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Sample records for arterial stiffness hypertension

  1. Hypertension and arterial stiffness in heart transplantation patients

    PubMed Central

    de Souza-Neto, João David; de Oliveira, Ítalo Martins; Lima-Rocha, Hermano Alexandre; Oliveira-Lima, José Wellington; Bacal, Fernando

    2016-01-01

    OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension. PMID:27652829

  2. Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension

    PubMed Central

    Palatini, Paolo; Casiglia, Edoardo; Gąsowski, Jerzy; Głuszek, Jerzy; Jankowski, Piotr; Narkiewicz, Krzysztof; Saladini, Francesca; Stolarz-Skrzypek, Katarzyna; Tikhonoff, Valérie; Van Bortel, Luc; Wojciechowska, Wiktoria; Kawecka-Jaszcz, Kalina

    2011-01-01

    This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP) measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP reduction. Although many methodological problems still hinder the wide clinical application of parameters of arterial stiffness, these will likely contribute to cardiovascular assessment and management in future clinical practice. Each of the abovementioned parameters reflects a different characteristic of the atherosclerotic process, involving functional and/or morphological changes in the vessel wall. Therefore, acquiring simultaneous measurements of different parameters of vascular function and structure could theoretically enhance the power to improve risk stratification. Continuous technological effort is necessary to refine our methods of investigation in order to detect early arterial abnormalities. Arterial stiffness and its consequences represent the great challenge of the twenty-first century for

  3. Aerobic, resistance and combined exercise training on arterial stiffness in normotensive and hypertensive adults: A review.

    PubMed

    Li, Yanlei; Hanssen, Henner; Cordes, Mareike; Rossmeissl, Anja; Endes, Simon; Schmidt-Trucksäss, Arno

    2015-01-01

    Exercise training has different effects on arterial stiffness according to training modalities. The optimal exercise modality for improvement of arterial function in normotensive and hypertensive individuals has not been well established. In this review, we aim to evaluate the effects of aerobic, resistance and combined aerobic and resistance training on arterial stiffness in individuals with and without hypertension. We systematically searched the Pubmed and Web of Science database from 1985 until December 2013 for relevant randomised controlled trials (RCTs). The data were extracted by one investigator and checked by a second investigator. The training effects on arterial stiffness were estimated using weighted mean differences of the relative changes (%) with 95% confidence intervals (CIs). We finally reviewed the results from 17 RCTs. The available evidence indicates that aerobic exercise tends to have a beneficial effect on arterial stiffness in normotensive and hypertensive patients, but does not affect arterial stiffness in patients with isolated systolic hypertension. Resistance exercise has differing effects on arterial stiffness depending on type and intensity. Vigorous resistance training is associated with an increase in arterial stiffness. There seem to be no unfavourable effects on arterial stiffness if the training is of low intensity, in a slow eccentric manner or with lower limb in healthy individuals. Combined training has neutral or even a beneficial effect on arterial stiffness. In conclusion, our review shows that exercise training has varying effects on arterial stiffness depending on the exercise modalities.

  4. Central Artery Stiffness in Hypertension and Aging: A Problem with Cause and Consequence

    PubMed Central

    Humphrey, Jay D.; Harrison, David G.; Figueroa, C. Alberto; Lacolley, Patrick; Laurent, Stéphane

    2015-01-01

    Systemic hypertension is a risk factor for many diseases affecting the heart, brain, and kidneys. It has long been thought that hypertension leads to a thickening and stiffening of central arteries (i.e., stiffness is a consequence) while more recent evidence suggests that stiffening precedes hypertension (i.e., stiffness is a cause). We submit, however, that consideration of the wall biomechanics and hemodynamics reveals an insidious positive feedback loop that may render it irrelevant whether hypertension causes or is caused by central arterial stiffening. A progressive worsening can ensue in either case, thus any onset of stiffening merits early intervention. PMID:26846637

  5. Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

    PubMed

    Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A

    2016-01-01

    Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline.

  6. Reciprocal relationship between plasma ghrelin level and arterial stiffness in hypertensive subjects.

    PubMed

    Zhao, Yin-Tao; Yang, Hai-Bo; Li, Ling; Gao, Ke; Li, Peng-Fei; Xie, Wei-Wei

    2013-11-01

    Arterial stiffness, considered an independent predictor of cardiovascular morbidity and mortality, is closely associated with hypertension. Futhermore, the role of ghrelin in the development of hypertension has been widely recognized. The purpose of the present study was to explore the potential relationship between circulating ghrelin and arterial stiffness in hypertensive subjects. A total of 192 patients with primary hypertension and 107 normotensive (NT) control subjects were enrolled in the present cross-sectional study. Plasma ghrelin was determined by ELISA. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV) and the augmentation index (AIx). Both baPWV and AIx values were markedly higher in the hypertensive compared with NT group (P < 0.01). In contrast, plasma ghrelin concentrations were significantly lower in hypertensive patients compared with NT subjects (P < 0.01). Plasma ghrelin concentrations were negatively correlated with age (odds ratio (OR) -1.836; P < 0.001), smoking (OR -1.347; P = 0.042), baPWV (OR -1.762; P < 0.001) and AIx (OR -1.516; P = 0.005), but positively associated with fasting plasma glucose (OR 1.293; P = 0.047) and HbA1c (OR 1.413; P = 0.025). The inverse correlation between circulating ghrelin and the extent of arterial stiffness suggests that ghrelin is an independent determinant of arterial stiffness, even after adjustment for confounding cardiovascular risk factors, and it actively participates in the pathophysiology of arterial stiffness in hypertensive subjects.

  7. Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

    PubMed

    Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R

    2016-01-01

    Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.

  8. Add-on therapy with doxazosin in patients with hypertension influences arterial stiffness and albuterol-mediated arterial vasodilation

    PubMed Central

    Wykretowicz, Andrzej; Guzik, Przemyslaw; Krauze, Tomasz; Adamska, Karolina; Milewska, Agata; Wysocki, Henryk

    2007-01-01

    What is already known about this subject Hypertension is associated with increased arterial stiffness and impaired endothelial function. Arterial vasodilation depends on endothelial function and can be regulated by β2-adrenergic stimulation. Doxazosin is a known and potent antihypertensive agent. However, its effects on arterial stiffness and vasodilation have not been fully established. What this study adds Sixteen-week add-on antihypertensive therapy with 4 mg of doxazosin extended release daily: Reduces arterial stiffness. Improves albuterol-mediated, i.e. endothelium-dependent, arterial vasodilation. Does not influence nitroglycerin-mediated, i.e. endothelium-independent, arterial vasodilation. Aims Doxazosin is an antihypertensive agent with largely unknown effects on arterial stiffness and vasodilation. The aim of this study was to determine the effect of the addition of doxazosin extended-release (ER) to the standard management of hypertension in patients with inadequately controlled blood pressure (BP) on arterial stiffness and arterial vasodilation. Methods Twenty patients with inadequately controlled hypertension were treated with 4 mg doxazosin ER daily for 16 weeks as an adjunct to their existing antihypertensive regimen. Results Doxazosin ER add-on therapy was associated with significantly reduced systolic (P < 0.0001) and diastolic (P = 0.0003) BP, improved arterial stiffness (determined by digital volume pulse analysis (P = 0.048) and albuterol-mediated arterial vasodilation (P = 0.030). Conclusions Add-on therapy with 4 mg of doxazosin ER daily reduces BP and arterial stiffness and improves arterial vasodilation in response to adrenergic stimulation. PMID:17635498

  9. Hypertension, Diabetes Type II, and Their Association: Role of Arterial Stiffness.

    PubMed

    Smulyan, Harold; Lieber, Ari; Safar, Michel E

    2016-01-01

    In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions.

  10. Arterial stiffness evaluated by cardio-ankle vascular index (CAVI) in adolescent hypertension.

    PubMed

    Mestanik, Michal; Jurko, Alexander; Mestanikova, Andrea; Jurko, Tomas; Tonhajzerova, Ingrid

    2016-01-01

    Elevated blood pressure (BP) is a major risk factor for atherosclerosis. As the studies concerning vascular alterations in pediatric patients are rare, we aimed to study the relationship between hypertension and arterial stiffness in adolescence by novel method independent from BP during examination. Twenty nonobese adolescent boys (16.5 ± 0.4 years) with newly diagnosed essential hypertension, 20 adolescent boys (16.7 ± 0.4 years) with newly diagnosed white-coat hypertension, and 20 healthy controls matched to age and body mass index were examined. Cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), pre-ejection period (PEP), and ejection time (ET) were evaluated. CAVI was significantly increased in essential hypertension patients compared with controls (p < 0.05) with no significant difference in white-coat hypertension patients. Significantly higher baPWV was found in essential and white-coat hypertension patients compared with controls (both p < 0.001). White-coat hypertension patients showed significantly shortened PEP and ET compared with controls (p < 0.01 and p < 0.001, respectively) and essential hypertension patients (both p < 0.05). For the first time, the arterial stiffness in adolescents with newly diagnosed essential and white-coat hypertension was studied using BP-independent index CAVI combined with conventional baPWV. Our study revealed significantly increased CAVI in adolescents with newly diagnosed essential hypertension compared with controls. Our findings could help to understand hypertension-atherosclerosis interaction.

  11. Arterial Stiffness is Associated with Increase in Blood Pressure Over Time in Treated Hypertensives

    PubMed Central

    Coutinho, T; Bailey, KR; Turner, ST; Kullo, IJ

    2014-01-01

    Background Arterial stiffness is associated with incident hypertension. We hypothesized that arterial stiffness would predict increases in systolic (SBP), mean (MAP) and pulse pressure (PP) over time in treated hypertensives. Methods Blood pressure (BP) was measured a mean of 8.5±0.9 years apart in 414 non-Hispanic white hypertensives (mean age 60±8 years, 55% women). The average of 3 supine right brachial BPs was recorded. Measures of arterial stiffness including carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx) and central pulse pressure (CPP) were obtained at baseline by applanation tonometry. We performed stepwise multivariable linear regression analyses adjusting for potential confounders to assess the associations of arterial stiffness parameters with BP changes over time. Results Systolic, mean and pulse pressure increased in 80% of participants. After adjustment for the covariates listed above, cfPWV was significantly associated with increases in SBP (β±SE: 0.71±0.31) and PP (β±SE: 1.09±0.27); AIx was associated with increases in SBP (β±SE: 0.23±0.10) and MAP (β±SE: 0.27±0.07); and CPP was associated with increases in SBP (β±SE: 0.44±0.07), MAP (β±SE: 0.24±0.05) and PP (β±SE: 0.42±0.06) over time (P≤0.02 for all). Conclusions Baseline arterial stiffness measures were associated with longitudinal increases in SBP, MAP and PP in treated hypertensives. PMID:24952654

  12. Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

    SciTech Connect

    Poreba, Rafal; Gac, Pawel; Poreba, Malgorzata; Antonowicz-Juchniewicz, Jolanta; Andrzejak, Ryszard

    2011-08-01

    Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 {+-} 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I - men occupationally exposed to lead (n = 53), and group II - men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently in group I than in group II. In eTracking examination mean values of stiffness parameter ({beta}), augmentation index (AI) and one-point pulse wave velocity (PWV-{beta}) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness. - Highlights: > Amongst persons with AH exposed to Pb higher ZnPP represent independent risk factor of increased local arterial stiffness

  13. The Use of the Ambulatory Arterial Stiffness Index in Patients Suspected of Secondary Hypertension

    PubMed Central

    Verbakel, Joshua R. A.; Adiyaman, Ahmet; Kraayvanger, Nicole; Dechering, Dirk G.; Postma, Cornelis T.

    2016-01-01

    The ambulatory arterial stiffness index (AASI) is a marker of arterial stiffness and is derived from ambulatory 24-h blood pressure registration. We studied whether the AASI could be used as a predictive factor for the presence of renal artery stenosis (RAS) in patients with a suspicion of secondary hypertension and as such as a diagnostic tool for RAS. We included 169 patients with difficult-to-treat hypertension. They all underwent 24-h ambulatory blood pressure monitoring registration, imaging of the renal arteries, and cardiovascular risk measurement, including smoking, history, biometrics, blood pressure, renal function, lipids, and glucose metabolism. Performing univariate and multivariate analyses, we investigated if AASI and the other cardiovascular risk factors were related to the presence of RAS. Of the 169 patients (49% women), 31% had RAS. The mean AASI was 0.44 (0.16). The presence of RAS showed no significant correlation with AASI (r = 0.14, P = 0.06). Age (r = 0.19, P = 0.01), hypercholesterolemia (r = 0.26, P = 0.001), history of CVD (r = 0.22, P = 0.004), and creatinine clearance (r = −0.34, P < 0.001) all demonstrated a correlation with RAS. Although AASI is higher in patients with RAS, AASI does not independently predict the presence of RAS in hypertensive subjects. PMID:28018907

  14. Cullin-3 mutation causes arterial stiffness and hypertension through a vascular smooth muscle mechanism

    PubMed Central

    Agbor, Larry N.; Ibeawuchi, Stella-Rita C.; Hu, Chunyan; Davis, Deborah R.; Keen, Henry L.; Quelle, Frederick W.; Sigmund, Curt D.

    2016-01-01

    Cullin-3 (CUL3) mutations (CUL3Δ9) were previously identified in hypertensive patients with pseudohypoaldosteronism type-II (PHAII), but the mechanism causing hypertension and whether this is driven by renal tubular or extratubular mechanisms remains unknown. We report that selective expression of CUL3Δ9 in smooth muscle acts by interfering with expression and function of endogenous CUL3, resulting in impaired turnover of the CUL3 substrate RhoA, increased RhoA activity, and augmented RhoA/Rho kinase signaling. This caused vascular dysfunction and increased arterial pressure under baseline conditions and a marked increase in arterial pressure, collagen deposition, and vascular stiffness in response to a subpressor dose of angiotensin II, which did not cause hypertension in control mice. Inhibition of total cullin activity increased the level of CUL3 substrates cyclin E and RhoA, and expression of CUL3Δ9 decreased the level of the active form of endogenous CUL3 in human aortic smooth muscle cells. These data indicate that selective expression of the Cul3Δ9 mutation in vascular smooth muscle phenocopies the hypertension observed in Cul3Δ9 human subjects and suggest that mutations in CUL3 cause human hypertension in part through a mechanism involving smooth muscle dysfunction initiated by a loss of CUL3-mediated degradation of RhoA. PMID:27882355

  15. Relation of epicardial adipose tissue with arterial compliance and stiffness in patients with hypertension.

    PubMed

    Korkmaz, Levent; Cirakoglu, Omer Faruk; Ağaç, Mustafa Tarik; Erkan, Hakan; Korkmaz, Ayca Ata; Acar, Zeydin; Kul, Selim; Hatem, Engin; Çelik, Şükrü

    2014-09-01

    The main aim of the present study was to investigate the association between epicardial adipose tissue (EAT) and arterial function in patients with asymptomatic hypertension. Patients with hypertension (n = 155) were enrolled consecutively. Patients with decreased arterial compliance (AC) and increased cardioankle vascular index (CAVI) had higher EAT values compared with those with normal AC and CAVI (6.23 ± 1.67 vs 4.91 ± 1.40, P < .001 and 6.02 ± 1.61 vs 4.96 ± 1.46, P = .01, respectively). Analysis using the receiver-operating characteristics curve demonstrated that EAT 5.5 mm constitutes the cutoff value for the presence of increased CAVI with 67% sensitivity and 62% specificity (area under the curve [AUC]: 0.702, 95% confidence interval [CI] 0.590-0.814) and decreased AC with 77% sensitivity and 65% specificity (AUC: 0.756, 95% CI 0.645-0.867). Assessment of EAT during echocardiography examination may provide information on arterial function in patients with asymptomatic hypertension. The link between EAT and arterial stiffness deserves further investigation.

  16. Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension.

    PubMed

    Milazzo, Valeria; Maule, Simona; Di Stefano, Cristina; Tosello, Francesco; Totaro, Silvia; Veglio, Franco; Milan, Alberto

    2015-12-01

    Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.

  17. Ambulatory Arterial Stiffness Index Is Higher in Hypertensive Patients with Chronic Kidney Disease

    PubMed Central

    Gismondi, Ronaldo Altenburg; Neves, Mario Fritsch; Oigman, Wille; Bregman, Rachel

    2012-01-01

    Ambulatory arterial stiffness index (AASI) is a parameter obtained from ambulatory blood pressure monitoring (ABPM) that correlates with clinical endpoints. The aim of this study was to compare AASI in nondiabetic hypertensive patients with and without chronic kidney disease (CKD). Subjects with systemic arterial hypertension (SAH, n = 30) with normal renal function, aged 40 to 75 years, were compared to hypertensive patients with CKD (n = 30) presenting estimated glomerular filtration rate (eGFR) <60 mL/min by MDRD formula. ABPM was carried out in all patients. In CKD group, eGFR was 35.3 ± 2.8 ml/min. The mean 24-hour systolic and diastolic blood pressure (BP) was similar in both groups. AASI was significantly higher in CKD group (0.45 ± 0.03 versus 0.37 ± 0.02, P < 0.05), positively correlated to age (r = 0.38, P < 0.01) and pulse pressure (r = 0.43, P < 0.01) and negatively correlated to nocturnal BP fall (r = -0.28, P = 0.03). These findings indicate the presence of stiffer vessels in CKD hypertensive patients. PMID:22675608

  18. Effect of Lysyl Oxidase Inhibition on Angiotensin II-Induced Arterial Hypertension, Remodeling, and Stiffness

    PubMed Central

    Eberson, Lance S.; Sanchez, Pablo A.; Majeed, Beenish A.; Tawinwung, Supannikar; Secomb, Timothy W.; Larson, Douglas F.

    2015-01-01

    It is well accepted that angiotensin II (Ang II) induces altered vascular stiffness through responses including both structural and material remodeling. Concurrent with remodeling is the induction of the enzyme lysyl oxidase (LOX) through which ECM proteins are cross-linked. The study objective was to determine the effect of LOX mediated cross-linking on vascular mechanical properties. Three-month old mice were chronically treated with Ang II with or without the LOX blocker, β -aminopropionitrile (BAPN), for 14 days. Pulse wave velocity (PWV) from Doppler measurements of the aortic flow wave was used to quantify in vivo vascular stiffness in terms of an effective Young’s modulus. The increase in effective Young’s modulus with Ang II administration was abolished with the addition of BAPN, suggesting that the material properties are a major controlling element in vascular stiffness. BAPN inhibited the Ang II induced collagen cross-link formation by 2-fold and PWV by 44% (P<0.05). Consistent with this observation, morphometric analysis showed that BAPN did not affect the Ang II mediated increase in medial thickness but significantly reduced the adventitial thickness. Since the hypertensive state contributes to the measured in vivo PWV stiffness, we removed the Ang II infusion pumps on Day 14 and achieved normal arterial blood pressures. With pump removal we observed a decrease of the PWV in the Ang II group to 25% above that of the control values (P=0.002), with a complete return to control values in the Ang II plus BAPN group. In conclusion, we have shown that the increase in vascular stiffness with 14 day Ang II administration results from a combination of hypertension-induced wall strain, adventitial wall thickening and Ang II mediated LOX ECM cross-linking, which is a major material source of vascular stiffening, and that the increased PWV was significantly inhibited with co-administration of BAPN. PMID:25875748

  19. Peripheral Augmentation Index is Associated With the Ambulatory Arterial Stiffness Index in Patients With Hypertension

    PubMed Central

    Heffernan, Kevin S.; Patvardhan, Eshan A.; Karas, Richard H.; Kuvin, Jeffrey T.

    2011-01-01

    Background Vascular dysfunction is highly prevalent if not ubiquitous in patients with hypertension. We compared two different measures of vascular function obtained from digital volume waveforms with measures of ventricular-vascular load derived from 24-hour blood pressure (BP) recordings in patients with hypertension. Methods Digital pulsatile volume waveforms were captured via plethysmography (peripheral arterial tone, PAT) and used to derive augmentation index (a measure of ventricular-vascular coupling) and the pulse wave amplitude-reactive hyperemia index (a measure of microvascular reactivity). Ambulatory arterial stiffness index (AASI) and the BP variability ratio (BPVR) were derived from 24-hour ambulatory BP recordings. Results There was a positive association between PAT-AIx and AASI (r = 0.52, P < 0.05). There was also a positive association between PAT-AIx and BPVR (r = 0.37, P < 0.05). PAT-AIx was not associated with PWA-RHI (r = -0.14, P > 0.05). PWA-RHI was not associated with AASI or BPVR (P > 0.05). Conclusions PAT-AIx is associated with ambulatory measures of vascular function and may offer clinical insight into vascular burden and cardiovascular disease risk in patients with hypertension independent of information obtained from PWA-RHI.

  20. Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension

    PubMed Central

    Kheyfets, Vitaly O.; Schroeder, Joyce D.; Dunning, Jamie; Shandas, Robin; Buckner, J. Kern; Browning, James; Hertzberg, Jean; Hunter, Kendall S.; Fenster, Brett E.

    2016-01-01

    Abstract Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = −0.74, P < 0.001), mean pulmonary pressure (ρ = −0.64, P = 0.006), and elastance (ρ = −0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = −0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR–based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH. PMID:27076906

  1. Long-term anti-hypertensive therapy with benidipine improves arterial stiffness over blood pressure lowering.

    PubMed

    Kita, Toshihiro; Suzuki, Yoshihiko; Eto, Tanenao; Kitamura, Kazuo

    2005-12-01

    Pulse wave velocity (PWV) reflects arterial stiffness and is an independent predictor of cardiovascular mortality and morbidity. However, because it is closely related to blood pressure (BP), PWV is an imperfect measure for evaluating the effects of anti-hypertensive drugs on arterial wall properties. To clarify the effect of benidipine on arterial properties, we first derived the regression line between BP and PWV changes in a short-term experiment. Using this line, we evaluated the long-term effect of benidipine on PWV changes. In the short-term experiment, 29 participants were intravenously administered nicardipine for 90 min. Maximum decreases of brachial-ankle PWV (baPWV) were plotted against the corresponding decreases in BP. In the long-term experiment, 9 hypertensive patients were treated with benidipine for 1 year, during which BP and baPWV were monitored. After 1 year, benidipine was suspended for 2 weeks, and BP and baPWV were reevaluated. In the short-term experiment, PWV was dependent on BP only, and the equation of the regression line was deltaPWV (cm/s) =10.114 x deltaMBP (mmHg) (r=0.913) or deltaPWV (%) =0.719 x deltaMBP (%) (r=0.926). In the long-term therapy, benidipine treatment achieved stable BP control within 3 months; the real PWV decreases (r-PWV) were almost identical to the PWV decrease estimated (e-PWV) from BP lowering at 3 months. However, r-PWV exceeded e-PWV after 6 months. Relative BP and PWV improvements compared to the control were maintained 2 weeks after suspension of benidipine. In conclusion, long-term benidipine administration improves arterial wall properties beyond what can be accounted for by changes in BP.

  2. Arterial Stiffness: Recommendations and Standardization

    PubMed Central

    Townsend, Raymond R.

    2017-01-01

    The use of arterial stiffness measurements in longitudinal cohorts of normal populations, hypertensive patients, diabetic patients, healthy elderly, and patients on hemodialysis have confirmed the value of this important measure of arterial health, and established its complementary role to measures of blood pressure. Its contribution to understanding cardiovascular and mortality risk beyond blood pressure measurements has moved measures of arterial stiffness into the ranks of factors such as elevated cholesterol, diabetes, and left ventricular hypertrophy in considering cardiovascular risk. The recent international collaboration's publication of reference ranges for normal people and those with hypertension, along with the American Heart Association's recent scientific statement on standardizing arterial stiffness measurements are important aspects to consider in future studies employing these valuable methods, particularly as interventions that not only lower blood pressure but improve arterial function are tested in the clinical arena. PMID:28275588

  3. Effect of continuous positive airway pressure on arterial stiffness in patients with obstructive sleep apnea and hypertension: a meta-analysis.

    PubMed

    Lin, Xin; Chen, Gongping; Qi, Jiachao; Chen, Xiaofang; Zhao, Jiangming; Lin, Qichang

    2016-12-01

    Arterial stiffness has been recognized as a predictor of cardiovascular and all-cause mortality in hypertensive patients. However, the impact of continuous positive airway pressure (CPAP) on arterial stiffness in patients with OSA and hypertension remains inconclusive. We performed a meta-analysis to determine whether effective CPAP therapy could decrease arterial stiffness. Two reviewers independently searched PubMed, Embase, Web of Science and Cochrane Library prior to March 5, 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of arterial stiffness was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy. Three articles with 186 patients were included in this meta-analysis, including two observational studies and one randomized controlled study. The meta-analysis showed that CPAP was associated with a statistically significant decrease in arterial stiffness in patients with OSA and hypertension (SMD = -0.65, 95 % confidence interval (CI) = -1.14 to -0.16, z = 2.60, p = 0.009). Our meta-analysis suggested that CPAP among OSA and hypertensive patients was significantly associated with a decrease in arterial stiffness. Further prospective large-scale multicenter RCTs are needed to explore the precise impact of CPAP therapy on arterial stiffness in patients with OSA and hypertension.

  4. The age-related increase in arterial stiffness is augmented in phases according to the severity of hypertension.

    PubMed

    Tomiyama, Hirofumi; Arai, Tomio; Koji, Yutaka; Yambe, Minoru; Motobe, Kohki; Zaydun, Glunisa; Yamamoto, Yoshio; Hori, Saburoh; Yamashina, Akira

    2004-07-01

    Although blood pressure and age are major determinants of arterial stiffness, it is still unclear whether age-related changes in arterial stiffness are similar among subjects with different degrees of severity of hypertension. The present study examined the association between age and pulse wave velocity in subjects with different degrees of hypertension stratified according to the JNC-7 classification (Normal, Prehypertensive, and Stage I or II Hypertensive subjects). A number of 5,312 subjects (age range, 30-79 years) with no atherosclerotic risk factors other than high blood pressure were selected from two cohorts who regularly underwent annual health checkups, including the measurement of brachial-ankle pulse wave velocity (baPWV). baPWV was increased according to the severity of hypertension in all age groups. The association between age and baPWV formed a quadratic curve in each stage in both genders. The steepness of the slope of the quadratic curve increased according to the severity of hypertension. In each stage of hypertension, age and the baPWV were divided into tertiles. After adjustment for systolic and diastolic blood pressure, the odds ratio of having an increased baPWV in the 3rd age tertile (the highest-age group) was found to increase according to the severity of hypertension. In conclusion, the age-related increase of baPWV was shown to be augmented in phases according to the severity of hypertension, and this augmentation occurred even between the Normal and Prehypertensive stages. These results support the JNC-7 recommendations for a strict control of blood pressure even in the elderly.

  5. Activation of SIRT1 Attenuates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhancing AMP-Activated Protein Kinase Activity.

    PubMed

    Gao, Diansa; Zuo, Zhong; Tian, Jing; Ali, Quaisar; Lin, Yi; Lei, Han; Sun, Zhongjie

    2016-11-01

    Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by ≈45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity and blood pressure in Klotho-haplodeficient (KL(+/-)) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in KL(+/-) mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/d, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in KL(+/-) mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase α (AMPKα) and endothelial NO synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720. In conclusion, this study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells. Pharmacological activation of SIRT1 may be an effective therapeutic strategy for arterial stiffness and hypertension.

  6. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension.

    PubMed

    Mackenzie, Isla S; McEniery, Carmel M; Dhakam, Zahid; Brown, Morris J; Cockcroft, John R; Wilkinson, Ian B

    2009-08-01

    Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening. Although various drug therapies are used to lower peripheral blood pressure (BP) in patients with isolated systolic hypertension, the effects of the 4 major classes of antihypertensive agents on central BP, pulse pressure (PP) amplification, and arterial stiffness in this condition are not clear. Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension (systolic BP > or =140 mm Hg and diastolic BP hypertension, the choice of therapy may be influenced by these findings in the future.

  7. Age, hypertension and arterial function.

    PubMed

    McEniery, Carmel M; Wilkinson, Ian B; Avolio, Albert P

    2007-07-01

    1. Ageing exerts a marked effect on the cardiovascular system and, in particular, the large arteries. Using a variety of techniques to assess arterial stiffness, many cross-sectional studies have demonstrated a significant relationship between age and aortic stiffness, although the age-related changes observed in peripheral arteries appear to be less marked. 2. The relationship between arterial stiffness and hypertension is more complex. The distending, or mean arterial, pressure is an important confounder of measurements of arterial stiffness and, therefore, must be taken into consideration when assessing arterial stiffness in hypertensive subjects or investigating the effect of antihypertensive agents. Current methods for correcting for differences in distending pressure involve pharmacological manipulation, statistical correction or mathematical manipulation of stiffness indices. 3. Many studies have provided evidence that both peripheral (muscular) and central (elastic) arteries are stiffer in subjects with mixed (systolic/diastolic) hypertension compared with normotensive subjects. However, it is unclear to what extent differences in mean arterial pressure explain the observed differences in hypertensive subjects. In contrast, isolated systolic hypertension is associated with increased aortic, but not peripheral artery, stiffness, although the underlying mechanisms are somewhat unclear. 4. Traditional antihypertensive agents appear to reduce arterial stiffness, but mostly via an indirect effect of lowering mean pressure. Therefore, therapies that target the large arteries to reduce stiffness directly are urgently required. Agents such as nitric oxide donors and phosphodiesterase inhibitors may be useful in reducing stiffness via functional mechanisms. In addition, inhibitors or breakers of advanced glycation end-product cross-links between proteins, such as collagen and elastin, hold substantial promise.

  8. A constitutive modeling interpretation of the relationship among carotid artery stiffness, blood pressure, and age in hypertensive subjects.

    PubMed

    Spronck, Bart; Heusinkveld, Maarten H G; Donders, Wouter P; de Lepper, Anouk G W; Op't Roodt, Jos; Kroon, Abraham A; Delhaas, Tammo; Reesink, Koen D

    2015-03-15

    Aging has a profound influence on arterial wall structure and function. We have previously reported the relationship among pulse wave velocity, age, and blood pressure in hypertensive subjects. In the present study, we aimed for a quantitative interpretation of the observed changes in wall behavior with age using a constitutive modeling approach. We implemented a model of arterial wall biomechanics and fitted this to the group-averaged pressure-area (P-A) relationship of the "young" subgroup of our study population. Using this model as our take-off point, we assessed which parameters had to be changed to let the model describe the "old" subgroup's P-A relationship. We allowed elastin stiffness and collagen recruitment parameters to vary and adjusted residual stress parameters according to published age-related changes. We required wall stress to be homogeneously distributed over the arterial wall and assumed wall stress normalization with age by keeping average "old" wall stress at the "young" level. Additionally, we required axial force to remain constant over the cardiac cycle. Our simulations showed an age-related shift in pressure-load bearing from elastin to collagen, caused by a decrease in elastin stiffness and a considerable increase in collagen recruitment. Correspondingly, simulated diameter and wall thickness increased by about 20 and 17%, respectively. The latter compared well with a measured thickness increase of 21%. We conclude that the physiologically realistic changes in constitutive properties we found under physiological constraints with respect to wall stress could well explain the influence of aging in the stiffness-pressure-age pattern observed.

  9. Epidemiology of the arterial stiffness.

    PubMed

    Breithaupt-Grögler, K; Belz, G G

    1999-06-01

    Aortic stiffening is as much an important risk factor in cardiovascular morbidity and mortality, as it serves as reliable surrogate marker for clinical endpoints like myocardial and cerebrovascular incidents. Elevated aortic stiffness induces high systolic blood pressure, augmented pulse pressure with increased ventricular afterload, reduced subendocardial blood flow and augmented pulsatile stress in the peripheral arteries. Factors with relevant impact on the epidemiology of arterial stiffness are widely spread. 3 major groups of parameters influencing the stiffness of the aorta and the large arteries have been studied and described up to now: (i) physiological properties like age, gender, body height, pressure, hormonal state, genetic factors; (ii) environmental factors like nutrition (fish-, salt-, garlic consumption), smoking, performance of sports and aerobic capacity; (iii) diseases like hypertension, hypercholesterolemia, diabetes, coronary heart disease, cerebrovascular disease, renal failure, Marfan-syndrome, growth hormone deficiency. Close association between several of these factors impedes analyzing them independently from each other. Age and blood pressure were found to be the most prominent predictors of arterial stiffness in normal as well as in disease populations. Physiological and environmental factors can modulate these effects of aging, diseases generally seem to amplify them.

  10. Reduction of plasma aldosterone and arterial stiffness in obese pre- and stage1 hypertensive subjects after aerobic exercise

    PubMed Central

    Collier, SR; Sandberg, K; Moody, AM; Frechette, V; Curry, CD; Ji, H; Gowdar, R; Chaudhuri, D; Meucci, M

    2017-01-01

    Obesity-related hypertension is associated with increased activity of the renin-angiotensin-aldosterone system (RAAS), increasing arterial stiffness. Aerobic exercise decreases pulse wave velocity (PWV), therefore a treatment option for hypertension and obesity. Assess RAAS activity and PWV before and after 4 weeks of aerobic training in unmedicated, pre-to-stage-1 hypertensives. Ten obese subjects (52±3.2 years, body mass index=33.5±1.4) performed 30 min of aerobic exercise on a treadmill 3 days per week at 65% of peak oxygen consumption (VO2peak). Descriptive characteristics, systolic and diastolic blood pressure (SBP and DBP), PWV, and a blood draw was performed at baseline, following the 4-week control and training interventions. No differences in descriptive characteristics during the control period were observed, however, a significant decrease in plasma aldosterone (ALDO) (255.4±75 to 215.8±66 pg ml−1, P=0.001), SBP (140±12 to 136±10.4 mm Hg; P=0.02), DBP (89±4.2 to 85±6.3 mm Hg; P =0.03) and central PWV (11.2±0.6 to 9.8±0.8 m s−1; P=0.04) was shown pre-to-post exercise training. Four weeks of moderate-intensity aerobic training in obese, hypertensives decreases plasma ALDO independently of body weight and is significantly correlated to decreases in PWV reductions. PMID:24785976

  11. Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction.

    PubMed

    Hummel, Scott L; Seymour, E Mitchell; Brook, Robert D; Kolias, Theodore J; Sheth, Samar S; Rosenblum, Hannah R; Wells, Joanna M; Weder, Alan B

    2012-11-01

    Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In salt-sensitive HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155-138 mm Hg; P=0.02) and diastolic blood pressure (79-72 mm Hg; P=0.04), 24-hour ambulatory systolic (130-123 mm Hg; P=0.02) and diastolic blood pressure (67-62 mm Hg; P=0.02), and carotid-femoral pulse wave velocity (12.4-11.0 m/s; P=0.03). Urinary F2-isoprostanes decreased by 31% (209-144 pmol/mmol Cr; P=0.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of salt-sensitive hypertension, a phenotype present in many HFPEF animal models and suggest shared pathophysiological mechanisms linking these 2 conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

  12. Arterial stiffness in diabetes mellitus.

    PubMed

    Prenner, Stuart B; Chirinos, Julio A

    2015-02-01

    Arterial stiffness is an age-related process that is a shared consequence of numerous diseases including diabetes mellitus (DM), and is an independent predictor of mortality both in this population and in the general population. While much has been published about arterial stiffness in patients with DM, a thorough review of the current literature is lacking. Using a systematic literature search strategy, we aimed to summarize our current understanding related to arterial stiffness in DM. We review key studies demonstrating that, among patients with established DM, arterial stiffness is closely related to the progression of complications of DM, including nephropathy, retinopathy, and neuropathy. It is also becoming clear that arterial stiffness can be increased even in pre-diabetic populations with impaired glucose tolerance, and in those with the metabolic syndrome (METS), well before the onset of overt DM. Some data suggests that arterial stiffness can predict the onset of DM. However, future work is needed to further clarify whether large artery stiffness and the pulsatile hemodynamic changes that accompany it are involved in the pathogenesis of DM, and whether interventions targeting arterial stiffness are associated with improved clinical outcomes in DM. We also review of the potential mechanisms of arterial stiffness in DM, with particular emphasis on the role of advanced glycation endproducts (AGEs) and nitric oxide dysregulation, and address potential future directions for research.

  13. Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk.

    PubMed

    Casanova, Marcela A; Medeiros, Fernanda; Trindade, Michelle; Cohen, Célia; Oigman, Wille; Neves, Mario Fritsch

    2017-01-01

    Association between hypertriglyceridemia and cardiovascular (CV) disease is still controversial. The purpose of this study was to compare omega-3 and ciprofibrate effects on the vascular structure and function in low and high CV risk hypertensive patients with hypertriglyceridemia. Twenty-nine adults with triglycerides 150-499 mg/dL were divided into low (<7.5%) and high (≥7.5%) CV risk, randomized to receive omega-3 fatty acids 1800 mg/d or ciprofibrate 100 mg/d for 12 weeks. Treatment was switched after 8-week washout. Clinical evaluation and vascular tests were assessed at baseline and after intervention. Peripheral (131 ± 3 to 125 ± 3 mm Hg, P < .05) and aortic (124 ± 3 to 118 ± 2 mg/dL, P < .05) systolic blood pressure were decreased by ciprofibrate in low-risk patients. In high-risk patients, pulse wave velocity was reduced (10.4 ± 0.4 to 9.4 ± 0.3 m/s, P < .05) and flow-mediated dilation was increased (11.1 ± 1.6 to 13.5 ± 1.2%, P < .05) by omega-3. In conclusion, omega-3 improved arterial stiffness and endothelial function, pointing out the beneficial effect of this therapy on vascular aging, in high-risk patients.

  14. Effect of angiotensin-converting enzyme inhibitors on arterial stiffness in hypertension: systematic review and meta-analysis.

    PubMed

    Mallareddy, Madhavi; Parikh, Chirag R; Peixoto, Aldo J

    2006-06-01

    Arterial stiffness is an independent cardiovascular prognostic factor and is modulated by angiotensin-converting enzyme inhibitors (ACEIs). The authors performed a meta-analysis of clinical trials investigating the effects of ACEIs on pulse wave velocity (PWV) or augmentation index. The search included randomized clinical trials as well as uncontrolled studies that measured in-treatment changes in arterial stiffness. The authors performed separate analyses for carotid-femoral PWV, brachioradial PWV, and augmentation index. Average absolute and relative reduction in mean arterial pressure and PWV were -15.4 mm Hg and -13.04% and -1.15 m/s and -9.74% for carotid-femoral PWV studies; and -11.2 mm Hg and -9.3% and -1.9 m/s and -16.7% for brachioradial PWV studies. There was a greater reduction in augmentation index by ACEIs when compared with controls (-1.0% to -5.3%). The authors conclude that ACEIs have modest beneficial effects on arterial stiffness measured as PWV and augmentation index, and this effect is at least partly independent of changes in blood pressure.

  15. Vascular Health Assessment of The Hypertensive Patients (VASOTENS) Registry: Study Protocol of an International, Web-Based Telemonitoring Registry for Ambulatory Blood Pressure and Arterial Stiffness

    PubMed Central

    Parati, Gianfranco; Avolio, Alberto; Rogoza, Anatoly N; Kotovskaya, Yulia V; Mulè, Giuseppe; Muiesan, Maria Lorenza; Orlova, Iana A; Grigoricheva, Elena A; Cardona Muñoz, Ernesto; Zelveian, Parounak H; Pereira, Telmo; Peixoto Maldonado, João Manuel

    2016-01-01

    Background Hypertension guidelines recommend ambulatory blood pressure (ABP), central aortic pressure (CAP), and pulse wave velocity (PWV) as parameters for estimating blood pressure (BP) control and vascular impairment. Recent advances in technology have enabled devices to combine non-invasive estimation of these parameters over the 24-hour ABP monitoring. However, currently there is limited evidence on the usefulness of such an approach for routine hypertension management. Objective We recently launched an investigator-initiated, international, multicenter, observational, prospective study, the Vascular health Assessment Of The Hypertensive patients (VASOTENS) Registry, aimed at (1) evaluating non-invasive 24-hour ABP and arterial stiffness estimates (through 24-hour pulse wave analysis, PWA) in hypertensive subjects undergoing ambulatory blood pressure monitoring (ABPM) for clinical reasons; (2) assessing the changes in estimates following treatment; (3) weighing the impact of 24-hour PWA on target organ damage and cardiovascular prognosis; (4) assessing the relationship between arterial stiffness, BP absolute mean level and variability, and prognosis; and (5) validating the use of a 24-hour PWA electronic health (e-health) solution for hypertension screening. Methods Approximately 2000 subjects, referred to 20 hypertension clinics for routine diagnostic evaluation and follow-up of hypertension of any severity or stage, will be recruited. Data collection will include ABPM, performed with a device allowing simultaneous non-invasive assessment of 24-hour CAP and arterial stiffness (BPLab), and clinical data (including cardiovascular outcomes). As recommended by current guidelines, each patient will be followed-up with visits occurring at regular intervals (ideally every 6 months, and not less than once a year depending on disease severity). A Web-based telemedicine platform (THOLOMEUS) will be used for data collection. The use of the telemedicine system will allow

  16. Arterial stiffness: pathophysiology and clinical impact.

    PubMed

    London, Gérard M; Marchais, Sylvain J; Guerin, Alain P; Pannier, Bruno

    2004-01-01

    The ill effects of hypertension are usually attributed to a reduction in the caliber or the number of arterioles, resulting in an increase in total peripheral resistance (TPR). This definition does not take into account the fact that BP is a cyclic phenomenon with systolic and diastolic BP being the limits of these oscillations. The appropriate term to define the arterial factor(s) opposing LV ejection is aortic input impedance which depends on TPR, arterial distensibility (D), and wave reflections (WR). D defines the capacitive properties of arterial stiffness, whose role is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of D. These parameters are BP dependent, and arteries become stiffer at high pressure. In to D which provides information about the of artery as a hollow structure, the elastic incremental modulus (Einc) characterizes the properties of the arterial wall biomaterials, independently of vessel geometry. As an alternative, arterial D can be evaluated by measuring the pulse wave velocity (PWV) which increases with the stiffening of arteries. Arterial stiffening increases left ventricular (LV) afterload and alters the coronary perfusion. With increased PWV, the WR impacts on the aorta during systole, increasing systolic pressures and myocardial oxygen consumption, and decreasing diastolic BP and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix (arteriosclerosis) as classically observed during aging or in arterial hypertension. The arterial stiffening estimated by changes in aortic PWV and intensity of WR are independent predictors of survival in end stage renal disease (ESRD) and general population. Improvement of arterial stiffening could be obtained by antihypertensive treatmen as observed with the calcium

  17. Arterial Stiffness and Cardiovascular Therapy

    PubMed Central

    Janić, Miodrag; Lunder, Mojca; Šabovič, Mišo

    2014-01-01

    The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE). PMID:25170513

  18. Therapeutic modification of arterial stiffness: An update and comprehensive review

    PubMed Central

    Wu, Ching-Fen; Liu, Pang-Yen; Wu, Tsung-Jui; Hung, Yuan; Yang, Shih-Ping; Lin, Gen-Min

    2015-01-01

    Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision. PMID:26635922

  19. Large Artery Stiffness Assessment Using SphygmoCor Technology

    PubMed Central

    Butlin, Mark; Qasem, Ahmad

    2017-01-01

    Large artery stiffness assessment has been an integral part of the SphygmoCor technology since 1998. Aortic stiffness is approximated with non-invasive measurement of carotid-femoral pulse wave velocity, with improvements made with time to make the assessment procedure quicker and more user independent. Also standard in the devices is the ability to reliably calculate the central aortic waveform shape from a peripheral pressure waveform from either the brachial or radial artery. This waveform contains much information beyond peak and trough (systolic and diastolic pressure). Relative waveform features such as the augmentation index, wave reflection magnitude, reflection time index, and subendocardial viability ratio are parameters that are influenced by the stiffness of systemic arteries. This article briefly describes these parameters related to large artery stiffness and provides reference to validation and repeatability studies relative to the clinical use of the SphygmoCor devices. It is beyond the scope to review here the 424 original research articles that have employed SphygmoCor devices in measuring arterial stiffness. Instead, the method of measurement across the devices is described, including tonometry, volumetric displacement through cuff placement around limbs, and ambulatory monitoring. Key population and subpopulation studies are cited where the average stiffness parameter progression with age and gender, as measured by SphygmoCor devices, is quantified in the healthy and general population. Finally, with reference to guidelines from working groups on arterial stiffness and hypertension, the clinical utility of large artery stiffness measurement is discussed in the context of the arterial stiffness parameters provided by the SphygmoCor systems. PMID:28229053

  20. Crosstalk between oxidative and nitrosative stress and arterial stiffness.

    PubMed

    Mozos, Ioana; Luca, Constantin Tudor

    2017-02-01

    Arterial stiffness, the expression of reduced arterial elasticity, is an effective predictor of cardiovascular disorders. Oxidative stress is an imbalance between exposure to toxic reactive oxygen species (ROS) and antioxidant systems. The increase in reactive nitrogen species (RNS) is termed nitrosative stress. We review the main mechanisms and products linking arterial stiffness with oxidative and nitrosative stress in several disorders, focusing on recent experimental and clinical data, and the mechanisms explaining benefits of antioxidant therapy. Oxidative and nitrosative stress play important roles in arterial stiffness elevation in several disorders, including diabetes mellitus, hypertension, metabolic syndrome, obesity, peripheral arterial disease, chronic obstructive pulmonary disease, systemic lupus erythematosus, thalassemia, Kawasaki disease and malignant disorders. Oxidative and nitrosative stress are responsible for endothelial dysfunction due to uncoupling of the nitric oxide synthase, oxidative damage to lipids, proteins and DNA in vascular endothelial cells, associated with inflammation, arteriosclerosis and atherosclerosis. Regular physical exercise, caloric restriction, red wine, statins, sartans, metformin, oestradiol, curcumin and combinations of antioxidant vitamins are therapeutic strategies that may decrease arterial stiffness and oxidative stress thus reducing the risk of cardiovascular events. ROS and RNS represent potential therapeutic targets for preventing progression of arterial stiffness.

  1. A Review of Genetics, Arterial Stiffness, and Blood Pressure in African Americans

    PubMed Central

    Hall, Jennifer L.; Duprez, Daniel A.; Barac, Ana; Rich, Stephen S.

    2012-01-01

    The prevalence of hypertension in African Americans in the United States is amongst the highest in the world and increasing. The identification of genes and pathways regulating blood pressure in African Americans has been challenging. An early predictor of hypertension is arterial stiffness. The prevalence of arterial stiffness is significantly higher in African Americans compared to Caucasians. Approximately 20% of the variance in arterial stiffness is estimated to be heritable. Identifying genes and biological pathways regulating arterial stiffness may provide insight into the genetics underlying the increased risk of hypertension in African Americans. This paper reviews the genetic findings to date in the area of arterial stiffness and blood pressure in African Americans with an emphasis on the current limitations and new efforts to move the field forward. PMID:22492025

  2. Arterial stiffness profiles: investigating various sections of the arterial tree of African and Caucasian people.

    PubMed

    Schutte, Aletta E; Huisman, Hugo W; Schutte, Rudolph; Van Rooyen, Johannes M; Malan, Leoné; Malan, Nicolaas T; Reimann, Manja

    2011-01-01

    In Africans, arterial stiffness progression seems more pronounced compared to Caucasians. We compared the arterial stiffness profiles of different age groups and focused on muscular arteries and two more central arterial segments in African and Caucasian people from South Africa. In African (N = 374) and Caucasian (N = 376) participants (20-70 years), we measured carotid-radial (C-R) and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic characteristic impedance (Zao). Major findings were that normotensive and high-normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P = .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with aging. High-normal/hypertensive Africans had significantly stiffer arteries than hypertensive Caucasians for almost all age groups, and for all stiffness measures. African C-R PWV correlated significantly with blood pressure (BP), but not with age. Opposite results were observed for Caucasians. In conclusion, the stiffness of muscular arteries is already elevated in young Africans, in both those with normal or elevated BP. This is possibly due to an earlier deterioration during childhood, or perhaps already present from birth. Also, in Caucasians stiffness seems more age-related, while in Africans it seems to be more pressure-related.

  3. Physical inactivity and arterial stiffness in COPD

    PubMed Central

    Sievi, Noriane A; Franzen, Daniel; Kohler, Malcolm; Clarenbach, Christian F

    2015-01-01

    Background Arterial stiffness is an important predictor of cardiovascular risk besides classic cardiovascular risk factors. Previous studies showed that arterial stiffness is increased in patients with COPD compared to healthy controls and exercise training may reduce arterial stiffness. Since physical inactivity is frequently observed in patients with COPD and exercise training may improve arterial stiffness, we hypothesized that low daily physical activity may be associated with increased arterial stiffness. Methods In 123 patients with COPD (72% men; mean [standard deviation] age: 62 [7.5] years; median [quartile] forced expiratory volume in 1 second 35 [27/65] %predicted), arterial stiffness was assessed by augmentation index (AI). Daily physical activity level (PAL) was measured by an activity monitor (SenseWear Pro™) >1 week. The association between AI and PAL was investigated by univariate and multivariate regression analysis, taking into account disease-specific characteristics and comorbidities. Results Patients suffered from moderate (35%), severe (32%), and very severe (33%) COPD, and 22% were active smokers. Median (quartile) PAL was 1.4 (1.3/1.5) and mean (standard deviation) AI 26% (9.2%). PAL showed a negative association with AI (B=−9.32, P=0.017) independent of age, sex, blood pressure, and airflow limitation. Conclusion In COPD patients, a higher PAL seems to favorably influence arterial stiffness and therefore may reduce cardiovascular risk. Clinical Trial Registration http://www.ClinicalTrials.gov, NCT01527773 PMID:26392763

  4. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Home Health Conditions pulmonary arterial hypertension pulmonary arterial hypertension Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

  5. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    PubMed

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  6. Arterial Stiffness in Nonhypertensive Type 2 Diabetes Patients in Ghana

    PubMed Central

    Antwi, Daniel A.; Gyan, Ben

    2016-01-01

    Background. Increased arterial stiffness is an independent cardiovascular risk factor in diabetes patients and general population. However, the contribution of diabetes to arterial stiffness is often masked by coexistent obesity and hypertension. In this study, we assessed arterial stiffness in nonhypertensive, nonobese type 2 diabetes (T2DM) patients in Ghana. Methods. In case-control design, 166 nonhypertensive, nonobese participants, comprising 96 T2DM patients and 70 nondiabetes controls, were recruited. Peripheral and central blood pressure (BP) indices were measured, and arterial stiffness was assessed as aortic pulse wave velocity (PWVao), augmentation index (AIx), cardioankle vascular index (CAVI), and heart-ankle pulse wave velocity (haPWV). Results. With similar peripheral and central BP indices, T2DM patients had higher PWVao (8.3 ± 1 versus 7.8 ± 1.3, p = 0.044) and CAVI (7.9 ± 1.2 versus 6.9 ± 0.7, p = 0.021) than nondiabetic control. AIx and haPWV were similar between T2DM and nondiabetic controls. Multiple regression models showed that, in the entire study participants, the major determinants of PWVao were diabetes status, age, gender, systolic BP, and previous smoking status (β = 0.22, 0.36, 0.48, 0.21, and 0.25, resp.; all p < 0.05); the determinants of CAVI were diabetes status, age, BMI, heart rate, HbA1c, total cholesterol, HDL cholesterol, and previous smoking status (β = 0.21, 0.38, 0.2, 0.18, 0.24. 0.2, −0.19, and 0.2, resp.; all p < 0.05). Conclusion. Our findings suggest that nonhypertensive, nonobese T2DM patients have increased arterial stiffness without appreciable increase in peripheral and central pressure indices. PMID:27774104

  7. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  8. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  9. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-07-06

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  10. Update in pulmonary arterial hypertension.

    PubMed

    Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

    2016-11-01

    Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.

