

    PubMed

    Bhatt, Hemal; Sanghani, Dharmesh; Apergis, George; Fernaine, George

    2016-06-01

    Pulse pressure (PP), estimated from the peripheral blood pressure measurements, has been linked with adverse cardiovascular events. But, the association of PP and coronary artery disease is not well studied. There is a lack of data on the association of invasively measured aortic PP and cardiovascular risk factors and severity of coronary atherosclerosis. We determined the predictive factors of aortic PP during cardiac catheterization. Electronic medical records from 2010 to 2013 were retrospectively reviewed. A total of 368 patients were eligible. The data on demographics, cardiovascular risk factors, coronary lesion characteristics, and medication use was collected. On multivariable regression analysis, aging (β = 0.34, p = 0.001, 95% confidence interval [CI] 0.14-0.53) and prior aspirin use (β = 5.09, p = 0.015, 95% CI 0.99-9.18) were associated with higher aortic PP. Increasing estimated glomerular filtration rate (β = - 0.52, p = 0.040, 95% CI -0.90 to -0.23) was associated with lower aortic PP. Severity and complexity of coronary lesions, SYNTAX score, and number of obstructed vessels were not associated with aortic PP. Aging, prior aspirin use, and declining renal function were associated with an increase in aortic PP. Aortic PP may not predict the severity and complexity of coronary atherosclerosis. Therefore, the risk of adverse cardiovascular events associated with an elevated aortic PP may not be mediated by the severity of coronary atherosclerosis. PMID:27231423

  19. Automatic quantification and characterization of coronary atherosclerosis with computed tomography coronary angiography: cross-correlation with intravascular ultrasound virtual histology.

    PubMed

    de Graaf, Michiel A; Broersen, Alexander; Kitslaar, Pieter H; Roos, Cornelis J; Dijkstra, Jouke; Lelieveldt, Boudewijn P F; Jukema, J Wouter; Schalij, Martin J; Delgado, Victoria; Bax, Jeroen J; Reiber, Johan H C; Scholte, Arthur J

    2013-06-01

    Plaque constitution on computed tomography coronary angiography (CTA) is associated with prognosis. At present only visual assessment of plaque constitution is possible. An accurate automatic, quantitative approach for CTA plaque constitution assessment would improve reproducibility and allows higher accuracy. The present study assessed the feasibility of a fully automatic and quantitative analysis of atherosclerosis on CTA. Clinically derived CTA and intravascular ultrasound virtual histology (IVUS VH) datasets were used to investigate the correlation between quantitatively automatically derived CTA parameters and IVUS VH. A total of 57 patients underwent CTA prior to IVUS VH. First, quantitative CTA quantitative computed tomography (QCT) was performed. Per lesion stenosis parameters and plaque volumes were assessed. Using predefined HU thresholds, CTA plaque volume was differentiated in 4 different plaque types necrotic core (NC), dense calcium (DC), fibrotic (FI) and fibro-fatty tissue (FF). At the identical level of the coronary, the same parameters were derived from IVUS VH. Bland-Altman analyses were performed to assess the agreement between QCT and IVUS VH. Assessment of plaque volume using QCT in 108 lesions showed excellent correlation with IVUS VH (r = 0.928, p < 0.001) (Fig. 1). The correlation of both FF and FI volume on IVUS VH and QCT was good (r = 0.714, p < 0.001 and r = 0.695, p < 0.001 respectively) with corresponding bias and 95 % limits of agreement of 24 mm(3) (-42; 90) and 7.7 mm(3) (-54; 70). Furthermore, NC and DC were well-correlated in both modalities (r = 0.523, p < 0.001) and (r = 0.736, p < 0.001). Automatic, quantitative CTA tissue characterization is feasible using a dedicated software tool. Fig. 1 Schematic illustration of the characterization of coronary plaque on CTA: cross-correlation with IVUS VH. First, the 3-dimensional centerline was generated from the CTA data set using an automatic tree extraction algorithm (Panel I). Using

  20. Associations between parameters of flow-mediated vasodilatation obtained by continuous measurement approaches and the presence of coronary artery disease and the severity of coronary atherosclerosis.

    PubMed

    Hitaka, Yuka; Miura, Shin-Ichiro; Koyoshi, Rie; Suematsu, Yasunori; Miyase, Yuiko; Norimatsu, Kenji; Adachi, Sen; Shiga, Yuhei; Morito, Natsumi; Nishikawa, Hiroaki; Saku, Keijiro

    2016-01-01

    We investigated the associations between the parameters of flow-mediated vasodilatation (FMD) obtained by continuous measurement approaches and the presence of coronary artery disease (CAD) and the severity of coronary atherosclerosis. The subjects consisted of 282 consecutive patients who underwent coronary angiography (CAG) and in whom we could measure FMD. Using continuous measurement approaches, we measured FMD as the magnitude of the percentage change from brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120 s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups, the CAD group and the non-CAD group, and defined the severity of coronary atherosclerosis according to the Gensini score. The CAD group showed significantly lower %FMD, FMD-MDR, FMD-AUC60, and FMD-AUC120. Gender, smoking, dyslipidemia (DL), and diabetes mellitus (DM), in addition to FMD-AUC120, were identified as significant independent variables that predicted the presence of CAD by a multivariate logistic regression. In addition, a multiple regression analysis indicated that gender, DL, and hypertension, in addition to FMD-AUC120, were predictors of the Gensini score. Finally, we defined the cutoff value of FMD-AUC120 for the prediction of CAD in all patients as 11.1 (sensitivity 0.582, specificity 0.652) by a receiver-operating characteristic (ROC) curve analysis. In conclusion, FMD-AUC120 as assessed by continuous measurement approaches may be a superior marker for evaluating the presence of CAD and the severity of coronary atherosclerosis. PMID:27359079

  1. [Indicators of inflammation in patients with coronary atherosclerosis - role of usCRP in diagnosis and disease progression prediction].

    PubMed

    Samoš, M; Pullmann, R; Funiak, S; Stančík, M; Mokáň, M

    2013-12-01

    Atherosclerosis is being nowadays defined as chronic subclinical inflammatory disease. Recently published clinical and laboratory studies have shown that subclinical inflammation represents main role in initiation of creation, in progress and destabilization of atherosclerotic plaque. Screening including traditional cardiovascular risk factors fails in identification in more than 50% of individuals with later development of acute coronary syndrome. According to above mentioned reason indicators are being searched for, which would be usable to monitor the activity of atherosclerotic process. According to role of subclinical inflammatory process in pathogenesis of atherosclerosis, the determination of C-reactive protein using ultrasensitive method is being showed as perspective marker. Ultrasensitive C-reactive protein represents a strong, independent predictor of future cardiovascular events in apparently heal-thy individuals and has also prognostic utility in patients with acute coronary syndromes. Predictive capacity of C-reactive protein determination is independent of traditional risk factors and offers prognostic advantage as opposed to determination of lipids alone. The paper provides a review of currently available knowledge of possibilities for utilization of C-reactive protein laboratory assessment, as the main representative of acute phase proteins, in monitoring of creation and severity of coronary atherosclerosis, in possibilities of the disease prognosis determination and prediction of its acute complications, and also in prediction of prognosis in patient with already existing acute complication. PMID:24350937

  2. Diagnostic Value of Nitroglycerin-Induced Headache as a Negative Predictor of Coronary Atherosclerosis

    PubMed Central

    Cho, Sook Hee; Sim, Doo Sun; Hong, Young Joon; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2011-01-01

    The purpose of the present study was to clarify the possible relationship between nitroglycerin (NTG)-induced headache and both vascular functional and organic atherosclerosis. The study included 96 patients with NTG-induced headache (group I: 54.7±9.5 years, 52 males) and 204 patients without headache (group II: 58.1±9.1 years, 127 males) who suffered from new-onset chest pain. Flow-mediated dilation and nitroglycerin-mediated dilation were significantly greater in group I than in group II (8.8±4.1% vs. 7.1±3.5%, p=0.001, and 23.1±7.3% vs. 17.1±11.8%, p<0.001, respectively). The carotid intima-media thickness was significantly smaller in group I than in group II (0.55±0.15 mm vs. 0.67±0.22 mm, p=0.001). Heart-carotid pulse wave velocity was significantly lower in group I than in group II (784.5±160.1 m/s vs. 979.1±215.6 m/s, p=0.003). In the multiple regression analysis, the absence of NTG-induced headache was a predictor of coronary artery disease (CAD) (odds ratio: 17.89, 95% confidence interval: 7.89-40.02, p<0.001). NTG-induced headache developed more frequently in patients with normal coronary arteries or minimal CAD than in patients with obstructive CAD. The presence of NTG-induced headache might be helpful and provide additional information in evaluating patients with chest pain syndrome. PMID:22111051

  3. HLA-DRBeta1, circulating Th1/Th2 cytokines and immunological homunculus in coronary atherosclerosis.

    PubMed

    Mostafazadeh, Amrollah; Saravi, Mehrdad; Niaki, Haleh Akhavan; Drabbels, Jos; Gholipour, Haji Mohammad; Minagar, Milad; Mosavi, Ezatola; Jalali, Farzad; Bijani, Ali

    2011-03-01

    Coronary atherosclerotic disease is one of the most endangering health disorder worldwide. This study was designed to investigate the correlation between HLA-DR1 alleles and circulating Th1/Th2 type cytokines in coronary atherosclerosis. By Elisa, Th1/Th2 type cytokines were determined in serum samples of 31 subjects with unstable angina, 27 subjects with chronic stable angina and 24 individuals as normal control. By SSP-PCR, more than 100 alleles of HLA-DRBeta1 were typed in 24 subjects who had skewed serum levels of Th1/Th2 type cytokines. Lipid profiles were determined by the routine methods of clinical laboratory in all subjects. The mean serum concentration of IL-10 in normal control subjects was higher in comparison to the patient groups.0.33±0.59 pg/ml versus 0.064±0.3 pg/ml in unstable angina pectoris group (p<0.028) and 0.22±0.6 pg/ml in chronic stable subjects. There was no statistically significant difference among the groups in serum levels of other desired cytokines (IFN-Gamma, IL-4). 33.33% of normal control subjects were HLA-DR16 positive whereas none of the subjects with chronic stable angina or individuals with unstable angina pectoris was positive for this antigen. The mean concentration of serum LDL-cholesterol in normal control group was high 142.046±35.40 (pg/ml).This preliminary study shows that the atherogenic effect of the LDL- cholesterol may be dampened by HDL-cholesterol through anti inflammatory cytokine IL-10 and HLA-DR16, a phenomenon interpretable via immunological homunculus theory. PMID:21358010

  4. Synergistic effect of hypertension with diabetes mellitus and gender on severity of coronary atherosclerosis: Findings from Tehran Heart Center registry

    PubMed Central

    Masoudkabir, Farzad; Poorhosseini, Hamidreza; Vasheghani-Farahani, Ali; Hakki, Elham; Roayaei, Pegah; Kassaian, Seyed Ebrahim

    2015-01-01

    BACKGROUND We performed this study to evaluate the possible synergism between hypertension and other conventional risk factors of coronary artery disease (CAD) on an angiographic severity of coronary atherosclerosis. METHODS A cross-sectional study was conducted on 10502 consecutive patients who underwent coronary angiography in the cardiac catheterization laboratory of Tehran Heart Center Hospital (Tehran University of Medical Sciences, Iran), and their conventional risk factors including male gender, hypertension, diabetes mellitus (DM), dyslipidemia, smoking, and family history of premature CAD were recorded. The severity of coronary atherosclerosis evaluated by calculation of Gensini’s score. RESULTS All aforementioned conventional risk factors of CAD were independently associated with severity of CAD. Multivariate linear regression analysis demonstrated that hypertension had synergistic effect with male gender [Excess Gensini’s score: 5.93, 95% confidence interval (CI): 2.72-9.15, P < 0.001] and also with DM (Excess Gensini’s score: 3.99, 95% CI: 0.30-7.69, P = 0.034) on severity of CAD. No interaction was observed between hypertension and smoking, dyslipidemia and also with a family history of CAD. CONCLUSION Hypertension has a synergistic effect with DM and male gender on the severity of CAD. These findings imply that more effective screening and treatment strategies should be considered for early diagnosis and tight control of hypertension in male and diabetic people for prevention of advanced CAD. PMID:26862339

  5. HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population

    PubMed Central

    Sabina, Shrestha; Cui, Ning-hua; Zhang, Shuai; Liu, Ze-jin; Li, Cong; Zheng, Fang

    2016-01-01

    A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors. In a two-stage case-control study with a total of 2317 CAD patients and 2404 controls, the AG + AA genotypes of SNP rs2107595 were significantly associated with increased CAD risk (Adjusted odds ratio (OR) = 1.23, Padj = 0.001) and higher modified Gensini scores (Adjusted OR = 1.38, Padj < 0.001). These associations remained significant in subtype analyses for unstable angina pectoris (UAP), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Subgroup and multifactor dimensionality reduction analyses (MDR) further found the gene-environment interactions among SNP rs2107595, body mass index, type 2 diabetes and hyperlipidemia in CAD risk and the severity of coronary atherosclerosis. Moreover, patients with CAD had higher levels of HDAC9 mRNA expression and plasma HDAC9 than controls. Subsequent genotype-phenotype analyses observed the significant correlations of SNP rs2107595 with HDAC9 mRNA expression and plasma HDAC9 levels in controls and patients with NSTEMI and STEMI. Taken together, our data suggest that SNP rs2107595 may contribute to coronary atherosclerosis and CAD risk through a possible mechanism of regulating HDAC9 expression and gene-environment interactions. PMID:27494404

  6. HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population.

    PubMed

    Wang, Xue-Bin; Han, Ya-di; Sabina, Shrestha; Cui, Ning-Hua; Zhang, Shuai; Liu, Ze-Jin; Li, Cong; Zheng, Fang

    2016-01-01

    A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors. In a two-stage case-control study with a total of 2317 CAD patients and 2404 controls, the AG + AA genotypes of SNP rs2107595 were significantly associated with increased CAD risk (Adjusted odds ratio (OR) = 1.23, Padj = 0.001) and higher modified Gensini scores (Adjusted OR = 1.38, Padj < 0.001). These associations remained significant in subtype analyses for unstable angina pectoris (UAP), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Subgroup and multifactor dimensionality reduction analyses (MDR) further found the gene-environment interactions among SNP rs2107595, body mass index, type 2 diabetes and hyperlipidemia in CAD risk and the severity of coronary atherosclerosis. Moreover, patients with CAD had higher levels of HDAC9 mRNA expression and plasma HDAC9 than controls. Subsequent genotype-phenotype analyses observed the significant correlations of SNP rs2107595 with HDAC9 mRNA expression and plasma HDAC9 levels in controls and patients with NSTEMI and STEMI. Taken together, our data suggest that SNP rs2107595 may contribute to coronary atherosclerosis and CAD risk through a possible mechanism of regulating HDAC9 expression and gene-environment interactions. PMID:27494404

  7. Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine

    PubMed Central

    Rocchiccioli, Silvia; Cecchettini, Antonella; Ucciferri, Nadia; Terreni, Marianna; Viglione, Federica; Trivella, Maria Giovanna; Citti, Lorenzo; Parodi, Oberdan; Pelosi, Gualtiero

    2015-01-01

    A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation (R2 = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease. PMID:26379359

  8. What Causes Coronary Microvascular Disease?

    MedlinePlus

    ... Living With Clinical Trials Links Related Topics Angina Atherosclerosis Coronary Heart Disease Coronary Heart Disease Risk Factors ... Microvascular Disease? The same risk factors that cause atherosclerosis may cause coronary microvascular disease. Atherosclerosis is a ...

  9. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA)123

    PubMed Central

    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

    2009-01-01

    Background: 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. Objective: We investigated whether pericardial fat predicts future coronary heart disease events. Design: 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. Results: 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. Conclusion: Pericardial fat predicts incident coronary heart disease independent of conventional risk factors, including body mass index. PMID:19571212

  10. The Association between Plasma 25OHD3 Concentrations, C-Reactive Protein Levels, and Coronary Artery Atherosclerosis in Postmenopausal Monkeys

    PubMed Central

    Schnatz, Peter F.; Vila-Wright, Sharon; Jiang, Xuezhi; Register, Thomas C.; Kaplan, Jay R.; Clarkson, Thomas B.; Appt, Susan E.

    2012-01-01

    Objective To identify potential relationships between plasma 25OHD, C-reactive protein (CRP), coronary artery atherosclerosis (CAA), and coronary artery remodeling in monkeys consuming atherogenic diets. Methods Female cynomolgus monkeys (n=74) were fed a casein-lactalbumin (C/L) based, moderately atherogenic diet for 12 months. They then consumed either a soy (n=35) or C/L (n=39) based diet for 32 months. CRP concentrations were then determined and monkeys underwent surgical menopause. Each diet group was then re-randomized to receive soy (n=36) or C/L (n=38). After 32 post-menopausal months, 25OHD, CRP, CAA, and coronary artery remodeling were determined. All monkeys received a women’s equivalent of 1,000 IU/day of 25OHD3 and 1,200 mg/day of calcium, throughout the study. Results The pre and post-menopausal dietary protein sources had no effect on post-menopausal 25OHD3 concentrations (p=0.6). Across treatment groups, there was a statistically significant inverse relationship between 25OHD3 concentrations and CRP at necropsy (r=-0.35, p=0.003). A significant inverse correlation between 25OHD3 concentration and the change in CRP, from pre-menopause to post-menopause, was observed (r=-0.32, p=0.007). The significant associations identified between plasma 25OHD3 and CRP remained after controlling for postmenopausal diet. Those monkeys with a greater increase in CRP also had significantly more CAA and less ability to maintain normal lumens by remodeling. Conclusions Higher plasma concentrations of 25OHD3 were associated with lower CRP. Lower CRP was associated with less coronary atherosclerosis and improved coronary artery remodeling. These findings suggest that 25OHD3 concentrations are associated with an anti-inflammatory state and may support an association between oral 25OHD3 and cardioprotection. PMID:22713861

  11. Anti-Inflammatory Diet for Atherosclerosis and Coronary Artery Disease: Antioxidant Foods

    PubMed Central

    Saita, Emi; Kondo, Kazuo; Momiyama, Yukihiko

    2014-01-01

    Oxidative stress plays a role in atherosclerotic diseases such as coronary artery disease (CAD), and much attention has been paid to antioxidant foods. The relationships between the consumption of vegetables and fruits and atherosclerotic diseases have been reported in many epidemiological studies showing a reduced risk of such diseases. In addition to the antioxidant vitamins C and E, green and yellow vegetables contain abundant quantities of carotenoids and polyphenols. The consumption of carotenoids and vitamins C and E has been shown to be inversely associated with CAD. However, supplementation with beta-carotene and vitamins C and E shows no beneficial effect, but rather mortality is increased with beta-carotene and vitamin E supplements. Therefore, it is recommended to consume vegetables and fruits, but vitamin supplementation is not recommended. Many epidemiological studies also report that higher consumption of fish, rich in n-3 polyunsaturated fatty acids (PUFAs), is associated with a lower risk of CAD and stroke. Antiatherosclerotic effects of n-3 PUFAs include reduced platelet aggregation, triglyceride-lowering effect, anti-inflammatory effect, and plaque stabilization, but the anti-inflammatory effect is principally responsible for preventing atherosclerosis. It is recommended to consume fish at least twice a week in patients without CAD and to consider n-3 PUFA supplements in patients with documented CAD. Regarding soy products, soy protein consumption reduces low-density-lipoprotein cholesterol and triglyceride levels. Isoflavone, a polyphenol contained in soybeans, has antiatherosclerotic property because it has a structure similar to that of estrogen and bonds with estrogen receptors. High consumption of isoflavone has been reported to be associated with a reduced risk of CAD and stroke only in women, but the preventative effect of soy products in the general population has not yet been clarified. Thus, many epidemiological studies report the

  12. Evading the fate of Pheidippides: acute coronary thrombosis in a young marathon runner with minimal atherosclerosis but sickle cell trait.

    PubMed

    Murray, Scott W; Cooper, Robert M; Mills, Joseph D; Palmer, Nicholas D

    2015-08-01

    Marathon running transiently increases the risk of sudden cardiac death. Some previous studies have suggested that this is due to relatively advanced but asymptomatic atherosclerosis. Other theories suggest that potentiation of inflammation and the coagulation cascade, by extremes of exertion, is more important. We present a clinical case of a young, previously fit athlete who felt chest discomfort eight miles into a marathon but finished the race. Shortly after completion he felt very unwell and had chest pain. Ambulance electrocardiograms showed evidence of an evolving anterior myocardial infarction. Invasive assessment with coronary angiography and intravascular ultrasound was able to show the mechanism of thrombosis. Fissuring of a small rim of atherosclerosis potentiated a large pro-thrombotic response, the patient was also found to have sickle cell trait. Medical treatment with blood thinning drugs was able to restore normality to the vessel over a period of two weeks, without the need for angioplasty or stent implantation. PMID:26331117

  13. Risk Factors for Coronary Heart Disease Among Inpatients Who Have Mild Intellectual Disability and Mental Illness

    ERIC Educational Resources Information Center

    Merriman, S.; Haw, C.; Kirk, J.; Stubbs, J.

    2005-01-01

    Coronary heart disease (CHD) is a major cause of morbidity and mortality in the UK. The aim of this study was to screen inpatients with mild or borderline intellectual disability, many of whom also have mental illness, for risk factors for CHD. Participants were interviewed, measured and had blood samples taken. Of the 53 participants, 20 (37.7%)…

  14. 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…

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

    PubMed Central

    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.; Pfeffer, M.; Brown, V.; Rouleau, J.; Watkins, P.; Wei, L.J.; Gosselin, G.; Chayer, C.; Lanthier, S.; Pelletier, G.B.; Racine, N.; Agarwal, H.; Brilakis, E.; Cannon, L.; Carrié, D.; Corbelli, J.; Coste, P.; de Winter, R.; Diaz, A.; Eisenberg, S.; Ennis, B.; Fajadet, J.; Fam, N.; Fortuin, D.; Gessler, C.; Grines, C.; Guerra, D.; Gum, H.; Haldis, T.; Heestermans, T.; Herrman, J.P.; Huynh, T.; Kedhi, E.; Koren, M.; Kouz, S.; Krolick, M.; Kumkumian, G.; Lavi, S.; Li, R.J.; Masud, ARZ; McAlhany, C.; McGrew, F.A.; O'Shaughnessy, C.; Oude Ophuis, A.J.M.; Parr, K.; Penny, W.; Pesant, Y.; Post, H.; Robinson, S.; Rodes-Cabau, J.; Roy, A.; Schulman, S.; Spence, F.; Stouffer, G.; Stys, T.; Sussex, B.; Tahirkheli, N.; Tardif, J-C.; Grégoire, J.; ten Berg, J.; van Boven, A.J.; von Birgelen, C.; Weinstein, D.

    2014-01-01

    Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting 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. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures 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. Results The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 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. Conclusion CER-001 infusions did not reduce coronary

  16. The mediation of coronary calcification in the association between risk scores and cardiac troponin T elevation in healthy adults: Is atherosclerosis a good prognostic precursor of coronary disease?

    PubMed Central

    Lazzarino, Antonio Ivan; Hamer, Mark; Carvalho, Livia; Gaze, David; Collinson, Paul; Steptoe, Andrew

    2015-01-01

    Background Conventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease. In UK in 2006–2008 (Whitehall II study) we tested the ability of several risk scores to identify individuals with cardiac cell damage and assessed to what extent their estimates were mediated by the presence of atherosclerosis. Methods 430 disease-free, low-risk participants were tested for high-sensitivity cardiac troponin-T (HS-CTnT) and for coronary calcification using electron-beam, dual-source, computed tomography (CAC). We analysed the data cross-sectionally using ROC curves and mediation tests. Results When the risk scores were ranked according to the magnitude of ROC areas for HS-CTnT prediction, a score based only on age and gender came first (ROC area = 0.79), followed by Q-Risk2 (0.76), Framingham (0.70), Joint-British-Societies (0.69) and Assign (0.68). However, when the scores were ranked according to the extent of mediation by CAC (proportion of association mediated), their order was essentially reversed (age&gender = 6.8%, Q-Risk2 = 9.7%, Framingham = 16.9%, JBS = 17.8%, Assign = 17.7%). Therefore, the more accurate a score is in predicting detectable HS-CTnT, the less it is mediated by CAC; i.e. the more able a score is in capturing atherosclerosis the less it is able to predict cardiac damage. The P for trend was 0.009. Conclusions The dynamics through which cardiac cell damage is caused cannot be explained by ‘classic’ heart disease risk factors alone. Further research is needed to identify precursors of heart disease other than atherosclerosis. PMID:26051205

  17. Tortuosity of coronary bifurcation as a potential local risk factor for atherosclerosis: CFD steady state study based on in vivo dynamic CT measurements.

    PubMed

    Malvè, M; Gharib, A M; Yazdani, S K; Finet, G; Martínez, M A; Pettigrew, R; Ohayon, J

    2015-01-01

    The purpose of the present study was to determine whether in vivo bifurcation geometric factors would permit prediction of the risk of atherosclerosis. It is worldwide accepted that low or oscillatory wall shear stress (WSS) is a robust hemodynamic factor in the development of atherosclerotic plaque and has a strong correlation with the local site of plaque deposition. However, it still remains unclear how coronary bifurcation geometries are correlated with such hemodynamic forces. Computational fluid dynamics simulations were performed on left main (LM) coronary bifurcation geometries derived from CT of eight patients without significant atherosclerosis. WSS amplitudes were accurately quantified at two high risk zones of atherosclerosis, namely at proximal left anterior descending artery (LAD) and at proximal left circumflex artery (LCx), and also at three high WSS concentration sites near the bifurcation. Statistical analysis was used to highlight relationships between WSS amplitudes calculated at these five zones of interest and various geometric factors. The tortuosity index of the LM-LAD segment appears to be an emergent geometric factor in determining the low WSS amplitude at proximal LAD. Strong correlations were found between the high WSS amplitudes calculated at the endothelial regions close to the flow divider. This study not only demonstrated that CT imaging studies of local risk factor for atherosclerosis could be clinically performed, but also showed that tortuosity of LM-LAD coronary branch could be used as a surrogate marker for the onset of atherosclerosis. PMID:24986333

  18. CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cytochromes P450 epoxygenases CYP2J2 and CYP2C8 synthesize epoxyeicosatrienoic acids, which regulate endothelial function. We sought to determine if genetic variation in CYP2J2 and CYP2C8 was associated with coronary heart disease risk. We genotyped 2065 Atherosclerosis Risk in Communities stud...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

    PubMed Central

    Calfon, Marcella A.; Vinegoni, Claudio; Ntziachristos, Vasilis; Jaffer, Farouc A.

    2010-01-01

    New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics. PMID:20210433

  1. Coronary atherosclerosis in outlier subjects at the opposite extremes of traditional risk factors: Rationale and preliminary results of the Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation (CAPIRE) study.

    PubMed

    Magnoni, Marco; Andreini, Daniele; Gorini, Marco; Moccetti, Tiziano; Modena, Maria Grazia; Canestrari, Mauro; Berti, Sergio; Casolo, Giancarlo; Gabrielli, Domenico; Marraccini, Paolo; Pontone, Gianluca; Masson, Serge; Latini, Roberto; Maggioni, Aldo Pietro; Maseri, Attilio

    2016-03-01

    Although it is generally accepted that cardiac ischemic events develop when coronary atherosclerosis (coronary artery disease [CAD]) has reached a critical threshold, this is true only to a first approximation. Indeed, there are patients with severe CAD who do not develop ischemic events; conversely, at the other extreme, individuals with minimal CAD may do. Similar exceptions to this paradigm include patients with diffuse CAD with a low risk factor (RF) profile and others with multiple RFs who develop only mild or no CAD. Therefore, the CAPIRE project was designed to investigate whether the specific study of these extreme outlier populations could provide clues for identification of yet unknown risk or protective factors for CAD and ischemic events. In the CAPIRE study, 481 subjects without previous symptoms or history of ischemic heart disease and normal left ventricular systolic function undergoing coronary computed tomography angiography have been selected based on coronary computed tomography angiography findings and cardiovascular RF profile. Therefore, in the whole population, 2 extreme outlier populations have been identified: (1) subjects with no CAD despite multiple RFs, and (2) at the opposite extreme, subjects with diffuse CAD despite a low-risk profile. Each subject has been characterized by clinical, anatomical imaging variables of CAD and baseline circulating biomarkers. Blood samples were collected and stored in a biological bank for further advanced investigations. The project is designed as a prospective, observational, international multicenter study with an initial cross-sectional analysis of clinical, imaging, and biomolecular variables in the selected groups and a longitudinal 5-year follow-up. PMID:26920592

  2. Comparison of diagnostic utilities of ankle–brachial index and Carotid intima-media thickness as surrogate markers of significant coronary atherosclerosis in Indians

    PubMed Central

    Ezhumalai, Babu; Dharanipragada Krishnasuri, Subrahmanyam; Jayaraman, Balachander

    2013-01-01

    Aim We aimed to compare Ankle–brachial index (ABI) and Carotid intima-media thickness (CIMT) as surrogate markers of significant coronary atherosclerosis in South Indians with coronary artery disease (CAD). Methods and results There were two groups: CAD group (n = 59) and Control group (n = 55). Mean ABI (0.82 ± 0.06 vs. 1.16 ± 0.11, p < 0.0001) and mean CIMT (0.74 ± 0.22 mm vs. 0.45 ± 0.09 mm, p < 0.0001) were statistically different between two groups. ABI < 0.9 (sensitivity: 91.53%, specificity: 100%) and CIMT > 0.63 mm (sensitivity: 61.02%, specificity: 98.18%) implied significant CAD. ABI and CIMT were negatively correlated to one another. With increasing severity of CAD, ABI decreased but CIMT increased. Conclusion ABI and CIMT are simple noninvasive tools providing insight into coronary atherosclerosis. They can be done at bedside and easily repeated than coronary angiography. ABI < 0.9 is a better surrogate marker of significant coronary atherosclerosis than CIMT > 0.63 mm in South Indians with CAD. PMID:23647891

  3. Matrix Gla Protein is Associated with Risk Factors for Atherosclerosis but not with Coronary Artery Calcification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: Atherosclerotic coronary artery calcification (CAC) is associated with increased coronary heart disease (CHD) risk. Matrix Gla Protein (MGP) is an inhibitor of calcification in vivo. However, little is known regarding the distribution of circulating MGP, and its associations with CHD...

  4. Higher Fibrinogen Level is Independently Linked with the Presence and Severity of New-Onset Coronary Atherosclerosis among Han Chinese Population

    PubMed Central

    Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Xu, Rui-Xia; Li, Sha; Dong, Qian; Li, Jian-Jun

    2014-01-01

    Background Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. However, no data is currently available regarding the association of fibrinogen level with the presence and severity of new-onset coronary atherosclerosis assessed by Gensini score (GS), particularly in Han Chinese with a large sample size. Methods and Results We studied 2288 consecutive, new-onset subjects undergoing coronary angiography with angina-like chest pain. Clinical and laboratory data were collected. Coronary stenotic lesions were considered to be the incidence of coronary atherosclerosis. The severity of coronary stenosis was determined by the GS system. Data indicated that patients with high GS had significantly elevated fibrinogen level (p<0.001). The prevalence and severity of coronary atherosclerosis were dramatically increased according to fibrinogen tertiles. Spearman correlation analysis revealed a positive association between fibrinogen level and GS (r = 0.138, p<0.001). Multivariate logistic regression analysis demonstrated that plasma fibrinogen level was independently associated with high GS (OR = 1.275, 95% CI 1.082–1.502, p = 0.004) after adjusting for potential confounders. Moreover, fibrinogen level was also independently related to the presence of coronary atherosclerosis (fibrinogen tertile 2: OR = 1.192, 95% CI 0.889–1.598, p = 0.241; tertile 3: OR = 2.003, 95% CI 1.383–2.903, p <0.001) and high GS (fibrinogen tertile 2: OR = 1.079, 95% CI 0.833–1.397, p = 0.565; tertile 3: OR = 1.524, 95% CI 1.155–2.011, p = 0.003) in a dose-dependent manner. Receiver-operating characteristic curve analysis showed that the best fibrinogen cut-off value for predicting the severity of coronary stenosis was 3.21 g/L. Conclusions Higher fibrinogen level is independently linked with the presence and severity of new-onset coronary atherosclerosis in Han Chinese population. PMID:25426943

  5. Association of brachial-ankle pulse wave velocity with atherosclerosis and presence of coronary artery disease in older patients

    PubMed Central

    Chung, Chang-Min; Tseng, Yu-Hsiang; Lin, Yu-Sheng; Hsu, Jen-Te; Wang, Po-Chang

    2015-01-01

    Objective Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess risk of cardiovascular disease in Asia. We examined whether baPWV was associated with coronary atherosclerosis and presence and extent of coronary artery disease (CAD) in older patients with chest pain. Methods This cross-sectional study enrolled 370 consecutive patients >65 years old who underwent baPWV measurement and elective coronary angiogram for suspected CAD at a single cardiovascular center, between June 2013 and July 2014. Results In addition to diabetes mellitus and body mass index, baPWV was one of the statistically meaningful predictors of significant CAD (diameter of stenosis >50%) in a multivariate analysis. When the extent of CAD was classified as nonsignificant or significant CAD (ie, one-, two-, and three-vessel disease), there was a significant difference in baPWV between the significant and nonsignificant CAD groups, but not between the three significant CAD groups. Multivariate linear regression analyses showed that the number of diseased vessels and baPWV were both significantly associated with the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score. The cutoff value of baPWV at 1,874 cm/s had a sensitivity of 60.1%, specificity of 70.8%, and area under receiver operating characteristic curve of 0.639 in predicting CAD. Conclusion Arterial stiffness determined by baPWV was associated independently with CAD severity, as assessed by angiography and the SYNTAX score in older patients with chest pain. As a result, increased arterial stiffness assessed by baPWV is associated with the severity and presence of CAD in older patients. PMID:26316732

  6. Improved correlation between carotid and coronary atherosclerosis SYNTAX score using automated ultrasound carotid bulb plaque IMT measurement.

    PubMed

    Ikeda, Nobutaka; Gupta, Ajay; Dey, Nilanjan; Bose, Soumyo; Shafique, Shoaib; Arak, Tadashi; Godia, Elisa Cuadrado; Saba, Luca; Laird, John R; Nicolaides, Andrew; Suri, Jasjit S

    2015-05-01

    automated cIMT that does not include bulb plaque and SYNTAX score and had an improvement of 44.58%. By sampling cIMT in the bulb region, the automated cIMT technique improves the degree of correlation between coronary artery disease lesion complexity and carotid atherosclerosis characteristics. PMID:25638311

  7. Analysis of Turbulent flow in early stages of atherosclerosis of coronary artery

    NASA Astrophysics Data System (ADS)

    Bhaganagar, Kiran

    2005-11-01

    During the early stages of atherosclerotic heart disease, fatty material accumulates in the coronary artery resulting in development of streaks of plaque and creating high levels of turbulence, and with significantly modified flow parameters. Diagnostic measures performed during this early stage may not show any evidence of coronary artery disease, because the lumen of the coronary artery has not decreased in caliber. These streaks do not obstruct the flow of blood but alter the flow characteristics, even at this preclinical stage. This talk presents the preliminary results for the analysis of turbulent flow characteristics for a range of atherosclerotic plaque configurations in the left main coronary artery. For this purpose a CAD/medical imaging based direct-simulation (DNS) tool has been developed. The Navier-stokes equations are solved in the vertical vorticity-velocity formulation. The plaque is introduced using immersed body technique. The geometric acquisition of the artery geometry and plaque morphology is obtained using CAD based commercial software.

  8. 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

  9. Cholesterol-Lowering Atherosclerosis Study (CLAS)

    ClinicalTrials.gov

    2013-12-12

    Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis

  10. Associations of Inflammatory Markers with Coronary Artery Calcification: Results from the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Jenny, Nancy Swords; Brown, Elizabeth R.; Detrano, Robert; Folsom, Aaron R.; Saad, Mohammed F.; Shea, Steven; Szklo, Moyses; Herrington, David M.; Jacobs, David R.

    2009-01-01

    Objective Inflammatory markers predict coronary heart disease (CHD). However, associations with coronary artery calcium (CAC), a marker of subclinical CHD, are not established. Methods We examined cross-sectional associations of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen with CAC presence (Agatston score > 0 by computed tomography) in 6,783 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Results In all participants, those in the highest, compared to lowest, quartile of CRP had a relative risk (RR, 95% confidence interval) of 1.13 (1.06-1.19; p<0.01) for CAC in age, sex and ethnicity adjusted models. For highest versus lowest quartiles, relative risks were 1.22 (1.15-1.30; p<0.01) for IL-6 and 1.18 (1.11-1.24; p<0.01) for fibrinogen. Adjusting for CHD risk factors (smoking, diabetes, blood pressure, obesity and dyslipidemia) attenuated RRs. RRs for CAC were 1.05 (0.99-1.12; p=0.63) for CRP, 1.12 (1.06-1.20; p<0.01) for IL-6 and 1.09 (1.02-1.16; p=0.01) for fibrinogen in multivariable adjusted models. Results were similar for men and women and across ethnic groups. Conclusion Inflammatory markers were weakly associated with CAC presence and burden in MESA. Our data support the hypothesis that inflammatory biomarkers and CAC reflect distinct pathophysiology. PMID:19766217

  11. Relationships between components of metabolic syndrome and coronary intravascular ultrasound atherosclerosis measures in women without obstructive coronary artery disease: the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation Study

    PubMed Central

    Khaliq, Asma; Johnson, B. Delia; Anderson, R. David; Bavry, Anthony A.; Cooper-DeHoff, Rhonda M.; Handberg, Eileen M.; Bairey Merz, C. Noel; Nicholls, Stephen J.; Nissen, Steven; Pepine, Carl J.

    2015-01-01

    Objective In women, metabolic syndrome (MetS) is associated with higher risk of ischemic heart disease-related adverse outcomes versus individual components. We examined the relationship of MetS to subclinical coronary atherosclerosis. Methods Women (n = 100) undergoing coronary angiography for suspected ischemia but without obstructive coronary artery disease (CAD) underwent intravascular ultrasound (IVUS) of a segment of the left coronary artery. A core lab, masked to other findings, assessed IVUS measures and normalized volume measures to pull-back length. MetS [defined using ATPIII criteria (fasting glucose ≥ 100 mg/dl per revised NCEP guideline)] and its components were entered into multiple regression models to assess associations with IVUS measures. Results Detailed IVUS measurements were available in 87 women. Mean age was 54 ± 10 years, 36% had MetS, and 78% had atheroma. Comparing women with MetS versus without MetS, significant differences were observed for seven IVUS atherosclerosis measures, but were not significant after adjusting for the MetS components. Systolic blood pressure and waist circumference components remained independently positively associated with the IVUS measures after adjusting for age, diabetes, CAD family history, dyslipidemia, smoking, and hormone replacement. Conclusion In women with signs and symptoms of ischemia and no obstructive CAD, MetS is associated with coronary atherosclerosis presence and severity. However, these associations appear largely driven by components of waist circumference and systolic blood pressure versus MetS cluster. This supports the concept that MetS is a convenient clustering of risk factors rather than an independent risk predictor, and emphasizes that the critical factors for coronary atherosclerosis are potentially modifiable. PMID:26665010

  12. 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. PMID:25794984

  13. Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR(-/-) mice: a paradox of preserved V'O2max and exercise capacity despite coronary atherosclerosis.

    PubMed

    Wojewoda, M; Tyrankiewicz, U; Gwozdz, P; Skorka, T; Jablonska, M; Orzylowska, A; Jasinski, K; Jasztal, A; Przyborowski, K; Kostogrys, R B; Zoladz, J A; Chlopicki, S

    2016-01-01

    We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR(-/-) mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V'O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR(-/-) mice V'O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR(-/-) mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR(-/-) mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V'O2max and exercise capacity. PMID:27108697

  14. Acute coronary syndrome and decompression illness: a challenge for the diving physician.

    PubMed

    Brauzzi, Marco; Andreozzi, Fabio; De Fina, Laura; Tanasi, Paolo; Falini, Stefano

    2013-12-01

    Decompression illness (DCI) is a syndrome with diverse clinical manifestations but in which cardiac symptoms are rare. In the presence of cardiac symptoms, the necessity to rule out an acute coronary syndrome (ACS) which requires prompt treatment may result in delay to appropriate recompression treatment. We describe three cases with cardiologic symptoms referred to our centre by the Emergency Department (ED) of our facility. The first was a 48-year-old woman who lost consciousness during a dive and required cardiopulmonary resuscitation. The final diagnosis was acute myocardial infarction and the patient did not undergo recompression treatment. The second case was that of a 27-year-old man who complained of tachycardia, dyspnoea and vertigo soon after a dive. He was referred by helicopter ambulance and in the ED was diagnosed with new-onset atrial fibrillation. Recompression resulted in disappearance of his vertigo, and sinus rhythm was restored pharmacologically. The third case was a 43-year-old man, with a history of coronary artery disease, who had undergone coronary artery bypass grafting three years previously. After a repetitive dive without adequate decompression, he complained of crushing retrosternal pain and numbness in the upper left arm. All cardiovascular examinations were negative and the patient was recompressed, with resolution of his symptoms. Features to consider in arriving at the correct differential diagnosis in divers presenting with cardiac symptoms are discussed in the light of these three illustrative cases. PMID:24510330

  15. [Role of the immune response in atherosclerosis and acute coronary syndromes].

    PubMed

    Caligiuri, Giuseppina

    2004-02-01

    Cardiovascular diseases represent one of the most important causes of death in the world. The underlying pathogenetic process is atherosclerosis which leads to the progressive reduction of the arterial lumen and therefore to the ischemia of the perfused organs. Atherogenesis results from the interaction between the biology of the arterial wall and the various stress stimuli present in the circulating blood. The first steps of atherogenesis occur very early, already during the fetal life. Those arterial segments that are subjected to the initiating causes (including hemodynamic stress) show altered endothelial permeability and allow the infiltration of macromolecules, like lipoproteins, in the subintimal space. At the same time, the smooth muscle cells that are subjected to the same local factors produce proteoglycans able to bind lipoproteins and to promote their oxidation. Oxidized lipoproteins induce the expression of chemokines and adhesion molecules on the luminal surface of the endothelium, which then allow the local recruitment of monocytes-macrophages and T lymphocytes. This is a local inflammatory process that, in theory, should contribute to reestablish the homeostasis of the vascular wall by promoting the elimination of injured tissue and its repair. Unfortunately, for unknown reasons, the immuno-inflammatory reaction persists and autoamplifies, the various components of the immune response finally contributing to the pathogenesis of atherosclerosis as well as of atherosclerotic complications. PMID:14997437

  16. Association between rs1761667 polymorphism of CD36 gene and risk of coronary atherosclerosis in Egyptian population

    PubMed Central

    Arafa, Usama Ahmed; Sabet, Eman A.; Salama, Eman; El Sharawy, Ahmed; Elbadry, Mahmoud I.