  11. Early intervention of long-acting nifedipine GITS reduces brachial–ankle pulse wave velocity and improves arterial stiffness in Chinese patients with mild hypertension: a 24-week, single-arm, open-label, prospective study

    PubMed Central

    Zhang, Jidong; Wang, Yan; Hu, Haijuan; Yang, Xiaohong; Tian, Zejun; Liu, Demin; Gu, Guoqiang; Zheng, Hongmei; Xie, Ruiqin; Cui, Wei

    2016-01-01

    Background Nifedipine gastrointestinal therapeutic system (GITS) is used to treat angina and hypertension. The authors aimed to study the early intervention impact on arterial stiffness and pulse wave velocity (PWV) independent of its blood-pressure-(BP) lowering effect in mild hypertensive patients. Methods This single-center, single-arm, open-label, prospective, Phase IV study recruited patients with mild hypertension and increased PWV from December 2013 to December 2014 (N=138; age, 18–75 years; systolic blood pressure, 140–160 mmHg; diastolic BP, 90–100 mmHg; increased brachial–ankle pulse wave velocity [baPWV, ≥12 m/s]). Nifedipine GITS (30 mg/d) was administered for 24 weeks to achieve target BP of <140/90 mmHg. The dose was uptitrated at 60 mg/d in case of unsatisfactory BP reduction after 4 weeks. Primary study end point was the change in baPWV after nifedipine GITS treatment. Hemodynamic parameters (office BP, 24-hour ambulatory BP monitoring, and heart rate and adverse events) were evaluated at baseline and followed-up at 2, 4, 8, 12, 18, and 24 weeks. Results Majority of patients (n=117; 84.8%) completed the study. baPWV decreased significantly at 4 weeks compared with baseline (1,598.87±239.82 vs 1,500.89±241.15 cm/s, P<0.001), was stable at 12 weeks (1,482.24±215.14 cm/s, P<0.001), and remained steady through 24 weeks (1,472.58±205.01 cm/s, P<0.001). Office BP reduced from baseline to week 4 (154/95 vs 136/85 mmHg) and remained steady until 24 weeks. Nifedipine GITS significantly decreased 24-hour ambulatory BP monitoring (P<0.001) after 24 weeks from baseline. Mean arterial pressure and pulse pressure were lowered significantly after 4, 12, and 24 weeks of treatment (P<0.001). These changes in baPWV were significantly correlated with changes in systolic blood pressure, diastolic BP, and mean arterial pressure (P<0.05), but not with changes in pulse pressure (P>0.05). There were no other drug-related serious adverse events. Conclusion

  12. Effects of safflower seed extract on arterial stiffness.

    PubMed

    Suzuki, Katsuya; Tsubaki, Shigekazu; Fujita, Masami; Koyama, Naoto; Takahashi, Michio; Takazawa, Kenji

    2010-11-03

    Safflower seed extract (SSE) contains characteristic polyphenols and serotonin derivatives (N-( p-coumaroyl) serotonin and N-feruloylserotonin), which are reported to inhibit oxidation of low-density lipoprotein (LDL), formation of atherosclerotic plaques, and improve arterial stiffness as assessed by pulse wave analysis in animal models. The effects of long-term supplementation with SSE on arterial stiffness in human subjects were evaluated. This doubleblind, placebo-controlled study was conducted in 77 males (35-65 years) and 15 postmenopausal females (55-65 years) with high-normal blood pressure or mild hypertension who were not undergoing treatment. Subjects received SSE (70 mg/day as serotonin derivatives) or placebo for 12 weeks, and pulse wave measurements, ie, second derivative of photoplethysmogram (SDPTG), augmentation index, and brachial-ankle pulse wave velocity (baPWV) were conducted at baseline, and at weeks 4, 8, and 12. Vascular age estimated by SDPTG aging index improved in the SSE-supplemented group when compared with the placebo group at four (P = 0.0368) and 12 weeks (P = 0.0927). The trend of augmentation index reduction (P = 0.072 versus baseline) was observed in the SSE-supplemented group, but reduction of baPWV by SSE supplementation was not observed. The SSE-supplemented group also showed a trend towards a lower malondialdehyde-modified-LDL autoantibody titer at 12 weeks from baseline. These results suggest long-term ingestion of SSE in humans could help to improve arterial stiffness.

  13. Stiffness Indices and Fractal Dimension relationship in Arterial Pressure and Diameter Time Series in-Vitro

    NASA Astrophysics Data System (ADS)

    Cymberknop, L.; Legnani, W.; Pessana, F.; Bia, D.; Zócalo, Y.; Armentano, R. L.

    2011-12-01

    The advent of vascular diseases, such as hypertension and atherosclerosis, is associated to significant alterations in the physical properties of arterial vessels. Evaluation of arterial biomechanical behaviour is related to the assessment of three representative indices: arterial compliance, arterial distensibility and arterial stiffness index. Elasticity is the most important mechanical property of the arterial wall, whose natures is strictly non-linear. Intervention of elastin and collagen fibres, passive constituent elements of the arterial wall, is related to the applied wall stress level. Concerning this, appropriate tools are required to analyse the temporal dynamics of the signals involved, in order to characterize the whole phenomenon. Fractal geometry can be mentioned as one of those techniques. The aim of this study consisted on arterial pressure and diameter signals processing, by means of nonlinear techniques based on fractal geometry. Time series morphology was related to different arterial stiffness states, generated by means of blood flow variations, during experiences performed in vitro.

  14. The role of pulmonary arterial stiffness in COPD

    PubMed Central

    Weir-McCall, Jonathan R.; Struthers, Allan D.; Lipworth, Brian J.; Houston, J. Graeme

    2015-01-01

    COPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests. The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs. PMID:26095859

  15. Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic subjects.

    PubMed

    Yang, Soo Jin; Lee, Seung-Tae; Kim, Won Jun; Park, Se Eun; Park, Sung Woo; Kim, Jong-Won; Park, Cheol-Young

    2012-01-01

    Hypertension and arterial stiffness are associated with an increasing risk of diabetes and cardiovascular diseases. This study aimed to identify genetic variants affecting hypertension and arterial stiffness in diabetic subjects and to compare genetic associations with hypertension between prediabetic and diabetic subjects. A total of 1,069 participants (326 prediabetic and 743 diabetic subjects) were assessed to determine the genetic variants affecting hypertension by analyzing 52 SNPs previously reported to be associated with hypertension. Moreover, the SNPs were tested for association with hemodynamic parameters related to hypertension. Out of the 52 SNPs analyzed, four SNPs including rs5326 (DRD1), rs1004467 (CYP17A1), rs2960306 (GRK4), and rs11191548 (near NT5C2) in diabetic subjects and rs1530440 (C10orf107) in prediabetic subjects showed a modest association with hypertension (P = 0.0265, 0.0020, 0.0066, 0.0078, and 0.0015, resp; all were insignificant after Bonferroni correction). Of these SNPs, rs1004467 in CYP17A1 was significantly associated with augmentation index in diabetic subjects who were not taking antihypertensive medication (P = 0.0001; corrected P = 0.006) but not in diabetic subjects receiving antihypertensive medication. This finding suggests that certain genetic variations found in diabetic subjects may confer arterial stiffness and the development of hypertension and also be affected by antihypertensive medication.

  16. Cerebral Small Vessel Disease and Arterial Stiffness: Tsunami Effect in the Brain?

    PubMed Central

    Saji, Naoki; Toba, Kenji; Sakurai, Takashi

    2016-01-01

    Background Cerebral small vessel diseases, including silent lacunar infarcts, white matter hyperintensities, and microbleeds, pose a risk for cerebrovascular disease, cognitive impairment, and the geriatric syndrome via effects on arterial stiffness. However, the vascular, physiological, and metabolic roles of arterial stiffness in cerebral small vessel diseases remain unclear. Summary Arterial stiffness can be assessed using various indicators such as the ankle-brachial index, pulse wave velocity, cardio-ankle vascular index, and augmentation index. Arterial stiffness is independently associated with all components of cerebral small vessel disease including silent lacunar infarcts, white matter hyperintensities, and microbleeds, although there are some methodological differences between the various surrogate markers. Evidence of arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. Further, vascular narrowing due to atherosclerosis and vascular stiffness due to lipohyalinosis can accelerate the pulse waves. This hemodynamic stress, pulsatile pressure, or blood pressure variability can cause a ‘tsunami effect’ towards the cerebral parenchyma and lead to cerebral small vessel disease. Previous studies have shown that silent lacunar infarcts and white matter hyperintensities are strongly associated with arterial stiffness. However, the association between microbleeds and arterial stiffness remains controversial, as there are two vessel mechanisms related to microbleeds: cerebral amyloid angiopathy and hypertensive small vessel disease. Key Messages Cerebral small vessel disease with associated arterial stiffness is a risk factor for silent cerebral lesions, stroke, and cognitive impairment. Improvement of the living environment, management of risk factors, and innovation and development of novel drugs that improve arterial stiffness may suppress the progression of cerebral small vessel disease, and may reduce

  17. [Arterial hypertension in children].

    PubMed

    Mota-Hernández, F

    1993-07-01

    It is considered hypertension in children, the persistent increase of the blood pressure values above percentile 95 for age and sex, in no less than three determinations, with adequate register techniques. Blood pressure is maintained mainly by the regulation of metabolism of sodium and water in the intravascular space, through the adequate balance of intake, filtration, reabsorption and renal throughout. It is also regulated by hormonal factors. Weight gain control in teen-agers could be useful to prevent high blood pressure in adults. In children, it is generally secondary to renal, reno-vascular, endocrinological or tumoral diseases. Clinical manifestations and the recommended diagnostic procedures are analysed to detect the most frequent causes of hypertension at different ages. Most cases response with antihypertensive drugs in combination with hyposodic diet. For the hypertensive crisis, asa diuretics and powerful antihypertensive drugs may be employed. Patients with chronic renal insufficiency could also need dialytic treatments. Renovascular diseases require almost always invasive treatments. Better prognosis in children with severe high blood pressure is related with recent diagnostic procedures, surgical techniques and antihypertensive drugs improvements.

  18. Capsaicin and arterial hypertensive crisis.

    PubMed

    Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; La Rocca, Roberto

    2010-10-08

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment can deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs have significantly increased mean arterial blood pressure compared with controls, and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. A case has also been reported of an arterial hypertensive crisis in a patient with a large ingestion of peppers and chili peppers the day before. We present a case of an arterial hypertensive crisis in a 19-year-old Italian man with an abundant ingestion of peppers and of chili peppers the preceding day. This case describes an unusual pattern of arterial hypertensive crisis due to capsaicin.

  19. [Chronotherapy in arterial hypertension].

    PubMed

    Bendersky, M

    2015-01-01

    The blood pressure profile in most normo- and hypertensive subjects are currently known, as well as the impact their changes induced on the cardio- and cerebrovascular risk. Ambulatory blood pressure monitoring (ABPM) has contributed greatly to the knowledge of this parameter. It to correct the schedule of drug administration (chronotherapy) with changes in any component of the BP profile that have better correlation with risk. These include the nocturnal decrease and the morning BP surge. Investigations in this direction are still scarce, and multicenter studies need to be conducted that can answer the true preventive impact of such modifications.

  20. Arterial Stiffness and Renal Replacement Therapy: A Controversial Topic

    PubMed Central

    Fischer, Edmundo Cabrera; Zócalo, Yanina; Galli, Cintia; Bia, Daniel

    2015-01-01

    The increase of arterial stiffness has been to have a significant impact on predicting mortality in end-stage renal disease patients. Pulse wave velocity (PWV) is a noninvasive, reliable parameter of regional arterial stiffness that integrates the vascular geometry and arterial wall intrinsic elasticity and is capable of predicting cardiovascular mortality in this patient population. Nevertheless, reports on PWV in dialyzed patients are contradictory and sometimes inconsistent: some reports claim the arterial wall stiffness increases (i.e., PWV increase), others claim that it is reduced, and some even state that it augments in the aorta while it simultaneously decreases in the brachial artery pathway. The purpose of this study was to analyze the literature in which longitudinal or transversal studies were performed in hemodialysis and/or peritoneal dialysis patients, in order to characterize arterial stiffness and the responsiveness to renal replacement therapy. PMID:26064684

  1. Etiology of End-Stage Renal Disease and Arterial Stiffness among Hemodialysis Patients

    PubMed Central

    El Ghoul, Balsam; Korjian, Serge; El Alam, Andrew; Samad, Salam; Dahdah, Georges; Blacher, Jacques; Safar, Michel E.

    2017-01-01

    Background. Prior studies have demonstrated that conventional and emerging CV risk factors are associated with worsening arterial stiffness among end-stage renal disease (ESRD) patients on hemodialysis. The present cross-sectional study evaluates the association between the etiology of ESRD and arterial stiffness among a cohort of hemodialysis patients. Methods. Etiology of ESRD was identified from patients' medical records and classified as either vascular renal disease, diabetic nephropathy, nondiabetic glomerulopathy, tubular interstitial nephropathy, hereditary nephropathy, or ESRD of unconfirmed etiology. Results. A total of 82 subjects were enrolled. cfPWV was independently associated with the composite of either diabetic nephropathy or vascular renal disease (p = 0.022), pulse pressure (p = 0.001), and a history of CV events (p = 0.025), but not history of hypertension or diabetes mellitus alone. The median cfPWVs in diabetic nephropathy and vascular renal disease were comparable and significantly higher than median cfPWVs in other etiologies of ESRD. Conclusion. The study suggests that the etiology of ESRD is independently associated with arterial stiffness among hemodialysis patients. Furthermore, arterial stiffness was higher among patients who developed renal sequelae of either diabetes mellitus or hypertension as compared with those who have a history of either diabetes mellitus or hypertension alone. PMID:28299320

  2. Hormones and arterial stiffness in patients with chronic kidney disease.

    PubMed

    Gungor, Ozkan; Kircelli, Fatih; Voroneanu, Luminita; Covic, Adrian; Ok, Ercan

    2013-01-01

    Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population.

  3. Genetics of pulmonary arterial hypertension.

    PubMed

    Elliott, C Gregory

    2013-12-01

    Painstaking research led to the discovery of gene mutations responsible for heritable forms of pulmonary arterial hypertension (PAH). Mutations in the gene BMPR2, which codes for a cell surface receptor (BMPRII), cause the approximately 80% of heritable cases of PAH. Less commonly mutations in ALK1, CAV1, ENG, and SMAD9, and newly discovered mutations in KCNK3, may cause heritable PAH. Other family members of many patients diagnosed with idiopathic PAH may be diagnosed with PAH. Genetic counseling and testing should be offered to patients diagnosed with heritable or idiopathic PAH.

  4. Relationship between sympathetic baroreflex sensitivity and arterial stiffness in elderly men and women.

    PubMed

    Okada, Yoshiyuki; Galbreath, M Melyn; Shibata, Shigeki; Jarvis, Sara S; VanGundy, Tiffany B; Meier, Rhonda L; Vongpatanasin, Wanpen; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Previous human studies have shown that large-artery stiffness contributes to an age-related decrease in cardiovagal baroreflex sensitivity. Whether this is also true with sympathetic baroreflex sensitivity is unknown. We tested the hypothesis that sympathetic baroreflex sensitivity is associated with the stiffness of baroreceptor segments (the carotid artery and the aorta) in elderly individuals and that sex affects this relationship. Sympathetic baroreflex sensitivity was assessed from the spontaneous changes in beat-by-beat diastolic pressure and corresponding muscle sympathetic nerve activity (microneurography) during supine rest in 30 men (mean±SEM: 69±1 years) and 31 women (68±1 years). Carotid artery stiffness (B-mode ultrasonography) and aortic stiffness (MRI) were also determined. We found that elderly women had lower sympathetic baroreflex sensitivity than elderly men (-2.33±0.25 versus -3.32±0.25 bursts · 100 beats(-1) · mm Hg(-1); P=0.007). β-Stiffness indices of the carotid artery and the aorta were greater in elderly women than in men (6.68±0.48 versus 5.10±0.50 and 4.03±0.47 versus 2.68±0.42; both P<0.050). Sympathetic baroreflex sensitivity was inversely correlated with carotid artery stiffness in both men and women (r=0.49 and 0.50; both P<0.05), whereas this relation was shifted in parallel upward (toward a reduced sensitivity) in women with no changes in the slope (0.26 versus 0.24 arbitrary units). Sympathetic baroreflex sensitivity and aortic stiffness showed similar trends. Thus, barosensory artery stiffness seems to be one independent determinant of sympathetic baroreflex sensitivity in elderly men and women. The lower sympathetic baroreflex sensitivity in elderly women may predispose them to an increased prevalence of hypertension.

  5. Estimation of Stiffness Parameter on the Common Carotid Artery

    NASA Astrophysics Data System (ADS)

    Koya, Yoshiharu; Mizoshiri, Isao; Matsui, Kiyoaki; Nakamura, Takashi

    The arteriosclerosis is on the increase with an aging or change of our living environment. For that reason, diagnosis of the common carotid artery using echocardiogram is doing to take precautions carebropathy. Up to the present, several methods to measure stiffness parameter of the carotid artery have been proposed. However, they have analyzed at the only one point of common carotid artery. In this paper, we propose the method of analysis extended over a wide area of common carotid artery. In order to measure stiffness parameter of common carotid artery from echocardiogram, it is required to detect two border curves which are boundaries between vessel wall and blood. The method is composed of two steps. The first step is the detection of border curves, and the second step is the calculation of stiffness parameter using diameter of common carotid artery. Experimental results show the validity of the proposed method.

  6. The two faces of hypertension: role of aortic stiffness.

    PubMed

    Smulyan, Harold; Mookherjee, Saktipada; Safar, Michel E

    2016-02-01

    Adult hypertension can be divided into two relatively distinct forms-systolic/diastolic hypertension in midlife and systolic hypertension of the aged. The two types differ in prevalence, pathophysiology, and therapy. The prevalence of systolic hypertension in the elderly is twice that of midlife hypertension. The systolic pressure is elevated in both forms, but the high diastolic pressure in midlife is due to a raised total peripheral resistance, whereas the normal or low diastolic pressure in the elderly is due to aortic stiffening. Aortic stiffness, as measured by the carotid/femoral pulse wave velocity, has been found to be a cardiovascular risk marker independent of traditional risk factors for atherosclerosis. Instead, it is related to microcirculatory disease of the brain and kidney and to disorders of inflammation. Loss of aortic distensibility is an inevitable consequence of aging, but a review of its causes suggests that it may be amenable to future pharmacologic therapy.

  7. Gender Difference in Arterial Stiffness in a Multicenter Cross-Sectional Study: The Korean Arterial Aging Study (KAAS)

    PubMed Central

    Kim, Jang-Young; Park, Jeong Bae; Kim, Dong Soo; Kim, Kee Sik; Jeong, Jin Won; Park, Jong Chun; Oh, Byung Hee; Chung, Namsik

    2014-01-01

    Elevated arterial stiffness has emerged as an important risk factor for future cardiovascular (CV) events in men and women. However, gender-related differences in arterial stiffness have not been clearly demonstrated. We thus determine whether gender affects arterial stiffness in subjects with and without CV risk factors. We consecutively enrolled 1,588 subjects aged 17-87 years (mean age: 46.5; 51% women) from the Korean Arterial Aging Study (KAAS), which is a multicenter registry from 13 university hospitals in Korea for the evaluation of arterial stiffness. We compared markers of arterial stiffness – central augmentation index (AIx), aortic pulse wave velocity (PWV), and pulse pressure (PP) amplification – in apparently healthy men and women without risk factors with those in high-risk subjects with a smoking habit, hypertension, diabetes, and dyslipidemia but without drug treatment. Aortic PWV and PP amplification were significantly higher in men than in women (7.78 ± 1.16 vs. 7.64 ± 1.15 m/s, p = 0.015, and 1.39 ± 0.22 vs. 1.30 ± 0.18, p < 0.001, respectively). However, women had a significantly higher central AIx than men (23.5 ± 11.9 vs. 16.1 ± 12.6%, p < 0.001). The central AIx and aortic PWV values were significantly higher in the high-risk group than in the healthy group for both men and women. In men, central AIx and aortic PWV were associated positively with age and blood pressure, and negatively with body mass index. In women, central AIx was positively related to age, diastolic blood pressure, and serum cholesterol levels. Aortic PWV was positively related to age, systolic blood pressure, fasting glucose, and heart rate. PP amplification was associated negatively with age and blood pressure and positively with heart rate in both men and women. In conclusion, arterial stiffness is mainly determined by sex, age, and blood pressure. Markers of arterial stiffness differ between men and women. Dyslipidemia and glucose contribute to a modest

  8. [Treatment of pulmonary arterial hypertension].

    PubMed

    Roman, Antonio; López-Meseguer, Manuel; Domingo, Enric

    2015-06-22

    Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease.

  9. Anticoagulation in Pulmonary Arterial Hypertension.

    PubMed

    Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B

    2016-06-01

    Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.

  10. Heart Rate Dependency of Large Artery Stiffness.

    PubMed

    Tan, Isabella; Spronck, Bart; Kiat, Hosen; Barin, Edward; Reesink, Koen D; Delhaas, Tammo; Avolio, Alberto P; Butlin, Mark

    2016-07-01

    Carotid-femoral pulse wave velocity (cfPWV) quantifies large artery stiffness, it is used in hemodynamic research and is considered a useful cardiovascular clinical marker. cfPWV is blood pressure (BP) dependent. Intrinsic heart rate (HR) dependency of cfPWV is unknown because increasing HR is commonly accompanied by increasing BP. This study aims to quantify cfPWV dependency on acute, sympathovagal-independent changes in HR, independent of BP. Individuals (n=52, age 40-93 years, 11 female) with in situ cardiac pacemakers or cardioverter defibrillators were paced at 60, 70, 80, 90, and 100 bpm. BP and cfPWV were measured at each HR. Both cfPWV (mean [95% CI], 0.31 [0.26-0.37] m/s per 10 bpm; P<0.001) and central aortic diastolic pressure (3.78 [3.40-4.17] mm Hg/10 bpm; P<0.001) increased with HR. The HR effect on cfPWV was isolated by correcting the BP effects by 3 different methods: (1) statistically, by a linear mixed model; (2) mathematically, using an exponential relationship between BP and cross-sectional lumen area; and (3) using measured BP dependency of cfPWV derived from changes in BP induced by orthostatic changes (seated and supine) in a subset of subjects (n=17). The BP-independent effects of HR on cfPWV were quantified as 0.20 [0.11-0.28] m/s per 10 bpm (P<0.001, method 1), 0.16 [0.11-0.22] m/s per 10 bpm (P<0.001, method 2), and 0.16 [0.11-0.21] m/s per 10 bpm (P<0.001, method 3). With a mean HR dependency in the range of 0.16 to 0.20 m/s per 10 bpm, cfPWV may be considered to have minimal physiologically relevant changes for small changes in HR, but larger differences in HR must be considered as contributing to significant differences in cfPWV.

  11. Arterial Stiffness in the Young: Assessment, Determinants, and Implications

    PubMed Central

    2010-01-01

    Arterial stiffness describes the rigidity of the arterial wall. Its significance owes to its relationship with the pulsatile afterload presented to the left ventricle and its implications on ventricular-arterial coupling. In adults, the contention that arterial stiffness as a marker and risk factor for cardiovascular morbidity and mortality is gaining support. Noninvasive methods have increasingly been adopted in both the research and clinical arena to determine local, segmental, and systemic arterial stiffness in the young. With adoption of these noninvasive techniques for use in children and adolescents, the phenomenon and significance of arterial stiffening in the young is beginning to be unveiled. The list of childhood factors and conditions found to be associated with arterial stiffening has expanded rapidly over the last decade; these include traditional cardiovascular risk factors, prenatal growth restriction, vasculitides, vasculopathies associated with various syndromes, congenital heart disease, and several systemic diseases. The findings of arterial stiffening have functional implications on energetic efficiency, structure, and function of the left ventricle. Early identification of arterial dysfunction in childhood may provide a window for early intervention, although longitudinal studies are required to determine whether improvement of arterial function in normal and at-risk paediatric populations will be translated into clinical benefits. PMID:20421954

  12. Assessment of Arterial Stiffness Using the Cardio-Ankle Vascular Index

    PubMed Central

    Miyoshi, Toru; Ito, Hiroshi

    2016-01-01

    Background Arterial stiffness is an independent predictor of outcomes for patients with cardiovascular disease. Although measurement of pulse wave velocity is a widely accepted, noninvasive approach for the assessment of arterial stiffness, its accuracy is affected by changes in blood pressure. Summary The cardio-ankle vascular index (CAVI) is an index of the overall stiffness of the artery from the origin of the aorta to the ankle and is theoretically independent of blood pressure at the time of measurement. CAVI increases linearly with age and is elevated even in mild arteriosclerotic disease. It can identify differences in the degree of arteriosclerosis among patients with severe arteriosclerotic disease and better reflects the severity of disease of the coronary artery than does brachial-ankle pulse wave velocity. Patients with higher CAVI values show a poor prognosis compared with those with lower CAVI values. Furthermore, CAVI can be lowered by controlling diabetes mellitus and hypertension. Key Messages The primary aims of assessing arterial stiffness using CAVI are to assist in the early detection of arteriosclerosis, allowing timely treatment and lifestyle modification, and to quantitatively evaluate the progression of disease and the effectiveness of treatment. Whether CAVI-guided therapy can improve prognosis in high-risk patients needs to be further examined to confirm the clinical usefulness of this measure. PMID:27493899

  13. [Arterial hypertension and metabolic disorders].

    PubMed

    Dzherieva, I S; Volkova, N I

    2010-01-01

    Combination of arterial hypertension (AH) and metabolic disorders accelerates development of organic lesions in target organs. As shown in recent prospective studies, myocardial hypertrophy rate closely correlated with severity of metabolic disturbance. The thickness of interventricular septum and posterior wall show stronger dependence of severity of metabolic disorders than left ventricular density while left atrial enlargement is correlates with fasting glycemia and excess body mass. There is close relationship between microalbuminurea and hyperinsulinemia and the number of metabolic syndrome components is linearly correlated with glomerular filtration rate below 60 ml/min. It is shown that rigidity of arteries is a new independent risk factor of cardiovascular complications in obese patients. Moreover, metabolic disturbances cause affective disorders that impair quality of life and therapy motivation. Combination of AH, metabolic disturbances, and borderline psychic disorders dictated consideration of abnormal melatonin secretion as a condition developing as a consequence of disturbed adaptive circadian rhythms. This hypothesis was prompted by the discovery of the so-called "clock genes" in the central nervous system and practically all peripheral organs including heart, vessels, and adipose tissue.

  14. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    PubMed

    Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen

    2016-10-01

    Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.

  15. Pulmonary Vascular Stiffness: Measurement, Modeling, and Implications in Normal and Hypertensive Pulmonary Circulations

    PubMed Central

    Hunter, Kendall S.; Lammers, Steven R.; Shandas, Robin

    2014-01-01

    This article introduces the concept of pulmonary vascular stiffness, discusses its increasingly recognized importance as a diagnostic marker in the evaluation of pulmonary vascular disease, and describes methods to measure and model it clinically, experimentally, and computationally. It begins with a description of systems-level methods to evaluate pulmonary vascular compliance and recent clinical efforts in applying such techniques to better predict patient outcomes in pulmonary arterial hypertension. It then progresses from the systems-level to the local level, discusses proposed methods by which upstream pulmonary vessels increase in stiffness, introduces concepts around vascular mechanics, and concludes by describing recent work incorporating advanced numerical methods to more thoroughly evaluate changes in local mechanical properties of pulmonary arteries. PMID:23733649

  16. Which prognostic factors should be used in pulmonary arterial hypertension in elderly patients?

    PubMed Central

    Akdeniz, Bahri; Ozpelit, Ebru

    2017-01-01

    In recent times, the prevalence of pulmonary arterial hypertension (PAH) is more commonly seen among elderly populations. The increased prevalence of hypertension, diabetes, obesity, arterial stiffness, as well as diastolic dysfunction, may cause endothelial dysfunction and affect pulmonary vasculature. Furthermore, older patients have certain differences in clinical characteristics and outcomes. In this article, the special characteristics of aging in PAH patients have been reviewed, while the risk predictors of elderly patients are also discussed. PMID:28270839

  17. Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

    PubMed

    Briet, M; Bozec, E; Laurent, S; Fassot, C; London, G M; Jacquot, C; Froissart, M; Houillier, P; Boutouyrie, P

    2006-01-01

    Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

  18. Tinnitus and arterial hypertension: a systematic review.

    PubMed

    Figueiredo, Ricardo Rodrigues; de Azevedo, Andréia Aparecida; Penido, Norma de Oliveira

    2015-11-01

    Tinnitus is considered a multi-factorial symptom. Arterial hypertension has been cited as a tinnitus etiological factor. To assess the scientific evidence on the associations between arterial hypertension and tinnitus. A systematic review was performed using PubMed, ISI Web, Lilacs and SciELO scientific databases. This review included articles published in Portuguese, Spanish, French and English correlating tinnitus with hypertension. Letters to editors and case reports were excluded. A total of 424 articles were identified, of which only 20 met the inclusion criteria. Studies that analyzed the incidence of hypertension in tinnitus patients tended to show an association, while those that evaluated the incidence of tinnitus in hypertensive patients did not. There is evidence of an association between tinnitus and hypertension, although a cause and effect relationship is uncertain. Changes in the cochlear microcirculation, resulting in hearing loss, may be an adjuvant factor in tinnitus pathophysiology.

  19. Pulmonary arterial hypertension in congenital heart diseases.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2009-08-01

    Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.

  20. Aerobic training-induced improvements in arterial stiffness are not sustained in older adults with multiple cardiovascular risk factors

    PubMed Central

    Madden, K M; Lockhart, C; Cuff, D; Potter, T F; Meneilly, G S

    2013-01-01

    There is a well-established relationship between increased arterial stiffness and cardiovascular mortality. We examined whether a long-term aerobic exercise intervention (6 months) would increase arterial compliance in older adults with hypertension complicated by Type 2 diabetes (T2DM) and hyperlipidemia. A total of 52 older adults (mean age 69.3±0.6 years, 30 males and 22 females) with diet/oral hypoglycemic-controlled T2DM, hypertension and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (6 months vigorous aerobic exercise, AT group) and a non-aerobic group (6 months of no aerobic exercise, NA group). Arterial stiffness was measured as pulse-wave velocity (PWV) using the Complior device. Aerobic training decreased arterial stiffness as measured by both radial (P=0.001, 2-way analysis of variance with repeated measures) and femoral (P=0.002) PWV. This was due to a decrease in arterial stiffness in the AT group after 3 months of training, which was not maintained after 6-month training for either radial (P=0.707) or femoral (P=0.680) PWV. Our findings indicate that in older adults with multiple cardiovascular risk factors, short-term improvements in arterial stiffness became attenuated over the long term. PMID:22951625

  1. Modifiable risk factors for increased arterial stiffness in outpatient nephrology.

    PubMed

    Elewa, Usama; Fernandez-Fernandez, Beatriz; Alegre, Raquel; Sanchez-Niño, Maria D; Mahillo-Fernández, Ignacio; Perez-Gomez, Maria Vanessa; El-Fishawy, Hussein; Belal, Dawlat; Ortiz, Alberto

    2015-01-01

    Arterial stiffness, as measured by pulse wave velocity (PWV), is an independent predictor of cardiovascular events and mortality. Arterial stiffness increases with age. However, modifiable risk factors such as smoking, BP and salt intake also impact on PWV. The finding of modifiable risk factors may lead to the identification of treatable factors, and, thus, is of interest to practicing nephrologist. We have now studied the prevalence and correlates of arterial stiffness, assessed by PWV, in 191 patients from nephrology outpatient clinics in order to identify modifiable risk factors for arterial stiffness that may in the future guide therapeutic decision-making. PWV was above normal levels for age in 85/191 (44.5%) patients. Multivariate analysis showed that advanced age, systolic BP, diabetes mellitus, serum uric acid and calcium polystyrene sulfonate therapy or calcium-containing medication were independent predictors of PWV. A new parameter, Delta above upper limit of normal PWV (Delta PWV) was defined to decrease the weight of age on PWV values. Delta PWV was calculated as (measured PWV) - (upper limit of the age-adjusted PWV values for the general population). Mean±SD Delta PWV was 0.76±1.60 m/sec. In multivariate analysis, systolic blood pressure, active smoking and calcium polystyrene sulfonate therapy remained independent predictors of higher delta PWV, while age, urinary potassium and beta blocker therapy were independent predictors of lower delta PWV. In conclusion, arterial stiffness was frequent in nephrology outpatients. Systolic blood pressure, smoking, serum uric acid, calcium-containing medications, potassium metabolism and non-use of beta blockers are modifiable factors associated with increased arterial stiffness in Nephrology outpatients.

  2. POA 02-2 ATHEROGENIC VASCULAR STIFFNESS AND HYPERTENSION: CAUSE OR EFFECT?

    PubMed

    Avolio, Alberto

    2016-09-01

    integrity of medial elastin, leading to arterial calcification and altered arterial stiffness. The changes in smooth muscle function are also affected by anchoring properties of integrins, in turn modifying wall properties. Superimposed on the cell-signalling phenomena modulating intimal and medial function is the modification of wall properties due to distending pressure. The task of assessing whether the relationship between atherosclerosis and arteriosclerosis and hypertension constitutes a cause or effect presents a formidable challenge. However, emerging evidence suggests that investigating the inter-relationships may elucidate potential feedback signalling pathways that may be interrogated to possibly delay the ill effects of compromised vascular function and development of hypertension.

  3. A review of pulmonary arterial hypertension

    PubMed Central

    Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.

    2004-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003. PMID:25696347

  4. Gender-related difference in arterial elastance during exercise in patients with hypertension.

    PubMed

    Park, Sungha; Ha, Jong-Won; Shim, Chi Young; Choi, Eui-Young; Kim, Jin-Mi; Ahn, Jeong-Ah; Lee, Se-Wha; Rim, Se-Joong; Chung, Namsik

    2008-04-01

    Exercise intolerance and heart failure with preserved ejection fraction are common in females. Recently, arterial stiffness has been suggested to be a significant contributor in the development of heart failure. How gender difference affects arterial stiffening and its response to exercise is not well known. We hypothesized that arterial elastance index during exercise would be more abnormal in females with hypertension than males. Arterial elastance index was estimated as arterial end systolic pressure/stroke volume controlled for body surface area and was measured at rest and during graded supine bicycle exercise (25 watts, 3-minute increments) in 298 patients with hypertension (149 males; 149 females; mean age, 59). The subjects were divided into 2 groups by gender. Exercise duration was significantly shorter in females compared to males (692+/-222 versus 483+/-128 seconds, P<0.001). Although arterial elastance index at baseline was significantly higher in males, the magnitude of increase was steeper in females with the magnitude of change at 75 W of exercise being significantly higher in females compared to males (0.69+/-0.83 versus 0.43+/-0.69, P=0.018). Arterial elastance index at each stage of exercise up to 75 W was independently associated with decreased exercise duration. In conclusion, despite lower arterial elastance index at rest, the increase during exercise was steeper in women with hypertension, suggesting a gender-related difference in dynamic arterial stiffness. The arterial elastance index during exercise was significantly associated with exercise duration in patients with hypertension.

  5. Cardiovascular Health and Arterial Stiffness: The Maine Syracuse Longitudinal Study

    PubMed Central

    Crichton, Georgina E; Elias, Merrill F; Robbins, Michael A

    2014-01-01

    Ideal cardiovascular health is a recently defined construct by the American Heart Association (AHA) to promote cardiovascular disease reduction. Arterial stiffness is a major risk factor for cardiovascular disease. The extent to which the presence of multiple prevalent cardiovascular risk factors and health behaviors is associated with arterial stiffness is unknown. The aim of this study was to examine the association between the AHA construct of cardiovascular health and arterial stiffness, as indexed by pulse wave velocity and pulse pressure. The AHA health metrics, comprising of four health behaviors (smoking, body mass index, physical activity, and diet) and three health factors (total cholesterol, blood pressure, and fasting plasma glucose) were evaluated among 505 participants in the Maine-Syracuse Longitudinal Study. Outcome measures were carotid-femoral pulse wave velocity (PWV) and pulse pressure measured at 4 to 5-year follow-up. Better cardiovascular health, comprising both health factors and behaviors, was associated with lower arterial stiffness, as indexed by pulse wave velocity and pulse pressure. Those with at least five health metrics at ideal levels had significantly lower PWV (9.8 m/s) than those with two or less ideal health metrics (11.7 m/s) (P<0.001). This finding remained with the addition of demographic and PWV-related variables (P=0.004). PMID:24384629

  6. Inhibition of SRF/myocardin reduces aortic stiffness by targeting vascular smooth muscle cell stiffening in hypertension

    PubMed Central

    Zhou, Ning; Lee, Jia-Jye; Stoll, Shaunrick; Ma, Ben; Wiener, Robert; Wang, Charles; Costa, Kevin D.; Qiu, Hongyu

    2017-01-01

    Aims Increased aortic stiffness is a fundamental manifestation of hypertension. However, the molecular mechanisms involved remain largely unknown. We tested the hypothesis that abnormal intrinsic vascular smooth muscle cell (VSMC) mechanical properties in large arteries, but not in distal arteries, contribute to the pathogenesis of aortic stiffening in hypertension, mediated by the serum response factor (SRF)/myocardin signalling pathway. Methods and results Four month old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied. Using atomic force microscopy, significant VSMC stiffening was observed in the large conducting aorta compared with the distal arteries in SHR (P < 0.001), however, this regional variation was not observed in WKY rats (P > 0.4). The increase of VSMC stiffness was accompanied by a parallel increase in the expression of SRF by 9.8-fold and of myocardin by 10.5-fold in thoracic aortic VSMCs from SHR vs. WKY rats, resulting in a significant increase of downstream stiffness-associated genes (all, P < 0.01 vs. WKY). Inhibition of SRF/myocardin expression selectively attenuated aortic VSMC stiffening, and normalized downstream targets in VSMCs isolated from SHR but not from WKY rats. In vivo, 2 weeks of treatment with SRF/myocardin inhibitor delivered by subcutaneous osmotic minipump significantly reduced aortic stiffness and then blood pressure in SHR but not in WKY rats, although concomitant changes in aortic wall remodelling were not detected during this time frame. Conclusions SRF/myocardin pathway acts as a pivotal mediator of aortic VSMC mechanical properties and plays a central role in the pathological aortic stiffening in hypertension. Attenuation of aortic VSMC stiffening by pharmacological inhibition of SRF/myocardin signalling presents a novel therapeutic strategy for the treatment of hypertension by targeting the cellular contributors to aortic stiffness. PMID:28003268

  7. Arterial stiffness and inflammatory response to psychophysiological stress.

    PubMed

    Ellins, Elizabeth; Halcox, Julian; Donald, Ann; Field, Bryony; Brydon, Lena; Deanfield, John; Steptoe, Andrew

    2008-08-01

    The processes through which psychological stress influences cardiovascular disease are poorly understood, but may involve activation of hemodynamic, neuroendocrine and inflammatory responses. We assessed the relationship between carotid arterial stiffness and inflammatory responses to acute psychophysiologic stress. Participants were 155 healthy men and women aged 55.3, SD 2.7 years. Blood samples for the assessment of plasma fibrinogen, tumor necrosis factor (TNF) alpha and interleukin (IL) 6 were drawn at baseline, immediately following standardized behavioral tasks, and 45 min later. Carotid artery stiffness was measured ultrasonically three years later, and blood pressure and heart rate responses were recorded. The tasks induced substantial increases in blood pressure and heart rate, together with increased fibrinogen, TNFalpha and IL-6 concentration. Carotid stiffness was positively associated with body mass, waist/hip ratio, blood pressure, low density lipoprotein cholesterol, and C-reactive protein, and inversely with high density lipoprotein and grade of employment. Baseline levels of inflammatory variables were not related to carotid artery stiffness. But carotid stiffness was greater in participants with larger fibrinogen (p=0.037) and TNFalpha (p=0.036) responses to psychophysiological stress. These effects were independent of age, gender, grade of employment, smoking, body mass, waist/hip ratio, systolic and diastolic pressure, high and low density lipoprotein cholesterol, and C-reactive protein. There were no associations between carotid stiffness and stress responses in IL-6, blood pressure, or heart rate. We conclude that individual differences in inflammatory responses to psychophysiological stress are independently related to structural changes in artery walls that reflect increased cardiovascular disease risk.

  8. Diagnosis and assessment of pulmonary arterial hypertension.

    PubMed

    Badesch, David B; Champion, Hunter C; Sanchez, Miguel Angel Gomez; Hoeper, Marius M; Loyd, James E; Manes, Alessandra; McGoon, Michael; Naeije, Robert; Olschewski, Horst; Oudiz, Ronald J; Torbicki, Adam

    2009-06-30

    The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.

  9. Medical treatment update on pulmonary arterial hypertension.

    PubMed

    Enderby, Cher Y; Burger, Charles

    2015-09-01

    Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.

  10. Uteroplacental insufficiency and lactational environment separately influence arterial stiffness and vascular function in adult male rats.

    PubMed

    Tare, Marianne; Parkington, Helena C; Bubb, Kristen J; Wlodek, Mary E

    2012-08-01

    Early life environmental influences can have lifelong consequences for health, including the risk of cardiovascular disease. Uteroplacental insufficiency causes fetal undernutrition and impairs fetal growth. Previously we have shown that uteroplacental insufficiency is associated with impaired maternal mammary development, compromising postnatal growth leading to hypertension in male rat offspring. In this study we investigated the roles of prenatal and postnatal nutritional environments on endothelial and smooth muscle reactivity and passive wall stiffness of resistance arteries of male rat offspring. Fetal growth restriction was induced by maternal bilateral uterine vessel ligation (restricted) on day 18 of pregnancy. Control offspring were from mothers that had sham surgery (control) and another group from mothers with their litter size reduced (reduced; litter size reduced to 5 at birth, equivalent to the restricted group). On postnatal day 1, offspring (control, restricted, and reduced) were cross-fostered onto control or restricted mothers. At 6 months, mesenteric and femoral arteries were studied using wire and pressure myography. In restricted-on-restricted rats, wall stiffness was increased, and sensitivity to phenylephrine and relaxation evoked by endothelium-derived hyperpolarizing factor and sodium nitroprusside were impaired in mesenteric arteries. In femoral arteries, relaxation to sodium nitroprusside was reduced, whereas wall stiffness was unaltered. Cross-fostering restricted offspring onto control mothers alleviated deficits in vascular stiffness and reactivity. Control or reduced offspring who suckled a restricted mother had marked vascular stiffening. In conclusion, prenatal and early postnatal environments separately influence vascular function and stiffness. Furthermore, the early postnatal lactational environment is a determinant of later cardiovascular function.

  11. Pulmonary arterial hypertension in primary amyloidosis

    PubMed Central

    Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.

    2016-01-01

    Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  12. Arterial–ventricular coupling and parameters of vascular stiffness in hypertensive patients: Role of gender

    PubMed Central

    Bruno, Rosa Maria; Buralli, Simona; Barzacchi, Marta; Dal Canto, Elisa; Ghiadoni, Lorenzo; Taddei, Stefano

    2017-01-01

    Objective Non-invasive estimation of arterial–ventricular coupling has been extensively used for the evaluation of cardiovascular performance, however, a relative small amount of data is available regarding arterial–ventricular coupling and its components in hypertension. The present study was designed to investigate the relationship between left ventricular elastance, arterial elastance, parameters of vascular stiffness and the influence of gender in a population of hypertensive individuals. Methods In 102 patients, trans-thoracic cardiac ultrasound, parameters of aortic stiffness (carotid-femoral pulse wave velocity) and wave reflection (augmentation index) were recorded. Ultrasound images of common carotid arteries were acquired for the assessment of intima-media thickness as well as carotid compliance and distensibility coefficient. Results Mean age was 61 years, 32% diabetes, 56% dyslipidemia, 9% previous cardiovascular events; women (n = 32) and men were superimposable for cardiovascular risk factors prevalence. In the population, ventricular elastance was significantly correlated with arterial elastance (r = 0.887), age (r = 0.334), gender (r = −0.494), BMI (r = −0.313), augmentation index (r = 0.479) (all p < 0.001); and with carotid compliance and distensibility coefficient (r = 0.229 and r = − 0.250, respectively, both p < 0.05); however, only arterial elastance and gender were independently associated with ventricular elastance in multiple regression models adjusted for confounding factors. Gender-specific analysis revealed that arterial elastance and augmentation index remained statistically significant associated with ventricular elastance in men (r = 0.275, p = 0.04); instead augmentation index was no longer significant (r = 0.052, p = 0.77) in the female sex. Conclusions In hypertensive patients, main determinants of ventricular elastance are arterial elastance, as an integrated

  13. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  14. Effect of upper body aerobic exercise on arterial stiffness in older adults.

    PubMed

    Aizawa, Kunihiko; Mendelsohn, Marissa E; Overend, Tom J; Petrella, Robert J

    2009-10-01

    The authors evaluated the effects of acute arm-cycling exercise on arterial stiffness of the brachial artery (BA: working limb) and posterior tibial artery (PTA: nonworking limb) in healthy older participants. Eleven participants were tested to evaluate BA and PTA stiffness. Blood pressure (BP), heart rate (HR), and arterial stiffness indices of the BA and PTA measured by Doppler ultrasound were determined before and 10 min after graded arm-cycling exercise to volitional fatigue on 2 separate days. After the exercise, although BA diameter, brachial systolic BP, pulse pressure, and HR increased significantly (all p < .05), arterial stiffness indices of the BA remained unchanged. Similarly, arterial stiffness indices of the PTA remained unchanged after the exercise, whereas HR increased significantly (p < .05). These results show that acute arm-cycling exercise failed to modify arterial stiffness of the BA and PTA, suggesting that it has no systemic effect on arterial stiffness in healthy older adults.

  15. Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

    PubMed

    Agafonova, I G; Bogdanovich, R N; Kolosova, N G

    2015-12-01

    Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration.

  16. [Left ventricular function in pulmonary arterial hypertension].

    PubMed

    Khomaziuk, V A

    1998-12-01

    Echocardiographic evaluation was done of left ventricular functional state in 90 patients with primary and secondary pulmonary arterial hypertension with and without intercavitary shunting. Changes in left ventricular function were identified in 86% cases; they reflected disturbances in both ventricles compensatory interaction. The degree of changes depended on the degree of dilatation of the right ventricle and level of interchamber shunting.

  17. Pulmonary Function and Arterial Stiffness in Chronic Heart Failure

    PubMed Central

    Hu, Bangchuan; Gong, Shijin; Yu, Yihua; Dai, Haiwen

    2016-01-01

    Arterial stiffness contributes to heart failure and is decreased by angiotensin receptor blockers (ARBs). This cross-sectional study aimed to assess associations of lung function and ARB with arterial stiffness in patients with chronic heart failure. 354 outpatients (168 males; 186 females; 68.2 ± 7.2 years old) with chronic heart failure were evaluated. Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1 to FVC ratio (FEV1/FVC), were assessed. The cardio-ankle vascular index (CAVI) was used to estimate arterial stiffness. Unadjusted correlation analyses revealed a positive association of CAVI with ARB but not ACEI, and a negative correlation with FEV1 (r = −0.2987, p < 0.0001). Multiple stepwise regression analyses showed that ARB and FEV1 (p < 0.0001) were independent predicting factors for CAVI. These findings suggest that reduced pulmonary function is associated with increased CAVI. Pulmonary function protection could be used to improve the prognosis in heart failure, but additional studies are necessary. PMID:28097138

  18. Arterial Stiffness, Oxidative Stress, and Smoke Exposure in Wildland Firefighters

    PubMed Central

    Gaughan, Denise M.; Siegel, Paul D.; Hughes, Michael D.; Chang, Chiung-Yu; Law, Brandon F.; Campbell, Corey R.; Richards, Jennifer C.; Kales, Stefanos F.; Chertok, Marcia; Kobzik, Lester; Nguyen, Phuongson; O’Donnell, Carl R.; Kiefer, Max; Wagner, Gregory R.; Christiani, David C.

    2015-01-01

    Objectives To assess the association between exposure, oxidative stress, symptoms, and cardiorespiratory function in wildland firefighters. Methods We studied two Interagency Hotshot Crews with questionnaires, pulse wave analysis for arterial stiffness, spirometry, urinary 8-iso-prostaglandin F2α (8-isoprostane) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the smoke exposure marker (urinary levoglucosan). Arterial stiffness was assessed by examining levels of the aortic augmentation index, expressed as a percentage. An oxidative stress score comprising the average of z-scores created for 8-OHdG and 8-isoprostane was calculated. Results Mean augmentation index % was higher for participants with higher oxidative stress scores after adjusting for smoking status. Specifically for every one unit increase in oxidative stress score the augmentation index % increased 10.5% (95% CI: 2.5, 18.5%). Higher mean lower respiratory symptom score was associated with lower percent predicted forced expiratory volume in one second/forced vital capacity. Conclusions Biomarkers of oxidative stress may serve as indicators of arterial stiffness in wildland firefighters. PMID:24909863

  19. MicroRNAs in Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Guofei; Chen, Tianji

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  20. Epoprostenol Therapy for Pulmonary Arterial Hypertension.

    PubMed

    Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Ogawa, Aiko; Sarashina, Toshihiro; Ejiri, Kentaro; Ito, Hiroshi

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.

  1. Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

    PubMed

    Tarumi, Takashi; de Jong, Daan L K; Zhu, David C; Tseng, Benjamin Y; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B; Kerwin, Diana R; Lu, Hanzhang; Munro Cullum, C; Zhang, Rong

    2015-04-15

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65 ± 6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults.

  2. [Pulmonary arterial hypertension and BMP system abnormality].

    PubMed

    Otsuka, Fumio

    2008-11-01

    Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.

  3. Relation of arterial stiffness with gestational age and birth weight

    PubMed Central

    Cheung, Y; Wong, K; Lam, B.; Tsoi, N

    2004-01-01

    Background: The cardiovascular risk of individuals who are born small as a result of prematurity remains controversial. Given the previous findings of stiffer peripheral conduit arteries in growth restricted donor twins in twin–twin transfusion syndrome regardless of gestational age, we hypothesised that among children born preterm, only those with intrauterine growth retardation are predisposed to an increase in cardiovascular risks. Aim: To compare brachioradial arterial stiffness and systemic blood pressure (BP) among children born preterm and small for gestational age (group 1, n = 15), those born preterm but having birth weight appropriate for gestational age (group 2, n = 36), and those born at term with birth weight appropriate for gestational age (group 3, n = 35). Methods: Systemic BP was measured by an automated device (Dinamap), while stiffness of the brachioradial arterial segment was assessed by measuring pulse wave velocity (PWV). The birth weight was adjusted for gestational age and expressed as a z score for analysis. Results: The 86 children were studied at a mean (SD) age of 8.2 (1.7) years. Subjects from group 1, who were born at 32.3 (2.0) weeks' gestation had a significantly lower z score of birth weight (-2.29 (0.63), p<0.001), compared with those from groups 2 and 3. They had a significantly higher mean blood pressure (p<0.001) and their diastolic blood pressure also tended to be higher (p = 0.07). Likewise, their brachioradial PWV, and hence arterial stiffness, was the highest of the three groups (p<0.001). While subjects from group 2 were similarly born preterm, their PWV was not significantly different from that of group 3 subjects (p = 1.00) and likewise their z score of birth weight did not differ (-0.01 (0.71) v -0.04 (1.1), p = 1.00). Brachioradial PWV correlated significantly with systolic (r = 0.31, p = 0.004), diastolic (r = 0.38, p<0.001), and mean (0.47, p<0.001) BP, and with z score of birth weight (r = -0.43, p<0

  4. Increased arterial stiffness in South Dakota American Indian children.

    PubMed

    Litz, Andrew M; Van Guilder, Gary P

    2016-02-01

    Arterial stiffness has been observed in white American obese children, yet there are no data in American Indian youth, who are affected disproportionately by the cardiovascular consequences of childhood obesity and its accompanying risk factors. The purpose of this study was to determine the association of childhood overweight-obesity and cardiometabolic risk factors with arterial stiffness in South Dakota white American and American Indian children. Thirty-six (28 white American and 8 American Indian) children (age, 13 ± 1 years; grades 6-8) from a rural South Dakota elementary and middle school were studied: 18 had a healthy weight (body mass index (BMI), 19.5 ± 1.9 kg/m(2)) and 18 were overweight-obese (BMI, 26.8 ± 3.5 kg/m(2)). Arterial stiffness was assessed using applanation tonometry via pulse wave analysis to determine carotid-radial pulse wave velocity (crPWV) and aortic augmentation index (AIx). There were no differences (P = 0.94) in crPWV between healthy weight (7.1 ± 1.4 m/s) and overweight-obese (7.3 ± 1.0 m/s) children, even after controlling for risk factors. However, crPWV was markedly elevated (P = 0.002) in overweight-obese American Indian children (7.7 ± 1.1 m/s) compared with white American children (6.8 ± 0.5 m/s), and these differences remained after controlling for blood pressure and more severe obesity in the American Indians. An obesity-matched subgroup analysis indicated that crPWV (7.7 ± 1.1 vs 6.8 ± 0.4 m/s) remained significantly greater in the American Indians (P = 0.03). There were no between-group differences in aortic AIx. These findings indicate an adverse influence of American Indian ethnicity on arterial stiffening in children with elevated adiposity. Arterial stiffness in American Indian children may accelerate early adulthood vascular disease.