    2016-01-01

    Background Recent studies have demonstrated that CD36 is involved in the progression of atherosclerosis. Associations between rs1761667 polymorphisms of the CD36 gene and susceptibility to coronary artery disease (CAD) are not obvious. Methods We studied the relationship between single nucleotide polymorphisms (SNPs), rs1761667 of CD36 gene and the risk of coronary atherosclerosis in a case-control study composed of 71 CAD patients and 76 healthy controls by assessment of allele frequencies and genotype distributions using real-time polymerase chain reaction (PCR) and the allele discrimination technique. Additionally, we detected CD36 expression by flow cytometry. Results The distribution of rs1761667 genotypes between the two groups was significantly different (P<0.001), with the frequency of the AG genotype being significantly higher in the CAD group than in the control group (P<0.001). The expression level of CD36 in the CAD group was significantly higher than that in the control group (P<0.001), with significant differences in the CAD patients with an AG genotype compared with those with an AA and GG genotype (P<0.001). The plasma levels (mg/dL) of low-density lipoprotein (LDL) in the CAD group were much higher than that in the control group (P<0.001). On the other hand, the plasma LDL levels in CAD patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.046) and AG genotype was significantly more prevalent among type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) patients (P<0.05). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CAD (OR=17.97, 95% CI, 3.19–87.85, P=0.001). Conclusions The AG genotype of the rs1761667 polymorphism in the CD36 gene may be involved in CAD pathogenesis as well as increased body mass index (BMI), T2DM and MetS in the Sohag population of Egypt. PMID:27054101

  17. 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

  18. Carotid Endothelial VCAM-1 Is an Early Marker of Carotid Atherosclerosis and Predicts Coronary Artery Disease in Swine

    PubMed Central

    Masseau, I.; Bowles, D. K.

    2015-01-01

    Objective The aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers of endothelial cell function and would predict coronary artery disease (CAD). Methods and results Carotid arterial segments (bifurcation, proximal and distal CCA) were harvested from 14 and 24 month-old male castrated familial hypercholesterolemic (FH) swine, a model of spontaneous atherosclerosis. Quantification of local expression of eVCAM-1, intimal macrophage accumulation, oxidative stress, intima-media (I/M) ratio, intima-media thickness (IMT), endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) in selected regions of the carotids revealed a relationship between local inflammation and atheroscle-rotic plaque progression. Importantly, inflammation was not uniform throughout the CCA. Endo-thelial VCAM-1 expression was the greatest at the bifurcation and increased with age. Finally, eV-CAM-1 best estimated the severity of CAD compared to blood levels of glucose, hypercholestero-lemia, carotid IMT, and p-eNOS. Conclusion Our data suggested that eVCAM-1 was closely associated with atherosclerotic plaque progression and preceded impairment of EDD. Thus, this study supported the use of carotid VCAM-1 targeting agents to estimate the severity of CAD. PMID:26702331

  19. Predominant location of coronary artery atherosclerosis in the left anterior descending artery. The impact of septal perforators and the myocardial bridging effect

    PubMed Central

    Wasilewski, Jarosław; Niedziela, Jacek; Osadnik, Tadeusz; Duszańska, Agata; Sraga, Wojciech; Desperak, Piotr; Jackowska, Zuzanna; Nowakowski, Andrzej; Głowacki, Jan

    2015-01-01

    Introduction Coronary artery atherosclerosis presents characteristic patterns of plaque distribution despite systemic exposure to risk factors. We hypothesized that local hemodynamic forces induced by the systolic compression of intramuscular septal perforators could be involved in atherosclerotic processes in the left anterior descending artery (LAD) adjacent to the septal perforators’ origin. Therefore we studied the spatial distribution of atherosclerosis in coronary arteries, especially in relation to the septal perforators’ origin. Material and methods 64-slice computed tomography angiography was performed in 309 consecutive patients (92 male and 217 female) with a mean age of 59.9 years. Spatial plaque distribution in the LAD was analyzed in relation to the septal perforators’ origin. Additionally, plaque distribution throughout the coronary artery tree is discussed. Results The coronary calcium score (CCS) was positive in 164 patients (53.1%). In subjects with a CCS > 0, calcifications were more frequent in the LAD (n = 150, 91.5%) compared with the right coronary artery (RCA) (n = 94, 57.3%), circumflex branch (CX) (n = 76, 46.3%) or the left main stem (n = 42, 25.6%) (p < 0.001). Total CCS was higher in the LAD at 46.1 (IQR: 104.2) and RCA at 34.1 (IQR: 90.7) than in the CX at 16.8 (IQR: 61.3) (p = 0.007). In patients with calcifications restricted to a single vessel (n = 54), the most frequently affected artery was the LAD (n = 42, 77.8%). In patients with lesions limited to the LAD, the plaque was located mostly (n = 37, 88.1%) adjacent to the septal perforators’ origin. Conclusions We demonstrated that coronary calcifications are most frequently located in the LAD in proximity to the septal branch origin. A possible explanation for this phenomenon could be the dynamic compression of the tunneled septal branches, which may result in disturbed blood flow in the adjacent LAD segment (milking effect). PMID:26855661

  20. Decreased mRNA levels of cardiac Cx43 and ZO1 in sudden cardiac death related to coronary atherosclerosis: a pilot study.

    PubMed

    Xue, Ye; Zhao, Rui; Du, Si-Hao; Zhao, Dong; Li, Dong-Ri; Xu, Jing-Tao; Xie, Xiao-Li; Wang, Qi

    2016-07-01

    Sudden cardiac death (SCD) is the most frequent cause of sudden unexplained death in forensic practice. The most common cause of SCD is coronary artery disease related to coronary atherosclerosis. Previous study suggested the possible application of connexin 43 (Cx43) and zonula occludens-1 (ZO1) immunostaining in the early diagnosis of myocardial ischemia. However, there appears to be insufficient data with regard to their mRNA levels. The present study investigated the cardiac mRNA levels of Cx43 and ZO1, using forensic autopsy materials consisting of 41 control cases without any disease or structural abnormality of the heart (group 1), 32 deaths due to acute ischemic heart disease related to coronary atherosclerosis without apparent myocardial necrosis (group 2), and 29 traumatic deaths with coronary atherosclerosis (group 3). Ten candidate reference genes were evaluated in the left ventricles of 10 forensic autopsy cases. EEF1A1, PPIA, TPT1, and RPL13A were identified as the most stable reference genes. Using these validated reference genes, mRNA levels of Cx43 and ZO1 were examined in the bilateral ventricles and atria of the heart. Relative mRNA quantification demonstrated decreased calibrated normalized relative quantity (CNRQ) values of Cx43 and ZO1 in bilateral ventricles of group 2. When using one conventional reference gene (GAPDH or ACTB) for normalization, nearly no difference was detected among the three groups. These findings indicate that ventricular gap junction remodeling may be a key contributor to rhythm disturbances. Analysis of cardiac Cx43 and ZO1 using real-time PCR is useful in diagnosis of SCD, and validation of reference genes is crucial. PMID:26972693

  1. Effect of mild atherosclerosis on flow resistance in a coronary artery casting of man

    NASA Technical Reports Server (NTRS)

    Back, L. H.; Cho, Y. I.; Crawford, D. W.; Cuffel, R. F.

    1984-01-01

    An in-vitro flow study was conducted in a mildly atherosclerotic main coronary artery casting of man using sugar-water solutions simulating blood viscosity. Steady flow results indicated substantial increases in pressure drop, and thus flow resistance at the same Reynolds number, above those for Poiseuille flow by 30 to 100 percent in the physiological Reynolds number range from about 100 to 400. Time-averaged pulsatile flow data showed additional 5 percent increases in flow resistance above the steady flow results. Both pulsatile and steady flow data from the casting were found to be nearly equal to those from a straight, axisymmetric model of the casting up to a Reynolds number of about 200, above which the flow resistance of the casting became gradually larger than the corresponding values from the axisymmetric model.

  2. Subclinical coronary atherosclerosis, HIV infection and antiretroviral therapy: Multicenter AIDS Cohort Study

    PubMed Central

    Kingsley, Lawrence A.; Cuervo-Rojas, Juliana; Muñoz, Alvaro; Palella, Frank J.; Post, Wendy; Witt, Mallory D.; Budoff, Matthew; Kuller, Lewis

    2010-01-01

    Objective To evaluate the association of HIV infection and cumulative exposure to highly active antiretroviral therapy (HAART) with the presence and extent of coronary artery calcification (CAC). Design A cross-sectional study of 947 male participants (332 HIV-seronegative, 84 HAART-naive and 531 HAART-experienced HIV-infected) from the Multicenter AIDS Cohort Study. Methods The main outcome was CAC score calculated as the geometric mean of the Agatston scores of two computed tomography replicates. Presence of CAC was defined as calcification score above 10, and extent of CAC by the score for those with CAC present. Multivariable regression was used to evaluate the association between HIV infection and HAART and presence and extent of calcification. Results Increasing age was most strongly associated with both prevalence and extent of CAC for all study groups. After adjustment for age, race, family history, smoking, high-density lipoprotein-C, low-density lipoprotein-C and hypertension, HIV infection (odds ratio, 1.35; 95% confidence interval, 0.70, 2.61) and long-term HAART use (odds ratio, 1.33; 95% confidence interval, 0.87, 2.05) increased the odds for presence of CAC. In contrast, after adjustment for these covariates, the extent of CAC was lower among HAART users. Among those not taking lipid-lowering therapy, HAART usage of at least 8 years was associated with significantly reduced CAC scores (relative CAC score, 0.43; 95% confidence interval, 0.24, 0.79). Conclusion HAART use may have different effects on the presence and extent of coronary calcification. Although prevalence of calcification was marginally increased among long-term HAART users, the extent of calcification was significantly reduced among HAART users compared with HIV-seronegative controls. PMID:18670218

  3. Coronary arteriosclerosis and atherosclerosis in fast neutron or photon irradiated dogs

    SciTech Connect

    Bradley, E.W.; Zook, B.C.; Casarett, G.W.

    1981-08-01

    Thirty-nine adult male beagles received either fast neutron or photon irradiation to the right thorax to obtain values for the relative biological effectiveness (RBE) of fast neutrons as assessed by quantitative parameters of lung function. Fast neutrons (15 MeV avg.) were delivered in 4 fx/wk for six weeks to total doses of 1000, 1500, 2250, or 3375 rad while the photon irradiated dogs received total doses of 3000, 4500, or 6750 rad in the same fractionation schedule. The right atrium and coronary groove of the heart were included in the irradiated field. Cholesterol levels (and triglyceride levels when obtainable) were measured prior to irradiation and every three months until death. Arteries were graded (0, negative to 5, severe) for endothelial proliferation, disruption and duplication of the elastic lamina, perivascular fibrosis and the presence of foamy macrophages. All dogs that survived 75 days post-irradiation developed arterial changes; two neutron irradiated dogs showed severe atherosclerotic plaque formation. Data suggest an RBE between 4 and 5.

  4. Usefulness of Insulin Resistance Estimation and the Metabolic Syndrome in Predicting Coronary Atherosclerosis in Type 2 Diabetes Mellitus

    PubMed Central

    Mehta, Nehal N.; Krishnamoorthy, Parasuram; Martin, Seth S.; Clair, Caitlin St; Schwartz, Stanley; Iqbal, Nayyar; Braunstein, Seth; Schutta, Mark; Rader, Daniel J.; Reilly, Muredach P.

    2011-01-01

    Metabolic syndrome (MS) definitions predict cardiovascular events beyond traditional risk factors in type 2 diabetic (DM) as well as non-diabetics subjects. We and other have shown that apolipoprotein B (apoB) and non-HDL cholesterol (non-HDL-C) are associated with coronary artery calcification (CAC) in DM. However, the relative value of MS, apoB lipoproteins and estimates of insulin resistance is unknown in predicting atherosclerosis in DM. We performed cross sectional analyses of white subjects in 2 community based studies (N= 611 type 2 diabetic subjects, N= 803 non-diabetic subjects) using multivariate analysis of traditional risk factors and then adding MS, apoB and homeostatic model assessment for insulin resistance (HOMA-IR). Incremental value was tested with likelihood ratio testing. Beyond traditional risk, HOMA-IR [Tobit regression ratio 1.86 (p=0.002)], apoB [1.55 (p=0.001)] and MS [2.37 (p=0.007)] were independently associated with CAC. In nested models, HOMA-IR added value to apoB [1.72 (p=0.008)], MS [1.72 (p=0.011)] and both apoB and MS [1.64 (p=0.021)]. ApoB showed a similar pattern when added to HOMA-IR [1.51 (p=0.004)], MS [1.46 (p=0.005)] and both HOMA-IR and MS [1.48 (p=0.006)]. MS added to apoB [1.99 (p=0.032)], but not HOMA-IR [1.54 (p=0.221)] or both apoB and HOMA-IR [1.32 (p=0.434)]. In conclusion, insulin resistance estimates add value to MS and apoB in predicting CAC scores in DM and warrant further evaluation in clinic for identification of DM patients at higher risk for atherosclerotic cardiovascular disease. PMID:21257006

  5. 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

  6. Ten-Year Trends in Coronary Calcification in Individuals without Clinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    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

    Background 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. Methods and Findings 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. Conclusions 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. PMID:24743658

  7. Coronary Artery Calcification Compared with Carotid Intima-Media Thickness in Prediction of Cardiovascular Disease Incidence: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Folsom, Aaron R.; Kronmal, Richard A.; Detrano, Robert C.; O’Leary, Daniel H.; Bild, Diane E.; Bluemke, David A.; Budoff, Matthew J.; Liu, Kiang; Shea, Steven; Szklo, Moyses; Tracy, Russell P.; Watson, Karol E.; Burke, Gregory L.

    2008-01-01

    Context Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence. Objective To assess whether maximum carotid IMT or CAC (Agatston Score) is the better predictor of incident CVD. Design, Setting, Patients Prospective cohort study of 45–84 year-olds initially free of CVD (n = 6,698) in four ethnic groups, with standardized carotid IMT and CAC measures at baseline, in six field centers of the Multi-Ethnic Study of Atherosclerosis (MESA). Main Outcome Measure(s) Incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. Results There were 222 CVD events during follow-up. CAC was associated more strongly than carotid IMT with risk of incident CVD. After adjustment for each other and traditional CVD risk factors, the hazard of CVD increased 2.1-fold (95% CI 1.8–2.5) for each standard deviation greater level of log-transformed CAC, versus 1.3-fold (95% CI 1.1–1.4) for each standard deviation greater maximum IMT. For coronary heart disease, the hazard ratios per standard deviation increment were 2.5-fold (95% CI 2.1–3.1) for CAC and 1.2-fold (95% CI 1.0–1.4) for IMT. An ROC analysis also suggested that CAC predicted incident CVD better than IMT did. Conclusions Although whether and how to clinically use bio-imaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC predicts subsequent CVD events better than does carotid IMT. PMID:18574091

  8. Osteoprotegerin (OPG), but not Receptor Activator for Nuclear Factor Kappa B Ligand (RANKL), is Associated with Subclinical Coronary Atherosclerosis in HIV-infected Men

    PubMed Central

    Ketlogetswe, Kerunne S; McKibben, Rebeccah; Jacobson, Lisa P; Li, Xuihong; Dobs, Adrian S; Budoff, Matthew; Witt, Mallory D; Palella, Frank J; Kingsley, Lawrence; Margolick, Joseph B.; Post, Wendy S; Brown, Todd T.

    2015-01-01

    Context Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease pathogenesis in the general population. Objective To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis. Design Cross-sectional study nested within the Multicenter AIDS Cohort Study Setting Four US academic medical centers Participants There were 578 HIV-infected and 344 HIV-uninfected men. Main Outcome Measures Coronary artery calcium (CAC) was measured by non-contrast cardiac computed tomography (CT), and coronary stenosis and plaque characteristics (composition, presence and extent) were measured by coronary CT angiography. All statistical models were adjusted for traditional cardiovascular risk factors. Results OPG concentrations were higher and RANKL concentrations were lower among HIV-infected men compared to –uninfected men (p<0.0001 each). Among the HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis > 50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with extent of both CAC and calcified plaque, but not their presence. RANKL concentrations were not associated with plaque presence or extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque. Conclusions OPG and RANKL are dysregulated in HIV-infected men and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV-status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men. PMID:26090754

  9. Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study.

    PubMed

    Carr, J Jeffrey; Nelson, Jennifer Clark; Wong, Nathan D; McNitt-Gray, Michael; Arad, Yadon; Jacobs, David R; Sidney, Stephan; Bild, Diane E; Williams, O Dale; Detrano, Robert C

    2005-01-01

    Calcified coronary artery plaque, measured at cardiac computed tomography (CT), is a predictor of cardiovascular disease and may play an increasing role in cardiovascular disease risk assessment. The Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study of the National Heart, Lung, and Blood Institute are population-based studies in which calcified coronary artery plaque was measured with electron-beam and multi-detector row CT and a standardized protocol in 6814 (MESA) and 3044 (CARDIA study) participants. The studies were approved by the appropriate institutional review board from the study site or agency, and written informed consent was obtained from each participant. Participation in the CT examination was high, image quality was good, and agreement for the presence of calcified plaque was high (kappa = 0.92, MESA; kappa = 0.77, CARDIA study). Extremely high agreement was observed between and within CT image analysts for the presence (kappa > 0.90, all) and amount (intraclass correlation coefficients, >0.99) of calcified plaque. Measurement of calcified coronary artery plaque with cardiac CT is well accepted by participants and can be implemented with consistently high-quality results with a standardized protocol and trained personnel. If predictive value of calcified coronary artery plaque for cardiovascular events proves sufficient to justify screening a segment of the population, then a standardized cardiac CT protocol is feasible and will provide reproducible results for health care providers and the public. PMID:15618373

  10. The Combined Impact of Neutrophil-to-Lymphocyte Ratio and Type 2 Diabetic Mellitus on Significant Coronary Artery Disease and Carotid Artery Atherosclerosis

    PubMed Central

    Kim, Bong-Joon; Cho, Sang-Hoon; Kim, Hyun-Su; Heo, Jung-Ho; Cha, Tae-Joon

    2016-01-01

    Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a new important inflammatory marker for predicting cardiovascular events. This study aimed to evaluate the combined impact of NLR and type 2 diabetes mellitus (T2DM) on significant coronary artery disease (CAD) and carotid artery atherosclerosis. Methods This study includes a total of 828 patients evaluated by coronary angiography and carotid ultrasonography. Significant CAD was defined as at least one vessel with stenosis greater than 50%. We employed logistic regression models to investigate the association of NLR and T2DM with significant CAD. The goodness-of-fit and discriminability of the models were assessed by the loglikelihood ratio test and C-index, respectively. Also, we investigated the clinical relevance of the categorized NLR that classifies patients into three risk groups (low, intermediate, high). Results According to logistic regression analysis, both NLR {adjusted odds ratio (OR) 1.31, p < 0.001} and T2DM (adjusted OR 2.46, p = 0.006) were independent risk factors of significant CAD. The addition of NLR and T2DM into a logistic regression model including conventional cardiovascular risk factors significantly improved the goodness-of-fit (p < 0.001) and the discriminability of the model (p = 0.004). Also, T2DM patients assigned into the high risk group (NLR > 2) showed the greater prevalence of significant CAD and carotid artery atherosclerosis compared with patients without T2DM or type 2 diabetic patients assigned into the low risk group (NLR ≤ 1). Conclusion Our results suggest that type 2 diabetic patients with high inflammatory state would be more vulnerable to significant CAD and carotid artery atherosclerosis. PMID:27358703

  11. Plasma ghrelin levels are closely associated with severity and morphology of angiographically-detected coronary atherosclerosis in Chineses patients with diabetes mellitus

    PubMed Central

    Zhang, Min; Fang, Wei-yi; Yuan, Fang; Qu, Xin-kai; Liu, Hua; Xu, Ying-jia; Chen, Hui; Yu, Yong-fu; Shen, Yan; Zheng, Zhi-chun

    2012-01-01

    Aim: Low plasma ghrelin level was found to be associated with diabetes, and ghrelin was shown to inhibit pro-atherogenic changes in experimental models of atherosclerosis. The aim of this study was to investigate the relationship between plasma ghrelin levels and coronary atherosclerotic lesions in Chinese patients with diabetes. Methods: Plasma ghrelin levels were measured using an ELISA kit. The severity of coronary artery disease (CAD) was determined via angiography. Composition of atherosclerotic plaques was detected via coronary CT angiography. Results: A total of 178 patients with diabetes were recruited. Among the patients, 70 were diagnosed with acute coronary syndrome (ACS), 82 with stable angina pectoris (SAP) and 26 without coronary angiographic finding (controls). A negative correlation was found between ghrelin levels and the severity of the CAD, as determined via the Gensini score (r=-0.2434; P=0.0217). In diabetic patients with CAD and a complex lesion, the plasma ghrelin levels were significantly lower than in those with a simple lesion (ACS group: 3.81±0.49 ng/mL vs 4.72±0.50 ng/mL, P<0.0001; SAP group: 4.21±0.52 ng/mL vs 4.76±0.59 ng/mL, P=0.0397). Angiographically-detected complex lesion was an independent factor associated with ghrelin levels (adjusted beta coefficient=-0.67, 95% CI -0.97 to -0.37, P<0.0001). Conclusion: Low plasma ghrelin level is closely related to angiographically-detected severity and the complex lesion morphology in Chinese diabetic patients with CAD. PMID:22367281

  12. Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians

    PubMed Central

    Qasim, Atif N.; Metkus, Thomas S.; Tadesse, Mahlet; Lehrke, Michael; Restine, Stephanie; Wolfe, Megan L.; Hannenhalli, Sridhar; Cappola, Thomas; Rader, Daniel J.; Reilly, Muredach P.

    2011-01-01

    Summary Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the −420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans. Design and methods We examined the association of three resistin polymorphisms, −852A>G, −420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851). Results Resistin levels were higher, dose-dependently, with the −420G allele (CC 5·9 ± 2·7 ng/ml, GC 6·5 ± 4·0 ng/ml and GG 7·2 ± 4·8 ng/ml, trend P = 0·04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1·07 (1·00–1·15), P < 0·05)]. The −852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1·06 (95% CI 1·01–1·11), P = 0·01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0·04) and the AGT haplotype was related to CRP (P = 0·04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5′ variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis. PMID:18710472

  13. Intra-Section Analysis of Human Coronary Arteries Reveals a Potential Role for Micro-Calcifications in Macrophage Recruitment in the Early Stage of Atherosclerosis

    PubMed Central

    Chatrou, Martijn L. L.; Cleutjens, Jack P.; van der Vusse, Ger J.; Roijers, Ruben B.; Mutsaers, Peter H. A.; Schurgers, Leon J.

    2015-01-01

    Background Vascular calcification is associated with poor cardiovascular outcome. Histochemical analysis of calcification and the expression of proteins involved in mineralization are usually based on whole section analysis, thereby often ignoring regional differences in atherosclerotic lesions. At present, limited information is available about factors involved in the initiation and progression of atherosclerosis. Aim of This Study This study investigates the intra-section association of micro-calcifications with markers for atherosclerosis in randomly chosen section areas of human coronary arteries. Moreover, the possible causal relationship between calcifying vascular smooth muscle cells and inflammation was explored in vitro. Technical Approach To gain insights into the pathogenesis of atherosclerosis, we performed analysis of the distribution of micro-calcifications using a 3-MeV proton microbeam. Additionally, we performed systematic analyses of 30 to 40 regions of 12 coronary sections obtained from 6 patients including histology and immuno-histochemistry. Section areas were classified according to CD68 positivity. In vitro experiments using human vascular smooth muscle cells (hVSMCs) were performed to evaluate causal relationships between calcification and inflammation. Results From each section multiple areas were randomly chosen and subsequently analyzed. Depositions of calcium crystals at the micrometer scale were already observed in areas with early pre-atheroma type I lesions. Micro-calcifications were initiated at the elastica interna concomitantly with upregulation of the uncarboxylated form of matrix Gla-protein (ucMGP). Both the amount of calcium crystals and ucMGP staining increased from type I to IV atherosclerotic lesions. Osteochondrogenic markers BMP-2 and osteocalcin were only significantly increased in type IV atheroma lesions, and at this stage correlated with the degree of calcification. From atheroma area type III onwards a considerable

  14. The role of 64-slice multi-detector computed tomography in the detection of subclinical atherosclerosis of the coronary artery.

    PubMed

    Jeong, Hae Chang; Ahn, Youngkeun; Ko, Jum Suk; Lee, Min Goo; Sim, Doo Sun; Park, Keun Ho; Yoon, Nam Sik; Youn, Hyun Ju; Hong, Young Joon; Kim, Kye Hun; Park, Hyung Wook; Kim, Ju Han; Kim, Yun-Hyeon; Jeong, Myung Ho; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2010-12-01

    Multi-detector computed tomography (MDCT) has been used for detecting or excluding coronary atherosclerotic stenosis in symptomatic patients. However, the role of MDCT for routine medical examination in asymptomatic, high-risk patients has not been established. We therefore conducted the present study to test the hypothesis that MDCT could be a valuable method for detecting subclinical coronary artery stenosis in asymptomatic patients. An observational, retrospective, single-centre study was conducted with a cohort of 1,529 patients (mean age, 56.4 ± 8.3 years; 1,353 males) who had undergone MDCT as part of their general medical checkups from November 2005 to April 2008. The patients who had a past history of coronary artery disease, typical chest pain, or evidence of myocardial ischemia were excluded. During clinical follow up of these patients, the incidence of subclinical coronary stenosis and the usefulness of MDCT for routine medical examination in asymptomatic patients were investigated. Of the 1,529 enrolled patients, 42.3% had hypertension, 13.5% had diabetes mellitus, 7.7% had hyperlipidemia, and 40.4% were current smokers. Abnormal MDCT findings were noted in 560 (36.6%) patients, who were classified into two groups. One group had the presence coronary calcium with a luminal diameter stenosis of the coronary artery of <50% (n = 508, 33.2%). These patients were treated with medication or clinical follow-up. The other group had a luminal diameter stenosis of the coronary artery of ≥50% with the presence or absence of coronary calcium (n = 52, 3.4%). These patients underwent a conventional coronary angiogram and intravascular ultrasound. A total of 29 of the 1,529 patients (1.9%) presented with insignificant stenosis or myocardial bridge, and 23 patients (1.5%) presented with significant stenosis. The patients with significant stenosis underwent percutaneous coronary intervention (PCI) with stent implantation. Major adverse cardiac events occurred

  15. 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. PMID:25921917

  16. HIV and coronary artery calcium score: comparison of the Hawaii Aging with HIV Cardiovascular Study and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts

    PubMed Central

    Chow, Dominic; Young, Rebekah; Valcour, Nicole; Kronmal, Richard A.; Lum, Corey J.; Parikh, Nisha I.; Tracy, Russell P.; Budoff, Matthew; Shikuma, Cecilia M.

    2015-01-01

    Objectives To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. Methods Cross-sectional study comparing baseline data of males from Hawaii Aging with HIV –Cardiovascular Study (HAHCS) with the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The cohorts were pooled to determine effects of HIV on CAC and explore immunologic and inflammatory factors that may explain development of CAC in HIV. Multivariable regression models compared CAC prevalence in HAHCS with MESA adjusting for coronary heart disease (CHD) risk profiles. Results We studied 100 men from HAHCS and 2733 men from MESA. Positive CAC was seen in 58% HAHCS participants and 57% MESA participants. Mean CAC was 260.8 in HAHCS and 306.5 in MESA. Using relative risk (RR) regression, HAHCS participants had a greater risk (RR=1.20, P<0.05) of having positive CAC than MESA when adjusting for age, smoking status, diabetes, antihypertensive therapy, BMI, systolic blood pressure, total cholesterol, and HDL cholesterol. Among participants with positive CAC, HIV infection was not associated with larger amounts of CAC. Among HAHCS participants, current HIV viral load, CD4, length of HIV, interleukin 6 (IL-6), fibrinogen, C-reactive protein (CRP), and D-dimer were not associated with the presence or amount of CAC. Discussion HIV was independently associated with a positive CAC in men with increased likelihood occurring between 45 and 50 years of age. Current HIV viral load, CD4 count, length of HIV, and inflammatory markers were unrelated to either presence or amount of CAC. PMID:26038953

  17. When and how to start prevention of atherosclerosis? Lessons from the Cardiovascular Risk in the Young Finns Study and the Special Turku Coronary Risk Factor Intervention Project.

    PubMed

    Magnussen, Costan G; Niinikoski, Harri; Juonala, Markus; Kivimäki, Mika; Rönnemaa, Tapani; Viikari, Jorma S A; Simell, Olli; Raitakari, Olli T

    2012-09-01

    This review provides an up-to-date summary of findings from two ongoing population-based, prospective studies conducted in Finland: The Cardiovascular Risk in Young Finns Study, and the Special Turku Coronary Risk Factor Intervention Project (STRIP), which have contributed significantly to the scientific literature concerning the childhood origin of cardiovascular disease, and whether prevention efforts in adults can be expanded to young people. From the Young Finns Study, we summarize evidence demonstrating childhood risk factors to be associated with both risk factors and preclinical markers of atherosclerosis in adulthood, and from STRIP, we summarize evidence showing that supervised dietary counseling of a low saturated fat diet effectively decreases exposure to cardiovascular risk factors without affecting growth and development of healthy children and adolescents. The evidence available from these studies supports that the ability to prevent or delay the risk of premature atherosclerosis and its clinical sequelae later in life lies in maintaining a low lifetime risk by preventing the development of risk factors in early life. PMID:21877168

  18. Alcohol and coronary artery calcium prevalence, incidence and progression: results from the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    McClelland, Robyn L.; Bild, Diane E.; Burke, Gregory L.; Mukamal, Kenneth J.; Lima, João A.; Kronmal, Richard A.

    2012-01-01

    Background Alcohol use has been consistently found to have a J-shaped association with coronary heart disease, with moderate drinkers exhibiting a decreased risk compared to both heavy drinkers and non-drinkers. However, studies of the association between alcohol use and subclinical coronary artery disease have conflicted. Objective To determine whether alcohol is associated with the presence, amount, or progression of coronary calcium over a 2- to 4-year period. Design MESA is a prospective community-based cohort study of subclinical cardiovascular disease in a multi-ethnic cohort. In 2000–2002, 6814 participants free of clinical cardiovascular disease were enrolled at 6 participating centers. Results There were 3766 (55.5%) current drinkers, 1635 (24.1%) former drinkers, and 1390 (20.5%) never drinkers included in the analysis. Although light to moderate alcohol consumption was associated with lower coronary heart disease risk, we found no evidence of a protective or J-shaped association of alcohol and coronary artery calcium (CAC). In fact there was evidence that heavy consumption of hard liquor was associated with greater CAC accumulation. Other alcoholic beverages were not associated with CAC prevalence, incidence or progression. Conclusions This is the first large study to evaluate the association of alcohol and coronary artery calcium in four racial/ethnic groups, and to evaluate progression of calcification. These results suggest that the cardiovascular benefits that may be derived from light to moderate alcohol consumption are not mediated through reduced CAC accumulation. PMID:19064520

  19. Coronary artery disease

    MedlinePlus Videos and Cool Tools

    ... heart muscle itself. Damage to or blockage of a coronary artery can result in injury to the heart. Normally, blood flows through a coronary artery unimpeded. However, a process called atherosclerosis ...

  20. The effect of 9p21.3 coronary artery disease locus neighboring genes on atherosclerosis in mice

    PubMed Central

    Kim, Juyong Brian; Deluna, Andres; Mungrue, Imran N.; Vu, Christine; Pouldar, Delila; Civelek, Mete; Orozco, Luz; Wu, Judy; Wang, Xuping; Charugundla, Sarada; Castellani, Lawrence W.; Rusek, Marta; Jakobowski, Hieronim; Lusis, Aldons J.

    2013-01-01

    Background The human 9p21.3 chromosome locus has been shown to be an independent risk factor for atherosclerosis in multiple large scale genome-wide association studies, but the underlying mechanism remains unknown. We set out to investigate the potential role of the 9p21.3 locus neighboring genes, including Mtap, the two isoforms of Cdkn2a, p16Ink4a and p19Arf, and Cdkn2b in atherosclerosis using knockout mice models. Methods and Results Gene targeted mice for neighboring genes, including Mtap, Cdkn2a, p19Arf, and Cdkn2b, were each bred to mice carrying the human APO*E3 Leiden transgene which sensitizes the mice for atherosclerotic lesions through elevated plasma cholesterol. We found that the mice heterozygous for Mtap developed larger lesion compared to wild-type mice (49623±21650 vs. 18899±9604 μm2/section (Mean±SD); p=0.01), with similar morphology as wild type mice. The Mtap heterozygous mice demonstrated changes in metabolic and methylation profiles and CD4+ cell counts. The Cdkn2a knockout mice had smaller lesions compared to wild-type and heterozygous mice and there were no significant differences in lesion size in p19Arf and Cdkn2b mutants as compared to wild type. We observed extensive, tissue-specific compensatory regulation of the Cdkn2a and Cdkn2b genes among the various knockout mice, making the effects on atherosclerosis difficult to interpret. Conclusions Mtap plays a protective role against atherosclerosis, whereas Cdkn2a appears to be modestly proatherogenic. However, no relation was found between the 9p21 genotype and the transcription of 9p21 neighboring genes in primary human aortic vascular cells in vitro. There is extensive compensatory regulation in the highly conserved 9p21 orthologous region in mice. PMID:22952318

  1. [Cardiac SPECT/CT: correlation between atherosclerosis, significant coronary artery stenoses and myocardial perfusion parameters in patients with known coronary artery disease].

    PubMed

    Ubleis, C; Rist, C; Griesshammer, I; Becker, A; Becker, C; Hacker, M

    2010-04-01

    Invasive coronary angiography (ICA) and CT angiography (CTA) both enable significant coronary artery stenoses to be detected, but they are not suitable for assessing their hemodynamic relevance. This can be accomplished using myocardial perfusion scintigraphy (MPS) which, however, has limited specificity and spatial resolution. Regarding patients with known coronary artery disease (CAD) it is furthermore important to stratify patient's individual risk for severe cardiac events to guide therapy management.The results of our investigations in 158 patients with CAD indicate that global and regional calcium scores (CAC) do not correlate with the presence of myocardial perfusion defects and significant coronary artery stenoses, respectively. However, published literature has reported CAC as being an independent predictor of long-time survival.For clinical purposes it seems that non-invasive diagnostics with CTA, MPS and CAC screening can be useful even in patients with known CAD. CAC and global scar burden enable long-term risk-stratification, whereas fusion of CTA and MPS is useful to detect the culprit lesion of relevant perfusion defects and to select options for revascularization. PMID:20333503

  2. Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR−/− mice: a paradox of preserved V’O2max and exercise capacity despite coronary atherosclerosis

    PubMed Central

    Wojewoda, M.; Tyrankiewicz, U.; Gwozdz, P.; Skorka, T.; Jablonska, M.; Orzylowska, A.; Jasinski, K.; Jasztal, A.; Przyborowski, K.; Kostogrys, R. B.; Zoladz, J. A.; Chlopicki, S.

    2016-01-01

    We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR−/− mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V’O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR−/− mice V’O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR−/− mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR−/− mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V’O2max and exercise capacity. PMID:27108697

  3. 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

  4. Genetic variation in CYP2J2 and risk of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CYP2J2 metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs) which regulate endothelial function and serve as a reserve system to endothelial nitric oxide synthase (NOS3). We sought to determine if genetic variation in CYP2J2 was associated with risk of coronary heart disease (CHD) events...

  5. The relationship between insulin resistance and vascular calcification in coronary arteries, and the thoracic and abdominal aorta: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Ong, Kwok-Leung; McClelland, Robyn L.; Rye, Kerry-Anne; Cheung, Bernard M.Y.; Post, Wendy S.; Vaidya, Dhananjay; Criqui, Michael H.; Cushman, Mary; Barter, Philip J.; Allison, Matthew A.

    2014-01-01

    Objective Insulin resistance may be related to vascular calcification as both are associated with abdominal obesity. We investigated the association of insulin resistance with abdominal aortic calcium (AAC), coronary artery calcium (CAC) and thoracic aortic calcium (TAC), and whether it differs according to different levels of subcutaneous fat area (SFA) and visceral fat area (VFA) in a cross-sectional study design. Methods We investigated 1632 participants without diabetes from the Multi-Ethnic Study of Atherosclerosis with valid data on homeostasis model assessment index (HOMA-IR), AAC, CAC, and TAC. Adipocytokines, SFA, and VFA were also determined. Results HOMA-IR was associated with the presence of CAC, but not AAC and TAC, and the association remained significant after adjusting for traditional risk factors, adipocytokines, abdominal muscle mass, SFA, and VFA (prevalence ratio=1.04 per one interquartile range [IQR] increase, P=0.01). As the strength of the association of HOMA-IR with vascular calcification may differ by abdominal fat composition, subgroup analysis was performed among participants with different tertiles of SFA and VFA. Significant interactions between HOMA-IR with SFA and VFA separately were observed for the presence of TAC, but not AAC and CAC, even after adjusting for confounding factors. The association of HOMA-IR with TAC tended to be stronger in participants with more SFA and VFA. Conclusions Atherosclerotic calcification, especially in the coronary arteries, is related to insulin resistance. Further studies are needed to delineate the mechanisms by which visceral obesity can lead to vascular calcification. PMID:25108074

  6. Long-term patency (9 1/2 years) and atherosclerosis of a polytetrafluoroethylene (Gortex) coronary artery bypass graft.

    PubMed

    Vlay, S C; Malik, A Z

    1998-01-01

    The patency of a polytetrafluoroethylene (Gortex) graft 9 1/2 years after coronary artery bypass graft surgery (CABG) is demonstrated. While this material is not commonly used as a conduit because of limited success in the past, this case demonstrates that, given the right circumstances, long-term patency is possible. Since available conduits for CABG are quite often limited, viable alternatives may be lifesaving and require further evaluation. In addition to mechanical considerations such as size, length, and material, anticoagulation and strict management of hyperlipidemia may be critical. PMID:9474468

  7. Distribution of Coronary Artery Calcium Scores by Framingham 10-Year Risk Strata in the Multi-Ethnic Study of Atherosclerosis (MESA): Potential Implications for Coronary Risk Assessment

    PubMed Central

    Okwuosa, Tochi M.; Greenland, Philip; Ning, Hongyan; Liu, Kiang; Bild, Diane E.; Burke, Gregory L.; Eng, John; Lloyd-Jones, Donald M.

    2011-01-01

    Objectives By examining the distribution of CAC across FRS strata in a large, multi-ethnic, community-based sample of men and women, we sought to determine if lower risk persons could potentially benefit from CAC screening. Background The 10-year Framingham risk scores (FRS) and coronary artery calcium (CAC) are predictors of coronary heart disease (CHD). CAC ≥300 is associated with the highest risk for CHD even in low risk (FRS <10%) persons; however expert groups have suggested CAC screening only in intermediate risk (FRS 10–20%) groups. Methods We included 5660 MESA participants. The number needed to screen [number of people that need to be screened to detect one person with CAC above the specified cut-point (NNS)] was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests. Results CAC >0, ≥100 and ≥300 were present in 46.4%, 20.6% and 10.1% of participants, respectively. Prevalence and amount of CAC increased with higher FRS. CAC ≥300 was observed in 1.7% and 4.4% of those with FRS 0–2.5% and 2.6–5%, respectively (NNS =59.7 and 22.7). Likewise, CAC ≥300 was observed in 24% and 30% of those with FRS 15.1–20% and >20%, respectively (NNS =4.2 and 3.3). Trends were similar when stratified by age, gender and race/ethnicity. Conclusions Our study suggests that in very low risk individuals (FRS ≤5%), the yield of screening and probability of identifying persons with clinically significant levels of CAC is low, but becomes greater in low and intermediate risk persons (FRS 5.1–20%). PMID:21527159

  8. Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)

    PubMed Central

    Garcia-Rios, Antonio; Delgado-Casado, Nieves; Gomez-Luna, Purificacion; Gomez-Garduño, Angela; Gomez-Delgado, Francisco; Alcala-Diaz, Juan F.; Yubero-Serrano, Elena; Marin, Carmen; Perez-Caballero, Ana I.; Fuentes-Jimenez, Francisco J.; Camargo, Antonio; Rodriguez-Cantalejo, Fernando; Tinahones, Francisco J.; Ordovas, Jose M.; Perez- Jimenez, Francisco; Perez-Martinez, Pablo; Lopez-Miranda, Jose

    2016-01-01

    Background Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities. Methods 1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC. Results Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10−6). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese). Conclusions In coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity. Trial Registration ClinicalTrials.gov NCT00924937 PMID:27064675

  9. Effects of Low Dose Pioglitazone on Restenosis and Coronary Atherosclerosis in Diabetic Patients Undergoing Drug Eluting Stent Implantation

    PubMed Central

    Lee, Hye Won; Kim, Bo Won; Yang, Mi Jin; Park, Jin Sup; Oh, Jun Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Kim, Sang-Pil; Song, Seunghwan; Park, Jong-Ha

    2013-01-01

    Purpose Thiazolidinediones are insulin-sensitizing agents that reduce neointimal proliferation and the adverse clinical outcomes associated with percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). There is little data on whether or not low dose pioglitazone reduces adverse clinical outcomes. Materials and Methods The study population included 121 DM patients with coronary artery disease and they were randomly assigned to 60 patients taking 15 mg of pioglitazone daily in addition to their diabetic medications and 61 patients with placebo after the index procedure with drug-eluting stents (DESs). The primary end points were rate of in-stent restenosis (ISR) and change in atheroma volume and in-stent neointimal volume. The secondary end points were all-cause death, myocardial infarction (MI), stent thrombosis and re-PCI. Results There were no statistical differences in the clinical outcomes and the rate of ISR between the two groups [all-cause death; n=0 (0%) in the pioglitazone group vs. n=1 (1.6%) in the control group, p=0.504, MI; n=2 (3.3%) vs. n=1 (1.6%), p=0.465, re-PCI; n=6 (10.0%) vs. n=6 (9.8%), p=0.652, ISR; n=4 (9.3%) vs. n=4 (7.5%), p=1.000, respectively]. There were no differences in changes in neointimal volume, percent neointimal volume, total plaque volume and percent plaque volume between the two groups on intravascular ultrasonography (IVUS) study. Conclusion Our study demonstrated that low dose pioglitazone does not reduce rate of ISR, neointimal volume nor atheroma volume in DM patients who have undergone PCI with DESs, despite the limitations of the study. PMID:24142633

  10. 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

  11. 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.

  12. Primary Low Level of High-Density Lipoprotein Cholesterol and Risks of Coronary Heart Disease, Cardiovascular Disease, and Death: Results From the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Ahmed, Haitham M; Miller, Michael; Nasir, Khurram; McEvoy, John W; Herrington, David; Blumenthal, Roger S; Blaha, Michael J

    2016-05-15

    Prior studies observing associations between low levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease (CVD) have often been conducted among persons with metabolic or other lipid abnormalities. In this study, we investigated the association between primary low HDL cholesterol and coronary heart disease (CHD), CVD, and all-cause death after adjustment for confounders in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants who were free of clinical CVD were recruited from 6 US research centers from 2000 to 2002 and followed for a median duration of 10.2 years. We defined "primary low HDL cholesterol" as HDL cholesterol level <40 mg/dL (men) or <50 mg/dL (women), triglyceride level <100 mg/dL, and low-density lipoprotein cholesterol level <100 mg/dL (n = 158). We defined an "optimal" lipid profile as HDL cholesterol ≥40 mg/dL (men) or ≥50 mg/dL (women) and triglycerides and low-density lipoprotein cholesterol <100 mg/dL (n = 780). For participants with primary low HDL cholesterol versus those with an optimal lipid profile, adjusted hazard ratios for total CHD, CVD, and death were 2.25 (95% confidence interval (CI): 1.20, 4.21; P = 0.011), 1.93 (95% CI: 1.11, 3.34; P = 0.020), and 1.11 (95% CI: 0.67, 1.84; P = 0.69), respectively. Participants with primary low HDL cholesterol had higher risks of CHD and CVD than participants with optimal lipid profiles but no difference in survival after a median 10.2 years of follow-up. PMID:27189327

  13. Electrocardiographic Predictors of Coronary Heart Disease and Sudden Cardiac Deaths in Men and Women Free From Cardiovascular Disease in the Atherosclerosis Risk in Communities Study

    PubMed Central

    Rautaharju, Pentti M.; Zhang, Zhu‐Ming; Warren, James; Gregg, Richard E.; Haisty, Wesley K.; Kucharska‐Newton, Anna M.; Rosamond, Wayne D.; Soliman, Elsayed Z.

    2013-01-01

    Background We evaluated predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results The study population included 13 621 men and women 45 to 65 years of age free from manifest cardiovascular disease at entry. Hazard ratios from Cox regression with 95% confidence intervals were computed for 18 dichotomized repolarization‐related ECG variables. The average follow‐up was 14 years. Independent predictors of CHD death in men were TaVR‐ and rate‐adjusted QTend (QTea), with a 2‐fold increased risk for both, and spatial angles between mean QRS and T vectors and between Tpeak (Tp) and normal R reference vectors [θ(Rm|Tm) and θ(Tp|Tref), respectively], with a >1.5‐fold increased risk for both. In women, independent predictors of the risk of CHD death were θ(Rm|Tm), with a 2‐fold increased risk for θ(Rm|Tm), and θ(Tp|Tref), with a 1.7‐fold increased risk. Independent predictors of SCD in men were θ(Tp|Tref) and QTea, with a 2‐fold increased risk, and θ(Tinit|Tterm), with a 1.6‐fold increased risk. In women, θ(Tinit|Tterm) was an independent predictor of SCD, with a >3‐fold increased risk, and θ(Rm|Tm) and TV1 were >2‐fold for both. Conclusions θ(Rm|Tm) and θ(Tp|Tref), reflecting different aspects of ventricular repolarization, were independent predictors of CHD death and SCD, and TaVR and TV1 were also independent predictors. The risk levels for independent predictors for both CHD death and SCD were stronger in women than in men, and QTea was a significant predictor in men but not in women. PMID:23723252

  14. Long- and short-term weight change and incident coronary heart disease and ischemic stroke: the Atherosclerosis Risk in Communities Study.

    PubMed

    Stevens, June; Erber, Eva; Truesdale, Kimberly P; Wang, Chin-Hua; Cai, Jianwen

    2013-07-15

    Weight gain increases the prevalence of obesity, a risk factor for cardiovascular disease. Nevertheless, unintentional weight loss can be a harbinger of health problems. The Atherosclerosis Risk in Communities Study (1987-2009) included 15,792 US adults aged 45-64 years at baseline and was used to compare associations of long-term (30 years) and short-term (3 years) weight change with the risks of coronary heart disease (CHD) and ischemic stroke. Age-, gender-, and race-standardized incidence rates were 4.9 (95% confidence interval (CI): 4.6, 5.2) per 1,000 person-years for CHD and 2.5 (95% CI: 2.3, 2.8) per 1,000 person-years for stroke. After controlling for baseline body mass index and other covariates, long-term weight gain (since age 25 years) of more than 2.7% was associated with elevated CHD risk, and any long-term weight gain was associated with increased stroke risk. Among middle-aged adults, short-term (3-year) weight loss of more than 3% was associated with elevated immediate CHD risk (hazard ratio = 1.46, 95% CI: 1.18, 1.81) and stroke risk (hazard ratio = 1.45, 95% CI: 1.10, 1.92). Risk tended to be larger in adults whose weight loss did not occur through dieting. Avoidance of weight gain between early and middle adulthood can reduce risks of CHD and stroke, but short-term, unintentional weight loss in middle adulthood may be an indicator of immediate elevated risk that has not previously been well recognized. PMID:23645623

  15. The non-thyroidal illness syndrome in acute coronary syndrome is associated with increased cardiac morbidity and mortality

    PubMed Central

    Adawiyah, J; Norasyikin, A W; Mat, N H; Shamsul, A S; Azmi, K Nor

    2010-01-01

    Introduction The non-thyroidal illness syndrome (NTIS) or the sick euthyroid syndrome refers to abnormal changes in circulating thyroid hormones due to systemic illnesses. Thyroid hormones are pivotal in the regulation of normal cardiac functions. However, the effects of the NTIS on the heart in acute coronary syndrome (ACS) are still unclear. Methods A 6-month prospective cohort study involving 85 patients admitted with ACS was carried out. TSH, FT4 and FT3 were assessed on days 1, 5 and 42. Antithyroid peroxidase antibodies, antithyroglobulin antibodies, fasting blood sugar, HbA1c and fasting serum lipid were obtained on admission. Mortality, functional status (Killip and New York Heart Association Classifications), arrhythmias and readmission rate were recorded. Results The prevalence of NTIS was 53%. It was seen in 48% of unstable angina (UA), 54% of non-ST elevation myocardial infarction (NSTEMI) and 56% of ST elevation myocardial infarction (STEMI) patients. NTIS is associated with cardiovascular mortality, all-cause mortality, severe heart failure and a higher readmission rate. The levels of FT3 correlate with severity of myocardial damage as measured by CK and Troponin T. Lower TSH was seen in the non-survivors and in those with ventricular arrhythmias. The most common presentation of NTIS was low FT3 (43.5%), followed by low TSH (12.9%) and FT4 (4.7%). None of the predisposing factors analysed were associated with the development of NTIS. Conclusions NTIS in patients with ACS is associated with increased cardiovascular mortality and morbidity, and affects UA, NSTEMI and STEMI equally. PMID:27325934

  16. Molecular imaging in atherosclerosis

    PubMed Central

    Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.; Bozzao, Alessandro; Bonanno, Elena; Arca, Marcello; Dierckx, Rudi A. J. O.

    2010-01-01

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  17. Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis.

    PubMed

    Cheung, Yiu-Fai

    2014-11-01

    Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term. PMID:25550701

  18. Inflammation in atherosclerosis: new opportunities for drug discovery.

    PubMed

    Meng, Charles Q

    2005-01-01

    Many lines of evidence indicate that inflammation is the ultimate cause of atherosclerosis; high cholesterol levels cause atherosclerosis through mechanism of inflammation. Drugs designed to address inflammatory aspects of atherosclerosis will likely be more effective than current therapies in treating and preventing coronary artery disease. PMID:15638790

  19. Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis123

    PubMed Central

    Shea, M Kyla; Booth, Sarah L; Miller, Michael E; Burke, Gregory L; Chen, Haiying; Cushman, Mary; Tracy, Russell P; Kritchevsky, Stephen B

    2013-01-01

    Background: Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited. Objective: We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design. Design: Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial. Results: The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01]. Conclusions: Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention

  20. Development of a New Diabetes Risk Prediction Tool for Incident Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study

    PubMed Central

    Yeboah, Joseph; Erbel, Raimund; Delaney, Joseph Chris; Nance, Robin; Guo, Mengye; Bertoni, Alain G.; Budoff, Matthew; Moebus, Susanne; Jöckel, Karl-Heinz; Burke, Gregory L; Wong, Nathan D; Lehmann, Nils; Herrington, David M; Möhlenkamp, Stefan; Greenland, Philip

    2014-01-01

    Objective We develop a new diabetes CHD risk estimator using traditional risk factors plus coronary artery calcium (CAC), ankle-brachial index (ABI), high sensitivity C-reactive protein, family history of CHD, and carotid intima-media thickness and compared it with United Kingdom Prospective Diabetes study (UKPDS), Framingham risk and the NCEP/ATP III risk scores in type 2 diabetes mellitus (T2DM). Methods and Results We combined data from T2DM without clinical CVD in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (N=1343). After a mean follow-up of 8.5 years, 85(6.3%) participants had incident CHD. Among the novel risk markers, CAC best predicted CHD independent of the FRS [hazard ratio: HR (95% CI): log (CAC +25):1.69(1.45 – 1.97), p<0.0001; CAC categories: CAC ≤ 25 as reference, >25 and ≤ 125:2.29(0.87 – 5.95), >125 and ≤ 400: 3.87(1.57– 9.57), >400: 5.97(2.57– 13.84), respectively). The MESA-HNR diabetes CHD risk score has better accuracy for the main outcome versus the FRS or UKPDS [area under curve (AUC) of 0.76 vs. 0.70 and 0.69, respectively; all p<0.05]. The MESA-HNR risk score improved risk classification versus the FRS (net reclassification improvement (NRI) = 0.19 and integrated discrimination improvement (IDI) =0.046, p<0.05) and UKPDS (NRI=0.215 and IDI = 0.046, p<0.05). Compared with the ATP III guidelines, the MESA-HNR score has an NRI of 0.74 for the main outcome. Conclusions This new CHD risk estimator has better discriminative ability for incident CHD than the FRS, UKPDS, and the ATP III/NCEP recommendations in a multi-ethnic cohort with T2DM. PMID:25150939

  1. Low serum docosahexaenoic acid is associated with progression of coronary atherosclerosis in statin-treated patients with diabetes mellitus: results of the treatment with statin on atheroma regression evaluated by intravascular ultrasound with virtual histology (TRUTH) study

    PubMed Central

    2014-01-01

    Background Diabetes mellitus (DM) accelerates plaque progression despite the use of statin therapy. The purpose of the present study was to evaluate the determinants of atheroma progression in statin-treated patients with DM. Methods Coronary atherosclerosis in nonculprit lesions in a vessel undergoing percutaneous coronary intervention (PCI) was evaluated using virtual histology intravascular ultrasound. The study included 50 patients with DM who had been taking statin therapy for 8 months at the time of PCI. Results Twenty-six patients (52%) showed atheroma progression (progressors) and the remaining 24 patients (48%) showed atheroma regression (regressors) after 8 months of follow-up. Fewer progressors than regressors received intensive lipid-lowering therapy with pitavastatin (31% vs. 50%, p = 0.17) and the frequency of insulin use was higher in progressors (31% vs. 13%, p = 0.18). However, neither of these differences reached statistical significance. Risk factor control at baseline and at the 8-month follow-up did not differ between the 2 groups except for serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Univariate regression analysis showed that serum EPA (r = -0.317, p = 0.03) and DHA (r = -0.353, p = 0.02) negatively correlated with atheroma progression. Multivariate stepwise regression analysis showed that low serum DHA and pravastatin use were significant independent predictors for atheroma progression during statin therapy (DHA: β = -0.414, type of statin: β = -0.287, p = 0.001). Conclusions Low serum DHA is associated with progression of coronary atherosclerosis in statin-treated patients with DM. Trial registration UMIN Clinical Trials Registry, UMIN ID: C000000311. PMID:24410834

  2. Illness cognition as a predictor of exercise habits and participation in cardiac prevention and rehabilitation programs after acute coronary syndrome

    PubMed Central

    2013-01-01

    Background Despite well-established medical recommendations, many cardiac patients do not exercise regularly either independently or through formal cardiac prevention and rehabilitation programs (CPRP). This non-adherence is even more pronounced among minority ethnic groups. Illness cognition (IC), i.e. the way people perceive the situation they encounter, has been recognized as a crucial determinant of health-promoting behavior. Few studies have applied a cognitive perspective to explain the disparity in exercising and CPRP attendance between cardiac patients from different ethnic backgrounds. Based on the Health Belief Model (HBM) and the Common Sense Model (CSM), the objective was to assess the association of IC with exercising and with participation in CPRP among Jewish/majority and Arab/minority patients hospitalized with acute coronary syndrome. Methods Patients (N = 420) were interviewed during hospitalization (January-2009 until August- 2010) about IC, with 6-month follow-up interviews about exercise habits and participation in CPRP. Determinants that predict active lifestyle and participation in CPRP were assessed using backward stepwise logistic regression. Results Perceived susceptibility to heart disease and sense and personal control were independently associated with exercising 6 months after the acute event (OR = 0.58, 95% CI: 0.42-0.80 and OR = 1.09, 95% CI: 1.02-1.17, per unit on a 5-point scale). Perceived benefits of regular exercise and a sense of personal control were independently associated with participation in CPRP (OR = 1.56, 95% CI: 1.12-2.16 and OR = 1.08, 95% CI: 1.01-1.15, per unit on a 5-point scale). None of the IC variables assessed could explain the large differences in health promoting behaviors between the majority and minority ethnic groups. Conclusions IC should be taken into account in future interventions to promote physical activity and participation in CPRP for both ethnic groups. Yet, because IC failed

  3. Ectasia and Severe Atherosclerosis

    PubMed Central

    Adiloglu, Ali K.; Can, Rabia; Nazli, Cem; Ocal, Ahmet; Ergene, Oktay; Tinaz, Gulgun; Kisioglu, Nesimi

    2005-01-01

    To date, there has been no convincing evidence for an association between Chlamydia pneumoniae or Helicobacter pylori and ectasia. In this case-control study, we have investigated the association of H. pylori and C. pneumoniae seropositivity with ectasia, severe coronary atherosclerosis, and normal vessels, which were so classified by coronary angiography. We have also evaluated the influence of these infections on inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6). Of the 796 patients undergoing coronary angiography for suspected ischemic heart disease, 244 patients were recruited. Of these, 91 had normal vessels, 88 had 3 or more obstructed vessels, and 65 had ectatic vessels without atherosclerosis. Eighty-seven atherosclerotic patients (98.9%) were positive for C. pneumoniae IgG, as were 64 ectatic patients (98.5%) and 76 controls (83.5%) (P < 0.001). Forty-two atherosclerotic patients (47.7%) were positive for C. pneumoniae IgM, as were 43 ectatic patients (66.2%) and 43 controls (47.3%) (P = 0.036). Seventy-two atherosclerotic patients (81.8%) were positive for H. pylori IgA, as were 26 ectatic patients (40.0%) and 44 controls (48.4%) (P < 0.001). High-sensitive CRP levels were significantly higher in ectatic patients (5.639 mg/L) than in controls (4.390 mg/L) (P = 0.032), and IL-6 levels were significantly higher in atherosclerotic patients (33.92 U/L) than in controls (14.01 U/L) (P < 0.001). Interleukin-6 levels were higher in H. pylori seropositive patients, and hsCRP levels were higher in C. pneumoniae seropositive patients, when compared with seronegatives. We suggest that, as in atherosclerosis, C. pneumoniae infection is related to ectasia, with raised CRP levels. PMID:15902817

  4. POST CORONARY ARTERY BYPASS GRAFT STUDY (CABG)

    EPA Science Inventory

    Relative effectiveness of moderate versus more aggressive lipid lowering, and of low dose anticoagulation versus placebo, in delaying saphenous vein coronary bypass graft atherosclerosis and preventing occlusion of saphenous grafts of patients with saphenous vein coronary bypass ...

  5. 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. PMID:25174928

  6. 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.

  7. The paradoxical role of IL-17 in atherosclerosis.

    PubMed

    Gong, Fangchen; Liu, Zhengxia; Liu, Jingning; Zhou, Ping; Liu, Ying; Lu, Xiang

    2015-09-01

    Atherosclerosis is a chronic inflammatory disease mediated by innate and adaptive immune responses. In recent years, CD4(+) T cells (Th1, Th2, Treg, and Th17) have been increasingly studied for their role in atherosclerosis pathophysiology, atheroma stability, plaque rupture, and life-threatening acute coronary syndrome. IL-17, a marker cytokine of Th17 cells, has been reported to be involved in the pathogenesis of rheumatoid arthritis, inflammatory bowel disease, and asthma. However, its role in atherosclerosis has been poorly characterized. This article provides a comprehensive overview of the role of IL-17 in the development of atherosclerosis and human coronary artery diseases. PMID:26077826

  8. GENETIC VARIATION IN SOLUBLE EPOXIDE HYDROLASE (EPHX2) AND RISK OF CORONARY HEART DISEASE: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the vasculature and regulates endothelial function. We sought to determine whether genetic variation in soluble epoxide hydrolase (EPHX2) was ass...

  9. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the vasculature and regulates endothelial function. We sought to determine whether genetic variation in soluble epoxide hydrolase (EPHX2) was ass...

  10. [Pregnancy and coronary artery dissection].

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna

    2015-01-01

    Acute myocardial infarction during pregnancy is associated with high maternal and fetal mortality. Coronary atherosclerosis is the most common cause due to an increase in the age of the patients and the association with cardiovascular risk factors such as smoking, hypertension, diabetes mellitus, preeclampsia, and the existence of family history of coronary disease. However, thrombosis, coronary dissection or coronary vasospasms are other causes that may justify it. We report the case of a 33 weeks pregnant first-time mother, without cardiovascular risk factors, who presented an acute coronary event in the context of atherosclerotic disease and coronary dissection after percutaneous coronary intervention. PMID:25795261

  11. Atherosclerosis and the internal mammary arteries

    SciTech Connect

    Singh, R.N.

    1983-06-01

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

  12. Comparison of Insulin Resistance to Coronary Atherosclerosis in Human Immunodeficiency Virus Infected and Uninfected Men (from the Multicenter AIDS Cohort Study).

    PubMed

    Brener, Michael I; Post, Wendy S; Haberlen, Sabina A; Zhang, Long; Palella, Frank J; Jacobson, Lisa P; Dobs, Adrian S; George, Richard T; Witt, Mallory D; Budoff, Matthew; Kingsley, Lawrence A; Brown, Todd T

    2016-03-15

    The relation between insulin resistance (IR) and coronary artery disease in patients with human immunodeficiency virus (HIV) infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study were collected at semiannual visits from 2003 to 2013 and used to compute the homeostatic model assessment of IR (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10-year study period) and the prevalence of coronary plaque or stenosis ≥50% were assessed with multivariate logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs 2.7, p = 0.002) and when averaged over the study period (3.4 vs 3.0, p <0.001). The prevalence of coronary stenosis ≥50% was similar between both groups (17% vs 15%, p = 0.41). Both measurements of HOMA-IR were associated with greater odds of coronary stenosis ≥50% in models comparing men with values in the highest versus the lowest tertiles, although the effect of mean HOMA-IR was stronger than the single measurement of HOMA-IR before CTA (odds ratio 2.46, 95% CI 1.95 to 3.11, vs odds ratio 1.43, 1.20 to 1.70). This effect was not significantly modified by HIV serostatus. In conclusion, IR over nearly a decade was greater in HIV-infected men than HIV-uninfected men, and in both groups, was associated with significant coronary artery stenosis. PMID:26830260

  13. Atherosclerosis Induced by Chlamydophila pneumoniae: A Controversial Theory.

    PubMed

    Honarmand, Hamidreza

    2013-01-01

    More than a century ago, inflammation and infection were considered to have atherogenic effects. The old idea that coronary heart disease (CHD) possibly has an infectious etiology has only reemerged in recent years. Atherosclerosis is the main pathological process involved in CHD and is, logically, the first place to look for infectious etiology. The process of atherosclerosis itself provides the first hints of potential infectious cause. Smooth muscle proliferation, with subsequent intimal thickening, luminal narrowing, and endothelial degeneration, constitutes the natural history of atherosclerosis, being with the severity and speed of these changes. Both viral and bacterial pathogens have been proposed to be associated with the inflammatory changes found in atherosclerosis. Recently, Chlamydophila pneumoniae (C. pneumoniae) has been implicated as a possible etiologic agent of coronary artery disease and atherosclerosis. New evidence which supports a role for C. pneumoniae in the pathogenesis of atherosclerosis has emerged. C. pneumoniae has been detected in atherosclerotic arteries by several techniques, and the organism has been isolated from both coronary and carotid atheromas. Recent animal models have suggested that C. pneumoniae is capable of inducing atherosclerosis in both rabbit and mouse models of atherosclerosis. Furthermore, human clinical treatment studies which examined the use of antichlamydial macrolide antibiotics in patients with coronary atherosclerosis have been carried out. The causal relationship has not yet been proven, but ongoing large intervention trials and research on pathogenetic mechanisms may lead to the use of antimicrobial agents in the treatment of CHD in the future. PMID:23956742

  14. 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 Central

    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.

    2015-01-01

    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. PMID:26674973

  15. Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic conditions

    PubMed Central

    Hong, Jison; Maron, David J; Shirai, Tsuyoshi; Weyand, Cornelia M

    2015-01-01

    Atherosclerosis is a complex inflammatory disease involving aberrant immune and tissue healing responses, which begins with endothelial dysfunction and ends with plaque development, instability and rupture. The increased risk for coronary artery disease in patients with rheumatologic diseases highlights how aberrancy in the innate and adaptive immune system may be central to development of both disease states and that atherosclerosis may be on a spectrum of immune-mediated conditions. Recognition of the tight association between chronic inflammatory disease and complications of atherosclerosis will impact the understanding of underlying pathogenic mechanisms and change diagnostic and therapeutic approaches in patients with rheumatologic syndromes as well as patients with coronary artery disease. In this review, we provide a summary of the role of the immune system in atherosclerosis, discuss the proposed mechanisms of accelerated atherosclerosis seen in association with rheumatologic diseases, evaluate the effect of immunosuppression on atherosclerosis and provide updates on available risk assessment tools, biomarkers and imaging modalities. PMID:27042216

  16. Marital Status, Hypertension, Coronary Heart Disease, Diabetes, and Death among African American Women and Men: Incidence and Prevalence in the Atherosclerosis Risk in Communities (ARIC) Study Participants

    ERIC Educational Resources Information Center

    Schwandt, Hilary M.; Coresh, Josef; Hindin, Michelle J.

    2010-01-01

    Heart disease is the leading cause of death in the United States, and African Americans disproportionately experience more cardiovascular disease, including coronary heart disease (CHD), hypertension, and diabetes. The literature documents a complex relationship between marital status and health, which varies by gender. We prospectively examine…

  17. Correlation between high density lipoprotein-cholesterol and remodeling index in patients with coronary artery disease: IDEAS (IVUS diagnostic evaluation of atherosclerosis in Singapore)-HDL study.

    PubMed

    Lee, Chi-Hang; Tai, Bee-Choo; Lim, Gek-Hsiang; Chan, Mark Y; Low, Adrian F; Tan, Kathryn C; Chia, Boon-Lock; Tan, Huay-Cheem

    2012-01-01

    Serum level of high density lipoprotein (HDL)-cholesterol is associated with risk of coronary artery disease. We correlated the serum level of cholesterol with coronary artery remodeling index of patients with coronary artery disease. A total of 120 patients with de novo lesions located in native coronary artery were studied. Remodeling index was based on intravascular ultrasound (IVUS) interrogation of the lesions using the static approach, and was defined as external elastic membrane (EEM) area at lesion/average EEM area at proximal and distal reference segments. The average remodeling index was 0.9 (SD: 0.2). The remodeling index was not associated with any of the demographic and coronary risk factors. Stable angina was associated with a low remodeling index. Remodeling index correlated with white blood cell count and HDL-cholesterol, but not with total cholesterol, LDL-cholesterol and triglyceride. In the multiple linear regression analysis, HDL-cholesterol and procedure indication were the only 2 significant predictors of remodeling index. An increase of 1 mg/dL of HDL-cholesterol resulted in a decrease of 0.003 (95% CI: 0.0001, 0.007; P = 0.046) in remodeling index, after adjusting for procedural indications. When stratified according to diabetic status, the negative correlation persisted in non-diabetic (P = 0.023), but not in diabetic, patients (P = 0.707). We found a negative correlation between HDL-cholesterol level and remodeling index. Diabetic status may have an influence on the observed relationship. PMID:21197580

  18. Imaging Atherosclerosis.

    PubMed

    Tarkin, Jason M; Dweck, Marc R; Evans, Nicholas R; Takx, Richard A P; Brown, Adam J; Tawakol, Ahmed; Fayad, Zahi A; Rudd, James H F

    2016-02-19

    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

  19. 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

  20. ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY (ARIC)

    EPA Science Inventory

    Epidemiology Study -- ARIC is a large-scale, long-term prospective study that measures associations of established and suspected coronary heart disease risk factors with both atherosclerosis and new CHD events in men and women from four geographically diverse communities. The pro...

  1. Usefulness of High-Sensitivity Cardiac Troponin T for the Identification of Outlier Patients With Diffuse Coronary Atherosclerosis and Low-Risk Factors.

    PubMed

    Magnoni, Marco; Masson, Serge; Andreini, Daniele; Moccetti, Tiziano; Modena, Maria Grazia; Canestrari, Mauro; Berti, Sergio; Casolo, Giancarlo; Gabrielli, Domenico; Marraccini, Paolo; Pontone, Gianluca; Latini, Roberto; Maggioni, Aldo Pietro; Maseri, Attilio

    2016-05-01

    Novel high-sensitivity assay can detect very low levels of circulating cardiac troponin (hs-cTnT) in apparently healthy subjects. Within normal range, higher levels are associated with coronary artery disease (CAD) and cardiac abnormalities commonly associated to traditional risk factors (RFs) for CAD. Therefore, we investigated the relation between circulating hs-cTnT and CAD in patients with a spectrum of RF burden aiming to assess the added value of hs-cTnT to identify "outlier" patients with CAD despite a low RF burden. Hs-cTnT was measured in 525 stable patients without previous diagnosis of ischemic heart disease with 0 to 1 RF, excluded diabetes, (low-RF group, n = 263) or ≥2 RFs (multiple-RF group, n = 262) and without CAD (segment involvement score = 0) or diffuse CAD (segment involvement score >5) at coronary computed tomography angiography. Outlier patients with diffuse CAD despite low-RF burden had similar extent, severity, and plaque composition than patients with multiple RFs. Overall, hs-cTnT was measurable in 81% of patients with median value of 6.0 ng/L. In both groups, hs-cTnT concentration was higher in patients with CAD than in patients with normal coronary arteries (p <0.0001). Hs-cTnT was more accurate to detect patients with CAD in the low-RF group than in the multiple-RF group (p = 0.04). In multivariate analysis, higher level of hs-cTnT (>6 ng/L) was independently associated with CAD in low-RF group only. Despite very low circulating concentrations, hs-cTnT may identify with a good accuracy the outlier patients with diffuse CAD despite low-RF burden. PMID:26976791

  2. What Causes Atherosclerosis?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Causes Atherosclerosis? The exact cause of atherosclerosis isn't known. ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  3. How Is Atherosclerosis Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Atherosclerosis Treated? Treatments for atherosclerosis may include heart-healthy ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  4. High resolution three-dimensional visualization and characterization of coronary atherosclerosis in vitro by synchrotron radiation x-ray microtomography and highly localized x-ray diffraction

    NASA Astrophysics Data System (ADS)

    Jin, Hua; Ham, Kyungmin; Chan, Julia Y.; Butler, Leslie G.; Kurtz, Richard L.; Thiam, Serigne; Robinson, James W.; Agbaria, Rezik A.; Warner, Isiah M.; Tracy, Richard E.

    2002-12-01

    Human atherosclerotic plaques in both native and bypass arteries have been visualized using microtomography to provide additional information on the nature of coronary artery disease. Plaques contained within arteries removed from three white males aged 51, 55 and 70 are imaged in three-dimensions with monochromatic synchrotron x-ray radiation. Fields of view are 658 × 658 × 517 voxels, with cubic voxels ranging from 12 to 13 µm on a side. X-ray energies range from 11 to 15 keV (bandpass approximately 10 eV). At lower energies, high local absorption tends to generate reconstruction artefacts, while at higher energies the arterial wall is scarcely visible. At all energies, calcifications are clearly visible and differences are observed between plaques in native arteries (lifetime accumulations) versus bypass arteries (plaques developing in the interval between the heart bypass operation and the autopsy). In order to characterize coronary calcification, a micro-focused, 50 µm2, 25 keV x-ray beam was used to acquire powder diffraction data from selected calcifications. Also, large calcifications were removed from the native arteries and imaged with 25 keV x-ray energy. Calcifications are composed of hydroxyapatite crystallites and an amorphous phase. In summary, native calcifications are larger and have a higher fraction of hydroxyapatite than calcifications from the bypass arteries.

  5. [The infection theory in atherosclerosis].

    PubMed

    Capron, L; Wyplosz, B

    1998-10-01

    Atherosclerosis displays all the features of a chronic inflammatory process. Aggressions that ignite and fuel atherosclerotic inflammation warrant keen attention. Infection is a potential clue, implying microbes with certain discrete characteristics: a wide epidemiologic distribution, a tropism for the arterial wall, and an aptitude for persistence, latency and recurrence. The infectious theory has built up from the pioneering observations of Fabricant et al. (1978) on the arterial lesions provoked by Marek's disease herpesvirus in chicken. So far one virus (cytomegalovirus) and two bacteria (Chlamydia pneumoniae and Helicobacter pylori) have been implicated in human atherosclerosis, based upon experimental, sero-epidemiologic, or pathologic evidence. None of these potential contributions has yet been established beyond reasonable doubt. However, grounded on the suspicion about C. pneumoniae, provocative therapeutic evidence has added recently: according to two pilot studies, treatment with macrolide antibiotics appear to improve the prognosis of coronary artery disease in both its chronic and acute forms. If ongoing larger-scale studies confirm these preliminary results, a novel era will open in our capacity for explaining, treating and preventing atherosclerosis. An infectious aetiology of atherosclerosis is now to be considered earnestly, and is already being submitted to more intensive clinical and experimental investigation. PMID:9833076

  6. Coronary microvascular dysfunction: an update

    PubMed Central

    Crea, Filippo; Camici, Paolo G.; Bairey Merz, Cathleen Noel

    2014-01-01

    Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy. PMID:24366916

  7. Coronary Thrombosis without Dissection following Blunt Trauma

    PubMed Central

    Sibel, Michael; Thomas, Peter; Burt, Francis; Cipolla, James; Puleo, Peter; Baker, Keith

    2016-01-01

    Blunt trauma to the chest resulting in coronary thrombosis and ST elevation myocardial infarction (STEMI) is a rare but well-described occurrence in adults. Angiography in such cases has generally disclosed complete epicardial coronary occlusion with thrombus, indistinguishable from the findings commonly found in spontaneous plaque rupture due to atherosclerotic disease. In all previously reported cases in which coronary interrogation with intravascular ultrasound (IVUS) was performed in association with acute revascularization, coronary artery dissection was implicated as the etiology of coronary thrombosis. We present the first case report of blunt trauma-associated coronary thrombosis without underlying atherosclerosis or coronary dissection, as documented by IVUS imaging. PMID:27006836

  8. Association between type 2 diabetes mellitus, biochemical factors and UCSNP-43 polymorphisms of CALPIN-10 gene in patients with atherosclerosis of coronary artery disease in Southern Iran population

    PubMed Central

    Senemar, Sara; Edraki, Mohammad Reza; Toosi, Samane

    2016-01-01

    Introduction: Genetic variations in the calpain 10 gene (CALPIN-10), single nucleotide polymorphisms-43 (SNP-43), have increased the risk of type 2 diabete mellitus (T2DM) and coronary artery disease (CAD). Methods: We studied the control and CAD groups for association of association of SNP-43 in the CALPIN-10 gene with T2DM and other risk factors of its complications. Overall, we examined 452 individuals, 224 patients with CAD and 228 healthy subjects for CAD in Iranian population. All the subjects were genotyped for the CALPIN-10, SNP-43 by polymorphism chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, using biochemical methods to detect fasting glucose and other biochemical factors in the blood sample. We assessed frequencies of SNP-43 alleles between CAD and normal population groups. Results: In CAD patients, the GG allele was significantly associated with T2DM and GG allele was causing high level of glucose. But in control group, there was no relationship between them. Between clinical and biochemical risk factors with different genotypes there was no significant difference in the compared group. Conclusion: The results of our study suggest no significant association between SNP-43 and the risk of T2DM. In other words, CALPIN-10 did not show a major diabetes gene pool capacity in normal southern Iranian population. PMID:27069562

  9. Association of Isolated Minor Non-specific ST-Segment and T-Wave Abnormalities with Subclinical Atherosclerosis in a Middle-Aged, Biracial Population: Coronary Artery Risk Development in Young Adults (CARDIA) Study

    PubMed Central

    Walsh, Joseph A; Prineas, Ronald; Soliman, Elsayed Z.; Liu, Kiang; Ning, Hongyan; Daviglus, Martha L.; Lloyd-Jones, Donald M.

    2016-01-01

    Aims Isolated minor non-specific ST segment and T wave abnormalities (NSSTTA) are common and known to be independent electrocardiographic risk markers for future cardiovascular disease (CVD) events. The association of NSSTTA with subclinical atherosclerosis is not well defined, but has been postulated as a potential mechanism of association with future clinical events. Methods and Results We studied participants from the Year 20 examination of the middle-aged, biracial CARDIA cohort. This examination included measurement of traditional risk factors, 12-lead electrocardiograms (ECG), coronary artery calcium (CAC) measurement and common carotid intima-media thickness (CCIMT). ECGs were coded using both Minnesota Code (MC) and Novacode (NC) criteria. Isolated minor STTA was defined by MC as presence of MC 4-3, 4-4, 5-3, or 5-4, and by NC as presence of NC 5.8. ECGs with secondary causes of STTA (i.e. LVH) were excluded. Multivariable logistic regression was used to determine the cross-sectional association of isolated minor NSSTTA with CAC and CC-IMT. The study sample consisted of 2175 participants with an average age of 45 years (57% women and 43% black). No association was observed between NSSTTA and CAC. After multivariable-adjustment for traditional CVD risk factors, the presence of isolated minor NSSTTA remained significantly associated with the extent of CCIMT (OR 1.25 (1.06 – 1.48), p < 0.01). This association remained significant after further adjustment for CAC. Conclusions Isolated minor NSSTTA were associated with the extent of CCIMT, but not with CAC, in this middle-aged biracial cohort. Further study is needed to elucidate potential mechanisms for these findings. PMID:22952292

  10. The relationship between adiposity-associated inflammation and coronary artery and abdominal aortic calcium differs by strata of central adiposity: The Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Hughes-Austin, Jan M; Wassel, Christina L; Jiménez, Jessica; Criqui, Michael H; Ix, Joachim H; Rasmussen-Torvik, Laura J; Budoff, Matthew J; Jenny, Nancy S; Allison, Matthew A

    2014-06-01

    Adipokines regulate metabolic processes linked to coronary artery (CAC) and abdominal aorta calcification (AAC). Because adipokine and other adiposity-associated inflammatory marker (AAIM) secretions differ between visceral and subcutaneous adipose tissue, we hypothesized that central adiposity modifies associations between AAIMs and CAC and AAC. We evaluated 1878 MESA participants with complete measures of AAIMs, anthropometry, CAC, and AAC. Associations of AAIMs with CAC and AAC prevalence and severity were analyzed per standard deviation of predictors (SD) using log binomial and linear regression models. The waist-to-hip ratio (WHR) was dichotomized at median WHR values based on sex/ethnicity. CAC and AAC prevalence were defined as any calcium (Agatston score >0). Severity was defined as ln (Agatston score). Analyses examined interactions with WHR and were adjusted for traditional cardiovascular disease risk factors. Each SD higher interleukin-6 (IL-6), fibrinogen and CRP was associated with 5% higher CAC prevalence; and each SD higher IL-6 and fibrinogen was associated with 4% higher AAC prevalence. Associations of IL-6 and fibrinogen with CAC severity, but not CAC prevalence, were significantly different among WHR strata. Median-and-above WHR: each SD higher IL-6 was associated with 24.8% higher CAC severity. Below-median WHR: no association (p interaction=0.012). Median-and-above WHR: each SD higher fibrinogen was associated with 19.6% higher CAC severity. Below-median WHR: no association (p interaction=0.034). Adiponectin, leptin, resistin, and tumor necrosis factor-alpha were not associated with CAC or AAC prevalence or severity. These results support findings that adiposity-associated inflammation is associated with arterial calcification, and further add that central adiposity may modify this association. PMID:24907349

  11. Hyperhomocysteinemia and atherosclerosis.

    PubMed

    Yang, Fan; Tan, Hong-Mei; Wang, Hong

    2005-04-25

    Arteriosclerosis and its complications, such as heart attack and stroke, are the major causes of death in developed countries. It was believed that age, hyperlipidemia, hypertension, diabetes and smoking are common risk factors for cardiovascular disease. In addition, overwhelming clinical and epidemiological studies have identified homocysteine (Hcy) as a significant and independent risk factor for cardiovascular disease. In healthy individuals, plasma Hcy is between 5 and 10 micromol/L. One cause of severe hypehomocys- teinemia (HHcy) is the deficiency of cystathionine beta-synthase (CBS), which converts Hcy to cystathionine. CBS homozygous deficiency results in severe HHcy with Hcy levels up to 100 to 500 micromol/L. Patients with severe HHcy usually present with neurological abnormalities, premature arteriosclerosis. It has been reported that lowering plasma Hcy improved endothelial dysfunction and reduced incidence of major adverse events after percutaneous coronary intervention. The mechanisms by which Hcy induces atherosclerosis are largely unknown. Several biological mechanisms have been proposed to explain cardiovascular pathological changes associated with HHcy. These include: (1) endothelial cell damage and impaired endothelial function; (2) dysregulation of cholesterol and triglyceride biosynthesis; (3) stimulation of vascular smooth muscle cell proliferation; (4) thrombosis activation and (5) activation of monocytes. Four major biochemical mechanisms have been proposed to explain the vascular pathology of Hcy. These include: (1) autooxidation through the production of reactive oxygen species; (2) hypomethylation by forming SAH, a potent inhibitor of biological transmethylations; (3) nitrosylation by binding to nitric oxide or (4) protein homocysteinylation by incorporating into protein. In summary, our studies, as well as data from other laboratories support the concept that Hcy is causally linked to atherosclerosis, and is not merely associated with

  12. Relationship between myocardial bridging and coronary arteriosclerosis.

    PubMed

    Sun, Jian Ling; Huang, Wei Min; Guo, Ji Hong; Li, Xiao Ying; Ma, Xian Lin; Wang, Chong Yu

    2013-04-01

    The objective of the study was to explore the prevalence and characteristics of myocardial bridging in patients who underwent coronary angiography and to also evaluate the correlation between bridged coronary segments and atherosclerosis. For this purpose, clinical materials of 1,500 patients who had received coronary angiography were retrospectively analyzed. The location and length of the myocardial bridge were recorded as well as the extent and location of coronary artery stenosis was described. Segments proximal and distal to the bridging were evaluated for coronary arteriosclerosis as were the remaining coronary segments. We found that myocardial bridging was present in 179 (11.9 %) patients. Bridges were frequently (84.9 %) localized in the mid-distal segment of the left anterior descending (LAD) artery. Myocardial bridging was not considered a significant risk factor for coronary atherosclerosis (odds ratio 0.58) compared with traditional cardiovascular risk factors. The incidence of coronary arteriosclerosis in the distal segments was significantly less affected than the proximal segments (P < 0.01). It was, therefore, concluded that myocardial bridging frequently localized in the mid-distal segment of the LAD artery. The presence of myocardial bridging promotes proximal atherosclerosis but it is not an additional risk factor for coronary atherosclerosis. PMID:23076634

  13. Atherosclerosis and Stroke

    MedlinePlus

    ... Stroke When the Beat is Off - Atrial Fibrillation Atherosclerosis and Stroke How Cardiovascular & Stroke Risks Relate Problems ... of LDL cholesterol contribute to the development of atherosclerosis as the cholesterol is deposited in artery walls, ...

  14. 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.

  15. Diagnosis & Treatment | Coronary Artery Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... this page please turn Javascript on. Feature: Coronary Artery Disease Diagnosis & Treatment Past Issues / Fall 2010 Table of Contents Diagnosis Your healthcare provider diagnoses coronary artery disease (atherosclerosis) based on your medical and family ...

  16. Inflammation: a trigger for acute coronary syndrome.

    PubMed

    Sager, Hendrik B; Nahrendorf, Matthias

    2016-09-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis' most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes. PMID:27273431

  17. Atherosclerosis Prevention in Youth

    PubMed Central

    2012-01-01

    Atherosclerosis-associated circulatory disturbance is one of the most important global issues. In patients with atherosclerosis, eccentric intimal thickening and lipid deposition progress over a long period (at least 20 to 30 years). On the other hand, in patients with atherosclerosis-associated circulatory disturbance represented by myocardial infarction, the direct cause of death is thrombus formation rather than marked stenosis; wall destruction may lead to a fatal outcome. In the future, atherosclerosis susceptibility, that is, intrinsic genes, should be investigated. PMID:23641261

  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. Intracranial atherosclerosis following radiotherapy

    SciTech Connect

    Werner, M.H.; Burger, P.C.; Heinz, E.R.; Friedman, A.H.; Halperin, E.C.; Schold, S.C. Jr.

    1988-07-01

    We describe a case of severe intracranial atherosclerosis in a young man who had received therapeutic radiation for a presumed brain neoplasm. Since there was no evidence of vascular disease outside the radiation ports, we speculate that accelerated atherosclerosis was induced by radiation and that hyperlipidemia may have predisposed him to this effect.

  20. [Carotid atherosclerosis and dementia].