  5. Physical exercise improves arterial stiffness after spinal cord injury

    PubMed Central

    Hubli, Michèle; Currie, Katharine D.; West, Christopher R.; Gee, Cameron M.; Krassioukov, Andrei V.

    2014-01-01

    Objective/background Aortic pulse wave velocity (PWV), the gold-standard assessment of central arterial stiffness, has prognostic value for cardiovascular disease risk in able-bodied individuals. The aim of this study was to compare aortic PWV in athletes and non-athletes with spinal cord injury (SCI). Design Cross-sectional comparison. Methods Aortic PWV was assessed in 20 individuals with motor-complete, chronic SCI (C2–T5; 18 ± 8 years post-injury) using applanation tonometry at the carotid and femoral arterial sites. Ten elite hand-cyclists were matched for sex to 10 non-athletes; age and time since injury were comparable between the groups. Heart rate and discrete brachial blood pressure measurements were collected throughout testing. Outcome measures Aortic PWV, blood pressure, heart rate. Results Aortic PWV was significantly lower in athletes vs. non-athletes (6.9 ± 1.0 vs. 8.7 ± 2.5 m/second, P = 0.044). There were no significant between-group differences in resting supine mean arterial blood pressure (91 ± 19 vs. 81 ± 10 mmHg) and heart rate (60 ± 10 vs. 58 ± 6 b.p.m.). Conclusion Athletes with SCI exhibited improved central arterial stiffness compared to non-athletes, which is in agreement with the previous able-bodied literature. This finding implies that chronic exercise training may improve arterial health and potentially lower cardiovascular disease risk in the SCI population. PMID:24976366

  6. Pulmonary Arterial Hypertension: The Clinical Syndrome

    PubMed Central

    Lai, Yen-Chun; Potoka, Karin C.; Champion, Hunter C.; Mora, Ana L.; Gladwin, Mark T.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation. PMID:24951762

  7. Arterial Stiffness in Patients Taking Second-generation Antipsychotics

    PubMed Central

    Fındıklı, Ebru; Gökçe, Mustafa; Nacitarhan, Vedat; Camkurt, Mehmet Akif; Fındıklı, Hüseyin Avni; Kardaş, Selçuk; Şahin, Merve Coşgun; Karaaslan, Mehmet Fatih

    2016-01-01

    Objective That treatment with second-generation antipsychotics (SGAs) causes metabolic side effects and atherosclerosis in patients with schizophrenia and bipolar disorder (BD) is well-known. Increased arterial stiffness is an important marker of arteriosclerosis and has been identified as an independent risk factor for cardiovascular diseases. We measured pulse wave velocity (PWV) as a marker of arteriosclerosis in patients with schizophrenia and BD who use SGAs. Methods Patients and controls were collected from our psychiatry outpatient clinics or family medicine. Mental illness was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Mean age, gender, systolic and diastolic blood pressure, body mass index, Framingham risk score (FRS), etc. were determined. Simultaneous electrocardiography and pulse wave were recorded with an electromyography device. The photo-plethysmographic method was used to record the pulse wave. Inclusion criteria included use of SGAs for at least the last six months. Patients with diseases that are known to cause stiffness and the use of typical antipsychotics were excluded. Results Ninety-six subject (56 patients, 40 controls) were included in our study. There were 49 females, 47 males. Patients had schizophrenia (n=17) and BD (n=39). Their treatments were quetiapine (n=15), risperidone (n=13), olanzapine (n=15), and aripiprazole (n=13). Although differences in mean age, gender, and FRS in the patient and control groups were not statistically significant (p=1), PWV was greater in patients in the antipsychotic group (p=0.048). Conclusion This study supported the liability to stiffness in patients with schizophrenia and BD. Using SGAs may contribute to arterial stiffness in these patients. PMID:27776389

  8. A review of pulmonary arterial hypertension

    PubMed Central

    Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.

    2004-01-01

    Medical therapy for pulmonary arterial hypertension (PAH) focuses on pulmonary vascular remodelling and smooth muscle cell proliferation. This article covers the drugs which are approved or are in sight and the evidence-based treatment strategies that target the different pathobiological pathways, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice, June 2003. In addition we briefly look at the 'Venice consensus' on surgical treatment. In the past five and a half years more than 360 patients were seen for pulmonary hypertension in the Free University Medical Centre (VUmc). Present-day treatment, research studies and novel treatment strategies in the VUmc will be reviewed. Future treatments will be on the basis of insights into pathobiology, pathogenesis and genes in PAH and should focus on drug combinations, which theoretically target different or similar pathobiological pathways. PMID:25696358

  9. Blood pressure and arterial stiffness in obese children and adolescents.

    PubMed

    Hvidt, Kristian Nebelin

    2015-03-01

    Obesity, elevated blood pressure (BP) and arterial stiffness are risk factors for cardiovascular disease. A strong relationship exists between obesity and elevated BP in both children and adults. Obesity and elevated BP in childhood track into adult life increasing the risk of cardiovascular disease in adulthood. Ambulatory BP is the most precise measure to evaluate the BP burden, whereas carotid-femoral pulse wave velocity (cfPWV) is regarded as the gold standard for evaluating arterial (i.e. aortic) stiffness. These measures might contribute to a better understanding of obesity's adverse impact on the cardiovascular system, and ultimately a better prevention and treatment of childhood obesity. The overall aim of the present PhD thesis is to investigate arterial stiffness and 24-hour BP in obese children and adolescents, and evaluate whether these measures are influenced by weight reduction. The present PhD thesis is based on four scientific papers.  In a cross-sectional design, 104 severe obese children and adolescents with an age of 10-18 years were recruited when newly referred to the Children's Obesity Clinic, Holbæk University Hospital, and compared to 50 normal weighted age and gender matched control individuals. Ambulatory BP was measured, and cfPWV was investigated in two ways in respect to the distance measure of aorta; the previously recommended length - the so called subtracted distance, and the currently recommended length - the direct distance. In a longitudinal design, the obese patients were re-investigated after one-year of lifestyle intervention at the Children's Obesity Clinic in purpose of reducing the degree of obesity. In the cross-sectional design, the obese group had higher measures of obesity, while matched for age, gender and height, when compared to the control group. In the longitudinal design, 74% of the 72 followed up obese patients experienced a significant weight reduction. CfPWV was dependent on the method used to measure the

  10. Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women.

    PubMed

    Matsubara, Tomoko; Miyaki, Asako; Akazawa, Nobuhiko; Choi, Youngju; Ra, Song-Gyu; Tanahashi, Koichiro; Kumagai, Hiroshi; Oikawa, Satoshi; Maeda, Seiji

    2014-02-01

    The Klotho gene is a suppressor of the aging phenomena, and the secretion as well as the circulation of Klotho proteins decrease with aging. Although habitual exercise has antiaging effects (e.g., a decrease in arterial stiffness), the relationship between Klotho and habitual exercise remains unclear. In the present study, we investigated the effect of habitual exercise on Klotho, with a particular focus on arterial stiffness. First, we examined the correlation between plasma Klotho concentration and arterial stiffness (carotid artery compliance and β-stiffness index) or aerobic exercise capacity [oxygen uptake at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50-76 years old) by conducting a cross-sectional study. Second, we tested the effects of aerobic exercise training on plasma Klotho concentrations and arterial stiffness. A total of 19 healthy, postmenopausal women (50-76 years old) were divided into two groups: control group and exercise group. The exercise group completed 12 wk of moderate aerobic exercise training. In the cross-sectional study, plasma Klotho concentrations positively correlated with carotid artery compliance and VT and negatively correlated with the β-stiffness index. In the interventional study, aerobic exercise training increased plasma Klotho concentrations and carotid artery compliance and decreased the β-stiffness index. Moreover, the changes in plasma Klotho concentration and arterial stiffness were found to be correlated. These results suggest a possible role for secreted Klotho in the exercise-induced modulation of arterial stiffness.

  11. [Azilsartan Medoxomil Capabilities in Arterial Hypertension and Obesity].

    PubMed

    Vasyuk, Y A; Shupenina, E Y; Nesvetov, V V; Nesterova, E A; Golubkova, E I

    2016-12-01

    Arterial hypertension (AH) is one of the most common cardiovascular disease. Angiotensin II (AT II), the hormone of renin-angiotensin-aldosterone system, realizes its negative effects through AT 1 receptors - application point of angiotensin receptor blockers (ARB). Due to different dissociation AT 1 receptors properties some ARBs are more effective than others. Multiply multicenter randomized and observational studies approve the effectiveness and safety of azilsartan medoxomil in patients with AH 1-2 grade. Several preclinical studies have shown the additional properties of azilsartan, including increase of insulin sensitivity, cardio- and nephron protection in obesity. In our clinical case we showed the positive influence of azilsartan medoxomil on clinic and ambulatory blood pressure, 24-hour aortic stiffness parameters, longitudinal left ventricular strain in patient with AH and obesity.

  12. [Resistant arterial hypertension and coarctation of the aorta].

    PubMed

    Martínez-Quintana, Efrén; Rossique-Delmas, Pilar; Rodríguez-González, Fayna

    2014-01-01

    Coarctation of the aorta accounts for around 5 percent of all congenital heart defects. Many of these patients develop arterial hypertension, and occasionally resistant arterial hypertension, despite adequate correction. This may lead to potentially fatal complications such as heart failure, aortic dissection, cerebrovascular events, or myocardial infarction. Therefore, a correct diagnosis must be made and an appropriate treatment started to reduce arterial hypertension, arteriosclerotic vascular disease, as well as the increased risk of cardiovascular morbidity and mortality.

  13. Bone Strength and Arterial Stiffness Impact on Cardiovascular Mortality in a General Population

    PubMed Central

    Avramovska, Maja; Sikole, Aleksandar

    2016-01-01

    Osteoporosis and increased arterial stiffness independently have been found to be associated with higher cardiovascular events rates in the general population (GP). We examined 558 patients from GP by dual-energy X-ray absorptiometry (DXA) and pulse wave velocity (PWV) measurements at baseline, with 36-month follow-up period. DXA assessed bone mineral density of femoral neck (BMD FN) and lumbar spine (BMD LS). Carotid-femoral PWV was assessed by pulsed-Doppler. The aim of our study is to find correlation between bone strength and arterial stiffness and their impact on cardiovascular mortality in GP. The mean ± SD of BMD FN, BMD LS, and PWV was 0.852 ± 0.1432 g/cm2, 0.934 ± 0.1546 g/cm2, and 9.209 ± 1.9815 m/s. In multiple regression analysis we found BMD FN (βst = −6.0094, p < 0.0001), hypertension (βst = 1.7340, p < 0.0091), and diabetes (βst = 0.4595, p < 0.0046). With Cox-regression analysis, after 17 cardiovascular events, the significant covariates retained by the backward model were BMD FN (b = −2.4129, p = 0.015) and PWV (b = 0.2606, p = 0.0318). The cut-off values were PWV = 9.4 m/s, BMD FN = 0.783 g/cm2, and BMD LS = 0.992 g/cm2. The results for BMD FN and PWV hazard ratio risk were 1.116 and 1.297, respectively. BMD FN as a measure of bone strength and PWV as a measure of arterial stiffness are strong independent predictors of cardiovascular mortality in GP. PMID:27047700

  14. [Novel immunopathological approaches to pulmonary arterial hypertension].

    PubMed

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition.

  15. Differential effects of nebivolol and metoprolol on arterial stiffness, circulating progenitor cells, and oxidative stress.

    PubMed

    Hayek, Salim S; Poole, Joseph C; Neuman, Robert; Morris, Alanna A; Khayata, Mohamed; Kavtaradze, Nino; Topel, Matthew L; Binongo, Jose G; Li, Qunna; Jones, Dean P; Waller, Edmund K; Quyyumi, Arshed A

    2015-03-01

    Unlike traditional beta receptor antagonists, nebivolol activates nitric oxide. We hypothesized that therapy with nebivolol compared with metoprolol would improve arterial stiffness, increase levels of circulating progenitor cells (PC), and decrease oxidative stress (OS). In a randomized, double-blind, cross-over study, 30 hypertensive subjects received either once daily nebivolol or metoprolol succinate for 3 months each. Pulse wave velocity and augmentation index were measured using tonometry. Flow cytometry was used to measure circulating PC. OS was measured as plasma aminothiols. Measurements were performed at baseline, and repeated at 3 and 6 months. No significant differences were present between the levels of OS, arterial stiffness, and PC numbers during treatment with metoprolol compared with nebivolol. In subgroup analyses of beta-blocker naïve subjects (n = 19), nebivolol reduced pulse wave velocity significantly compared with metoprolol (-1.4 ± 1.9 vs. -0.1 ± 2.2; P = .005). Both nebivolol and metoprolol increased circulating levels of CD34+/CD133 + PC similarly (P = .05), suggesting improved regenerative capacity.

  16. Developing treatments for pulmonary arterial hypertension

    PubMed Central

    Wilkins, Martin R.

    2013-01-01

    Developing new treatments for pulmonary arterial hypertension (PAH) is a challenge. We have enjoyed success with regulatory approvals for three drug classes—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. But we have also seen some disappointing results, for example, from studies with vasoactive intestinal polypeptide, statins and tergolide. Animal models are an unreliable predictor of efficacy in humans. The best model for the disease is the patient. This review discusses three major issues facing the evaluation of drugs in PAH patients—target validation, choosing the right dose, and early trial design. PMID:23662193

  17. "Nocturnal seizures" in idiopathic pulmonary arterial hypertension.

    PubMed

    Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V

    2013-10-15

    The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children.

  18. [Anticoagulation therapy in pulmonary arterial hypertension].

    PubMed

    Akagi, Satoshi; Kusano, Kengo Fukushima

    2008-11-01

    Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.

  19. Decreased elastic energy storage, not increased material stiffness, characterizes central artery dysfunction in fibulin-5 deficiency independent of sex.

    PubMed

    Ferruzzi, J; Bersi, M R; Uman, S; Yanagisawa, H; Humphrey, J D

    2015-03-01

    Central artery stiffness has emerged over the past 15 years as a clinically significant indicator of cardiovascular function and initiator of disease. Loss of elastic fiber integrity is one of the primary contributors to increased arterial stiffening in aging, hypertension, and related conditions. Elastic fibers consist of an elastin core and multiple glycoproteins; hence defects in any of these constituents can adversely affect arterial wall mechanics. In this paper, we focus on mechanical consequences of the loss of fibulin-5, an elastin-associated glycoprotein involved in elastogenesis. Specifically, we compared the biaxial mechanical properties of five central arteries-the ascending thoracic aorta, descending thoracic aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and common carotid artery-from male and female wild-type and fibulin-5 deficient mice. Results revealed that, independent of sex, all five regions in the fibulin-5 deficient mice manifested a marked increase in structural stiffness but also a marked decrease in elastic energy storage and typically an increase in energy dissipation, with all differences being most dramatic in the ascending and abdominal aortas. Given that the primary function of large arteries is to store elastic energy during systole and to use this energy during diastole to work on the blood, fibulin-5 deficiency results in a widespread diminishment of central artery function that can have significant effects on hemodynamics and cardiac function.

  20. Potassium channels in pulmonary arterial hypertension.

    PubMed

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien

    2015-10-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.

  1. Aortic stiffness determines diastolic blood flow reversal in the descending thoracic aorta: potential implication for retrograde embolic stroke in hypertension.

    PubMed

    Hashimoto, Junichiro; Ito, Sadayoshi

    2013-09-01

    Aortic stiffening often precedes cardiovascular diseases, including stroke, but the underlying pathophysiological mechanisms remain obscure. We hypothesized that such abnormalities could be attributable to altered central blood flow dynamics. In 296 patients with uncomplicated hypertension, Doppler velocity pulse waveforms were recorded at the proximal descending aorta and carotid artery to calculate the reverse/forward flow ratio and diastolic/systolic flow index, respectively. Tonometric waveforms were recorded on the radial artery to estimate aortic pressure and characteristic impedance (Z0) and to determine carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities. In all subjects, the aortic flow waveform was bidirectional, comprising systolic forward and diastolic reverse flows. The aortic reverse/forward flow ratio (35 ± 10%) was positively associated with parameters of aortic stiffness (including pulse wave velocity, Z0, and aortic/peripheral pulse wave velocity ratio), independent of age, body mass index, aortic diameter, and aortic pressure. The carotid flow waveform was unidirectional and bimodal with systolic and diastolic maximal peaks. There was a positive relationship between the carotid diastolic/systolic flow index (28 ± 9%) and aortic reverse/forward flow ratio, which remained significant after adjustment for aortic stiffness and other related parameters. The Bland-Altman plots showed a close time correspondence between aortic reverse and carotid diastolic flow peaks. In conclusion, aortic stiffness determines the extent of flow reversal from the descending aorta to the aortic arch, which contributes to the diastolic antegrade flow into the carotid artery. This hemodynamic relationship constitutes a potential mechanism linking increased aortic stiffness, altered flow dynamics, and increased stroke risk in hypertension.

  2. [French as 2005-recommendations on the management of arterial hypertension].

    PubMed

    Chamontin, B; Halimi, J M

    2007-01-01

    Self blood pressure measurements (home BP) and/or ambulatory BP measurements are recommended in mild to moderate hypertension (140/90 - 179/109 mmHg) in order to confirm sustained hypertension and identify white coat and masked hypertension. The evaluation of target organ damages (TOD) has to be integrated in cardiovascular risk estimate and taken into account in the management of hypertensive patients. Beside echocardiography, there is a place for the screening of microalbuminuria in non diabetic hypertensive patients, but these investigations should not be performed systematically. Arterial stiffness evaluation and carotid intima-media thickness quantification are not yet recommended. Cardiovascular risk (CV risk) estimate plays a pivotal role in the therapeutic decision and strategy. The cardiovascular risk grade is based on [1] the list of cardiovascular risk factors (same list AFSSAPS recommendations on dyslipidemia), [2] the presence or absence of TOD and [3] cardiovascular complications: "low", "medium", and "high" CV risk. Lifestyle modifications are recommended in all hypertensive patients. Five antihypertensive drugs are recommended for first line therapy: beta-blockers, thiazide diuretics, ACEIs, ARA II and CCBs (and fixed low dose combinations with AFSSAPS agreement for first line). In order to initiate the treatment, Evidence-based therapy (according to clinical trials conducted in different clinical situations), certain comorbid conditions (compelling indications), efficacy and side-effects in a previous experience, and the cost are the determinants of the first choice. Most hypertensive patients require more than one agent to achieve target blood pressure and for second line therapy the recommended combinations are: betablockers-diuretics, ACEIs-diuretics, ARAII-diuretics, betablockers-CCBs (DHP), ACEIs-CCBs, ARA II-CCBs and CCBs-diuretics. The delay to establish a combination therapy depend on CV risk. The BP goals are those recommended by ESH

  3. Tadalafil as treatment for idiopathic pulmonary arterial hypertension.

    PubMed

    de Carvalho, Adriana Castro; Hovnanian, André Luiz; Fernandes, Caio Julio César dos Santos; Lapa, Mônica; Jardim, Carlos; Souza, Rogério

    2006-11-01

    Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.

  4. [Arterial hypertension in females engaged into penal system work].

    PubMed

    Tagirova, M M; El'garov, A A; Shogenova, A B; Murtazov, A M

    2010-01-01

    The authors proved significant prevalence of arterial hypertension and atherosclerosis risk factors in women engaged into penal system work--so these values form cardiovascular risk caused by environmental parameters. Teveten and Nebilet were proved effective in the examinees with arterial hypertension.

  5. Inhaled treprostinil and pulmonary arterial hypertension

    PubMed Central

    Nadler, Samuel T; Edelman, Jeffrey D

    2010-01-01

    Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432

  6. Treatment of idiopathic/hereditary pulmonary arterial hypertension.

    PubMed

    Matsubara, Hiromi; Ogawa, Aiko

    2014-10-01

    Treatment of pulmonary hypertension has progressed by recently developed pulmonary arterial hypertension-targeted drugs. However, long-term survival of the patients with idiopathic/heritable pulmonary arterial hypertension is still suboptimal. To improve the outcomes, treatment goals of pulmonary hypertension were proposed at the 5th World Symposium on Pulmonary Hypertension held at Nice, France in 2013; parameters were obtained from cardiopulmonary exercise test, blood tests, echocardiography, and magnetic resonance imaging. In particular, parameters evaluating right ventricular function have been highlighted because survival of the patients with pulmonary arterial hypertension is closely related to right ventricular function. However, treatment specifically targeted to improve right ventricular function in pulmonary hypertension is not yet established. In this setting, we need to maintain or improve right ventricular function with available vasodilators. In this review, we focus on the following two points: (1) Why can pulmonary arterial hypertension-targeted drugs improve right ventricular function without an apparent decrease in pulmonary artery pressure? (2) Are proposed goals sufficient to improve long-term prognosis of the patients? Further, we will discuss what would be the appropriate goal in treating patients with pulmonary arterial hypertension.

  7. Modern Age Pathology of Pulmonary Arterial Hypertension

    PubMed Central

    Stacher, Elvira; Graham, Brian B.; Hunt, James M.; Gandjeva, Aneta; Groshong, Steve D.; McLaughlin, Vallerie V.; Jessup, Marsha; Grizzle, William E.; Aldred, Michaela A.; Cool, Carlyne D.

    2012-01-01

    Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH. PMID:22679007

  8. Mitochondrial Dynamics in Pulmonary Arterial Hypertension

    PubMed Central

    Ryan, John; Dasgupta, Asish; Huston, Jessica; Chen, Kuang-Huieh; Archer, Stephen L.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an idiopathic cardiopulmonary disease characterized by obstruction of small pulmonary arteries by excessive proliferation and apoptosis-resistance of vascular cells, as well as inflammation, thrombosis and vasoconstriction. Vascular obstruction increases the afterload faced by the right ventricle (RV), leading to RV failure. The proliferative, obstructive vasculopathy of PAH shares several mitochondrial abnormalities with cancer, notably a shift to aerobic glycolysis and mitochondrial fragmentation. Mitochondria in the pulmonary artery smooth muscle cell (PASMC) normally serve as oxygen sensors. In PAH, acquired mitochondrial abnormalities, including epigenetic silencing of superoxide dismutase (SOD2), disrupt oxygen sensing creating a pseudo-hypoxic environment characterized by normoxic activation of Hypoxia-Inducible Factor-1α (HIF-1α). The resulting metabolic shift to aerobic glycolysis (the Warburg phenomenon) reflects inhibition of pyruvate dehydrogenase by pyruvate dehydrogenase kinases. In addition, altered mitochondrial dynamics result in mitochondrial fragmentation. The molecular basis of this structural change includes upregulation and activation of fission mediators, notably dynamin-related protein 1 (DRP-1), and downregulation of fusion mediators, especially mitofusin-2 (MFN2). These pathogenic mitochondrial abnormalities offer new therapeutic targets. Inhibition of mitotic fission or enhancement of fusion in PAH PASMC slows cell proliferation, causes cell cycle arrest, and induces apoptosis. DRP-1 inhibition or MFN2 gene therapy can regress PAH in experimental models of PAH. This review focuses on the etiology of mitochondrial fragmentation in PAH and explores the therapeutic implications of mitochondrial dynamics in the pulmonary vasculature and RV. PMID:25672499

  9. Structural and functional changes of the coronary arteries in elderly senile patients with essential hypertension.

    PubMed

    Hu, Jun; Zhu, Fu; Xie, Jun; Cheng, Xinhai; Chen, Guiyu; Tai, Haifen; Fan, Shaohua

    2013-11-01

    The aim of this study was to evaluate the effect of aging on the changes to the structure and function of coronary arteries in senile elderly patients with essential hypertension. Patients (aged 60-80 years) were divided into three groups. The 195 hypertensive patients were divided into four sub-groups according to the duration of hypertension. The changes to the coronary arteries (left and right) of all those patients were tested using the following index by 64 coronary computed tomography (CT) scans. The 24 h systolic blood pressure (SBP) and other blood biochemical parameters were assayed for all patients. We found that the value of the body mass index (BMI), total cholesterol (TC) and low density lipoproteins (LDL) were lower, but age and high density lipoproteins (HDL) were higher in the group of very elderly patients with hypertension (Group I; P<0.05) compared with those of a group of elderly patients with hypertension (Group III). The left anterior descending branch calcification score (CSLAD), total calcification score (CST), pulse pressure (PP), the left main branch calcification score (CSLM), the left circumflex branch calcification score (CSLCX) were significantly increased in Group I compared with Group III (P<0.01 and P<0.05, respectively). In addition, the 24 h SBP value for Group I was higher than in the 'very elderly without hypertension' group (Group II). Hence, in elderly patients, a decrease in the levels of BMI, HDL, TC and LDL accompanies aging. Furthermore, the decline of arterial compliance and increase in arterial stiffness develops with age. Aging is more likely to lead to atherosclerosis in the coronary arteries, particularly in the left main coronary artery and its main branches. Aging is an uncontrollable risk factor, which plays a crucial role in coronary artery atherosclerosis.

  10. Arterial hypertension in chronic glomerulonephritis. An analysis of 310 cases.

    PubMed

    Danielsen, H; Kornerup, H J; Olsen, S; Posborg, V

    1983-06-01

    310 cases of glomerulonephritis classified morphologically according to the criteria of the WHO were analyzed retrospectively in order to determine the frequency of arterial hypertension. The overall prevalence of arterial hypertension was 61%. Hypertension was most frequent and severe in membranoproliferative and sclerotic glomerulonephritis, but often mild and transient in extracapillary glomerulonephritis. Hypertension usually developed during the early stages of the disease when kidney function was well preserved and in only 16% was hypertension first seen during the uremic stage. No correlation was found between hypertension and the presence of the nephrotic syndrome. During dialysis, hypertension was present in 78%; in 90% of these patients hypertension was "controllable" and in 10% it was "uncontrollable".

  11. Arterial pressure measurement: Is the envelope curve of the oscillometric method influenced by arterial stiffness?

    NASA Astrophysics Data System (ADS)

    Gelido, G.; Angiletta, S.; Pujalte, A.; Quiroga, P.; Cornes, P.; Craiem, D.

    2007-11-01

    Measurement of peripheral arterial pressure using the oscillometric method is commonly used by professionals as well as by patients in their homes. This non invasive automatic method is fast, efficient and the required equipment is affordable with a low cost. The measurement method consists of obtaining parameters from a calibrated decreasing curve that is modulated by heart beats witch appear when arterial pressure reaches the cuff pressure. Diastolic, mean and systolic pressures are obtained calculating particular instants from the heart beats envelope curve. In this article we analyze the envelope of this amplified curve to find out if its morphology is related to arterial stiffness in patients. We found, in 33 volunteers, that the envelope waveform width correlates to systolic pressure (r=0.4, p<0.05), to pulse pressure (r=0.6, p<0.05) and to pulse pressure normalized to systolic pressure (r=0.6, p<0.05). We believe that the morphology of the heart beats envelope curve obtained with the oscillometric method for peripheral pressure measurement depends on arterial stiffness and can be used to enhance pressure measurements.

  12. Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension.

    PubMed

    Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel', A L

    2016-08-01

    Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension.

  13. Surrogates of Large Artery versus Small Artery Stiffness and Ankle-Brachial Index

    PubMed Central

    Korhonen, Päivi; Syvänen, Kari; Aarnio, Pertti

    2011-01-01

    Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = −0.347, p = 0.004) and with ABI-lower (r = −0.424, p < 0.001). PAT hyperemic response was not significantly correlated with either ABI-higher (r = −0.148, p = 0.24) or with ABI-lower (r = −0.208, p = 0.095). Measurement of ABI using the lower of the two ankle pressures is an efficient method to identify patients with clinical or subclinical atherosclerosis and worth performing on subjects with pulse pressure above 65 mm Hg. The usefulness of PAT measurement in detecting PAD is vague. PMID:22942632

  14. [Pulmonary arterial hypertension in connective tissue diseases].

    PubMed

    Cordier, Jean-François

    2009-11-01

    Among connective tissue diseases, pulmonary arterial hypertension (PAH) is frequently associated with systemic sclerosis and systemic lupus erythematosus. PAH is less common in mixed connective tissue diseases and Sjögren's syndrome, and rare in rheumatoid arthritis. PAH in systemic sclerosis may be either isolated (prevalence about 8%) or associated with interstitial lung disease. Echocardiographic screening for PAH is worthwhile in patients with systemic sclerosis, especially as treatments for idiopathic PAH (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids) are effective in this setting. The prevalence of PAH among patients with systemic lupus erythematosus is poorly known; immunosuppressive treatment is sometimes effective by itself but most patients benefit from PAH treatment. PAH associated with connective tissue diseases has a worse prognosis than idiopathic PAH.

  15. [Segmental arterial mediolysis and renovascular hypertension].

    PubMed

    Gaud, Simon; Cridlig, Joelle; Claudon, Michel; Diarrassouba, Assetou; Kessler, Michèle; Frimat, Luc

    2010-12-01

    Segmental arterial mediolysis (SAM) is a rare nonarteriosclerotic, noninflammatory vascular disease of unknown origin that causes vascular occlusion or massive life-threatening intraabdominal hemorrhages. SAM is an acute disease. The initial injurious phase consist in mediolysis, then evolves in chronic vascular lesions. Diagnostic criteria are histologic, but rarely accessible apart from surgical complications. To our knowledge, there is no recommendation concerning therapy and follow-up of these patients. In our patient, we were interested in the atypical clinical presentation with renovascular hypertension, and the coexistence of acute and chronic vascular lesions that suppose the existence of recurrences in the evolution of this disease. We are interested also in the link that might exist between renal infarct and SAM, SAM's chronic vascular lesions and fibromuscular dysplasia vascular lesions.

  16. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    PubMed

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.

  17. Sildenafil in pediatric pulmonary arterial hypertension

    PubMed Central

    Dhariwal, AK; Bavdekar, SB

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children. PMID:26119438

  18. [Pulmonary arterial hypertension: changing approaches to management].

    PubMed

    Sidorenko, B A; Preobrazhenskiĭ, D V; Batyraliev, T A; Belenkov, Iu N

    2011-01-01

    The review is devoted to different aspects of pulmonary arterial hypertension (PAH); new classification of PAH is published in 2010. There are idiopathic PAH and PAH associated with other diseases. Current guidelines recommend to treat PAH only after the verification of diagnosis with right heart catheterization and acute tests with vasodilators. Patients-reactors should be treated with calcium antagonists. The following drugs related to one of three categories should be used in PAH: (1) prostanoids (epoprostenol, iloprost et al.); (2) blockers of endothelin receptors (bosentan, ambrisentan, sitaxsentan); (3) phosphodiesterase 5 type inhibitors (sildenafil, tadalafil et al.) In majority of cases the combined treatment is used, usually the combination of bosentan and sildenafil is used.

  19. Sildenafil in pediatric pulmonary arterial hypertension.

    PubMed

    Dhariwal, A K; Bavdekar, S B

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.

  20. Evaluation and management of the patient with pulmonary arterial hypertension.

    PubMed

    Rubin, Lewis J; Badesch, David B

    2005-08-16

    Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.

  1. Arterial stiffness and sedentary lifestyle: Role of oxidative stress.

    PubMed

    Lessiani, Gianfranco; Santilli, Francesca; Boccatonda, Andrea; Iodice, Pierpaolo; Liani, Rossella; Tripaldi, Romina; Saggini, Raoul; Davì, Giovanni

    2016-04-01

    Sedentary lifestyle is a risk factor for the development of cardiovascular disease, and leads to a quantifiable impairment in vascular function and arterial wall stiffening. We tested the hypothesis of oxidative stress as a determinant of arterial stiffness (AS) in physically inactive subjects, and challenged the reversibility of these processes after the completion of an eight-week, high-intensity exercise training (ET). AS was assessed before and after ET, measuring carotid to femoral pulse wave velocity (PWV) with a Vicorder device. At baseline and after ET, participants performed urine collection and underwent fasting blood sampling. Urinary 8-iso-PGF2α, an in vivo marker of lipid peroxidation, total, HDL and LDL cholesterol, and triglyceride concentrations were measured. ET was associated with significantly reduced urinary 8-iso-PGF2α(p<0.0001) levels. PWV was significantly reduced after ET completion (p<0.0001), and was directly related to urinary 8-iso-PGF2α(Rho=0.383, p=0.021). After ET, cardiovascular fitness improved [peak oxygen consumption (p<0.0001), peak heart rate (p<0.0001)]. However, no improvement in lipid profile was observed, apart from a significant reduction of triglycerides (p=0.022). PWV and triglycerides were significantly related (Rho=0.466, p=0.005) throughout the study period. PWV levels were also related to urinary 8-iso-PGF2α in our previously sedentary subjects. We conclude that regular physical exercise may be a natural antioxidant strategy, lowering oxidant stress and thereby the AS degree.

  2. Computational modeling of hypertensive growth in the human carotid artery

    NASA Astrophysics Data System (ADS)

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-06-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively.

  3. Arterial pulmonary hypertension in noncardiac intensive care unit

    PubMed Central

    Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen

    2008-01-01

    Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752

  4. Acute effects of firefighting on arterial stiffness and blood flow.

    PubMed

    Fahs, Christopher A; Yan, Huimin; Ranadive, Sushant; Rossow, Lindy M; Agiovlasitis, Stamatis; Echols, George; Smith, Denise; Horn, Gavin P; Rowland, Thomas; Lane, Abbi; Fernhall, Bo

    2011-04-01

    Sudden cardiac events are responsible for 40-50% of line-of-duty firefighter fatalities, yet the exact cause of these events is unknown. Likely, combinations of thermal, physical, and mental factors impair cardiovascular function and trigger such events. Therefore, the purpose of this study was to examine the impact of firefighting activities on vascular function. Sixty-nine young (28 ± 1 years) male firefighters underwent 3 hours of firefighting activities. Carotid, aortic, and brachial blood pressures (BP), heart rate (HR), augmentation index (AIx), wave reflection timing (TR), aortic pulse wave velocity (PWV), forearm blood flow (FBF), and forearm reactive hyperemia (RH) were measured before and after firefighting activities. Paired samples t-tests revealed significant (p < 0.05) increases in aortic diastolic BP, HR, AIx, PWV, RH, and FBF, and significant decreases in brachial and aortic pulse pressure and TR following firefighting activities. In conclusion, these results suggest that 3 hours of firefighting activities increase both arterial stiffness and vasodilation.

  5. The right ventricle in pulmonary arterial hypertension.

    PubMed

    Naeije, Robert; Manes, Alessandra

    2014-12-01

    Pulmonary arterial hypertension (PAH) is a right heart failure syndrome. In early-stage PAH, the right ventricle tends to remain adapted to afterload with increased contractility and little or no increase in right heart chamber dimensions. However, less than optimal right ventricular (RV)-arterial coupling may already cause a decreased aerobic exercise capacity by limiting maximum cardiac output. In more advanced stages, RV systolic function cannot remain matched to afterload and dilatation of the right heart chamber progressively develops. In addition, diastolic dysfunction occurs due to myocardial fibrosis and sarcomeric stiffening. All these changes lead to limitation of RV flow output, increased right-sided filling pressures and under-filling of the left ventricle, with eventual decrease in systemic blood pressure and altered systolic ventricular interaction. These pathophysiological changes account for exertional dyspnoea and systemic venous congestion typical of PAH. Complete evaluation of RV failure requires echocardiographic or magnetic resonance imaging, and right heart catheterisation measurements. Treatment of RV failure in PAH relies on: decreasing afterload with drugs targeting pulmonary circulation; fluid management to optimise ventricular diastolic interactions; and inotropic interventions to reverse cardiogenic shock. To date, there has been no report of the efficacy of drug treatments that specifically target the right ventricle.

  6. A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy

    PubMed Central

    Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan

    2016-01-01

    Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways. PMID:27929408

  7. A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy.

    PubMed

    Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan

    2016-12-06

    Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways.

  8. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    PubMed

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.

  9. Recapitulation of developing artery muscularization in pulmonary hypertension.

    PubMed

    Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M

    2014-03-13

    Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.

  10. [FEATURES OF ARTERIAL HYPERTENSION IN THE WORKING POPULATION].

    PubMed

    Mershenova, G; Kossybayeva, M; Chancharov, B; Mirzayeva, B; Amangeldiyeva, K

    2017-01-01

    Purpose of the research was to study clinical features of arterial hypertension in the working population in Karaganda. The number of participants (500 patients): base group (250 patients) and control group (250 patients). The criteria for inclusion (age and gender characteristics, diseases/conditions and etc): age from 18 to 63 years; presence of arterial hypertension 1, 2 and 3 grades; possibility to measure the arterial pressure in dynamic; patients, who agreed to participate in the research work (the existence of informed consent). The criteria for an exception: children under 18 years, pregnant, the patient's refusal to participate in the research work. Methods of research - retrospective analysis of patients card in base and control groups at the working population of the city of Karaganda; physical examinations (anthropometrical indicators) in base and control groups. The processing and analysis of materials was conducted by using the average values and their standard errors. Significance of differences of independent sets of were estimated with parametric and nonparametric methods. In the study group compared with control were more common all the risk factors of hypertension, especially hypercholesterolemia and dyslipidemia in half of the cases in patients with arterial hypertension working age. We believe that the main factors of risk in arterial hypertension are hypercholesterolemia and dyslipidemia with combination in other factors, affecting mainly on the course and outcome of hypertension. Degrees of hypertension was dependent from age of patients and duration of illness, there was a trend more pronounced degree of hypertension in men than in women. In men with slavic nationality was more pronounced hypertension 1,2 and 3 degree, while in Kazakh nationality men often was observed hypertension 1, 2 degree. The degree of hypertension in the study group depending on the mental and physical labor did not observed. Hypertension 2-3 degrees was observed at

  11. Deterioration in Renal Function Is Associated With Increased Arterial Stiffness

    PubMed Central

    2014-01-01

    BACKGROUND Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS We conducted a 4–5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS Decline in renal functioning from baseline levels measured 4–5 years before measurement of PWV is related to higher levels of PWV in a community sample. PMID:24080989

  12. A knowledge-based approach to arterial stiffness estimation using the digital volume pulse.

    PubMed

    Jang, Dae-Geun; Farooq, Umar; Park, Seung-Hun; Goh, Choong-Won; Hahn, Minsoo

    2012-08-01

    We have developed a knowledge based approach for arterial stiffness estimation. The proposed new approach reliably estimates arterial stiffness based on the analysis of age and heart rate normalized reflected wave arrival time. The proposed new approach reduces cost, space, technical expertise, specialized equipment, complexity, and increases the usability compared to recently researched noninvasive arterial stiffness estimators. The proposed method consists of two main stages: pulse feature extraction and linear regression analysis. The new approach extracts the pulse features and establishes a linear prediction equation. On evaluating proposed methodology with pulse wave velocity (PWV) based arterial stiffness estimators, the proposed methodology offered the error rate of 8.36% for men and 9.52% for women, respectively. With such low error rates and increased benefits, the proposed approach could be usefully applied as low cost and effective solution for ubiquitous and home healthcare environments.

  13. Clinical appraisal of arterial stiffness: the Argonauts in front of the Golden Fleece

    PubMed Central

    Vlachopoulos, C; Aznaouridis, K; Stefanadis, C

    2006-01-01

    Interest in evaluating arterial elastic properties has grown in parallel with the widespread availability of non‐invasive methods for assessing arterial stiffness. A clinically useful diagnostic index must be pathophysiologically relevant, must be readily measurable, and must indicate the severity of the disease and predict the corresponding risk. Interventional modification of this index must parallel disease regression and benefit prognosis. The current evidence for the clinical value of estimating arterial stiffness (mainly of large, elastic‐type arteries, such as the aorta and the carotids) in the contemporary era of cardiovascular medicine is reviewed. PMID:16339817

  14. Clinical appraisal of arterial stiffness: the Argonauts in front of the Golden Fleece.

    PubMed

    Vlachopoulos, C; Aznaouridis, K; Stefanadis, C

    2006-11-01

    Interest in evaluating arterial elastic properties has grown in parallel with the widespread availability of non-invasive methods for assessing arterial stiffness. A clinically useful diagnostic index must be pathophysiologically relevant, must be readily measurable, and must indicate the severity of the disease and predict the corresponding risk. Interventional modification of this index must parallel disease regression and benefit prognosis. The current evidence for the clinical value of estimating arterial stiffness (mainly of large, elastic-type arteries, such as the aorta and the carotids) in the contemporary era of cardiovascular medicine is reviewed.

  15. Arterial Stiffness and Trace Elements in Apparently Healthy Population- A Cross-sectional Study

    PubMed Central

    Subrahmanyam, Gangapatnam; Ramalingam, Krishnan; Indira, Selvam Armugam; Kantha, Katari; Soren, Bhemasen

    2016-01-01

    Introduction Stiffening of arteries is a natural ageing process. Any diseases/disorders or risk factors that escalate oxidative stress, microvascular inflammation and endothelial damage may promote to premature vascular stiffening. Any imbalance in these trace element levels may independently contribute to the changes in the components in the arterial wall and thus, arterial stiffness via one or more mechanisms. Aim To evaluate the severity of arterial stiffness in apparently healthy population and also to evaluate role of various risk factors and trace elements in the severity of arterial stiffness Materials and Methods Male and female subjects living in urban and rural areas of Nellore district, Andhra Pradesh, India, between 20-60 years, apparently normal as judged by the clinician basing on clinical and laboratory findings, were studied. Carotid-Femoral Pulse Wave Velocity (cf-PWV) a marker of arterial stiffness was assessed using non-invasive blood pressure curve monitoring (periscope). Furthermore, we also estimated serum levels of Copper (Cu), Zinc (Zn), Selenium (Se), chromium (Cr), Aluminium (Al), silicon (Si), Manganese (Mn), Molybdenum (Mb), Vanadium (Vn) and lead (Pb) using atomic absorption spectrophotometer. ANOVA and Chi-Square test were used to study the clinical correlations between severity of arterial stiffness, risk factors and trace elements. Results A total of 737 apparently healthy subjects participated in this cross-sectional study. Of the total 542 (73.5%) were from rural and the remaining 195 (26.5%) were living in urban areas, 328 (44.5%) were males, and 409 (55.5%) were females. A 63.5% (468/737) had normal arterial stiffness followed by 14.5% (107/737) with mild stiffness, 7% (57/737) had moderate stiffness and 14.2% (105/737) had severe arterial stiffness. Smoking, alcohol, blood pressures, fasting blood sugar, and total cholesterol, Cu, Al and Vn correlated (p<0.05) with different grades of arterial stiffness. Conclusion A 36.5% had

  16. A higher baseline plasma uric acid level is an independent predictor of arterial stiffness

    PubMed Central

    Ding, Xiao-Han; Wang, Xiaona; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei; Ye, Ping

    2017-01-01

    Abstract Hyperuricemia has been demonstrated to be a risk factor for cardiovascular diseases. Though the association between uric acid (UA) and arterial stiffness has been investigated previously in patients with basic diseases, the predictive value of baseline UA level for arterial stiffness has not been conducted. We aimed at identifying the predictive role of UA for arterial stiffness prospectively. A longitudinal follow-up study in a routine health check-up population was performed with an average follow-up of 4.8 years. The demographic information, baseline and follow-up anthropometric parameters, arterial stiffness (pulse-wave velocity, PWV), and biomarker variables including UA have been measured and analyzed. A total of 1447 valid follow-ups were available for the final analysis. Both of the baseline and follow-up UA levels were significantly higher in the arterial stiffness groups than that in the nonarterial stiffness groups (all P values <0.001). The follow-up carotid-femoral PWV [(cf-PWV), r = 0.161, P < 0.001] was strongly correlated with baseline UA. At the follow-up cross-section, cf-PWV was also closely associated with UA (r = 0.101, P < 0.001). Logistic regressions revealed that a higher baseline UA level was an independent predictor of follow-up arterial stiffness assessed by cf-PWV [odds ratio (OR): 1.824; P = 0.046]. A higher baseline level of UA is closely related to arterial stiffness and is an independent predictor of arterial stiffening. PMID:28178136

  17. Arterial stiffness and hand osteoarthritis: a novel relationship?

    PubMed Central

    Saleh, A. S.; Najjar, S. S.; Muller, D. C.; Shetty, V.; Ferrucci, L.; Gelber, A. C.; Ling, S. M.

    2009-01-01

    Summary Objective Osteoarthritis (OA) and vascular stiffening may share elements of common pathogenesis, but their potential relatedness has been the focus of little prior inquiry. We tested the hypothesis that these two aging-associated conditions are related to each other. Method We analyzed cross-sectional data from 256 participants of the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging. All underwent measurement of arterial pulse wave velocity (PWV), an index of vascular stiffness, as well as hand radiographs that were graded for evidence of OA. Twenty total joints across three joint groups (distal interphalangeal [DIP], proximal interphalangeal [PIP], carpal-metacarpal [CMC]) were each assigned a Kellgren–Lawrence grade (K–L) of 0 (normal) through 4 (severe), with K–L grades ≥2 considered evidence of definite OA. Radiographic hand OA was defined as definite OA changes in at least two of the three anatomic hand sites (DIP, PIP, CMC). OA burden was represented by the total number of affected OA joints, and a cumulative K–L grade was aggregated across all hand joint groups. The relationship of PWV with these three measures of hand OA was assessed by linear regression. Results Upon univariate analysis, the presence of radiographic hand OA (β = 218.1, P < 0.01), the total number of OA joints (β = 32.9, P < 0.01), and the cumulative K–L grade across all joint groups (β = 12.2, P < 0.01) were each associated with increased PWV. These associations, however, were no longer significant in age-adjusted models. Conclusion Although significant individual relationships between PWV and several measures of hand OA were observed, these associations were largely attributable to the confounding effect of age. PMID:17097316

  18. Prostanoid therapy for pulmonary arterial hypertension.

    PubMed

    Badesch, David B; McLaughlin, Vallerie V; Delcroix, Marion; Vizza, Carmine Dario; Olschewski, Horst; Sitbon, Olivier; Barst, Robyn J

    2004-06-16

    Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients

  19. [Systemic arterial hypertension in child and adolescent].

    PubMed

    Rosas-Peralta, Martín; Medina-Concebida, Luz Elena; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    The epidemic of childhood obesity, the risk of developing left ventricular hypertrophy, and evidence of the early development of atherosclerosis in children would make the detection of and intervention in childhood hypertension important to reduce long-term health risks; however, supporting data are lacking. Secondary hypertension is more common in preadolescent children, with most cases caused by renal disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. Evaluation involves a through history and physical examination, laboratory tests, and specialized studies. Management is multifaceted. Nonpharmacologic treatments include weight reduction, exercise, and dietary modifications. Although the evidence of first line therapy for hypertension is still controversial, the recommendations for pharmacologic treatment are based on symptomatic hypertension, evidence of end-organ damage, stage 2 of hypertension, or stage 1 of hypertension unresponsive to lifestyle modifications, and hypertension with diabetes mellitus where is the search for microalbuminuria justified.

  20. Quantitative Indexes of Leukocytes in Spontaneously Hypertensive Rats During Various Periods of Arterial Hypertension Development.

    PubMed

    Aliev, O I; Anishchenko, A M; Sidekhmenova, A V; Shamanaev, A Yu; Fedorova, E P; Plotnikov, M B

    2015-10-01

    SHR rats were examined in the period before arterial hypertension development (5th week), during the increase in BP (6th-10th weeks), and under conditions of constantly elevated BP (11th-12th weeks). The total number of leukocytes did not differ in SHR and normotensive WKY rats. However, the relative number of lymphocytes and monocytes was shown to differ in various periods of arterial hypertension development. Our results suggest that white blood cells (primarily lymphocytes) are involved in the development of arterial hypertension.

  1. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.

  2. Pulmonary arterial hypertension in idiopathic inflammatory myopathies

    PubMed Central

    Sanges, Sébastien; Yelnik, Cécile M.; Sitbon, Olivier; Benveniste, Olivier; Mariampillai, Kuberaka; Phillips-Houlbracq, Mathilde; Pison, Christophe; Deligny, Christophe; Inamo, Jocelyn; Cottin, Vincent; Mouthon, Luc; Launay, David; Lambert, Marc; Hatron, Pierre-Yves; Rottat, Laurence; Humbert, Marc; Hachulla, Eric

    2016-01-01

    Abstract Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients. All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH. Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM-PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment. By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06). Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone. Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement

  3. Research on red cell membrane permeability in arterial hypertension.

    PubMed

    Gatina, R; Balta, N; Moisin, C; Burtea, C; Botea, S; Ioan, M; Teleianu, C

    1998-01-01

    Arterial hypertension, including the elucidation of hypertension pathogenic mechanisms involving elements in the composition of the blood, continues to represent a topical research area. Recent work, such as nuclear magnetic resonance studies looking into red cell permeability, illustrates the presence of modifications of red cell permeability to water (RCPW) related to the stage of arterial hypertension. The identification of a significant increase of RCPW compared to that present in the population with normal arterial pressure values can be useful both in early diagnosis and in warning about a possible predisposition for this condition. At the same time, the dynamic investigation of protonic relaxation time of both intra- and extra-erythrocytic water, the assessment of proton exchange time across the red cell and the calculation of permeability to water enable one not only to diagnose arterial hypertension but also to ascertain the evolution of the disease, its complications and the effectiveness of anti-hypertensive medication. Our studies have also proven the existence of a correlation between the values of systolic arterial pressure and red cell permeability to water. The curve describing the interdependence of the two values has the shape of a bell, in the case of males. The peak of the curve is reached for a systolic pressure of 160 mmHg and gets below the values of the control group in the case of systolic pressures above 200 mmHg. The RCPW test can also be considered a valuable indicator in evaluating the risk of stroke in hypertensive patients. In the chronic therapy of arterial hypertension with various types of anti-hypertensive drugs, one can note differences in the RCPW values related to the effectiveness of the respective medication, to the clinical form and stage of the disease, the sex of the patient as well as to the existence of cerebro-vascular complications.

  4. Genetics and genomics of pulmonary arterial hypertension.

    PubMed

    Soubrier, Florent; Chung, Wendy K; Machado, Rajiv; Grünig, Ekkehard; Aldred, Micheala; Geraci, Mark; Loyd, James E; Elliott, C Gregory; Trembath, Richard C; Newman, John H; Humbert, Marc

    2013-12-24

    Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes. To identify additional genetic variants predisposing to PAH, investigators harnessed the power of next-generation sequencing to successfully identify additional genes that will be described in this report. Furthermore, common genetic predisposing factors for PAH can be identified by genome-wide association studies and are detailed in this paper. The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease. High-throughput genomic techniques, on the basis of next-generation sequencing, now allow the accurate quantification and analysis of ribonucleic acid, species, including micro-ribonucleic acids, and allow for a genome-wide investigation of epigenetic or

  5. Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.

    PubMed

    Fransen, Paul; Van Hove, Cor E; Leloup, Arthur J A; Schrijvers, Dorien M; De Meyer, Guido R Y; De Keulenaer, Gilles W

    2016-02-01

    Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.

  6. [Treatment of arterial hypertension in children].

    PubMed

    Bensman, A

    1988-01-01

    Hypertension in children is divided in 2 groups: primary hypertension and the secondary forms which are more severe and mostly due to kidney diseases. The medical management of hypertension includes non pharmacological intervention (diet, exercise, life-style) and pharmacological agents. The children with primary and mild hypertension may need only non pharmacological strategies. The main pharmacological agents used are: diuretics, vasodilators, sympathetic blockers, centrally acting agents, converting enzyme inhibitors. Except for hypertensive emergencies, the management of children with hypertension is facilitated by a stepped-care titration approach. Step 1: beta adrenergic blockers or vaso-dilators; step 2: combine beta adrenergic blockers with vaso-dilators or with diuretics or converting enzyme inhibitors alone; step 3: combine converting enzyme inhibitors with vaso-dilators and/or diuretics and/or beta adrenergic blockers; step 4: drugs include minoxidil, prazosin, labetalol.

  7. Structural abnormalities of small resistance arteries in essential hypertension.

    PubMed

    Rizzoni, Damiano; Agabiti-Rosei, Enrico

    2012-06-01

    Regardless of the mechanisms that initiate the increase in blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, the small arteries smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, while in some secondary forms of hypertension, a hypertrophic remodeling may be detected. Also, in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling of subcutaneous small arteries is present. The results from our own group have suggested that indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Therefore, the regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure, both in human and in animal models of genetic and experimental hypertension. A complete normalization of small resistance artery structure is demonstrated in hypertensive patients, after long-term and effective therapy with ACE inhibitors, angiotensin II receptor blockers and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard. In conclusion, there are several pieces of evidence that suggest that small resistance artery structure may be considered an intermediate endpoint in the evaluation of the effects of antihypertensive therapy; however, there are presently no data available about the prognostic impact of the regression of vascular structural alterations in hypertension and diabetes.

  8. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  9. [Arterial hypertension and alcoholism among workers in an oil refinery].

    PubMed

    Lima, C T; Carvalho, F M; Quadros, C de A; Gonçalves, H R; Silva Júnior, J A; Peres, M F; Bonfim, M S

    1999-09-01

    The role of alcohol ingestion in the incidence of arterial hypertension has not been completely established. In addition, there are few studies addressing this point in relation to populations of workers. The objective of this study was to evaluate the association between alcoholism and arterial hypertension among workers in an oil refinery in Mataripe, Bahia, Brazil, from 1986 to 1993. We designed a retrospective cohort study with a 7-year follow-up in a stratified systematic sample of 335 workers from the refinery. Arterial hypertension was diagnosed based on blood pressure measurements done during routine medical examinations. At the beginning of follow-up, three groups were defined using the CAGE test of alcohol dependency: nondrinkers (n = 121), CAGE-negative workers (n = 116), and CAGE-positive workers (n = 98). In comparison with the CAGE-negative group, the CAGE-positive group had both greater relative risk and greater attributable risk for developing arterial hypertension (RR = 2.58; AR = 24.95 per 1,000 person-years). The CAGE-positive group also had greater risks compared to nondrinkers (RR = 2.06; AR = 20.97 per 1,000 person-years). The attributable fractions for the same two comparisons of groups were 61% and 51%, respectively. Rate standardization by age or smoking habit did not substantially change the results. Alcoholism is an important risk factor for arterial hypertension.

  10. Arterial stiffness is not increased in patients with short duration rheumatoid arthritis and ankylosing spondylitis.

    PubMed

    Dzieża-Grudnik, Anna; Sulicka, Joanna; Strach, Magdalena; Siga, Olga; Klimek, Ewa; Korkosz, Mariusz; Grodzicki, Tomasz

    2017-04-01

    Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is an independent predictor of CV events. The aim of the study was to assess arterial stiffness and inflammatory markers in patients with short duration chronic arthritis. We assessed carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), traditional CV risk factors and inflammatory and endothelial markers in 71 chronic arthritis patients (RA and AS) and in 29 healthy controls. We did not find differences in PWV (for RA, AS and controls, respectively: 10 [8.8-10.9] versus 10.7 [9.1-11.8] versus 9.2 [8.3-11.4] m/s; p = .14) and AIx (for RA, AS and controls, respectively: 24.3 ± 11.5 versus 5.7 ± 12.4 versus 10 ± 12.8%; p = .22). Both groups of arthritis patients had active disease with significantly elevated inflammatory markers compared to controls. There were no correlations between endothelial and inflammatory markers and parameters of arterial stiffness in arthritis patients. When analyzing arthritis patients according to median of PVW, there were no significant differences in inflammatory and endothelial markers. We found that in patients with short duration active RA and AS arterial stiffness was not increased and furthermore, there was no association between markers of systemic inflammation and arterial stiffness.

  11. Relation between coronary artery disease, risk factors and intima-media thickness of carotid artery, arterial distensibility, and stiffness index.

    PubMed

    Alan, Sait; Ulgen, Mehmet S; Ozturk, Onder; Alan, Bircan; Ozdemir, Levent; Toprak, Nizamettin

    2003-01-01

    Atherosclerosis is a diffuse process that involves vessel structures. In recent years, the relation of noninvasive parameters such as intima-media thickening (IMT), arterial distensibility (AD), and stiffness index (SI) to cardiovascular diseases has been researched. However, we have not found any study that has included all these parameters. The aim of this study is to examine the relation between the presence of coronary artery disease (CAD) and its risk factors to AD, SI, and IMT, which are the noninvasive predictors of atherosclerotic process in the carotid artery. Included in the study were 180 patients who were diagnosed as having CAD by coronary angiography (those with at least > or = 30% stenosis in the coronary arteries) and, as a control group, 53 persons who had normal appearing coronary angiographies. IMT, AD, and SI values of all the patients in the study were measured by echo-Doppler imaging (AD formula = 2 x (AoS - AoD)/PP x AoD, SI formula = (SBP/DBP)/([AoS - AoD]/AoD). Significantly increased IMT (0.82 +/- 0.1, 0.57 +/- 0.1, p<0.05), decreased AD (0.25 +/- 0.9, 0.37 +/- 0.1, p<0.05), and increased SI (13 +/- 4, 8 +/- 3, p<0.05) values were detected in the CAD group compared to the control group. A significant correlation was found between IMT and presence of diabetes mellitus (DM), systolic blood pressure, total cholesterol, and presence of plaque in carotids, and age. In the coronary artery disease group there was a significant correlation between AD and age, systolic blood pressure, and HDL cholesterol levels, while there was no significant correlation with plaque development. A significant correlation was also found between stiffness index and systolic blood pressure and age; however, there was no relation between number of involved vessels and IMT, AD, and SI. We found sensitivity, specificity, and positive predictive and negative predictive values for CAD diagnosis to be 70%, 75%, 77%, and 66%, respectively. In CAD cases, according to data in

  12. Norepinephrine release in arteries of spontaneously hypertensive rats

    SciTech Connect

    Zsoter, T.T.; Wolchinsky, C.; Lawrin, M.; Sirko, S.

    1982-01-01

    The role of the sympathetic nervous system in arterial hypertension cannot be properly evaluated until it is known about the activity in the vessels themselves. In this study researchers investigated the effect of transmural stimulation on the tail artery - labelled in vitro with /sup 3/H-norepinephrine - of 7-9 week old spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKR). Electrical stimulation using two frequencies (2 and 10 Hz) resulted in significantly more /sup 3/H overflow in vessels from SHR than from WKR. With 10 Hz stimulation the fractional release was also greater. Column chromatographic analysis of /sup 3/H overflow revealed that transmural stimulation in arteries of SHR enhanced mainly the release of norepinephrine and not of its metabolites. Significantly, an increased release of /sup 3/H-norepinephrine on stimulation was observed in SHR before the full development of hypertension suggesting that it might be a cause rather than a consequence of high blood pressure.

  13. Therapy for Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

    PubMed Central

    Mathai, Stephen C.; Hassoun, Paul M.

    2010-01-01

    Purpose of review Systemic sclerosis is commonly complicated by pulmonary arterial hypertension (PAH-SSc) and is a leading cause of death in this population. We will review existing challenges and recent advances in the treatment of this disease. Recent findings Traditionally employed outcome measures in pulmonary arterial hypertension research may not be applicable in PAH-SSc. Importantly, new therapies that target abnormal cellular proliferation in the pulmonary vasculature are currently under investigation and may be particularly relevant to PAH-SSc. Summary Pulmonary arterial hypertension complicating systemic sclerosis occurs commonly and portends a poor prognosis. However, recent advances in our understanding of the disease in the context of systemic sclerosis may lead to novel diagnostic and therapeutic strategies that will ultimately improve quality of life and survival in this population. PMID:19667994

  14. HIV infection and arterial stiffness among older-adults taking antiretroviral therapy in rural Uganda

    PubMed Central

    Siedner, Mark J.; Kim, June-Ho; Nakku, Ruth Sentongo; Hemphill, Linda; Triant, Virginia A.; Haberer, Jessica E.; Martin, Jeffrey N.; Boum, Yap; Kwon, Douglas S.; Tsai, Alexander C.; Hunt, Peter W.; Okello, Samson; Bangsberg, David R.

    2015-01-01

    HIV infection is associated with arterial stiffness, but no studies have assessed this relationship in sub-Saharan Africa. We enrolled 205 participants over 40 years old in Uganda: 105 on antiretroviral therapy for a median of 7 years, and a random sample of 100 age and gender-matched HIV-uninfected controls from the clinic catchment area. The prevalence of arterial stiffness (ABI>1.2) was 33%, 18%, 19% and 2% in HIV+ men, HIV- men, HIV+ women, and HIV- women. In multivariable models adjusted for cardiovascular risk factors, HIV+ individuals had over double the prevalence of arterial stiffness (APR 2.86, 95%CI 1.41–5.79, P=0.003). PMID:26636926

  15. Development of easy operating arterial stiffness assessment instrument for home care.

    PubMed

    Wu, Hsien-Tsai; Yao, Cheng-Tso; Wu, Tsang-Chih; Liu, An-Bang

    2007-01-01

    In this study, 41 asymptomatic subjects (22 men and 19 women, 20 to 60 years of age) were enrolled. The PWV was measured both by dual-channel PPG (PWV-DVP) and by the proposed PWV instrument, Pulse Wave Velocity by Digital Volume Pulse Easy (PWV-DVPE). The developed system recorded digital volume pulse simultaneously from both the finger and ear. Time of pulse transition was measured on the time delay difference between two digital volume pulses. The PWV was calculated by dividing the distance between finger and ear by that of transit time. PWV-DVPE's capability of precise self-monitoring arterial stiffness is being proven in this study. In home care area, only few minutes is needed for self arterial stiffness assessment. Therefore, early self-monitoring of cardio-vascular dys-function and arterial stiffness is easily and effectively achieved.

  16. Developments in pulmonary arterial hypertension-targeted therapy for chronic thromboembolic pulmonary hypertension.

    PubMed

    Hadinnapola, Charaka; Pepke-Zaba, Joanna

    2015-10-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.

  17. Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension

    PubMed Central

    Schroer, Alison K.; Chen, Peter; Ryzhova, Larisa M.; Gladson, Santhi; Shay, Sheila; Hutcheson, Joshua D.; Merryman, W. David

    2016-01-01

    Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID:26863209

  18. Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study.

    PubMed

    Gijsbers, L; Dower, J I; Mensink, M; Siebelink, E; Bakker, S J L; Geleijnse, J M

    2015-10-01

    We performed a randomised, placebo-controlled, crossover study to examine the effects of sodium and potassium supplementation on blood pressure (BP) and arterial stiffness in untreated (pre)hypertensive individuals. During the study, subjects were on a fully controlled diet that was relatively low in sodium and potassium. After a 1-week run-in period, subjects received capsules with supplemental sodium (3 g d(-1), equals 7.6 g d(-1) of salt), supplemental potassium (3 g d(-1)) or placebo, for 4 weeks each, in random order. Fasting office BP, 24-h ambulatory BP and measures of arterial stiffness were assessed at baseline and every 4 weeks. Of 37 randomized subjects, 36 completed the study. They had a mean pre-treatment BP of 145/81 mm Hg and 69% had systolic BP ⩾140 mm Hg. Sodium excretion was increased by 98 mmol per 24 h and potassium excretion by 63 mmol per 24 h during active interventions, compared with placebo. During sodium supplementation, office BP was significantly increased by 7.5/3.3 mm Hg, 24-h BP by 7.5/2.7 mm Hg and central BP by 8.5/3.6 mm Hg. During potassium supplementation, 24-h BP was significantly reduced by 3.9/1.6 mm Hg and central pulse pressure by 2.9 mm Hg. Pulse wave velocity and augmentation index were not significantly affected by sodium or potassium supplementation. In conclusion, increasing the intake of sodium caused a substantial increase in BP in subjects with untreated elevated BP. Increased potassium intake, on top of a relatively low-sodium diet, had a beneficial effect on BP. Arterial stiffness did not materially change during 4-week interventions with sodium or potassium.

  19. Arterial hypertension in nursing personnel of an emergency hospital.

    PubMed

    Urbanetto, Janete de Souza; Prado Lima Figueiredo, Ana Elizabeth; da Silva Gustavo, Andreia; Bosi de Souza Magnago, Tânia Solange; Pinheiro da Costa, Bartira Ercilia; Poli-de-Figueiredo, Carlos Eduardo

    2015-08-01

    Risk factors related to the workplace environment are being studied to identify positive associations with hypertension disorders. Hypertension is considered as one of the main modifiable risk factors and most important public health issues. The study aims to describe the prevalence of hypertension and associate it with sociodemographic, labour and health aspects, in the health-care nursing staff of an emergency hospital.Cross-sectional study enrolled 606 nursing workers. The data were collected from February to June, and the analysis was conducted in November 2010. Arterial blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) were assessed, and sociodemographic and labour variables were investigated by means of a questionnaire. The data were analysed by descriptive statistics, univariate and multivariate analysis. The prevalence of hypertension was 32% (n = 388), with positive associations with age > 49 years (OR = 2.55 (CI: 1.19 to 5.43)), ethnicity (non-white) (odds ratio (OR) = 2.22, confidence interval (CI) 1.16 to 1.24), BMI (OR = 2.24 (CI: 1.25 to 4.01)) and WHR (OR = 2.65 (CI: 1.95 to 7.763)). Arterial hypertension was frequent in the nursing staff of this emergency hospital. Further studies are needed to better understand the relationship between occupational aspects and arterial hypertension.

  20. End points and clinical trial design in pulmonary arterial hypertension.

    PubMed

    McLaughlin, Vallerie V; Badesch, David B; Delcroix, Marion; Fleming, Thomas R; Gaine, Sean P; Galiè, Nazzareno; Gibbs, J Simon R; Kim, Nick H; Oudiz, Ronald J; Peacock, Andrew; Provencher, Steeve; Sitbon, Olivier; Tapson, Victor F; Seeger, Werner

    2009-06-30

    New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.

  1. Inhaled iloprost for therapy in pulmonary arterial hypertension.

    PubMed

    Ewert, Ralf; Gläser, Sven; Bollmann, Tom; Schäper, Christoph

    2011-04-01

    Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.

  2. Surrogate and combined end points in pulmonary arterial hypertension.

    PubMed

    Ventetuolo, Corey E; Benza, Raymond L; Peacock, Andrew J; Zamanian, Roham T; Badesch, David B; Kawut, Steven M

    2008-07-15

    Pulmonary arterial hypertension is a rare and often devastating disease, although various effective therapies are now available. Clinical trials have used hemodynamic, cardiac imaging, laboratory, and exercise measurements as surrogate and intermediate end points in pulmonary arterial hypertension. Yet, based on the current literature, it is difficult to surmise which of these (if any) have been definitively validated. In addition, investigators have advocated the use of combined clinical end points in future clinical trials. The dependence of clinical trials and clinical management on such end points warrants a review of their use.

  3. A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

    PubMed Central

    Liu, Chang-Yuan; Huang, Qi-Fang; Cheng, Yi-Bang; Guo, Qian-Hui; Chen, Qi; Li, Yan; Wang, Ji-Guang

    2017-01-01

    Background We compared skin and plasma measurements of advanced glycation end products (AGEs), with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension. Methods Skin AGE accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using the SphygmoCor system (Sydney, Australia). Results The 218 participants (96 [44.0%] men, mean age 51.9 years) had a mean skin autofluorescence of 1.89 arbitrary units, plasma AGE concentration of 4.47 μg/ml, and cfPWV of 8.0 m/s. Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients (n = 31, r = 0.37, p = 0.04) but not in subjects with normoglycemia (n = 187, r = −0.05, p = 0.48). Nonetheless, both measurements were significantly (p ≤ 0.001) higher in men (2.00 arbitrary units and 6.73 μg/ml, respectively) than women (1.81 arbitrary units and 3.60 μg/ml, respectively) and in diabetic or prediabetic (2.03 arbitrary units and 6.61 μg/ml, respectively) than normoglycemia subjects (1.87 arbitrary units and 4.17 μg/ml, respectively), but similar in hypertensive (n = 105) and normotensive subjects (n = 113, p ≥ 0.35). In adjusted multiple regression analyses, plasma AGE concentration, but not skin autofluorescence (p ≥ 0.37), was significantly associated with cfPWV in all subjects (β 0.44 m/s for each 10-fold increase; p = 0.04) and in subgroups of men and diabetes and prediabetes (β 0.12-0.55 m/s for each 10-fold increase; p ≤ 0.02). Conclusions Although skin and plasma AGEs were similarly associated with

  4. Computational modeling of hypertensive growth in the human carotid artery

    PubMed Central

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-01-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively. PMID:25342868

  5. Practical considerations for the pharmacotherapy of pulmonary arterial hypertension.

    PubMed

    Bishop, Bryan M; Mauro, Vincent F; Khouri, Samer J

    2012-09-01

    Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.

  6. Current insights on the pathogenesis of pulmonary arterial hypertension.

    PubMed

    Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc

    2005-08-01

    Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.

  7. Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

    PubMed

    Dykes, John C; Torres, Marilyn; Alexander, Plato J

    2016-03-01

    This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.

  8. Relationship between sleep duration and arterial stiffness in a multi-ethnic population: The HELIUS study

    PubMed Central

    Anujuo, Kenneth; Stronks, Karien; Snijder, Marieke B.; Jean-Louis, Girardin; van den Born, Bert-Jan; Peters, Ron J.; Agyemang, Charles

    2017-01-01

    We examined the relationship between sleep duration and arterial stiffness among a multi-ethnic cohort, and whether the associations differed among ethnic minority groups in the Netherlands. Data were derived from 10 994 participants (aged 18–71 years) of the Healthy Life in an Urban Setting (HELIUS) study. Self-reported sleep duration was categorized into: short (<7 h/night), healthy (7–8 h/night) and long (≥9 h/night). Arterial stiffness was assessed by duplicate pulse-wave velocity (PWV in m/s) measurements using the Arteriograph system. The association of sleep duration with PWV was analysed using linear regression (β) with 95% confidence interval (CI). Results showed that neither short nor long sleep was related to PWV in all ethnic groups, except for long sleep in Dutch men which was associated with higher PWV (indicating stiffer arteries) after adjustment for potential confounders (β = 0.67, 95%CI, 0.23–1.11). Our study showed no convincing evidence that sleep duration was related to arterial stiffness among various ethnic groups. The link between sleep duration and cardiovascular outcomes does not seem to operate through arterial stiffness. Further research is needed to consolidate these findings. PMID:27058653

  9. How to manage hypertension with atherosclerotic renal artery stenosis?

    PubMed

    Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

    2017-04-01

    The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

  10. WILLIAMS SYNDROME PREDISPOSES TO VASCULAR STIFFNESS MODIFIED BY ANTI-HYPERTENSIVE USE AND COPY NUMBER CHANGES IN NCF1

    PubMed Central

    Kozel, Beth A.; Danback, Joshua; Waxler, Jessica; Knutsen, Russell H.; Fuentes, Lisa de las; Reusz, Gyorgy S.; Kis, Eva; Bhatt, Ami; Pober, Barbara R

    2014-01-01

    Williams syndrome, is caused by the deletion of 26-28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln+/− mouse suggests that affected persons may also have stiff vasculature, a risk factor for stroke, myocardial infarction and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the NAD(P)H oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (p<0.001), with increased stiffness observed in even the youngest Williams children. Pulse wave velocity increased with age at comparable rates in cases and controls and, although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of anti-hypertension medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with anti-hypertensives and/or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive. PMID:24126171

  11. Association between arterial stiffness and peritoneal small solute transport rate.

    PubMed

    Zhe, Xing-wei; Tian, Xin-kui; Chen, Wei; Guo, Li-juan; Gu, Yue; Chen, Hui-min; Tang, Li-jun; Wang, Tao

    2008-05-01

    While cardiovascular disease accounts for 40-50% of the mortality in dialysis patients, and while a high peritoneal transport in continuous ambulatory peritoneal dialysis (CAPD) is an independent predictor of outcome, it is unclear if there are any links. Aortic stiffness has become established as a cardiovascular risk factor. We thus studied pulse wave velocity (PWV) in CAPD patients to explore the possible link between peritoneal small solute transport and aortic stiffness. CAPD patients (n = 76, 27 M/49 F) in our center were included in the present study. Aortic stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral PWV. Patients' peritoneal small solute transport rate was assessed by D/P(cr) at 4 h. Extracellular water over total body water (E/T ratio) was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Carotid-femoral PWV was positively associated with patients' age (r = 0.555; P < 0.01), time on peritoneal dialysis (r = 0.332; P < 0.01), diabetic status (r = 0.319; P < 0.01), D/P(cr) (r = 0.241; P < 0.05), PP (r = 0.475; P < 0.01), and E/T (r = 0.606; P < 0.01). In a multivariate regression analysis, carotid-femoral PWV was independently determined by E/T (P < 0.01), PP (P < 0.01), age (P < 0.01), and D/P(cr) (P < 0.05). D/P(cr), in addition to E/T, age, and PP, was an independent predictor of elevated carotid-femoral PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased peritoneal small solute transport rate.

  12. Patients with resistant hypertension have more peripheral arterial disease than other uncontrolled hypertensives.

    PubMed

    Korhonen, P E; Kautiainen, H; Kantola, I

    2015-01-01

    The aim of this study was to investigate whether resistant hypertension differs from uncontrolled and controlled hypertension in terms of target organ damage. Hypertensive subjects with antihypertensive medication (n=385) were identified in a population survey conducted in southwestern Finland. None of the study subjects had previously diagnosed cardiovascular or renal disease or diabetes. Ankle-brachial index, estimated glomerular filtration rate, electrocardiogram-determined left ventricular hypertrophy and cardiometabolic risk factors were assessed. The prevalence of peripheral arterial disease among subjects with resistant, uncontrolled and controlled hypertension was 6/37 (16%), 22/275 (8%) and 0/73 (0%), respectively (P=0.006). There were no differences in the prevalence of renal insufficiency, left ventricular hypertrophy or metabolic parameters between the groups. Resistant hypertension affects vasculature more than uncontrolled hypertension, and thus it can be regarded as a marker of more severe disease.

  13. A pathogenic role of complement in arterial hypertension and hypertensive end organ damage.

    PubMed

    Wenzel, Ulrich O; Bode, Marlies; Köhl, Jörg; Ehmke, Heimo

    2017-03-01

    The self-amplifying cascade of messenger and effector molecules of the complement system serves as a powerful danger-sensing system that protects the host from a hostile microbial environment, while maintaining proper tissue and organ function through effective clearance of altered or dying cells. As an important effector arm of innate immunity, it also plays important roles in the regulation of adaptive immunity. Innate and adaptive immune responses have been identified as crucial players in the pathogenesis of arterial hypertension and hypertensive end organ damage. In line with this view, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses. It is well known that complement activation can cause tissue inflammation and injury and complement-inhibitory drugs are effective treatments for several inflammatory diseases. In addition to these proinflammatory properties, complement cleavage fragments of C3 and C5 can exert anti-inflammatory effects that dampen the inflammatory response to injury. Recent experimental data strongly support a role for complement in arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest a role for complement also in the development of malignant nephrosclerosis. Herein, we will review canonical and noncanonical pathways of complement activation as the framework to understand the multiple roles of complement in arterial hypertension and hypertensive end organ damage.

  14. [Ultrasonographic study of blood flow in the renal arteries of patients with arterial hypertension].

    PubMed

    Makarenko, E S; Dombrovskiĭ, V I; Nelasov, N Iu

    2012-01-01

    Vascular duplex ultrasound duplex with simultaneous ECG registration was made to estimate the quantitative and time parameters of blood flow in the renal arteries with grade 1-2 arterial hypertension. There were increases in vascular resistance indices and acceleration phase index and a reduction in systolic phase index. There were correlations of the time parameters of blood flow in the renal arteries with age and lipidogram values.

  15. Visit-to-visit blood pressure variability, average BP level and carotid arterial stiffness in the elderly: a prospective study.

    PubMed

    Nagai, M; Dote, K; Kato, M; Sasaki, S; Oda, N; Kagawa, E; Nakano, Y; Yamane, A; Kubo, Y; Higashihara, T; Miyauchi, S; Harada, W; Masuda, H

    2016-10-20

    In a cross-sectional study, visit-to-visit blood pressure (BP) variability was shown to be associated with artery remodelling. Here, we investigated the impact of visit-to-visit BP variability and average BP on the carotid artery remodelling progression in high-risk elderly according to different classes of antihypertension medication use/non-use. BP measurements and carotid ultrasound were performed in the common carotid artery in 164 subjects (mean age 79.7 years at baseline, 74.7% females) with one or more cardiovascular risk factors. Based on 12 visits (1 × /month for 1 year), we calculated visit-to-visit BP variability expressed as the standard deviation (s.d.), coefficient of variation (CV), maximum BP, minimum BP and delta (maximum-minimum) BP. We measured mean intima-media thickness (IMT) as well as stiffness parameter β were measured at baseline and at the mean 4.2-year follow-up. In a multiple regression analysis, the maximum, minimum, s.d. and average of systolic BP (SBP) were significantly associated with a change in β-values between the baseline and follow-up after adjustment for age, smoking, lower high-density lipoprotein level, baseline β-value and follow-up period. There were no significant associations between the visit-to-visit BP variability measures and the change in mean IMT. Significant associations of maximum, minimum, s.d. and average SBP were found with increased β-values in the subjects without calcium channel blocker (CCB) use and in the subjects using renin-angiotensin system inhibitors (RASIs). Thus, exaggerated visit-to-visit SBP variability and a high average SBP level were significant predictors of progression in carotid arterial stiffness in high-risk elderly without CCBs use and in those using a RASI.Journal of Human Hypertension advance online publication, 20 October 2016; doi:10.1038/jhh.2016.77.

  16. Time course and factors predicting arterial stiffness reversal in patients with aldosterone-producing adenoma after adrenalectomy: prospective study of 102 patients

    PubMed Central

    Liao, Che-Wei; Lin, Lian-Yu; Hung, Chi-Sheng; Lin, Yen-Tin; Chang, Yi-Yao; Wang, Shuo-Meng; Wu, Vin-Cent; Wu, Kwan-Dun; Ho, Yi-Lwun; Satoh, Fumitoshi; Lin, Yen-Hung

    2016-01-01

    Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone-producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p < 0.001), but no further reduction in the following 6 months. The determinant factors for baseline baPWV were age, duration of hypertension, and baseline systolic blood pressure (SBP) in multivariate linear regression analysis, similar with baseline haPWV (determinants: age, duration of hypertension, baseline SBP and diastolic blood pressure (DBP)). In multivariate linear regression analysis, the decrease in DBP at 6 months (ΔDBP0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (ΔbaPWV0-6mo). The associated factors of the change in haPWV at 6 months (ΔhaPWV0-6mo) were baseline haPWV, ΔDBP0-6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors. PMID:26883298

  17. [Clinical utility of inhaled iloprost in pulmonary arterial hypertension].

    PubMed

    Santos-Martínez, Luis Efren; Moreno-Ruiz, Luis Antonio; Jiménez-Santos, Moisés; Olmos-Temois, Sergio Gabriel; Bojorquez-Guerrero, Luis Armando; Baranda-Tovar, Francisco Martín

    2014-01-01

    Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

  18. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

  19. Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis

    PubMed Central

    Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904

  20. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves

    PubMed Central

    Lammers, Steven R.; Kao, Phil H.; Qi, H. Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R.; Shandas, Robin

    2008-01-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue. PMID:18660454

  1. Risk factors of arterial hypertension after renal transplantation.

    PubMed

    Béji, S; Abderrahim, E; Kaaroud, H; Jebali, H; Ben Abdallah, T; El Younsi, F; Ben Moussa, F; Ben Hamida, F; Sfaxi, A; Blah, M; Chebil, M; Ayed, M; Bardi, R; Gorgi, Y; Kheder, A

    2007-10-01

    Arterial hypertension often present after kidney transplantation is of multifactorial origin. The aim of this study was to determine the role of donor and recipient factors in the development of hypertension after renal transplantation. We retrospectively analyzed the data of 280 patients transplanted between 1985 and 2005, who still had functioning grafts at 1 year after transplantation. We recorded donor and recipient parameters. One hundred eighty-seven patients (66.8%) were hypertensive. Upon multivariate analysis of recipient factors, pretransplant hypertension (odds ratio) [OR]: 8.5, 95% confidence interval [CI]: 4.5 to 16.1); serum creatinine level > 130 micromol/L at 6 months (OR: 2.5, 95% CI: 1.3 to 4,7), male gender (OR: 2.02, 95% CI: 1.2 to 3.4), and chronic rejection (OR: 2.4, 95% CI: 1.2 to 4.7) were independent predisposing factors. Among donor factors, age was significantly associated with arterial hypertension upon univariate analysis. In conclusion, recipient factors, especially pretransplant hypertension, contribute to the disorder in renal transplant patients.

  2. Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus.

    PubMed

    Harashima, Keiichiro; Hayashi, Junichi; Miwa, Takashi; Tsunoda, Tooru

    2009-06-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

  3. Is arterial stiffness predicted by continuous metabolic syndrome score in obese children?

    PubMed

    Prochotska, Katarina; Kovacs, Laszlo; Vitariusova, Eva; Feber, Janusz

    2016-01-01

    The aim of the article was to evaluate arterial stiffness, an early marker of increased cardiovascular risk, in relation to obesity. The continuous metabolic syndrome (cMetS) score was calculated as sum of Z score of mean arterial pressure, body mass index, serum glucose, triglyceride, and high-density lipoprotein cholesterol in 144 obese patients and 66 nonobese controls. Ambulatory arterial stiffness index (AASI) was calculated as 1 minus regression slope of diastolic on systolic blood pressure from ambulatory blood pressure measurements. The mean AASI increased progressively with severity of obesity. The receiver operator curve analysis of body mass index and AASI showed area under the curve of 0.64 ± 0.06; cMetS area under the curve was 0.72 ± 0.05 suggesting a better predictive power of the cMetS for an increased AASI (>0.3). Patients with obesity have significantly higher arterial stiffness. A composite score such as cMetS seems to be better predictor of an increased stiffness than individual risk factors.

  4. Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans.

    PubMed

    Rakobowchuk, Mark; Harris, Emma; Taylor, Annabelle; Cubbon, Richard M; Birch, Karen M

    2013-04-01

    Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p < 0.01), but metabolic stress-specific alterations were not apparent. There was a trend for increased absolute high-frequency (HF) power (p = 0.10) whereas both absolute low-frequency (LF) power (p = 0.05) and overall power (p = 0.02) were increased to a similar degree following both training programmes. Non-linear heart rate dynamics such as detrended fluctuation analysis [Formula: see text] also improved (p > 0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress.

  5. Acute effects of aerobic exercise intensity on arterial stiffness after glucose ingestion in young men.

    PubMed

    Kobayashi, Ryota; Hashimoto, Yuto; Hatakeyama, Hiroyuki; Okamoto, Takanobu

    2016-10-18

    Arterial stiffness increases after glucose ingestion. Acute low- and moderate-intensity aerobic exercise decreases arterial stiffness. However, the acute effects of 30 min of cycling at low- and moderate-intensity [25% (LE trial) and 65% (ME trial) peak oxygen uptake, respectively] on arterial stiffness at 30, 60 and 120 min of a postexercise glucose ingestion. Ten healthy young men (age, 22·4 ± 0·5 years) performed LE and ME trials on separate days in a randomized controlled crossover fashion. Carotid-femoral (aortic) pulse wave velocity (PWV), femoral-ankle (leg) PWV, carotid augmentation index (AIx) and carotid blood pressure (BP) (applanation tonometry), brachial and ankle BP (oscillometric device), heart rate (HR) (electrocardiography), blood glucose (UV-hexokinase method) and blood insulin (CLEIA method) levels were measured at before (baseline) and at 30, 60 and 120 min after the 75-g OGTT. Leg PWV, ankle pulse pressure and BG levels significantly increased from baseline after the 75-g OGTT in the LE trial (P<0·05), but not in the ME trial. Insulin levels and HR significantly increased from baseline after the 75-g OGTT in both trials (P<0·05). Aortic PWV, carotid AIx, brachial BP and carotid BP did not change from baseline after the 75-g OGTT in both trials. The present findings indicate that aerobic exercise at moderate intensity before glucose ingestion suppresses increases leg arterial stiffness after glucose ingestion.

  6. Optical imaging of resting-state functional connectivity in a novel arterial stiffness model.

    PubMed

    Guevara, Edgar; Sadekova, Nataliya; Girouard, Hélène; Lesage, Frédéric

    2013-01-01

    This study aims to assess the impact of unilateral increases in carotid stiffness on cortical functional connectivity measures in the resting state. Using a novel animal model of induced arterial stiffness combined with optical intrinsic signals and laser speckle imaging, resting state functional networks derived from hemodynamic signals are investigated for their modulation by isolated changes in stiffness of the right common carotid artery. By means of seed-based analysis, results showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Furthermore, a graph analysis indicated a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex lateral to the treated carotid, which however did not translate in differentiated metabolic activity.

  7. Arterial stiffness is not associated with bone parameters in an elderly hyperhomocysteinemic population.

    PubMed

    van Dijk, S C; de Jongh, R T; Enneman, A W; Ham, A C; Swart, K M A; van Wijngaarden, J P; van der Zwaluw, N L; Brouwer-Brolsma, E M; van Schoor, N M; Dhonukshe-Rutten, R A M; Lips, P; de Groot, C P G M; Smulders, Y M; Blom, H J; Feskens, E J; Geleijnse, J M; van den Meiracker, A H; Mattace Raso, F U S; Uitterlinden, A G; Zillikens, M C; van der Velde, N

    2016-01-01

    Several studies have observed positive associations between bone disease and cardiovascular disease. A potential common pathway is hyperhomocysteinemia; however, to date, there is a lack of data regarding hyperhomocysteinemic populations. Therefore, we examined both cross-sectionally and longitudinally, whether there is an association between bone parameters and arterial stiffness in a hyperhomocysteinemic population, and investigated the potential common role of homocysteine (hcy) level on these associations. Cross-sectional and longitudinal data of the B-PROOF study were used (n = 519). At both baseline and 2-year follow-up we determined bone measures-incident fractures and history of fractures, bone-mineral density (BMD) and quantitative ultrasound (QUS) measurement. We also measured arterial stiffness parameters at baseline-pulse wave velocity, augmentation index and aortic pulse pressure levels with applanation tonometry. Linear regression analysis was used to examine these associations and we tested for potential interaction of hcy level. The mean age of the study population was 72.3 years and 44.3 % were female. Both cross-sectionally and longitudinally there was no association between arterial stiffness measures and BMD or QUS measurements or with incident fractures (n = 16) within the 2-3 years of follow-up. Hcy level did not modify the associations and adjustment for hcy did not change the results. Arterial stiffness was not associated with bone parameters and fractures, and hcy neither acted as a pleiotropic factor nor as a mediator. The potential association between bone and arterial stiffness is therefore not likely to be driven by hyperhomocysteinemia.

  8. Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD

    PubMed Central

    Rodriguez-Miguelez, Paula; Seigler, Nichole; Bass, Leon; Dillard, Thomas A; Harris, Ryan A

    2015-01-01

    Background Elevated cardiovascular disease risk is observed in patients with COPD. Non-invasive assessments of endothelial dysfunction and arterial stiffness have recently emerged to provide mechanistic insight into cardiovascular disease risk in COPD; however, the reproducibility of endothelial function and arterial stiffness has yet to be investigated in this patient population. Objectives This study sought to examine the within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD. Methods Baseline diameter, peak diameter, flow-mediated dilation, augmentation index, augmentation index at 75 beats per minute, and pulse wave velocity were assessed three times in 17 patients with COPD (six males, eleven females, age range 47–75 years old; forced expiratory volume in 1 second =51.5% predicted). Session A and B were separated by 3 hours (within-day), whereas session C was conducted at least 7 days following session B (between-day). Reproducibility was assessed by: 1) paired t-tests, 2) coefficients of variation, 3) coefficients of variation prime, 4) intra-class correlation coefficient, 5) Pearson’s correlations (r), and 6) Bland–Altman plots. Five acceptable assessments were required to confirm reproducibility. Results Six out of six within-day criteria were met for endothelial function and arterial stiffness outcomes. Six out of six between-day criteria were met for baseline and peak diameter, augmentation index and pulse wave velocity, whereas five out of six criteria were met for flow-mediated dilation. Conclusion The present study provides evidence for within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD. PMID:26396509

  9. Physical Activity Correlates with Arterial Stiffness in Community-dwelling Individuals with Stroke

    PubMed Central

    Tang, Ada; Eng, Janice J.; Brasher, Penelope M.; Madden, Kenneth M.; Mohammadi, Azam; Krassioukov, Andrei V.; Tsang, Teresa S. M.

    2013-01-01

    Background Physical inactivity contributes to atherosclerotic processes, which manifest as increased arterial stiffness. Arterial stiffness is associated with myocardial demand and coronary perfusion and is a risk factor for stroke and other adverse cardiac outcomes. Poststroke mobility limitations often lead to physical inactivity and sedentary behaviors. This exploratory study aimed to identify functional correlates, reflective of daily physical activity levels, with arterial stiffness in community-dwelling individuals >1 year poststroke. Methods Carotid–femoral pulse wave velocity (cfPWV) was measured in 35 participants (65% men; mean ± SD age 66.9 ± 6.9 years; median time poststroke 3.7 years). Multivariable regression analyses examined the relationships between cfPWV and factors associated with daily physical activity: aerobic capacity (VO2 peak), gait speed, and balance ability (Berg Balance Scale). Age and the use of antihypertensive medications, known to be associated with pulse wave velocity, were also included in the model. Results Mean cfPWV was 11.2 ± 2.4 m/s. VO2 peak and age were correlated with cfPWV (r = −0.45 [P = .006] and r = 0.46 [P = .004], respectively). In the multivariable regression analyses, age and the use of antihypertensive medication accounted for 20.4% of the variance of cfPWV, and the addition of VO2 peak explained an additional 4.5% of the variance (R2 = 0.249). Conclusions We found that arterial stiffness is elevated in community-dwelling, ambulatory individuals with stroke relative to healthy people. Multivariable regression analysis suggests that aerobic capacity (VO2 peak) may contribute to the variance of cfPWV after accounting for the effects of age and medication use. Whether intense risk modification and augmented physical activity will improve arterial stiffness in this population remains to be determined. PMID:23473623

  10. Mean Platelet Volume and Arterial Stiffness – Clinical Relationship and Common Genetic Variability

    PubMed Central

    Panova-Noeva, Marina; Arnold, Natalie; Hermanns, M. Iris; Prochaska, Jürgen H.; Schulz, Andreas; Spronk, Henri M.; Binder, Harald; Pfeiffer, Norbert; Beutel, Manfred; Blankenberg, Stefan; Zeller, Tanja; Lotz, Johannes; Münzel, Thomas; Lackner, Karl J.; ten Cate, Hugo; Wild, Philipp S.

    2017-01-01

    Vessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific medians had worse survival. Association analysis between MPV-related genetic variants and arterial stiffness identified four genetic variants in males and one in females related with AIx. Cox regression analysis for mortality identified one of these joint genetic variants close to ring finger protein 145 gene (RNF145, rs10076782) linked with increased mortality (hazard ratio 2.02; 95thCI [1.35;3.02]; p = 0.00061). Thus, these population-based data demonstrate a close relation between platelet volume as a potential marker of platelet activation and arterial stiffness in both sexes. Further research is warranted to further elucidate the mechanisms underlying larger platelets‘ role in arterial stiffening including the role of shared common genetics. PMID:28059166

  11. Manipulation of arterial stiffness, wave reflections, and retrograde shear rate in the femoral artery using lower limb external compression.

    PubMed

    Heffernan, Kevin S; Lefferts, Wesley K; Kasprowicz, Ari G; Tarzia, Brendan J; Thijssen, Dick H; Brutsaert, Tom D

    2013-07-01

    Exposure of the arterial wall to retrograde shear acutely leads to endothelial dysfunction and chronically contributes to a proatherogenic vascular phenotype. Arterial stiffness and increased pressure from wave reflections are known arbiters of blood flow in the systemic circulation and each related to atherosclerosis. Using distal external compression of the calf to increase upstream retrograde shear in the superficial femoral artery (SFA), we examined the hypothesis that changes in retrograde shear are correlated with changes in SFA stiffness and pressure from wave reflections. For this purpose, a pneumatic cuff was applied to the calf and inflated to 0, 35, and 70 mmHg (5 min compression, randomized order, separated by 5 min) in 16 healthy young men (23 ± 1 years of age). Doppler ultrasound and wave intensity analysis was used to measure SFA retrograde shear rate, reflected pressure wave intensity (negative area [NA]), elastic modulus (Ep), and a single-point pulse wave velocity (PWV) during acute cuff inflation. Cuff inflation resulted in stepwise increases in retrograde shear rate (P < 0.05 for main effect). There were also significant cuff pressure-dependent increases in NA, Ep, and PWV across conditions (P < 0.05 for main effects). Change in NA, but not Ep or PWV, was associated with change in retrograde shear rate across conditions (P < 0.05). In conclusion, external compression of the calf increases retrograde shear, arterial stiffness, and pressure from wave reflection in the upstream SFA in a dose-dependent manner. Wave reflection intensity, but not arterial stiffness, is correlated with changes in peripheral retrograde shear with this hemodynamic manipulation.

  12. Arterial hypertension perpetuates alveolar bone loss.

    PubMed

    de Medeiros Vanderlei, Janine Montenegro Toscano Moura; Messora, Michel Reis; Fernandes, Patrícia Garani; Novaes, Arthur B; Palioto, Daniela Bazan; de Moraes Grisi, Marcio Fernando; Scombatti de Souza, Sergio Luis; Gerlach, Raquel Fernanda; Antoniali, Cristina; Taba, Mario

    2013-01-01

    Few studies have focused on the impact of hypertension on the progression of periodontitis (PD). The purpose of this study was to evaluate whether hypertension affects PD by enhancing bone loss even after the stimulus for PD induction is removed. Ligature-induced PD was created on the first mandibular molars of spontaneously hypertensive rats (SHR) and normotensive rats (Wistar Kyoto-WKY). The animals were assigned to non-ligated controls (C) and PD groups: WKY-C, WKY-PD, SHR-C, and SHR-PD. After 10 days, five animals of each group were killed and the ligatures of the other animals were removed. On the 21st day (11 days without PD induced), the remaining animals were killed. The jaws were defleshed and the amount of bone loss was measured. After 10 days, the PD groups showed more bone loss than its controls (P < .05); SHR-PD = 0.72 ± 0.05 mm, SHR-C = 0.39 ± 0.04 mm, WKY-PD = 0.75 ± 0.04 mm, and WKY-C = 0.56 ± 0.04 mm. The cumulative bone loss on day 21 (0.94 ± 0.13 mm) was significantly worse than on day 10 only in SHR-PD group (P < .05). The final bone loss differences between PD and C groups accounted for 102% (SHR) and 26% (WKY) increase in comparison with the initial control levels. Hypertension is associated with progressive alveolar bone loss even when the stimulus for PD induction is removed and it may be speculated that host condition perpetuates alveolar bone loss.

  13. [Clinico-statistical analysis of arterial hypertension complicated with hypertensive crisis in Moscow in 2005-2009].

    PubMed

    Gaponova, N I; Plavunov, N F; Tereshchenko, S N; Baratashvili, V L; Abdurakhmanov, V R; Komissarenko, I A; Filippov, D V; Podkopaev, D V

    2011-01-01

    Clinicostatistical analysis of arterial hypertension complicated with hypertensive crisis using data of Moscow A.S.Puchkov Station of Urgent and Emergent Medical Aid revealed 14% rise in number of hypertensive crises during the period from 2005 to 2009. Number of hypertensive crises increased among persons of young age (18-35 years). Frequency of cerebrovascular complications of hypertensive crises was age dependent with maximal values among men aged 36-74 years and women older than 75 years.

  14. Lineage Analysis in Pulmonary Arterial Hypertension

    DTIC Science & Technology

    2013-06-01

    SMA with some globular domains, predominantly colocalizing with GFP endothelial lineage-marked cells in the neointima (Figure 4F). Figure 4. VE...whether the neointima arises from a small population of apoptosis- resistant pulmonary artery endothelial cells that proliferate after injury to produce

  15. Relationship between carotid intima‐media thickness and arterial stiffness in children after Kawasaki disease

    PubMed Central

    Cheung, Y‐f; Wong, S J; Ho, M H K

    2007-01-01

    Background Evidence of premature atherosclerosis and systemic arterial stiffening in patients after Kawasaki disease is accumulating. Aim To test the hypothesis that carotid intima‐media thickness (IMT), a surrogate marker of atherosclerosis, is associated with systemic arterial stiffness in children after Kawasaki disease. Methods A cohort of 72 patients was studied, comprising 26 patients with Kawasaki disease and coronary aneurysms (group I), 24 patients with Kawasaki disease and normal coronary arteries (group II) and 22 healthy age‐matched children (group III). The carotid IMT, carotid artery stiffness index, brachioradial pulse wave velocity (PWV), fasting total cholesterol, high‐density lipoprotein (HDL) cholesterol and low‐density lipoprotein (LDL) cholesterol were determined and compared among the three groups. Results The carotid IMT was related to indices of arterial stiffness, and significant determinants of carotid IMT were identified by multivariate analysis. The mean (standard deviation (SD)) carotid IMT of both group I (0.41 (0.04) mm) and group II (0.39 (0.04) mm) was significantly greater than that of group III (0.36 (0.04) mm; p<0.001 and p = 0.008, respectively). For the entire cohort, carotid IMT correlated positively with LDL cholesterol (r = 0.31, p = 0.009), carotid artery stiffness index (r = 0.40, p = 0.001) and brachioradial PWV (r = 0.28, p = 0.016), but not with age, body mass index, systemic blood pressure, and HDL and total cholesterol. Multiple linear regression analysis identified carotid artery stiffness index (β = 0.25, p = 0.028) and subject grouping (β = −0.39, p = 0.001; model R2 = 0.29) as significant correlates of carotid IMT. Conclusion The increased carotid IMT in children after Kawasaki disease is associated with systemic arterial stiffening. PMID:16820386

  16. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

  17. [Advances in arterial hypertension and diabetes mellitus].

    PubMed

    Cordero, Alberto; Lekuona, Iñaki; Galve, Enrique; Mazón, Pilar

    2012-01-01

    In 2011, the importance of hypertension and diabetes mellitus as the two main risk factors responsible for the development of cardiovascular disease became clear, as did their significance as major public health issues. Compared with previous years, in which publication of the results of large clinical trials dominated scientific progress, in the last year, the focus has shifted to evidence that novel mechanisms associated with blood pressure, glucose metabolism and diabetes can influence cardiovascular disease. Of particular importance were clinical trials in the area of renal dysfunction, such as the SHARP and ROADMAP trials.

  18. Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy.

    PubMed

    van Leeuwen-Segarceanu, Elena M; Dorresteijn, Lucille D A; Vogels, Oscar J M; Biesma, Douwe H; Bos, Willem-Jan W

    2013-08-01

    Radiotherapy has been associated with an increased risk for cardiovascular disease (CVD) in Hodgkin lymphoma survivors (HLS). Identifying subjects most likely to develop these complications is challenging. Arterial stiffness has been frequently used as an early marker of CVD, but has never previously been investigated in patients treated with radiotherapy. The carotid-femoral pulse wave velocity (PWV) and the distensibility coefficient (DC) of the common carotid artery were used as markers of arterial stiffness. Eighty-two HLS and 40 age- and gender-matched control subjects were studied. The aorta and the carotid arteries were situated within the radiation field in 50 and 39 patients. Mean PWV was not significantly different in HLS treated with radiotherapy on the mediastinum when compared to HLS treated without mediastinal radiotherapy and to controls. If HLS were 40 years or older at radiotherapy their PWV was significantly higher (8.54 m/s) than patients irradiated at a younger age (7.14 m/s, p = 0.004) and controls (6.91 m/s, p < 0.001), after adjusting for current age and other CVD risk factors. Mean DC was lower, indicative of stiffer arteries, in HLS treated with radiotherapy on the common carotid artery (2.79) than in HLS without radiotherapy (3.35, p = 0.029) and versus controls (3.60, p = 0.001). DC was lowest in HLS treated at 35 years of age or later (2.05), compared to HLS irradiated at a younger age (2.98, p = 0.046). In HLS, radiotherapy is associated with increased arterial stiffness. The effect of radiotherapy seems most evident when radiotherapy is administered at ages above 35-40 years.

  19. Influence of Postprandial Hyperglycemic Conditions on Arterial Stiffness in Patients With Type 2 Diabetes

    PubMed Central

    Gordin, Daniel; Saraheimo, Markku; Tuomikangas, Jaana; Soro-Paavonen, Aino; Forsblom, Carol; Paavonen, Karri; Steckel-Hamann, Birgit; Vandenhende, Francois; Nicolaou, Loizos; Pavo, Imre; Koivisto, Veikko

    2016-01-01

    Context: Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. Objective: The objective of the study was to determine whether postprandial hyperglycemia affects arterial function in T2D. Design: A single-center, open-label study of three groups of men were studied: 1) T2D patients with albuminuria (n = 22), 2) T2D patients without albuminuria (n = 24), and 3) nondiabetic controls (n = 25). Patients were randomized to a two-period crossover study schedule, ingesting breakfast, with or without insulin lispro (to induce low or high postprandial glycemia). Main Outcome Measures: Arterial stiffness was assessed by calculating pulse wave velocity (PWV) and augmentation index using applanation tonometry, and endothelial dysfunction was assessed using peripheral arterial tonometry, 30 minutes before breakfast and up to 240 minutes after breakfast. Results: At baseline, arterial stiffness was increased in patients. When adjusted for age and body mass index, in a combined group of patients with and without albuminuria, brachial PWV was higher during low (P = .032) and high (P = .038) postprandial glycemia vs controls. These differences were driven by the albuminuria group vs controls during low (P = .014) and high (P = .018) postprandial glycemia. No differences were observed in aortic PWV, augmentation index, or peripheral arterial tonometry ratio between patients and controls. Endothelin-1 and IL-6 were higher, and superoxide dismutase was lower, during postprandial hyperglycemia in T2D patients vs controls. Conclusions: In patients with T2D and albuminuria, brachial PWV was higher under postprandial hyperglycemic conditions, relative to controls. These data suggest that hyperglycemia induces an increase in stiffness of intermediate-sized arteries. We found no changes in other parts of the arterial bed. PMID:26731258

  20. Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia

    PubMed Central

    Ballard, Kevin D.; Lorson, Lindsay; White, C. Michael; Thompson, Paul D.; Taylor, Beth A.