    PubMed

    Harlé, Louise-Marine; Plichart, Matthieu

    2015-09-01

    Over the past decade a growing interest has been devoted to exploring the role of atherosclerosis in the development of dementia. Despite a well-known association between atherosclerosis risk factors in middle-life with later cognitive decline, the pathophysiological pathways underlying this association remain unclear. The current hypothesis is that neurodegenerative and vascular lesions coexist and have a synergistic role in the development of cognitive impairment and dementia. Carotid atherosclerosis (e.g. carotid plaques and intima-media thickness as measured by carotid ultrasonography) has been associated with cognitive decline and dementia and may help to better understand the complex interaction between the vascular and neurodegenerative processes. Furthermore, carotid atherosclerosis has been used in the recent field for dementia risk prediction. In this review, we discuss the physiopathological implications from the current available data on the relationship between carotid atherosclerosis and dementia as well as the interest of carotid biomarkers for individual dementia risk prediction. PMID:26395304

  1. Short-term administration of basic fibroblast growth factor enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction.

    PubMed

    Zhang, Chunxiang; Yang, Jian; Feng, Jianzhang; Jennings, Lisa K

    2002-08-01

    We evaluated the effect of basic fibroblast growth factor (bFGF) on the extent of atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic animals with acute myocardial infarction (AMI). Fifty-six rabbits were fed a 1% cholesterol diet. Balloon injury of iliac arteries and experimental acute myocardial infarction were induced in the same animals. Rabbits were then randomized to a bFGF group (20 pg/day, intravenously) or a control group (intravenous saline solution). The beneficial effects of bFGF on cardiac function, infarct size, and collateral vessel development, and the possible effect on vasoproliferation of balloon-injured vessels, were measured after 1 and 2 weeks. The extent of atherosclerosis was measured after 1, 2, and 4 weeks. Our results showed that bFGF significantly reduced infarct size and increased collateral-vessel density (P <.01) in infarct areas. Cardiac function was better in the bFGF group than in corresponding controls (P <.05). Similar beneficial effects of bFGF were noted in animals after 1- and 2-week treatments. However, the extent of atherosclerosis and the vasoproliferation in chronic atherosclerotic vessels induced by balloon injury and cholesterol diet were not significantly different between the two groups. Our results suggest that short-term treatment with bFGF enhances collateral development and produces maximum therapeutic benefits without exacerbating atherosclerosis and cell proliferation in stenotic vessels after AMI in atherosclerotic rabbits. PMID:12228768

  2. 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. PMID:26809711

  3. Animal models of atherosclerosis

    PubMed Central

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

    2014-01-01

    In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans’ stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

  4. 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. PMID:25875381

  5. Left Main Coronary Artery Aneurysm

    PubMed Central

    Doustkami, Hossein; Maleki, Nasrollah; Tavosi, Zahra

    2016-01-01

    Aneurysms of the left main coronary artery are exceedingly rare clinical entities, encountered incidentally in approximately 0.1% of patients who undergo routine angiography. The most common cause of coronary artery aneurysms is atherosclerosis. Angiography is the gold standard for diagnosis and treatment. Depending on the severity of the coexisting coronary stenosis, patients with left main coronary artery aneurysms can be effectively managed either surgically or pharmacologically. We herein report a case of left main coronary artery aneurysm in a 72-year-old man with a prior history of hypertension presenting to our hospital because of unstable angina. The electrocardiogram showed ST-segment depression and T-wave inversion in the precordial leads. All the data of blood chemistry were normal. Echocardiography showed akinetic anterior wall, septum, and apex, mild mitral regurgitation and ejection fraction of 45%. Coronary angiography revealed a saccular aneurysm of the left main coronary artery with significant stenosis in the left anterior descending, left circumflex, and right coronary artery. The patient immediately underwent coronary artery bypass grafting and ligation of the aneurysm. At six months’ follow-up, he remained asymptomatic. PMID:27403190

  6. [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. PMID:26088002

  7. How Is Atherosclerosis Diagnosed?

    MedlinePlus

    ... sign that you're at risk for atherosclerosis. EKG (Electrocardiogram) An EKG is a simple, painless test that detects and ... beating and its rhythm (steady or irregular). An EKG also records the strength and timing of electrical ...

  8. Diet and atherosclerosis.

    PubMed Central

    Kritchevsky, D.

    1976-01-01

    Because of the statistical establishment of elevated blood lipids as a risk factor in the development of atherosclerotic heart disease, most of the attempts to regulate blood lipids by diet are centered on the fat in the diet. The levels of blood lipids and the course of experimental atherosclerosis can be affected by other dietary components such as type and amount of protein, carbohydrate, and nonnutritive fiber. Interaction among the dietary components further affects serum lipids and atherosclerosis. PMID:786036

  9. Nutrition and Atherosclerosis.

    PubMed

    Torres, Nimbe; Guevara-Cruz, Martha; Velázquez-Villegas, Laura A; Tovar, Armando R

    2015-07-01

    Cardiovascular disease (CVD) is a universal problem in modern society. Atherosclerosis is the leading cause of CVD resulting in high rate of mortality in the population. Nutrition science has focused on the role of essential nutrients in preventing deficiencies, at the present time, the nutritional strategies are crucial to promote health and intervene with these global noncommunicable diseases. In many cases, diet is a major driving force, which is much easier to change and follow than other factors. It is important to establish that the first strategy to treat atherosclerosis is to modify lifestyle habits, focusing on the beneficial properties of specific nutrients. In the last decades, epidemiological, clinical and experimental studies have demonstrated that diet plays a central role in the prevention of atherosclerosis. In this review we will focus on the effect of specific foods, nutrients and bioactive compounds, including epidemiological facts, potential mechanisms of action and dietary recommendations to reduce the risk of atherosclerosis. In particular, we include information about fiber, plant sterols and stanols, niacin, taurine, olive oil, omega 3 fatty acids, antioxidants, minerals, methyl nutrients and soy. In addition, we also show that dysbiosis of the intestinal microbiota associated with a consumption of certain animal food sources can generate some metabolites that are involved in the development of atherosclerosis and its consequences on CVD. According to the epidemiological, clinical and experimental studies we suggest a recommendation for some dietary foods, nutrients and bioactive compounds to support the complementary clinical management of patients with atherosclerosis. PMID:26031780

  10. Who Is at Risk for Atherosclerosis?

    MedlinePlus

    ... NHLBI on Twitter. Who Is at Risk for Atherosclerosis? The exact cause of atherosclerosis isn't known. ... role in atherosclerosis risk. Other Factors That Affect Atherosclerosis Other factors also may raise your risk for ...

  11. Coronary Angioplasty

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Percutaneous Coronary Intervention? Español Percutaneous (per-ku-TA-ne-us) coronary intervention (PCI), commonly known as coronary angioplasty (AN-jee- ...

  12. Subclinical Atherosclerosis Measures for Cardiovascular Prediction in CKD

    PubMed Central

    Sang, Yingying; Ballew, Shoshana H.; Shlipak, Michael; Katz, Ronit; Rosas, Sylvia E.; Peralta, Carmen A.; Woodward, Mark; Kramer, Holly J.; Jacobs, David R.; Sarnak, Mark J.; Coresh, Josef

    2015-01-01

    Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45–84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intima-media thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% CI, 1.00 to 1.25 and HR, 1.20; 95% CI, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score. PMID:25145930

  13. Nitric oxide function in atherosclerosis

    PubMed Central

    Matthys, K. E.

    1997-01-01

    Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

  14. Spontaneous Atherosclerosis in Pigeons

    PubMed Central

    Santerre, Robert F.; Wight, Thomas N.; Smith, Samuel C.; Brannigan, David

    1972-01-01

    The interpretation of metabolic studies related to early changes in spontaneous atherosclerosis has been hampered by the focal nature of the disease and by the lack of a well-defined model system of the disease process. Gross, histologic and ultrastructural observations of lesion development at the celiac bifurcation of the aorta in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons are compared and discussed in terms of hemodynamics, muscular aggregation and altered metabolism of smooth muscle cells. Detailed knowledge of the morphologic sequence of events in lesion localization makes the celiac bifurcation in White Carneau and Show Racer pigeons a useful model for genetic comparisons of arterial wall metabolism and for investigating metabolic alterations occurring with atherogenesis. ImagesFig 9Fig 10Fig 1Fig 2Fig 10Fig 11Fig 3Fig 4Fig 12Fig 5Fig 6Fig 7Fig 8 PMID:4261591

  15. Macrophage Autophagy in Atherosclerosis

    PubMed Central

    Maiuri, Maria Chiara; Grassia, Gianluca; Platt, Andrew M.; Carnuccio, Rosa; Ialenti, Armando; Maffia, Pasquale

    2013-01-01

    Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility. PMID:23401644

  16. The UPR in atherosclerosis.

    PubMed

    Zhou, Alex X; Tabas, Ira

    2013-05-01

    Multiple systemic factors and local stressors in the arterial wall can disturb the functions of endoplasmic reticulum (ER), causing ER stress in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation and progression of atherosclerosis. As a protective response to restore ER homeostasis, the unfolded protein response (UPR) is initiated by three major ER sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α), and activating transcription factor 6 (ATF6). The activation of the various UPR signaling pathways displays a temporal pattern of activation at different stages of the disease. The ATF6 and IRE1α pathways that promote the expression of protein chaperones in ER are activated in ECs in athero-susceptible regions of pre-lesional arteries and before the appearance of foam cells. The PERK pathway that reduces ER protein client load by blocking protein translation is activated in SMCs and macrophages in early lesions. The activation of these UPR signaling pathways aims to cope with the ER stress and plays a pro-survival role in the early stage of atherosclerosis. However, with the progression of atherosclerosis, the extended duration and increased intensity of ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this circumstance, the PERK pathway induces expression of death effectors, and possibly IRE1α activates apoptosis signaling pathways, leading to apoptosis of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death is associated with plaque instability and the clinical progression of atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly to macrophage differentiation in lesions. Therapeutic approaches targeting the UPR may have promise in the prevention and/or regression of atherosclerosis. However, more progress is needed to fully understand all of the roles of the UPR in atherosclerosis and to harness this information

  17. Role of Helicobacter pylori infection in pathogenesis of atherosclerosis

    PubMed Central

    Vijayvergiya, Rajesh; Vadivelu, Ramalingam

    2015-01-01

    Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect. PMID:25810813

  18. [Lipoproteins, free radicals and atherosclerosis].

    PubMed

    Manso, C

    1990-10-01

    The Author reviews vascular, lipidic and oxidative factors in the genesis of atherosclerosis. He admits the possibility that an alteration in the arterial wall, an increase in circulating lipids or an oxidative stress may influence the precocity of atherosclerosis. The transport of lipoperoxides or of oxidized cholesterol by lipoproteins renders them toxic and susceptible to aggravate atherosclerosis. PMID:2291852

  19. 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. PMID:25667093

  20. Anti-inflammatory and anti-atherogenic role of BMP receptor II in atherosclerosis.

    PubMed

    Simic, Tatjana

    2013-09-01

    Evaluation of: Kim CW, Song H, Kumar S et al. Anti-inflammatory and anti-atherogenic role of BMP receptor II in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 33, 1350-1359 (2013). Increased expression of BMPs in atherosclerosis suggested that the knockdown of the receptor mediating BMP action would prevent endothelial inflammation and atherosclerosis. Based on this hypothesis, Kim et al. performed a series of experiments in which the effect of BMP receptor type II (BMPRII) knockout was tested in in vitro and in vivo models of atherogenesis. Unexpectedly, they found that the loss of BMPRII induces endothelial inflammation and atherosclerosis. Knockdown of BMPRII in endothelial cells induced monocyte adhesion through the expression of ICAM-1 and VCAM-1. The loss of BMPRII induced endothelial inflammation and atherosclerosis in apoE-deficient mice. Besides, BMPRII expression was gradually lost over the course of atherosclerosis progression in human coronary arteries. PMID:24020661

  1. Effects of ezetimibe on atherosclerosis in preclinical models.

    PubMed

    Davis, Harry R; Lowe, Robert S; Neff, David R

    2011-04-01

    Ezetimibe (Zetia(®), Ezetrol(®), Merck, Whitehouse Station, NJ) is a potent inhibitor of sterol absorption, which selectively blocks the uptake of biliary and dietary cholesterol in the small intestine. Clinical trials have demonstrated the beneficial effects of ezetimibe on the reduction of atherogenic lipoproteins and the attainment of guideline-recommended lipid levels. Direct evidence that these improvements translate to a reduction in atherosclerosis or cardiovascular events is limited, although reductions in major atherosclerotic events that are consistent with the LDL-C lowering achieved have recently been presented for patients with chronic kidney disease treated with ezetimibe/simvastatin 10/20mg in the SHARP trial. Animal models of atherosclerosis have played a central role in defining the mechanisms involved in initiation and development of disease and have been used in drug development to evaluate potential therapeutic efficacy. The effect of ezetimibe on atherosclerosis has been examined in several of these animal model systems. ApoE knockout mice develop severe hypercholesterolemia and premature atherosclerosis with features similar to that seen in humans and techniques ranging from gross visualization of plaque to high-resolution MRI have demonstrated the consistent ability of ezetimibe to significantly inhibit atherosclerosis. sr-b1(-/-)/apoE(-/-) double knockout mice exhibit additional characteristics common to human coronary heart disease (CHD), and the one study of ezetimibe in sr-b1(-/-)/apoE(-/-) mice showed a significant reduction in aortic sinus plaque (57%), coronary arterial occlusion (68%), myocardial fibrosis (57%), and cardiomegaly (12%) compared with untreated controls. The effects of ezetimibe have also been evaluated in ldlr(-/-)/apoE(-/-) double knockout mice, demonstrating that functional LDL receptors were not required for ezetimibe-mediated reduction of plasma cholesterol or atherosclerosis. For the few studies that have been

  2. 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. PMID:26438419

  3. Cutaneous markers of coronary artery disease.

    PubMed

    Dwivedi, Shridhar; Jhamb, Rajat

    2010-09-26

    Coronary artery disease (CAD) is rapidly increasing in prevalence across the world and particularly in south Asians at a relatively younger age. As atherosclerosis starts in early childhood, the process of risk evaluation must start quite early. The present review addresses the issue of cutaneous markers associated with atherosclerosis, and the strengths and weaknesses of the markers in identifying early coronary atherosclerosis. A diligent search for such clinical markers, namely xanthelasma, xanthoma, arcus juvenilis, acanthosis nigricans, skin tags, ear lobe crease, nicotine stains, premature graying in smokers, hyperpigmented hands in betel quid sellers, central obesity, and signs of peripheral vascular disease may prove to be a rewarding exercise in identifying asymptomatic CAD in high risk individuals. PMID:21160602

  4. 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

  5. Coronary Artery Fistula Presenting as Unstable Angina Pectoris in Patients with Antiphospholipid Syndrome

    PubMed Central

    Demir, Şerafettin; Yucel, Ceyhun; Tufenk, Mucahit; Tosu, Aydin Rodi; Selcuk, Murat; Bozkurt, Abdi

    2013-01-01

    The cardiovascular system is one of the primary targets in patients with antiphospholipid syndrome. The valves are the most frequently affected. Atherosclerosis and coronary thrombosis are also seen. The risk of acute coronary syndrome is 10 times higher in patients with APS. We present an APS patient case who was hospitalized with acute coronary syndrome and who was later found to have coronary artery fistula. PMID:24023543

  6. Infectious and coronary artery disease

    PubMed Central

    Rezaee-Zavareh, Mohammad Saeid; Tohidi, Mohammad; Sabouri, Amin; Ramezani-Binabaj, Mahdi; Sadeghi-Ghahrodi, Mohsen; Einollahi, Behzad

    2016-01-01

    BACKGROUND Atherosclerotic event is one of the most causes of death in the world. Coronary artery disease (CAD) is one manifestation of atherosclerosis. It is well-known that several risk factors, such as diabetes mellitus (DM), smoking, hypertension (HTN), have effects on it. It is proposed that infection can lead to atherosclerosis or even make its process faster. Here, we discuss about the effect of some of infectious agents on the atherosclerosis and CAD. METHODS In this study, first we did a comprehensive search in PubMed, Scopus, and Science Direct using some related keywords such as atherosclerosis, CAD, myocardial infarction (MI), infection, and name of viruses and bacteria. After finding the related papers, we reviewed the correlation between some microbial agents and risk of CAD. RESULTS Literature has reported several infectious agents (viruses, bacteria, and parasites) that can be associated with risk of CAD. This association for some of them like Helicobacter pylori (H. pylori), Chlamydia pneumonia (C. pneumoniae), and Cytomegalovirus (CMV) is a very strong. On the other hand, there are some other agents like influenza that still need to be more investigated through original studies. Furthermore, different mechanisms (general and special) have been reported for the association of each agent with CAD. CONCLUSION Based on the studies in databases and our literature review, it is so clear that some microbes and infectious agents can be involved in the process of atherosclerosis. Therefore, controlling each type of infections especially among people with a traditional risk factor for atherosclerosis should be taken into account for reducing the risk of CAD and atherosclerosis. PMID:27114736

  7. Preliminary and early stages of atherosclerosis in childhood.

    PubMed

    Pesonen, E

    1989-01-01

    According to the unified theory of atherosclerosis, endothelial cell injury and lipid infiltration play an important role in atherogenesis. Newborn babies may suffer endothelial cell damage, as may be detected by electron microscopy. Connective tissue elements are occasionally abundant already in newborns. Chondroitin sulfate A and C increase with age. The children may exhibit continuous accumulation of cholesterol esters in the intima of coronary arteries. Cholesteryl ester fatty acid composition, along with age, tends to approach that of serum low-density lipoproteins. Fatty streaks appear in coronary arteries in puberty, and fibrous plaques are recordable beyond the age of 20 years. The topography of myo-intimal thickenings, fatty streaks, and fibrous plaques is similar to complicated atherosclerotic lesions. Even newborn babies have obstructive myo-intimal thickenings in their coronary arteries. One fifth of all infants under one week of age suffer 20% stenosis, with percentile manifestation of stenosis in the arterial cross-section being established as ratio of intimal area to luminal area of a dilated coronary artery multiplied by 100. Occasionally, the intima is very thick, in our series initiating up to 57% of all narrowing. There are probably noxious factors which temporarily damage the endothelial cells and initiate a rapid, partially reversible thickening reaction. Some of this response of the intima to exogenous stimuli might be genetically determined. A thickened intima is susceptible to lipid deposition and atherosclerosis. PMID:2683501

  8. Responses of coronary arteries of cardiac transplant patients to acetylcholine.

    PubMed Central

    Fish, R D; Nabel, E G; Selwyn, A P; Ludmer, P L; Mudge, G H; Kirshenbaum, J M; Schoen, F J; Alexander, R W; Ganz, P

    1988-01-01

    Accelerated coronary atherosclerosis is a major cause of graft failure after heart transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an association of endothelial dysfunction and atherosclerosis. In this report, we tested the hypothesis that coronary arteries of heart transplant patients can show endothelial dysfunction before or in the early stages of angiographically evident coronary atherosclerosis. Acetylcholine was infused into the left anterior descending artery of 13 heart transplant patients at 12 (n = 9) and 24 (n = 4) mo after transplantation. Vascular responses were evaluated by quantitative angiography. Among patients with angiographically smooth coronary arteries, relatively few (6/25) arterial segments had preserved vasodilator responses, while the majority failed to dilate (10/25) or paradoxically constricted (9/25). Angiographically irregular coronary arteries were present in three patients, in whom 8/10 segments showed marked paradoxical constriction and the remaining 2/10 failed to dilate. Only 1 of 13 patients retained appropriate dilation to acetylcholine in all segments. Nitroglycerin, which acts directly on vascular smooth muscle, dilated nearly all segments. No clinical features of the patients, including myocardial rejection appeared to correlate with the impaired functional response of vessels. Thus impaired response to acetylcholine is a common early finding in heart transplant patients and emphasizes the potential importance of endothelial dysfunction in the development of atherosclerosis. Images PMID:3121675

  9. Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

    PubMed

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

    2016-07-01

    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

  10. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype. PMID:25319333

  11. 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

  12. Bisphenol A exposure enhances atherosclerosis in WHHL rabbits.

    PubMed

    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

  13. (1) Coronary Events Caused by Myocardial Bridge

    PubMed Central

    Yoko, Kawawa; Ehiichi, Kohda; Toshiharu, Ishii

    2009-01-01

    Myocardial bridge (MB), which covers a part of the left anterior descending coronary artery (LAD), is a normal anatomical variant structure (45% in frequency by autopsy) in LAD. MB contraction plays the role of a “double-edged sword” on the coronary events, suppressing coronary atherosclerosis under the MB, yet generating abnormal blood flow associated with coronary heart diseases (CHDs). High shear stress driven by MB compression causes the suppression of vascular permeability and vasoactive protein expression such as e-NOS and endothelin-1, which leads to the suppression of atherosclerosis in the LAD segment under the MB. However, despite the prevalent view of MB as benignancy by conventional coronary angiography (5-6% in frequency), with advance of imaging technique such as multislice spiral computed tomography [(MSCT); 16% in frequency], cardiologists are now frequently aware of symptomatic MB occurring not only in hospitalized patients, but also in young athletes free from atherosclerosis. Moreover, the large mass volume of MB muscle induces atherosclerosis evolution at the settled site in LAD proximal to MB and contributes to the occurrence of myocardial infarction. These events upon the coronary events result from the different pathophysiological mechanisms induced by contractile force of MB, which is solely determined just by the integration of anatomical properties of MB, such as the location, length and thickness of MB in an individual LAD. A recent MSCT provides the objective quantification of the anatomical variables that correlate with the histopathological results in relation to the occurrence of CHD. In this review, we therefore discuss the necessity to explore MB as a inherent chance anatomical risk factor for CHD. PMID:23555365

  14. S100A12 and the S100/Calgranulins: Emerging Biomarkers for Atherosclerosis and Possibly Therapeutic Targets.

    PubMed

    Oesterle, Adam; Bowman, Marion A Hofmann

    2015-12-01

    Atherosclerosis is mediated by local and systematic inflammation. The multiligand 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 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 apolipoprotein E 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

  15. Coronary Artery Disease Risk Factors, Coronary Artery Calcification and Coronary Bypass Surgery

    PubMed Central

    Ulusoy, Fatih Rifat; Ipek, Emrah; Korkmaz, Ali Fuat; Gurler, Mehmet Yavuz; Gulbaran, Murat

    2015-01-01

    Introduction Atherosclerosis is an intimal disease which affects large and medium size arteries including aorta and carotid, coronary, cerebral and radial arteries. Calcium accumulated in the coronary arterial plaques have substantial contribution to the plaque volume. The aim of our study is to investigate the relationship between coronary artery disease (CAD) risk factors and coronary arterial calcification, and to delineate the importance of CACS in coronary artery bypass surgery. Materials and Methods The current study is retrospective and 410 patients admitted to our clinic with atypical chest pain and without known CAD were included. These individuals were evaluated by 16 slice electron beam computed tomography with suspicion of CAD and their calcium scores were calculated. Detailed demographic and medical history were obtained from all of the patients. Results In our study, we employed five different analyses using different coronary arterial calcification score (CACS) thresold levels reported in previous studies. All of the analyses, performed according to the previously defined thresold levels, showed that risk factors had strong positive relationship with CACS as mentioned in previous studies. Conclusion Coronary arterial calcification is part of the athero-sclerotic process and although it can be detected in atherosclerotic vessel, it is absent in a normal vessel. It can be concluded that the clinical scores, even they are helpful, have some limitations in a significant part of the population for cardiovascular risk determination. It is important for an anastomosis region to be noncalcified in coronary bypass surgery. In a coronary artery, it will be helpness for showing of calcific field and anostomosis spot. PMID:26155507

  16. Association of Fat Density With Subclinical Atherosclerosis

    PubMed Central

    Alvey, Nicholas J.; Pedley, Alison; Rosenquist, Klara J.; Massaro, Joseph M.; O'Donnell, Christopher J.; Hoffmann, Udo; Fox, Caroline S.

    2014-01-01

    Background Ectopic fat density is associated with cardiovascular disease (CVD) risk factors above and beyond fat volume. Volumetric measures of ectopic fat have been associated with CVD risk factors and subclinical atherosclerosis. The aim of this study was to investigate the association between fat density and subclinical atherosclerosis. Methods and Results Participants were drawn from the Multi‐Detector Computed Tomography (MDCT) substudy of the Framingham Heart Study (n=3079; mean age, 50.1 years; 49.2% women). Fat density was indirectly estimated by computed tomography attenuation (Hounsfield Units [HU]) on abdominal scan slices. Visceral fat (VAT), subcutaneous fat (SAT), and pericardial fat HU and volumes were quantified using standard protocols; coronary and abdominal aortic calcium (CAC and AAC, respectively) were measured radiographically. Multivariable‐adjusted logistic regression models were used to evaluate the association between adipose tissue HU and the presence of CAC and AAC. Overall, 17.1% of the participants had elevated CAC (Agatston score [AS]>100), and 23.3% had elevated AAC (AS>age‐/sex‐specific cutoffs). Per 5‐unit decrement in VAT HU, the odds ratio (OR) for elevated CAC was 0.76 (95% confidence interval [CI], 0.65 to 0.89; P=0.0005), even after adjustment for body mass index or VAT volume. Results were similar for SAT HU. With decreasing VAT HU, we also observed an OR of 0.79 (95% CI, 0.67 to 0.92; P=0.004) for elevated AAC after multivariable adjustment. We found no significant associations between SAT HU and AAC. There was no significant association between pericardial fat HU and either CAC or AAC. Conclusions Lower VAT and SAT HU, indirect estimates of fat quality, are associated with a lower risk of subclinical atherosclerosis. PMID:25169793

  17. CYCLOOXYGENASE POLYMORPHISMS AND RISK OF CARDIOVASCULAR EVENTS: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 an...

  18. [Coronary endarterectomy].

    PubMed

    Murtra, M; González, I; Igual, A

    1998-01-01

    The technique of coronary endarterectomy, in coronary artery surgery, has been controversial and alternatively indicated or contraindicated by different authors. In this paper coronary endarterectomy is reviewed, including its definition, history and development of different techniques. Early and late results of the main papers in the literature are commented on as well as our results. The surgical technique of endarterectomy in the different coronary artery territories is described with the primary indications and contraindications. Coronary endarterectomy is a valid and well established technique that can provide possibilities of revascularization in patients with extended and diffused coronary artery obstructions, which are unable to be treated with conventional coronary artery bypass grafts. Operative mortality and morbidity are slightly higher, but long-term results, as far as survival and functional class are concerned, are similar to standard coronary artery surgical procedures. PMID:9717404

  19. Paradoxical coronary artery embolism - a rare cause of myocardial infarction.

    PubMed

    Hakim, Fayaz A; Kransdorf, Evan P; Abudiab, Muaz M; Sweeney, John P

    2014-01-01

    Paradoxical coronary artery embolism is a rare, but often an underdiagnosed cause of acute myocardial infarction. It should be considered in patient who presents with chest pain and otherwise having a low risk profile for atherosclerosis coronary artery disease. We describe a case of paradoxical coronary artery embolism causing ST segment elevation myocardial infarction in a patient with upper extremity venous thrombosis. Echocardiography demonstrated a patent foramen ovale (PFO) with bidirectional shunt. In addition to treatment of acute coronary event closure of the PFO should be considered to prevent a recurrence. PMID:25774255

  20. Paradoxical Coronary Artery Embolism - A Rare Cause of Myocardial Infarction

    PubMed Central

    Hakim, Fayaz A.; Kransdorf, Evan P.; Abudiab, Muaz M.; Sweeney, John P.

    2014-01-01

    Paradoxical coronary artery embolism is a rare, but often an underdiagnosed cause of acute myocardial infarction. It should be considered in patient who presents with chest pain and otherwise having a low risk profile for atherosclerosis coronary artery disease. We describe a case of paradoxical coronary artery embolism causing ST segment elevation myocardial infarction in a patient with upper extremity venous thrombosis. Echocardiography demonstrated a patent foramen ovale (PFO) with bidirectional shunt. In addition to treatment of acute coronary event closure of the PFO should be considered to prevent a recurrence. PMID:25774255

  1. AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

    PubMed Central

    Zhu, Laurence; Fang, Longhou

    2015-01-01

    Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the number-one cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for final elimination.1 In atherosclerosis, intraplaque angiogenesis promotes plaque growth and increases plaque vulnerability. Conceivably, the acceleration of RCT and disruption of intraplaque angiogenesis would inhibit atherosclerosis and reduce CAD. We have identified a protein called apoA-I binding protein (AIBP) that augments HDL functionality by accelerating cholesterol efflux. Furthermore, AIBP inhibits vascular endothelial growth factor receptor 2 activation in endothelial cells and limits angiogenesis.2 The following discusses the prospect of using AIBP as a novel therapeutic approach for the treatment of CAD. PMID:26634023

  2. Cannabinoids and atherosclerotic coronary heart disease.

    PubMed

    Singla, Sandeep; Sachdeva, Rajesh; Mehta, Jawahar L

    2012-06-01

    Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis. PMID:22278660

  3. Plasma IL-5 concentration and subclinical carotid atherosclerosis

    PubMed Central

    Silveira, Angela; McLeod, Olga; Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Deleskog, Anna; Persson, Jonas; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Gustafsson, Sven; Söderberg, Stefan; Öhrvik, John; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Hamsten, Anders

    2015-01-01

    Objective Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). Methods We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. Results IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. Conclusions Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease. PMID:25587992

  4. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old).

    PubMed Central

    Kuo, C C; Grayston, J T; Campbell, L A; Goo, Y A; Wissler, R W; Benditt, E P

    1995-01-01

    An association of Chlamydia pneumoniae with atherosclerosis of coronary and carotid arteries and aorta has been found by seroepidemiology and by demonstration of the organism in atheromata. Age-matched control tissue from persons without atherosclerosis was usually not available. We studied autopsy tissue from young persons, many with no atherosclerosis, to determine whether C. pneumoniae is present in atheroma in young persons with early atherosclerosis and to compare the findings in age- and sex-matched persons without atherosclerosis. A left anterior descending coronary artery sample, formalin-fixed, from 49 subjects, 15-34 years of age, from the multicenter study called Pathobiological Determinants of Atherosclerosis in Youth (PDAY), was examined by immunocytochemistry and the polymerase chain reaction (PCR) for the presence of C. pneumoniae and by PCR for cytomegalovirus. A hematoxylin/eosin-stained section was used to determine disease present in the studied sample. Seven of the artery samples were found to have atheromatous plaque, 11 had intimal thickening, and 31 had no lesions. Eight of the samples were positive for C. pneumoniae by immunocytochemistry (n = 7) and/or PCR (n = 3). Six of the 7 (86%) atheroma, 2 of the 11 (18%) with intimal thickening, and none of the 31 normal-appearing coronary samples were positive. Four were positive by PCR for cytomegalovirus, 2 from diseased arteries and 2 from normal arteries. Examination of the adjacent left coronary artery sample with a fat stain found abnormalities in 25 of the patients, but 19 still showed no evidence of atherosclerosis as a result of either examination. Thus, C. pneumoniae is found in coronary lesions in young adults with atherosclerosis but is not found in normal-appearing coronary arteries of both persons with and without other evidence of atherosclerosis. Images Fig. 1 PMID:7624342

  5. Neutrophil's weapons in atherosclerosis.

    PubMed

    Chistiakov, Dimitry A; Bobryshev, Yuri V; Orekhov, Alexander N

    2015-12-01

    Neutrophils are important components of immunity associated with inflammatory responses against a broad spectrum of pathogens. These cells could be rapidly activated by proinflammatory stimuli and migrate to the inflamed and infected sites where they release a variety of cytotoxic molecules with antimicrobial activity. Neutrophil antibacterial factors include extracellular proteases, redox enzymes, antimicrobial peptides, and small bioactive molecules. In resting neutrophils, these factors are stored in granules and released upon activation during degranulation. These factors could be also secreted in a neutrophil-derived microparticle-dependent fashion. Neutrophils exhibit a unique property to produce neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins to catch and kill bacteria. Neutrophil-released factors are efficient in inactivation and elimination of pathogens through oxidation-dependent or independent damage of bacterial cells, inactivation and neutralization of virulence factors and other mechanisms. However, in chronic atherosclerosis-associated inflammation, protective function of neutrophils could be impaired and misdirected against own cells. This could lead to deleterious effects and progressive vascular injury. In atherogenesis, a pathogenic role of neutrophils could be especially seen in early stages associated with endothelial dysfunction and induction of vascular inflammation and in late atherosclerosis associated with plaque rupture and atherothrombosis. Assuming a prominent impact of neutrophils in cardiovascular pathology, developing therapeutic strategies targeting neutrophil-specific antigens could have a promising clinical potential. PMID:26551083

  6. 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.

  7. Atherosclerosis in Alaska Natives and non-natives.

    PubMed

    Newman, W P; Middaugh, J P; Propst, M T; Rogers, D R

    1993-04-24

    Low mortality from coronary heart disease (CHD) among Eskimos has been attributed to less atherosclerosis in the coronary arteries because of a high dietary intake of omega-3 fatty acids. Other investigators attribute this low mortality to the fact that Eskimos have a high mortality from other causes before middle age, when CHD is common. However, most studies have been epidemiological, either by death-certificate review or risk-factor evaluation. We evaluated the extent of atherosclerotic lesions in the coronary arteries and aortas from Alaska Natives. Standardised comparisons between samples from 103 Native and 101 non-native residents show that the extent of raised lesions increases with age in both groups, but the prevalence of raised lesions in native specimens was consistently lower than in those from non-natives. This difference was statistically significant. The data suggest that the differences in CHD mortality between Alaska Natives and non-natives are, at least in part, the result of less atherosclerosis in natives. PMID:8096960

  8. Lysophospholipids and their G protein-coupled receptors in atherosclerosis.

    PubMed

    Li, Ya-Feng; Li, Rong-Shan; Samuel, Sonia B; Cueto, Ramon; Li, Xin-Yuan; Wang, Hong; Yang, Xiao-Feng

    2016-01-01

    Lysophospholipids (LPLs) are bioactive lipid-derived signaling molecules generated by the enzymatic and chemical processes of regiospecific phospholipases on substrates such as membrane phospholipids (PLs) and sphingolipids (SLs). They play a major role as extracellular mediators by activating G-protein coupled receptors (GPCRs) and stimulating diverse cellular responses from their signaling pathways. LPLs are involved in various pathologies of the vasculature system including coronary heart disease and hypertension. Many studies suggest the importance of LPLs in their association with the development of atherosclerosis, a chronic and severe vascular disease. This paper focuses on the pathophysiological effects of different lysophospholipids on atherosclerosis, which may promote the pathogenesis of myocardial infarction and strokes. Their atherogenic biological activities take place in vascular endothelial cells, vascular smooth muscle cells, fibroblasts, monocytes and macrophages, dendritic cells, T-lymphocytes, platelets, etc. PMID:26709762

  9. [Major pathogenic links of atherosclerosis].

    PubMed

    Antelava, N A; Pachkoriia, K Z; Kezeli, T D; Nikuradze, N S; Shamkulashvili, G G

    2005-11-01

    The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, re-modulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases. PMID:16369071

  10. Recent Highlights of ATVB Atherosclerosis

    PubMed Central

    Lu, Hong; Daugherty, Alan

    2015-01-01

    Summary Mechanistic studies over the past decades using in vitro systems, animal models, and human tissues have highlighted the complexity of pathophysiological processes of atherosclerosis. Hypercholesterolemia, as one of the major risk factors for the development and progression of atherosclerosis, is still the focus of many mechanistic studies and the major therapeutic target of atherosclerosis. Although there is a dire need to validate many experimental findings in humans, there is a large number of approaches that have been showing promise for contributing to future therapeutic strategies. PMID:25717174

  11. [PREDICTORS OF ATHEROSCLEROSIS: NEW DEVELOPMENTS].

    PubMed

    Gozhenko, A I; Kotyuzhinskaya, S G; Kovalevskaya, L A

    2014-12-01

    The article describes known atherosclerosis predictors of endothelial origin, which are diagnostic criteria for identifying's early stages of atherosclerosis, and can prevent the development of this disease and are used to monitor the effectiveness of the therapy The authors analyzed the possibility of using heparin as an early marker of atherosclerosis, based on the fact that the inhibition of lipoprotein lipase activity due hyperheparinemia resulting from depletion of mast cells due to endothelial dysfunction, leads to the disorders of lipid transporting system in the form of the resistant hyperlipidemia with the phenomena of dyslipidemia. PMID:26638463

  12. Foodborne Illness

    MedlinePlus

    ... people in the U.S. get sick from contaminated food. Common culprits include bacteria, parasites and viruses. Symptoms ... are the most common cause of foodborne illness. Foods may have some bacteria on them when you ...

  13. Heat Illness

    MedlinePlus

    ... high humidity, sweating just isn't enough. Your body temperature can rise to dangerous levels and you can ... include Heatstroke - a life-threatening illness in which body temperature may rise above 106° F in minutes; symptoms ...

  14. Foodborne Illnesses

    MedlinePlus

    ... Some parasites and chemicals also cause foodborne illnesses. Bacteria Bacteria are tiny organisms that can cause infections of the GI tract. Not all bacteria are harmful to humans. Some harmful bacteria may ...

  15. Heat Illness

    MedlinePlus

    ... humidity, sweating just isn't enough. Your body temperature can rise to dangerous levels and you can ... Heatstroke - a life-threatening illness in which body temperature may rise above 106° F in minutes; symptoms ...

  16. MR Imaging of Coronary Arteries and Plaques.

    PubMed

    Dweck, Marc R; Puntman, Valentina; Vesey, Alex T; Fayad, Zahi A; Nagel, Eike

    2016-03-01

    Cardiac magnetic resonance offers the promise of radiation-free imaging of the coronary arteries, providing information with respect to luminal stenosis, plaque burden, high-risk plaque characteristics, and disease activity. In combination, this would provide a comprehensive, individualized assessment of coronary atherosclerosis that could be used to improve patient risk stratification and to guide treatment. However, the technical challenges involved with delivering upon this promise are considerable, requiring sophisticated approaches to both data acquisition and post-processing. In this review, we describe the current status of this technology, its capabilities, its limitations, and what will be required in the future to translate this technology into routine clinical practice. PMID:26965732

  17. A diet rich in green and yellow vegetables inhibits atherosclerosis in mice.

    PubMed

    Adams, Michael R; Golden, Deborah L; Chen, Haiying; Register, Thomas C; Gugger, Eric T

    2006-07-01

    Although dietary patterns characterized by a high intake of fruits and vegetables are associated with reduced risk of coronary heart disease, the mechanisms involved are uncertain. We determined the effects of a diet rich in green and yellow vegetables on the development of atherosclerosis, the underlying cause of coronary heart disease, in a mouse model of atherosclerosis, the LDL receptor -/-, apolipoprotein B transgenic mouse. The mice were randomized into 2 diet groups: 1) a vegetable-free control diet (n = 53) and 2) the same diet with 30% (w:w) replaced by an equal-parts mixture of freeze-dried peas, green beans, broccoli, corn, and carrots (n = 54). Mice were fed these diets for 16 wk. Aortic atherosclerosis, as estimated by cholesteryl ester content, was reduced 38% (P < 0.001) in mice fed the vegetable-rich diet. Plasma total cholesterol (-12%), VLDL + ILDL cholesterol (-32%), serum amyloid A (-37%), and body weight (-7%) (all P < 0.01) were also lower in these mice at the end of the treatment period. In a regression model, antiatherogenic effects of the vegetable diet remained largely unexplained by the variation in plasma lipoproteins or body weight. Although the pathway(s) involved remain uncertain, the results indicate that a diet rich in green and yellow vegetables inhibits the development of atherosclerosis and may therefore lead to a reduction in the risk of coronary heart disease. PMID:16772454

  18. Non‐invasive coronary angiography using multislice computed tomography

    PubMed Central

    Schussler, Jeffrey M; Grayburn, Paul A

    2007-01-01

    Non‐invasive methods for detection of coronary atherosclerosis have been limited to indirect markers, such as myocardial perfusion or wall motion during exercise or pharmacological stress. However, advances in multislice computed tomography (MSCT) not allow sufficient spatial resolution for direct non‐invasive imaging of the coronary arteries. This review focuses on imaging techniques and clinical applications of MSCT in human studies. Published studies of the diagnostic accuracy of MSCT in native coronary arteries and bypass grafts indicate excellent sensitivity and specificity for detection of 50% diameter stenosis. MSCT is particularly good for evaluating the origin and course of anomalous coronary arteries. MSCT offers the ability to visualise both the lumen and wall of artery, as well as to quantify coronary classification. Further technical developments promise to render MSCT the ideal non‐invasive tool for direct visualisation of the coronary arteries. PMID:16387814

  19. Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population

    PubMed Central

    Kutikhin, Anton G.; Ponasenko, Anastasia V.; Khutornaya, Maria V.; Yuzhalin, Arseniy E.; Zhidkova, Irina I.; Salakhov, Ramil R.; Golovkin, Alexey S.; Barbarash, Olga L.; Barbarash, Leonid S.

    2016-01-01

    Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011–2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID:27200266

  20. Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population.

    PubMed

    Kutikhin, Anton G; Ponasenko, Anastasia V; Khutornaya, Maria V; Yuzhalin, Arseniy E; Zhidkova, Irina I; Salakhov, Ramil R; Golovkin, Alexey S; Barbarash, Olga L; Barbarash, Leonid S

    2016-09-01

    Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011-2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID:27200266

  1. Inflammatory markers in coronary artery disease.

    PubMed

    Ikonomidis, Ignatios; Michalakeas, Christos A; Parissis, John; Paraskevaidis, Ioannis; Ntai, Konstantina; Papadakis, Ioannis; Anastasiou-Nana, Maria; Lekakis, John

    2012-01-01

    Coronary artery disease (CAD) is one of the most common manifestations of atherosclerosis. Inflammation is considered one of the major processes that contribute to atherogenesis. Inflammation plays an important role not only on the initiation and progression of atherosclerosis but also on plaque rupture, an event that leads to acute vascular events. Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, and inflammatory biomarkers express different parts of the atherogenic process, regarding the initiation and progression of atherosclerosis or the destabilization of the atherosclerotic plaque. Therefore, inflammatory biomarkers may prove to be useful in the detection, staging, and prognosis of patients with CAD. Furthermore, the fact that inflammatory processes are essential steps in the course of the disease offers future therapeutic targets for the interruption of the atherogenic process or for the management of acute events. PMID:22628054

  2. Multiple coronary aneurysms in a young adult with acquired immunodeficiency syndrome

    PubMed Central

    Heizer, Justin; Petersen, Timothy C.; Flemmer, Mark C.