    2015-01-01

    Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n = 115) completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV) were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%). Compared to baseline, central PWV decreased (P = 0.01) following simvastatin treatment but not placebo (drug ∗ time interaction: P = 0.047). Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P ≥ 0.15). Change in central PWV after simvastatin treatment was inversely correlated with age (r = −0.207, P = 0.030), suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness. PMID:26257959

  1. A systematic review on the effect of acute aerobic exercise on arterial stiffness reveals a differential response in the upper and lower arterial segments.

    PubMed

    Mutter, Andrew F; Cooke, Alexandra B; Saleh, Olivier; Gomez, Yessica-Haydee; Daskalopoulou, Stella S

    2017-02-01

    The objective of this systematic review was to provide insight into the controversy that still abounds as to the impact of acute aerobic exercise on immediate changes in arterial stiffness. Electronic databases were searched to identify articles assessing the effects of acute aerobic exercise on parameters of arterial stiffness. Eligible studies included arterial stiffness measurements before and after acute aerobic exercise in healthy human subjects. Forty-three studies were included. The effect of acute aerobic exercise on arterial stiffness was found to be dependent on the anatomical segment assessed, and on the timing of the measurement post-exercise. Arterial stiffness of the central and upper body peripheral arterial segments was found to be increased relative to resting values immediately post-exercise (0-5 min), whereas, thereafter (>5 min), decreased to a level at or below resting values. In the lower limbs, proximal to the primary working muscles, arterial stiffness decreased immediately post-exercise (0-5 min), which persisted into the recovery period post-exercise (>5 min). This systematic review reveals a differential response to acute exercise in the lower and upper/central arterial segments in healthy adult subjects. We further showed that the effect of acute aerobic exercise on arterial stiffness is dependent on the timing of the measurements post-exercise. Therefore, when assessing the overall impact of exercise on arterial stiffness, it is important to consider the arterial segment being analyzed and measurement time point, as failure to contextualize the measurement can lead to conflicting results and misleading clinical inferences.

  2. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

    PubMed Central

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra

    2016-01-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower (< 2.061%), middle (2.061%-3.235%) and higher (> 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men. PMID:27482523

  3. Effect of passive heat stress on arterial stiffness in smokers versus non-smokers.

    PubMed

    Moyen, N E; Ganio, M S; Burchfield, J M; Tucker, M A; Gonzalez, M A; Dougherty, E K; Robinson, F B; Ridings, C B; Veilleux, J C

    2016-04-01

    In non-smokers, passive heat stress increases shear stress and vasodilation, decreasing arterial stiffness. Smokers, who reportedly have arterial dysfunction, may have similar improvements in arterial stiffness with passive heat stress. Therefore, we examined the effects of an acute bout of whole-body passive heat stress on arterial stiffness in smokers vs. non-smokers. Thirteen smokers (8.8 ± 5.5 [median = 6] cigarettes per day for > 4 years) and 13 non-smokers matched for age, mass, height, and exercise habits (27 ± 8 years; 78.8 ± 15.4 kg; 177.6 ± 6.7 cm) were passively heated to 1.5 °C core temperature (T C) increase. At baseline and each 0.5 °C T C increase, peripheral (pPWV) and central pulse wave velocity (cPWV) were measured via Doppler ultrasound. No differences existed between smokers and non-smokers for any variables (all p >  .05), except cPWV slightly increased from baseline (526.7 ± 81.7 cm · s(-1)) to 1.5 °C ΔT C (579.7 ± 69.8 cm · s(-1); p < 0.005), suggesting heat stress acutely increased central arterial stiffness. pPWV did not change with heating (grand mean: baseline = 691.9 ± 92.9 cm · s(-1); 1.5 °C ΔT C = 691.9 ± 79.5 cm · s(-1); p > 0.05). Changes in cPWV and pPWV during heating correlated (p < 0.05) with baseline PWV in smokers (cPWV: r = -0.59; pPWV: r = -0.62) and non-smokers (cPWV: r = -0.45; pPWV: r = -0.77). Independent of smoking status, baseline stiffness appears to mediate the magnitude of heating-induced changes in arterial stiffness.

  4. Effect of passive heat stress on arterial stiffness in smokers versus non-smokers

    NASA Astrophysics Data System (ADS)

    Moyen, N. E.; Ganio, M. S.; Burchfield, J. M.; Tucker, M. A.; Gonzalez, M. A.; Dougherty, E. K.; Robinson, F. B.; Ridings, C. B.; Veilleux, J. C.

    2016-04-01

    In non-smokers, passive heat stress increases shear stress and vasodilation, decreasing arterial stiffness. Smokers, who reportedly have arterial dysfunction, may have similar improvements in arterial stiffness with passive heat stress. Therefore, we examined the effects of an acute bout of whole-body passive heat stress on arterial stiffness in smokers vs. non-smokers. Thirteen smokers (8.8 ± 5.5 [median = 6] cigarettes per day for >4 years) and 13 non-smokers matched for age, mass, height, and exercise habits (27 ± 8 years; 78.8 ± 15.4 kg; 177.6 ± 6.7 cm) were passively heated to 1.5 °C core temperature ( T C) increase. At baseline and each 0.5 °C T C increase, peripheral (pPWV) and central pulse wave velocity (cPWV) were measured via Doppler ultrasound. No differences existed between smokers and non-smokers for any variables (all p > 0.05), except cPWV slightly increased from baseline (526.7 ± 81.7 cm · s-1) to 1.5 °C Δ T C (579.7 ± 69.8 cm · s-1; p < 0.005), suggesting heat stress acutely increased central arterial stiffness. pPWV did not change with heating (grand mean: baseline = 691.9 ± 92.9 cm · s-1; 1.5 °C Δ T C = 691.9 ± 79.5 cm · s-1; p > 0.05). Changes in cPWV and pPWV during heating correlated ( p < 0.05) with baseline PWV in smokers (cPWV: r = -0.59; pPWV: r = -0.62) and non-smokers (cPWV: r = -0.45; pPWV: r = -0.77). Independent of smoking status, baseline stiffness appears to mediate the magnitude of heating-induced changes in arterial stiffness.

  5. Computational model of collagen turnover in carotid arteries during hypertension.

    PubMed

    Sáez, P; Peña, E; Tarbell, J M; Martínez, M A

    2015-02-01

    It is well known that biological tissues adapt their properties because of different mechanical and chemical stimuli. The goal of this work is to study the collagen turnover in the arterial tissue of hypertensive patients through a coupled computational mechano-chemical model. Although it has been widely studied experimentally, computational models dealing with the mechano-chemical approach are not. The present approach can be extended easily to study other aspects of bone remodeling or collagen degradation in heart diseases. The model can be divided into three different stages. First, we study the smooth muscle cell synthesis of different biological substances due to over-stretching during hypertension. Next, we study the mass-transport of these substances along the arterial wall. The last step is to compute the turnover of collagen based on the amount of these substances in the arterial wall which interact with each other to modify the turnover rate of collagen. We simulate this process in a finite element model of a real human carotid artery. The final results show the well-known stiffening of the arterial wall due to the increase in the collagen content.

  6. Stress-sensitive arterial hypertension, hemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

    PubMed

    Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

    2017-03-08

    The study of early development of the arterial hypertension in association with emotional stress is of great importance for better understanding of etiolody and pathogenesis of the hypertensive disease. MRI technique was applied to evaluate the hemodynamic and brain metabolites changes in 1- and 3-Mo-old ISIAH rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive WAG rats (8 male rats). In the 3-Mo-old ISIAH rats, age-dependent increase in the blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of abdominal aorta. The renal vascular resistance in the ISIAH rats decreased while aging, though, at both ages it remained higher than the renal vascular resistance in WAG rats. Integral metabolome portrait demonstrated that hypertension development in the ISIAH rats was associated with attenuation of excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats, the opposite age-dependent changes were observed. In contrast, in hypothalamus of 3-Mo-old ISIAH rats, an increase in energetic activity and prevalence of excitatory neurotransmitters over inhibitory was noticed. The blood flow through the main arteries showed positive correlation with glutamate and glutamine levels in hypothalamus, and negative one - with hypothalamic GABA level. The blood pressure values positively correlated with hypothalamic choline levels. Thus, the early development of the stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries. This article is protected by copyright. All rights reserved.

  7. [Physiopathology of pulmonary arterial hypertension. Cellular and molecular aspects].

    PubMed

    Perros, Frédéric; Humbert, Marc

    2005-02-12

    The combined effects of vasoconstriction, remodelling of the pulmonary vessel walls and in situ thrombosis contribute to the increase in pulmonary vascular resistance during pulmonary arterial hypertension. Vascular remodelling involves all the sheaths of the vessel wall and all the cell types of which it is composed (endothelial cells, smooth muscle cells, fibroblasts, inflammatory cells and platelets). Excessive vasoconstriction has been related to a defect in the function of expression of the potassium channels and endothelial dysfunction. This leads to chronic insufficiency in the production of vasodilators, notably nitrogen monoxide and prostacyclin and the excessive production of vasoconstrictors such as endotheline-1. These defects contribute to the increase in vascular tonus and pulmonary vascular remodelling and represent pertinent pharmacological targets. Certain growth factors, including those of the super-family of transforming growth factor beta, angiopoietine-1 and serotonin, may play a part in the pathogenesis of pulmonary arterial hypertension.

  8. [Pulmonary arterial hypertension in adult patients with congenital heart disease].

    PubMed

    Serino, G; Giacomazzi, F

    2010-01-01

    Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.

  9. Nesiritide for pulmonary arterial hypertension with decompensated cor pulmonale.

    PubMed

    Kingman, Martha S; Thompson, Brenda S; Newkirk, Trixie; Torres, Fernando

    2005-01-01

    Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B-type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B-type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.

  10. Macitentan for the treatment of pulmonary arterial hypertension

    PubMed Central

    Kholdani, Cyrus A; Fares, Wassim H; Trow, Terence K

    2014-01-01

    Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug–drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial. PMID:25473292

  11. Arterial hypertension and neurofibromatosis: renal artery stenosis and coarctation of abdominal aorta.

    PubMed Central

    Schürch, W.; Messerli, F. H.; Genest, J.; Lefebvre, R.; Roy, P.; Carter, P.; Rojo-Ortega, J. M.

    1975-01-01

    A 10-year-old girl had arterial hypertension, generalized neurofibromatosis, coarctation of the abdominal aorta and multiple stenoses at the origin of each renal artery. After resection of the stenotic areas and reimplantation of the renal arteries in the aorta, her arterial pressure decreased substantially. However, hypertension recurred and radiologic follow-up 4 1/2 years later showed distinct progression of the coarctation and renewed stenosis of all renal arteries at their origin. The stenotic areas showed eccentric intimal proliferation, frequently bulging into the lumen, with small nodular aggregates of smooth muscle cells and proliferation of fibrous tissue containing spindle-shaped nuclei in a palisading pattern. Hypertension associated with neurofibromatotic vascular disease has been described in 47 other patients in the literature. These patients have been young (mean age, 14 years) and predominantly male. In contrast to fibromuscular dysplasia, in which 95% of all stenoses are found in the distal two thirds of the renal arteries, in vascular neurofibromatosis more than 50% of the stenoses are found at the origin. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:810239

  12. [Treatment of arterial hypertension in pregnancy in relation to current guidelines of the Polish Society of Arterial Hypertension from 2011].

    PubMed

    Szczepaniak-Chicheł, Ludwina; Tykarski, Andrzej

    2012-10-01

    Arterial hypertension concerns 7-10% of pregnancies and leads to an increased risk of complications for both, the mother and the child. This rate will probably rise in the years to come due to the notable tendency among women to delay the decision to become pregnant - values of blood pressure and occurrence of arterial hypertension increase with age, as well as due to the growing problem of obesity resulting from inappropriate dietary habits and lack of regular everyday physical activity. Difficulties with management of that clinical condition are partly related with lack of unified and widely accepted guidelines. Different opinions in the subject of terminology and classification of pregnancy hypertension or indications for pharmacotherapy as well as choice of the optimal antihypertensive drug, emerge from objective causes such as combination of various pathogenetic factors typical for arterial hypertension itself and those connected with pregnancy elsewhere stressed priorities of therapy from the point of view of the health of the mother and of the fetus, as well as lack of randomized clinical trials due to obvious ethical purposes, but also from the fact that pregnancy hypertension is a focus of attention for different specialists - obstetricians, hypertensiologists and perinatologists. A good cooperation regarding experience and information among all of these specializations would be the most beneficial for pregnant women and their children. Lack of new modern antihypertensive agents, safe and effective in pregnancy while the older ones are being withdrawn from the market as their production is no longer cost-effective for pharmacological companies, has become an increasing problem in many countries, and Poland among them. The aim of the following publication was to present the statement on management of pregnancy hypertension from the current guidelines of the Polish Society of Arterial Hypertension 2011 to gynecologists and obstetricians, with a commentary

  13. Angiotensin Receptor Blockades Effect on Peripheral Muscular and Central Aortic Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials and Systematic Review

    PubMed Central

    Yen, Chih-Hsuan; Lai, Yau-Huei; Hung, Chung-Lieh; Lee, Ping-Ying; Kuo, Jen-Yuan; Yeh, Hung-I; Hou, Charles Jia-Yin; Chien, Kuo-Liong

    2014-01-01

    Background Previous clinical trials have demonstrated the impact of blocking upstream renin-angiotensin-axis with angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness as evaluated by pulse-wave velocity (PWV). We ran a meta-analysis to evaluate the anti-stiffness effect of powerful downstream angiotensin receptor blockades (ARBs) on peripheral and central arterial stiffness (brachial to ankle, ba-PWV; carotid to femoral, cf-PWV, respectively), using a systematic review to assess the clinical arterial stiffness issues. Methods For our study, we searched the PubMed and Cochrane Library databases from inception to June 2013, targeting randomized controlled trials. ARBs along with other antihypertensive agents, ACEIs, calcium channel blockers (CCBs), beta-blockers and diuretics were evaluated to ascertain their comparable effect on ba-PWV and cf-PWV, respectively. A meta-analysis was conducted utilizing the fixed or random effect of the weighted mean change difference between the ARB and comparator groups, depending on the I2 statistic heterogeneity measurement. Results In 2 trials treating patients with ARBs (n = 30), the ARBs insignificantly reduced levels of ba-PWV (pooled mean change difference -188, 95% CI -687, 311, p = 0.24 with significant heterogeneity) as compared to other hypertensive agents (ACEIs and CCBs, n = 77). Interestingly, ARBs (n = 20) had a superior capacity to reduce levels of ba-PWV than CCBs (n = 20) in single study results (mean change difference -400, 95% CI -477, -322, p < 0.05). In 7 trials which included a total of 653 patients, treatment with ARBs (n = 308) also insignificantly reduced cf-PWV (pool mean change difference -0.197, 95% CI -0.54, 0.14, p = 0.218) as compared to other anti-hypertensive agents. Conclusions Our data suggested that ARBs had a similar effect as other anti-hypertensive agents in reducing ba-PWV and cf-PWV. Upon systematic review, the renin-angiotensin-axis system mechanism seems more significant

  14. Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

    PubMed

    Khammy, Makhala M; Angus, James A; Wright, Christine E

    2016-02-15

    In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction.

  15. Intravenous Epoprostenol for Management of Pulmonary Arterial Hypertension during Pregnancy

    PubMed Central

    Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W.

    2013-01-01

    Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown. PMID:24147238

  16. Intravenous Epoprostenol for Management of Pulmonary Arterial Hypertension during Pregnancy.

    PubMed

    Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W

    2013-10-01

    Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown.

  17. Children and Adolescent Obesity Associates with Pressure-Dependent and Age-Related Increase in Carotid and Femoral Arteries' Stiffness and Not in Brachial Artery, Indicative of Nonintrinsic Arterial Wall Alteration

    PubMed Central

    García-Espinosa, Victoria; Curcio, Santiago; Castro, Juan Manuel; Arana, Maite; Giachetto, Gustavo; Chiesa, Pedro; Zócalo, Yanina

    2016-01-01

    Aim. To analyze if childhood obesity associates with changes in elastic, transitional, and/or muscular arteries' stiffness. Methods. 221 subjects (4–15 years, 92 females) were assigned to normal weight (NW, n = 137) or obesity (OB, n = 84) groups, considering their body mass index z-score. Age groups were defined: 4–8; 8–12; 12–15 years old. Carotid, femoral, and brachial artery local stiffness was determined through systodiastolic pressure-diameter and stress-strain relationships. To this end, arterial diameter and peripheral and aortic blood pressure (BP) levels and waveforms were recorded. Carotid-femoral, femoropedal, and carotid-radial pulse wave velocities were determined to evaluate aortic, lower-limb, and upper-limb regional arterial stiffness, respectively. Correlation analysis between stiffness parameters and BP was done. Results. Compared to NW, OB subjects showed higher peripheral and central BP and carotid and femoral stiffness, reaching statistical significance in subjects aged 12 and older. Arterial stiffness differences disappeared when levels were normalized for BP. There were no differences in intrinsic arterial wall stiffness (elastic modulus), BP stiffness relationships, and regional stiffness parameters. Conclusion. OB associates with BP-dependent and age-related increase in carotid and femoral (but not brachial) stiffness. Stiffness changes would not be explained by intrinsic arterial wall alterations but could be associated with the higher BP levels observed in obese children. PMID:27066273

  18. Application of a four-channel vibrometer system for detection of arterial stiffness

    NASA Astrophysics Data System (ADS)

    Campo, Adriaan; Waz, Adam; Dudzik, Grzegorz; Dirckx, Joris; Abramski, Krzysztof

    2016-06-01

    Cardiovascular diseases (CD) are the most important cause of death in the world and their prevalence is only rising. A significant aspect in the etiology of CD is the stiffening of the large arteries (arteriosclerosis) and plaque formation (atherosclerosis) in the common carotid artery (CCA) in the neck. As shown by increasing evidence, both conditions can be detected by assessing pulse wave velocity (PWV) in the CCA, and several approaches allow local detection of PWV, including ultrasound (US) and magnetic resonance imaging (MRI). In previous studies, laser Doppler vibrometry (LDV) was introduced as an approach to assess arterial stiffness. In the present work, a new, compact four-channel LDV system is used for PWV detection in four phantom arteries mimicking real life CCA conditions. The high sensitivity of the LDV system allowed PWV to be assessed, and even local changes in phantom architecture could be detected. This method has potential for cardiovascular screening, as it allows arteriosclerosis assessment and plaque detection.

  19. [Consensus on Systemic Arterial Hypertension In México].

    PubMed

    Rosas-Peralta, Martín; Palomo-Piñón, Silvia; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Almeida-Gutiérrez, Eduardo; Galván-Oseguera, Héctor; Magaña-Serrano, José Antonio; Saturno-Chiu, Guillermo; Ramírez-Arias, Erick; Santos-Martínez, Efrén; Díaz-Díaz, Enrique; Salgado-Pastor, Selene Janette; Morales-Mora, Gerardo; Medina-Concebida, Luz Elena; Mejía-Rodríguez, Oliva; Pérez-Ruiz, Claudia Elsa; Chapa-Mejía, Luis Raúl; Álvarez-Aguilar, Cleto; Pérez-Rodríguez, Gilberto; Castro-Martínez, María Guadalupe; López-Bárcena, Joaquín; Paniagua-Sierra, José Ramón

    2016-01-01

    This Consenso Nacional de Hipertensión Arterial Sistémica (National Consensus on Systemic Arterial Hypertension) brings together experiences and joint work of 79 specialists who have been in contact with the patient affected by systemic arterial hypertension. All concepts here presented were outlined on the basis of the real world practice of Mexican hypertensive population. The consensus was developed under strict methodological guidelines. The Delphi technique was applied in two rounds for the development of an appropriate statistical analysis of the concepts exposed by all the specialists, who posed key questions, later developed by the panel of experts of the Hospital de Cardiología, and specialists from the Centro Médico Nacional. Several angles of this illness are shown: detection, diagnosis, pathophysiology, classification, treatment and prevention. The evidence analysis was carried out using PRISMA method. More than 600 articles were reviewed, leaving only the most representative in the references. This document concludes with practical and useful recommendations for the three levels of health care of our country.

  20. High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency

    PubMed Central

    Zaleski, Amanda; Panza, Gregory; Swales, Heather; Arora, Pankaj; Newton-Cheh, Christopher; Wang, Thomas; Thompson, Paul D.; Taylor, Beth

    2015-01-01

    Introduction. Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD). However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension. Methods. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP), carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation. Results. There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (all p > 0.202). High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p = 0.047) and 4.0 ± 1.5 mmHg (p = 0.02), respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p = 0.425). Conclusion. High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity. Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier: NCT01240512). PMID:26451070

  1. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  2. Taurine supplementation attenuates delayed increase in exercise-induced arterial stiffness.

    PubMed

    Ra, Song-Gyu; Choi, Youngju; Akazawa, Nobuhiko; Ohmori, Hajime; Maeda, Seiji

    2016-06-01

    There is a delayed increase in arterial stiffness after eccentric exercise that is possibly mediated by the concurrent delayed increase in circulating oxidative stress. Taurine has anti-oxidant action, and taurine supplementation may be able to attenuate the increase in oxidative stress after exercise. The purpose of the present study was to investigate whether taurine supplementation attenuates the delayed increase in arterial stiffness after eccentric exercise. In the present double-blind, randomized, and placebo-controlled trial, we divided 29 young, healthy men into 2 groups. Subjects received either 2.0 g of placebo (n = 14) or taurine (n = 15) 3 times per day for 14 days prior to the exercise, on the day of exercise, and the following 3 days. The exercise consisted of 2 sets of 20 maximal-effort eccentric repetitions with the nondominant arm only. On the morning of exercise and for 4 days thereafter, we measured serum malondialdehyde (MDA) and carotid-femoral pulse wave velocity (cfPWV) as indices of oxidative stress and arterial stiffness, respectively. On the third and fourth days after exercise, both MDA and cfPWV significantly increased in the placebo group. However, these elevations were significantly attenuated in the taurine group. The increase in MDA was associated with an increase in cfPWV from before exercise to 4 days after exercise (r = 0.597, p < 0.05) in the placebo group, but not in the taurine group. Our results suggest that delayed increase in arterial stiffness after eccentric exercise was probably affected by the exercise-induced oxidative stress and was attenuated by the taurine supplementation.

  3. Effect of acute aerobic exercise and histamine receptor blockade on arterial stiffness in African Americans and Caucasians.

    PubMed

    Yan, Huimin; Ranadive, Sushant M; Lane-Cordova, Abbi D; Kappus, Rebecca M; Behun, Michael A; Cook, Marc D; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Halliwill, John R; Fernhall, Bo

    2017-02-01

    African Americans (AA) exhibit exaggerated central blood pressure (BP) and arterial stiffness measured by pulse wave velocity (PWV) in response to an acute bout of maximal exercise compared with Caucasians (CA). However, whether potential racial differences exist in central BP, elastic, or muscular arterial distensibility after submaximal aerobic exercise remains unknown. Histamine receptor activation mediates sustained postexercise hyperemia in CA but the effect on arterial stiffness is unknown. This study sought to determine the effects of an acute bout of aerobic exercise on central BP and arterial stiffness and the role of histamine receptors, in AA and CA. Forty-nine (22 AA, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either histamine receptor antagonist or control placebo. Central blood BP and arterial stiffness measurements were obtained at baseline, and at 30, 60, and 90 min after 45 min of moderate treadmill exercise. AA exhibited greater central diastolic BP, elevated brachial PWV, and local carotid arterial stiffness after an acute bout of submaximal exercise compared with CA, which may contribute to their higher risk of cardiovascular disease. Unexpectedly, histamine receptor blockade did not affect central BP or PWV in AA or CA after exercise, but it may play a role in mediating local carotid arterial stiffness. Furthermore, histamine may mediate postexercise carotid arterial dilation in CA but not in AA. These observations provide evidence that young and healthy AA exhibit an exaggerated hemodynamic response to exercise and attenuated vasodilator response compared with CA.NEW & NOTEWORTHY African Americans are at greater risk for developing cardiovascular disease than Caucasians. We are the first to show that young and healthy African Americans exhibit greater central blood pressure, elevated brachial stiffness, and local carotid arterial stiffness following an acute bout of submaximal exercise

  4. Relation of Habitual Chocolate Consumption to Arterial Stiffness in a Community-Based Sample: Preliminary Findings

    PubMed Central

    Crichton, Georgina E.; Elias, Merrill F.; Alkerwi, Ala'a; Stranges, Saverio; Abhayaratna, Walter P.

    2016-01-01

    Background The consumption of chocolate and cocoa has established cardiovascular benefits. Less is known about the effects of chocolate on arterial stiffness, a marker of subclinical cardiovascular disease. The aim of this study was to investigate whether chocolate intakes are independently associated with pulse wave velocity (PWV), after adjustment for cardiovascular, lifestyle and dietary factors. Methods Prospective analyses were undertaken on 508 community-dwelling participants (mean age 61 years, 60% women) from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intakes, measured using a food frequency questionnaire, were related to PWV, measured approximately 5 years later. Results Chocolate intake was significantly associated with PWV in a non-linear fashion with the highest levels of PWV in those who never or rarely ate chocolate and lowest levels in those who consumed chocolate once a week. This pattern of results remained and was not attenuated after multivariate adjustment for diabetes, cardiovascular risk factors and dietary variables (p = 0.002). Conclusions Weekly chocolate intake may be of benefit to arterial stiffness. Further studies are needed to explore the underlying mechanisms that may mediate the observed effects of habitual chocolate consumption on arterial stiffness. PMID:27493901

  5. Arterial stiffness is inversely associated with a better running record in a full course marathon race

    PubMed Central

    Jung, Su-Jeen; Park, Jae-Hyoung; Lee, Sewon

    2014-01-01

    [Purpose] Arterial stiffness is an independent predictor of cardiovascular risk and may contribute to reduced running capacity in humans. This study investigated the relationship between course record and arterial stiffness in marathoners who participated in the Seoul International Marathon in 2012. [Methods] A total of 30 amateur marathoners (Males n = 28, Females n = 2, mean age = 51.6 ± 8.3 years) were assessed before and after the marathon race. Brachial-ankle pulse wave velocity (ba-PWV) was assessed by VP-1000 plus (Omron Healthcare Co., Ltd., Kyoto, Japan) before and immediately after the marathon race. Pearson's correlation coefficient was used to determine the relationship between race record and ba-PWV. In addition, Wilcoxon signed rank test was used to determine the difference in ba-PWV between before and after the race. [Results] There was no significant change in the ba-PWV of marathoners before and after the race (1271.1 ± 185 vs. 1268.8 ± 200 cm/s, P=0.579). Both the full course record (Pearson's correlation coefficient = 0.416, P = 0.022) and the record of half line (Pearson's correlation coefficient = 0.482, P = 0.007) were positively related with the difference in ba-PWV, suggesting that reduced arterial stiffness is associated with a better running record in the marathon. [Conclusion] These results may suggest that good vascular function contributes to a better running record in the marathon race. PMID:25671202

  6. Influence of detraining on temporal changes in arterial stiffness in endurance athletes: a prospective study

    PubMed Central

    Koshiba, Hiroya; Maeshima, Etsuko

    2015-01-01

    [Purpose] We examined the effects of detraining on temporal changes in arterial stiffness in endurance athletes. [Subjects] Eighteen female university athletes requiring high endurance exercise capabilities were classified into 2 groups: 10 retired players (detraining group) and 8 active players (training group). [Methods] Brachial-ankle pulse wave velocity, an index of arterial stiffness, was measured a total of 6 times: immediately before retirement of the detraining group and at 1, 2, 3, 6, and 12 months after retirement. [Results] Brachial-ankle pulse wave velocity was measured in the training group at the same 6 points to allow comparison with the detraining group. The brachial-ankle pulse wave velocity in the detraining group increased significantly at 3 and 12 months as compared with that at 0 months and showed a significant increase at 12 months compared with that at 1 month. Moreover, the brachial-ankle pulse wave velocity in the detraining group was significantly higher at 3, 6, and 12 months than in the training group. [Conclusion] These results revealed that detraining may result in increased arterial stiffness from 3 months onward in endurance athletes. PMID:26834331

  7. [Treatment of pulmonary arterial hypertension in children].

    PubMed

    Fraisse, A; Habib, G

    2004-08-01

    Treatment strategies for pulmonary hypertension in children have dramatically evolved. Traditional therapy with calcium channel blockers and pulmonary transplantation is only indicated in selected patients and does not reduce mortality very significantly. New pulmonary vasodilators are emerging from recent trials in the adult population. Their indications are based on the patient's NYHA classification. The epoprostenol (prostacyclin, Flolan) has shown reduction in mortality and improvement in functional symptoms in pediatric patients. The frequent side effects and continuous intravenous infusion limit the indication of prostacyclin in NYHA class IV children. The endothelin receptor blocker bosentan (Tracleer) is an orally given agent. It improves functional symptoms in adults and hemodynamic measures in children. It can be started in children with moderate functional symptoms (NYHA class II and III). The type V phosphodiesterase inhibitor sildenafil (Viagra) is being evaluated and may represent a promising therapy in the future. Invasive strategies like catheter-based atrial septostomy may be useful in particular cases. Randomized-controlled studies are urgently needed to evaluate the safety and efficacy of these new therapies.

  8. Intra--and Intercellular Calcium Handling in Pulmonary Arterial Hypertension.

    PubMed

    Mouratoglou, Sophia-Anastasia; Giannakoulas, George; Deftereos, Spyridon; Giannopoulos, Georgios; Angelidis, Christos; Cleman, Michael W; Vassilikos, Vassilios P

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.

  9. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke

    PubMed Central

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood–brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte–leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  10. [Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

    PubMed

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

  11. Increased Pulse Wave Velocity Reflecting Arterial Stiffness in Patients with Colorectal Adenomas

    PubMed Central

    Lim, Yun Jeong; Kwack, Won Gun; Lee, Youg-Sup; Hahm, Ki Baik; Kim, Young-Kwon

    2010-01-01

    The obese patients with diabetes or cardiovascular risk factors are associated with increased risk of colorectal cancer as well as adenomas under the shared pathogenesis related to atherosclerosis. Here we determined the association between increased arterial stiffness and colorectal adenomas incorporating parameters including age, gender, waist circumference, body mass index, lipid profiles, fasting glucose, and blood pressure. Subjects who simultaneously underwent colonoscopies and pulse wave velocity (PWV) determinations between July 2005 and September 2006 were analyzed, based on which the subjects were classified into two groups as patients group with colorectal adenomas (n = 49) and control group (n = 200) with normal, non-polypoid benign lesions or hyperplastic polyps. Uni- and multi-variate analyses were performed to calculate the odd ratio for colon adenomas. Based on uni-variate analysis, age, waist circumference, body mass index, heart-femoral PWV (hfPWV), and brachial-ankle PWV were significantly associated with adenomas (p<0.05) and multiple logistic regression analysis showed that the heart-femoral PWV, waist circumference, and the levels of LDL-C were significant risk factor for colorectal adenoma. However, arterial stiffness did not affect the progression of colon adenoma. The finding that hfPWV, reflecting aortic stiffness, was increased in patients with colorectal adenomas lead to conclusion that patients who have prominently increased arterial stiffness can be recommended to undergo colonoscopic examinations and at the same time we also recommend counseling about the risk for atherosclerosis in those who have colorectal adenomas. PMID:21103036

  12. Electrical carotid sinus stimulation in treatment resistant arterial hypertension.

    PubMed

    Jordan, Jens; Heusser, Karsten; Brinkmann, Julia; Tank, Jens

    2012-12-24

    Treatment resistant arterial hypertension is commonly defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. The sympathetic nervous system promotes arterial hypertension and cardiovascular as well as renal damage, thus, providing a logical treatment target in these patients. Recent physiological studies suggest that baroreflex mechanisms contribute to long-term control of sympathetic activity and blood pressure providing an impetus for the development of electrical carotid sinus stimulators. The concept behind electrical stimulation of baroreceptors or baroreflex afferent nerves is that the stimulus is sensed by the brain as blood pressure increase. Then, baroreflex efferent structures are adjusted to counteract the perceived blood pressure increase. Electrical stimulators directly activating afferent baroreflex nerves were developed years earlier but failed for technical reasons. Recently, a novel implantable device was developed that produces an electrical field stimulation of the carotid sinus wall. Carefully conducted experiments in dogs provided important insight in mechanisms mediating the depressor response to electrical carotid sinus stimulation. Moreover, these studies showed that the treatment success may depend on the underlying pathophysiology of the hypertension. Clinical studies suggest that electrical carotid sinus stimulation attenuates sympathetic activation of vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus lowering blood pressure. Yet, not all patients respond to treatment. Additional clinical trials are required. Patients equipped with an electrical carotid sinus stimulator provide a unique opportunity gaining insight in human baroreflex physiology.

  13. Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults.

    PubMed

    West, Sheila G; McIntyre, Molly D; Piotrowski, Matthew J; Poupin, Nathalie; Miller, Debra L; Preston, Amy G; Wagner, Paul; Groves, Lisa F; Skulas-Ray, Ann C

    2014-02-01

    The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6% (+2 mm) and basal blood flow volume by 22%. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.

  14. Arterial Stiffness Is Significantly Associated With Left Ventricular Diastolic Dysfunction in Patients With Cardiovascular Disease.

    PubMed

    Namba, Takayuki; Masaki, Nobuyuki; Matsuo, Yuki; Sato, Atsushi; Kimura, Toyokazu; Horii, Shunpei; Yasuda, Risako; Yada, Hirotaka; Kawamura, Akio; Takase, Bonpei; Adachi, Takeshi

    2016-12-02

    Left ventricular (LV) diastolic dysfunction is considered the main cause of heart failure with preserved ejection fraction (HFpEF). There have been few reports on the correlation between LV diastolic dysfunction and arterial stiffness in patients with clinical cardiovascular disease.This cross-sectional study enrolled 100 patients (67 men, 33 women; mean age, 70 years). All participants were diagnosed with cardiovascular disease. A total of 89 (89%) patients had coronary artery disease or HF. Patients with reduced EF and valvular disease were excluded. Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and LV diastolic dysfunction was estimated using echocardiography. The patients were divided into two groups based on the median value of CAVI. In all patients the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') was significantly higher in the high CAVI group than in the low CAVI group (15.5 ± 6.4 versus 12.5 ± 2.9, P = 0.003). In the HF subgroup, E/e' was also significantly higher in the high CAVI group than in the low CAVI group (17.2 ± 5.9 versus 13.0 ± 3.1, P = 0.026). In univariate regression analysis, CAVI was significantly associated with E/e' in all patients (β = 0.28, P = 0.004) and in HF patients (β = 0.4, P = 0.028). Also in multivariate analysis, CAVI remained as an independent predictive factor of E/e' (β = 0.252, P = 0.037).A high CAVI was independently associated with LV diastolic dysfunction in patients with clinical cardiovascular disease. These results suggested that arterial stiffness contributed to the development of LV diastolic dysfunction.

  15. Berry splenic artery aneurysm rupture in association with segmental arterial mediolysis and portal hypertension.

    PubMed

    Imai, Miwa Akasofu; Kawahara, Ei; Katsuda, Shogo; Yamashita, Tatsuya

    2005-05-01

    A rare case of berry splenic artery aneurysm (SAA) rupture associated with segmental arterial mediolysis (SAM) and portal hypertension is reported. A 66-year-old woman, diagnosed as having liver cirrhosis and portal hypertension 6 years earlier, suddenly developed a lancinating pain in the upper abdomen and lost consciousness. She recovered consciousness while being transferred to hospital by ambulance. During the investigations, her level of consciousness suddenly deteriorated. Ultrasonography showed a massive intraperitoneal hemorrhage, and she died 5(1/2) h after admission. On gross examination at autopsy it was not possible to find the rupture point of the vessel because the pancreas was embedded in a massive hematoma. However, careful dissection of the pancreatic tail after fixation revealed a berry aneurysm measuring 0.8 cm in diameter in a branch adjacent to the bifurcation in the distal third of the main splenic artery. Microscopic examination detected a rupture of the aneurysm. The histology of the arterial wall proximal to the aneurysm showed typical SAM. In general, berry SAA caused by SAM is rare and unlikely to rupture. The SAA in the present case likely occurred and ruptured due to the combination of SAM and portal hypertension.

  16. Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension

    PubMed Central

    Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

    2013-01-01

    Background and Purpose Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Experimental Approach Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Key Results Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O2− production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Conclusions and Implications Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. PMID:22994554

  17. Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.

    PubMed

    Fujio, Hideki; Nakamura, Kazufumi; Matsubara, Hiromi; Kusano, Kengo Fukushima; Miyaji, Katsumasa; Nagase, Satoshi; Ikeda, Tetsuya; Ogawa, Aiko; Ohta-Ogo, Keiko; Miura, Daiji; Miura, Aya; Miyazaki, Masahiro; Date, Hiroshi; Ohe, Tohru

    2006-02-01

    Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension

  18. Pulmonary Arterial Hypertension: A Focus on Infused Prostacyclins.

    PubMed

    Stewart, Traci

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed.

  19. Genomics of Pulmonary Arterial Hypertension: Implications for Therapy

    PubMed Central

    Geraci, Mark W.; Bull, Todd M.; Tuder, Rubin M.

    2009-01-01

    Synopsis Pulmonary arterial hypertension remains a vexing clinical disease with no cure. Despite advances and the discovery of a gene (BMPR2) associated with many of the hereditary forms of the disease, and some cases not previously known to be inherited, the reasons for mutations in this gene as a cause remain somewhat elusive. Clearly, a complex interplay exists between genetic alterations, environmental exposures (including infections) and disease development. This article addresses the advances in the genetics of PAH, including the identification of genetic etiologies and modulators, and the role of genetics in predicting disease progression and targeting therapeutics. PMID:19945066

  20. Therapies for scleroderma-related pulmonary arterial hypertension

    PubMed Central

    Hassoun, Paul M

    2009-01-01

    Pulmonary arterial hypertension (PAH), a common complication of systemic sclerosis, carries a very severe prognosis and is one of the leading causes of death in patients who suffer from it. Indeed, response to modern medical therapy has been disappointing in scleroderma-related PAH compared with other forms of PAH from the WHO group 1 classification of diseases, despite similar histological changes involving the pulmonary vasculature. This review discusses specific features of scleroderma-related PAH, currently available and US FDA-approved therapy for this syndrome, as well as potential future therapeutic developments based on newly acquired knowledge of this disorder. PMID:19885388

  1. The study of risk in pulmonary arterial hypertension.

    PubMed

    Rubin, Lewis J; Simonneau, Gerald; Badesch, David; Galiè, Nazzareno; Humbert, Marc; Keogh, Anne; Massaro, Joseph; Matucci Cerinic, Marco; Sitbon, Olivier; Kymes, Steven

    2012-09-01

    A growing body of published evidence exists on the risk factors for disease progression in pulmonary arterial hypertension (PAH). The Scientific Steering Committee for the Study of Risk in PAH was established to bring together leading clinical and statistical experts in PAH and risk modelling, for the purpose of advancing the understanding of the risk of development and progression of PAH. Herein, we discuss the impact of this information on three key areas: 1) clinical decision-making; 2) policy and reimbursement; and 3) future trials and research.

  2. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness.

    PubMed

    Mozos, Ioana; Stoian, Dana; Luca, Constantin Tudor

    2017-01-01

    Arterial stiffness is associated with cardiovascular risk, morbidity, and mortality. The present paper reviews the main vitamins related to arterial stiffness and enabling destiffening, their mechanisms of action, providing a brief description of the latest studies in the area, and their implications for primary cardiovascular prevention, clinical practice, and therapy. Despite inconsistent evidence for destiffening induced by vitamin supplementation in several randomized clinical trials, positive results were obtained in specific populations. The main mechanisms are related to antiatherogenic effects, improvement of endothelial function (vitamins A, C, D, and E) and metabolic profile (vitamins A, B12, C, D, and K), inhibition of the renin-angiotensin-aldosterone system (vitamin D), anti-inflammatory (vitamins A, D, E, and K) and antioxidant effects (vitamins A, C, and E), decrease of homocysteine level (vitamin B12), and reversing calcification of arteries (vitamin K). Vitamins A, B12, C, D, E, and K status is important in evaluating cardiovascular risk, and vitamin supplementation may be an effective, individualized, and inexpensive destiffening therapy.

  3. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness

    PubMed Central

    Luca, Constantin Tudor

    2017-01-01

    Arterial stiffness is associated with cardiovascular risk, morbidity, and mortality. The present paper reviews the main vitamins related to arterial stiffness and enabling destiffening, their mechanisms of action, providing a brief description of the latest studies in the area, and their implications for primary cardiovascular prevention, clinical practice, and therapy. Despite inconsistent evidence for destiffening induced by vitamin supplementation in several randomized clinical trials, positive results were obtained in specific populations. The main mechanisms are related to antiatherogenic effects, improvement of endothelial function (vitamins A, C, D, and E) and metabolic profile (vitamins A, B12, C, D, and K), inhibition of the renin-angiotensin-aldosterone system (vitamin D), anti-inflammatory (vitamins A, D, E, and K) and antioxidant effects (vitamins A, C, and E), decrease of homocysteine level (vitamin B12), and reversing calcification of arteries (vitamin K). Vitamins A, B12, C, D, E, and K status is important in evaluating cardiovascular risk, and vitamin supplementation may be an effective, individualized, and inexpensive destiffening therapy. PMID:28167849

  4. Arterial stiffness and influences of the metabolic syndrome: a cross-countries study.

    PubMed

    Scuteri, Angelo; Cunha, Pedro G; Rosei, E Agabiti; Badariere, Jolita; Bekaert, Sofie; Cockcroft, John R; Cotter, Jorge; Cucca, Francesco; De Buyzere, Marc L; De Meyer, Tim; Ferrucci, Luigi; Franco, Osca; Gale, Nichols; Gillebert, Thierry C; Hofman, A; Langlois, Michel; Laucevicius, Aleksandras; Laurent, Stephane; Mattace Raso, Francesco U S; Morrell, Cristopher H; Muiesan, Maria Lorenza; Munnery, Margaret M; Navickas, Rokas; Oliveira, Pedro; Orru', Marco; Pilia, Maria Grazia; Rietzschel, Ernst R; Ryliskyte, Ligita; Salvetti, Massimo; Schlessinger, David; Sousa, Nuno; Stefanadis, Christodoulos; Strait, James; Van daele, Caroline; Villa, Isabel; Vlachopoulos, Charalambos; Witteman, Jacqueline; Xaplanteris, Panagiotis; Nilsson, Peter; Lakatta, Edward G

    2014-04-01

    Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in ≥3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components--even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus--in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV).

  5. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  6. Arterial Stiffness and Carotid Intima-Media Thickness in Diabetic Peripheral Neuropathy

    PubMed Central

    Avci, Ahmet; Demir, Kenan; Kaya, Zeynettin; Marakoglu, Kamile; Ceylan, Esra; Ekmekci, Ahmet Hakan; Yilmaz, Ahmet; Demir, Aysegul; Altunkeser, Bulent Behlul

    2014-01-01

    Background We investigated the relationship between peripheral neuropathy and parameters of arterial stiffness and carotid intima media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). Material/Methods The study included 161 patients (80 females and 81 males), 69 of whom had peripheral neuropathy. All patients underwent 24-h blood pressure monitoring, and arterial stiffness parameters were measured. The CIMT was measured using B-mode ultrasonography and patients also underwent transthoracic echocardiographic examination. Results Patients with peripheral neuropathy, compared with those without it, were older (54.68±8.35 years vs. 51.04±7.89 years; p=0.005) and had T2DM for longer periods (60 vs. 36 months; p=0.004). Glycated hemoglobin (HbA1c) values (8.55±1.85 mg/dL vs. 7.30±1.51 mg/dL; p<0.001), pulse wave velocity (PWV) (7.74±1.14 m/s vs. 7.15±1.10 m/s; p=0.001), CIMT (anterior 0.74±0.15 mm vs. 0.67±0.13 mm; p=0.01), and left ventricular mass (LVM) index (98.68±26.28 g/m2 vs. 89.71±19.70 g/m2; p=0.02) were all significantly increased in the group with peripheral neuropathy compared to the group without peripheral neuropathy. We determined that duration of diabetes, HbA1c, and LVM index were predictors of peripheral neuropathy. Conclusions A significant relationship was found between diabetic neuropathy and increased PWV, a parameter of arterial stiffness, as well as CIMT, a marker of systemic atherosclerosis. Diabetic peripheral neuropathy may be a determinant of subclinical atherosclerosis in T2DM. PMID:25351260

  7. The effects of single hemodialysis session on arterial stiffness in hemodialysis patients.

    PubMed

    Öğünç, Handan; Akdam, Hakan; Alp, Alper; Gencer, Fatih; Akar, Harun; Yeniçerioğlu, Yavuz

    2015-07-01

    Increased arterial stiffness in hemodialysis patients is a strong predictor of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) and augmentation index (AIx), which are markers of arterial stiffness, were used to determine the severity of vascular damage noninvasively. This study aimed to investigate the effects of solute volume removal and hemodynamic changes on PWV and AIx of a single hemodialysis session. Thirty hemodialysis patients were enrolled in the study. Before initiation of hemodialysis, every 15 minutes during hemodialysis, and 30 minutes after the completion of the session, measurements of PWV and AIx@75 (normalized with heart rate 75 bpm) were obtained from each patient. Body composition was analyzed by bioimpedance spectroscopy device before and 30 minutes after completion of the hemodialysis session. During the hemodialysis, no significant change was observed in AIx@75. However, PWV decreased steadily during the session reaching statistically significant level at 135th minute (P = 0.026), with a maximal drop at 210th minute (P < 0.001). At 210th minute, decrease in PWV correlated positively with the decrease in central systolic blood pressure, central diastolic blood pressure, central pulse pressure, augmentation pressure, and AIx@75. Multiple regression analysis showed that decrease in PWV at 210th minute was associated with decrease in central systolic blood pressure and central pulse pressure. Ultrafiltration during hemodialysis had no significant effect on PWV and AIx@75. Delta urea correlated positively with delta PWV at 240th minute. A significant decrease in PWV was observed during hemodialysis and correlated with urea reduction; however, we were unable to document any effect of volume removal on arterial stiffness.

  8. Developing an effective arterial stiffness monitoring system using the spring constant method and photoplethysmography.

    PubMed

    Wei, Ching-Chuan

    2013-01-01

    This study aimed to develop a fast and effective arterial stiffness monitoring system for diabetic patients using the spring constant method and photoplethysmography (PPG). The experimental group comprised 70 patients (4 type 1 diabetes mellitus patients and 66 type 2 diabetes mellitus patients); 23 participants suffered from atherosclerosis. All were subjected to the measurements of both the carotid-femoral pulse wave velocity (cfPWV) and the spring constants evaluated using the PPG pulse as well as the radial pulse. The control group comprised 70 normal participants (39 men and 31 women) who did not have diabetes mellitus, with an age range of 40-84 years. All control group members were only subjected to the measurement by the spring constant method. For the experimental group, statistical analysis indicated a significantly high correlation between the spring constants computed using PPG and the radial pulse (p < 0.001, correlation coefficient =0.89). The result also showed a significant negative correlation between the cfPWV and the spring constant of PPG (p < 0.001, correlation coefficient = - 0.72); multivariate analysis similarly indicated a close relationship. In addition, we used Student's t test to examine the difference between the experimental and control groups for the spring constant of PPG. A P value less than 0.05 confirmed that the difference between the two groups was statistically significant. In the receiver operating characteristic curve, area under curve (=0.82) indicates a good discrimination, and a spring constant of PPG below 516 (g/s (2)) may imply a risk of arterial stiffness for diabetic patients. These findings imply that the spring constant of PPG could effectively identify normal versus abnormal characteristics of elasticity in normal and diabetic participants. As a result of some excellent characteristics in clinical monitoring, the spring constant computed using PPG shows the effectiveness and feasibility in the monitoring system of

  9. Nox4 Is Expressed In Pulmonary Artery Adventitia And Contributes To Hypertensive Vascular Remodeling

    PubMed Central

    Barman, Scott A.; Chen, Feng; Su, Yunchao; Dimitropoulou, Christiana; Wang, Yusi; Catravas, John D.; Han, Weihong; Orfi, Laszlo; Szantai-Kis, Csaba; Keri, Gyorgy; Szabadkai, Istvan; Barabutis, Nektarios; Rafikova, Olga; Rafikov, Ruslan; Black, Stephen M.; Jonigk, Danny; Giannis, Athanassios; Asmis, Reto; Stepp, David W.; Ramesh, Ganesan; Fulton, David J.R.

    2014-01-01

    OBJECTIVE Pulmonary Hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PA and determine the functional relevance of Nox4 in PH. APPROACH AND RESULTS Elevated expression of Nox4 was detected in hypertensive PA from 3 rat PH models and human PH using qRT-PCR, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of ROS production. Small molecule inhibitors of Nox4 reduced adventitial ROS generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and non-invasive indices of PA stiffness in monocrotaline (MCT)-treated rats as determined by morphometric analysis and high resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PA. In fibroblasts, Nox4 over-expression stimulated migration and proliferation and was necessary for matrix gene expression. CONCLUSIONS These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling and the development of PH. PMID:24947524

  10. Assessment of Arterial Stiffness, Volume, and Nutritional Status in Stable Renal Transplant Recipients

    PubMed Central

    Czyzewski, Lukasz; Wyzgal, Janusz; Czyzewska, Emilia; Kurowski, Andrzej; Sierdzinski, Janusz; Truszewski, Zenon; Szarpak, Lukasz

    2016-01-01

    Abstract Reduction of cardiovascular death might have a significant effect on the long-term survival rates of renal transplant recipients (RTRs). The aim of the study was to assess the relation between arterial stiffness and graft function, adipose tissue content, and hydration status in patients after kidney transplantation (KTx). The study included 83 RTR patients (mean age: 55 ± 13 years) who had been admitted to a nephrology-transplantation outpatient clinic 0.5 to 24 years after KTx. Clinical and laboratory data were analyzed and eGFR was calculated with the CKD-EPI formula. Arterial stiffness was assessed in all RTRs with pulse wave propagation velocity (PWV) with the use of a complior device. In addition, fluid and nutritional status was assessed with a Tanita BC 418 body composition analyzer. The control group consisted of 31 hospital workers who received no medication and had no history of cardiovascular disease. Multivariable linear regression analysis, with PWV as a dependent variable, retained the following independent predictors in the final regression model: red blood cell distribution width (RDW) (B = 0.323; P = 0.004), age (B = 0.297; P = 0.005), tacrolimus therapy (B = −0.286; P = 0.004), and central DBP (B = 0.185; P = 0.041). Multivariable linear regression analysis with eGFR as a dependent variable retained the following independent predictors in the final regression model; creatinine concentration (B = −0.632; P = 0.000), hemoglobin (B = 0.280; P = 0.000), CRP (B = −0.172; P = 0.011), tacrolimus therapy (B = 0.142; P = 0.039), and triglycerides (B = −0.142; P = 0.035). Our data indicates that: kidney transplant recipients can present modifiable CVD risk factors linked to increased arterial stiffness, DBP, waist circumference, SCr, time on dialysis, CyA therapy, and visceral fat mass; RDW is a parameter associated with arterial stiffness; and parameters such as

  11. Anti-tumor necrosis factor-alpha therapy improves endothelial function and arterial stiffness in patients with moderate to severe psoriasis: A 6-month prospective study.

    PubMed

    Pina, Trinitario; Corrales, Alfonso; Lopez-Mejias, Raquel; Armesto, Susana; Gonzalez-Lopez, Marcos A; Gómez-Acebo, Ines; Ubilla, Begoña; Remuzgo-Martínez, Sara; Gonzalez-Vela, M Carmen; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A

    2016-11-01

    The aim of the present study was to determine if the use of the anti-tumor necrosis factor (TNF)-α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow-mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty-nine patients were studied. Anti-TNF-α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti-TNF-α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.

  12. [Effect of complex sanatorium treatment including magnetotherapy on hemodynamics in patients with arterial hypertension].