    2016-01-01

    HIV infection can cause multiple deleterious effects on the cardiovascular system. Emerging evidence has supported a direct association between HIV infection and accelerated atherosclerosis. The mechanism for atherosclerosis in HIV-positive patients is multifactorial, an interplay between conventional risk factors, HIV itself and highly active antiretroviral therapy. The case described is a 29-year-old man with HIV, non-adherent to antiretroviral therapy and with few cardiovascular risk factors, who presented with chest pain and non-ST elevation myocardial infarction. Cardiac catheterization revealed multiple coronary artery aneurysms in the left main coronary artery and the right coronary artery. Aneurysmal formation may develop from vasculitis, HIV itself, accelerated atherosclerosis, congenital formation or medications (e.g. protease inhibitors). The researchers provide a review of coronary artery disease, aneurysmal formation and vasculitic processes in the context of HIV. As this clinical entity becomes more apparent, alternative therapeutic options may need to be explored. PMID:27168940

  3. MicroRNAs and atherosclerosis

    PubMed Central

    Madrigal-Matute, Julio; Rotllan, Noemi; Aranda, Juan F.; Fernández-Hernando, Carlos

    2014-01-01

    MicroRNAs (miRNAs) are small (~22nucleotide) sequences of RNA that regulate gene expression at posttranscriptional level. MiRNA/mRNA base pairing complementarity provokes mRNA decay and consequent gene silencing. These endogenous gene expression inhibitors were primarily described in cancer but recent exciting findings have also demonstrated a key role in cardiovascular diseases (CVDs) including atherosclerosis. MiRNAs controls endothelial cell (EC), vascular smooth muscle cell (VSMC) and macrophage functions, and thereby regulate the progression of atherosclerosis. MiRNAs expression is modulated by different stimuli involved in every stage of atherosclerosis and conversely miRNAs modulates several pathways implicated in plaque development such as cholesterol metabolism. In the present review, we focus on the importance of miRNAs in atherosclerosis and we further discuss their potential use as biomarkers and therapeutic targets in CVDs. PMID:23512606

  4. 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…

  5. 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

  6. Microdomains, Inflammation, and Atherosclerosis.

    PubMed

    Sorci-Thomas, Mary G; Thomas, Michael J

    2016-02-19

    Elevated levels of cholesteryl ester (CE)-enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of atherosclerosis. Unregulated uptake of low-density lipoprotein cholesterol by circulating monocytes and other peripheral blood cells takes place through scavenger receptors and over time causes disruption in cellular cholesterol homeostasis. As lipoproteins are taken up, their CE core is hydrolyzed by liposomal lipases to generate free cholesterol (FC). FC can be either re-esterified and stored as CE droplets or shuttled to the plasma membrane for ATP-binding cassette transporter A1-mediated efflux. Because cholesterol is an essential component of all cellular membranes, some FC may be incorporated into microdomains or lipid rafts. These platforms are essential for receptor signaling and transduction, requiring rapid assembly and disassembly. ATP-binding cassette transporter A1 plays a major role in regulating microdomain cholesterol and is most efficient when lipid-poor apolipoprotein AI (apoAI) packages raft cholesterol into soluble particles that are eventually catabolized by the liver. If FC is not effluxed from the cell, it becomes esterified, CE droplets accumulate and microdomain cholesterol content becomes poorly regulated. This dysregulation leads to prolonged activation of immune cell signaling pathways, resulting in receptor oversensitization. The availability of apoAI or other amphipathic α-helix-rich apoproteins relieves the burden of excess microdomain cholesterol in immune cells allowing a reduction in immune cell proliferation and infiltration, thereby stimulating regression of foam cells in the artery. Therefore, cellular balance between FC and CE is essential for proper immune cell function and prevents chronic immune cell overstimulation and proliferation. PMID:26892966

  7. Atomic Force Microscopy Study of Atherosclerosis Progression in Arterial Walls.

    PubMed

    Timashev, Peter S; Kotova, Svetlana L; Belkova, Galina V; Gubar'kova, Ekaterina V; Timofeeva, Lidia B; Gladkova, Natalia D; Solovieva, Anna B

    2016-04-01

    Cardiovascular disease remains the leading cause of mortality worldwide. Here we suggest a novel approach for tracking atherosclerosis progression based on the use of atomic force microscopy (AFM). Using AFM, we studied cross-sections of coronary arteries with the following types of lesions: Type II-thickened intima; Type III-thickened intima with a lipid streak; Type IV-fibrotic layer over a lipid core; Type Va-unstable fibrotic layer over a lipid core; Type Vc-very thick fibrotic layer. AFM imaging revealed that the fibrotic layer of an atherosclerotic plaque is represented by a basket-weave network of collagen fibers and a subscale network of fibrils that become looser with atherosclerosis progression. In an unstable plaque (Type Va), packing of the collagen fibers and fibrils becomes even less uniform than that at the previous stages, while a stable fibrotic plaque (Vc) has significantly tighter packing. Such alterations of the collagen network morphology apparently, led to deterioration of the Type Va plaque mechanical properties, that, in turn, resulted in its instability and propensity to rupture. Thus, AFM may serve as a useful tool for tracking atherosclerosis progression in the arterial wall tissue. PMID:26843417

  8. Assessment of coronary artery disease using coronary computed tomography angiography and biochemical markers

    PubMed Central

    Gitsioudis, Gitsios; Katus, Hugo A; Korosoglou, Grigorios

    2014-01-01

    Chronic inflammatory mechanisms in the arterial wall lead to atherosclerosis, and include endothelial cell damage, inflammation, apoptosis, lipoprotein deposition, calcification and fibrosis. Cardiac computed tomography angiography (CCTA) has been shown to be a promising tool for non-invasive assessment of theses specific compositional and structural changes in coronary arteries. This review focuses on the technical background of CCTA-based quantitative plaque characterization. Furthermore, we discuss the available evidence for CCTA-based plaque characterization and the potential role of CCTA for risk stratification of patients with coronary artery disease. PMID:25068026

  9. Left Main Percutaneous Coronary Intervention and Transcatheter Aortic Valve Replacement in a Young Male with Rheumatic Heart Disease and Porcelain Aorta

    PubMed Central

    Chainani, Vinod; Hanno, Ram; Rengifo-Moreno, Pablo; Martinez-Clark, Pedro; Alfonso, Carlos E.

    2016-01-01

    We highlight the presence of a calcified mass in the left main coronary artery without significant atherosclerosis seen in the other coronary arteries or in the peripheral large arteries. In our view, the calcified character of the obstruction and the calcification of the aortic valve are characteristic of a variant type of coronary artery disease (CAD) not associated with the same risk factors as diffuse coronary atherosclerosis, but, in this case, with rheumatic heart disease. This case report also emphasizes the interventional approach for patients with aortic valve stenosis secondary to rheumatic heart disease. PMID:27418982

  10. Left Main Percutaneous Coronary Intervention and Transcatheter Aortic Valve Replacement in a Young Male with Rheumatic Heart Disease and Porcelain Aorta.

    PubMed

    Chainani, Vinod; Perez, Osman; Hanno, Ram; Hourani, Patrick; Rengifo-Moreno, Pablo; Martinez-Clark, Pedro; Alfonso, Carlos E

    2016-01-01

    We highlight the presence of a calcified mass in the left main coronary artery without significant atherosclerosis seen in the other coronary arteries or in the peripheral large arteries. In our view, the calcified character of the obstruction and the calcification of the aortic valve are characteristic of a variant type of coronary artery disease (CAD) not associated with the same risk factors as diffuse coronary atherosclerosis, but, in this case, with rheumatic heart disease. This case report also emphasizes the interventional approach for patients with aortic valve stenosis secondary to rheumatic heart disease. PMID:27418982

  11. The association between periodontal disease parameters and severity of atherosclerosis

    PubMed Central

    Ketabi, Mohammad; Meybodi, Fatemeh Rashidi; Asgari, Mohammad Reza

    2016-01-01

    Background: Atherosclerosis is the most common cause for heart attack and stroke. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. The aim of this research was to determine the possible association between chronic periodontal disease and severity of atherosclerosis. Materials and Methods: Eighty-two subjects that were referred to Chamran Heart Hospital in Isfahan for angiography were involved in this study. Fifty-nine subjects had coronary artery obstruction (CAO) and 23 showed no obstruction after angiography. The severity of CAO was assessed. Periodontal parameters including pocket depth (PD), gingival recession (R), clinical attachment level (CAL), and bleeding on probing (BOP) of all subjects were recorded. The decayed-missing-filled (DMF) index of all subjects was also measured. For statistical analysis, Pearson correlation test, Chi-square, and independent t-test were used. Results: There were significant positive correlation between variables R, PD, CAL, decayed (D), missing (M), DMF, BOP, and degree of CAO. However, there were no significant differences between filling variable degree of CAO (left anterior descending, left circumflex, and right coronary artery). Independent t-test showed that the mean of variables R, PD, AL, D, M, and DMF in patients with obstructed arteries were significantly higher than subjects without CAO. But there were no significant differences between variable F in two groups. Conclusion: The results of this cross-section analytical study showed an association between periodontal disease and dental parameters with the severity of CAO measured by angiography. However, this association must not interpret as a cause and effect relationship. PMID:27274346

  12. Detailed analysis of association between common single nucleotide polymorphisms and subclinical atherosclerosis: The Multi-ethnic Study of Atherosclerosis.

    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

    2016-06-01

    Previously identified single nucleotide polymorphisms (SNPs) in genome wide association studies (GWAS) of cardiovascular disease (CVD) in participants of mostly European descent were tested for association with subclinical cardiovascular disease (sCVD), coronary artery calcium score (CAC) and carotid intima media thickness (CIMT) in the Multi-Ethnic Study of Atherosclerosis (MESA). The data in this data in brief article correspond to the article Common Genetic Variants and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis [1]. This article includes the demographic information of the participants analyzed in the article as well as graphical displays and data tables of the association of the selected SNPs with CAC and of the meta-analysis across ethnicities of the association of CIMT-c (common carotid), CIMT-I (internal carotid), CAC-d (CAC as dichotomous variable with CAC>0) and CAC-c (CAC as continuous variable, the log of the raw CAC score plus one) and CVD. The data tables corresponding to the 9p21 fine mapping experiment as well as the power calculations referenced in the article are also included. PMID:26958643

  13. Detailed analysis of association between common single nucleotide polymorphisms and subclinical atherosclerosis: The Multi-ethnic Study of Atherosclerosis

    PubMed Central

    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.

    2016-01-01

    Previously identified single nucleotide polymorphisms (SNPs) in genome wide association studies (GWAS) of cardiovascular disease (CVD) in participants of mostly European descent were tested for association with subclinical cardiovascular disease (sCVD), coronary artery calcium score (CAC) and carotid intima media thickness (CIMT) in the Multi-Ethnic Study of Atherosclerosis (MESA). The data in this data in brief article correspond to the article Common Genetic Variants and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis [1]. This article includes the demographic information of the participants analyzed in the article as well as graphical displays and data tables of the association of the selected SNPs with CAC and of the meta-analysis across ethnicities of the association of CIMT-c (common carotid), CIMT-I (internal carotid), CAC-d (CAC as dichotomous variable with CAC>0) and CAC-c (CAC as continuous variable, the log of the raw CAC score plus one) and CVD. The data tables corresponding to the 9p21 fine mapping experiment as well as the power calculations referenced in the article are also included. PMID:26958643

  14. Oxidative stress in atherosclerosis and diabetes.

    PubMed

    Lankin, V Z; Lisina, M O; Arzamastseva, N E; Konovalova, G G; Nedosugova, L V; Kaminnyi, A I; Tikhaze, A K; Ageev, F T; Kukharchuk, V V; Belenkov, Yu N

    2005-07-01

    We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus. PMID:16254616

  15. Genomic correlates of atherosclerosis in ancient humans.

    PubMed

    Zink, Albert; Wann, L Samuel; Thompson, Randall C; Keller, Andreas; Maixner, Frank; Allam, Adel H; Finch, Caleb E; Frohlich, Bruno; Kaplan, Hillard; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Watson, Lucia; Cox, Samantha L; Miyamoto, Michael I; Narula, Jagat; Stewart, Alexandre F R; Thomas, Gregory S; Krause, Johannes

    2014-06-01

    Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Iceman's genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world. PMID:25667090

  16. A Histoenzymatic Study of Human Intracranial Atherosclerosis

    PubMed Central

    Hoff, Henry F.

    1972-01-01

    A light microscopy study on the localization of enzyme activity within atherosclerotic human intracranial arteries was performed on autopsy material obtained within 4 hours of death. The data suggests that the atherosclerotic process first goes through a proliferative phase and then a degenerative phase culminating in the formation of a plaque. In the proliferative phase, smooth muscle cell proliferation has formed a thickened intima. Tetrazolium reductase, adenosine triphosphatase (ATPase) and adenosine monophosphatase (AMPase) activities are present in these cells, while all dehydrogenases and acid phosphatase activities were weak or not present. As the degenerative phase commences, an area of necrosis, lipid and macrophage accumulation is formed on the lumen side of the elastica. This area increases in size until a plaque is formed. Unsaturated polar and nonpolar lipid, cholesterol, α-glycerophosphate dehydrogenase, acid phosphatase, and AMPase activities are associated with these areas and in foam cells, which are often found in the thickened intima of the proliferative phase. Tetrazolium reductase and ATPase activities decrease in the thickened intima as the area of necrosis increases in size, while dehydrogenase activity, except that for α-glycerophosphate, remains low or not present. Patterns of enzyme alterations for various stages of the disease process in intracranial arteries, the aorta and coronary arteries suggest a similar, if not identical, progression of the atherosclerotic process, irrespective of known differences in the prevalence of atherosclerosis. ImagesFig 2Fig 3Fig 5Fig 1Fig 4 PMID:4260721

  17. Genetic Links between Diabetes Mellitus and Coronary Atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diabetes mellitus is one of the most common endocrine disorders affecting almost 6% of the world's population and with clear indication that its prevalence continues to increase. The causes of diabetes mellitus are multifactorial and in the general population, both genetic and environmental factors ...

  18. Atherosclerosis in parrots. A review.

    PubMed

    Bavelaar, F J; Beynen, A C

    2004-06-01

    Atherosclerosis is a common disease in parrots. The disease is found in all common parrot species, but especially in African Grey parrots and Amazons. It is a disease of older birds that is seen in both males and females. The most common sign is sudden death, but clinical symptoms that can be found include dyspnea, lethargy and nervous signs, such as paresis and collapses. Because the clinical signs are seldomly seen, it is difficult to diagnose atherosclerosis and therefore it is mostly an unexpected finding at necropsy. Age and species are determinants of atherosclerosis in parrots. Suggested risk factors include an elevated plasma cholesterol level, diet composition, social stress and inactivity, but research is needed to confirm this. PMID:15230050

  19. New therapy via targeting androgen receptor in monocytes/macrophages to battle atherosclerosis.

    PubMed

    Huang, Chiung-Kuei; Pang, Haiyan; Wang, Lin; Niu, Yuanjie; Luo, Jie; Chang, Eugene; Sparks, Janet D; Lee, Soo Ok; Chang, Chawnshang

    2014-06-01

    The male sex has a higher risk to develop coronary artery diseases, including atherosclerosis. The androgen receptor (AR) is expressed in several atherosclerosis-associated cell types, including monocytes/macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs), but its pathophysiological role in each cell type during the development of atherosclerotic lesions remains unclear. Using the Cre-loxP system, we selectively knocked out AR in these 3 cell types and the resultant AR knockout (ARKO) mice, monocyte/macrophage ARKO, EC-ARKO, and SMC-ARKO, were then crossed with the low-density lipoprotein receptor (LDLR) deficient (LDLR(-/-)) mice to develop monocyte/macrophage ARKO-LDLR(-/-), EC-ARKO-LDLR(-/-), and SMC-ARKO-LDLR(-/-) mice for the study of atherosclerosis. The results showed that the monocyte/macrophage ARKO-LDLR(-/-) mice had reduced atherosclerosis compared with the wild-type-LDLR(-/-) control mice. However, no significant difference was detected in EC-ARKO-LDLR(-/-) and SMC-ARKO-LDLR(-/-) mice compared with wild-type-LDLR(-/-) mice, suggesting that the AR in monocytes/macrophages, and not in ECs and SMCs, plays a major role to promote atherosclerosis. Molecular mechanism dissection suggested that AR in monocytes/macrophages upregulated the tumor necrosis factor-α, integrin β2, and lectin-type oxidized LDL receptor 1 molecules that are involved in 3 major inflammation-related processes in atherosclerosis, including monocytes/macrophages migration and adhesion to human umbilical vein ECs, and subsequent foam cell formation. Targeting AR via the AR degradation enhancer, ASC-J9, in wild-type-LDLR(-/-) mice showed similar effects as seen in monocyte/macrophage ARKO-LDLR(-/-) mice with little influence on lipid profile. In conclusion, the AR in monocytes/macrophages plays key roles in atherosclerosis and targeting AR with ASC-J9 may represent a new potential therapeutic approach to battle atherosclerosis. PMID:24688120

  20. Coronary Arteries

    MedlinePlus

    ... side of the heart is smaller because it pumps blood only to the lungs. The left coronary artery, ... heart is larger and more muscular because it pumps blood to the rest of the body. Updated August ...

  1. Coronary angiography

    MedlinePlus

    Coronary angiography is often done along with cardiac catheterization . This is a procedure which measures pressures in ... Cardiac catheterization carries a slightly increased risk when compared with other heart tests. However, the test is very safe ...

  2. How Can Atherosclerosis Be Prevented or Delayed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Can Atherosclerosis Be Prevented or Delayed? Taking action to control ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  3. Redistribution of heart failure as the cause of death: the Atherosclerosis Risk in Communities Study

    PubMed Central

    2014-01-01

    Background Heart failure is sometimes incorrectly listed as the underlying cause of death (UCD) on death certificates, thus compromising the accuracy and comparability of mortality statistics. Statistical redistribution of the UCD has been used to examine the effect of misclassification of the UCD attributed to heart failure, but sex- and race-specific redistribution of deaths on coronary heart disease (CHD) mortality in the United States has not been examined. Methods We used coarsened exact matching to infer the UCD of vital records with heart failure as the UCD from 1999 to 2010 for decedents 55 years old and older from states encompassing regions under surveillance by the Atherosclerosis Risk in Communities (ARIC) Study (Maryland, Minnesota, Mississippi, and North Carolina). Records with heart failure as the UCD were matched on decedent characteristics (five-year age groups, sex, race, education, year of death, and state) to records with heart failure listed among the multiple causes of death. Each heart failure death was then redistributed to plausible UCDs proportional to the frequency among matched records. Results After redistribution the proportion of deaths increased for CHD, chronic obstructive pulmonary disease, diabetes, hypertensive heart disease, and cardiomyopathy, P < 0.001. The percent increase in CHD mortality after redistribution was the highest in Mississippi (12%) and lowest in Maryland (1.6%), with variations by year, race, and sex. Redistribution proportions for CHD were similar to CHD death classification by a panel of expert reviewers in the ARIC study. Conclusions Redistribution of ill-defined UCD would improve the accuracy and comparability of mortality statistics used to allocate public health resources and monitor mortality trends. PMID:24716810

  4. Coronary heart disease

    MedlinePlus

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... Coronary heart disease is the leading cause of death in the United States for men and women. Coronary heart ...

  5. Coronary Calcium Scan

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  6. Coronary Artery Bypass Grafting

    MedlinePlus

    ... Rehabilitation Coronary Heart Disease Heart Attack Heart Surgery Percutaneous Coronary Intervention Send a link to NHLBI to someone by ... include lifestyle changes, medicines, and a procedure called percutaneous coronary intervention (PCI), also known as coronary angioplasty. PCI is ...

  7. [The current opinion on inflammatory, biochemistry and hemostatic markers and factors in atherosclerosis. Part I].

    PubMed

    Rajtar, Renata; Kloch, Małgorzata; Bober, Maria; Kolasińska-Kloch, Władysława

    2006-01-01

    Atherosclerosis remains the leading cause of morbidity and mortality in many countries. Recent studies have established an immuno-inflammatory theory of atherosclerosis where the process of atherosclerosis has a chronic, fibroproliferative character as an immuno-inflammatory response to factors that damage vessel endothelium. The development of coronary artery disease in subjects without traditional risk factors has prompted a search for new markers of the disease, which may improve primary prevention strategies. The relationship between markers of chronic inflammation and infection and development and progression of atherosclerotic may provide a basis for establishing new methods for causative treatment of cardiovascular diseases. The markers of endothelial damage and activation of inflammatory response have a prognostic value independent of traditional risk factors. PMID:17479866

  8. [The current opinion on inflammatory, biochemistry and hemostatic markers and factors in atherosclerosis. Part II].

    PubMed

    Rajtar, Renata; Kloch, Małgorzata; Bober, Maria; Kolasińska-Kloch, Władysława

    2006-01-01

    Atherosclerosis remains the leading cause of morbidity and mortality in many countries. Recent studies have established an immuno-inflammatory theory of atherosclerosis where the process of atherosclerosis has a chronic, fibroproliferative character as an immuno-inflammatory response to factors that damage vessel endothelium. The development of coronary artery disease in subjects without traditional risk factors has prompted a search for new markers of the disease, which may improve primary prevention strategies. The relationship between markers of chronic inflammation and infection and development and progression of atherosclerotic may provide a basis for establishing new methods for causative treatment of cardiovascular diseases. The markers of endothelial damage and activation of inflammatory response have a prognostic value independent of traditional risk factors. PMID:17479867

  9. Kcne2 deletion promotes atherosclerosis and diet-dependent sudden death.

    PubMed

    Lee, Soo Min; Nguyen, Dara; Hu, Zhaoyang; Abbott, Geoffrey W

    2015-10-01

    Coronary artery disease (CAD) is the leading cause of death worldwide. An estimated half of cases involve genetic predisposition. Sequence variants in human KCNE2, which encodes a cardiac and epithelial K(+) channel β subunit, cause inherited cardiac arrhythmias. Unexpectedly, human KCNE2 polymorphisms also associate with predisposition to atherosclerosis, with unestablished causality or mechanisms. Here, we report that germline Kcne2 deletion promotes atherosclerosis in mice, overcoming the relative resistance of this species to plaque deposition. In female western diet-fed mice, Kcne2 deletion increased plaque deposition >6-fold and also caused premature ventricular complexes and sudden death. The data establish causality for the first example of ion channel-linked atherosclerosis, and demonstrate that the severity of Kcne2-linked cardiac arrhythmias is strongly diet-dependent. PMID:26307149

  10. Endoplasmic reticulum stress and atherosclerosis

    PubMed Central

    Hotamisligil, Gökhan S

    2010-01-01

    Atherosclerosis and related cardiovascular diseases represent one of the greatest threats to human health worldwide. Despite important progress in prevention and treatment, these conditions still account for one third of all deaths annually. Often presented together with obesity, insulin resistance and type 2 diabetes, these chronic diseases are strongly influenced by pathways that lie at the interface of chronic inflammation and nutrient metabolism. Here I discuss recent advances in the study of endoplasmic reticulum stress as one mechanism that links immune response with nutrient sensing in the pathogenesis of atherosclerosis and its complications. PMID:20376052

  11. Computed tomographic coronary angiography: experience at Baylor University Medical Center/Baylor Jack and Jane Hamilton Heart and Vascular Hospital

    PubMed Central

    2005-01-01

    Noninvasive cardiac computed tomographic imaging using multislice or electron beam technology has been shown to be highly specific and sensitive in diagnosing coronary heart disease. It is about a fifth of the cost of coronary angiography and is particularly well suited for evaluating patients with a low or low to moderate probability of having obstructive coronary atherosclerosis. In addition, it offers more information than calcium scoring: because of the intravenous contrast used, it temporarily increases the density of the lumen and allows differentiation of soft plaque from calcified plaque. The Baylor Hamilton Heart and Vascular Hospital now uses this modality to define coronary atherosclerosis in patients who would otherwise have needed invasive coronary angiography; several research protocols with the technique are also under way. Baylor has recently upgraded to the 64-slice scanner. It is expected that computed tomographic coronary angiography will replace a significant percentage of invasive cardiac catheterizations. PMID:16200178

  12. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

    PubMed Central

    Husain, Kazim; Hernandez, Wilfredo; Ansari, Rais A; Ferder, Leon

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice. PMID:26322175

  13. Myocardial perfusion echocardiography and coronary microvascular dysfunction

    PubMed Central

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-01-01

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  14. Myocardial perfusion echocardiography and coronary microvascular dysfunction.

    PubMed

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-12-26

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  15. Clinical potential of vorapaxar in cardiovascular risk reduction in patients with atherosclerosis.

    PubMed

    Diehl, Philipp; Bode, Christoph; Duerschmied, Daniel

    2015-01-01

    Vorapaxar (ZONTIVITY™, formerly known as SCH 530348) is a specific, orally active antagonist of the protease-activated receptor-1 (PAR-1) on platelets. It inhibits thrombin-induced platelet activation by binding to the ectodomain of PAR-1. After animal studies and Phase II studies showed that vorapaxar sufficiently inhibits platelet activation without significantly increasing bleeding complications, safety and efficacy of vorapaxar were assessed in two large multicenter trials in patients with coronary artery disease and atherosclerosis. The Thrombin-Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndromes (TRACER) trial investigated safety and efficacy of vorapaxar in patients with an acute coronary syndrome without ST-segment elevation. The Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50 (TRA 2°P-TIMI 50) investigated atherothrombotic events in patients with stable atherosclerosis. Results of both studies suggested that vorapaxar given in addition to standard antiplatelet therapy can reduce atherothrombotic events, but increases the risk of mild and moderate bleeding complications. This review article summarizes the main results of TRACER and TRA 2°P-TIMI 50 and suggests patient cohorts that might benefit from treatment with vorapaxar in addition to standard antiplatelet therapy. PMID:26346960

  16. Vitamin K Intake and Atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been hypothesized that insufficient intake of vitamin K may increase soft tissue calcification due to impaired gamma-carboxylation of the vitamin K-dependent protein, matrix gamma-carboxyglutamic acid (MGP). The evidence to support this putative role of vitamin K intake in atherosclerosis is ...

  17. Life Event, Stress and Illness

    PubMed Central

    Salleh, Mohd. Razali

    2008-01-01

    The relationship between stress and illness is complex. The susceptibility to stress varies from person to person. Among the factors that influenced the susceptibility to stress are genetic vulnerability, coping style, type of personality and social support. Not all stress has negative effect. Studies have shown that short-term stress boosted the immune system, but chronic stress has a significant effect on the immune system that ultimately manifest an illness. It raises catecholamine and suppressor T cells levels, which suppress the immune system. This suppression, in turn raises the risk of viral infection. Stress also leads to the release of histamine, which can trigger severe broncho-constriction in asthmatics. Stress increases the risk for diabetes mellitus, especially in overweight individuals, since psychological stress alters insulin needs. Stress also alters the acid concentration in the stomach, which can lead to peptic ulcers, stress ulcers or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries (atherosclerosis), especially if combined with a high-fat diet and sedentary living. The correlation between stressful life events and psychiatric illness is stronger than the correlation with medical or physical illness. The relationship of stress with psychiatric illness is strongest in neuroses, which is followed by depression and schizophrenia. There is no scientific evidence of a direct cause-and-effect relationship between the immune system changes and the development of cancer. However, recent studies found a link between stress, tumour development and suppression of natural killer (NK) cells, which is actively involved in preventing metastasis and destroying small metastases. PMID:22589633

  18. An Integrative Predictive Model of Coronary Artery Calcification in Arteriosclerosis

    PubMed Central

    McGeachie, Michael; Ramoni, Rachel L Badovinac; Mychaleckyj, Josyf C.; Furie, Karen L; Dreyfuss, Jonathan M.; Liu, Yongmei; Herrington, David; Guo, Xiuqing; Lima, João A.; Post, Wendy; Rotter, Jerome I.; Rich, Stephen; Sale, Michèle; Ramoni, Marco F.

    2010-01-01

    Background: Many different genetic and clinical factors have been identified as causes or contributors to atherosclerosis. We present a model of preclinical atherosclerosis based on genetic and clinical data that predicts the presence of coronary artery calcification in healthy Americans of European descent aged 45 to 84 in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results: We assessed 712 individuals for the presence or absence of coronary artery calcification, and their genotypes for 2882 single-nucleotide polymorphisms (SNPs). Using these SNPs and relevant clinical data, a Bayesian network that predicts the presence of coronary calcification was constructed. The model contains 13 SNPs (from genes AGTR1, ALOX15, INSR, PRKAB1, IL1R2, ESR2, KCNK1, FBLN5, PPARA, VEGFA, PON1, TDRD6, PLA2G7, and one ancestry informative marker) and 5 clinical variables (sex, age, weight, smoking, and diabetes) and achieves 85% predictive accuracy, as measured by area under the ROC curve (AUC). This is a significant (p < 0.001) improvement upon models using just the SNP data or using just the clinical variables. Conclusions: We present an investigation of joint genetic and clinical factors associated with atherosclerosis that shows predictive results for both cases, and enhanced performance for the combination. PMID:19948975

  19. Chlamydia in canine or feline coronary arteriosclerotic lesions

    PubMed Central

    2011-01-01

    Background There are numerous reports linking Chlamydia infection to human coronary atherosclerosis. However, there is a lack of data regarding this correlation in dogs and cats, and there are no reports investigating coronary arteriosclerosis and Chlamydia in these species. The aim of the present study was to examine whether there is a correlation between canine and feline spontaneous atherosclerosis or arteriosclerosis and the presence of Chlamydia. Archived histopathological samples of dogs (n = 16) and cats (n = 13) with findings of atherosclerosis or arteriosclerosis in heart tissue were examined for the presence of Chlamydiaceae using real-time PCR, ArrayTube Microarray and immunohistochemistry. Additionally, arteriosclerotic lesions of all cases were histologically classified and graded. Results Both canine atherosclerotic cases, and all 14 canine arteriosclerotic cases were negative for Chlamydia. Only one of the 13 arteriosclerotic feline cases was positive for Chlamydia by real-time PCR, revealing C. abortus by ArrayTube Microarray. To our knowledge, this is the first description of C. abortus in a cat. Overall, the type and grade of canine and feline arteriosclerotic lesions revealed similarities, and were predominantly moderate and hyperplastic. Conclusions These findings suggest that there is no obvious correlation between canine and feline coronary arteriosclerosis and the presence of Chlamydia. In order to draw final conclusions about the correlation between Chlamydia and canine atherosclerosis, examination of more samples is required. PMID:21906306

  20. Giant Right Coronary Artery Aneurysm Associated with a Fistula Draining into the Superior Vena Cava

    PubMed Central

    Dolapoglu, Ahmet

    2016-01-01

    Giant coronary artery aneurysm associated with a coronary–cameral fistula is an uncommon condition. Such aneurysms are usually associated with other cardiac diseases, such as coronary atherosclerosis, and therefore might augment myocardial ischemia in adults. The main indications for surgical intervention are severe coexisting coronary artery disease, evidence of embolization, and aneurysmal enlargement or rupture. We describe a large right coronary artery aneurysm and a coronary–cameral fistula that drained into the superior vena cava. The surgical repair was successful. PMID:27547153

  1. MRI of the Coronary vasculature: Imaging the Lumen, Wall and Beyond

    PubMed Central

    Lin, Kai; Carr, James C.

    2015-01-01

    The characteristics of coronary artery disease (CAD) are gradual thickening of the coronary walls and narrowing of the vascular lumen due to the built-up of atherosclerosis plaques. Those morphological changes can be noninvasively detected by coronary MRI/MRA. In addition, functional changes, such as coronary wall distensibility and flow changes may also be evaluated with MRI. However, the application of current MRI/MRA techniques is limited in clinical practice due to several adverse technical and physiological factors, such as cardiac motion and respiratory motion. Many technical innovations have been adopted to address those problems from multiple aspects. PMID:25726999

  2. Decompression illness.

    PubMed

    Vann, Richard D; Butler, Frank K; Mitchell, Simon J; Moon, Richard E

    2011-01-01

    Decompression illness is caused by intravascular or extravascular bubbles that are formed as a result of reduction in environmental pressure (decompression). The term covers both arterial gas embolism, in which alveolar gas or venous gas emboli (via cardiac shunts or via pulmonary vessels) are introduced into the arterial circulation, and decompression sickness, which is caused by in-situ bubble formation from dissolved inert gas. Both syndromes can occur in divers, compressed air workers, aviators, and astronauts, but arterial gas embolism also arises from iatrogenic causes unrelated to decompression. Risk of decompression illness is affected by immersion, exercise, and heat or cold. Manifestations range from itching and minor pain to neurological symptoms, cardiac collapse, and death. First-aid treatment is 100% oxygen and definitive treatment is recompression to increased pressure, breathing 100% oxygen. Adjunctive treatment, including fluid administration and prophylaxis against venous thromboembolism in paralysed patients, is also recommended. Treatment is, in most cases, effective although residual deficits can remain in serious cases, even after several recompressions. PMID:21215883

  3. Coronary Computed Tomography Angiography of Spontaneous Coronary Artery Dissection: A Case Report and Review of the Literature

    PubMed Central

    Torres-Ayala, Stephanie C.; Maldonado, Jose; Scott Bolton, J.; Bhalla, Sanjeev

    2015-01-01

    Patient: Male, 23 Final Diagnosis: Spontaneous coronary artery dissection Symptoms: Chest discomfort • chest pain Medication: — Clinical Procedure: Coronary computed tomography angiography Specialty: Radiology Objective: Rare disease Background: Multidetector computed tomography (MDCT) has gained wide acceptance in the evaluation of the cardiovascular system. Of particular clinical interest is its ability to non-invasively evaluate coronary arteries in patients presenting to the emergency room. In acute coronary syndromes, myocardial ischemia is most often caused by atherosclerosis. We present a case of a rare cause of acute coronary syndrome, spontaneous coronary artery dissection (SCAD), which was initially evaluated with MDCT and followed by intravascular ultrasound (IVUS) and invasive coronary angiography (ICA). We discuss the findings and role of each modality with particular attention to coronary computed tomographic angiography (CCTA) in the diagnosis and management of SCAD. As the use of CCTA in the emergency department continues to rise, radiologists must become familiar with CT appearance of SCAD. Case Report: We report the multidetector computed tomography (MDCT), intravascular ultrasound (IVUS), and invasive coronary angiography (ICA) findings in a case of spontaneous coronary artery dissection of the left anterior descending artery in a previously healthy 23-year-old man. The role of coronary computed tomographic angiography (CCTA) in diagnosis and management of this potentially life-threatening condition is discussed. Conclusions: In the clinical setting of acute coronary syndrome, SCAD must be a consideration, particularly in young patients without clear risk factors for coronary artery disease and in women in the peripartum period. CCTA is a very helpful diagnostic tool to diagnose the condition in a non-invasive manner and to follow up after treatment. PMID:25738889

  4. Keloid scarring, but not Dupuytren’s contracture, is associated with unexplained carotid atherosclerosis

    PubMed Central

    Bhavsar, Sankalp; Nimigan, Andre; Hackam, Daniel G.; O’Gorman, David B.; Gan, Bing Siang; Spence, J. David

    2016-01-01

    Background Atherosclerosis, a response to injury, may be thought of as scarring in the artery wall. TGF-β and associated signaling molecules have been implicated in the pathophysiology of keloid scarring, Dupuytren’s Contracture and atherosclerotic plaques in independent studies. Purpose To test the hypothesis that excess cutaneous scarring and Dupuytren’s contractures predispose independently to carotid atherosclerosis. Methods Among 1,747 patients with plaque measurements and complete data for multivariable regression analysis, 57 Caucasian patients had Dupuytren’s contractures and 12 had keloid scars. Carotid total plaque area (TPA) was measured by 2-Dimensional ultrasound. Results In linear multivariable regression analysis with coronary risk factors, keloid scars were associated with TPA (P= 0.018), but Dupuytren’s contractures were not. Patients with keloid scarring were younger (P<0.0001), and more likely to be diabetic (P<0.0001) Conclusions Keloid scarring is a clinical clue to excess atherosclerosis not explained by traditional risk factors. Such patients may benefit from therapy directed at targets related to signalling molecules common to both the process of keloid scarring and atherosclerosis. These findings suggest previously unexplored possibilities for the prevention and treatment of atherosclerosis. The differences between Dupuytren’s and keloid scars that may identify such targets are discussed. PMID:19331810

  5. Effect of MTHFR Gene Polymorphism Impact on Atherosclerosis via Genome-Wide Methylation

    PubMed Central

    Lin, Xuefeng; Zhang, Wei; Lu, Qun; Lei, Xinjun; Wang, Tingzhong; Han, Xuanmao; Ma, Aiqun

    2016-01-01

    Background Atherosclerosis seriously threats human health. Homocysteine is an independent risk factor closely related to DNA methylation. MTHFR C667T loci polymorphism is closely associated with homocysteine level. This study aimed to investigate the relationship among MTHFR C667T loci polymorphism, genome-wide methylation, and atherosclerosis. Material/Methods Blood sample was collected from 105 patients with coronary atherosclerosis and 105 healthy controls. Pyrosequencing methylation was used to detect LINE-1 methylation level. Polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP) was used to test MTHFR. Results LINE-1 methylation level in the patient group was significantly lower than in the controls (t=5.007, P<0.001). MTHFR C667T genotype distribution presented marked differences in the 2 groups. TT genotype carriers had significantly increased risk of atherosclerosis (OR=3.56, P=0.009). Three different genotypes of MTHFR C667T loci showed different LINE-1 methylation level between the 2 groups (P<0.01). LINE-1 methylation level in TT and CT genotype carriers was obviously lower than in CC genotype carriers (P<0.05). Conclusions MTHFR C667T loci polymorphism may affect atherosclerosis by regulating genome methylation level. PMID:26828698

  6. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation

    PubMed Central

    Cuff, Carolyn A.; Kothapalli, Devashish; Azonobi, Ijeoma; Chun, Sam; Zhang, Yuanming; Belkin, Richard; Yeh, Christine; Secreto, Anthony; Assoian, Richard K.; Rader, Daniel J.; Puré, Ellen

    2001-01-01

    Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50–70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the “synthetic” state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms. PMID:11581304

  7. Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes

    PubMed Central

    Nilsson, Roland; Noori, Peri; Maleki, Shohreh; Köhler, Marina; Hamsten, Anders; Tegnér, Jesper; Björkegren, Johan

    2008-01-01

    Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr−/−Apo100/100 Mttpflox/flox Mx1-Cre). Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins) at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies. PMID:18369455

  8. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

    PubMed

    Slocum, C; Kramer, C; Genco, C A

    2016-07-01

    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease. PMID:26791914

  9. The Association between Circulating MicroRNA Levels and Coronary Endothelial Function

    PubMed Central

    Widmer, R. Jay; Chung, Woo-Young; Herrmann, Joerg; Jordan, Kyra L.; Lerman, Lilach O.; Lerman, Amir

    2014-01-01

    Human microRNAs (miRs) have been implicated in human diseases presumably through the downregulation and silencing of targeted genes via post-translational modifications. However, their role in the early stage of coronary atherosclerosis is not known. The aim of this study was to test the hypothesis that patients with early atherosclerosis and coronary endothelial dysfunction (CED) have alterations in transcoronary miR gradients. Patients underwent coronary angiography and endothelial function testing in the cardiac catheterization laboratory. Patients were divided into abnormal (n = 26) and normal (n = 22) microvascular coronary endothelial function based on intracoronary response to infused acetylcholine measured as a percent change in coronary blood flow (CBF) and arterial diameter. Blood samples were obtained simultaneously from the aorta and coronary sinus at the time of catheterization for RNA isolation, and miR subsequently assessed. Baseline characteristics were similar in both groups. Patients with microvascular CED displayed transcoronary gradients significantly elevated in miR-92a and miR-133 normalized to C-elegans-39 miR. Percent change in CBF and the transcoronary gradient of miR-133 displayed a significant inverse correlation (r2 = 0.11, p = 0.03). Thus, we present novel data whereupon selected miRs demonstrate elevated transcoronary gradients in patients with microvascular CED. The current findings support further studies on the mechanistic role of miRs in coronary atherosclerosis and in humans. PMID:25310838

  10. Human-like atherosclerosis in minipigs: a new model for detection and treatment of vulnerable plaques.

    PubMed

    Thim, Troels

    2010-07-01

    Advanced atherosclerosis, through thrombosis, leads to ischemic heart disease and ischemic stroke, the leading causes of death and disability worldwide. Advanced atherosclerosis and imaging of atherosclerosis are the focus of this dissertation with particular emphasis on the vulnerable plaque and vulnerable plaque detection. Aspects of advanced atherosclerosis and the vulnerable plaque in humans are described along with the basis for the selected minipig models and methods for atherosclerosis acceleration used. The overall aims of the studies were to develop an animal model of advanced atherosclerosis with human like vulnerable plaque morphology and use this animal model to test an imaging modality aimed at vulnerable plaque detection. The first aim is addressed in 3 papers, where accelerated plaque development in the coronary and carotid arteries is investigated in down sized Rapacz pigs. Down-sized Rapacz pigs are minipigs with familial hypercholesterolemia caused by a mutation in the low density lipoprotein receptor. Paper 1 describes the lipid profile in the down-sized Rapacz on chow and atherogenic diets and spontaneously developed and balloon accelerated coronary plaque with a morphology that resembles the morphology of human vulnerable plaque. Paper 2 describes vein graft disease in internal jugular vein grafts inserted into the common carotid artery. Plaques with necrotic cores were found in oversized vein grafts only indicating an effect of flow and shear stress on plaque development. Paper 3 describes the effects of wall shear stress on local plaque development in surgically stenosed common carotid arteries in the down-sized Rapacz pigs. This study indicated that the combination of low and oscillatory wall shear stress was needed for development of advanced plaque. In paper 4, we interrogated coronary lesions in the down-sized Rapacz with a commercially available diagnostic tool VH IVUS. It is claimed that VH IVUS can characterize the tissue components

  11. Leukotriene A4 Hydrolase Haplotype, Diet and Atherosclerosis: A Twin Study

    PubMed Central

    Zhao, Jinying; Goldberg, Jack; Vaccarino, Viola

    2012-01-01

    Objective Atherosclerosis is an inflammatory process resulting from the interaction between genetic and environmental factors. Leukotrienes are inflammatory mediators generated from arachidonic acid, and genetic polymorphisms involved in leukotriene metabolism are implicated in atherosclerosis. The objectives of this study are to examine whether genetic variants in key leukotriene enzymes are associated with atherosclerosis, and whether dietary intake of competing leukotriene substrates modifies the effect of leukotriene variants on atherosclerosis. Methods Atherosclerosis was assessed by common carotid intima-media thickness (IMT) using ultrasound. Sequence variants within arachidonate 5-lipoxygenase activating protein (ALOX5AP) and leukotriene A4 hydrolase (LTA4H) genes were analyzed with 32 single nucleotide polymorphisms (SNPs) in 169 Caucasian twin pairs from the Vietnam Era Twin Registry. The associations between genetic polymorphisms and carotid atherosclerosis, and gene × diet interactions were examined by generalized estimating equation controlling for potential confounders. Results A six-SNP haplotype in LTA4H, designated HapE, was significantly associated with carotid IMT after adjusting for known coronary risk factors. Twins carrying HapE had a much lower IMT compared to twins not carrying (695 μm vs. 750 μm, p=0.0007). Moreover, dietary intake of polyunsaturated fatty acids strongly augmented the cardioprotective effect of HapE among those with this haplotype but not those without, suggesting a haplotype × diet interaction (Interaction PHapE × n-3 = 0.03, PHapE × n-6 = 0.015). Conclusion We identified a novel leukotriene haplotype that appears to be protective towards subclinical atherosclerosis. This association is modified by dietary intake of polyunsaturated fatty acids. PMID:23153620

  12. Differential associations between blood biomarkers of inflammation, oxidation, and lipid metabolism with varying forms of coronary atherosclerotic plaque as quantified by coronary CT angiography

    PubMed Central

    Truong, Quynh A.; Koenig, Wolfgang; Schlett, Christopher L.; Nasir, Khurram; Butler, Javed; Kurtz, Emily; Nikolaou, Konstantin; Hoffmann, Udo; Januzzi, James L.

    2011-01-01

    Although epidemiologic data link biomarkers of cardiovascular risk with incident and prevalent coronary artery disease, exact anatomic relationships between biomarkers and coronary atherosclerosis as measured by coronary CT angiography remain unclear. Patients with acute chest pain who ultimately had no evidence of acute coronary syndrome underwent contrast-enhanced 64-slice coronary CT angiography to determine presence, extent and composition of coronary atherosclerotic plaque. We determined the differences in levels of blood biomarkers measured at the time of the CT scan between different CT-based atherosclerotic plaque groups. Among 313 patients (mean age: 51.6 ± 11 years, 62% male) high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-2 were associated with the extent of calcified plaque (P = 0.03 and P<0.001), while hs-CRP and apolipoprotein A1 were associated with the extent of non-calcified plaque (P = 0.03 and P = 0.004; respectively). Despite a generally lower risk profile, subjects with exclusively non-calcified plaque had significantly higher levels of hs-CRP and oxidized low-density lipoprotein (P = 0.01 and P = 0.03; respectively) and lower levels of adiponectin (P = 0.03) when compared to subjects with calcified plaque (n = 130, 42%). Biomarkers reflecting inflammation, vascular remodeling, oxidation, and lipoprotein metabolism maybe associated with different patterns of coronary atherosclerosis as quantified by coronary CT angiography. PMID:21222039

  13. Apelin Levels In Isolated Coronary Artery Ectasia

    PubMed Central

    Kaplan, İbrahim; Yıldız, Abdulkadir; Akıl, Mehmet Ata; Acet, Halit; Yüksel, Murat; Polat, Nihat; Aydın, Mesut; Oylumlu, Mustafa; Ertaș, Faruk; Kaya, Hasan; Alan, Sait

    2015-01-01

    Background and Objectives The etiopathogenesis of coronary artery ectasia (CAE) is not known completely. In most of the cases, CAE is associated with atherosclerosis; however, isolated CAE has a nonatherosclerotic mechanism. The association between atherosclerotic coronary artery disease and apelin has been examined in previous studies. However, the role of plasma apelin in isolated coronary artery ectasia has not been studied. In this study, we investigated the relationship between plasma apelin levels and isolated coronary artery ectasia. Subjects and Methods The study population included a total of 54 patients. Twenty-six patients had isolated CAE (53.6±8.1 years); 28 patients with normal coronary arteries (51.6±8.8 years) and with similar risk factors and demographic characteristics served as the control group. Apelin levels were measured using an enzyme-linked immunoassay kit. Results Apelin level in the CAE group was significantly lower (apelin=0.181±0.159 ng/mL) than that in the control group (apelin=0.646±0.578 ng/mL) (p=0.033). Glucose, creatinine, total cholesterol, triglyceride, low density lipoprotein cholesterol, and high density lipoprotein cholesterol levels were not significantly different between the two groups. Conclusion In this study, we showed that patients with isolated CAE have decreased plasma apelin levels compared with the control group. Based on the data, a relationship between plasma apelin and isolated CAE was determined. PMID:26413106

  14. The relation of antemortem factors to atherosclerosis at autopsy. The Puerto Rico Heart Health Program.

    PubMed Central

    Sorlie, P. D.; Garcia-Palmieri, M. R.; Castillo-Staab, M. I.; Costas, R.; Oalmann, M. C.; Havlik, R.

    1981-01-01

    Among 9824 Puerto Rican men, aged 35-79, participating in a prospective study of cardiovascular risk factors, there were 970 deaths during the period 1965-1977. About 14%, or 139, of these deaths had a protocol autopsy following the procedures of the International Atherosclerosis Project. The percentage of involvement with raised atherosclerotic lesions in the coronary arteries was higher in the urban deceased than in the rural. The coronary heart disease death rate was also found to be higher in urban than in rural men in this population. Serum cholesterol and systolic blood pressure measured from up to 8 years before death were related both to raised lesions in the coronary arteries and in the aorta. Age and previous smoking status were associated with lesions only in the aorta. These results lend support for an etiologic relationship between serum cholesterol and blood pressure and the atherosclerotic process. PMID:7234969

  15. Plasmacytoid Dendritic Cells in Atherosclerosis

    PubMed Central

    Döring, Yvonne; Zernecke, Alma

    2012-01-01

    Atherosclerosis, a chronic inflammatory disease of the vessel wall and the underlying cause of cardiovascular disease, is initiated and maintained by innate and adaptive immunity. Accumulating evidence suggests an important contribution of autoimmune responses to this disease. Plasmacytoid dendritic cells (pDCs), a specialized cell type known to produce large amounts of type I interferons (IFNs) in response to bacterial and viral infections, have recently been revealed to play important roles in atherosclerosis. For example, the development of autoimmune complexes consisting of self-DNA and antimicrobial peptides, which trigger chronic type I IFN production by pDCs, promote early atherosclerotic lesion formation. pDCs and pDC-derived type I IFNs can also induce the maturation of conventional DCs and macrophages, and the development of autoreactive B cells and antibody production. These mechanisms, known to play a role in the pathogenesis of other autoimmune diseases such as systemic lupus erythematosus and psoriasis, may also affect the development and progression of atherosclerotic lesion formation. This review discusses emerging evidence showing a contribution of pDCs in the onset and progression of atherosclerosis. PMID:22754539

  16. Immunity, atherosclerosis and cardiovascular disease

    PubMed Central

    2013-01-01

    Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed. PMID:23635324

  17. Intestinal Microbiota Metabolism and Atherosclerosis

    PubMed Central

    Liu, Tian-Xing; Niu, Hai-Tao; Zhang, Shu-Yang

    2015-01-01

    Objective: This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. Data Sources: This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: “Intestinal microbiota”, “trimethylamine N-oxide (TMAO)”, “trimethylamine (TMA)”, “cardiovascular”, and “atherosclerosis”. Study Selection: Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results: A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions: Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management. PMID:26481750

  18. 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

  19. Human neutrophil elastase: mediator and therapeutic target in atherosclerosis.

    PubMed

    Henriksen, Peter A; Sallenave, Jean-Michel

    2008-01-01

    Human neutrophil elastase (HNE) is present within atherosclerotic plaques where it contributes to matrix degradation and weakening of the vessel wall associated with the complications of aneurysm formation and plaque rupture. It is joined by other extracellular proteases in these actions but the broad range of substrates and potency of HNE coupled with the potential for rapid increases in HNE activity associated with neutrophil degranulation in acute coronary syndromes single this disruptive protease out as therapeutic target in atherosclerotic disease. This review summarises the role of HNE in neutrophil-mediated endothelial injury and the evidence for HNE as a mediator of atherosclerotic plaque development. The therapeutic potential of HNE neutralising antiproteases, alpha-1-antitrypsin and elafin, in atherosclerosis, is discussed. PMID:18289916

  20. 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

  1. SIRT1 improves VSMC functions in atherosclerosis.

    PubMed

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Xu; Long, Chun-Yan; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-05-01

    Despite advancements in diagnosis and treatment of cardiovascular diseases (CVDs), the morbidity and mortality of CVDs are still rising. Atherosclerosis is a chronic inflammatory disease contributing to multiple CVDs. Considering the complexity and severity of atherosclerosis, it is apparent that exploring the mechanisms of atherosclerotic formation and seeking new therapies for patients with atherosclerosis are required to overcome the heavy burden of CVDs on the quality and length of life of the global population. Vascular smooth muscle cells (VSMCs) play a dominant role in functional and structural changes of the arterial walls in response to atherogenic factors. Therefore, improvement of VSMC functions will slow down the development of atherosclerosis to a large extent. Given its protective performances on regulation of cholesterol metabolism and inflammatory responses, SIRT1 has long been known as an anti-atherosclerosis factor. In this review, we focus on the effects of SIRT1 on VSMC functions and thereby the development of atherosclerosis. PMID:27080738

  2. Sex Differences in Inflammation During Atherosclerosis

    PubMed Central

    Fairweather, DeLisa

    2014-01-01

    Atherosclerosis is the leading cause of death in the United States and worldwide, yet more men die from atherosclerosis than women, and at a younger age. Women, on the other hand, mainly develop atherosclerosis following menopause, and particularly if they have one or more autoimmune diseases, suggesting that the immune mechanisms that increase disease in men are different from those in women. The key processes in the pathogenesis of atherosclerosis are vascular inflammation, lipid accumulation, intimal thickening and fibrosis, remodeling, and plaque rupture or erosion leading to myocardial infarction and ischemia. Evidence indicates that sex hormones alter the immune response during atherosclerosis, resulting in different disease phenotypes according to sex. Women, for example, respond to infection and damage with increased antibody and autoantibody responses, while men have elevated innate immune activation. This review describes current knowledge regarding sex differences in the inflammatory immune response during atherosclerosis. Understanding sex differences is critical for improving individualized medicine. PMID:25983559

  3. Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.

    PubMed

    Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin; Tellides, George; Simons, Michael

    2016-01-01

    The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFβ signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFβ signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFβ activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2α led to a profound inhibition of atherosclerotic plaque growth when these animals were crossed on Apoe(-/-) background and subjected to a high-fat diet. In particular, there was a significant reduction in plaque cellularity, increase in fibrous cap area, and decrease in necrotic core size. In agreement with these findings, examination of human coronary arteries with various degrees of atherosclerosis revealed a strong correlation between the activation of FGF signaling, loss of TGFβ activity, and increased disease severity. These results identify SMC FGF/TGFβ signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth. PMID:27189169

  4. Role of apoptosis in atherosclerosis and its therapeutic implications.

    PubMed

    Stoneman, Victoria E A; Bennett, Martin R

    2004-10-01

    Atherosclerotic plaques develop as a consequence of the accumulation of circulating lipid and the subsequent migration of inflammatory cells (macrophages and T-lymphocytes) and VSMCs (vascular smooth muscle cells). Advanced plaques consist of a lipid-rich core, separated from the lumen by a fibrous cap composed of VSMCs, collagen and extracellular matrix. Plaque enlargement ultimately narrows the lumen (stenosis) causing angina. However, recent studies have emphasized that acute coronary syndromes (unstable angina/myocardial infarction) are caused by lesion erosion/rupture with superimposed thrombus formation on often small non-stenotic plaques. Thus current therapies work predominantly on stabilization of plaques rather than plaque regression. Apoptosis (programmed cell death) is increasingly observed as plaques develop, although the exact mechanisms and consequences of apoptosis in the development and progression of atherosclerosis are still controversial. Increased endothelial cell apoptosis may initiate atherosclerosis, whereas apoptosis of VSMCs and macrophages localizes in 'vulnerable' lesions, i.e. those most likely to rupture, and at sites of rupture. This review will focus on the regulation of apoptosis of cells within the vasculature, concentrating on the relevance of apoptosis to plaque progression and clinical consequences of vascular cell apoptosis. PMID:15230690

  5. Translational studies of lipoprotein-associated phospholipase A2 in inflammation and atherosclerosis

    PubMed Central

    Ferguson, Jane F; Hinkle, Christine C; Mehta, Nehal N; Bagheri, Roshanak; DerOhannessian, Stephanie L; Shah, Rhia; Mucksavage, Megan I; Bradfield, Jonathan P; Hakonarson, Hakon; Wang, Xuexia; Master, Stephen R; Rader, Daniel J; Li, Mingyao; Reilly, Muredach P

    2012-01-01

    Objectives To examine the role of lipoprotein-associated phospholipase A2 (Lp-PLA2/PLA2G7) in human inflammation and coronary atherosclerosis. Background Lp-PLA2 has emerged as a potential therapeutic target in coronary heart disease (CHD). Data supporting Lp-PLA2 are indirect and confounded by species differences; whether Lp-PLA2 is causal in CHD remains in question. Methods We examined inflammatory regulation of Lp-PLA2 during experimental endotoxemia in human, probed the source of Lp-PLA2 in human leukocytes under inflammatory conditions, and assessed the relationship of variation in PLA2G7, the gene encoding Lp-PLA2, with coronary artery calcification (CAC). Results In contrast to circulating TNFα and CRP, blood and monocyte Lp-PLA2 mRNA decreased transiently, and plasma Lp-PLA2 mass declined modestly during endotoxemia. In vitro, Lp-PLA2 expression increased dramatically during human monocyte to macrophage differentiation and further in inflammatory macrophages and foam like-cells. Despite only a marginal association of SNPs in PLA2G7 with Lp-PLA2 activity or mass, numerous PLA2G7 SNPs were associated with CAC. In contrast, several SNPs in CRP were significantly associated with plasma CRP levels but had no relation with CAC. Conclusions Circulating Lp-PLA2 did not increase during acute phase response in human, while inflammatory macrophages and foam cells, but not circulating monocytes, are major leukocyte sources of Lp-PLA2. Common genetic variation in PLA2G7 is associated with sub-clinical coronary atherosclerosis. These data link Lp-PLA2 to atherosclerosis in human while highlighting the challenge in using circulating Lp-PLA2 as a biomarker of Lp-PLA2 actions in the vasculature. PMID:22340269

  6. Coronary artery disease

    MedlinePlus Videos and Cool Tools

    The coronary arteries supply blood to the heart muscle itself. Damage to or blockage of a coronary artery can result in injury to the heart. Normally, blood flows through a coronary artery unimpeded. However, a ...

  7. Coronary Slow Flow Phenomenon Clinical Findings and Predictors

    PubMed Central

    Sanati, Hamidreza; Kiani, Reza; Shakerian, Farshad; Firouzi, Ata; Zahedmehr, Ali; Peighambari, Mohammadmehdi; Shokrian, Leila; Ashrafi, Peiman

    2016-01-01

    Background: In some patients with chest pain, selective coronary angiography reveals slow contrast agent passage through the epicardial coronary arteries in the absence of stenosis. This phenomenon has been designated the slow coronary flow (SCF) phenomenon. Objectives: In this study, we aimed to describe the demographic and clinical findings and presence of common atherosclerosis risk factors in patients with the SCF phenomenon. Patients and Methods: Between October 2014 and March 2015, demographic data, clinical histories, atherosclerosis risk factors, and laboratory and angiographic findings were recorded for all consecutive patients scheduled for coronary angiography and diagnosed with the SCF phenomenon, as well as a control group (patients with normal epicardial coronary arteries; NECA). SCF was diagnosed based on the thrombolysis in myocardial infarction frame count (TFC). A TFC > 27 indicated a diagnosis of SCF phenomenon. Results: Among the 3600 patients scheduled for selective coronary angiography, 75 (2%) met the SCF criteria. SCF and NECA patients did not exhibit statistically significant differences in traditional risk factors except for hypertension, which was more prevalent in SCF than NECA patients (52% versus 31%, P = 0.008). A multivariable analysis indicated a low body mass index, presence of hypertension, low high-density lipoprotein cholesterol (HDL-c) level, and high hemoglobin level as independent predictors of the SCF phenomenon; of these, hypertension was the strongest predictor (odds ratio = 6.3, 95% confidence interval: 2.2 - 17.9, P = 0.001). Conclusions: The SCF phenomenon is relatively frequent, particularly among patients with acute coronary syndrome who are scheduled for coronary angiography. Hypertension, a low HDL-c level, and high hemoglobin level can be considered independent predictors of this phenomenon. PMID:26889458

  8. 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. PMID:27372847

  9. What Are the Signs and Symptoms of Atherosclerosis?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Atherosclerosis? Atherosclerosis usually doesn't cause signs and symptoms ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  10. Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective.

    PubMed

    Mallika, V; Goswami, Binita; Rajappa, Medha

    2007-01-01

    Atherosclerosis is the root cause of the biggest killer of the 21st century. Mechanisms contributing to atherogenesis are multiple and complex. A number of theories-including the role of dyslipidemia, hypercoagulability, oxidative stress, endothelial dysfunction, and inflammation and infection by certain pathogens-have been propounded from time to time explain this complex phenomenon. Recently it has been suggested that atherosclerosis is a multifactorial, multistep disease that involves chronic inflammation at every step, from initiation to progression, and that all the risk factors contribute to pathogenesis by aggravating the underlying inflammatory process. A better understanding of the pathogenesis of atherosclerosis will aid in devising pharmaceutical and lifestyle modifications for reducing mortality resulting from coronary artery disease (CAD).A comprehensive literature search was conducted using the Web sites of the National Library of Medicine (http:// www.ncbl.nlm.nih.gov/) and PubMed Central, the US National Library of Medicine's digital archive of life sciences literature (http:// www.pubmedcentral.nih.gov/). The data were accessed from books and journals in which relevant articles in this field were published. The whole spectrum of coronary artery disease evolves through various events that lead to the formation and progression of atherosclerotic plaque and finally its complications. Atherosclerosis is the culprit behind coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The pathogenic mechanisms are varied and complex. Of late, the role of lipoprotein (a), homocysteine, and inflammation and infection as prime culprits in pathogenesis of CAD is the subject of intense research and debate. The appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework to understand the clinical benefits of newer therapeutic strategies, and a better understanding of pathogenesis aids in formulating

  11. The iatrogenic pathology of percutaneous interventions in coronary arteries.

    PubMed

    Li, X; De Winter, R J; Van Der Wal, A C

    2012-12-01

    Acute coronary syndromes (ACS) represent the clinical manifestations of sudden flow limiting coronary artery disease leading to acute myocardial ischemia or necrosis. Treatment of progressive coronary stenosis or acute thrombotic occlusion by means of percutaneous coronary intervention (PCI) with balloon dilatation and stent placement aims to reduce the risk of myocardial ischemia or necrosis by restoring coronary flow. But, being an invasive technique, it is associated with a periprocedural and also eventually long-term risk of complications. Pathological examination of atherosclerotic coronary arteries after PCI treatment has been shown to be very helpful in providing insights in this iatrogenic pathology. Importantly, the pathological substrate of the treated coronary artery segment in patients with ACS differs significantly from coronary artery segments in patients with stable coronary artery disease. Such studies have shown that besides the physical trauma induced by a balloon or a stent also the specific histomorphological and biological properties of the treated coronary plaques play an important role in the risk of PCI related vascular complications. Major complications, which are thrombosis and restenosis, have reduced significantly over the past years. Still, late stent thrombosis remains a small but clinically important problem after placement of drug eluting stents DES, mainly related to delayed in stent wound healing and early withdrawal of antiplatelet therapy. Moreover, restenosis remains a problem in the still large group of patients treated with bare metal stents (BMS) worldwide. Both in case of BMS and DES emerging evidence from recent histopathological studies on coronary resected stents shows that the outcome of PCI can be influenced by the occurrence of in stent neo- atherosclerosis, in DES more frequent than in BMS, which in turn may stimulate both thrombosis and restenosis on the very long term. PMID:23229368

  12. Chlamydia pneumoniae and coronary artery disease: the antibiotic trials.

    PubMed

    Higgins, John P

    2003-03-01

    Parallel with the mounting evidence that atherosclerosis has a major inflammatory component, provoking agents that may initiate and drive this process have been sought. Infectious agents such as Chlamydia pneumoniae have been alleged to be activators of inflammation that may contribute to atherosclerosis and thus coronary artery disease (CAD) and its associated complications. A logical pneumoniae extension of this theory whether treating C pneumoniae infection with antibiotics and/or modulating inflammatory processes can affect CAD and its sequelae. This article discusses the potential role of C pneumoniae in atherosclerosis, its detection, and the rationale for antibiotics. Additionally, it summarizes the current randomized clinical trials of antichlamydial antibiotics in patients with CAD and draws conclusions based on the results. PMID:12630585

  13. Targeted Disruption of LDLR Causes Hypercholesterolemia and Atherosclerosis in Yucatan Miniature Pigs

    PubMed Central

    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. PMID:24691380

  14. Oxyradical Stress, Endocannabinoids, and Atherosclerosis

    PubMed Central

    Matthews, Anberitha T.; Ross, Matthew K.

    2015-01-01

    Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS) have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB) is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ) is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG). Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS) in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology. PMID:26702404

  15. Motexafin lutetium in graft coronary artery disease

    NASA Astrophysics Data System (ADS)

    Woodburn, Kathryn W.; Rodriquez, Shari L.; Yamaguchi, Atsushi; Hayase, Motoya; Robbins, Robert C.; Kessel, David

    2000-03-01

    Graft coronary artery disease (GCAD) is the chief complication following cardiac transplantation. Presently, there are limited treatment options. Insights into more expedient diagnosis and amelioration, if only partially, of GCAD are fervently sought. The selectivity of Antrin Injection (Lu-Tex) with subsequent photoactivation has been evaluated in several preclinical atherosclerosis models. The inhibitory effect of Lu-Tex induced photosensitization was demonstrated with human bypass coronary smooth muscle cells. The biodistribution of Lu-Tex was evaluated in a rat model of heterotopic cardiac allografts 60 days following transplantation. Lu-Tex was retained in the cardiac allograft, exhibiting a five-fold increase in retention between the allograft and native heart. These findings lead us to suggest that further studies are warranted to ascertain the merits of Lu-Tex for the diagnosis and possible attenuation of chronic graft vascular disease.

  16. Severe familial hypercholesterolemia impairs the regulation of coronary blood flow and oxygen supply during exercise.

    PubMed

    Bender, Shawn B; de Beer, Vincent J; Tharp, Darla L; Bowles, Douglas K; Laughlin, M Harold; Merkus, Daphne; Duncker, Dirk J

    2016-11-01

    Accelerated development of coronary atherosclerosis is a defining characteristic of familial hypercholesterolemia (FH). However, the recent data highlight a significant cardiovascular risk prior to the development of critical coronary stenosis. We, therefore, examined the hypothesis that FH produces coronary microvascular dysfunction and impairs coronary vascular control at rest and during exercise in a swine model of FH. Coronary vascular responses to drug infusions and exercise were examined in chronically instrumented control and FH swine. FH swine exhibited ~tenfold elevation of plasma cholesterol and diffuse coronary atherosclerosis (20-60 % plaque burden). Similar to our recent findings in the systemic vasculature in FH swine, coronary smooth muscle nitric oxide sensitivity was increased in vivo and in vitro with maintained endothelium-dependent vasodilation in vivo in FH. At rest and during exercise, FH swine exhibited increased myocardial O2 extraction resulting in reduced coronary venous SO2 and PO2 versus control. During exercise in FH swine, the transmural distribution of coronary blood flow was unchanged; however, a shift toward anaerobic cardiac metabolism was revealed by increased coronary arteriovenous H(+) concentration gradient. This shift was associated with a worsening of cardiac efficiency (relationship between cardiac work and O2 consumption) in FH during exercise owing, in part, to a generalized reduction in stroke volume which was associated with increased left atrial pressure in FH. Our data highlight a critical role for coronary microvascular dysfunction as a contributor to impaired myocardial O2 balance, cardiac ischemia, and impaired cardiac function prior to the development of critical coronary stenosis in FH. PMID:27624732

  17. Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis

    PubMed Central

    He, Ka; Liu, Kiang; Daviglus, Martha L.; Mayer-Davis, Elisabeth; Jenny, Nancy Swords; Jiang, Rui; Ouyang, Pamela; Steffen, Lyn M.; Siscovick, David; Wu, Colin; Barr, R. Graham; Tsai, Michael; Burke, Gregory L.

    2014-01-01

    Background Data on the relations of different types of fish meals and long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) with measures of atherosclerosis are sparse. Objective We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis. Design A cross-sectional study was conducted in 5,488 multiethnic adults aged 45–84 years and free of clinical cardiovascular disease. Diet was assessed using self-administered food frequency questionnaires. Subclinical atherosclerosis was determined by common carotid intima-media thickness (cCIMT, >80th percentile), internal CIMT (iCIMT, >80th percentile), coronary artery calcium score (CAC, >0) or ankle-brachial index (ABI, <0.90), respectively. Results After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and non-fried (broiled, steamed, baked or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not iCIMT, CAC or ABI. The multivariable odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; p for trend<0.01) for n-3 PUFA intake, 0.80 (95% CI: 0.64, 1.01; p=0.054) for non-fried fish and 0.90 (95% CI: 0.73, 1.10; p=0.33) for fried fish consumption. Conclusions This study indicates that dietary intake of long-chain n-3 PUFAs or non-fried fish is associated with lower prevalence of subclinical atherosclerosis classified by cCIMT although significant changes in iCIMT, CAC and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis. PMID:18842801

  18. Multi-Ethnic Study of Atherosclerosis: objectives and design.

    PubMed

    Bild, Diane E; Bluemke, David A; Burke, Gregory L; Detrano, Robert; Diez Roux, Ana V; Folsom, Aaron R; Greenland, Philip; Jacob, David R; Kronmal, Richard; Liu, Kiang; Nelson, Jennifer Clark; O'Leary, Daniel; Saad, Mohammed F; Shea, Steven; Szklo, Moyses; Tracy, Russell P

    2002-11-01

    The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality. PMID:12397006

  19. Therapeutic approaches to drug targets in atherosclerosis.

    PubMed

    Jamkhande, Prasad G; Chandak, Prakash G; Dhawale, Shashikant C; Barde, Sonal R; Tidke, Priti S; Sakhare, Ram S

    2014-07-01

    Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

  20. Endothelium Preserving Microwave Treatment for Atherosclerosis

    NASA Technical Reports Server (NTRS)

    Fink, Patrick; Arndt, G. D.; Ngo, Phong

    2003-01-01

    This slide presentation reviews the use of microwave technology for treating Atherosclerosis while preserving the endothelium. The system uses catheter antennas as part of the system that is intended to treat atherosclerosis. The concept is to use a microwave catheter for heating the atherosclerotic lesions, and reduce constriction in the artery.

  1. Anomalous origin of the right coronary artery from the left anterior descending artery: review of the literature.

    PubMed

    Yurtdaş, Mustafa; Gülen, Oktay

    2012-01-01

    Coronary artery anomalies that take place during fetal development are determined in approximately 1.3% of coronary angiograms. The right coronary artery originating from the left coronary system is an extremely rare variation of the single coronary artery anomaly in which the prognosis is usually benign provided that the anomalous vessel dose not pass between the aorta and the pulmonary artery. Anomalous right coronary artery anomaly has been rarely associated with other congenital cardiovascular anomalies such as transposition of the great vessels and tetralogy of Fallot. To date, a few attempts at classification have been made for coronary artery anomalies, but none of them seems comprehensive or practical for clinicians. The clinical significance of coronary anomalies is usually determined by underlying anatomic features of the wrong coronary origin and/or coronary atherosclerosis. Although coronary angiography is an important diagnostic method, new non-invasive methods such as coronary computed tomography angiography and cardiac magnetic resonance imaging have important roles to play in characterizing this coronary anomaly. It should be noted that the management strategy of these patients may vary based on clinical presentation, anatomical details and additional findings. PMID:22461044

  2. Quantification of carotid vessel atherosclerosis

    NASA Astrophysics Data System (ADS)

    Chiu, Bernard; Egger, Micaela; Spence, J. D.; Parraga, Grace; Fenster, Aaron

    2006-03-01

    Atherosclerosis is characterized by the development of plaques in the arterial wall, which ultimately leads to heart attacks and stroke. 3D ultrasound (US) has been used to screen patients' carotid arteries. Plaque measurements obtained from these images may aid in the management and monitoring of patients, and in evaluating the effect of new treatment options. Different types of measures for ultrasound phenotypes of atherosclerosis have been proposed. Here, we report on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US images obtained at two different time points. We evaluated our technique using manual segmentations of the wall and lumen of the carotid artery from images acquired in two US scanning sessions. To incorporate the effect of intraobserver variability in our evaluation, manual segmentation was performed five times each for the arterial wall and lumen. From this set of five segmentations, the mean wall and lumen surfaces were reconstructed, with the standard deviation at each point mapped onto the surfaces. A correspondence map between the mean wall and lumen surfaces was then established, and the thickness of the atherosclerotic plaque at each point in the vessel was estimated to be the distance between each correspondence pairs. The two-sample Student's t-test was used to judge whether the difference between the thickness values at each pair corresponding points of the arteries in the two 3D US images was statistically significant.

  3. Role of LCAT in Atherosclerosis.

    PubMed

    Ossoli, Alice; Simonelli, Sara; Vitali, Cecilia; Franceschini, Guido; Calabresi, Laura

    2016-01-01

    Lecithin:cholesterol acyltransferase (LCAT) is the only enzyme capable of esterifying cholesterol in plasma, thus determining the maturation of high-density lipoproteins. Because it maintains an unesterified cholesterol gradient between peripheral cells and extracellular acceptors, for a long time, LCAT has been considered as a key enzyme in reverse cholesterol transport. However, despite the fact that it has been more than 50 years since the identification of LCAT, the role of this enzyme in the pathogenesis of atherosclerosis is still debated. A number of studies have been conducted in different animal models, with contradictory results. Studies in humans, in particular in the general population, in subjects at high cardiovascular risk, and in carriers of genetic LCAT deficiency in an excellent model to evaluate the correlation between the reduction of LCAT activity and atherosclerosis also gave conflicting results. This review provides a comprehensive overview of the controversial findings obtained in animals and humans, strengthening the necessity of further investigation to establish how LCAT could be regulated in a promising therapeutic strategy to reduce cardiovascular risk. PMID:26607351

  4. Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits

    PubMed Central

    Wang, Yao; Niimi, Manabu; Nishijima, Kazutoshi; Waqar, Ahmed Bilal; Yu, Ying; Koike, Tomonari; Kitajima, Shuji; Liu, Enqi; Inoue, Tomohiro; Kohashi, Masayuki; Keyamura, Yuka; Yoshikawa, Tomohiro; Zhang, Jifeng; Ma, Loretta; Zha, Xiaohui; Watanabe, Teruo; Asada, Yujiro; Chen, Y. Eugene; Fan, Jianglin

    2013-01-01

    Objective Apolipoprotein A-II (apo A-II) is the second major apolipoprotein of HDLs, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and if so, to elucidate the mechanism involved. Methods and Results We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma CRP and blood leukocytes compared to non-Tg rabbits and HDLs of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than HDLs isolated from non-Tg rabbits. In addition, β-VLDLs of Tg rabbits were less sensitive to copper-induced oxidation than β-VLDLs of non-Tg rabbits. Conclusions These results suggest that enrichment of apo A-II in HDL particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis. PMID:23241412

  5. The roles of macrophage autophagy in atherosclerosis

    PubMed Central

    Shao, Bo-zong; Han, Bin-ze; Zeng, Yan-xia; Su, Ding-feng; Liu, Chong

    2016-01-01

    Although various types of drugs and therapies are available to treat atherosclerosis, it remains a major cause of mortality throughout the world. Macrophages are the major source of foam cells, which are hallmarks of atherosclerotic lesions. Consequently, the roles of macrophages in the pathophysiology of atherosclerosis are increasingly investigated. Autophagy is a self-protecting cellular catabolic pathway. Since its discovery, autophagy has been found to be associated with a variety of diseases, including cardiovascular diseases, malignant tumors, neurodegenerative diseases, and immune system disorders. Accumulating evidence demonstrates that autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis and cholesterol efflux. These facts suggest the induction of autophagy may be exploited as a potential strategy for the treatment of atherosclerosis. In this review we mainly discuss the relationship between macrophage autophagy and atherosclerosis and the molecular mechanisms, as well as the recent advances in targeting the process of autophagy to treat atherosclerosis. PMID:26750103

  6. Vasa Vasorum in Atherosclerosis and Clinical Significance

    PubMed Central

    Xu, Junyan; Lu, Xiaotong; Shi, Guo-Ping

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. PMID:26006236

  7. Anxiety, Depression, and General Psychological Distress in Patients with Coronary Slow Flow

    PubMed Central

    Karataş, Mehmet Baran; Şahan, Ebru; Özcan, Kazım Serhan; Çanga, Yiğit; Güngör, Barış; Onuk, Tolga; İpek, Göktürk; Çakıllı, Yasin; Arugaslan, Emre; Bolca, Osman

    2015-01-01

    Background The relationship between psychiatric illness and heart disease has been frequently discussed in the literature. The aim of the present study was to investigate the relationship between anxiety, depression and overall psychological distress, and coronary slow flow (CSF). Methods In total, 44 patients with CSF and a control group of 50 patients with normal coronary arteries (NCA) were prospectively recruited. Clinical data, admission laboratory parameters, and echocardiographic and angiographic characteristics were recorded. Symptom Checklist 90 Revised (SCL-90-R), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scales were administered to each patient. Results The groups were comparable with respect to age, sex, and atherosclerotic risk factors. In the CSF group, BAI score, BDI score, and general symptom index were significantly higher than controls (13 [18.7] vs. 7.5 [7], p = 0.01; 11 [14.7] vs. 6.5 [7], p = 0.01; 1.76 [0.81] vs. 1.1[0.24], p = 0.01; respectively). Patients with CSF in more than one vessel had the highest test scores. In univariate correlation analysis, mean thrombolysis in myocardial infarction (TIMI) frame counts were positively correlated with BAI (r = 0.56, p = 0.01), BDI (r = 0.47, p = 0.01), and general symptom index (r = 0.65, p = 0.01). The psychiatric tests were not correlated with risk factors for atherosclerosis. Conclusion Our study revealed higher rates of depression, anxiety, and overall psychological distress in patients with CSF. This conclusion warrants further studies. PMID:26559983

  8. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Atherosclerosis

    MedlinePlus

    ... disease in which plaque builds up inside your arteries. Plaque is a sticky substance made up of ... blood. Over time, plaque hardens and narrows your arteries. That limits the flow of oxygen-rich blood ...

  11. Atherosclerosis

    MedlinePlus

    ... heart health as EPA and DHA. Red yeast rice. A common seasoning in Asian countries, red yeast rice may help reduce the amount of cholesterol your ... Talk to your doctor before taking red yeast rice, especially if you take another cholesterol-lowering medicine ...

  12. Individual with Subclinical Atherosclerosis Have Impaired Proliferation of Blood Outgrowth Endothelial Cells, Which Can Be Restored by Statin Therapy

    PubMed Central

    Hofman, Menno; Bierings, Ruben; Creemers, Esther E.; Meijers, Joost C. M.; Voorberg, Jan; Pinto-Sietsma, Sara-Joan

    2014-01-01

    Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Methods and Results Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21–0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. Conclusion BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration. PMID:24955753

  13. Sex Differences in Subclinical Atherosclerosis by Race/Ethnicity in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Kim, Catherine; Diez-Roux, Ana V.; Nettleton, Jennifer A.; Polak, Joseph F.; Post, Wendy S.; Siscovick, David S.; Watson, Karol E.; Vahratian, Anjel M.

    2011-01-01

    Sex differences in cardiovascular disease mortality are more pronounced among non-Hispanic whites than other racial/ethnic groups, but it is unknown whether this variation is present in the earlier subclinical stages of disease. The authors examined racial/ethnic variation in sex differences in coronary artery calcification (CAC) and carotid intimal media thickness at baseline in 2000–2002 among participants (n = 6,726) in the Multi-Ethnic Study of Atherosclerosis using binomial and linear regression. Models adjusted for risk factors in several stages: age, traditional cardiovascular disease risk factors, behavioral risk factors, psychosocial factors, and adult socioeconomic position. Women had a lower prevalence of any CAC and smaller amounts of CAC when present than men in all racial/ethnic groups. Sex differences in the prevalence of CAC were more pronounced in non-Hispanic whites than in African Americans and Chinese Americans after adjustment for traditional cardiovascular disease risk factors, and further adjustment for behavioral factors, psychosocial factors, and socioeconomic position did not modify these results (for race/sex, Pinteraction = 0.047). Similar patterns were observed for amount of CAC among adults with CAC. Racial/ethnic variation in sex differences for carotid intimal media thickness was less pronounced. In conclusion, coronary artery calcification is differentially patterned by sex across racial/ethnic groups. PMID:21685409

  14. Helicobacter pylori: Does it add to risk of coronary artery disease

    PubMed Central

    Sharma, Vishal; Aggarwal, Amitesh

    2015-01-01

    Helicobacter pylori (H. pylori) is a known pathogen implicated in genesis of gastritis, peptic ulcer disease, gastric carcinoma and gastric lymphoma. Beyond the stomach, the organism has also been implicated in the causation of immune thrombocytopenia and iron deficiency anemia. Although an area of active clinical research, the role of this gram negative organism in causation of atherosclerosis and coronary artery disease (CAD) remains enigmatic. CAD is a multifactorial disease which results from the atherosclerosis involving coronary arteries. The major risk factors include age, diabetes mellitus, smoking, hypertension and dyslipidemia. The risk of CAD is believed to increase with chronic inflammation. Various organisms like Chlamydia and Helicobacter have been suspected to have a role in genesis of atherosclerosis via causation of chronic inflammation. This paper focuses on available evidence to ascertain if the role of H. pylori in CAD causation has been proven beyond doubt and if eradication may reduce the risk of CAD or improve outcomes in these patients. PMID:25632315

  15. 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

  16. [Prevention of coronary heart disease: smoking].

    PubMed

    Heitzer, T; Meinertz, T

    2005-01-01

    Smoking is the leading preventable cause of illness and premature death in Germany, claiming over 110,000 lives a year because it directly increases the risk of dying from heart disease, stroke, emphysema and a variety of cancers. The overwhelming majority of smokers begin tobacco use before they reach adulthood. Among those young people who smoke, the average age is now 13-14. In Germany, about 39% of male and 31% of female adults (age 18-60 years) continue to smoke, despite information about the unequivocally negative health consequences of smoking. The exact mechanisms of smoking-related vascular disease are not yet known. Smoking causes acute hemodynamic alterations such as increase in heart rate, systematic and coronary vascular resistance, myocardial contractility, and myocardial oxygen demand. These short-term effects could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for acute cardiovascular events. Endothelial damage is thought to be an initiating event in atherosclerosis and early studies have demonstrated that long-term smoking has direct toxic effects with structural changes of human endothelial cells. Recent research has shown the importance of the functional role of the endothelium in regulating vascular tone, platelet-endothelial interactions, leukocyte adhesion and smooth muscle cell proliferation via synthesis and release of a variety of substances such as nitric oxide. There is strong evidence that smoking leads to endothelial dysfunction mainly by increased inactivation of nitric oxide by oxygen-derived free radicals. Smoking also increases oxidative modification of LDL and is associated with lower HDL plasma levels. Smoking induces a systemic inflammatory response with increased leukocyte count and elevation of the C-reactive protein level. Importantly, the prothrombotic effects of smoking have been repeatedly demonstrated to cause alterations in platelet function, imbalance of

  17. 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.

  18. A Case of Isolated Coronary Artery Ectasia in the Setting of Chronic Inflamation From human Immunodeficiency Virus Infection.

    PubMed

    Heckle, Mark R; Askari, Raza; Morsy, Mohamed; Ibebuogu, Uzoma N

    2016-01-01

    Coronary artery ectasia also known as dilated coronopathy is a relatively rare finding that is most commonly associated with atherosclerosis. Several alternative reasons including congenital malformations and chronic inflammation have been identified as a cause of CAE. In this case, we discuss a 61-year-old male with postoperative chest pain who was found to have localized CAE in the absence of significant atherosclerosis. We also elucidate the recently proposed markers of chronic inflammation that might be associated with coronary artery ectasia. PMID:27598894

  19. Decreased Naive and Increased Memory CD4+ T Cells Are Associated with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Olson, Nels C.; Doyle, Margaret F.; Jenny, Nancy Swords; Huber, Sally A.; Psaty, Bruce M.; Kronmal, Richard A.; Tracy, Russell P.

    2013-01-01

    Background Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis. Methods and Findings We examined cross-sectional relationships of circulating CD4+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Circulating CD4+ naive cells were higher in women than men and decreased with age (all p-values <0.0001). European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005). Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV) and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05). Higher memory cells were associated with coronary artery calcification (CAC) level in the overall population [β-Coefficient (95% confidence interval (CI))  = 0.20 (0.03, 0.37)]. Memory and naive (inversely) cells were associated with common carotid artery intimal media thickness (CC IMT) in European-Americans [memory: β =  0.02 (0.006, 0.04); naive: β = −0.02 (−0.004, −0.03)]. Conclusions These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4+ T cells, and with innate immunity (inflammation), in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by

  20. Quantitative Relation between Coronary Calcium Content and Coronary Flow Reserve as Assessed by Integrated PET-CT Imaging

    PubMed Central

    Curillova, Zelmira; Yaman, Bettina F.; Dorbala, Sharmila; Kwong, Raymond Y.; Sitek, Arkadius; El Fakhri, Georges; Anagnostopoulos, Constantinos; Di Carli, Marcelo F.

    2011-01-01

    Background Coronary artery calcium (CAC) is a marker of atherosclerosis. Whether epicardial calcium reflects more widespread atherosclerosis affecting coronary vascular function is unknown. Methods We evaluated 136 consecutive patients without known coronary disease (age 62 ±12 years, 68 % females) undergoing vasodilator stress 82Rb PET and CAC scoring based on clinical grounds. Patients with normal myocardial perfusion on standard semi-quantitative analysis were included. The Agatston CAC score, rest and stress myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary vascular resistance (CVR) were quantified and analyzed on a per patient and per vascular territory basis. Results Global and regional CAC scores showed modest but significant correlation with hyperemic MBF (r= −0.31 and r= −0.26, p≤0.0002, respectively), CFR (r= −0.28 and r= −0.2, p≤0.001, respectively), and CVR during peak hyperemia (r=0.32 and r= 0.26, p≤0.0002, respectively). There was a modest stepwise decline of mean CFR with increasing CAC score on per patient analysis (1.8 ±0.5 vs 1.7 ±0.5 vs 1.5±0.4, p=0.048 with total CAC= 0, 1-400 and >400 respectively) and per vessel analysis (1.8 ±0.6 vs 1.6 ±0.4 vs 1.5 ±0.5 vs 1.5 ±0.5, p=0.004 with vessel CAC score= 0, 1-100, 101-400 and >400 respectively). In multivariable modeling only body mass index (p=0.005), CAC score (p =0.04) and hypertension (p=0.05) remained predictive. Conclusions In patients without overt CAD, there is a modest but statistically significant inverse relationship between CAC content and coronary vasodilator function, which persists after adjusting for the effect of coronary risk factors. PMID:19387640

  1. A new method for IVUS-based coronary artery disease risk stratification: A link between coronary & carotid ultrasound plaque burdens.