    PubMed

    Efremushkin, G G; Duruda, N V

    2003-01-01

    Forty nine patients with arterial hypertension of stage I-II received combined sanatorium treatment. Of them, 21 had adjuvant total magnetotherapy. All the patients were examined for parameters of central, cerebral hemodynamics and microcirculation. The adjuvant magnetotherapy produced a beneficial effect on hypertension: clinical symptoms attenuated, arterial pressure became more stable, hemodynamics improved, duration of hospitalization reduced, requirement in hypotensive drugs diminished.

  13. Role of oxidized lipids in pulmonary arterial hypertension

    PubMed Central

    Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603

  14. Arginase inhibitor attenuates pulmonary artery hypertension induced by hypoxia.

    PubMed

    Chu, YanBiao; XiangLi, XiaoYing; Niu, Hu; Wang, HongChao; Jia, PingDong; Gong, WenBin; Wu, DaWei; Qin, WeiDong; Xing, ChunYan

    2016-01-01

    Hypoxia-induced pulmonary arterial hypertension (HPAH) is a refractory disease characterized by increased proliferation of pulmonary vascular smooth cells and progressive pulmonary vascular remodeling. The level of nitric oxide (NO), a potential therapeutic vasodilator, is low in PAH patients. L-arginine can be converted to either beneficial NO by nitric oxide synthases or to harmful urea by arginase. In the present study, we aimed to investigate whether an arginase inhibitor, S-(2-boronoethyl)-L-cysteine ameliorates HPAH in vivo and vitro. In a HPAH mouse model, we assessed right ventricle systolic pressure (RVSP) by an invasive method, and found that RSVP was elevated under hypoxia, but was attenuated upon arginase inhibition. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions, and their proliferative capacity was determined by cell counting and flow cytometry. The levels of cyclin D1, p27, p-Akt, and p-ERK were detected by RT-PCR or Western blot analysis. Compared to hypoxia group, arginase inhibitor inhibited HPASMCs proliferation and reduced the levels of cyclin D1, p-Akt, p-ERK, while increasing p27 level. Moreover, in mouse models, compared to control group, hypoxia increased cyclin D1 expression but reduced p27 expression, while arginase inhibitor reversed the effects of hypoxia. Taken together, these results suggest that arginase plays an important role in increased proliferation of HPASMCs induced by hypoxia and it is a potential therapeutic target for the treatment of pulmonary hypertensive disorders.

  15. Pulmonary arterial hypertension (ascites syndrome) in broilers: a review.

    PubMed

    Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B

    2013-01-01

    Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary

  16. Current therapeutics and practical management strategies for pulmonary arterial hypertension.

    PubMed

    Agarwal, Richa; Gomberg-Maitland, Mardi

    2011-08-01

    Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary vasculature and is characterized by a progressive rise in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. Currently, 3 classes of drugs are approved for the treatment of PAH based on results from small short-term clinical trials-prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. The pharmacologic management of PAH is rapidly evolving as newer therapeutic targets that stabilize or reverse pulmonary vascular disease and target right ventricular function are being sought and as clinical practice patterns shift in favor of earlier diagnosis and aggressive treatment. This manuscript will review the practical management aspects of currently approved PAH treatments and briefly discuss combination therapy and novel pharmacologic targets. In addition, the treatment of acute right ventricular failure and evidence (or lack thereof) for therapies in non-PAH pulmonary hypertension, such as pulmonary hypertension from left side of the heart disease, are addressed.

  17. The predictive value of arterial stiffness on major adverse cardiovascular events in individuals with mildly impaired renal function

    PubMed Central

    Han, Jie; Wang, Xiaona; Ye, Ping; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei

    2016-01-01

    Objectives Despite growing evidence that arterial stiffness has important predictive value for cardiovascular disease in patients with advanced stages of chronic kidney disease, the predictive significance of arterial stiffness in individuals with mildly impaired renal function has not been established. The aim of this study was to evaluate the predictive value of arterial stiffness on cardiovascular disease in this specific population. Materials and methods We analyzed measurements of arterial stiffness (carotid–femoral pulse-wave velocity [cf-PWV]) and the incidence of major adverse cardiovascular events (MACEs) in 1,499 subjects from a 4.8-year longitudinal study. Results A multivariate Cox proportional-hazard regression analysis showed that in individuals with normal renal function (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m2), the baseline cf-PWV was not associated with occurrence of MACEs (hazard ratio 1.398, 95% confidence interval 0.748–2.613; P=0.293). In individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2), a higher baseline cf-PWV level was associated with a higher risk of MACEs (hazard ratio 2.334, 95% confidence interval 1.082–5.036; P=0.031). Conclusion Arterial stiffness is a moderate and independent predictive factor for MACEs in individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2). PMID:27621605

  18. Habitual cocoa intake reduces arterial stiffness in postmenopausal women regardless of intake frequency: a randomized parallel-group study

    PubMed Central

    Okamoto, Takanobu; Kobayashi, Ryota; Natsume, Midori; Nakazato, Koichi

    2016-01-01

    Arterial stiffness is substantially higher in postmenopausal than in premenopausal women. Daily cocoa intake has been shown to reduce central arterial stiffness in health adults, regardless of age; however, the effect of cocoa-intake frequency on arterial stiffness in postmenopausal women remains unclear. Therefore, the purpose of this study was to investigate the effects of cocoa-intake frequency on arterial stiffness in postmenopausal women. A total of 26 postmenopausal women (mean age ± standard deviation 64±12 years) were randomly assigned to two groups with different cocoa-intake frequencies: one group ingested 17 g of cocoa once daily except on Sundays (every-day group, n=13), and the other ingested 17 g of cocoa twice daily every other day (every-other-day group, n=13). These intake regimens were maintained in both groups for 12 weeks. Carotid–femoral pulse-wave velocity and femoral–ankle pulse-wave velocity were measured in both groups at baseline and again at the end of the 12-week study period. Compared to baseline, both pulse-wave velocities had significantly decreased after the 12-week study period in both groups (P<0.05). However, no significant difference in degree of change was observed between the two groups. Although this study did not include a sedentary control group, these results suggest that regardless of frequency, habitual cocoa intake reduces central and peripheral arterial stiffness in postmenopausal women. PMID:27881914

  19. Habitual cocoa intake reduces arterial stiffness in postmenopausal women regardless of intake frequency: a randomized parallel-group study.

    PubMed

    Okamoto, Takanobu; Kobayashi, Ryota; Natsume, Midori; Nakazato, Koichi

    2016-01-01

    Arterial stiffness is substantially higher in postmenopausal than in premenopausal women. Daily cocoa intake has been shown to reduce central arterial stiffness in health adults, regardless of age; however, the effect of cocoa-intake frequency on arterial stiffness in postmenopausal women remains unclear. Therefore, the purpose of this study was to investigate the effects of cocoa-intake frequency on arterial stiffness in postmenopausal women. A total of 26 postmenopausal women (mean age ± standard deviation 64±12 years) were randomly assigned to two groups with different cocoa-intake frequencies: one group ingested 17 g of cocoa once daily except on Sundays (every-day group, n=13), and the other ingested 17 g of cocoa twice daily every other day (every-other-day group, n=13). These intake regimens were maintained in both groups for 12 weeks. Carotid-femoral pulse-wave velocity and femoral-ankle pulse-wave velocity were measured in both groups at baseline and again at the end of the 12-week study period. Compared to baseline, both pulse-wave velocities had significantly decreased after the 12-week study period in both groups (P<0.05). However, no significant difference in degree of change was observed between the two groups. Although this study did not include a sedentary control group, these results suggest that regardless of frequency, habitual cocoa intake reduces central and peripheral arterial stiffness in postmenopausal women.

  20. Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension

    PubMed Central

    Hao, Mingwen; Li, Miaomiao; Li, Wenjun

    2016-01-01

    Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal-3−/− mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal-3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal-3 in wild type murine pulmonary arteries. Gal-3 deletion reduced the hypoxia-induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal-3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal-3 inhibition alleviated the hypoxia-induced inflammatory response in HPAECs, including tumor necrosis factor-α and interleukin-1 secretion, expression of intercellular adhesion molecule-1 and adhesion of THP-1 monocytes. Gal-3 inhibition also reduced hypoxia-induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal-3 inhibition suppressed HPASMC switching from a ‘contractile’ to a ‘synthetic’ phenotype. In conclusion, Gal-3 serves a fundamental role in hypoxia-induced PAH, and inhibition of Gal-3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH. PMID:27959409

  1. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension.

    PubMed

    Meyer, F J; Lossnitzer, D; Kristen, A V; Schoene, A M; Kübler, W; Katus, H A; Borst, M M

    2005-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.

  2. [Pediatric pulmonary hypertension and pulmonary arterial hypertension secondary to congenital heart diseases].

    PubMed

    Olguntürk, Rana

    2010-08-01

    Causes of pulmonary arterial hypertension (PAH) are similar in adults and children. The main difference is that PAH secondary to congenital heart diseases, is the predominant cause in pediatric patients. Persistent pulmonary hypertension of the newborn shows completely different clinical course and pathophysiological mechanisms. It is usually seen in full term babies with a high morbidity and mortality rate. Improved prognosis has been reported with inhaled nitric oxide (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in well equipped and experienced newborn centers. Primary pulmonary hypertension and familial pulmonary hypertension are rare in pediatric age group because the diagnosis is initially made in adolescence. The incidence of PAH secondary to congenital heart disease is estimated as 1.6 - 12.5 case/million/year. Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left to right shunts are the main group who develop pulmonary vascular disease if not treated in the early infancy. Some cyanotic congenital heart diseases are also the causes of PAH. The best treatment of patients at risk for the development of pulmonary vascular disease is prevention by early surgical elimination of defects or repairing the anatomy. Treatment options with vasodilating agents like NO, prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor antagonists are used to improve survival and quality of life. Heart lung or bilateral lung transplantation is the only surgical option for many of these patients. Results of national and international registries will bring valuable epidemiological and prognostic perspectives to pediatric PAH.

  3. [CHANGES OF CAROTID AND VERTEBRAL ARTERIES IN PATENTS WITH ARTERIAL HYPERTENSION AND HEPATOBILIARY PATHOLOGY].

    PubMed

    Polyakov, V Ya; Nikolaev, Yu A; Pegova, S V; Matsievskaya, T R; Obukhov, I V

    2016-01-01

    The study included 1172 patients (410 men and 762 women) at the mean age of 60.3 ± 10.4 years with grade I-II (stage I-II) arterial hypertension (AH) admitted to the clinic of Institute of Experimental Medicine. The patients were divided into 2 groups based on the results of clinical and laboratory diagnostics. Group 1 (n = 525) included patients with AH and hepatobiliary system (HBS) diseases, group 2 (n = 647) patients with AH without HBS diseases. The patients group 1 had a thicker intima-media complex of carotid arteries, higher peak systolic bloodflow rate in the internal and vertebral carotid arteries, more pronounced coiling of internal carotid arteries than patients of group 2. Patients with AH and HBS diseases exhibited correlation between bloodflow rate in external carotid arteries and atherogenicity coefficient. Duplex scanning of neck vessels of in patients with AH without HBS diseases revealed peculiar changes of the intima-media thickness and hemodynamically significant changes of the blood flow in the internal carotid arteries that may be of prognostic value in this nosological syntropy and require the personified approach to diagnostics, treatment, and prevention of these conditions.

  4. Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors

    PubMed Central

    Howard, Luke S.; Tzoulaki, Ioanna; Gin-Sing, Wendy; Grapsa, Julia; Wilkins, Martin R.; Davies, Rachel J.; Nihoyannopoulos, Petros; Connolly, Susan B.; Gibbs, J. Simon R.

    2014-01-01

    Abstract The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH–No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH–No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH–No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH–No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH. PMID:25610602

  5. Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

    PubMed

    Charalampopoulos, Athanasios; Howard, Luke S; Tzoulaki, Ioanna; Gin-Sing, Wendy; Grapsa, Julia; Wilkins, Martin R; Davies, Rachel J; Nihoyannopoulos, Petros; Connolly, Susan B; Gibbs, J Simon R

    2014-12-01

    The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH.

  6. Factors associated with arterial stiffness in children aged 9-10 years

    PubMed Central

    Batista, Milena Santos; Mill, José Geraldo; Pereira, Taisa Sabrina Silva; Fernandes, Carolina Dadalto Rocha; Molina, Maria del Carmen Bisi

    2015-01-01

    OBJECTIVE To analyze the factors associated with stiffness of the great arteries in prepubertal children. METHODS This study with convenience sample of 231 schoolchildren aged 9-10 years enrolled in public and private schools in Vitória, ES, Southeastern Brazil, in 2010-2011. Anthropometric and hemodynamic data, blood pressure, and pulse wave velocity in the carotid-femoral segment were obtained. Data on current and previous health conditions were obtained by questionnaire and notes on the child’s health card. Multiple linear regression was applied to identify the partial and total contribution of the factors in determining the pulse wave velocity values. RESULTS Among the students, 50.2% were female and 55.4% were 10 years old. Among those classified in the last tertile of pulse wave velocity, 60.0% were overweight, with higher mean blood pressure, waist circumference, and waist-to-height ratio. Birth weight was not associated with pulse wave velocity. After multiple linear regression analysis, body mass index (BMI) and diastolic blood pressure remained in the model. CONCLUSIONS BMI was the most important factor in determining arterial stiffness in children aged 9-10 years. PMID:25902563

  7. Treating Heart Failure with Preserved Ejection Fraction Related to Arterial Stiffness. Can we Kill Two Birds With One Stone?

    PubMed

    Athyros, Vasilios G; Pagourelias, Efstathios D; Gossios, Thomas D; Vasilikos, Vasilios G

    2015-01-01

    Heart failure with preserved ejection fraction (HFpEF). Arterial hypertension (AH), arterial stiffness (AS), older age, and female gender are the main determinants of HFpEF, but several cardiac or extra-cardiac pathologies are also possible causes. The combined ventricular-vascular stiffening (abnormal left atrium-left ventricle coupling related to AS) is the main contributor of the increased prevalence of HFpEF in elderly persons, particularly elderly women, and in younger persons with AH. The hospitalization and mortality rates of HFpEF are similar to those of heart failure with reduced EF (HFrEF). However, although the prognosis of HFrEF has been substantially improved during the last 2 decades, the effective treatment of HFpEF remains an unmet need. Regimens effective in HFrEF have no substantial effect on HFpEF, because of different pathophysiologies of the 2 syndromes. Pipeline drugs seem promising, but it will take some years before they are commercially available. Aggressive treatment of noncardiac comorbidities seems to be the only option at hand. Treatment of anaemia, sleep disorders, chronic kidney disease (CKD), non-alcoholic fatty liver (NAFLD), atrial fibrillation, diabetes, and careful use of diuretics to reduce preload are effective to some degree. Statin treatment, despite the presence of dyslipidaemia, deserves special attention because it has been proven, mainly in small studies or post hoc analyses of trials, that it offers a substantial improvement in quality of life and a reduction in mortality rates. We need to urgently utilize these recourses to relieve a considerable part of the general population suffering from HFpEF, a deadly disease.

  8. Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

    PubMed

    Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G

    2014-02-01

    Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

  9. miR-223 reverses experimental pulmonary arterial hypertension.

    PubMed

    Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien

    2015-09-15

    Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH.

  10. The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension.

    PubMed

    Kherbeck, Nada; Tamby, Mathieu C; Bussone, Guillaume; Dib, Hanadi; Perros, Frederic; Humbert, Marc; Mouthon, Luc

    2013-02-01

    Pulmonary arterial hypertension is characterized by a remodeling of pulmonary arteries with endothelial cell, fibroblast, and vascular smooth muscle cell activation and proliferation. Since pulmonary arterial hypertension occurs frequently in autoimmune conditions such as systemic sclerosis, inflammation and autoimmunity have been suspected to play a critical role in both idiopathic pulmonary arterial hypertension and systemic sclerosis-associated pulmonary arterial hypertension. High levels of pro-inflammatory cytokines such as interleukin-1 and interleukin-6, platelet-derived growth factor, or macrophage inflammatory protein 1 have been found in lung samples of patients with pulmonary arterial hypertension, along with inflammatory cell infiltrates mainly composed of macrophages and dendritic cells, T and B lymphocytes. In addition, circulating autoantibodies are found in the peripheral blood of patients. Thus, autoimmunity and inflammation probably play a role in the development of pulmonary arterial hypertension. In this setting, it would be important to set-up new experimental models of pulmonary arterial hypertension, in order to define novel therapeutics that specifically target immune disturbances in this devastating condition.

  11. Reduced hemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension

    PubMed Central

    Bellofiore, Alessandro; Dinges, Eric; Naeije, Robert; Mkrdichian, Hamorabi; Beussink-Nelson, Lauren; Bailey, Melissa; Cuttica, Michael J.; Sweis, Ranya; Runo, James R.; Keevil, Jon G.; Francois, Christopher J.; Shah, Sanjiv J.; Chesler, Naomi C.

    2016-01-01

    Objective Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterization with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Methods Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterization and Doppler echocardiography at rest and during incremental exercise, and cardiac magnetic resonance imaging (MRI) at rest. Measurements at rest included basic hemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA). Results In PAH patients, the proximal PAs were significantly stiffer at maximum exercise (ZC = 2.31 ± 0.38 vs. 1.33 ± 0.15 mmHg min/ml/m2 at rest; p=0.003) and PA compliance was decreased (CPA = 0.88 ± 0.10 vs. 1.32 ± 0.17 mL/mmHg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (1.00 ± 0.07 at vs. 0.67 ± 0.05 s; p<10−6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited CPA reduction at maximum exercise. Conclusions In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor hemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated. PMID:27566296

  12. Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. PMID:23937620

  13. Correlation of ascending aorta elasticity and the severity of coronary artery stenosis in hypertensive patients with coronary heart disease assessed by M-mode and tissue Doppler echocardiography.

    PubMed

    Lu, Qixiu; Liu, Houlin

    2015-03-01

    The main objective of this study is to investigate the relationship between ascending aorta elasticity and the severity of coronary artery stenosis in essential hypertensive patients with coronary heart disease (CHD) using M-mode and tissue Doppler echocardiography. A total of 184 hypertensive patients with CHD were enrolled. Patients were divided into three groups based on the severity of coronary stenosis measured by coronary arteriography (CAG): slight stenosis (group 1), moderate stenosis (group 2) and serious stenosis (group 3). M-mode and tissue Doppler echocardiography were performed, and elasticity indexes of ascending aorta including stiffness index, distensibility index, and S wave speed of anterior wall were calculated and correlated with the severity of coronary stenosis. Ascending aorta stiffness index was increased, whereas distensibility index and S wave speed of anterior wall were decreased in moderate and severe stenosis groups compared with slight stenosis group (P < 0.01). Elasticity indexes change in a stepwise pattern with the narrowness of coronary artery, and there was a significant correlation between aortic elasticity and severity of coronary artery by Pearson correlation analysis (P < 0.01). Elasticity indexes of ascending aorta correlate well with severity of coronary stenosis. Elasticity indexes of ascending aorta can serve as predictors for coronary arterial lesion in hypertensive patients.

  14. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension.

    PubMed

    Yang, Zhen; Chen, Long; Su, Chen; Xia, Wen-Hao; Wang, Yan; Wang, Jie-Mei; Chen, Fei; Zhang, Yuan-Yuan; Wu, Fang; Xu, Shi-Yue; Zhang, Xiao-Lin; Tao, Jun

    2010-01-01

    Endothelial dysfunction is related to reduced arterial elasticity in patients with essential hypertension. Circulating endothelial progenitor cells (EPCs), an important endogenous repair approach for endothelial injury, is altered in hypertensive patients. However, the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity has not been reported. The purpose of this study is to investigate the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity. We measured the artery elasticity profiles including brachial-ankle PWV (baPWV) and C1 large and C2 small artery elasticity indices in patients with essential hypertension (n = 20) and age-matched normotensive subjects (n = 21). The number and activity of circulating EPCs isolated from peripheral blood were determined. Compared to normotensive subjects, the patients with hypertension exhibited decreased C1 large and C2 small artery elasticity indices, as well as increased baPWV. The number of circulating EPCs did not differ between the two groups. The migratory and proliferative activities of circulating EPCs in hypertensive patients were lower than those in normotensive subjects. Both proliferatory and migratory activities of circulating EPCs closely correlated with arterial elasticity profiles, including baPWV and C1 large and C2 small artery elasticity indices. Multivariate analysis identified both proliferative and migratory activities of circulating EPCs as independent predictors of the artery elasticity profiles. The present study demonstrates for the first time that impaired activity of circulating EPCs is associated with reduced arterial elasticity in patients with hypertension. The fall in endogenous repair capacity of vascular endothelium may be involved in the pathogenesis of hypertension-related vascular injury.

  15. Versican accumulates in vascular lesions in pulmonary arterial hypertension

    PubMed Central

    Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N.; Tran-Lundmark, Karin

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID:27683612

  16. Acute effects of submaximal endurance training on arterial stiffness in healthy middle- and long-distance runners.

    PubMed

    Müller, Jan; Wilms, Michael; Oberhoffer, Renate

    2015-05-01

    Measures of arterial stiffness are indicators for cardiovascular health and predictors of cardiovascular events. Arterial stiffness is responsive to acute physiologic stressors such as exercise. However, the acute effects of intensive exercise and recovery on arterial stiffness are controversial. Thirty-seven healthy middle- and long-distance runners (33 men, mean age 26.5±6.6 years) underwent evaluation of their cardiovascular stiffness at rest, after a 15-minute warm-up, immediately after vigorous running 3 km at the pace of their 10-km personal best, and finally 30 minutes after terminating their workout. Peripheral and central systolic blood pressure, as well as augmentation index and pulse wave velocity (PWV), increased during exercise in comparison to baseline (P<.001, general linear model). Thirty minutes after terminating the workout, a drop in peripheral blood pressure (P<.001), central blood pressure (P<.001), and PWV (P=.001) below baseline was observed. Therefore, the authors found that exercise of either moderate or vigorous intensity causes a temporary increase in arterial stiffness in middle- and long-distance runners.

  17. [Ultrastructure of the intima of human pial arteries in arterial hypertension].

    PubMed

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Ultrastructure of the intima of human pial arteries obtained from 5 male cadavers of practically healthy individuals and from 8 cadavers of the patients with the intravitally diagnosed grade I arterial hypertension (AH) was studied by scanning and transmission electron microscopy. AH was found to be associated with the remodeling of the intimal structural elements in the pial arteries. In most arteries, the changes were detected in the microrelief of the luminal surface and in the permeability of the vascular endothelial lining and of the subendothelial layer. During this remodeling, some endothelial cells were found in the state of structural and functional adaptation to the elevated arterial pressure, while the others were undergoing the dystrophic changes. The latter include the cells containing lipid inclusions, as well as the endothelial cells presumably in the state of apoptosis. The destruction of the intercellular junctions, the disturbances in the endothelium permeability contributed to the development of subendothelial layer edema, resulting in its significant thickening. This layer became looser and contained abundant collagen fibrils.

  18. Persistent pulmonary artery hypertension in patients undergoing balloon mitral valvotomy

    PubMed Central

    Nair, Krishna Kumar Mohanan; Pillai, Harikrishnan Sivadasan; Titus, Thomas; Varaparambil, Ajitkumar; Sivasankaran, Sivasubramonian; Krishnamoorthy, Kavassery Mahadevan; Namboodiri, Narayanan; Sasidharan, Bijulal; Thajudeen, Anees; Ganapathy, Sanjay; Tharakan, Jaganmohan

    2013-01-01

    Pulmonary artery pressure (PAP) is known to regress after successful balloon mitral valvotomy (BMV). Data of persistent pulmonary artery hypertension (PPAH) following BMV is scarce. We analyzed the clinical, echocardiographic, and hemodynamic data of 701 consecutive patients who have undergone successful BMV in our institute from 1997 to 2003. Data of 287 patients who had PPAH (defined by pulmonary artery systolic pressure [PASP] of ≥ 40 mmHg at one year following BMV) were compared to the data of 414 patients who did not have PPAH. Patients who had PPAH were older (39.9 ± 9.9 years vs. 29.4 ± 10.1; P < 0.001). They had higher prevalence of atrial fibrillation (AF; 21.9 vs. 12.1%, P < 0.05), moderate or severe pulmonary artery hypertension (PAH) defined as PASP more than 50 mmHg (43.5 vs. 33.8%, P = 0.00), anatomically advanced mitral valve disease as assessed by Wilkin's echocardiographic score > 8 (33.7 vs. 23.2%, P < 0.001), and coexistent aortic valve disease (45.6 vs. 37.9%, P < 0.001) at the baseline. Those patients with PPAH had comparatively lower immediate postprocedural mitral valve area (MVA). On follow-up of more than five years, the occurrence of restenosis (39.3 vs. 10.1%, P = 0.000), new onset heart failure (14% vs. 4%, P < 0.05) and need for reinterventions (9.5% vs. 2.8%, P < 0.05) were higher in the PPAH group. Patients with PPAH were older, sicker, and had advanced rheumatic mitral valve disease. They had higher incidence of restenosis, new onset heart failure, and need for reinterventions on long term follow-up. PPAH represents an advanced stage of rheumatic valve disease and indicates chronicity of the disease, which may be the reason for the poorer prognosis of these patients. Patients with PPAH requires intense and more frequent follow-up. PMID:24015345

  19. Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: a systematic review and meta-analysis

    PubMed Central

    van Sloten, Thomas T; Protogerou, Athanase D; Henry, Ronald MA; Schram, Miranda T; Launer, Lenore J; Stehouwer, Coen DA

    2017-01-01

    Arterial stiffness may be a cause of cerebral small vessel disease and cognitive impairment. We therefore performed a systematic review and meta-analysis of studies on the association between stiffness, cerebral small vessel disease and cognitive impairment. For the associations between stiffness (i.e. carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), carotid stiffness and pulse pressure) on the one hand and cerebral small vessel disease and cognitive impairment on the other, we identified 23 (n=15,666/22 cross-sectional/3 longitudinal) and 41 studies (n=57,671/30 cross-sectional/15 longitudinal), respectively. Pooled analyses of cross-sectional studies showed that greater stiffness was associated with markers of cerebral small vessel disease with odds ratios, per +1 SD, of 1.29 to 1.32 (P<.001). Studies on cognitive impairment could not be pooled due to large heterogeneity. Some (but not all) studies showed an association between greater stiffness and cognitive impairment, and the strength of this association was relatively weak. The present study supports the hypothesis that greater arterial stiffness is a contributor to microvascular brain disease. PMID:25827412

  20. Influence of Distal Resistance and Proximal Stiffness on Hemodynamics and RV Afterload in Progression and Treatments of Pulmonary Hypertension: A Computational Study with Validation Using Animal Models

    PubMed Central

    Su, Zhenbi; Tan, Wei; Shandas, Robin; Hunter, Kendall S.

    2013-01-01

    We develop a simple computational model based on measurements from a hypoxic neonatal calf model of pulmonary hypertension (PH) to investigate the interplay between vascular and ventricular measures in the setting of progressive PH. Model parameters were obtained directly from in vivo and ex vivo measurements of neonatal calves. Seventeen sets of model-predicted impedance and mean pulmonary arterial pressure (mPAP) show good agreement with the animal measurements, thereby validating the model. Next, we considered a predictive model in which three parameters, PVR, elastic modulus (EM), and arterial thickness, were varied singly from one simulation to the next to study their individual roles in PH progression. Finally, we used the model to predict the individual impacts of clinical (vasodilatory) and theoretical (compliance increasing) PH treatments on improving pulmonary hemodynamics. Our model (1) displayed excellent patient-specific agreement with measured global pulmonary parameters; (2) quantified relationships between PVR and mean pressure and PVS and pulse pressure, as well as studiying the right ventricular (RV) afterload, which could be measured as a hydraulic load calculated from spectral analysis of pulmonary artery pressure and flow waves; (3) qualitatively confirmed the derangement of vascular wall shear stress in progressive PH; and (4) established that decreasing proximal vascular stiffness through a theoretical treatment of reversing proximal vascular remodeling could decrease RV afterload. PMID:24367392

  1. Optimising the management of pulmonary arterial hypertension patients: emergency treatments.

    PubMed

    Delcroix, M; Naeije, R

    2010-09-01

    Pulmonary arterial hypertension (PAH) is a rare and potentially fatal disease whose management is usually restricted to a few specialised centres. As patients do not necessarily live in the neighbourhood of these centres, daily care and emergencies have to be delegated to first and second lines. Treatment guidelines do not usually provide recommendations for acute emergency situations as evidence is scarce. This short review provides a description of our therapeutic protocols based on available data. A model of transmural organisation of care for PAH patients, currently applied in Belgium, is described. Thereafter, based on an analysis of the reasons of death in the PAH population, a review of the main emergencies is provided. Cardiac arrest and resuscitation, decompensated right heart failure, respiratory failure, arrhythmia, pericardial effusion, haemoptysis, surgery and drug-related adverse events will be discussed successively. Case reports showing the precariousness of PAH patients will enforce our thesis of the need for optimal patient management organisation.

  2. The role of endothelin-1 in pulmonary arterial hypertension

    PubMed Central

    Chester, Adrian H.; Yacoub, Magdi H.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH. PMID:25405182

  3. Immune and Inflammatory Mechanisms in Pulmonary Arterial Hypertension

    PubMed Central

    El Chami, Hala; Hassoun, Paul M.

    2012-01-01

    Altered immunity and inflammation are increasingly recognized features of pulmonary arterial hypertension (PAH). This is suggested by infiltration of various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled pulmonary vessels, and the presence of circulating chemokines and cytokines. In certain diseases associated with PAH, increased expression of growth and transcriptional (e.g., Nuclear Factor of Activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), appear to contribute directly to recruitment of inflammatory cells in remodeled vessels, and may potentially serve as specific therapeutic targets. This section provides an overview of inflammatory pathways highlighting their potential role in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy. PMID:23009917

  4. Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension.

    PubMed

    Bonnet, Sebastien; Provencher, Steeve; Guignabert, Christophe; Perros, Frédéric; Boucherat, Olivier; Schermuly, Ralph Theo; Hassoun, Paul M; Rabinovitch, Marlene; Nicolls, Mark R; Humbert, Marc

    2016-09-20

    Despite important advances in its therapeutic management, pulmonary arterial hypertension (PAH) remains an incurable disease. Although numerous drugs exhibited beneficial effects in preclinical settings, only few have reached clinical trial phases, highlighting the challenges of translating preclinical investigations into clinical trials. Potential reasons for delayed PAH drug development may include the inherent limitations of the currently available animal and in vitro models, potential lack of appropriate standardization of the experimental design, regulatory agencies requirements, competing clinical trials and insufficient funding. Although this is not unique to PAH, there is urgency for reducing the number of false positive signals in preclinical studies and optimizing the development of innovative therapeutic targets through performance of clinical trials based on more robust experimental data. The current review discusses the challenges and opportunities in preclinical research to foster drug development in PAH.

  5. [Experience with imatinib to treat pulmonary arterial hypertension].

    PubMed

    García Hernández, Francisco José; Castillo Palma, María Jesús; González León, Rocío; Garrido Rasco, Rocío; Ocaña Medina, Celia; Sánchez Román, Julio

    2008-12-01

    Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.

  6. Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension

    PubMed Central

    Al-Naamani, Nadine; Palevsky, Harold I.; Lederer, David J.; Horn, Evelyn M.; Mathai, Stephen C.; Roberts, Kari E.; Tracy, Russell P.; Hassoun, Paul M.; Girgis, Reda E.; Shimbo, Daichi; Post, Wendy S.

    2016-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction. Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods: We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results: Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions: In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865). PMID:26501464

  7. Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension.

    PubMed

    Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok

    2015-10-01

    Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

  8. Increased postflight carotid artery stiffness and inflight insulin resistance resulting from 6-mo spaceflight in male and female astronauts.

    PubMed

    Hughson, Richard L; Robertson, Andrew D; Arbeille, Philippe; Shoemaker, J Kevin; Rush, James W E; Fraser, Katelyn S; Greaves, Danielle K

    2016-03-01

    Removal of the normal head-to-foot gravity vector and chronic weightlessness during spaceflight might induce cardiovascular and metabolic adaptations related to changes in arterial pressure and reduction in physical activity. We tested hypotheses that stiffness of arteries located above the heart would be increased postflight, and that blood biomarkers inflight would be consistent with changes in vascular function. Possible sex differences in responses were explored in four male and four female astronauts who lived on the International Space Station for 6 mo. Carotid artery distensibility coefficient (P = 0.005) and β-stiffness index (P = 0.006) reflected 17-30% increases in arterial stiffness when measured within 38 h of return to Earth compared with preflight. Spaceflight-by-sex interaction effects were found with greater changes in β-stiffness index in women (P = 0.017), but greater changes in pulse wave transit time in men (P = 0.006). Several blood biomarkers were changed from preflight to inflight, including an increase in an index of insulin resistance (P < 0.001) with a spaceflight-by-sex term suggesting greater change in men (P = 0.034). Spaceflight-by-sex interactions for renin (P = 0.016) and aldosterone (P = 0.010) indicated greater increases in women than men. Six-month spaceflight caused increased arterial stiffness. Altered hydrostatic arterial pressure gradients as well as changes in insulin resistance and other biomarkers might have contributed to alterations in arterial properties, including sex differences between male and female astronauts.

  9. An international physician survey of pulmonary arterial hypertension management

    PubMed Central

    Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H.; Lang, Irene

    2016-01-01

    Abstract We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients’ New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID:27683611

  10. Review of bosentan in the management of pulmonary arterial hypertension

    PubMed Central

    Gabbay, Eli; Fraser, John; McNeil, Keith

    2007-01-01

    The dual endothelin receptor antagonist, bosentan, is an orally active therapy, which is effective in the treatment of pulmonary arterial hypertension (PAH). This review critically appraises the evidence for the efficacy of bosentan in idiopathic and familial PAH, in PAH associated with connective tissue disease and in PAH which may develop in association with other conditions. Data from the pivotal placebo controlled studies and their open labeled extensions as well as long term survival and quality of life data is presented. Data is also presented on the potential benefit of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension. The safety and tolerability of bosentan as well as drug interactions are discussed. Dosage recommendations in adults and pediatrics are presented. An algorithm is provided to guide the reader in monitoring potential increases in alanine and aspartate transaminase levels that may occur with bosentan use and the dose adjustments that are recommended as a result of any increase in the levels of these enzymes are shown. Finally, the role of bosentan as part of combination therapy in PAH is examined. PMID:18200808

  11. [Successful pregnancy in a patient with idiopathic pulmonary arterial hypertension. Case report].

    PubMed

    Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János

    2016-04-10

    Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken.

  12. [Etiology of endocrine arterial hypertensions: about a series of cases].

    PubMed

    Bouznad, Naima; El Mghari, Ghizlane; El Ansari, Nawal

    2016-01-01

    Arterial hypertensions (HTA) of endocrine origin are a rare cause of hypertension; HTA overall prevalence don't exceed 4% of hypertensive patients. Research interest in endocrine HTA is due to the severity of some life-threatening, potentially curable and reversible forms of HTA. The aim of our study was to determine the clinical, paraclinical, etiological and therapeutic profile of secondary HTA of endocrine origin in patients treated in endocrinology department at the University Hospital Mohamed VI in Marrakech. We conducted a prospective, descriptive study spanned 4 years, enrolling 45 patients with endocrine HTA. The average age was 44.89 years, with a clear predominance of women (sex ratio 0.49). Etiology of endocrine HTA was dominated by pheochromocytoma (17 cases), hypercorticism (11 cases) and acromegaly (8 cases). HTA were paroxysmal in 24.4%. HTA were immediately classified as grade 3 severe in 40% of cases. HTA were complicated by heart disease in 24% of cases and by renal disease in 20% of cases. Curative treatment cleared up HTA in 60% of cases (27 cases). The diagnosis of secondary endocrine HTA is sometimes difficult because of the lack of clinical specificity. It is not unusual for HTA to be the only manifestation of the disease. In our study we noted the paroxysmal and severe nature of HTA. The potentially curable nature of HTA in more than two thirds of cases, demostrates the importance of early diagnosis of each severe HTA resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

  13. Association between arterial stiffness and left ventricular diastolic function in relation to gender and age

    PubMed Central

    Kim, Hack-Lyoung; Lim, Woo-Hyun; Seo, Jae-Bin; Chung, Woo-Young; Kim, Sang-Hyun; Kim, Myung-A.; Zo, Joo-Hee

    2017-01-01

    Abstract Left ventricular (LV) diastolic dysfunction and subsequent overt heart failure are more prevalent in elderly women. Close interaction between arterial stiffness and LV morphology/function has been reported. The aim of this study was to investigate whether there is an age- and gender-dependent relationship between arterial stiffness and LV diastolic function. A total of 819 subjects (58.6 ± 13.3 years, 50.2% men) without structural heart disease (LV ejection fraction ≥50%) were retrospectively analyzed. All participants underwent transthoracic echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement on the same day. The association of baPWV with septal e′ velocity and average E/e′ was assessed. In the total study subjects, baPWV was negatively correlated with septal e′ velocity (r = 0.383, P < 0.001), and positively correlated with E/e′ (r = −0.266, P < 0.001). These linear correlations remained significant even after stratificaion of the study subjects by age (<65 years vs ≥65 years) and genders (P < 0.05 for each). There were obvious differences in baPWV according to groups with normal LV diastolic function, intermediate profile and LV diastolic dysfunction in young (P = 0.010) and elderly (≥65 years) women (P < 0.001) and eldery men (P = 0.012) but not in elderly men (P = 0.270). There was a significant association of baPWV with septal e′ velocity (β = −0.258, P = 0.020) and E/e′ (β = 0.122, P = 0.030) in elderly women even after controlling for multiple clinical covariates. This independent association was not seen in younger women and men (P > 0.05 for each). In conclusion, baPWV was independently associated with septal e′ velocity and E/e′ in elderly women but not in younger women or men. The results of this study provide additional evidence that increased arterial stiffness plays an important role in the development of heart failure with

  14. Association between aerobic exercise training effects of serum adropin level, arterial stiffness, and adiposity in obese elderly adults.

    PubMed

    Fujie, Shumpei; Hasegawa, Natsuki; Kurihara, Toshiyuki; Sanada, Kiyoshi; Hamaoka, Takafumi; Iemitsu, Motoyuki

    2017-01-01

    Serum levels of adropin, which enhances endothelial cell release of nitric oxide (NO), are lower in obese patients. Although habitual aerobic exercise reduces arterial stiffness and adiposity, the relationship between these effects and circulating levels of adropin remains unclear. The purpose of this study was to determine if serum adropin level is associated with the effects of aerobic exercise training on arterial stiffness and adiposity in obese adults. In Experiment 1, we examined whether serum adropin levels are associated with cardiorespiratory fitness, carotid β-stiffness, plasma nitrite/nitrate (NOx) level, and abdominal visceral fat in 27 normal, 20 overweight, and 25 obese adults (age, 41-79 years). In Experiment 2, we examined the effects of an 8-week aerobic exercise training program on the relationship between serum adropin level and arterial stiffness or adiposity in 13 obese adults (age, 54-76 years). Serum adropin levels in normal, overweight, and obese adults negatively correlated with carotid β-stiffness and abdominal visceral fat, and positively correlated with plasma NOx level and cardiorespiratory fitness. After the 8-week exercise program, serum adropin levels in obese adults were elevated, and correlated with training-induced changes in carotid β-stiffness (r = -0.573, P < 0.05), plasma NOx level (r = 0.671, P < 0.05), and abdominal visceral fat (r = -0.585, P < 0.05). These findings suggest that the exercise training-induced increase in serum adropin may be related to the training effects of arterial stiffness and adiposity in obese adults.

  15. Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations

    PubMed Central

    Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

    2016-01-01

    Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype. PMID:27630060

  16. LTB4 activates pulmonary artery adventitial fibroblasts in pulmonary hypertension

    PubMed Central

    Jiang, Xinguo; Tamosiuniene, Rasa; Sung, Yon K.; Shuffle, Eric M.; Tu, Allen B.; Valenzuela, Antonia; Jiang, Shirley; Zamanian, Roham T.; Fiorentino, David F.; Voelkel, Norbert F.; Peters-Golden, Marc; Stenmark, Kurt R.; Chung, Lorinda; Rabinovitch, Marlene; Nicolls, Mark R.

    2015-01-01

    A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of the current study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast (HPAAF) proliferation, migration and differentiation in a dose-dependent manner through its cognate G-protein coupled receptor, BLT1. LTB4 activated HPAAF by up-regulating p38 MAPK as well as Nox4 signaling pathways. In an autoimmune model of PH, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation and attenuated PH development. This study uncovers a novel mechanism by which LTB4 further promotes PAH pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID:26558820

  17. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

    PubMed

    Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J

    1983-05-01

    The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity.

  18. Initial experience with tadalafil in pediatric pulmonary arterial hypertension.

    PubMed

    Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar

    2012-06-01

    This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p < 0.05) and pulmonary vascular resistance index (12.2 ± 7.0 vs 10.6 ± 7.2 Units/m(2); p < 0.05). Clinical improvement was noted for four patients treated with tadalafil as initial therapy. The side effect profiles were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.

  19. Prostanoid therapies in the management of pulmonary arterial hypertension

    PubMed Central

    LeVarge, Barbara L

    2015-01-01

    Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. PMID:25848300

  20. Pulmonary arterial hypertension in critically ill elderly patients

    PubMed Central

    Zhang, Yun-yun; Xu, Fan; Chu, Ming; Bi, Li-qing

    2017-01-01

    Objective: To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. Methods: We selected 122 cases admitted to the ICU, ages 60–93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient’s pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. Results: Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. Conclusions: A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis. PMID:28367167

  1. Endothelial GATA-6 deficiency promotes pulmonary arterial hypertension.

    PubMed

    Ghatnekar, Angela; Chrobak, Izabela; Reese, Charlie; Stawski, Lukasz; Seta, Francesca; Wirrig, Elaine; Paez-Cortez, Jesus; Markiewicz, Margaret; Asano, Yoshihide; Harley, Russell; Silver, Richard; Feghali-Bostwick, Carol; Trojanowska, Maria

    2013-06-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by pulmonary vasculopathy with elevation of pulmonary artery pressure, often culminating in right ventricular failure. GATA-6, a member of the GATA family of zinc-finger transcription factors, is highly expressed in quiescent vasculature and is frequently lost during vascular injury. We hypothesized that endothelial GATA-6 may play a critical role in the molecular mechanisms underlying endothelial cell (EC) dysfunction in PAH. Here we report that GATA-6 is markedly reduced in pulmonary ECs lining both occluded and nonoccluded vessels in patients with idiopathic and systemic sclerosis-associated PAH. GATA-6 transcripts are also rapidly decreased in rodent PAH models. Endothelial GATA-6 is a direct transcriptional regulator of genes controlling vascular tone [endothelin-1, endothelin-1 receptor type A, and endothelial nitric oxide synthase (eNOS)], pro-inflammatory genes, CX3CL1 (fractalkine), 5-lipoxygenease-activating protein, and markers of vascular remodeling, including PAI-1 and RhoB. Mice with the genetic deletion of GATA-6 in ECs (Gata6-KO) spontaneously develop elevated pulmonary artery pressure and increased vessel muscularization, and these features are further exacerbated in response to hypoxia. Furthermore, innate immune cells including macrophages (CD11b(+)/F4/80(+)), granulocytes (Ly6G(+)/CD45(+)), and dendritic cells (CD11b(+)/CD11c(+)) are significantly increased in normoxic Gata6-KO mice. Together, our findings suggest a critical role of endothelial GATA-6 deficiency in development and disease progression in PAH.

  2. Left main bronchus compression due to main pulmonary artery dilatation in pulmonary hypertension: two case reports.

    PubMed

    Jaijee, Shareen K; Ariff, Ben; Howard, Luke; O'Regan, Declan P; Gin-Sing, Wendy; Davies, Rachel; Gibbs, J Simon R

    2015-12-01

    Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are no reports in the literature of its occurrence in idiopathic pulmonary arterial hypertension. Compression in infants with congenital heart disease has been well described. We report 2 cases of tracheobronchial compression: first, an adult patient with idiopathic pulmonary arterial hypertension who presents with symptomatic left main bronchus compression, and second, an adult patient with Eisenmenger ventricular septal defect and right-sided aortic arch, with progressive intermedius and right middle lobe bronchi compression in association with enlarged pulmonary arteries.

  3. Effects of a nitrate-rich meal on arterial stiffness and blood pressure in healthy volunteers.

    PubMed

    Liu, Alex H; Bondonno, Catherine P; Croft, Kevin D; Puddey, Ian B; Woodman, Richard J; Rich, Lisa; Ward, Natalie C; Vita, Joseph A; Hodgson, Jonathan M

    2013-11-30

    An increase in nitrate intake can augment circulating nitrite and nitric oxide. This may lead to lower blood pressure and improved vascular function. Green leafy vegetables, such as spinach, are rich sources of nitrate. We aimed to assess the acute effects of a nitrate-rich meal containing spinach on arterial stiffness and blood pressure in healthy men and women. Twenty-six participants aged 38-69years were recruited to a randomized controlled cross-over trial. The acute effects of two energy-matched (2000kJ) meals, administered in random order, were compared. The meals were either high nitrate (220mg of nitrate derived from spinach [spinach]) or low nitrate [control]. Outcome measurements were performed pre-meal and at specific time points up to 210min post meal. Spinach resulted in an eightfold increase in salivary nitrite and a sevenfold increase in salivary nitrate concentrations from pre-meal (P<0.001) to 120min post meal. Spinach compared with control resulted in higher large artery elasticity index (P<0.001), and lower pulse pressure (P<0.001) and systolic blood pressure (P<0.001). Post meal carotid-femoral pulse wave velocity (P=0.07), augmentation index (P=0.63), small artery elasticity index (P=0.98) and diastolic blood pressure (P=0.13) were not significantly altered by spinach relative to control. Therefore, consumption of a nitrate-rich meal can lower systolic blood pressure and pulse pressure and increase large artery compliance acutely in healthy men and women. If sustained, these effects could contribute to better cardiovascular health.

  4. Infant Arterial Stiffness and Maternal Iron Status in Pregnancy: A UK Birth Cohort (Baby VIP Study)

    PubMed Central

    Alwan, Nisreen A.; Cade, Janet E.; McArdle, Harry J.; Greenwood, Darren C.; Hayes, Helen E.; Ciantar, Etienne; Simpson, Nigel A.B.

    2015-01-01

    Background In animal studies, iron deficiency during pregnancy has been linked to increased offspring cardiovascular risk. No previous population studies have measured arterial stiffness early in life to examine its association with maternal iron status. Objective This study aimed to examine the association between maternal iron status in early pregnancy with infant brachio-femoral pulse wave velocity (PWV). Methods The Baby VIP (Baby's Vascular Health and Iron in Pregnancy) study is a UK-based birth cohort which recruited 362 women after delivery from the Leeds Teaching Hospitals postnatal wards. Ferritin and transferrin receptor levels were measured in maternal serum samples previously obtained in the first trimester. Infant brachio-femoral PWV was measured during a home visit at 2–6 weeks. Results Iron depletion (ferritin <15 µg/l) was detected in 79 (23%) women in early pregnancy. Infant PWV (mean = 6.7 m/s, SD = 1.3, n = 284) was neither associated with maternal ferritin (adjusted change per 10 µg/l = 0.02, 95% CI: −0.01, 0.1), nor with iron depletion (adjusted change = −0.2, 95% CI: −0.6, 0.2). No evidence of association was observed between maternal serum transferrin receptor level and its ratio to ferritin with infant PWV. Maternal anaemia (<11 g/dl) at <20 weeks’ gestation was associated with a 1.0-m/s increase in infant PWV (adjusted 95% CI: 0.1, 1.9). Conclusion This is the largest study to date which has assessed peripheral PWV as a measure of arterial stiffness in infants. There was no evidence of an association between markers of maternal iron status early in pregnancy and infant PWV. PMID:25790854

  5. Racial and socioeconomic disparities in arterial stiffness and intima media thickness among adolescents

    PubMed Central

    Thurston, Rebecca C.; Matthews, Karen A.

    2010-01-01

    Racial and socioeconomic status (SES) disparities in cardiovascular disease (CVD) risk are well established among adults. However, little is known about disparities in CVD risk among adolescents, particularly considering indices of subclinical CVD. Our aim was to examine socioeconomic and racial disparities in subclinical CVD indices among adolescents. We hypothesized that African American and lower SES adolescents would show greater arterial stiffness and intima media thickness compared to Caucasian and higher SES adolescents, respectively. Participants were 81 African American and 78 Caucasian adolescents (mean age = 17.8) from two schools in Pittsburgh, PA, USA. Measures of subclinical CVD were pulse wave velocity and intima media thickness, as assessed by Doppler and B-mode ultrasound, respectively. SES indices included parental education, family income, family assets, subjective social status, and census-derived neighborhood SES. Hypotheses were evaluated in multiple linear regression models with the covariates age, gender, body mass index, and systolic blood pressure. Results indicated that African American adolescents were more often in low SES positions than Caucasians. When considered individually, racial and SES disparities in pulse wave velocity, and to a lesser extent, intima media thickness, were evident. When race and SES were considered together, high school education, low or medium income, and low neighborhood SES were associated with higher pulse wave velocity. Fewer assets were associated with higher intima media thickness. In conclusion, racial and SES disparities in indices of subclinical CVD were observed, with findings most pronounced for SES disparities in pulse wave velocity. This study extends previous findings in adults to adolescents, indicating that disparities in arterial stiffness and intima media thickness occur as early as adolescence. Efforts to reduce socioeconomic and racial disparities in CVD should target disparities early in

  6. Arterial stiffness is associated with left ventricular dysfunction in patients with rheumatoid arthritis.

    PubMed

    Ilter, Abdulselam; Kiris, Abdulkadir; Karkucak, Murat; Sahin, Mursel; Serdar, Omer Faruk; Ugan, Yunus

    2016-11-01

    Arterial stiffness (AS) has a detrimental effect on cardiovascular system particularly on left ventricle (LV). The aim of the study was to evaluate the impact of AS on LV functions in patients with rheumatoid arthritis (RA). Forty patients with RA and 25 age-sex matched control subjects (mean age 48.5 ± 6.3 vs. 45.1 ± 6.9 years, respectively, p = 0.06) were enrolled in study. AS was assessed by carotid-femoral pulse wave velocity (CF-PWV) and heart rate corrected augmentation index (AIx@75) measured by applanation tonometry (SphygmoCor). LV function was evaluated using tissue Doppler-derived myocardial performance index (MPI) from lateral mitral annulus. CF-PWV (28.3 ± 10.3 vs. 21.8 ± 9.3 m/s, p = 0.03), AIx@75 (10.2 ± 2.3 vs. 9.2 ± 1, %, p = 0.01) and MPI (0.46 ± 0.12 vs. 0.36 ± 0.1, p < 0.001) were significantly higher in patients with RA than in controls. LV MPI was found to be significantly positive correlated with CF-PWV, AIx@75, and ESR (r = 0.360, p = 0.005; r = 0.334, p = 0.009; r = 0.293, p = 0.023, respectively). Arterial stiffness parameters including CF-PWV and AIx@75 are associated with subclinical left ventricular dysfunction in patients with RA.

  7. [Arterial hypertension among adolescents in Rio de Janeiro: prevalence and association with physical activity and obesity].

    PubMed

    Corrêa-Neto, Victor Gonçalves; Sperandei, Sandro; Silva, Luis Aureliano Imbiriba; Maranhão-Neto, Geraldo de Albuquerque; Palma, Alexandre

    2014-06-01

    The scope of this study was to identify the prevalence of systemic arterial hypertension among adolescent students (aged 17-19 years) in the third and final year of high school in state schools in the municipality of Rio de Janeiro, and to investigate associations between systemic arterial hypertension and obesity and physical activity levels. Data on arterial pressure, body mass index and physical activity were gathered. The analysis included 854 individuals. Descriptive statistical analysis was applied to the sample, along with a Poisson regression model to determine the impact of the variables on the prevalence of systemic arterial hypertension. The prevalence of systemic arterial hypertension was 19.4%. Male sex, overweight and obesity presented significant positive associations with systemic arterial hypertension (p < 0.05), while physical activity was not shown to be significantly associated with systemic arterial hypertension (p > 0.05). The nature of these relationships should be interpreted in the light of reflection and not of passive labeling based on hegemonic concepts.