    PubMed

    Araki, Tadashi; Ikeda, Nobutaka; Shukla, Devarshi; Londhe, Narendra D; Shrivastava, Vimal K; Banchhor, Sumit K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Suri, Jasjit S

    2016-02-01

    Interventional cardiologists have a deep interest in risk stratification prior to stenting and percutaneous coronary intervention (PCI) procedures. Intravascular ultrasound (IVUS) is most commonly adapted for screening, but current tools lack the ability for risk stratification based on grayscale plaque morphology. Our hypothesis is based on the genetic makeup of the atherosclerosis disease, that there is evidence of a link between coronary atherosclerosis disease and carotid plaque built up. This novel idea is explored in this study for coronary risk assessment and its classification of patients between high risk and low risk. This paper presents a strategy for coronary risk assessment by combining the IVUS grayscale plaque morphology and carotid B-mode ultrasound carotid intima-media thickness (cIMT) - a marker of subclinical atherosclerosis. Support vector machine (SVM) learning paradigm is adapted for risk stratification, where both the learning and testing phases use tissue characteristics derived from six feature combinational spaces, which are then used by the SVM classifier with five different kernels sets. These six feature combinational spaces are designed using 56 novel feature sets. K-fold cross validation protocol with 10 trials per fold is used for optimization of best SVM-kernel and best feature combination set. IRB approved coronary IVUS and carotid B-mode ultrasound were jointly collected on 15 patients (2 days apart) via: (a) 40MHz catheter utilizing iMap (Boston Scientific, Marlborough, MA, USA) with 2865 frames per patient (42,975 frames) and (b) linear probe B-mode carotid ultrasound (Toshiba scanner, Japan). Using the above protocol, the system shows the classification accuracy of 94.95% and AUC of 0.95 using optimized feature combination. This is the first system of its kind for risk stratification as a screening tool to prevent excessive cost burden and better patients' cardiovascular disease management, while validating our two hypotheses

  2. Cell-free nucleic acids as a non-invasive route for investigating atherosclerosis.

    PubMed

    Cerne, Darko; Bajalo, Jana Lukac

    2014-01-01

    Metabolic syndrome is directly linked with atherosclerotic burden and cell-free nucleic acids (cf-NA) analysis has recently emerged as a novel research tool in atherosclerosis practice and research. cf-NA are nucleic acids (DNA, mRNA, miRNA, mitochondrial DNA) found in plasma and cell-free fractions of various other biological fluids. They have all the characteristics of the nucleic acids in the cells of their origin, thus constituting an emerging field for non-invasive assessment. Initially, quantitative and qualitative analysis of cf-NA has been accepted as clinically useful in non-invasive prenatal diagnosis, and in the diagnosis and monitoring of numerous cancers. As to atherosclerosis, cf-NA analysis poses an important challenge in diagnosis and prognostic evaluation of acute coronary syndrome, in prediction of cardiovascular disease, in non-invasive early detection of atherosclerosis and understanding its pathological mechanism in vivo, in assessing various issues of treatment for atherosclerosis in vivo, and in the unique simultaneous measurement of mRNA levels and protein concentrations in a single sample of plasma. Examples of its use are presented in this review. Besides the advances in technologies, the precise evaluation and optimization of pre-analytical and analytical aspects of cf-NA analysis have impacted importantly on the reliability of test results. We have, therefore, reviewed the most important analytical considerations. Further clinical studies and analytical improvements will answer the question as to whether cf-NA, as novel biomarkers, can be reliably applied clinically in non-invasive, early diagnosis and monitoring of the vulnerable atherosclerotic plaques of patients who could suffer from acute coronary syndrome. PMID:24320033

  3. Effect of exercise-based cardiac rehabilitation on non-culprit mild coronary plaques in the culprit coronary artery of patients with acute coronary syndrome.

    PubMed

    Kurose, Satoshi; Iwasaka, Junji; Tsutsumi, Hiromi; Yamanaka, Yutaka; Shinno, Hiromi; Fukushima, Yaeko; Higurashi, Kyoko; Imai, Masaru; Masuda, Izuru; Takeda, Shinichi; Kawai, Chuichi; Kimura, Yutaka

    2016-06-01

    Approximately, 70 % of acute myocardial infarctions are known to develop from mild atherosclerotic lesions. Therefore, it is important to evaluate mild coronary plaques to prevent acute coronary syndrome (ACS). The aim of the present study was to investigate the effects of exercise-based cardiac rehabilitation (CR) on mild coronary atherosclerosis in non-culprit lesions in patients with ACS. Forty-one men with ACS who underwent emergency percutaneous coronary interventions and completed a 6-month follow-up were divided into CR and non-CR groups. Quantitative coronary angiography (QCA) was performed using the automatic edge detection program. The target lesion was a mild stenotic segment (10-50 % stenosis) at the distal site of the culprit lesion, and the segment to be analyzed was determined at a segment length ranging from 10 to 15 mm. The plaque area was significantly decreased in the CR group after 6 months, but was significantly increased in the non-CR group (P < 0.05). The low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL) ratio and high-sensitivity C-reactive protein (Hs-CRP) levels were significantly reduced in both groups (P < 0.01). Peak VO2 in the CR group was significantly increased (P < 0.01). Changes in the plaque area correlated with those in Hs-CRP in both groups, while that association with those in HDL-C was observed in only CR group. Stepwise regression analysis revealed the decrease in Hs-CRP as an independent predictor of plaque area regression in the CR group. CR prevented the progression of mild coronary atherosclerosis in patients with ACS. PMID:25896129

  4. The effect of mannan-binding lectin variant alleles on coronary artery reactivity in healthy young men.

    PubMed

    Aittoniemi, Janne; Fan, Yue-Mei; Laaksonen, Reijo; Janatuinen, Tuula; Vesalainen, Risto; Nuutila, Pirjo; Knuuti, Juhani; Hulkkonen, Janne; Hurme, Mikko; Lehtimäki, Terho

    2004-11-01

    Mannan-binding lectin (MBL) is a serum acute-phase protein and a complement component secreted by the liver. Its deficiency caused by point mutations in the MBL gene has recently been associated with severe atherosclerosis. In this study, we investigated the effect of MBL variant alleles on coronary artery reactivity, which is an early marker of coronary dysfunction and predicts the development of atherosclerosis and coronary artery disease. The study population consisted of 51 apparently healthy, normo- or mildly hypercholesterolemic young men. Myocardial blood flow was measured at baseline and during adenosine-induced hyperemia with positron emission tomography (PET), and MBL genotyping was performed using restriction fragment-length polymorphism. As a result, MBL variant alleles had no effect on coronary artery reactivity. This finding suggests that MBL deficiency is not an independent risk factor for coronary dysfunction and early atherogenic changes but rather a co-factor in the development of atherosclerosis. Thus, the connection of MBL variant alleles with environmental risk factors in atherosclerosis should further be assessed. PMID:15458704

  5. Naringenin and atherosclerosis: a review of literature.

    PubMed

    Orhan, Ilkay E; Nabavi, Seyed F; Daglia, Maria; Tenore, Gian C; Mansouri, Kowsar; Nabavi, Seyed M

    2015-01-01

    Atherosclerosis is a multifactorial disease mainly caused by deposition of low-density lipoprotein (LD) cholesterol in macrophages of arterial walls. Atherosclerosis leads to heart attacks as well as stroke. Epidemiological studies showed that there is an inverse correlation between fruit and vegetable consumption and the risk of atherosclerosis. The promising effect of high vegetable and fruit containing diet on atherosclerosis is approved by several experimental studies on isolated phytochemicals such as flavonoids. Flavonoids are known to up-regulate endogenous antioxidant system, suppress oxidative and nitrosative stress, decrease macrophage oxidative stress through cellular oxygenase inhibition as well as interaction with several signal transduction pathways and from these ways, have therapeutic effects against atherosclerosis. Naringenin is a well known flavonoid belonging to the chemical class of flavanones. It is especially abundant in citrus fruits, especially grapefruits. A plethora of evidences ascribes to naringenin antiatherosclerotic effects. Naringenin abilities to decrease LDL and triglycerides as well as inhibit glucose uptake; increase high-density lipoprotein (HDL); co-oxidation of NADH; suppress protein oxidation; protect against intercellular adhesion molecule-1(ICAM-1); suppress macrophage inflammation; inhibit leukotriene B4, monocyte adhesion and foam cell formation; induce of HO-1 and G 0/G 1 cell cycle arrest in vascular smooth muscle cells (VSMC) and down regulate atherosclerosis related genes are believed to have crucial role in the promising role against atherosclerosis. In the present review, we have summarized the available literature data on the anti-atherosclerotic effects of naringenin and its possible mechanisms of action. PMID:25483717

  6. Platelets and the complement cascade in atherosclerosis

    PubMed Central

    Patzelt, Johannes; Verschoor, Admar; Langer, Harald F.

    2015-01-01

    Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will focus on roles for platelets in the onset as well as progression of the disease, a possible dual role for complement in the genesis and development of atherosclerosis, and review emerging literature revealing previously unrecognized cross-talk between platelets and the complement system and discuss its possible impact for atherosclerosis. Finally, we identify limitations of current research approaches and discuss perspectives of complement modulation in the control of the disease. PMID:25784879

  7. Hypercholesterolemia links hematopoiesis with atherosclerosis.

    PubMed

    Soehnlein, Oliver; Swirski, Filip K

    2013-03-01

    Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to the necrotic core of lesions. Lipids and leukocytes also interact in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol-sensing pathways control the proliferation of hematopoietic stem-cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation, and propose several strategies that could target this axis for the treatment of cardiovascular disease. PMID:23228326

  8. Association between adiposity and systemic atherosclerosis: a protocol of a cross-sectional autopsy study

    PubMed Central

    Nishizawa, Aline; Suemoto, Claudia Kimie; Farias, Daniela Souza; Campos, Fernanda Marinho; da Silva, Karen Cristina Souza; Cuelho, Anderson; Leite, Renata Elaine Paraízo; Ferretti-Rebustini, Renata Eloah de Lucena; Grinberg, Lea Tenenholz; Farfel, José Marcelo; Jacob-Filho, Wilson; Pasqualucci, Carlos Augusto

    2016-01-01

    Introduction Adiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study. Methods and analysis A sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and α=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at −80°C for future studies. Ethics and dissemination Ethical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal. PMID:27621828

  9. Inflammatory therapeutic targets in coronary atherosclerosis—from molecular biology to clinical application

    PubMed Central

    Linden, Fabian; Domschke, Gabriele; Erbel, Christian; Akhavanpoor, Mohammadreza; Katus, Hugo A.; Gleissner, Christian A.

    2014-01-01

    Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over 3 years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecular inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis. PMID:25484870

  10. Spontaneous coronary artery dissection: a neglected cause of acute myocardial ischaemia and sudden death.

    PubMed Central

    Basso, C.; Morgagni, G. L.; Thiene, G.

    1996-01-01

    Spontaneous coronary artery dissection is a rare cause of acute myocardial ischaemia. Eight consecutive fatal cases which occurred in women aged 34-54 years (mean 43) are described. The dissection involved the left anterior descending coronary artery in four, the left main trunk in two, the right coronary artery in one, and both left anterior descending and circumflex arteries in one. The clinical presentation was sudden death in six cases, and acute myocardial infarction in two. Diagnosis was made at necropsy in every case but one, in which coronary dissection was diagnosed during life by selective coronary angiography. The only ascertained risk factor was hypertension in one patient; none of the women was in the puerperium, and Marfan syndrome was excluded in all. Histology showed a haematoma between the coronary tunica media and adventitia, that flattened and occluded the lumen; a coronary intimal tear was detected in only two cases. Unusual histological findings were cystic medial necrosis in one case, eosinophilic inflammatory infiltrates in four, and angiomatosis of the tunica adventitia in one. Patients dying of spontaneous coronary dissection are usually middle aged women, with no coronary atherosclerosis and apparently no risk factors. Spontaneous coronary artery dissection is unpredictable, and sudden death is the usual mode of clinical presentation. Prompt diagnosis and life saving treatment is far from being achieved. Images PMID:8665336

  11. Serum IgE levels in coronary artery disease.

    PubMed

    Kounis, Nicholas G; Hahalis, George

    2016-08-01

    The development and progression of atherosclerosis and its predisposition for unstable angina, myocardial infarction and stroke is associated with traditional risk factors such as family history, cigarette smoking, hypertension, dyslipidemia, diabetes mellitus, obesity, imbalance of the hemostatic/fibrinolytic system and sedentary lifestyle. However, much of the variability in atherosclerosis and its manifestations still remains unexplained. Nowadays, there is increasing evidence that immunologic mechanisms play a major role in etiology, prediction of coronary plaque instability and foreseeing severe reaction leading to an actual coronary event. Cells of the immune system such as macrophages, mast cells and T-lymphocytes are major components of human atheromatous plaque. These cells participate in a vicious immune cycle and activate each others via bidirectional stimuli. For example, mast cells can activate macrophages and may enhance T-cell activation. Inducible macrophage protein 1a may activate mast cells, while CD169+ macrophages activate CD8 T cells. T cells may mediate mast-cell activation and proliferation and regulate macrophage activity. Mediators secreted by these cells, including histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines, can induce coronary artery spasm and atheromatous plaque erosion and rupture, culminating in the development of acute coronary syndromes. PMID:27288268

  12. History of Discovery: Inflammation in Atherosclerosis

    PubMed Central

    Libby, Peter

    2012-01-01

    Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances. PMID:22895665

  13. Aorta Atherosclerosis Lesion Analysis in Hyperlipidemic Mice

    PubMed Central

    Mohanta, Sarajo; Yin, Changjun; Weber, Christian; Hu, Desheng; Habenicht, Andreas JR

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. Apolipoprotein E-deficient (ApoE-/-) mice are used as experimental models to study human atherosclerosis. ApoE-/- mice are constitutively hyperlipidemic and develop intima plaques that resemble human plaques. Various issues including experimental design for lesion analysis, dietary conditions, isolation of the aorta, staining methods, morphometry, group size, age, the location within the arterial tree, and statistical analyses are important parameters that need to be addressed to obtain robust data. Here, we provide detailed methods to quantify aorta atherosclerosis. PMID:27366759

  14. Methylarginines in Mice with Experimental Atherosclerosis.

    PubMed

    Gilinsky, M A; Sukhovershin, R A; Cherkanova, M S

    2015-11-01

    We studied the dynamics of indexes for the system of endogenous regulation of NO bioavailability. The content of NO synthase inhibitors (monomethylarginine and asymmetric dimethylarginine) in the blood of mice was measured after intraperitoneal injections of a nonionic surfactant poloxamer 407 for 2 and 14 weeks. The concentrations of both methylarginines in animals with atherosclerosis due to 14-week administration of poloxamer were much higher than in control specimens. The amount of arginine and symmetric dimethylarginine practically did not differ from the control. Poloxamer-induced model of atherosclerosis is characterized by increased content of NO synthase inhibitors. These changes contribute to the development of endothelial dysfunction and atherosclerosis. PMID:26601840

  15. Illness beliefs in schizophrenia.

    PubMed

    Kinderman, Peter; Setzu, Erika; Lobban, Fiona; Salmon, Peter

    2006-10-01

    Beliefs about health and illness shape emotional responses to illness, health-related behaviour and relationships with health-care providers in physical illness. Researchers are beginning to study the illness beliefs of people with psychosis, primarily using models developed in relation to physical illness. It is likely that modifications to these models will be necessary if they are to apply to mental disorders, and it is probable that some of the assumptions underlying the models will be inappropriate. In particular, different dimensions of understanding may be present in mental illness in comparison to those identified in physical illness. The present study examines the beliefs of 20 patients in the UK diagnosed with schizophrenia, including 10 currently psychotic inpatients and 10 outpatients in remission, about their experiences, using qualitative interviews and thematic analysis. Patients currently experiencing psychosis did not identify their experiences as separable 'illnesses' and did not have 'illness beliefs'. Patients currently in a period of remission appraised their experiences as distinct from their own normal behaviour, but used conceptual frameworks of understanding that deviated significantly from conventional 'health belief' models. Patients' ways of understanding mental illness did not parallel those described in physical illnesses. Methods for assessing beliefs about mental illness should therefore not be transferred directly from studies of beliefs about physical illness, but should be tailored to the nature of patients' beliefs about mental illness. PMID:16777306

  16. Coronary Artery Disease in the Human Immunodeficiency Virus Seropositive Population.

    PubMed

    Barakat, Michael G; Arora, Rohit R

    2016-01-01

    The development of efficient combined antiretroviral therapies has lengthened the mean life span of the population affected with human immunodeficiency virus (HIV) transforming this terminal infection to a chronic yet manageable disease. Nonetheless, patients with HIV--treatment naive or not--exhibit larger risks for coronary artery disease than the noninfected population. Moreover, coronary atherosclerosis/arteriosclerosis may be the most prevalent condition in the HIV-infected population that is being accentuated by the effects of viral agents and the antiretroviral drugs, especially protease inhibitors. Nonetheless, generalized metabolic dysfunctions and premature senescence are often attributed to the viremia caused by the HIV infection directly and primarily. Therefore, a multifactorial approach is to be considered when attempting to explain the strong correlation between HIV and coronary artery disease, including co-opportunistic viremias and vitamin D insufficiency/deficiency. PMID:23797758

  17. 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

  18. 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.

  19. Patient-Specific Computational Models of Coronary Arteries Using Monoplane X-Ray Angiograms

    PubMed Central

    Zifan, Ali

    2016-01-01

    Coronary artery disease (CAD) is the most common type of heart disease in western countries. Early detection and diagnosis of CAD is quintessential to preventing mortality and subsequent complications. We believe hemodynamic data derived from patient-specific computational models could facilitate more accurate prediction of the risk of atherosclerosis. We introduce a semiautomated method to build 3D patient-specific coronary vessel models from 2D monoplane angiogram images. The main contribution of the method is a robust segmentation approach using dynamic programming combined with iterative 3D reconstruction to build 3D mesh models of the coronary vessels. Results indicate the accuracy and robustness of the proposed pipeline. In conclusion, patient-specific modelling of coronary vessels is of vital importance for developing accurate computational flow models and studying the hemodynamic effects of the presence of plaques on the arterial walls, resulting in lumen stenoses, as well as variations in the angulations of the coronary arteries. PMID:27403203

  20. Percutaneous coronary angioscopy with a new steerable microangioscope: experimental and early clinical results

    NASA Astrophysics Data System (ADS)

    Ramee, Stephen R.; White, Christopher J.; Mesa, Juan E.; Murgo, Joseph P.; Doyle, Andrew T.; McQueen, Colleen L.

    1990-07-01

    We have developed a new, steerable microangioscope for performing percutaneous coronary angioscopy. The angioscopic catheter is made of polyethylene, contains a distal balloon for occlusion of blood flow during imaging, fits through an 8 Fr percutaneous coronary angioplasty (PTCA) guiding catheter and is steerable by means of a guidewire. Initial feasibility was demonstrated in animal studies involving both peripheral and coronary arteries. Angioscopic findings in normal vessels included normal endothelial surface, collateral blood flow, and side branches. Angioscopy was also performed after balloon denudation of the arteries, laser- assisted balloon angioplasty, and stent implantation. In early human clinical trials we have performed percutaneous angioscopy in six patients undergoing percutaneous coronary angioplasty without complications. Findings in these patients include atherosclerotic plaque, thrombus, and dissection. This new device has great potential for use in the research, diagnosis, and treatment of coronary atherosclerosis.

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

    PubMed

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

    2015-12-01

    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

  2. Vasoprotective Effects of Urocortin 1 against Atherosclerosis In Vitro and In Vivo

    PubMed Central

    Shirai, Remina; Watanabe, Rena; Yamamoto, Keigo; Watanabe, Kaho; Nohtomi, Kyoko; Hirano, Tsutomu; Watanabe, Takuya

    2014-01-01

    Aim Atherosclerosis is the complex lesion that consists of endothelial inflammation, macrophage foam cell formation, vascular smooth muscle cell (VSMC) migration and proliferation, and extracellular matrix production. Human urocortin 1 (Ucn1), a 40-amino acid peptide member of the corticotrophin-releasing factor/urotensin I family, has potent cardiovascular protective effects. This peptide induces potent and long-lasting hypotension and coronary vasodilation. However, the relationship of Ucn1 with atherosclerosis remains unclear. The present study was performed to clarify the effects of Ucn1 on atherosclerosis. Methods We assessed the effects of Ucn1 on the inflammatory response and proliferation of human endothelial cells (ECs), human macrophage foam cell formation, migration and proliferation of human VSMCs, extracellular matrix expression in VSMCs, and the development of atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Results Ucn1 significantly suppressed cell proliferation without inducing apoptosis, and lipopolysaccharide-induced up-regulation of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 in human ECs. Ucn1 significantly reduced oxidized low-density lipoprotein-induced foam cell formation with a significant down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase 1 in human monocyte-derived macrophages. Ucn1 significantly suppressed the migration and proliferation of human VSMCs and increased the activities of matrix metalloproteinase-2 (MMP2) and MMP9 in human VSMCs. Intraperitoneal injection of Ucn1 into Apoe−/− mice for 4 weeks significantly retarded the development of aortic atherosclerotic lesions. Conclusions This study provided the first evidence that Ucn1 prevents the development of atherosclerosis by suppressing EC inflammatory response and proliferation, macrophage foam cell formation, and VSMC migration and proliferation. Thus, Ucn1 could serve as a novel therapeutic target for

  3. Cytomegalovirus in Plasma of Acute Coronary Syndrome Patients

    PubMed Central

    Nikitskaya, E. A.; Grivel, J.C.; Maryukhnich, E. V.; Lebedeva, A. M.; Ivanova, O. I.; Savvinova, P. P.; Shpektor, A. V.; Margolis, L. B.; Vasilieva, E. Yu.

    2016-01-01

    The relationship between acute coronary syndrome (ACS) and local and systemic inflammation, including accumulation of macrophages in atherosclerotic plaques and upregulation of blood cytokines (e.g., C-reactive protein (CRP)), has been known for more than 100 years. The atherosclerosis-associated inflammatory response has been traditionally considered as an immune system reaction to low-density lipoproteins. At the same time, some data have indicated a potential involvement of cytomegalovirus (CMV) in the activation and progression of atherosclerosis-associated inflammation, leading to ACS. However, these data have been tangential and mainly concerned the relationship between a coronary artery disease (CAD) prognosis and the anti-CMV antibody titer. We assumed that ACS might be associated with CMV reactivation and virus release into the bloodstream. The study’s aim was to test this assumption through a comparison of the plasma CMV DNA level in patients with various CAD forms and in healthy subjects. To our knowledge, no similar research has been undertaken yet. A total of 150 subjects (97 CAD patients and 53 healthy subjects) were examined. Real- time polymerase chain reaction (RT-PCR) was used to determine the number of plasma CMV DNA copies. We demonstrated that the number of plasma CMV genome copies in ACS patients was significantly higher than that in healthy subjects (p = 0.01). The CMV genome copy number was correlated with the plasma CRP level (p = 0.002). These findings indicate a potential relationship between CMV activation and atherosclerosis exacerbation that, in turn, leads to the development of unstable angina and acute myocardial infarction. Monitoring of the CMV plasma level in CAD patients may be helpful in the development of new therapeutic approaches to coronary atherosclerosis treatment. PMID:27437144

  4. Comprehensive MRI for the detection of subtle alterations in diastolic cardiac function in apoE/LDLR(-/-) mice with advanced atherosclerosis.

    PubMed

    Tyrankiewicz, Urszula; Skorka, Tomasz; Orzylowska, Anna; Jablonska, Magdalena; Jasinski, Krzysztof; Jasztal, Agnieszka; Bar, Anna; Kostogrys, Renata; Chlopicki, Stefan

    2016-06-01

    ApoE/LDLR(-/-) mice represent a reliable model of atherosclerosis. However, it is not clear whether cardiac performance is impaired in this murine model of atherosclerosis. Here, we used MRI to characterize cardiac performance in vivo in apoE/LDLR(-/-) mice with advanced atherosclerosis. Six-month-old apoE/LDLR(-/-) mice and age-matched C57BL/6J mice (control) were examined using highly time-resolved cine-MRI [whole-chamber left ventricle (LV) imaging] and MR tagging (three slices: basal, mid-cavity and apical). Global and regional measures of cardiac function included LV volumes, kinetics, time-dependent parameters, strains and rotations. Histological analysis was performed using OMSB (orceine with Martius, Scarlet and Blue) and ORO (oil red-O) staining to demonstrate the presence of advanced coronary atherosclerosis. MR-tagging-based strain analysis in apoE/LDLR(-/-) mice revealed an increased frequency of radial and circumferential systolic stretch (25% and 50% of segments, respectively, p ≤ 0.012), increased radial post-systolic strain index (45% of segments, p = 0.009) and decreased LV untwisting rate (-30.3° (11.6°)/cycle, p = 0.004) when compared with control mice. Maximal strains and LV twist were unchanged. Most of the cine-MRI-based LV functional and anatomical parameters also remained unchanged in apoE/LDLR(-/-) mice, with only a lower filling rate, longer filling time, shorter isovolumetric contraction time and slower heart rate observed in comparison with control mice. The coronary arteries displayed severe atherosclerosis, as evidenced by histological analysis. Using comprehensive MRI methods, we have demonstrated that, despite severe coronary atherosclerosis in six-month-old apoE/LDLR(-/-) mice, cardiac performance including global parameters, twist and strains, was well preserved. Only subtle diastolic alterations, possibly of ischemic background, were uncovered. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27146203

  5. Innate and Adaptive Immunity in Atherosclerosis

    PubMed Central

    Packard, René R. S.; Lichtman, Andrew H.; Libby, Peter

    2010-01-01

    Atherosclerosis, a chronic inflammatory disorder, involves both the innate and adaptive arms of the immune response that mediate the initiation, progression, and ultimate thrombotic complications of atherosclerosis. Most fatal thromboses, which may manifest as acute myocardial infarction or ischemic stroke, result from frank rupture or superficial erosion of the fibrous cap overlying the atheroma, processes that occur in inflammatorily active, rupture-prone plaques. Appreciation of the inflammatory character of atherosclerosis has led to the application of C-reactive protein as a biomarker of cardiovascular risk, and the characterization of the anti-inflammatory and immunomodulatory actions of the statin class of drugs. An improved understanding of the pathobiology of atherosclerosis and further studies of its immune mechanisms provide avenues for the development of future strategies directed toward better risk stratification of patients as well as the identification of novel anti-inflammatory therapies. This review retraces leukocyte subsets involved in innate and adaptive immunity and their contributions to atherogenesis. PMID:19449008

  6. Atherosclerosis is an inflammatory disorder after all.

    PubMed

    Meng, Charles Q

    2006-01-01

    Inflammation has been increasingly recognized as an important player in the pathophysiology of numerous human disorders. Accumulating evidence has led to the conclusion that atherosclerosis is an inflammatory disease, although it was believed to be a disorder of high cholesterol levels in the bloodstream for over a century. Cholesterol does contribute to the pathogenesis of atherosclerosis, but through inflammatory mechanisms. Statins lower cholesterol levels and hence reduce inflammation in the vasculature and prevent heart disease. Statins may also exert anti-inflammatory effects through mechanisms independent of cholesterol lowering. Adhesion molecules, cytokines, oxidative stress, etc. appear to contribute to the inflammatory state of atherosclerosis and therapeutic approaches directed toward these markers or targets have the potential to be effective in reducing inflammation and treating atherosclerosis. PMID:16454761

  7. Environmental carcinogens and mutational pathways in atherosclerosis.

    PubMed

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A

    2015-05-01

    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms. PMID:25704189

  8. Vascular Smooth Muscle Cells in Atherosclerosis.

    PubMed

    Bennett, Martin R; Sinha, Sanjay; Owens, Gary K

    2016-02-19

    The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis. PMID:26892967

  9. Positron Emission Tomography Imaging of Atherosclerosis

    PubMed Central

    Orbay, Hakan; Hong, Hao; Zhang, Yin; Cai, Weibo

    2013-01-01

    Atherosclerosis-related cardiovascular events are the leading causes of death in the industrialized world. Atherosclerosis develops insidiously and the initial manifestation is usually sudden cardiac death, stroke, or myocardial infarction. Molecular imaging is a valuable tool to identify the disease at an early stage before fatal manifestations occur. Among the various molecular imaging techniques, this review mainly focuses on positron emission tomography (PET) imaging of atherosclerosis. The targets and pathways that have been investigated to date for PET imaging of atherosclerosis include: glycolysis, cell membrane metabolism (phosphatidylcholine synthesis), integrin αvβ3, low density lipoprotein (LDL) receptors (LDLr), natriuretic peptide clearance receptors (NPCRs), fatty acid synthesis, vascular cell adhesion molecule-1 (VCAM-1), macrophages, platelets, etc. Many PET tracers have been investigated clinically for imaging of atherosclerosis. Early diagnosis of atherosclerotic lesions by PET imaging can help to prevent the premature death caused by atherosclerosis, and smooth translation of promising PET tracers into the clinic is critical to the benefit of patients. PMID:24312158

  10. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    SciTech Connect

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  11. Neo-atherosclerosis in very late stent thrombosis of drug eluting stent

    PubMed Central

    Al Mamary, Ahmed; Dariol, Gilberto; Napodano, Massimo

    2014-01-01

    Background Recent studies have described neo-atherosclerosis, developing inside the stent, as cause of very late stent thrombosis. Case report A 59-year-old man, with family history of coronary artery disease, presented to our Department because of anterior ST-segment elevation myocardial infarction. Two years before he had underwent percutaneous coronary intervention with multiple drug-eluting stents (DES) implantation on proximal-mid left anterior descending artery (LAD), and mid-right coronary artery (RCA), respectively. The angiogram revealed stent thrombosis with total occlusion of proximal LAD. Multiple passages with manual thrombus-aspiration catheter were successfully performed with improvement in TIMI flow. Optical Coherence Tomography (OCT) imaging revealed fully expanded stents without areas of inappropriate apposition to vessel wall; and mild to moderate intimal hyperplasia throughout the stented segment, with full covered stent struts; areas of ulcerated and ruptured plaque within the proximal struts of stented segment was depicted with intraluminal protruding material. Thus, an additional bare metal stent (BMS) was deployed inside and overlapping the previous in order to seal this plaque. OCT post procedure revealed optimal stent expansion and apposition, without residual protruding material. At 9-month follow-up patient was alive and free from symptoms. Coronary angiogram revealed patency of implanted stents without significant restenosis. Conclusions Neo-atherosclerosis with thrombosis on top of ruptured necrotic plaque core may play a role in the pathophysiology of very late stent thrombosis in both BMS and DES. Our report highlights the role OCT to assess the mechanism of VLST. PMID:25278726

  12. Association between Obesity, hsCRP ≥2 mg/L, and Subclinical Atherosclerosis: Implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Blaha, Michael J.; Rivera, Juan J.; Budoff, Matthew J.; Blankstein, Ron; Agatston, Arthur; O’Leary, Daniel H.; Cushman, Mary; Lakoski, Susan; Criqui, Michael H.; Szklo, Moyses; Blumenthal, Roger S.; Nasir, Khurram

    2011-01-01

    Objective High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown. Methods and Results We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals. Conclusions High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status. PMID:21474823

  13. Coronary flow reserve estimated by positron emission tomography to diagnose significant coronary artery disease and predict cardiac events.

    PubMed

    Naya, Masanao; Tamaki, Nagara; Tsutsui, Hiroyuki

    2015-01-01

    Coronary artery disease (CAD) is a major cause of death in Japan. Coronary angiography is useful to assess the atherosclerotic burden in CAD patients, but its ability to predict whether patients will respond favorably to optimal medical therapy and revascularization is limited. The measurement of the fractional flow reserve with angiography is a well-validated method for identifying ischemic vessels. However, neither an anatomical assessment nor a functional assessment can delineate microvasculature or estimate its function. The quantitative coronary flow reserve (CFR) estimated from sequential myocardial perfusion images obtained by positron emission tomography (PET) during stress provides an accurate index of hyperemic reactivity to vasodilatory agents in the myocardium. In fact, there is growing evidence that the CFR reflects disease activity in the entire coronary circulation, including epicardial coronary artery stenosis, diffuse atherosclerosis, and microvascular dilatory function. Importantly, reduced CFR is observed even in patients without flow-limiting coronary stenosis, and its evaluation can improve the risk stratification of patients at any stage of CAD. This review focuses on the application of CFR estimated by cardiac PET for the diagnosis and risk stratification of patients with CAD. PMID:25744627

  14. 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

  15. Endothelial Dysfunction and Coronary Artery Disease: Assessment, Prognosis and Treatment

    PubMed Central

    Matsuzawa, Yasushi; Lerman, Amir

    2014-01-01

    Progress in modification of conventional coronary risk factors and lifestyle behavior reduced atherosclerotic coronary artery disease incidence, nonetheless it continues to be the leading cause of mortality in the world. It might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. Atherosclerotic coronary artery disease risk is estimated based on identifying and quantifying only traditional risk factors in current clinical settings, it does not consider non-traditional risk factors. In addition, most of prevailing therapies for atherosclerosis are targeted for traditional risk factors rather than atherosclerosis itself. It is desirable to have a methodology which can directly assess the activity of atherogenesis at each moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including non-traditional and heretofore unknown factors, and is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review methods that assess endothelial function. Finally we focus on the effects of major anti-atherosclerotic disease therapies on endothelial function, and argue the possibility of non-invasive assessment of endothelial function aiming at individualized cardiovascular medicine. PMID:25365643

  16. Studying Physically Ill Elderly.

    ERIC Educational Resources Information Center

    Young, Rosalie F.; Kahana, Eva

    Research with older persons suffering from physical illness presents numerous challenges to gerontologists. Issues of conceptualization pertaining to the definition of illness, its location in the research paradigm, and the context in which illness occurs must be addressed prior to dealing with methodological problems. Access to physically ill…

  17. [Is atherosclerosis an autoimmunological process?].

    PubMed

    Partyka, Ł; Hartwich, J; Kieć-Wilk, B; Polus, A; Wybrańska, I; Dembińska-Kieć, A

    2001-01-01

    The theories formulated to explain atherogenesis evolved from simple vessel wall lipid accumulation assumption to endothelial dysfunction with adverse vascular wall remodelling hypothesis. The theory that has been accepted lately integrates the former hypotheses and allows for introducing the local immunological activation concept. This immunological activation is initiated by negatively charged and oxidatively modified lipids (e.g. oxPAPC) and their complexes with proteins (like beta 2-GP I). Antibodies and cellular response against chaperonins: HSP 60 and their analogues from bacterial pathogens such as HSP 65, GroEi etc.) as well as release of cytokines, adhesion molecules and inflammatory mediators (CD 40/CD 40-L, IL 15, IFN gamma, IL 1 beta, TNF alpha) also take part in the process. Another important element of atherogenesis is the pathological angiogenic response within the plaque connected with the expression of angiogenic growth factors (such as VEGF, bFGF and PDGF), metallo-proteinases and local hemostasis regulators. This complex activation of local inflammatory and immunological process initiates such phenomena as development of unstable plaque, vascular remodelling, vessel lumen constriction and ischemic, thromboembolic complications of atherosclerosis. PMID:12041024

  18. Role of infections in atherosclerosis.

    PubMed

    Valtonen, V V

    1999-11-01

    A growing amount of epidemiologic, experimental, and clinical evidence has linked infection as a risk factor to variousatherosclerotic diseases including acute myocardial infarction and cerebral infarction. Bacteremic infections with and without endocarditis carry a high risk for both stroke and acute myocardial infarction. During the last decade, chronic bacterial infections such as Chlamydia pneumoniae and dental infections have been associated as risk factors for various atherosclerotic diseases. These chronic bacterial infections are risk factors for acute cardiovascular events, but they may also have some role in the etiopathogenesis of atherosclerotic process itself. There are many known mechanisms that might explain the observed association of infection and atherosclerotic diseases, but it is probable that these mechanisms are complex and multifactorial and probably differ from infection to infection and from patient to patient. Infection theory is by no means against classic risk factor theory in the etiopathogenesis of atherosclerosis. Infection may also act as a synergistic risk factor together with classic risk factors in the development of various atherosclerotic diseases. PMID:10539842

  19. Superoxide and peroxynitrite in atherosclerosis.

    PubMed Central

    White, C R; Brock, T A; Chang, L Y; Crapo, J; Briscoe, P; Ku, D; Bradley, W A; Gianturco, S H; Gore, J; Freeman, B A

    1994-01-01

    The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with .NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting .NO stimulation of vascular smooth muscle guanylate cyclase activity. Images PMID:8302829

  20. The chylomicron: relationship to atherosclerosis.

    PubMed

    Tomkin, Gerald H; Owens, Daphne

    2012-01-01

    The B-containing lipoproteins are the transporters of cholesterol, and the evidence suggests that the apo B48-containing postprandial chylomicron particles and the triglyceride-rich very low density lipoprotein (VLDL) particles play an important part in the development of the plaque both directly and indirectly by their impact on LDL composition. The ratio of dietary to synthesised cholesterol is variable but tightly regulated: hence intervention with diet at best reduces serum cholesterol by <20% andusually <10%. Statins are the mainstay of cholesterol reduction therapy, but they increase cholesterol absorption, an example of the relationship between synthesis and absorption. Inhibition of cholesterol absorption with Ezetimibe, an inhibitor of Niemann Pick C1-like 1 (NPC1-L1), the major regulator of cholesterol absorption, increases cholesterol synthesis and hence the value of adding an inhibitor of cholesterol absorption to an inhibitor of cholesterol synthesis. Apo B48, the structural protein of the chylomicron particle, is synthesised in abundance so that the release of these particles is dependent on the amount of cholesterol and triglyceride available in the intestine. This paper will discuss cholesterol absorption and synthesis, chylomicron formation, and the effect of postprandial lipoproteins on factors involved in atherosclerosis. PMID:22007304

  1. Counseling the Coronary Patient

    ERIC Educational Resources Information Center

    Semmler, Caryl; Semmler, Maynard

    1974-01-01

    The article discusses counseling sessions designed to a) help the coronary patient adjust to cardiovascular disease, b) diminish patient anxieties and fears, and c) educate the patient and family members on controlling risk factors to deter another coronary attack. (JS)

  2. Coronary artery fistula

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007315.htm Coronary artery fistula To use the sharing features on this page, please enable JavaScript. Coronary artery fistula is an abnormal connection between one of ...

  3. Coronary artery stents.

    PubMed Central

    Stewart, A. J.; Coltart, D. J.

    1996-01-01

    The use of coronary stents to treat the acute complications of percutaneous transluminal coronary angioplasty and to reduce the restenosis rate following this procedure is reviewed. Images Figure 1 Figure 2 Figure 3 PMID:8761499

  4. What Is Coronary Angiography?

    MedlinePlus

    ... OG-rah-fee) is a test that uses dye and special x rays to show the insides ... the coronary arteries. Overview During coronary angiography, special dye is released into the bloodstream. The dye makes ...

  5. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    PubMed

    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

    2015-12-01

    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

  6. The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes.

    PubMed

    Marfella, Raffaele; D' Amico, Michele; Di Filippo, Clara; Siniscalchi, Mario; Sasso, Ferdinando Carlo; Ferraraccio, Franca; Rossi, Francesco; Paolisso, Giuseppe

    2007-01-01

    We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia

  7. 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

  8. 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. PMID:22579086

  9. Assessment of coronary vasomotion by intracoronary ultrasound

    NASA Astrophysics Data System (ADS)

    Dupouy, Patrick J.; Dubois-Rande, Jean Luc; Pelle, Gabriel; Gallot, Dominique; Geschwind, Herbert J.

    1993-06-01

    Recently, new intravascular ultrasound devices for intracoronary use became available. The aim of the study was to evaluate the accuracy of intravascular ultrasound for the assessment of coronary artery vasomotion and endothelial function in patients with atherosclerosis. Twenty patients with luminal irregularities on coronary angiogram and a high cholesterol level (287 +/- 19 mg/dl) (group 1) and 6 patients with angiographically smooth arteries and a minimally elevated cholesterol level (197 +/- 12 mg/dl) (group 2) were studied. A mechanical intravascular ultrasound probe (4.3 French, 30 MHz, Cardiovascular Imaging Systems) was placed into the proximal segment of the coronary artery. Off-line measurements of the lumen area and calculation of mean intimal thickness indice was performed using digitized ultrasound images. Endothelial function was studied during a sympathetic stimulation by a cold pressor test and after intracoronary administration of papaverine and linsidomine. Mean intimal thickness was higher in group 1 than in group 2 (1.52 +/- 0.64 mm vs. 0.18 +/- 0.08 mm, p < 0.001). Linsidomine infusion induced a significant vasodilating effect in both groups (p < 0.001).

  10. Blood serum atherogenicity and coronary artery calcification.

    PubMed

    Sobenin, Igor A; Myasoedova, Veronica A; Anisimova, Elena V; Pavlova, Xenia N; Möhlenkamp, Stefan; Schmermund, Axel; Seibel, Rainer; Berenbein, Sina; Lehmann, Nils; Moebus, Susanne; Jöckel, KarlHeinz; Orekhov, Alexander N; Erbel, Raimund

    2014-01-01

    The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-media thickness progression. The present study was undertaken to test the hypothesis that blood serum atherogenicity and its changes in dynamics may be associated with accumulation of coronary calcium in subclinical atherosclerosis. It was performed in 782 CHD-free participants of The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) Study, in whom blood samples have been taken at the baseline and at the end of 5-year follow-up. Opposite to the previous findings, the changes in serum atherogenicity did not correlate neither with the extent of coronary artery calcification, nor with the changes in Agatston CAC score. There was a moderate but significant rise in serum atherogenicity after 5-year followup period, and the same dynamics was observed for Agatston CAC score, but not for convenient lipid-related risk factors. The absence of association of the changes in serum atherogenicity with the changes in Agatston CAC score, along with previous findings, provides a point of view that serum-induced intracellular cholesterol accumulation is not related to the processes of calcium deposition in arterial wall, since the last one reflects the progression of already existing subclinical atherosclerotic lesions. PMID:24533940

  11. Scanning protocol optimization and dose evaluation in coronary stenosis using multi-slices computed tomography

    NASA Astrophysics Data System (ADS)

    Huang, Yung-hui; Chen, Chia-lin; Sheu, Chin-yin; Lee, Jason J. S.

    2007-02-01

    Cardiovascular diseases are the most common incidence for premature death in developed countries. A major fraction is attributable to atherosclerotic coronary artery disease, which may result in sudden cardiac failure. A reduction of mortality caused by myocardial infarction may be achieved if coronary atherosclerosis can be detected and treated at an early stage before symptoms occur. Therefore, there is need for an effective tool that allows identification of patients at increased risk for future cardiac events. The current multi-detector CT has been widely used for detection and quantification of coronary calcifications as a sign of coronary atherosclerosis. The aim of this study is to optimize the diagnostic values and radiation exposure in coronary artery calcium-screening examination using multi-slice CT (MSCT) with different image scan protocols. The radiation exposure for all protocols is evaluated by using computed tomography dose index (CTDI) phantom measurements. We chose an optimal scanning protocol and evaluated patient radiation dose in the MSCT coronary artery screenings and preserved its expecting diagnostic accuracy. These changes make the MSCT have more operation flexibility and provide more diagnostic values in current practice.

  12. A Proteomic Focus on the Alterations Occurring at the Human Atherosclerotic Coronary Intima*

    PubMed Central

    de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Maroto, Aroa S.; Donado, Alicia; Zubiri, Irene; Posada, Maria; Padial, Luis R.; Pinto, Angel G.; Barderas, Maria G.; Vivanco, Fernando

    2011-01-01

    Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. PMID:21248247

  13. Elevated Levels of Monocyte Activation Markers Are Associated With Subclinical Atherosclerosis in Men With and Those Without HIV Infection

    PubMed Central

    McKibben, Rebeccah A.; Margolick, Joseph B.; Grinspoon, Steven; Li, Xiuhong; Palella, Frank J.; Kingsley, Lawrence A.; Witt, Mallory D.; George, Richard T.; Jacobson, Lisa P.; Budoff, Matthew; Tracy, Russell P.; Brown, Todd T.; Post, Wendy S.

    2015-01-01

    Background. Heightened immune activation among human immunodeficiency virus (HIV)–infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study. Methods. We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors. Results. Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4+ T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque. Conclusions. sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection. PMID:25362192

  14. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE−/− mice

    PubMed Central

    Kumar, Saran; Chen, Mo; Li, Yan; Wong, Fiona H. S.; Thiam, Chung Wee; Hossain, Md Zakir; Poh, Kian Keong; Hirohata, Satoshi; Ogawa, Hiroko; Angeli, Véronique; Ge, Ruowen

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE−/−) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE−/− mice. ApoE−/−Adamts4−/− double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE−/− mice. PMID:27491335

  15. Cardiovascular Autonomic Neuropathy and Early Atherosclerosis in Adolescent Type 1 Diabetic Patient

    PubMed Central

    Dayem, Soha M. Abd El; Battah, Ahmed A.; Bohy, Abo El Magd El

    2015-01-01

    AIM: To evaluate cardiovascular autonomic neuropathy (CAN) in type 1 Diabetics and to detect its relation to coronary artery calcification. PATIENTS AND METHODS: It is a cross sectional study included 62 diabetics and 30 controls. Clinical, laboratory assessment and 24 Hr holter were done for all patients and controls and coronary artery calcium (CAC) scoring by multisclice CT was done for all patients only. T-test, Mann Whitney U test, and stepwise multiple regression were used for statistical analyses. RESULTS: CAC score was positive in 8.1 % of patients. Heart rate variability (HRV) was significantly lower in diabetics. All parameters of HRV were insignificantly lower in diabetics with positive CAC score. Patients with microalbuminuria had a significantly lower HRV. HRV had a significant correlation with age of patients, duration of disease, HbA1, and Qtc in diabetics. CONCLUSION: Percentage of arrhythmia and early atherosclerosis is high in adolescent type 1 diabetic patients. CAN is associated with early atherosclerosis. Cardiac autonomic neuropathy is associated with older age, longer duration, and poor glycemic control and microalbuminuria.

  16. 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

  17. Increased Expression of Chitinase 3-Like 1 in Aorta of Patients with Atherosclerosis and Suppression of Atherosclerosis in Apolipoprotein E-Knockout Mice by Chitinase 3-Like 1 Gene Silencing

    PubMed Central

    Gong, Zushun; Xing, Shanshan; Zheng, Fei; Xing, Qichong

    2014-01-01

    Introduction. The purpose of this study was to investigate the changes of chitinase 3-like 1 (CHI3L1) in the aorta of patients with coronary atherosclerosis and to determine whether inhibition of CHI3L1 by lentivirus-mediated RNA interference could stabilize atherosclerotic plaques in apolipoprotein E-knockout (ApoE−/−) mice. Methods. We collected discarded aortic specimens from patients undergoing coronary artery bypass graft surgery and renal arterial tissues from kidney donors. A lentivirus carrying small interfering RNA targeting the expression of CHI3L1 was constructed. Fifty ApoE−/− mice were divided into control group and CHI3L1 gene silenced group. A constrictive collar was placed around carotid artery to induce plaques formation. Then lentivirus was transfected into carotid plaques. Results. We found that CHI3L1 was overexpressed in aorta of patients with atherosclerosis and its expression was correlated with the atherosclerotic risk factors. After lentivirus transduction, mRNA and protein expression of CHI3L1 were attenuated in carotid plaques, leading to reduced plaque content of lipids and macrophages, and increased plaque content of collagen and smooth muscle cells. Moreover, CHI3L1 gene silencing downregulated the expression of local proinflammatory mediators. Conclusions. CHI3L1 is overexpressed in aorta from patients with atherosclerosis and the lentivirus-mediated CHI3L1 gene silencing could represent a new strategy to inhibit plaques progression. PMID:24729664

  18. Low Density Lipoprotein-Containing Circulating Immune Complexes: Role in Atherosclerosis and Diagnostic Value

    PubMed Central

    Sobenin, Igor A.; Salonen, Jukka T.; Zhelankin, Andrey V.; Melnichenko, Alexandra A.; Kaikkonen, Jari; Bobryshev, Yuri V.; Orekhov, Alexander N.

    2014-01-01

    It has been suggested that low density lipoprotein-containing circulating immune complexes (LDL-CIC) play a role in atherogenesis and are involved in the formation of early atherosclerotic lesion. These complexes, as well as anti-LDL autoantibodies, have been found in the blood and in the atherosclerotic lesions of patients with different cardiovascular diseases, as well as in the blood of animals with experimental atherosclerosis. It can be suggested that the presence of anti-LDL antibodies in the blood is a result of immune response induced by lipoprotein modification. LDL-CIC differs from native LDL in many aspects. It has much lower sialic acid content, smaller diameter, and higher density and is more electronegative than native LDL. Fraction of LDL-CICs is fundamental to the serum atherogenicity manifested at the cellular level. LDL-CIC, unlike native LDL, is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol, in cells cultured from uninvolved human aortic intima and in macrophage cultures. After removal of LDL-CIC, the CHD patient's sera lose their atherogenic properties. Titer of LDL-CIC in blood serum significantly correlates with progression of atherosclerosis in human in vivo and has the highest diagnostic value among other measured serum lipid parameters. Elevated CIC-cholesterol might well be a possible risk factor of coronary atherosclerosis. PMID:25054132

  19. The effects of endothelial lipase gene (LIPG) variants on inflammation marker levels and atherosclerosis development.

    PubMed

    Dalan, Altay Burak; Toptaş, Bahar; Buğra, Zehra; Polat, Nihat; Yılmaz-Aydoğan, Hülya; Çimen, Arif; Isbir, Turgay

    2013-08-01

    Atherosclerosis is a major pathological process related with several important adverse vascular events including coronary artery disease, stroke, and peripheral arterial disease. Endothelial lipase is an enzyme the activity of which affects all of lipoproteins, whereas HDL is the main substrate. The purpose of our study was to investigate the effects of endothelial lipase gene polymorphism and inflammation markers (CRP, IL-1β, IL-6, IL-8 and TNF-α) in the atherosclerosis. 104 patients with atherosclerosis and 76 healthy individuals were included in the study. LIPG -584C/T polymorphism gene polymorphisms were assessed with PCR-RFLP method. The serum CRP levels were measured by turbidimetric method using a biochemistry autoanalyzer, whereas serum IL-1β, IL-6, IL-8, TNF-α levels were determined by enzyme-linked immunosorbent assay. In this study, we found that the frequencies of TC genotype are more prevalent in patients than controls. We found a statistically significant difference of IL-6 levels between patient and control group. Our findings suggest that T allele might play a potential role in the susceptibility to atherogenesis in the Turkish population. PMID:23673478

  20. 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

  1. Does High C-reactive Protein Concentration Increase Atherosclerosis? The Whitehall II Study

    PubMed Central

    Kivimäki, Mika; Lawlor, Debbie A.; Davey Smith, George; Kumari, Meena; Donald, Ann; Britton, Annie; Casas, Juan P.; Shah, Tina; Brunner, Eric; Timpson, Nicholas J.; Halcox, Julian P. J.; Miller, Michelle A.; Humphries, Steve E.; Deanfield, John; Marmot, Michael G.; Hingorani, Aroon D.

    2008-01-01

    Background C-reactive protein (CRP), a marker of systemic inflammation, is associated with risk of coronary events and sub-clinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis) and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis). Methodology/Principal Findings We genotyped 3 tag single nucleotide polymorphisms (SNPs) [+1444T>C (rs1130864); +2303G>A (rs1205) and +4899T>G (rs 3093077)] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT), a structural marker of atherosclerosis, in 4941 men and women aged 50–74 (mean 61) years (the Whitehall II Study). The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT. Conclusions/Significance Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal. PMID:18714381

  2. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production.

    PubMed

    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A; Zhou, Zhou; Sun, Lijie; Mathison, Angela J; Garcia-Barrio, Minerva T; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J; Rader, Daniel J; Urrutia, Raul; Chen, Y Eugene

    2015-10-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID:26368306

  3. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production

    PubMed Central

    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A.; Zhou, Zhou; Sun, Lijie; Mathison, Angela J.; Garcia-Barrio, Minerva T.; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J.; Rader, Daniel J.; Urrutia, Raul; Chen, Y. Eugene

    2015-01-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E–deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID:26368306

  4. Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: the CARDIA trace element study

    PubMed Central

    Xun, Pengcheng; Liu, Kiang; Morris, J Steven; Daviglus, Martha L; He, Ka

    2010-01-01

    Objectives To examine the longitudinal association between toenail selenium levels and sub-clinical atherosclerosis over an 18-year period. Methods Toenail selenium concentrations were examined among 3112 Americans age 20–32 years in 1987 and measured by instrumental neutron-activation analysis. Subclinical atherosclerosis, including common, bulb and internal carotid intima-media thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in 2000 and 2005. General linear regression was developed examining the relation between toenail selenium levels and CIMTs, and logistic regression for repeated outcomes was employed estimating the risk of having CAC>0. Results After adjustment for potential confounders, no associations were observed between toenail selenium levels and CIMTs as well as CAC score. Comparing participants in the highest with the lowest quintile of selenium, the CIMT was 0.005mm (SE=0.008mm, Ptrend=0.39), 0.018mm (SE=0.019mm, Ptrend=0.49), and 0.017mm (SE=0.014mm, Ptrend=0.21) thicker measured in common, bulb and internal carotid, respectively. The adjusted odds ratio of having CAC>0 was 0.95 (95%CI: 0.67–1.35; Ptrend=0.999). Conclusions No associations were observed between toenail selenium and measures of subclinical atherosclerosis among American young adults. This study does not support an atherosclerotic mechanism of selenium for risk reduction of cardiovascular disease. PMID:20138620

  5. Mitochondrial genome sequencing in atherosclerosis: what's next?

    PubMed

    Sazonova, Margarita A; Shkurat, Tatiana P; Demakova, Natalya A; Zhelankin, Andrey V; Barinova, Valeria A; Sobenin, Igor A; Orekhov, Alexander N

    2016-01-01

    Cardiovascular diseases are currently a basic cause of mortality in highly developed countries. The major reason for genesis and development of cardiovascular diseases is atherosclerosis. At the present time high technology methods of molecular genetic diagnostics can significantly simplify early presymptomatic recognition of patients with atherosclerosis, to detect risk groups and to perform a family analysis of this pathology. A Next-Generation Sequencing (NGS) technology can be characterized by high productivity and cheapness of full genome analysis of each DNA sample. We suppose that in the nearest future NGS methods will be widely used for scientific and diagnostic purposes, including personalized medicine. In the present review article literature data on using NGS technology were described in studying mitochondrial genome mutations associated with atherosclerosis and its risk factors, such as mitochondrial diabetes, mitochondrial cardiomyopathy, diabetic nephropathy and left ventricular hypertrophy. With the use of the NGS technology it proved to be possible to detect a range of homoplasmic and heteroplasmic mutations and mitochondrial genome haplogroups which are associated with these pathologies. Meanwhile some mutations and haplogroups were detected both in atherosclerosis and in its risk factors. It conveys the suggestion that there are common pathogenetic mechanisms causing these pathologies. What comes next? New paradigm of crosstalk between non-pharmaceutical (including molecular genetic) and true pharmaceutical approaches may be developed to fill the niche of effective and pathogenically targeted pretreatment and treatment of preclinical and subclinical atherosclerosis to avoid the development of chronic life-threatening disease. PMID:26561059

  6. Chemokines and their receptors in Atherosclerosis.

    PubMed

    van der Vorst, Emiel P C; Döring, Yvonne; Weber, Christian

    2015-09-01

    Atherosclerosis, a chronic inflammatory disease of the medium- and large-sized arteries, is the main underlying cause of cardiovascular diseases (CVDs) most often leading to a myocardial infarction or stroke. However, atherosclerosis can also develop without this clinical manifestation. The pathophysiology of atherosclerosis is very complex and consists of many cells and molecules interacting with each other. Over the last years, chemokines (small 8-12 kDa cytokines with chemotactic properties) have been identified as key players in atherogenesis. However, this remains a very active and dynamic field of research. Here, we will give an overview of the current knowledge about the involvement of chemokines in all phases of atherosclerotic lesion development. Furthermore, we will focus on two chemokines that recently have been associated with atherogenesis, CXCL12, and macrophage migration inhibitory factor (MIF). Both chemokines play a crucial role in leukocyte recruitment and arrest, a critical step in atherosclerosis development. MIF has shown to be a more pro-inflammatory and thus pro-atherogenic chemokine, instead CXCL12 seems to have a more protective function. However, results about this protective role are still quite debatable. Future research will further elucidate the precise role of these chemokines in atherosclerosis and determine the potential of chemokine-based therapies. PMID:26175090

  7. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming.

    PubMed

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T; Hawxhurst, Victoria; Fitzgerald, Michael L; Trebicka, Jonel; Björkhem, Ingemar; Gustafsson, Jan-Åke; Westerterp, Marit; Tall, Alan R; Wright, Samuel D; Espevik, Terje; Schultze, Joachim L; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke

    2016-04-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. PMID:27053774

  8. Vinpocetine attenuates lipid accumulation and atherosclerosis formation.

    PubMed

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-05-10

    Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis. PMID:23583194

  9. Vinpocetine Attenuates Lipid Accumulation and Atherosclerosis Formation

    PubMed Central

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-01-01

    Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis PMID:23583194

  10. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    PubMed Central

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S.; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I.; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T.; Hawxhurst, Victoria; Fitzgerald, Michael L; Trebicka, Jonel; Gustafsson, Jan-Åke; Westerterp, Marit; Tall, Alan R.; Wright, Samuel D.; Espevik, Terje; Schultze, Joachim L.; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke

    2016-01-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Since cholesterol accumulation and deposition of cholesterol crystals (CCs) triggers a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility, in preventing and reversing atherosclerosis. Here we show that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load, and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques, and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the anti-atherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Since CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. PMID:27053774

  11. Oxidative theory of atherosclerosis and antioxidants.

    PubMed

    Salvayre, R; Negre-Salvayre, A; Camaré, C

    2016-06-01

    Atherosclerosis is a multifactorial process that begins early in infancy and affects all the humans. Early steps of atherogenesis and the evolution towards complex atherosclerotic plaques are briefly described. After a brief history of the 'Lipid theory of atherosclerosis', we report the most prominent discoveries on lipoproteins, their receptors and metabolism, and their role in atherogenesis. The main focus is the 'oxidative theory of atherosclerosis', with emphasis on free radicals and reactive oxygen species, lipid peroxidation and LDL oxidation, biological properties of oxidized LDL and their potential role in atherogenesis. Then, we report the properties of antioxidants and antioxidant systems and their effects in vitro, on cultured cells, in animal models and in humans. The surprising discrepancy between the efficacy of antioxidants in vitro and in animal models of atherosclerosis and the lack of protective effect against cardiovascular events and death in epidemiological study and clinical trials are discussed. In contrast, epidemiological studies seem to indicate that the Mediterranean diet may protect (in part) against atherosclerosis complications (myocardial infarction and cardiovascular death). PMID:26717905

  12. Runs of Homozygosity: Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages

    PubMed Central

    Christofidou, Paraskevi; Nelson, Christopher P.; Nikpay, Majid; Qu, Liming; Li, Mingyao; Loley, Christina; Debiec, Radoslaw; Braund, Peter S.; Denniff, Matthew; Charchar, Fadi J.; Arjo, Ares Rocanin; Trégouët, David-Alexandre; Goodall, Alison H.; Cambien, Francois; Ouwehand, Willem H.; Roberts, Robert; Schunkert, Heribert; Hengstenberg, Christian; Reilly, Muredach P.; Erdmann, Jeanette; McPherson, Ruth; König, Inke R.; Thompson, John R.; Samani, Nilesh J.; Tomaszewski, Maciej

    2015-01-01

    Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4–0.8) excess of ROHs when compared to coronary-artery-disease-free control subjects (p = 1.49 × 10−9). The average total length of ROHs was approximately 1,046.92 (95% CI: 634.4–1,459.5) kb greater in individuals with coronary artery disease than control subjects (p = 6.61 × 10−7). None of the identified individual ROHs was associated with coronary artery disease after correction for multiple testing. However, in aggregate burden analysis, ROHs favoring increased risk of coronary artery disease were much more common than those showing the opposite direction of association with coronary artery disease (p = 2.69 × 10−33). Individual ROHs showed significant associations with monocyte and macrophage expression of genes in their close proximity—subjects with several individual ROHs showed significant differences in the expression of 44 mRNAs in monocytes and 17 mRNAs in macrophages when compared to subjects without those ROHs. This study provides evidence for an excess of homozygosity in coronary artery disease in outbred populations and suggest the potential biological relevance of ROHs in cells of importance to the pathogenesis of atherosclerosis. PMID:26166477

  13. Atherosclerosis: Process, Indicators, Risk Factors and New Hopes

    PubMed Central

    Rafieian-Kopaei, Mahmoud; Setorki, Mahbubeh; Doudi, Monir; Baradaran, Azar; Nasri, Hamid

    2014-01-01

    Background: Atherosclerosis is the major cause of morbidities and mortalities worldwide. In this study we aimed to review the mechanism of atherosclerosis and its risk factors, focusing on new findings in atherosclerosis markers and its risk factors. Furthermore, the role of antioxidants and medicinal herbs in atherosclerosis and endothelial damage has been discussed and a list of important medicinal plants effective in the treatment and prevention of hyperlipidemia and atherosclerosis is presented. Methods: The recently published papers about atherosclerosis pathogenesis and herbal medicines effective in the treatment and prevention of hyperlipidemia and atherosclerosis were searched. Results: Inflammation has a crucial role in pathogenesis of atherosclerosis. The disease is accompanied by excessive fibrosis of the intima, fatty plaques formation, proliferation of smooth muscle cells, and migration of a group of cells such as monocytes, T cells, and platelets which are formed in response to inflammation. The oxidation of low density lipoprotein (LDL) to Ox-LDL indicates the first step of atherosclerosis in cardiovascular diseases. Malondialdehyde factor shows the level of lipoperoxidation and is a sign of increased oxidative pressure and cardiovascular diseases. In special pathological conditions such as severe hypercholesterolemia, peroxynitrite concentration increases and atherosclerosis and vascular damage are intensified. Medicinal plants have shown to be capable of interacting these or other pathogenesis factors to prevent atherosclerosis. Conclusions: The pathogenesis factors involved in atherosclerosis have recently been cleared and the discovery of these factors has brought about new hopes for better prevention and treatment of atherosclerosis. PMID:25489440

  14. Chemokine RANTES is increased at early stages of coronary artery disease.

    PubMed

    Podolec, J; Kopec, G; Niewiara, L; Komar, M; Guzik, B; Bartus, K; Tomkiewicz-Pajak, L; Guzik, T J; Plazak, W; Zmudka, K

    2016-04-01

    Cardiovascular diseases, and in particular coronary artery disease (CAD), are the leading causes of death in Europe and represent around 50% of overall mortality. Numerous cardiovascular markers have been proposed in relation to cardiovascular risk prediction, in relation to cardiac and vascular and cerebral events. Chemokines which regulate immune cell vascular chemotaxis, including CCL5/RANTES are points of great interest. We hypothesized that chemokine RANTES level measured in peripheral blood may be associated with severity of atherosclerosis in patients with stable angina undergoing coronary angiography. RANTES and interleukin 18 (IL-18) levels were measured by ELISA. Classical and novel cardiovascular risk factors like brachial flow mediated dilation and intima-media thickness were analyzed in the context of chemokine levels and severity of atherosclerosis. Study included 62 consecutive patients with coronary atherosclerosis demonstrated by coronary angiography, (mean age 59.3 years (S.D. = 7.4)), divided into two groups: group I with lower severity of atherosclerosis, (n = 45) and group 2 with severe CAD (n = 17) based on coronary angiography. Groups were well balanced for classic risk factors for atherosclerosis. Mean RANTES level were significantly higher in patients in group I (67.9 ng/ml, S.E.M. = 3.97) than in group II (50.5 ng/ml, S.E.M. = 7.49; P = 0.03). In contrast, IL-18 levels were similar in both groups (255 pg/ml in group I and 315 pg/ml, S.E.M. = 40.91 in group I, P = 0.12), as well as hsCRP concentration (3.45 S.E.M. = 2.66 ng/ml and 4.69 ng/ml S.E.M.= 1.64 ng/ml respectively; P = 0.47). Flow-mediated dilatation (FMD) values have been significantly lower in group II than in group I (6.31; S.E.M. = 0.61; vs 4.41; S.E.M. = 0,56, respectively, P = 0.026), while nitroglycerine-mediated dilatation (NMD) did not differ, indicating more pronounced endothelial dysfunction. No significant correlations between chemokine RANTES levels and intima

  15. Morphology of atherosclerotic coronary arteries

    NASA Astrophysics Data System (ADS)

    Holme, Margaret N.; Schulz, Georg; Deyhle, Hans; Hieber, Simone Elke; Weitkamp, Timm; Beckmann, Felix; Herzen, Julia; Lobrinus, Johannes A.; Montecucco, Fabrizio; Mach, François; Zumbuehl, Andreas; Saxer, Till; Müller, Bert

    2012-10-01

    Atherosclerosis, the narrowing of vessel diameter and build-up of plaques in coronary arteries, leads to an increase in the shear stresses present, which can be used as a physics-based trigger for targeted drug delivery. In order to develop appropriate nanometer-size containers, one has to know the morphology of the critical stenoses with isotropic micrometer resolution. Micro computed tomography in absorption and phase contrast mode provides the necessary spatial resolution and contrast. The present communication describes the pros and cons of the conventional and synchrotron radiation-based approaches in the visualization of diseased human and murine arteries. Using registered datasets, it also demonstrates that multi-modal imaging, including established histology, is even more powerful. The tomography data were evaluated with respect to cross-section, vessel radius and maximal constriction. The average cross-section of the diseased human artery (2.31 mm2) was almost an order of magnitude larger than the murine one (0.27 mm2), whereas the minimal radius differs only by a factor of two (0.51 mm versus 0.24 mm). The maximal constriction, however, was much larger for the human specimen (85% versus 49%). We could also show that a plastic model used for recent experiments in targeted drug delivery represents a very similar morphology, which is, for example, characterized by a maximal constriction of 82%. The tomography data build a sound basis for flow simulations, which allows for conclusions on shear stress distributions in stenosed blood vessels.

  16. The European Atherosclerosis Research Study (EARS): design and objectives.

    PubMed

    1994-06-01

    The European Atherosclerosis Research Study--EARS--is a multicentre collaborative project sponsored by the European Community. Its main objective is to study, in young people, the biological expression of a paternal history of premature acute myocardial infarction (AMI) and the relative share of heredity and environment in this expression. In 14 centres in 11 European countries, the offspring of fathers who suffered from a documented AMI before the age of 55 years (cases) are compared with age- and sex-matched control individuals. Genetic variables (restriction fragment length polymorphisms of candidate genes), lifestyle variables and biochemical variables that are known or suspected to play a role in the development of coronary heart disease (CHD), are studied. The cultural and ethnic diversity within Europe allows a thorough investigation of the relative importance and the potential interactions of genetics and environment in the pathogenesis of CHD. A standardized core methodology and centralized storage of blood samples with particular types of analyses systematically carried out in one or a few specialized laboratories, from a strong basis for valid cross-cultural analyses. The results of this study will offer new clues for the modelling of individual risk for developing CHD. PMID:7960370

  17. Pentoxifylline Decreases Serum Level of Adhesion Molecules in Atherosclerosis Patients

    PubMed Central

    Mohammadpour, Amir Hooshang; Falsoleiman, Homa; Shamsara, Jamal; Abadi, Ghazaleh Allah; Rasooli, Ramin; Ramezani, Mohammad

    2014-01-01

    Background: Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 (MCP-1), IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline (PTX) reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease (CAD). Methods: Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX (400 mg three times daily) or placebo (3 tab/day) for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Results: Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment (P<0.05). Conclusion: Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels. PMID:24375159

  18. High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

    PubMed Central

    Ossoli, Alice; Pavanello, Chiara

    2016-01-01

    Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

  19. High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis.

    PubMed

    Ossoli, Alice; Pavanello, Chiara; Calabresi, Laura

    2016-06-01

    Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

  20. Coronary artery disease and its association with Vitamin D deficiency.

    PubMed

    Aggarwal, Ramesh; Akhthar, Tauseef; Jain, Sachin Kumar

    2016-01-01

    Coronary artery disease (CAD) has become the latest scourge of humankind and referred to in this article as CAD, is the end result of the accumulation of atheromatous plaques within the walls of coronary arteries that supply the myocardium, a process also known as atherosclerosis and manifests mostly in the form of chronic stable angina or acute coronary syndrome. Vitamin D has attracted considerable interest recently due to its role in a number of extraskeletal disease processes including multiple sclerosis, malignancies, diabetes mellitus, and CAD. It is also known as sunshine vitamin due to its production in the body following exposure to ultraviolet rays, and it is a unique vitamin as it acts like a hormone with its receptor present in a wide range of tissues including endothelium, which is the important mediator of atherosclerosis and subsequent CAD. A large number of studies conducted in the past have provided the basic scientific framework and this article attempts to explore the role of Vitamin D deficiency in the pathogenesis of CAD and stresses the need for further research to fill up gap in our knowledge. PMID:27499590

  1. Coronary artery disease and its association with Vitamin D deficiency

    PubMed Central

    Aggarwal, Ramesh; Akhthar, Tauseef; Jain, Sachin Kumar

    2016-01-01

    Coronary artery disease (CAD) has become the latest scourge of humankind and referred to in this article as CAD, is the end result of the accumulation of atheromatous plaques within the walls of coronary arteries that supply the myocardium, a process also known as atherosclerosis and manifests mostly in the form of chronic stable angina or acute coronary syndrome. Vitamin D has attracted considerable interest recently due to its role in a number of extraskeletal disease processes including multiple sclerosis, malignancies, diabetes mellitus, and CAD. It is also known as sunshine vitamin due to its production in the body following exposure to ultraviolet rays, and it is a unique vitamin as it acts like a hormone with its receptor present in a wide range of tissues including endothelium, which is the important mediator of atherosclerosis and subsequent CAD. A large number of studies conducted in the past have provided the basic scientific framework and this article attempts to explore the role of Vitamin D deficiency in the pathogenesis of CAD and stresses the need for further research to fill up gap in our knowledge.

  2. [Adipokines: adiponectin, leptin, resistin and coronary heart disease risk].

    PubMed

    Kopff, Barbara; Jegier, Anna

    2005-01-01

    Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic

  3. Inflammatory cytokines in atherosclerosis: current therapeutic approaches.

    PubMed

    Tousoulis, Dimitris; Oikonomou, Evangelos; Economou, Evangelos K; Crea, Filippo; Kaski, Juan Carlos

    2016-06-01

    The notion of atherosclerosis as a chronic inflammatory disease has intensified research on the role of cytokines and the way these molecules act and interact to initiate and sustain inflammation in the microenvironment of an atherosclerotic plaque. Cytokines are expressed by all types of cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects, and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leucocytes, and other vascular residing cells. It is now understood that widely used drugs such as statins, aspirin, methotrexate, and colchicine act in an immunomodulatory way that may beneficially affect atherogenesis and/or cardiovascular disease progression. Moreover, advancement in pharmaceutical design has enabled the production of highly specific antibodies against key molecules involved in the perpetuation of the inflammatory cascade, raising hope for advances in the treatment of atherosclerosis. This review describes the actions and effects of these agents, their potential clinical significance, and future prospects. PMID:26843277

  4. The thyromimetic T-0681 protects from atherosclerosis

    PubMed Central

    Tancevski, Ivan; Wehinger, Andreas; Demetz, Egon; Hoefer, Julia; Eller, Philipp; Huber, Eva; Stanzl, Ursula; Duwensee, Kristina; Auer, Kristina; Schgoer, Wilfried; Kuhn, Volker; Fievet, Catherine; Stellaard, Frans; Rudling, Mats; Foeger, Bernhard; Patsch, Josef R.; Ritsch, Andreas

    2009-01-01

    This report describes studies in hyperlipidemic New Zealand White (NZW) rabbits investigating the impact of the liver-selective thyromimetic T-0681 on lipoprotein metabolism and the development of atherosclerosis. Prolonged treatment with T-0681 increased the hepatic expression of both LDL receptor and scavenger receptor class B, type I without affecting cholesteryl ester transfer protein activity. Upregulation of hepatic lipoprotein receptors was accompanied by a marked decrease of apolipoprotein B-containing lipoproteins, reflected by a 60% reduction of plasma cholesterol and a >70% reduction of plasma triglyceride levels. Most importantly, T-0681 reduced the development of atherosclerosis by 80% in NZW rabbits on high-cholesterol chow. Our data suggest that liver-selective thyromimetics, such as T-0681, may prove to be useful therapeutic agents against the development of atherosclerosis in humans. PMID:19106072

  5. Atherosclerosis - A matter of unresolved inflammation.

    PubMed

    Viola, Joana; Soehnlein, Oliver

    2015-05-01

    Atherosclerosis is commonly looked upon as a chronic inflammatory disease of the arterial wall arising from an unbalanced lipid metabolism and a maladaptive inflammatory response. However, atherosclerosis is not merely an inflammation of the vessel wall. In fact, the cardinal signs of unstable atherosclerotic lesions are primarily characteristics of failed resolution of a chronic inflammation. In contrast to acute inflammatory events which are typically self-limiting, atherosclerosis is an unresolved inflammatory condition, lacking the switch from the pro-inflammatory to the pro-resolving phase, the latter characterized by termination of inflammatory cell recruitment, removal of inflammatory cells from the site of inflammation by apoptosis and dead cell clearance, reprogramming of macrophages toward an anti-inflammatory, regenerative phenotype, and finally egress of effector cells and tissue regeneration. Here we present an overview on mechanisms of failed resolution contributing to atheroprogression and deliver a summary of novel therapeutic strategies to restore resolution in inflamed arteries. PMID:25865626

  6. Five dramas of illness.

    PubMed

    Frank, Arthur W

    2007-01-01

    First-person narratives of illness experience are dramatic: the narrator, who is also the sufferer, is caught in conflicts of forces that permit understanding more than control. Among the dramas of illness, five occur frequently in autobiographical accounts of illness. These dramas overlap and have varying emphases in different people's stories. They are the drama of genesis (what instigated the illness); the drama of emotion work (what emotional displays are required or prohibited); the drama of fear and loss; the drama of meaning; and finally, the drama of self. This five-drama framework can focus critical and clinical attention on which conflicting forces the ill person is working to reconcile, what makes that work difficult, and how conceiving of one's illness as a drama can be a source of meaning and value. PMID:17660632

  7. Myocardial ischaemia in a case of a solitary coronary ostium in the right aortic sinus with retroaortic course of the left coronary artery: documentation of the underlying pathophysiological mechanisms of ischaemia by intracoronary Doppler and pressure measurements

    PubMed Central

    Schwarz, E; Hager, P; Uebis, R; Hanrath, P; Klues, H

    1998-01-01

    Only a few cases of a single coronary ostium and retroaortic course of the coronary artery have been described. Almost all cases reported so far had additional coronary artery or valvar disease. However, myocardial ischaemia may be caused by the coronary malformation alone. A 40 year old woman with severe myocardial ischaemia in the absence of clinically relevant coronary atherosclerosis is described. To clarify the origin and mechanisms of ischaemia, intracoronary Doppler, pressure and ultrasound studies were performed using microtransducers. In its outer portion along the course behind the ascending aorta, coronary blood flow velocities were increased, there was an external elliptical compression, and distal coronary flow reserve was reduced. Furthermore, an overshoot in diastolic pressure above aortic pressure was detectable within this portion. Dobutamine stimulation exaggerated the observed intracoronary haemodynamics and induced myocardial ischaemia. The intracoronary diagnostic procedures performed were helpful in clarifying the pathophysiological mechanisms of functional coronary obstruction and ischaemia in this malformation. Bypass surgery was successfully performed with symptomatic improvement.

 Keywords: coronary anomaly;  Doppler;  intravascular ultrasound;  single coronary ostium;  congenital disorders PMID:9875097

  8. [The best of coronary artery disease in 1999].

    PubMed

    Gayet, J L

    2000-01-01

    Despite the (modest) regression observed in the MONICA study, coronary artery disease remains the leading cause of mortality in industrialised countries and it is worryingly progressive in emerging countries. Therapeutic progress has been considerable but only a small number of coronary patients benefit from it. The techniques are costly and justify efforts to improve selection of high risk patients. The results of the VA-HIT study, which demonstrated the importance of HDL cholesterol level in prevention, now raise the question of the optimal treatment of these patients and that of the association of fibrates and statins. The value of ACE inhibitors in the HOPE study in coronary artery disease was outstanding. In parallel, the efficacy of Mediterranean diet has been confirmed in secondary prevention as that of supplements of omega-3 fatty acids in the GISSI-Prevenzione study. When reference anti-anginal agents are ineffective in the most resistant forms of coronary artery disease, other classes of drugs have been shown to be effective in association. Finally, the theory of inflammation and infection of atherosclerosis has found new indirect arguments, whereas angiogenesis and vasculogenesis have been confirmed as the main leaders in the future treatment of coronary artery disease. PMID:10721448

  9. Obesity Related Coronary Microvascular Dysfunction: From Basic to Clinical Practice

    PubMed Central

    Selthofer-Relatić, K.; Bošnjak, I.; Kibel, A.

    2016-01-01

    Obesity related coronary microvascular disease is a medical entity which is not yet fully elucidated. The pathophysiological basis of coronary microcirculatory dysfunction consists of a heterogeneous group of disorders with individual morphologic/functional/clinical presentation and prognosis. Coronary microcirculatory changes include mechanisms connected with vascular dysfunction, as well as extravascular and vasostructural changes in responses to neural, mechanical, and metabolic factors. Cardiometabolic changes that include obesity, dyslipidemia, diabetes mellitus type II, and hypertension are associated with atherosclerosis of epicardial coronary arteries and/or microvascular coronary dysfunction, with incompletely understood underlying mechanisms. In obesity, microvascular disease is mediated via adipokines/cytokines causing chronic, subclinical inflammation with (a) reduced NO-mediated dilatation, (b) changed endothelial- and smooth muscle-dependent vasoregulating mechanisms, (c) altered vasomotor control with increased sympathetic activity, and (d) obesity related hypertension with cardiomyocytes hypertrophy and impaired cardiac vascular adaptation to metabolic needs. From a clinical point of view it can present itself in acute or chronic form with different prognosis, as a practice problem for real-life diagnosis and treatment. PMID:27092288

  10. Heat-related illnesses.

    PubMed

    Khosla, R; Guntupalli, K K

    1999-04-01

    The majority of clinicians will encounter patients with heat-related illness in one form or the other. Early recognition and management are important to prevent morbidity and mortality. In children and elderly, the clinical signs may be subtle and in such situations a sound knowledge of heat-related illnesses is crucial. Besides diagnosing and treating heat-related illnesses, it is equally important to know how to prevent them as they are easily preventable. PMID:10331127

  11. Inflammation and its resolution as determinants of acute coronary syndromes

    PubMed Central

    Libby, Peter; Tabas, Ira; Fredman, Gabrielle; Fisher, Edward

    2014-01-01

    Inflammation contributes to many of the characteristics of plaques implicated in the pathogenesis of acute coronary syndromes (ACS). Moreover, inflammatory pathways not only regulate properties of plaques that precipitate ACS but also modulate the clinical consequences of the thrombotic complications of atherosclerosis. This synthesis will provide an update on the fundamental mechanisms of inflammatory responses that govern ACS, and also highlight the ongoing balance between pro-inflammatory mechanisms and endogenous pathways that can promote the resolution of inflammation. An appreciation of the countervailing mechanisms that modulate inflammation in relation to ACS enriches our fundamental understanding of the pathophysiology of this important manifestation of atherosclerosis. In addition, these insights furnish glimpses into potential novel therapeutic interventions to forestall this ultimate complication of the disease. PMID:24902971

  12. [Noninvasive diagnostic of coronary artery disease].

    PubMed

    Zuber, Michel; Zellweger, Michael; Bremerich, Jens; Auf der Mauer, Christoph; Buser, Peter T

    2009-04-01

    Noninvasive imaging of coronary artery disease has extensively evolved during the last decade. Today, at least four imaging techniques with excellent image quality such as echocardiography, myocardial perfusion scintigraphy and PET, cardiac magnetic resonance and cardiac CT are widely available in order to estimate the risk for future ischemic events, to corroborate the suspected diagnosis of coronary artery disease, to demonstrate the extent and localisation of myocardial ischemia, to diagnose myocardial infarction and measure it's size, to identify the myocardium at risk during acute ischemia, to differentiate between viable and nonviable myocardium and thereby provide the basis for indications of revascularisations, to follow revascularized patients over long time, to assess the risk for sudden cardiac death and the development of heart failure after myocardial infarction and to depict atheromatosis and atherosclerosis of the coronary artery tree. Echocardiography is the most widely used imaging method in cardiology. It provides excellent information on morphology and function of nearly all cardiac structures. Stress echocardiography has been proven to be a reliable tool for the demonstration of myocardial ischemia and for the acquisition of prognostic data. Newer ultrasound techniques may further improve investigator dependence and thereby reproducibility. The completeness of echocardiography will always depend on acoustic windows, which are given in a specific patient. Myocardial perfusion scintigraphy provides the largest database especially on prognosis in coronary artery disease. It has been the for the depictions of ischemic and infarcted myocardium. Radiation exposure will always be an issue. Newer hybrid techniques combining nuclear methods with cardiac CT may add arguments, which will be needed for clinical decision-making. Cardiac magnetic resonance has evolved as an important tool in the diagnosis of cardiovascular diseases. It is

  13. Adipokines, diabetes and atherosclerosis: an inflammatory association

    PubMed Central

    Freitas Lima, Leandro C.; Braga, Valdir de Andrade; do Socorro de França Silva, Maria; Cruz, Josiane de Campos; Sousa Santos, Sérgio H.; de Oliveira Monteiro, Matheus M.; Balarini, Camille de Moura

    2015-01-01

    Cardiovascular diseases can be considered the most important cause of death in diabetic population and diabetes can in turn increase the risk of cardiovascular events. Inflammation process is currently recognized as responsible for the development and maintenance of diverse chronic diseases, including diabetes and atherosclerosis. Considering that adipose tissue is an important source of adipokines, which may present anti and proinflammatory effects, the aim of this review is to explore the role of the main adipokines in the pathophysiology of diabetes and atherosclerosis, highlighting the therapeutic options that could arise from the manipulation of these signaling pathways both in humans and in translational models. PMID:26578976

  14. Long Noncoding RNA: Recent Updates in Atherosclerosis

    PubMed Central

    Li, Hao; Zhu, Hongming; Ge, Junbo

    2016-01-01

    Long noncoding RNAs belong to a class of noncoding RNAs longer than 200 nucleotides with the epigenetic regulation potential. As a novel molecular regulator, lncRNAs are often dysregulated in various pathological conditions and display multiple functions in a wide range of biological processes. Given that recent studies have indicated that lncRNAs are involved in atherosclerosis-related smooth muscle cell, endothelial cell, macrophage and lipid metabolism regulation, it is pertinent to understand the potential function of lncRNAs in atherosclerosis development. This review will highlight the recent updates of lncRNAs in atherogenesis and also discuss their potential roles as novel therapeutic targets. PMID:27314829

  15. HIV, inflammation, and calcium in atherosclerosis.

    PubMed

    Shrestha, Sadeep; Irvin, Marguerite R; Grunfeld, Carl; Arnett, Donna K

    2014-02-01

    Atherosclerosis is consistently higher among the HIV-positive patients, with or without treatment, than among the HIV-negative population. Risk factors linked to atherosclerotic cardiovascular disease in HIV infection are both traditional and HIV specific although the underlying mechanisms are not fully delineated. Three key sequential biological processes are postulated to accelerate progression of atherosclerosis in the context of HIV: (1) inflammation, (2) transformation of monocytes to macrophages and then foam cells, and (3) apoptosis of foam cells leading to plaque development through Ca(2+)-dependent endoplasmic reticulum stress. These proatherogenic mechanisms are further affected when HIV interacts with the genes involved in various phases within this network. PMID:24265418

  16. 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. PMID:26978582

  17. 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. PMID:25259746

  18. Coronary artery bypass grafting in a patient with organophosphate poisoning.

    PubMed

    Pieris, Rajeeva R; Fernando, Ravindra

    2015-01-01

    A 43-year-old male, with no previous history of mental illness, was diagnosed with coronary heart disease, after which he became acutely depressed and attempted suicide by ingesting an organophosphate pesticide. He was admitted to an intensive care unit and trea