  8. Stiffness of the large arteries in individuals with and without Down syndrome

    PubMed Central

    Rodrigues, Anabel N; Coelho, Luan Cesar; Goncalves, Washington LS; Gouvea, Sonia Alves; Vasconcellos, Maria José Rossi; Cunha, Roberto S; Abreu, Glaucia R

    2011-01-01

    Background: Down syndrome is known to cause premature aging in several organ systems. However, it remains unclear whether this aging effect also affects the structure and function of the large arterial trunks. In this controlled study, the possibility of changes in the large arteries due to aging was evaluated in patients with Down syndrome. Methods: Eighty-two subjects of both genders were selected. The Down syndrome group had 41 active subjects consisting of 19 males and 22 females (mean age 21 ± 1, range 13–42 years) without cardiovascular complications and who did not use vasoactive drugs. The control group consisted of 41 healthy individuals without trisomy 21 of the same gender and age as the Down syndrome group and who did not use vasoactive medication. Carotid–femoral pulse wave velocity was obtained as an index of aortic stiffness using an automatic noninvasive method. Results: Individuals with Down syndrome had significantly lower blood pressure than those in the control group. Systolic blood pressure for the Down syndrome group and control group was 106 ± 2 mmHg vs 117 ± 2 mmHg (P < 0.001), respectively; diastolic blood pressure was 66 ± 2 mmHg vs 77 ± 2 mmHg (P < 0.001); and mean arterial pressure was 80 ± 1 mmHg vs 90 ± 1 mmHg (P < 0.001). Only age and systolic blood pressure were shown to correlate significantly with pulse wave velocity, but the slopes of the linear regression curves of these two variables showed no significant difference between the two study groups. Pulse wave velocity, which was initially significantly lower in the Down syndrome group (7.51 ± 0.14 m/s vs 7.84 ± 0.12 m/s; P <0.05), was similar between the groups after systolic blood pressure adjustment (7.62 ± 0.13 m/s vs 7.73 ± 0.13 m/s). Conclusion: Despite evidence in the literature that patients with Down syndrome undergo early aging, this process does not seem to affect the large arterial trunks, given that values of carotid-femoral pulse wave velocity were

  9. Effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness of female patients with metabolic syndrome

    PubMed Central

    Kang, Seol-Jung; Kim,, Eon-ho; Ko, Kwang-Jun

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness or female patients with metabolic syndrome. [Subjects and Methods] Subjects were randomly assigned to an exercise group (n=12) or a control group (n=11). Subjects in the exercise group performed aerobic exercise at 60–80% of maximum heart rate for 40 min 5 times a week for 12 weeks. The changes in metabolic syndrome risk factors, resting heart rate, physical fitness, and arterial stiffness were measured and analyzed before and after initiation of the exercise program to determine the effect of exercise. Arterial stiffness was assessed based on brachial-ankle pulse wave velocity (ba-PWV). [Results] Compared to the control group; The metabolic syndrome risk factors (weight, % body fat, waist circumference, systolic blood pressure, diastolic blood pressure, and HDL-Cholesterol) were significantly improved in the exercise: resting heart rate was significantly decreased; VO2max, muscle strength and muscle endurance were significantly increased; and ba-PWV was significantly decreased. [Conclusion] Aerobic exercise had beneficial effects on the resting heart rate, physical fitness, and arterial stiffness of patients with metabolic syndrome. PMID:27390411

  10. Effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness of female patients with metabolic syndrome.

    PubMed

    Kang, Seol-Jung; Kim, Eon-Ho; Ko, Kwang-Jun

    2016-06-01

    [Purpose] The purpose of this study was to investigate the effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness or female patients with metabolic syndrome. [Subjects and Methods] Subjects were randomly assigned to an exercise group (n=12) or a control group (n=11). Subjects in the exercise group performed aerobic exercise at 60-80% of maximum heart rate for 40 min 5 times a week for 12 weeks. The changes in metabolic syndrome risk factors, resting heart rate, physical fitness, and arterial stiffness were measured and analyzed before and after initiation of the exercise program to determine the effect of exercise. Arterial stiffness was assessed based on brachial-ankle pulse wave velocity (ba-PWV). [Results] Compared to the control group; The metabolic syndrome risk factors (weight, % body fat, waist circumference, systolic blood pressure, diastolic blood pressure, and HDL-Cholesterol) were significantly improved in the exercise: resting heart rate was significantly decreased; VO2max, muscle strength and muscle endurance were significantly increased; and ba-PWV was significantly decreased. [Conclusion] Aerobic exercise had beneficial effects on the resting heart rate, physical fitness, and arterial stiffness of patients with metabolic syndrome.

  11. Effect of a tart cherry juice supplement on arterial stiffness and inflammation in healthy adults: a randomised controlled trial.

    PubMed

    Lynn, Anthony; Mathew, Shilpa; Moore, Chris T; Russell, Jean; Robinson, Emma; Soumpasi, Vithleem; Barker, Margo E

    2014-06-01

    Tart cherries are a particularly rich source of anthocyanins. Evidence indicates that dietary intake of anthocyanins is inversely associated with arterial stiffness. We conducted an open-label randomised placebo controlled study to determine whether a tart cherry juice concentrate (Cherry Active) reduced arterial stiffness, inflammation and risk markers for cardiovascular disease in 47 healthy adults (30-50 years). Participants consumed 30 ml of cherry concentrate diluted to a volume of 250 ml with water or the same volume of an energy matched control drink daily for six weeks. Measurements were taken at baseline and at the end of the intervention. There was no effect of the intervention on arterial stiffness (P = 0.218), c-reactive protein (P = 0.220), systolic blood pressure (P = 0.163), diastolic blood pressure (P = 0.121), total cholesterol (P = 0.342) and high density lipoprotein cholesterol (P = 0.127). At the end of the intervention, plasma antioxidant capacity (measured as the ferric reducing ability of plasma (FRAP)) was significantly higher in the intervention group than the control group (P = 0.012). We conclude that a tart cherry juice concentrate rich in anthocyanins has no effect on arterial stiffness, c-reactive protein and risk markers for cardiovascular disease, but evokes a minor increase in antioxidant status in healthy adults.

  12. [Treatment of compression of the left main coronary artery in patients with pulmonary hypertension].

    PubMed

    Talavera, María L; Diez, Mirta; Cáneva, Jorge O; Boughen, Roberto P; Valdivieso, León; Mendiz, Oscar

    2011-01-01

    Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.

  13. Congenital right pulmonary artery agenesis with atrial septal defect and pulmonary hypertension.

    PubMed

    Orun, Utku Arman; Yilmaz, Osman; Bilici, Meki; Karademir, Selmin; Uner, Cigdem; Senocak, Filiz; Dogan, Vehbi

    2012-01-01

    Unilateral pulmonary artery agenesis is a rare congenital anomaly caused by a backward displacement of the conical artery of the truncus arteriosus. It is commonly associated with additional cardiovascular abnormalities. A 7-year-old girl was admitted to our clinic with the complaint of shortness of breath upon exertion. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery with atrial septal defect and pulmonary hypertension was demonstrated by echocardiography, computed tomography, and cardiac catheterization. Bosentan is effectively used to treat pulmonary arterial hypertension.

  14. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial.

    PubMed

    Knapen, Marjo H J; Braam, Lavienja A J L M; Drummen, Nadja E; Bekers, Otto; Hoeks, Arnold P G; Vermeer, Cees

    2015-05-01

    Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness.

  15. [Female gender and pulmonary arterial hypertension: a complex relationship].

    PubMed

    Manes, Alessandra; Palazzini, Massimiliano; Dardi, Fabio; D'Adamo, Antonio; Rinaldi, Andrea; Galiè, Nazzareno

    2012-06-01

    Pulmonary arterial hypertension (PAH) is a severe clinical condition defined as mean pulmonary artery pressure ≥25 mmHg and normal pulmonary capillary wedge pressure (≤15 mmHg). In PAH the increase in pulmonary pressure is due to an intrinsic disease of the small pulmonary arteries (resistance vessels) characterized by vascular proliferation and remodeling. The increase in pulmonary vascular resistance with subsequent elevation of the right ventricular afterload leads to right ventricular failure after variable periods of time. Although targeted disease therapies have been developed over the last decade that resulted in improved quality of life and outcome for PAH patients, the prognosis is still severe and there remains no cure for this disease. From a clinical standpoint, PAH includes a group of heterogeneous pathological conditions: in idiopathic, heritable and drug- and toxin-induced PAH, since there are no predisposing clinical conditions, the structural changes in pulmonary circulation are "isolated"; on the other hand, PAH may be associated with some predisposing diseases such as connective tissue disease, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and chronic hemolytic anemia. PAH can affect individuals of all age groups, and mean age at diagnosis is around 50 years. Epidemiological data show a great preponderance of females in PAH; the high prevalence of females is particularly evident in the so-called "isolated" PAH forms, whereas in PAH associated with other diseases the female:male ratio is strongly influenced by the epidemiological features of the specific predisposing condition. The reason for the higher female prevalence in PAH has never been clarified: some hypotheses involve the role of sexual hormones (estrogens), autoimmunity, or an X-linked locus in disease predisposition. Female gender is not associated with a different clinical presentation. However, the age of onset tends to be earlier in females than

  16. Noninvasive pulse transit time measurement for arterial stiffness monitoring in microgravity.

    PubMed

    McCall, Corey; Rostosky, Rea; Wiard, Richard M; Inan, Omer T; Giovangrandi, Laurent; Cuttino, Charles Marsh; Kovacs, Gregory T A

    2015-01-01

    The use of a noninvasive hemodynamic monitor to estimate arterial stiffness, by measurement of pulse transit time (PTT), was demonstrated in microgravity. The monitor's utility for space applications was shown by establishing the correlation between ground-based and microgravity-based measurements. The system consists of a scale-based ballistocardiogram (BCG) and a toe-mounted photoplethysmogram (PPG). PTT was measured from the BCG I-wave to the intersecting tangents of the first trough and maximum first derivative of the PPG waveforms of each subject. The system was tested on a recent series of parabolic flights in which the PTT of nine subjects was measured on the ground and in microgravity. An average of 60.2 ms PTT increase from ground to microgravity environments was shown, and was consistent across all test subjects (standard deviation = 32.9 ms). This increase in PTT could be explained by a number of factors associated with microgravity and reported in previous research, including elimination of hydrostatic pressure, reduction of intrathoracic pressure, and reduction of mean arterial pressure induced by vasodilation.

  17. Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension*

    PubMed Central

    Gavilanes, Francisca; Jr, José Leonidas Alves; Fernandes, Caio; Prada, Luis Felipe Lopes; Jardim, Carlos Viana Poyares; Morinaga, Luciana Tamie Kato; Dias, Bruno Arantes; Hoette, Susana; Souza, Rogerio

    2014-01-01

    OBJECTIVE: To evaluate the role of right heart catheterization in the diagnosis of pulmonary arterial hypertension (PAH). METHODS: We evaluated clinical, functional, and hemodynamic data from all patients who underwent right heart catheterization because of diagnostic suspicion of PAH-in the absence of severe left ventricular dysfunction (LVD), significant changes in pulmonary function tests, and ventilation/perfusion lung scintigraphy findings consistent with chronic pulmonary thromboembolism-between 2008 and 2013 at our facility. RESULTS: During the study period, 384 patients underwent diagnostic cardiac catheterization at our facility. Pulmonary hypertension (PH) was confirmed in 302 patients (78.6%). The mean age of those patients was 48.7 years. The patients without PH showed better hemodynamic profiles and lower levels of B-type natriuretic peptide. Nevertheless, 13.8% of the patients without PH were categorized as New York Heart Association functional class III or IV. Of the 218 patients who met the inclusion criteria, 40 (18.3%) and 178 (81.7%) were diagnosed with PH associated with LVD (PH-LVD) and with PAH, respectively. The patients in the HP-LVD group were significantly older than were those in the PAH group (p < 0.0001). CONCLUSIONS: The proportional difference between the PAH and PH-LVD groups was quite significant, considering the absence of echocardiographic signs suggestive of severe LVD during the pre-catheterization investigation. Our results highlight the fundamental role of cardiac catheterization in the diagnosis of PAH, especially in older patients, in whom the prevalence of LVD that has gone undiagnosed by non-invasive tests is particularly relevant. PMID:25610501

  18. Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension

    PubMed Central

    Gomberg-Maitland, Mardi; Demarco, Teresa; Frost, Adaani E.; Torbicki, Adam; Langleben, David; Pulido, Tomas; Correa-Jaque, Priscilla; Passineau, Michael J.; Wiener, Howard W.; Tamari, Mayumi; Hirota, Tomomitsu; Kubo, Michiaki; Tiwari, Hemant K.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases. Objectives: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs). Methods: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Single-nucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort. Measurements and Main Results: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months. Conclusions: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed. PMID:26252367

  19. Association of Hypertension With Erectile Function in Chronic Peripheral Arterial Insufficiency Patients

    PubMed Central

    Spessoto, Luis Cesar Fava; Facio, Fernando Nestor; de Arruda, Jose Germano Ferraz; Arruda, Pedro Francisco F.; Gatti, Marcio; Antoniassi, Thiago Silveira; Facio, Maria Fernanda Warick; de Godoy, Jose Maria Pereira

    2016-01-01

    Background Risk factors may influence the improvement or worsening of erectile dysfunction (ED). The aim of the current study was to evaluate the effect of systemic hypertension on ED in patients with peripheral arterial disease. Methods The effect of hypertension on ED was assessed in 125 consecutive patients in a cross-sectional quantitative study. The ages of the patients ranged from 19 to 88 years old (mean: 59.82 ± 10.48 years). The only exclusion criterion was the amputation of one or both legs. The ankle-arm index was assessed and the international index of ED questionnaire was applied to all participants in the study. Results Of the 125 patients, 22 (17.6%) had mild (grade 1), 50 (40.0%) had moderate (grade 2) and 53 (42.4%) had severe (grade 3) ED. Hypertensive patients have more ED, with ED in hypertensive patients being associated to chronic arterial disease. However, in comparison with normotensive patients, hypertension exerts an immediate protective effect on erectile function. Conclusions In conclusion, although erectile function is initially protected by systemic arterial hypertension in patients with chronic arterial disease, both chronic arterial disease and ED deteriorate over the long term in hypertensive patients. PMID:27429678

  20. Are Hemodynamics Surrogate Endpoints in Pulmonary Arterial Hypertension?

    PubMed Central

    Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.

    2014-01-01

    Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771

  1. Mutations of NOTCH3 in childhood pulmonary arterial hypertension

    PubMed Central

    Chida, Ayako; Shintani, Masaki; Matsushita, Yoshihisa; Sato, Hiroki; Eitoku, Takahiro; Nakayama, Tomotaka; Furutani, Yoshiyuki; Hayama, Emiko; Kawamura, Yoichi; Inai, Kei; Ohtsuki, Shinichi; Saji, Tsutomu; Nonoyama, Shigeaki; Nakanishi, Toshio

    2014-01-01

    Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. PMID:24936512

  2. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms

    PubMed Central

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    Background The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. Methods This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Results Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Conclusion Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation. PMID:26257517

  3. Copper dependence of angioproliferation in pulmonary arterial hypertension in rats and humans.

    PubMed

    Bogaard, Harm J; Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C; Humbert, Marc; Vonk Noordegraaf, Anton; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F

    2012-05-01

    Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation-induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide-1 inhibition or lysyl-oxidase-1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension.

  4. Family history of hypertension and arterial elasticity characteristics in healthy young people.

    PubMed

    Zhou, Lin; Chen, Yuanyuan; Sun, Ningling; Liu, Xirong

    2008-05-01

    Family history of hypertension is a primary predictor of high blood pressure (BP). This study attempted to determine whether there is a gradual increase in BP and an early change in arterial elasticity characteristics between young healthy individuals with or without a family history of hypertension and whether or not this increase is apparent in males as well as in females. A total of 270 normotensive healthy individuals (112 men and 158 women, aged 16 to 30 years) with or without a family history of hypertension, participated in conventional BP measurement and completed questionnaires covering basic information and a detailed family history of cardiovascular disease. Large arterial (capacitive) compliance (C1) and small arterial (oscillatory or reflective) compliance (C2) were derived from HDI/PulseWave CR-2000 (Hypertension Diagnostics, Minneapolis, USA). Based on family history information about parents and grandparents, three groups were formed: subjects with at least one hypertensive parent (group A), subjects with only hypertensive grandparents (group B), and subjects with normotensive parents and grandparents (group C). Men in group A had lower C1 and C2 along with higher systolic BP (SBP), diastolic BP (DBP), and heart rate than men in group C. Those in group B had intermediate C1, C2 and BP levels. C1 had a linear relationship with SBP, DBP, and heart rate. In the logistic regression model of family history of hypertension, C2 was lower in young normotensive males with parental hypertension (B = -0.315, exp B = 0.73, p = 0.03), independently of SBP, DBP, and heart rate. Among females, subjects with parental hypertension had higher systolic, mean arterial pressure, and pulse pressure (p < 0.05), and there were no significant differences in C1 and C2 between those with and those without parental hypertension. In conclusion, compared with normotensive offspring of normotensive parents, normotensive offspring of hypertensive parents had increased BP and

  5. Digital capillaroscopy as important tool for early diagnostics of arterial hypertension

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yu. I.; Sasonko, M. L.; Priezzhev, A. V.

    2015-03-01

    The study is aimed to determine the digital capillaroscopy possibilities in early diagnostics of an arterial hypertension. A total of 123 adult persons were examined in the study. The first group consisted of 40 patients with prehypertension (BP 130-139/85-89 mm Hg). The second group included 36 patients with 1-2 stage of hypertension (mean systolic BP 152.7±12 mm Hg). Patients in both groups did not receive regular drug therapy. The group of volunteers (n=47) included healthy adults without signs of cardiovascular pathology. The capillary circulation was examined on the nailbed using the optical digital capillaroscope developed by the company "AET", Russia. Diameters of the arterial and venous segments, perivascular zone size, capillary blood velocity, the degree of arterial loops narrowing and the density of the capillary network were estimated. In patients with arterial hypertension and even in patients with prehypertension remodeling and rarefaction of capillaries and the expressed narrowing their arterial loops were manifested. The results of the study revealed the presence of abnormalities of microcirculation parameters in patients of both groups. The capillaries density in both groups of patients was significantly lower than in healthy persons. The significant narrowing of arterial loops was revealed in patients with both arterial hypertension and prehypertension, in comparison with healthy volunteers. Capillary blood velocity did not differ significantly between healthy volunteers group and the group of prehypertensive patients. However in patients with hypertension this parameter was significantly lower in comparison with control group.

  6. [Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension].

    PubMed

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    2015-01-01

    In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively.

  7. Recent advances in the management of pulmonary arterial hypertension

    PubMed Central

    de Jesus Perez, Vinicio

    2016-01-01

    Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease. PMID:27990270

  8. Clinical and molecular genetic features of hereditary pulmonary arterial hypertension.

    PubMed

    Brenner, Laura; Chung, Wendy K

    2011-10-01

    Pulmonary arterial hypertension (PAH) is a rare disorder that may be hereditary (HPAH), idiopathic (IPAH), or associated with either drug-toxin exposures or other medical conditions. Familial cases have long been recognised and are usually due to mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2), or, much less commonly, two other members of the transforming growth factor-β superfamily, activin-like kinase-type 1 (ALK1), and endoglin (ENG), which are associated with hereditary hemorrhagic telangiectasia. In addition, approximately 20% of patients with IPAH carry mutations in BMPR2. Clinical testing for BMPR2 mutations is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counselling, since lifetime penetrance is only 10% to 20%, and there are currently no known effective preventative measures. Identification of a familial mutation can be valuable in reproductive planning and identifying family members who are not mutation carriers and thus will not require lifelong surveillance. With advances in genomic technology and with international collaborative efforts, genome-wide association studies will be conducted to identify additional genes for HPAH, genetic modifiers for BMPR2 penetrance, and genetic susceptibility to IPAH. In addition, collaborative studies of BMPR2 mutation carriers should enable identification of environmental modifiers, biomarkers for disease development and progression, and surrogate markers for efficacy end points in clinical drug development, thereby providing an invaluable resource for trials of PAH prevention.

  9. The molecular targets of approved treatments for pulmonary arterial hypertension

    PubMed Central

    Humbert, Marc; Ghofrani, Hossein-Ardeschir

    2016-01-01

    Until recently, three classes of medical therapy were available for the treatment of pulmonary arterial hypertension (PAH)—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors. With the approval of the soluble guanylate cyclase stimulator riociguat, an additional drug class has become available targeting a distinct molecular target in the same pathway as PDE5 inhibitors. Treatment recommendations currently include the use of all four drug classes to treat PAH, but there is a lack of comparative data for these therapies. Therefore, an understanding of the mechanistic differences between these agents is critical when making treatment decisions. Combination therapy is often used to treat PAH and it is therefore important that physicians understand how the modes of action of these drugs may interact to work as complementary partners, or potentially with unwanted consequences. Furthermore, different patient phenotypes mean that patients respond differently to treatment; while a certain monotherapy may be adequate for some patients, for others it will be important to consider alternating or combining compounds with different molecular targets. This review describes how the four currently approved drug classes target the complex pathobiology of PAH and will consider the distinct target molecules of each drug class, their modes of action, and review the pivotal clinical trial data supporting their use. It will also discuss the rationale for combining drugs (or not) from the different classes, and review the clinical data from studies on combination therapy. PMID:26219978

  10. [Fluid overload and arterial hypertension in hemodialysis patients].

    PubMed

    Arkouche, Walid; Giaime, Philippe; Mercadal, Lucile

    2013-11-01

    The water sodium overload is a factor of morbi-mortality and its treatment is one of the markers of adequacy of the hemodialysis treatment. Its first clinical assessment was improved by tools such as echocardiography and ultrasonography of the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or proBNP and by impedancemetry. The combination of the evaluation of these parameters and of the clinical situation allows one to assess the extracellular overload, the state of the blood volume and the potential of plasma refilling. The latter is a key factor of the per-dialytic hemodynamic tolerance. It is itself a determining factor in weight can be achieved at the end of the session. Getting the "dry" weight can require modifications of the prescriptions of the hemodialysis sessions, a filling by albumin even a drugs support. Finally, the overload treatment is the central part of the treatment of arterial hypertension, which has to benefit however often from antihypertensive treatment the profit of which is demonstrated.

  11. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance.

    PubMed

    Rol, Nina; Timmer, Esther M; Faes, Theo J C; Noordegraaf, Anton Vonk; Grünberg, Katrien; Bogaard, Harm-Jan; Westerhof, Nico

    2017-03-01

    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall thickness, but information on number of vessels affected and internal diameter decreases for vessels of different sizes is limited. Our aim was to quantify numbers of affected vessels and their internal diameter decrease for differently sized vessels in PAH in comparison with non-PAH patients. Internal and external diameters of transversally cut vessels were measured in five control subjects and six PAH patients. Resistance vessels were classified in Strahler orders, internal diameters 13 μm (order 1) to 500 μm (order 8). The number fraction, that is, percentage of affected vessels, and the internal diameter fraction, that is, percentage diameter of normal diameter, were calculated. In PAH, not all resistance vessels are affected. The number fraction is about 30%, that is, 70% of vessels have diameters not different from vessels of control subjects. Within each order, the decrease in diameter of affected vessels is variable with an averaged diameter fraction of 50-70%. Narrowing of resistance vessels is heterogeneous: not all vessels are narrowed, and the decrease in internal diameters, even within a single order, vary largely. This heterogeneous narrowing alone cannot explain the large resistance increase in PAH We suggest that rarefaction could be an important contributor to the hemodynamic changes.

  12. A review of pulmonary arterial hypertension: role of ambrisentan

    PubMed Central

    Barst, Robyn J

    2007-01-01

    Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ETA] and/or type-B [ETB]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ETA-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5–10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ETA/ETB ERA, bosentan, and the ETA-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug–drug interactions support the role of ambrisentan for the treatment of PAH. PMID:17583171

  13. Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults

    PubMed Central

    Taichman, Darren B.; Chung, Lorinda; Klinger, James R.; Lewis, Sandra; Mandel, Jess; Palevsky, Harold I.; Rich, Stuart; Sood, Namita; Rosenzweig, Erika B.; Trow, Terence K.; Yung, Rex; Elliott, C. Gregory; Badesch, David B.

    2014-01-01

    OBJECTIVE: Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence. METHODS: This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus. RESULTS: Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded. CONCLUSIONS: Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH. PMID:24937180

  14. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario

    PubMed Central

    Vaid, Haris M.; Camacho, Ximena; Granton, John T.; Mamdani, Muhammad M.; Yao, Zhan; Singh, Samantha; Juurlink, David N.; Gomes, Tara

    2016-01-01

    Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96–$747) for those who survived and $2,021 (IQR $993–$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555

  15. Epoprostenol sodium for treatment of pulmonary arterial hypertension.

    PubMed

    Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi

    2015-01-01

    The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

  16. Epoprostenol sodium for treatment of pulmonary arterial hypertension

    PubMed Central

    Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi

    2015-01-01

    The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required. PMID:25999730

  17. Inflammatory mechanisms in HIV-associated pulmonary arterial hypertension.

    PubMed

    Tcherakian, Colas; Couderc, Louis-Jean; Humbert, Marc; Godot, Véronique; Sitbon, Olivier; Devillier, Philippe

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.

  18. Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

    PubMed

    Papathanasiou, Athanasios; Nakos, George

    2015-11-04

    Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, defined as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of

  19. Assessment of Pulmonary Artery Stiffness of Repaired Congenital Heart Disease Patients

    NASA Astrophysics Data System (ADS)

    Lee, Namheon; Banerjee, Rajit; Taylor, Michael; Hor, Kan

    2012-10-01

    Surgical correction or palliation of congenital heart disease (CHD) often requires augmenting the main pulmonary artery (MPA) with non-native material or placing a cylindrical graft. The degree to which this intervention affects PA compliance is largely unknown. In this study, the MPA stiffness characteristics were assessed by its compliance, distensibility, and pressure-strain modulus. Coregistered velocity encoded phase-contrast MRI and cardiac catheterization data were available for a cohort of repaired CHD patients (n=8) and controls (n=3). All patients were repaired with either an RV-PA conduit or a RV outflow tract patch. We measured the MPA area change by MRI and MPA pressure during the cath. The measurements were taken through or just distal to the conduit. The MPA compliance and distensibility for the patients were significantly lower than the controls: compliance (9.8±10.8 vs 28.3±7.7mm^2/mmHg, p<0.05), distensibility (2.2±1.5 vs 6.6±2.1%Area change/mmHg, p=0.05). The patients had a significantly higher pressure-strain modulus (152.3±116.4mmHg, p<0.05) than the controls (35.8±10.6mmHg). The abnormally elevated PA stiffness due to the rigidity of the conduit or patch material may cause a compliance mismatch resulting in high stress levels contributing to the observed progressive PA dilatation. This may be a factor in the progressive RV dilatation seen in this cohort of repaired CHD patients.

  20. MR and CT imaging of the structural and functional changes of pulmonary arterial hypertension

    PubMed Central

    Schiebler, Mark L.; Bhalla, Sanjeev; Runo, James; Jarjour, Nizar; Roldan, Alejandro; Chesler, Naomi; François, Christopher J.

    2013-01-01

    The current Dana Point classification system (2009) divides elevation of pulmonary artery pressure into Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension (PH). Fortunately, pulmonary arterial hypertension (PAH) is not a common disease. However, with the aging of the first world’s population, heart failure is now an important cause of pulmonary hypertension with up to 9% of the population involved. PAH is usually asymptomatic until late in the disease process. While there are indirect features of PAH found on noninvasive imaging studies, the diagnosis and management still requires right heart catheterization. Imaging features of PAH include: 1. Enlargement of the pulmonary trunk and main pulmonary arteries, 2. Decreased pulmonary arterial compliance, 3. Tapering of the peripheral pulmonary arteries, 4. Enlargement of the inferior vena cava, and 5. Increased mean transit time. The chronic requirement to generate high pulmonary arterial pressures measurably affects the right heart and main pulmonary artery. This change in physiology causes the following structural and functional alterations that have been shown to have prognostic significance: Relative area change of the pulmonary trunk, RVSVindex, RVSV, RVEDVindex, LVEDVindex, and baseline RVEF <35%. All of these variables can be quantified non-invasively and followed longitudinally in each patient using MRI to modify the treatment regimen. Untreated PAH frequently results in a rapid clinical decline and death within 3 years of diagnosis. Unfortunately, even with treatment, less than 1/2 of these patients are alive at four years. PMID:23612440

  1. Creatine supplementation attenuates hemodynamic and arterial stiffness responses following an acute bout of isokinetic exercise.

    PubMed

    Sanchez-Gonzalez, Marcos A; Wieder, Ralph; Kim, Jeong-Su; Vicil, Florence; Figueroa, Arturo

    2011-09-01

    Arterial stiffness and hemodynamics may be increased following a bout of resistance exercise. Oral creatine supplementation (Cr) may attenuate cardiovascular responses after exercise via improved anaerobic metabolism. This study was aimed to determine the effect of Cr on hemodynamic and arterial stiffness responses after acute isokinetic exercise. Sixteen healthy males (22.6 ± 0.6 year) were randomly assigned to either placebo (Pl, n = 8) or Cr (n = 8) (2 × 5 g/day) for 3 weeks. Brachial systolic blood pressure (SBP), heart rate (HR), brachial-ankle pulse wave velocity (baPWV), and leg PWV were measured in the supine position at rest before and after the interventions. After the supplementation period, parameters were also measured 5 min (PE5) and 15 min (PE15) after two sets of leg isokinetic exercise. There was no difference between the groups in resting measurements before and after the supplementation. Compared with the Pl group, the Cr group had attenuated (P < 0.05) increases in SBP at PE5 (Pl 14.0 ± 2.5, Cr 5.6 ± 2.3 mmHg), HR at both P5 (Pl 28 ± 4 vs. Cr 16 ± 2 beats/min) and PE15 (Pl 21 ± 3, Cr 11 ± 2 beats/min) and rate pressure product at P5 (Pl 45.8 ± 6.4, Cr 24.8 ± 2.2) and P15 (Pl 34.2 ± 5.0, Cr 15.9 ± 6.0). Compared with the Pl group, the Cr group had suppressed increases in baPWV at PE5 (Pl 1.5 ± 0.4, Cr -0.1 ± 0.4 m/s) and PE15 (Pl 1.1 ± 0.2, Cr -0.3 ± 0.3 m/s) and returned SBP to pre-exercise values at PE15 (Pl 10.6 ± 2.8, Cr 2.1 ± 2.6 mmHg). PWV in the exercised leg decreased at PE5 in both groups. These findings suggest that Cr supplementation attenuates the hemodynamic and baPWV responses after acute isokinetic exercise.

  2. Stress phase angle depicts differences in arterial stiffness: phantom and in vivo study

    NASA Astrophysics Data System (ADS)

    Niu, Lili; Meng, Long; Xu, Lisheng; Liu, Jia; Wang, Qiwen; Xiao, Yang; Qian, Ming; Zheng, Hairong

    2015-06-01

    The endothelial cells (ECs) lining of a blood vessel wall are exposed to both the wall shear stress (WSS) of blood flow and the circumferential strain (CS) of pulsing artery wall motion. Both WSS and CS keep involved in the modulation of ECs’ biochemical response and function and the temporal phase angle between the two is called stress phase angle (SPA). Previous studies at the cellular level have indicated that SPA is highly negative at sites that are prone to atherosclerosis, and hypothesized that large SPA may contribute to atherogenesis. Till now, there is no experimental data to support this hypothesis, probably due to the lack of a proper tool for measuring WSS and CS simultaneously and real time. In this study, a non-invasive ultrasonic biomechanics method was utilized to quantitatively calculate the SPA and experimentally evaluate the role of SPA in predicting early atherosclerosis. Three silicon tubes with a stiffness of 1.15, 3.62, 9.38 MPa were assembled in a pulsatile flow circuit and the values of SPA were measured to be -101.86 ± 3.65°,-170.19 ± 17.77° and -260.63 ± 18.62°, respectively. For the PVA-c phantoms, stiffness was 162.45, 235.68 and 374.24 kPa, the SPA corresponding to -170.32 ± 17.55°,-207.56 ± 10.78° and -261.08 ± 10.90°, respectively. Both phantom studies results demonstrated that SPA was highly negative in stiffer arteries. Further, experiments were taken in healthy living rats as control group (n = 3), atherosclerotic model group (n = 3), and drug treated group (n = 3), and the results showed that SPA was most negative in the model group, and SPA was least negative in the control group. Together, this study suggested that highly negative SPA appeared to be a prominent mechanical feature of vessels prone to atherosclerotic disease.

  3. The dissociation of arterial hypertension and lupus glomerulonephritis in systemic lupus erythematosus.

    PubMed

    Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P

    1993-06-01

    In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.

  4. Failure and Success of Percutaneous Angioplasty in a Hypertensive Child with Bilateral Renal Artery Stenosis

    SciTech Connect

    Giavroglou, Constantinos; Tsifountoudis, Ioannis; Boutzetis, Theodoros; Kiskinis, Dimitrios

    2009-01-15

    We describe the clinical course of a 5-year-old girl with severe arterial hypertension that was uncontrollable with antihypertensive medication. Renal angiography revealed bilateral renal artery stenoses. Because percutaneous transluminal renal angioplasty (PTRA) failed to dilate the stenotic lesions, a renal artery bypass grafting in both renal arteries was performed. The patient remained normotensive for 7 months, and after that the arterial pressure increased again. Digital subtraction angiography demonstrated stenosis at the peripheral and central anastomosis of the vein graft that was used for revascularization of the left kidney. PTRA was decided on and successful patency was achieved. The patient has now been normotensive for a period of 5 years.

  5. Role of the glomerular-tubular imbalance with tubular predominance in the arterial hypertension pathophysiology.

    PubMed

    Fox, María Ofelia Barber; Gutiérrez, Ernesto Barber

    2013-09-01

    In previous investigations we caused renal tubular reabsorption preponderance relating to the glomerular filtration (Glomerular-tubular imbalance) and we observed that this fact conducted to volume expansion and development of arterial hypertension, in rats that previously were normotens. We based on this evidence and other which are reflected in the literature arrived at the following hypothesis: a greater proportion of tubular reabsorption relating to the filtered volume is the base of the establishment of the glomerular-tubular imbalance with tubular predominance (GTI-T), which favors to the Na(+)-fluid retention and volume expansion. All of which conduced to arterial hypertension. These facts explain a primary hypertensive role of the kidney, consistent with the results of renal transplants performed in different lines of hypertensive rats and their respective controls and in humans: hypertension can be transferred with the kidney. GTI-T aims to be, a common phenomenon involved in the hypertension development in the multiple ways which is manifested the hypertensive syndrome. In secondary hypertension, GTI-T is caused by significant disruptions of hormone secretions that control renal function, or obvious vascular or parenchymal damage of these organs. In primary hypertension the GTI-T has less obvious causes inherently developed in the kidney, including humoral, cellular and subcellular mechanisms, which may insidiously manifest under environmental factors influence, resulting in insidious development of hypertension. This would explain the state of prehypertension that these individuals suffer. So it has great importance to study GTI-T before the hypertension is established, because when hypertensive state is established, other mechanisms are installed and they contribute to maintain the hypertension. Our hypothesis may explaining the inability of the kidneys to excrete salt and water in hypertension, as Guyton and colleagues have expressed and constitutes a

  6. Selexipag in the treatment of pulmonary arterial hypertension: design, development, and therapy

    PubMed Central

    Hardin, Elizabeth Ashley; Chin, Kelly M

    2016-01-01

    Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag. PMID:27895464

  7. Selexipag in the treatment of pulmonary arterial hypertension: design, development, and therapy.

    PubMed

    Hardin, Elizabeth Ashley; Chin, Kelly M

    2016-01-01

    Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag.

  8. Arterial stiffness in periodontitis patients and controls. A case–control and pilot intervention study.

    PubMed

    Houcken, W; Teeuw, W J; Bizzarro, S; Alvarez Rodriguez, E; Mulders, T A; van den Born, B-Jh; Loos, B G

    2016-01-01

    Increased arterial stiffness (AS) is an important indicator for atherosclerotic cardiovascular disease (ACVD). Epidemiologically, periodontitis and ACVD are associated. Therefore, we aimed to investigate AS in periodontitis patients and controls. In addition, we explored the effect of periodontal therapy on AS in a sub-group of cases. Pulse-wave velocity (PWV), a non-invasive chair-side function test for AS, was measured in periodontitis patients (n=57; mean age 46.6 years) and compared with a reference group (n=48; mean age 45.5 years). In addition, 45 cases (mean age 46.9 years) were 6 months followed after periodontal treatment, to explore a possible effect on arterial function. Periodontitis patients showed a significantly increased PWV compared with the reference group (8.01±0.20 vs. 7.36±0.22 m s(-1) respectively; P=0.029) and this remained significant after adjustments for ACVD risk factors (P=0.019). After periodontal therapy, no significant reduction in PWV was seen (8.00±1.8 to 7.82±1.6 m s(-1); P=0.13), but systolic blood pressure (SBP) was significantly reduced (119.8±14.6 to 116.9±15.1 mm Hg; P=0.040). It can be concluded that periodontitis is associated with increased AS. This confirms with a new parameter the association of periodontitis with ACVD. Although periodontal treatment did not lower AS significantly, a modest reduction of SBP after 6 months was observed.

  9. Diminished contractile responses of isolated conduit arteries in two rat models of hypertension.

    PubMed

    Zemancíková, Anna; Török, Jozef

    2013-08-31

    Hypertension is accompanied by thickening of arteries, resulting in marked changes in their passive and active mechanical properties. The aim of this study was to demonstrate that the large conduit arteries from hypertensive individuals may not exhibit enhanced contractions in vitro, as is often claimed. Mechanical responses to vasoconstrictor stimuli were measured under isometric conditions using ring arterial segments isolated from spontaneously hypertensive rats, N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated Wistar rats, and untreated Wistar rats serving as normotensive control. We found that thoracic aortas from both types of hypertensive rats had a greater sensitivity but diminished maximal developed tension in response to noradrenaline, when compared with that from normotensive rats. In superior mesenteric arteries, the sensitivity to noradrenaline was similar in all examined rat groups but in L-NAME-treated rats, these arteries exhibited decreased active force when stimulated with high noradrenaline concentrations, or with 100 mM KCl. These results indicate that hypertension leads to specific biomechanical alterations in diverse arterial types which are reflected in different modifications in their contractile properties.

  10. Arterial Hypertension and other risk factors associated with cardiovascular diseases among adults1

    PubMed Central

    Radovanovic, Cremilde Aparecida Trindade; dos Santos, Lucimary Afonso; Carvalho, Maria Dalva de Barros; Marcon, Sonia Silva

    2014-01-01

    OBJECTIVE: to identify the prevalence of arterial hypertension and its association with cardiovascular risk factors among adults. METHOD: cross-sectional, population-based, descriptive study conducted with 408 adult individuals. Data were collected through a questionnaire and measurements of weight, height and waist circumference. Person's Chi-square and multiple logistic regression were used in the data analysis. RESULTS: 23.03% of the individuals reported hypertension with a higher prevalence among women. Odds Ratio indicated that smoking, body mass index, waist circumference, diabetes mellitus and dyslipidemia were positively associated with arterial hypertension. CONCLUSION: high self-reported hypertension and its association with other cardiovascular risk factors such as diabetes, obesity and dyslipidemia show the need for specific nursing interventions and the implementation of protocols focused on minimizing complications arising from hypertension, as well as to prevent the emergence of other cardiovascular diseases. PMID:25296137

  11. [Efficacy of emoxipin in treatment of arterial hypertension in the Far North].

    PubMed

    Vershinina, A M; Gapon, L I; Shurkevich, N P; Bazhukhina, I F; Petelina, T I; Savel'eva, N Iu

    1999-01-01

    A total of 95 hypertensive men working in duty regimen in the extreme North were examined. The men were found to have lipid metabolism disorders, activation of lipid peroxidation, decreased antioxidant defense in red cell membranes in all the examinees vs control hypertensive men living in moderate climatic zone. Effect of 2-week monotherapy with emoxipin was studied in 29 males with mild arterial hypertension free of obesity and coexisting diseases. Placebo was given to 10 patients. Emoxipin had an antihypertensive and antioxidant effects, improved structural-functional condition of erythrocytes in hypertensive patients.

  12. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    SciTech Connect

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

    2014-07-18

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  13. Pathophysiology of infantile pulmonary arterial hypertension induced by monocrotaline.

    PubMed

    Dias-Neto, Marina; Luísa-Neves, Ana; Pinho, Sónia; Gonçalves, Nádia; Mendes, Maria; Eloy, Catarina; Lopes, José M; Gonçalves, Daniel; Ferreira-Pinto, Manuel; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

    2015-06-01

    Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.

  14. Associations and clinical relevance of aortic-brachial artery stiffness mismatch, aortic reservoir function, and central pressure augmentation.

    PubMed

    Schultz, Martin G; Hughes, Alun D; Davies, Justin E; Sharman, James E

    2015-10-01

    Central augmentation pressure (AP) and index (AIx) predict cardiovascular events and mortality, but underlying physiological mechanisms remain disputed. While traditionally believed to relate to wave reflections arising from proximal arterial impedance (and stiffness) mismatching, recent evidence suggests aortic reservoir function may be a more dominant contributor to AP and AIx. Our aim was therefore to determine relationships among aortic-brachial stiffness mismatching, AP, AIx, aortic reservoir function, and end-organ disease. Aortic (aPWV) and brachial (bPWV) pulse wave velocity were measured in 359 individuals (aged 61 ± 9, 49% male). Central AP, AIx, and aortic reservoir indexes were derived from radial tonometry. Participants were stratified by positive (bPWV > aPWV), negligible (bPWV ≈ aPWV), or negative stiffness mismatch (bPWV < aPWV). Left-ventricular mass index (LVMI) was measured by two-dimensional-echocardiography. Central AP and AIx were higher with negative stiffness mismatch vs. negligible or positive stiffness mismatch (11 ± 6 vs. 10 ± 6 vs. 8 ± 6 mmHg, P < 0.001 and 24 ± 10 vs. 24 ± 11 vs. 21 ± 13%, P = 0.042). Stiffness mismatch (bPWV-aPWV) was negatively associated with AP (r = -0.18, P = 0.001) but not AIx (r = -0.06, P = 0.27). Aortic reservoir pressure strongly correlated to AP (r = 0.81, P < 0.001) and AIx (r = 0.62, P < 0.001) independent of age, sex, heart rate, mean arterial pressure, and height (standardized β = 0.61 and 0.12, P ≤ 0.001). Aortic reservoir pressure independently predicted abnormal LVMI (β = 0.13, P = 0.024). Positive aortic-brachial stiffness mismatch does not result in higher AP or AIx. Aortic reservoir function, rather than discrete wave reflection from proximal arterial stiffness mismatching, provides a better model description of AP and AIx and also has clinical relevance as evidenced by an independent association of aortic reservoir pressure with LVMI.

  15. The effects of 12-week psyllium fibre supplementation or healthy diet on blood pressure and arterial stiffness in overweight and obese individuals.

    PubMed

    Pal, Sebely; Khossousi, Alireza; Binns, Colin; Dhaliwal, Satvinder; Radavelli-Bagatini, Simone

    2012-03-01

    Endothelial dysfunction and increased arterial stiffness occur early in the pathogenesis of the metabolic syndrome and they are both powerful independent predictors of cardiovascular risk. A high-fibre diet has been correlated with lower BMI and a lower incidence of hyperlipidaemia, CVD, hypertension and diabetes. The present randomised, parallel-design study compared the effects of fibre intake from a healthy diet v. fibre supplement diets on blood pressure (BP) and vascular function over 12 weeks. Overweight and obese adults were randomised to one of three groups: control (with placebo), fibre supplement (FIB) or healthy eating group with placebo (HLT). Systolic blood pressure (SBP) was lower in the FIB group compared with the control group at week 6, but not at week 12. However, SBP was lower in the HLT group compared with control group at week 12. At week 6, the FIB group presented lower diastolic blood pressure and augmentation index compared with the control group, but this result did not persist to the end of the study. The present study did not show any improvements in BP or vascular function in overweight and obese individuals with psyllium fibre supplementation over 12 weeks of intervention. However, a healthy diet provided the greatest improvements in BP in overweight and obese subjects. Further research with hypertensive individuals is necessary to elucidate whether increased fibre consumption in the form of psyllium supplementation may provide a safe and acceptable means to reduce BP, vascular function and the risk of developing CVD.

  16. Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity and arterial stiffness in very old Zucker rats.

    PubMed

    Sloboda, Natacha; Fève, Bruno; Thornton, Simon N; Nzietchueng, Rosine; Regnault, Véronique; Simon, Ginny; Labat, Carlos; Louis, Huguette; Max, Jean-Pierre; Muscat, Adeline; Osborne-Pellegrin, Mary; Lacolley, Patrick; Benetos, Athanase

    2012-09-01

    To analyze age-related interactions between obesity, its associated metabolic disorders, and macrocirculation, we studied large artery stiffness and fatty acid responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very old). Systolic arterial pressure was higher in old obese than in old lean rats (178 ± 10 vs 134 ± 8 mmHg, respectively). Carotid elastic modulus-wall stress curves showed increased age-dependent arterial stiffening, which was greater in obese animals. Old obese exhibited endothelial dysfunction with increased systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels (1,866 ± 177 vs 310 ± 34 μg/μL in lean animals). In old obese, linoleate and palmitate increased contractility to phenylephrine and reduced relaxation to acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial aging observed at 80 weeks. The early increase in free fatty acids may be a key effector in the severe arterial stiffness of the aged obese Zucker model.

  17. Endothelial function, arterial stiffness, and adherence to the 2010 Dietary Guidelines for Americans: a cross-sectional analysis

    PubMed Central

    Sauder, Katherine A.; Proctor, David N.; Chow, Mosuk; Troy, Lisa M.; Wang, Na; Vita, Joseph A.; Vasan, Ramachandran S.; Mitchell, Gary F.; Jacques, Paul F.; Hamburg, Naomi M.; West, Sheila G.

    2015-01-01

    Endothelial dysfunction and arterial stiffness are early predictors of cardiovascular disease. Intervention studies suggest that diet is related to vascular health, but most prior studies tested individual foods or nutrients and relied on small samples of younger adults. The purpose of this study was to examine relations between adherence to the 2010 Dietary Guidelines for Americans and vascular health in a large, cross-sectional analysis. In 5887 adults in the Framingham Heart Study Offspring and Third Generation cohorts, diet quality was quantified with the 2010 Dietary Guidelines for Americans Index (DGAI-2010). Endothelial function was assessed via brachial artery ultrasound and arterial stiffness via arterial tonometry. In age-, sex-, and cohort-adjusted analyses, higher DGAI-2010 score (greater adherence) was modestly associated with lower resting flow velocity, hyperemic response, mean arterial pressure, carotid-femoral pulse wave velocity, and augmentation index, but not associated with resting arterial diameter or flow-mediated dilation. In multivariable models adjusting for cardiovascular risk factors, only the association of higher DGAI-2010 with lower baseline flow and augmentation index persisted (β=−0.002, P=0.003 and β=−0.05 ± 0.02, P<0.001, respectively). Age-stratified multivariate-adjusted analyses suggested that the relation of higher DGAI-2010 scores with lower mean arterial pressure, pulse wave velocity, and augmentation index was more pronounced among adults younger than 50 years. Better adherence to the 2010 Dietary Guidelines for Americans, particularly in younger adults, is associated with lower peripheral blood flow velocity and arterial wave reflection but not flow-mediated dilation. Our results suggest a link between adherence to the Dietary Guidelines and favorable vascular health. PMID:25885520

  18. Anti-Platelet Factor 4/Heparin Antibody Plays a Significant Role in Progression of Arterial Stiffness among Hemodialysis Patients

    PubMed Central

    Kuo, Chieh; Tsai, Chiang-Chin; Chen, Chien-An; Tsai, Yueh-Feng; Chen, Yen-Hsun

    2017-01-01

    Background Arterial stiffness is a determinant of cardiovascular disease in end stage renal disease. Hemodialysis patients may develop anti-platelet factor 4/heparin antibody (PF4-H Ab) because of heparin treatment in dialysis. We tested whether PF4-H Ab was associated with progression of arterial stiffness in a 3-year follow-up. Methods We enrolled 74 hemodialysis patients and studied their clinical, biochemical and arterial stiffness measurement with brachial-ankle pulse wave velocity (baPWV) over 3 years. Baseline and changes in baPWV after 3 years (ΔbaPWV) were collected and compared with related clinical and biochemical parameters. PF4-H Ab was evaluated by the enzyme-linked immunosorbent assay and titer ≥ 0.4 was defined to have PF4-H Ab. Results We found a positive PF4-H Ab status in 25 of 74 patients. Mean baPWV was 16.1 ± 3.8 (m/s) at baseline and 17.6 ± 4.0 (m/s) after 3 years. Mean ΔbaPWV was 3.4 ± 2.2 (m/s) in the PF4-H Ab positive group, and 0.6 ± 1.2 (m/s) in the PF4-H Ab negative group. Baseline baPWV was only significantly associated with age (β = 0.49, p < 0.01). ΔbaPWV was significantly different between the PF4-H Ab positive and negative groups (p < 0.01). In multivariate regression analysis, only PF4-H Ab was positively associated with ΔbaPWV (β = 0.71, p < 0.01). Conclusions Our study concluded that PF4-H Ab was associated with progression of arterial stiffness in hemodialysis patients. PMID:28344423

  19. Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism: a cohort study

    PubMed Central

    Reece, Albert Stuart; Hulse, Gary Kenneth

    2013-01-01

    Objective To prospectively assess if opiate antagonist treatment or the opiate-free status could reverse opiate-related vasculopathy. Design Longitudinal Open Observational, Serial ‘N of One’, over 6.5 years under various treatment conditions: opiate dependence, naltrexone and opiate-free. Setting Primary care, Australia. Participants 20 opiate-dependent patients (16 males: 16 cases of buprenorphine 4.11±1.17 mg, two of methadone 57.5±12.5 mg and two of heroin 0.75±0.25 g). Intervention Studies of central arterial stiffness and vascular reference age (RA) were performed longitudinally by SphygmoCor Pulse Wave Analysis (AtCor, Sydney). Primary outcomes Primary outcome was vascular age and arterial stiffness accrual under different treatment conditions. Results The mean chronological age (CA) was 33.62±2.03 years. The opiate-free condition was associated with a lower apparent vascular age both in itself (males: p=0.0402 and females: p=0.0360) and in interaction with time (males: p=0.0001 and females: p=0.0004), and confirmed with other measures of arterial stiffness. The mean modelled RA was 38.82, 37.73 and 35.05 years in the opiate, naltrexone and opiate-free conditions, respectively. The opiate-free condition was superior to opiate agonism after full multivariate adjustment (p=0.0131), with modelled RA/CA of 1.0173, 0.9563 and 0.8985 (reductions of 6.1% and 11.9%, respectively). Conclusions Data demonstrate that opiate-free status improves vascular age and arterial stiffness in previous chronic opiate users. The role of opiate antagonist treatment in achieving these outcomes requires future clarification and offers hope of novel therapeutic remediation. PMID:23524044

  20. Relationship between Arterial Stiffness and Blood Pressure Drop During the Sit-to-stand Test in Patients with Diabetes Mellitus

    PubMed Central

    Kobayashi, Yusuke; Kobayashi, Hideo; Sumida, Koichiro; Suzuki, Shota; Kagimoto, Minako; Okuyama, Yuki; Ehara, Yosuke; Katsumata, Mari; Fujita, Megumi; Fujiwara, Akira; Saka, Sanae; Yatsu, Keisuke; Hashimoto, Tatsuo; Kuji, Tadashi; Hirawa, Nobuhito; Toya, Yoshiyuki; Yasuda, Gen; Umemura, Satoshi

    2017-01-01

    Aim: Patients with orthostatic hypotension (OH) have high arterial stiffness. Patients with diabetes mellitus (DM) often have cardiac autonomic neuropathy that leads to OH; however, whether OH is an indicator of arterial stiffness progression is unclear. We aimed to investigate whether the cardioankle vascular index (CAVI) varies between DM patients with and without OH using the sit-to-stand test (STST). Methods: One hundred and fifty-nine patients with DM underwent CAVI assessment and blood pressure (BP) and heart rate change evaluation during the STST. OH was defined as a decline in systolic BP (SBP) and/or diastolic BP of at least 20 mmHg or 10 mmHg, respectively, in the initial and late upright positions compared with that in the sitting position. Results: OH was diagnosed in 42 patients (26.4%). DM patients with OH had significantly higher CAVI (9.36 ± 1.15 versus 8.89 ± 1.18, p = 0.026) than those without OH. CAVI was significantly inversely correlated with systolic and diastolic BP changes (R = −0.347, p <0.001 and R = −0.314, p <0.001, respectively) in the initial upright position. Multivariate regression analysis revealed that age, SBP changes, and low frequency component in the initial upright position were independent determinants of CAVI. Conclusion: Patients with DM having large BP drops occurring when moving from sitting to standing have high arterial stiffness. A significant BP drop during the STST necessitates careful evaluation of advanced arterial stiffness in patient with DM. PMID:27453255

  1. Plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women

    PubMed Central

    Sheng, Li; Wu, Cai; Bai, Yong-Yi; Xiao, Wen-Kai; Feng, Dan; Ye, Ping

    2015-01-01

    Objectives To investigate the associations of the plasma homocysteine levels with the alterations in arterial stiffness in a community-based cohort. The gender differences in these associations were examined. Methods We evaluated the relationship between plasma homocysteine levels to three measures of vascular function [carotid-femoral pulse wave velocity (CF-PWV), carotid-ankle PWV (CA-PWV) and heart rate corrected augmentation index (AI)] in 1680 participants (mean age: 61.5 years; 709 men, 971 women) from communities of Beijing, China. Results In univariate analysis, plasma homocysteine levels was positively related to the CF-PWV (r = 0.211, P < 0.0001) and CA-PWV (r = 0.148, P < 0.0001), whereas inversely associated with AI (r = −0.052, P = 0.016). In multiple linear regression models adjusting for covariants, plasma homocysteine remained positively related to the CF-PWV (standardized β = 0.065, P = 0.007) in total cases. When the groups of men and women were examined separately, plasma homocysteine remained positively associated with the CF-PWV (standardized β = 0.082, P = 0.023) in men, whereas the relations between homocysteine and any of the arterial stiffness indices were not further present in women. Conclusions In Chinese population, plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women. PMID:26089849

  2. Calcium antagonist verapamil prevented pulmonary arterial hypertension in broilers with ascites by arresting pulmonary vascular remodeling.

    PubMed

    Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming

    2007-04-30

    Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers.

  3. Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights.

    PubMed

    Dardi, Fabio; Manes, Alessandra; Palazzini, Massimiliano; Bachetti, Cristina; Mazzanti, Gaia; Rinaldi, Andrea; Albini, Alessandra; Gotti, Enrico; Monti, Enrico; Bacchi Reggiani, Maria Letizia; Galiè, Nazzareno

    2015-08-01

    Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

  4. Arterial hypertension in children with hemolytic uremic syndrome after kidney transplantation.

    PubMed

    Hoenecke, Johannes; Hartmann, Hans; Melk, Anette

    2015-08-01

    The development of arterial hypertension after KTX is a well-known complication. HUS is a systemic disease associated with arterial hypertension during long-term follow-up. Our goal was to report on the severity of arterial hypertension after KTX in patients with typical and atypical HUS. We analyzed the course of 197 patients with HUS, of which 22 (n = 10 with typical HUS; n = 12 with atypical HUS) developed ESRF and received KTX as renal replacement therapy. We analyzed data from 1766 casual BP and 85 24-h ABPM measurements. In addition, we evaluated the used antihypertensive strategy. Comparison between the two patient groups revealed that patients with atypical HUS had significantly higher casual SBP-SDS and DBP-SDS values after KTX despite similar intensity of antihypertensive treatment. These data were supported by analysis of ABPM profiles showing comparable results for the interval 1-5 yr after KTX. Patients with atypical HUS had a greater severity of arterial hypertension despite similar treatment strategies and intensity of treatment. Our observation, even though in a small cohort, supports recent genetic studies showing arterial hypertension closely associated with HUS-causing mutations in patients with atypical HUS.

  5. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension

    PubMed Central

    Drexler, E. S; Bischoff, J. E; Slifka, A. J; McCowan, C. N; Quinn, T. P; Shandas, R; Ivy, D. D; Stenmark, K. R

    2008-01-01

    Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124

  6. Identification of artery wall stiffness: in vitro validation and in vivo results of a data assimilation procedure applied to a 3D fluid-structure interaction model.

    PubMed

    Bertoglio, Cristóbal; Barber, David; Gaddum, Nicholas; Valverde, Israel; Rutten, Marcel; Beerbaum, Philipp; Moireau, Philippe; Hose, Rodney; Gerbeau, Jean-Frédéric

    2014-03-21

    We consider the problem of estimating the stiffness of an artery wall using a data assimilation method applied to a 3D fluid-structure interaction (FSI) model. Recalling previous works, we briefly present the FSI model, the data assimilation procedure and the segmentation algorithm. We present then two examples of the procedure using real data. First, we estimate the stiffness distribution of a silicon rubber tube from image data. Second, we present the estimation of aortic wall stiffness from real clinical data.

  7. Pulmonary artery dissection: an emerging cardiovascular complication in surviving patients with chronic pulmonary hypertension.

    PubMed

    Khattar, R S; Fox, D J; Alty, J E; Arora, A

    2005-02-01

    Pulmonary arterial dissection is an extremely rare and usually lethal complication of chronic pulmonary hypertension. The condition usually manifests as cardiogenic shock or sudden death and is therefore typically diagnosed at postmortem examination rather than during life. However, recent isolated reports have described pulmonary artery dissection in surviving patients. The first case of pulmonary artery dissection in a surviving patient with cor pulmonale caused by chronic obstructive pulmonary disease is presented. The aetiology, pathophysiology, and clinical presentation of pulmonary artery dissection are reviewed and factors that may aid diagnosis during life are discussed.

  8. Prevalence of arterial stiffness and the risk of myocardial diastolic dysfunction in women

    PubMed Central

    Seeland, Ute; Brecht, Anna; Nauman, Ahmad T.; Oertelt-Prigione, Sabine; Ruecke, Mirjam; Knebel, Fabian; Stangl, Verena; Regitz-Zagrosek, Vera

    2016-01-01

    The present study determines the prevalence of vascular dysfunction and arterial stiffness (ASt) in a female urban population by measuring the brachial augmentation index (AIx) and aortic pulse wave velocity (PWV). The study tests the hypothesis that the measurement of AIx and PWV is useful in addition to that of traditional cardiovascular risk factors when assessing the risk for left ventricular diastolic dysfunction (LVDD). This cross-sectional study recruited 965 women aged 25–75 years from 12 districts of Berlin. The ASt indices, brachial AIx, aortic PWV and the central blood pressure were measured by an oscillometric method. A randomly selected subgroup (n=343) was examined by echocardiography. Trans-mitral inflow E/A ratio and diastolic mitral annulus velocity (é) were assessed. Questionnaires, medical history and blood sampling were used for the evaluation of individual risk factors. Normal vascular function was found in 55% of the women included. The prevalence of women with pathological AIx only (AIx ⩾ −10%, PWV normal) was 21.5%, whereas 17.9% were affected by increased AIx and PWV (AIx ⩾ −10%, PWV ⩾9.7 m/s), and 6% with only pathological PWV values. The prevalence of LVDD was 31.7%. LVDD was significantly associated with pathological PWV ⩾ 9.7 m/s [OR: 1.27, 95%CI: 1.02–1.57], age [OR: 4.17, 95%CI: 2.87–6.07] and a waist circumference >80 cm [OR: 3.61, 95%CI: 1.85–7.04] in multiple regression analysis. The high prevalence of markers for vascular dysfunction and ASt in a general female population and their importance as a mediator of diastolic dysfunction should encourage implementation of aortic PWV measurement to improve cardiovascular-risk assessment in particular to identify subclinical myocardial diastolic dysfunction. PMID:27653526

  9. AMBITION: An important piece in the therapeutic puzzle of pulmonary arterial hypertension.

    PubMed

    Said, Karim

    2015-01-01

    It is believed that simultaneous targeting of two or more of the three pathogenic pathways of pulmonary arterial hypertension (the endothelin, nitric oxide, and prostacyclin pathways) is associated with additive or synergistic effects with subsequent increasing efficacy and improving outcomes. However, there is lack of evidence to guide the use of combination strategy among pulmonary arterial hypertension patients and many questions remain to be answered. One of these vital questions is whether the strategy of upfront initiation of combination therapy could improve patients outcomes compared to the strategy of initial monotherapy. The recently published AMBITION trial represents an important forward step towards answering this question by comparing a strategy of first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in patients with pulmonary arterial hypertension.

  10. Association of fibroblast growth factor-23 with arterial stiffness in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Hsu, Jeffrey J.; Katz, Ronit; Ix, Joachim H.; de Boer, Ian H.; Kestenbaum, Bryan; Shlipak, Michael G.

    2014-01-01

    Background Serum fibroblast growth factor-23 (FGF-23) is associated with cardiovascular disease (CVD), yet the mechanisms remain uncertain. Our objective was to determine whether higher FGF-23 concentrations are associated with arterial stiffness. Methods In this cross-sectional study, serum FGF-23 concentrations were measured in 5977 participants without known CVD in the Multi-Ethnic Study of Atherosclerosis. The primary outcomes of interest were large (LAE) and small artery elasticity (SAE), pulse pressure and ankle-brachial index (ABI) > 1.30. LAE and SAE were measured by pulse contour analysis of the radial artery. Pulse pressure was measured with an automated sphygmomanometer using the average of two resting blood pressure measurements. ABI was calculated as the ratio of the ankle and brachial systolic blood pressures. Results Serum FGF-23 concentrations were not significantly associated with LAE [relative difference (RD) per doubling: 0%; 95% confidence interval (CI): −2–1%], SAE (RD per doubling: 0%; 95% CI: −3–2%), pulse pressure (β per doubling: 0.44; 95% CI: −0.31–1.19), or a high ABI (odds ratio per doubling: 1.14; 95% CI: 0.84–1.55). Findings were similar irrespective of chronic kidney disease status. Conclusions Higher serum FGF-23 concentrations are not associated with arterial stiffness, as measured by pulse pressure, LAE, SAE or high ABI, in a community-based population without CVD. PMID:24782533

  11. Arterial Resistance in Late First Trimester as a Predictor of Subsequent Pregnancy-Related Hypertension

    PubMed Central

    Kushtagi, Pralhad; Emani, Anoosha

    2016-01-01

    Objectives This study aimed to examine the association between indicators of arterial resistance occurring late in the first trimester and the subsequent development of pregnancy-related hypertension. Methods This study took place between May 2014 and August 2015 and included 329 consecutive women with singleton pregnancies attending the antenatal clinics of a medical college in Karnataka, India, during this period. Pulse pressure (PP) and uterine artery Doppler parameters were recorded between 11–14 gestational weeks. Consequently, women were followed-up until after delivery for subsequent hypertension. Results Hypertension occurred more frequently if PP was high (17.6% versus 14.4% of pregnancies without high PP; P = 0.713), if a diastolic notch (DN) was present (15.1% versus 12.8% of pregnancies with an absent DN; P = 0.612) and if the resistive index (RI) was raised (22.2% versus 14.3% of pregnancies without raised RI; P = 0.366). A raised pulsatility index (PI) was significantly associated with hypertension (P = 0.013). The risk of hypertension was approximately seven-fold higher if two or more arterial resistance indicators were used, except with a present DN plus a raised RI or a present DN plus high PP. All arterial resistance indicators showed negative predictability (>85.6%) and good specificity (≥95.0%), except for the presence of a DN. A population-specific cut-off PI value of 1.72 had high negative predictability (92.8%) and good sensitivity (70.8%) and specificity (65.1%). Conclusion Raised PI in the late first trimester was a significant predictor of hypertension later in pregnancy. A combination of arterial resistance indicators may enhance prediction of subsequent hypertension. PMID:28003891

  12. Health-related quality of life in patients with pulmonary arterial hypertension

    PubMed Central

    Taichman, Darren B; Shin, Jennifer; Hud, Laryssa; Archer-Chicko, Christine; Kaplan, Sandra; Sager, Jeffery S; Gallop, Robert; Christie, Jason; Hansen-Flaschen, John; Palevsky, Harold

    2005-01-01

    Background Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about health-related quality of life and its determinants in patients with pulmonary arterial hypertension. Methods Health-related quality of life was evaluated in a cross sectional study of 155 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with health-related quality of life scores. Results Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic ("primary") pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with better health-related quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with health-related quality of life scores. No differences in health-related quality of life were found between patients who were being treated with calcium channel antagonists, bosentan or continuously infused epoprostenol at the time of quality of life assessment. Conclusion Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. Specific associations with impaired health-related quality of life suggest potential areas for targeted intervention. PMID:16092961

  13. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension.

    PubMed

    Kossmann, Sabine; Lagrange, Jeremy; Jäckel, Sven; Jurk, Kerstin; Ehlken, Moritz; Schönfelder, Tanja; Weihert, Yvonne; Knorr, Maike; Brandt, Moritz; Xia, Ning; Li, Huige; Daiber, Andreas; Oelze, Matthias; Reinhardt, Christoph; Lackner, Karl; Gruber, Andras; Monia, Brett; Karbach, Susanne H; Walter, Ulrich; Ruggeri, Zaverio M; Renné, Thomas; Ruf, Wolfram; Münzel, Thomas; Wenzel, Philip

    2017-02-01

    Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 expression and integrin αMβ2- and platelet-dependent leukocyte adhesion to arterial vessels. The resulting vascular inflammation and dysfunction was mediated by activation of thrombin-driven factor XI (FXI) feedback, independent of factor XII. The FXI receptor glycoprotein Ibα on platelets was required for this thrombin feedback activation in angiotensin II-infused mice. Inhibition of FXI synthesis with an antisense oligonucleotide was sufficient to prevent thrombin propagation on platelets, vascular leukocyte infiltration, angiotensin II-induced endothelial dysfunction, and arterial hypertension in mice and rats. Antisense oligonucleotide against FXI also reduced the increased blood pressure and attenuated vascular and kidney dysfunction in rats with established arterial hypertension. Further, platelet-localized thrombin generation was amplified in an FXI-dependent manner in patients with uncontrolled arterial hypertension, suggesting that platelet-localized thrombin generation may serve as an inflammatory marker of high blood pressure. Our results outline a coagulation-inflammation circuit that promotes vascular dysfunction, and highlight the possible utility of FXI-targeted anticoagulants in treating hypertension, beyond their application as antithrombotic agents in

  14. [The influence of citoflavin on molecular mechanisms of hypertensive encephalopathy development in patients with systolic arterial hypertension].

    PubMed

    Kartashova, E A; Romantsov, M G; Sarvilina, I V

    2014-01-01

    The molecular pharmacological effects of cytoflavin in patients with hypertensive encephalopathy (HE) and isolated systolic arterial hypertension (ISAH) have been investigated using the following methods: assessment of complaints, 24-hour arterial pressure monitoring, ultrasound diagnostics including echocardiography, measurement of lipid profiles and coagulograms, and molecular phenotyping by MALDI-TOF/TOF-MS. A combination of cytoflavin administration with standard therapy of HE and ISAH led to the most expressed return development of clinical symptoms, restoration of the hemodynamic, structural, and geometrical parameters of cardiovascular system, and normalization of the indices of lipid profiles and coagulograms in comparison to patients with HE and ISAH, which accepted only standard therapy. Molecular mechanisms of cytoflavin action have been revealed, which include control of the activity of cellular signaling pathways by means of intermolecular interactions. The optimized therapy of HE and ISAH is recommended for clinical application, which assumes a combined use of standard therapy and cytoflavin and provides a geroprotective action upon the cardiovascular system.

  15. The effects of direct renin inhibitor, aliskiren, on arterial hypertension, chronic kidney disease and cardiovascular disease: optimal pharmacotherapy.

    PubMed

    Morishita, Yoshiyuki; Kusano, Eiji

    2013-03-01

    The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of progression of arterial hypertension, chronic kidney disease (CKD) and cardiovascular disease (CVD). Previous studies suggested that a direct renin inhibitor, aliskiren, may be effective for blood pressure lowering, renoprotection and cardiovascular protection. This review focuses on the effects of aliskiren for arterial hypertension, CKD and CVD.

  16. Arterial hypertension in migraine: Role of familial history and cardiovascular phenotype.

    PubMed

    Babayan, Laura; Mamontov, Oleg V; Amelin, Alexander V; Bogachev, Mikhail; Kamshilin, Alexei A

    2017-03-01

    Recent studies indicate that migraine is associated with increased risk of cardiovascular diseases. However, links between autonomic cardiovascular regulation, arterial hypertension (AH) and migraine are still little explored. In this study, we evaluated autonomic regulation in migraine patients with and without hypertension. We studied 104 patients with migraine, aged 34±10 y, including 28 with and 76 without hypertension (M+AH and M-AH groups, respectively). The control group consisted of 88 healthy volunteers matched by age and sex. The autonomic regulation of circulation was examined with the tilt-table test, deep-breathing and Valsalva Maneuver, handgrip test, cold-stress induced vasoconstriction, arterial baroreflex, and blood pressure variability measurements. We found that migraine patients with concomitant hypertension demonstrated reduced arterial baroreflex, whereas other parameters of cardiac autonomic regulation were unchanged. In contrast, most indicators of vasomotor reactivity (blood pressure response to the hand-grip, Valsalva maneuver and cold vasoconstriction) were enhanced in migraine patients with no significant differences between migraine patients with and without hypertension. Patients from both M+AH and M-AH groups more commonly had a family history of cardiovascular disorders. Our data revealed increased vasomotor reactivity in migraine patients, with or without concomitant hypertension. This was associated with the family history of cardiovascular diseases.

  17. [Influence of work intensity on development of arterial hypertension in metal-mining workers].

    PubMed

    Ustinova, O Iu; Alekseev, V B; Rumiantseva, A N; Orehova, Ia V

    2013-01-01

    The article covers data on influence of working shifts duration and shift work intensity on cardiovascular system functioning in operators of mining excavators. Findings are that 8 hours shift with regular shift schedule (40 working hours per week) gives significant load on cardiovascular system of workers engaged into underground activities. 50% of mining excavator operators following this working schedule develop transitory arterial hypertension within 10 years. Longer work shift over 8 hours and more intensive shifting schedule over 40 hours per week causes stable arterial hypertension within 3 months in 60% of workers, in 10% of cases associated with lower functioning of sinus node.

  18. Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment.

    PubMed

    Taçoy, Gülten; Ekim, Numan Nadir; Cengel, Atiye

    2010-04-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive increase in pulmonary vascular resistance, which may lead to right ventricular failure and death. Major cardiovascular and pulmonary alterations occur during pregnancy and therefore worsen or increase the complications of pulmonary arterial hypertension (PAH). A patient diagnosed with IPAH after a successful full-term pregnancy and cesarean section with epidural anesthesia is presented. The postoperative course was complicated by progressive dyspnea, and lower limb edema. The outcome of treatment with sildenafil during puerperium was favorable in this patient. The clinical course was complicated by an unexpected spontaneous pregnancy after primary infertility.

  19. [Analysis of changes in characteristics of arterial hypertension occupational risk in workers of nonferrous metallurgy].

    PubMed

    Vlasova, E M; Shliapnikov, D M; Lebedeva, T M

    2015-01-01

    The article covers changes in occupational cardiovascular risk for workers of nonferrous,metallurgy. Findings are that exposure to noise up to 94 dB with length of service increases possible atherosclerosis and metabolic syndrome. With 5 years of service, risk of the predicted conditions increases by 40.5%. When occupational exposure lasts over 5 years, risk of arterial hypertension increases. A group of workers without exposure to occupational factors appeared to have no connection between length of service and metabolic syndrome and arterial hypertension. Risk evolution modelling proved that risk of functional disorders in nonferrous metallurgy workers becomes unacceptable after 5 years of service (cardiovascular disorders are critical).

  20. Management of Sepsis in Patients with Pulmonary Arterial Hypertension in the Intensive Care Unit.

    PubMed

    Tartavoulle, Todd M

    2017-03-01

    Pulmonary arterial hypertension is a lethal condition, and the management of sepsis in patients with pulmonary arterial hypertension is challenging. As the disease progresses, the right ventricle is susceptible to failure due to a high pulmonary vascular resistance. The limited ability of the right ventricle to increase cardiac output in septic shock makes it difficult to deliver oxygen to the organ and tissues. Intravascular volume replacement and vasoactive drugs should only be considered after a thorough assessment. Priorities of care include improving cardiac output and oxygen delivery by optimizing preload, reducing afterload, and improving contractility.

  1. Arterial hypertension with brachydactyly in a 15-year-old boy.

    PubMed

    Litwin, Mieczysław; Jurkiewicz, Elzbieta; Nowak, Katarzyna; Kościesza, Andrzej; Grenda, Ryszard; Malczyk, Katarzyna; Kościesza, Iwona

    2003-08-01

    Autosomal dominant brachydactyly with hypertension is the only form of monogenic hypertension which is not sodium dependent. The disease is characterized by brachydactyly type E, short stature, arterial hypertension and aberrant loop of posterior inferior cerebellar artery (PICA) causing neurovascular conflict. So far the syndrome was described in one family in Turkey and two in Canada. We report a case of a 15-year-old boy who was admitted because of arterial hypertension 160/100 mmHg. He complained also of attacks of bilateral numbness of hands with deterioration of visual field. Examination revealed short stature (156 cm) and bone deformities of hands and feet consistent with brachydactyly type E. Ophthalmoscopy showed mild narrowing of retinal arteries. Serum electrolytes, blood gases, and renal function were normal. Renin activity and aldosterone concentrations were raised, and 24-h urinary excretion of catecholamines and urinary steroid profile were in normal range. Renal Doppler ultrasound was normal, but renal scintigraphy suggested vascular changes in the left kidney. Echocardiographic examination, besides mild left ventricular hypertrophy, was normal. Magnetic resonance angiography (angio-MR) revealed bilateral abnormal PICA loops and neurovascular conflict. Spiral angiotomography of renal arteries revealed narrow additional left renal artery. Both nonconsanguineous parents and younger brother were healthy, with normal height, without bone deformities, and had normal intracranial vessels. Amlodipine and metoprolol were given, and blood pressure lowered to 143/87. Adding rilmenidine gave no effect and enalapril was then added. It led to further improvement in blood pressure control. To our knowledge, this is the first pediatric description of a sporadic form of autosomal dominant brachydactyly with hypertension with abnormalities of brain and renal arteries.

  2. Peripheral pulmonary artery stenosis as a cause of pulmonary hypertension in adults

    PubMed Central

    Ahmed, Mostafa; Hamed, Fadi; Prieto, Lourdes R.

    2015-01-01

    Abstract Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in the adult population. PPAS can lead to pulmonary hypertension but is likely misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. We retrospectively identified adult patients with PPAS either in its isolated form or related to other congenital defects from January 1998 to September 2012. We reviewed the patients’ clinical data by using our hospital electronic medical records and/or their paper charts. We identified 6 adult patients with PPAS with an age range of 16–56 years (1 woman and the rest men). Presenting signs and symptoms were thoracic murmurs, progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome. Pulmonary angiography showed that PPAS was predominantly located in main branches or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial narrowing was at the level of the segmental pulmonary arteries. Right heart catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to 60 mmHg. Balloon dilation was performed in all patients, predominantly in the lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46% in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had follow-up echocardiograms at 1 year that showed stable echocardiographic findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic challenge. Therefore, a high index of suspicion during the initial evaluation of pulmonary hypertension is essential for its prompt diagnosis and adequate treatment. PMID:25992283

  3. [Innovative instruction for assisting patients with arterial hypertension].

    PubMed

    Bontemps, S; Pechère-Bertschi, A

    2015-09-09

    The MOOC In The Heart of Hypertension is an innovative online training for students and health providers. Its aim is to strengthen skills for professionals caring people suffering from hypertension. A MOOC is a free online training aiming unlimited participation. It widely promotes a high quality education. Medical and paramedical training recently seized upon this powerful tool, for initial and continuing training. Indeed, MOOC responds to several pedagogic challenges, particularly through educational strategies focused on the learner's skills: mastery of pedagogy, retrieval practice and peer grading. This MOOC about hypertension aims at responding to the needs of caregivers to enhance their therapeutic support skills.

  4. Light and scanning electron microscopic and immunohistochemical studies on permeability of hypertensive rat mesenteric arteries.

    PubMed

    Suzuki, K; Kawaharada, U; Takatama, M; Ooneda, G

    1985-09-01

    Experimental hypertensive rats were intravenously injected with carbon and iron as tracers, and their mesenteric arteries exhibiting hypertensive arterial lesions were observed by light and scanning electron microscopy and immunohistochemistry. Early arterial lesions showing intense medial damages, deposition of fibrinoid substance consisting of fibrin in the intima and/or media, and granulation tissue in the adventitia were characterized by marked insudation of intravenously injected tracers. Scanning electron microscopy demonstrated numerous leukocytes and platelets adhering to endothelial surface, opened endothelial cell junctions, and desquamation of these cells. Immunohistochemistry revealed laminin and low stainability of fibronectin in the subendothelium. Advanced lesions showed deposition of a large amount of fibrinoid substance and no insudation of tracers in the intima, but scanning electron microscopy manifested opening of endothelial cell junctions, desquamation of endothelial cells, and adherence of leukocytes and platelets. Immunohistochemistry revealed fibronectin in the intima and laminin just beneath the endothelium. In the healed lesions disclosing fibrocellular intimal thickening, there was no insudation of tracers. Scanning electron microscopy showed opened endothelial cell junctions, endothelial cell defects, and adherence of leukocytes and platelets. There were fibronectin in the intima and laminin beneath the endothelium. It was suggested that the opening of endothelial cells junctions and desquamation of endothelial cells would be necessary for the arterial increased permeability in hypertensive rats, and that fibrin-fibronectin complex, fibronectin-acid mucopolysaccharide complex, and basement membrane would together inhibit the increased permeability in the mesenteric arteries of hypertensive rats in spite of endothelial cell injuries and their defects.

  5. Renal artery stenosis and hypertension after abdominal irradiation for Hodgkin disease. Successful treatment with nephrectomy

    SciTech Connect

    Salvi, S.; Green, D.M.; Brecher, M.L.; Magoos, I.; Gamboa, L.N.; Fisher, J.E.; Baliah, T.; Afshani, E.

    1983-06-01

    Hypertension secondary to stenosis of the left renal artery developed in a thirteen-year-old male six years after completion of inverted Y irradiation (3,600 rad) for abdominal Hodgkin disease. Surgical treatment with nephrectomy resulted in control of the hypertension without the use of antihypertensive agents. We review the literature for this unusual complication of abdominal irradiation, and recommend that a 99mTc-DMSA renal scan, selective renal vein sampling for renin determinations, and renal arteriography be performed on any patient in whom hypertension develops following abdominal irradiation in childhood.

  6. Hypertension and impairment of endothelium-dependent relaxation of arteries from spontaneously hypertensive and L-NAME-treated Wistar rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Hirakawa, A; Nakahira, T; Yamaoka, M; Shimamura, K; Yamamoto, K; Sunano, S

    2001-04-01

    Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

  7. Associations of atherosclerosis in the descending thoracic aorta on CTA with arterial stiffness and chronic kidney disease in asymptomatic patients with diabetes mellitus.

    PubMed

    Roos, Cornelis J; Delgado, V; de Koning, Eelco J; Rabelink, Ton J; Jukema, J Wouter; Bax, Jeroen J; Scholte, Arthur J

    2014-08-01

    The relation between atherosclerosis in the descending thoracic aortic (DTA), arterial stiffness and chronic kidney disease (CKD) in patients with diabetes mellitus (DM) remains unclear. The current aim was to evaluate associations of DTA atherosclerosis with arterial stiffness and parameters of CKD in asymptomatic patients with DM. A total of 213 asymptomatic patients with diabetes (mean age 52 years, 56% men) underwent cardiovascular risk assessment including multi-slice computed tomography (for non-invasive coronary angiography, from which DTA atherosclerosis can be derived), non-invasive assessment of arterial stiffness with applanation tonometry and assessment of renal function. Measurements of DTA atherosclerosis included assessment of DTA thickening and calcium score. Arterial stiffness was determined by the carotid-femoral pulse wave velocity (PWV), parameters of CKD included estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). DTA atherosclerosis was present in 180 (84%) patients. Patients with DTA atherosclerosis had increased arterial stiffness, lower eGFR and higher UACR values. After multivariate correction, DTA calcium score was independently associated with PWV (β = 0.18, p = 0.04). Furthermore, both DTA maximal wall thickness and DTA calcium score were independently associated with eGFR (β = -7.37, p < 0.001 and β = -1.99, p < 0.003, respectively), but not with UACR. The increase in arterial stiffness by atherosclerosis seemed to be mediated by arterial calcification, while the DTA calcium score was independently associated with arterial stiffness, but not DTA maximal wall thickness. Furthermore, parameters of CKD in patients with DM had a distinct relationship with DTA atherosclerosis: DTA atherosclerosis was associated with eGFR but not with UACR.

  8. Mathematical Model Analysis of Heart-Arterial Interaction in Hypertension

    DTIC Science & Technology

    2007-11-02

    in vivo data show that in hypertensives with LVH, systolic and diastolic blood pressure increase by about 40% while cardiac output is constant and wall...compliance 25% lower and peripheral resistance 40% higher in hypertensives than in normotensive controls [13], and predicted blood pressure , cardiac output...thickness increases by 30-55%. In both (i) and (ii), blood pressure increased by only 10% while cardiac output dropped by 20%. In (ii), LV wall

  9. Transcatheter Embolization of Pulmonary Artery False Aneurysm Associated with Primary Pulmonary Hypertension

    SciTech Connect

    Hiraki, T. Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.

    2004-03-15

    A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred.

  10. Sudden death caused by unsuspected pulmonary arterial hypertension, 10 years after surgery for extrahepatic biliary atresia.

    PubMed

    Moscoso, G; Mieli-Vergani, G; Mowat, A P; Portmann, B

    1991-04-01

    A case of extrahepatic biliary atresia presenting with an acute respiratory episode and rapid deterioration, 10 years after a successful portoenterostomy and a very active life, was the setting of unsuspected severe pulmonary arterial hypertension leading to sudden death. The pulmonary arteries showed widespread plexiform lesions, thickening of the muscular media, and subendothelial proliferation. Occasionally, eccentric arterial obstructive lesions and fibrinous thrombi were observed. There was marked reduction of preacinar arterioles with a consequent increase in the alveolar/arterial ratio. The pulmonary veins showed arterialization of their walls. There was marked hypertrophy of myocardial fibres in the right ventricle together with foci of myocardial degeneration and fibrosis. Areas of endocardial thickening were observed in both ventricles. The absence of clinical indicators of pulmonary arterial hypertension at any but the terminal stages of the disease precluded any form of conservative management. Lung-heart and presumably liver transplantation might have been the only option. Prospective assessment of pulmonary function and haemodynamic studies should be considered in cirrhotic patients with portal hypertension.

  11. Pulmonary artery haemodynamic properties in patients with pulmonary hypertension secondary to rheumatic mitral stenosis.

    PubMed

    Yan, Tao; Zhang, Guan-xin; Li, Bai-lin; Zhong, Keng; Xu, Zhi-yun; Han, Lin

    2012-12-01

    We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P<0.01); (2) linear correlation analyses showed that preoperative mean pulmonary artery pressure (mPAP) closely correlated with zero-pressure compliance in the mitral stenosis group (r=-0.745, P<0.05); (3) PAP and pulmonary vascular resistance decreased significantly in both groups with mitral stenosis after infusing 0.5 μg kg(-1) min(-1) of sodium nitroprusside (P<0.01). The pulmonary zero pressure compliance and mean pressure compliance increased significantly in the group with mild pulmonary hypertension; whereas in the severe group, the mean compliance changed with significance as the mPAP decreased (1.51 ± 0.59 vs 1.81 ± 0.77 ml/mmHg), however no significant change occurred in the pulmonary zero pressure compliance (2.35 ± 1.24 ml/mmHg vs. 2.24 ± 1.53 ml/mmHg, P>0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.

  12. The Impact of Remote Ischemic Preconditioning on Arterial Stiffness and Heart Rate Variability in Patients with Angina Pectoris

    PubMed Central

    Zagidullin, Naufal; Scherbakova, Elena; Safina, Yuliana; Zulkarneev, Rustem; Zagidullin, Shamil

    2016-01-01

    Remote ischemic preconditioning (RIPC) is the set of ischemia episodes that protects against subsequent periods of prolonged ischemia through the cascade of adaptive responses; however, the mechanisms of RIPC are not entirely clear. Here, we aimed to study the impact of RIPC in patients with stable angina pectoris and compare it with healthy individuals with respect to arterial stiffness and heart rate variability. In the randomized, sham-controlled, crossover blind design study, a group of 30 coronary heart disease (CHD) patients (63.9 ± 1.6 years) with stable angina pectoris NYHA II-III and a control group of 20 healthy individuals (58.2 ± 2.49) were both randomly allocated for remote RIPC or sham RIPC. Arterial stiffness, pulse wave velocity (Spygmacor, Australia), and heart rate variability (HRV) were recorded before and after the procedure followed by the crossover examination. In the group of healthy individuals, RIPC showed virtually no impact on the cardiovascular parameters, while, in the CHD group, the systolic and central systolic blood pressure, central pulse pressure, and augmentation decreased, and total power of HRV improved. We conclude that ischemic preconditioning reduces not only systolic blood pressure, but also reduces central systolic blood pressure and improves arterial compliance and heart rate modulation reserve, which may be associated with the antianginal effect of preconditioning. PMID:27348009

  13. Left Ventricular Mass and Intrarenal Arterial Stiffness as Early Diagnostic Markers in Cardiorenal Syndrome Type 5 due to Systemic Sclerosis

    PubMed Central

    Gigante, Antonietta; Barilaro, Giuseppe; Barbano, Biagio; Romaniello, Antonella; Di Mario, Francesca; Quarta, Silvia; Gasperini, Maria Ludovica; Di Lazzaro Giraldi, Gianluca; Laviano, Alessandro; Amoroso, Antonio; Cianci, Rosario; Rosato, Edoardo

    2016-01-01

    Background Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. Methods Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. Results Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36), resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. Conclusions SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression. © 2016 S. Karger AG, Basel PMID:27022332

  14. Non-HDL cholesterol is a good predictor of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population

    PubMed Central

    de Oliveira Alvim, Rafael; Mourao, Carlos Alberto; Magalhães, Géssica Lopes; de Oliveira, Camila Maciel; Krieger, José Eduardo; Mill, José Geraldo; Pereira, Alexandre Costa

    2017-01-01

    OBJECTIVES: Increased arterial stiffness is an important determinant of the risk of cardiovascular disease. Lipid profile impairment, especially hypercholesterolemia, is associated with stiffer blood vessels. Thus, the aim of this study was to determine which of the five circulating lipid components (high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL), total cholesterol (TC) and triglycerides) is the best predictor of increased arterial stiffness in an urban Brazilian population. METHODS: A random sample of 1,662 individuals from the general population of Vitoria, Brazil (25-64 years), was selected, and lipid components were measured using standard methods. Pulse wave velocity was measured using a non-invasive automatic device, and increased arterial stiffness was defined as a pulse wave velocity ≥10 m/s. RESULTS: In men, only total cholesterol (OR=1.59; CI=1.02 to 2.48, p=0.04) was associated with the risk of increased arterial stiffness. In women, HDL-C (OR=1.99; CI=1.18 to 3.35, p=0.01) and non-HDL-C (OR=1.61; CI=1.01 to 2.56, p=0.04) were good predictors of the risk of increased arterial stiffness. However, these associations were only found in postmenopausal women (OR=2.06; CI=1.00 to 4.26, p=0.05 for HDL-C and OR=1.83; CI=1.01 to 3.33, p=0.04 for non-HDL-C). CONCLUSION: Our findings indicate that both HDL-C and non-HDL-C are good predictors of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population and may be useful tools for assessing the risk of arterial stiffness. PMID:28273234

  15. Intrapulmonary arteries respond to serotonin and adenosine triphosphate in broiler chickens susceptible to idiopathic pulmonary arterial hypertension.

    PubMed

    Kluess, H A; Stafford, J; Evanson, K W; Stone, A J; Worley, J; Wideman, R F

    2012-06-01

    This study examined factors contributing to increased vascular resistance and plexiform lesion formation in broiler chickens susceptible to idiopathic pulmonary arterial hypertension (IPAH). A diet supplemented with excess tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary arterial pressures than broilers fed the control diet, and plexiform lesion incidences tended to be higher (P = 0.11) in the high-Trp group than in the control group at 30 d of age. The intrapulmonary arteries were assessed for vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and for activities of key metabolic enzymes for serotonin and ATP. The pulmonary artery (defined as the first major branch of the pulmonary artery inside the lung) and the primary pulmonary arterial rami (defined as the second major branch of the pulmonary artery inside the lung) both exhibited vasoconstriction in response to serotonin and ATP. This is the first study to demonstrate purinergic-mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole responsiveness did not differ between broilers fed the control diet or the high-Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase activity, responsible for the breakdown of serotonin, was severely impaired in pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin may persist longer and elicit an amplified response in broilers fed the high-Trp diet.

  16. Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension.

    PubMed

    Courand, Pierre-Yves; Pina Jomir, Géraldine; Khouatra, Chahéra; Scheiber, Christian; Turquier, Ségolène; Glérant, Jean-Charles; Mastroianni, Bénédicte; Gentil, Béatrice; Blanchet-Legens, Anne-Sophie; Dib, Alfred; Derumeaux, Geneviève; Humbert, Marc; Mornex, Jean-François; Cordier, Jean-François; Cottin, Vincent

    2015-01-01

    Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.

  17. Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

    PubMed Central

    2014-01-01

    Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions. PMID:25343007

  18. Nodular transformation of the liver associated with portal and pulmonary arterial hypertension.

    PubMed

    Portmann, B; Stewart, S; Higenbottam, T W; Clayton, P T; Lloyd, J K; Williams, R

    1993-02-01

    A case of multiple focal nodular hyperplasia (FNH) of the liver associated with noncirrhotic portal hypertension and later complicated by pulmonary arterial hypertension leading to death from right heart failure is reported. In retrospect, the portal hypertension diagnosed in early life was most likely due to a congenital hypoplasia of portal vein branches and multiple FNH, a hyperplastic response of the liver parenchyma in association with anomalies of hepatic arterial branches as found within the lesions. This case may represent a form of multiple FNH syndrome restricted to the liver, because neither extrahepatic vascular malformation nor brain tumor was identified at autopsy. The FNH lesions had considerably expanded over the years, and the severe sinusoidal congestion due to chronic right-sided heart failure with subsequent prolonged parenchymal exposure to blood-borne hepatotrophic factors is a likely explanation for both the massive enlargement of FNH lesions and the nodular regenerative hyperplasia observed in the intervening parenchyma.

  19. Relations between a novel, reliable, and rapid index of arterial compliance (PP-HDI) and well-established inidices of arterial blood pressure (ABP) in a sample of hypertensive elderly subjects.

    PubMed

    Bergamini, L; Finelli, M E; Bendini, C; Ferrari, E; Veschi, M; Neviani, F; Manni, B; Pelosi, A; Rioli, G; Neri, M

    2009-01-01

    Hypertension is a risk factor for a long-lasting arterial wall-remodelling leading to stiffness. The rapid method measuring the pulse pressure (PP) by means of the tool of Hypertension Diagnostic Instruments (HDI) called PP-HDI, overcomes some of the problems arising with more-time consuming methods, like ambulatory blood pressure monitoring (ABPM), and give information about the elasticity of the arterial walls. We studied the relationship between the PP-HDI, the large artery compliance (LA-C) and small artery compliance (SA-C) and few well-established indices of arterial blood pressure (ABP) in a sample of 75 hypertensive subjects, aged 65 years and over. Significant correlations between LA-C and heart rate (HR), PP-ABPM and PP-HDI were found. SA-C relates with HR and systolic blood pressure (SBP) measured in lying and standing positions. Applying a stepwise regression analysis, we found that LA-C variance stems from PP-HDI and HR, while SA-C variance stems from SBP in lying position. Receiver operator characteristic (ROC) curves for thresholds of PP showed that PP-HDI reached levels of sensitivity/specificity similar to PP-ABPM. In conclusion, surveillance of ABP through hemo-dynamic indices, in particular of SBP, is essential, nevertheless the advantage of this control is not known in an elderly population where the organ damage is already evident. PP needs necessarily an instrumental measurement. The PP-HDI result is similar in reliability with respect to PPABPM, but is more rapid and well applicable in an elderly population.

  20. Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

    2008-03-01

    Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

  1. Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

    PubMed

    Adams, Dustin S; Marolf, Angela J; Valdés-Martínez, Alejandro; Randall, Elissa K; Bachand, Annette M

    2017-03-29

    Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected

  2. The effects of acute hypobaric hypoxia on arterial stiffness and endothelial function and its relationship to changes in pulmonary artery pressure and left ventricular diastolic function.

    PubMed

    Boos, C J; Hodkinson, P; Mellor, A; Green, N P; Woods, D R

    2012-06-01

    This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800 m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e'), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO₂ (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3 mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e' filling velocity or E/e'. There was a significant inverse correlation between SpO₂ and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO₂ and change (Δ) in RI (baseline vs. 150 min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.

  3. Systemic antioxidant properties of L-carnitine in two different models of arterial hypertension.

    PubMed

    Mate, Alfonso; Miguel-Carrasco, José L; Monserrat, María T; Vázquez, Carmen M

    2010-06-01

    In spite of a wide range of drugs being available in the market, treatment of arterial hypertension still remains a challenge, and new therapeutic strategies could be developed in order to improve the rate of success in controlling this disease. Since oxidative stress has gained importance in the last few years as one of the mechanisms involved in the origin and development of hypertension, and considering that L-carnitine (LC) is a useful compound in different pathologies characterized by increased oxidative status, the aim of the present study was to investigate the systemic antioxidant effect of LC and its correlation to blood pressure in two experimental models of hypertension: (1) spontaneously hypertensive rats (SHR) and (2) rats with hypertension induced by N(omega)-nitro-L-arginine methyl ester (L-NAME). Treatment with captopril was also performed in SHR in order to compare the antioxidant and antihypertensive effects of LC and captopril. The antioxidant defense capacity, in terms of antioxidant enzyme activity, glutathione system availability and plasma total antioxidant capacity, was measured in both animal models with or without an oral, chronic treatment with LC. All the antioxidant parameters studied were diminished in SHR and in L-NAME-treated animals, an alteration that was in general reversed after treatments with LC and captopril. In addition, LC produced a significant but not complete reduction of systolic and diastolic blood pressure levels in these two models of hypertension, whereas captopril was able to normalize blood pressure. Both LC and captopril prevented the reduction in nitric oxide (NO) levels observed in hypertensive animals. This suggests a decrease in the systemic oxidative stress and a higher availability of NO induced by LC in a similar way to captopril's effects, which could be relevant in the management of arterial hypertension eventually.

  4. Association of Serum 25-hydroxy-vitamin D Concentration and Arterial Stiffness among Korean Adults in Single Center

    PubMed Central

    Lee, Jung Hae

    2017-01-01

    Background There are growing concerns about the role of vitamin D deficiency in cardiovascular diseases. Therefore, we investigated the correlation between serum 25-hydroxy-vitamin D (25[OH]D) and arterial stiffness among Korean adults. Methods We retrospectively reviewed the medical charts of 302 people (115 women and 187 men) who visited a tertiary hospital from January 2015 to December 2016. Serum 25(OH)D was measured using the radioimmunoassay technique, and brachial-ankle pulse wave velocity (baPWV) was measured using an automatic wave analyzer. We obtained the doctor's report on the medical history of the participants, their alcohol consumption and smoking habits, and their exercise status. Metabolic syndrome was diagnosed based on guidelines from the National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP III) and the International Diabetes Federation (IDF). Results of basic blood tests and physical assessment were also collected. Results In the Pearson correlation analysis, serum 25(OH)D and baPWV showed a statistically significant inverse relationship (r=-0.279, P<0.001). Using multiple regression analysis, and after adjusting for possible confounders, serum 25(OH)D concentration was found to be significantly associated with baPWV (β=-0.121, P=0.011). Conclusions We observed an association between serum 25(OH)D concentration and arterial stiffness. Further studies involving larger sample sizes will be needed to confirm this associations. PMID:28326301

  5. [State of the dopamine system activity, as one of factors for the development of arterial hypertension and obesity].

    PubMed

    Lyzogub, V H; Dolynna, O V; Bogdan, T V; Sobol', V O

    2012-01-01

    The discovery of 5 subtypes of dopamine receptors revealed their important role in development of arterial hypertension and obesity. Reduce of their functional activity or number with age conduces to the increase of tone of the sympathetic nervous system, dyspoiesis of leptin, hyperphagia, development of obesity and arterial hypertension. Prescription of dopamine agonists conduces to reduction of in, normalization of leptin, diminishing of appetite and body mass, decrease of blood pressure. Combination of arterial hypertension and obesity is recommended to determine dopamine excretion and to appoint dopamine agonists at level of < 600 nmol/24 hours.

  6. Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

    PubMed

    Zaveljcina, Janez; Legan, Mateja; Gaberšček, Simona

    2016-05-01

    We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension.

  7. [Non-pharmacologic treatment of arterial hypertension in hemodialysis patients].

    PubMed

    Chazot, C; Charra, B

    2007-10-01

    High blood pressure in dialysis patients is related to extracellular volume excess and the related increase of systemic vascular resistances. Scribner has early described the treatment of hypertension with ultrafiltration and low salt diet, without any drugs. The dry weight method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. Additional measures are needed such as low salt diet, neutral sodium balance during dialysis treatment, stop of antihypertensive drugs, adequate length of the dialysis session, and patient education. It may exist a lag time between the normalization of the extracellular volume and blood pressure. It is related to the correction of the hemodynamic consequences of the extracellular volume overload. Moreover, the dry weight may potentially vary in patients undergoing catabolic intercurrent events. The complications of these changes (severe hypertension, pulmonary oedema) must be anticipated by the nephrologist and the staff to avoid additional morbidity to the patient.

  8. Improved Pulse Transit Time Estimation by System Identification Analysis of Proximal and Distal Arterial Waveforms

    DTIC Science & Technology

    2011-10-01

    only), electrical im- pedance, pulse oximetry, and even noncontact laser Doppler vibrometry (8). The disadvantage of the approach is that it may not...Morbiducci U, Scalise L, Tomasini EP, Delbeke D, Baets R, Van Bortel LM, Segers P. A noncontact approach for the evaluation of large artery stiffness: a...management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the

  9. Fat utilization and arterial hypertension in overweight/obese subjects

    PubMed Central

    2013-01-01

    Background The Respiratory Quotient is a parameter reflecting the utilization of the nutrients by a subject. It is associated with an high rate of subsequent weight gain and with the atherosclerosis. Subjects tending to burn less fat have an increased Respiratory Quotient. Aim of this study was to investigate on the relationship between the Respiratory Quotient and the cardiovascular risk factors. Methods In this cross-sectional study we enrolled 223 individuals of both sexes aged 45–75 ys that were weight stable, receiving a balanced diet, and not affected by debilitating disease or cardiovascular disease. The Respiratory Quotient was measured by Indirect Calorimetry. The measurement of the Blood Pressure was obtained by a mercury sphygmomanometer. Results We enrolled 133 female and 90 male. Systolic blood pressure only was positively correlated to the Respiratory Quotient in univariate and multivariate regression analysis (p=0,017). The prevalence of hypertension was significatively different between the quartiles of the Respiratory Quotient, with the highest prevalence in the IV quartile (p=0,024). Conclusion High value of the Respiratory Quotient, an index of nutrients utilization, is associated to an high prevalence of Hypertension. It is possible that in the subjects with high Respiratory Quotient and high body mass index, the activation of the renin angiotensin system, in concert to the reduction of the utilization of the endogenous fat stores, could increase the risk of hypertension. PMID:23815947

  10. [Systemic arterial hypertension in the elderly. Recommendations for clinical practice].

    PubMed

    Rosas-Peralta, Martín; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    Hypertension is common in people aged 65 and older. In those aged 70 and older, hypertension is more poorly controlled than in those whose age is between 60 and 69 years. The number of trials available concerning the elderly population is limited; therefore, strong recommendations on blood pressure (BP) goals are limited. The American College of Cardiology has recently published a consensus report of management of hypertension in the elderly population. This review presents an overview of that consensus report and reviews specific studies that provide some novel findings regarding BP goals and the progression of nephropathy. In general, the evidence strongly supports a BP goal < 150/80 mm Hg for the elderly with scant data in those aged 80 and older. However, it was decided to set the goal < 140/90 mm Hg, unless the patient cannot tolerate it, and then try to achieve 140-145 mm Hg. Diuretics and calcium antagonists are the most efficient treatment; however, most patients will require two or more drugs to achieve such goals.

  11. Beat-to-Beat Blood Pressure and Two-dimensional (axial and radial) Motion of the Carotid Artery Wall: Physiological Evaluation of Arterial Stiffness

    PubMed Central

    Xu, Chenchu; Xiong, Huahua; Gao, Zhifan; Liu, Xin; Zhang, Heye; Zhang, Yanping; Du, Xiuquan; Wu, Wanqing; Liu, Guotao; Li, Shuo

    2017-01-01

    The physiological relationship between local arterial displacement and blood pressure (BP) plays an integral role in assess- ment of the mechanical properties of arteries. In this study, we used more advanced methods to obtain reliable continuous BP and the displacement of the common carotid artery (CCA) simultaneously. We propose a novel evaluation method for arterial stiffness that relies on determining the physiological relationship between the axial and radial displacements of the CCA wall and beat-to-beat BP. Patients (total of 138) were divided into groups according to the following three criteria: essential hyper- tension (EH) and normotension, male and female, elderly and younger. The Pearson correlation test and canonical correlation analysis showed that the CCA indices were significantly correlated with BP indices (r = 0:787; p < 0:05). The slope of the CCA displacement/pressure curve showed a progressive reduction with increasing age and EH disease occurrence (EH: 0.496 vs. normotension: 0.822; age <= 60:0.585 vs. age > 60:0.783). Our method provides an explicit reference value and relationship for the manner in which the CCA wall responds to changes in BP. Short-term and continuous BP were significantly correlated with CCA displacement and exhibited a close inverse relationship with each subject’s BP and EH, age, and systolic blood pressure. PMID:28198819

  12. Subclinical arterial and cardiac damage in white-coat and masked hypertension.

    PubMed

    Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Olszanecka, Agnieszka; Klima, Łukasz; Gąsowski, Jerzy; Grodzicki, Tomasz; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta

    2016-08-01

    The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima-media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians.

  13. Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

    PubMed

    Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M

    2012-01-01

    1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.

  14. Impact of pulmonary vascular stiffness and vasodilator treatment in pediatric pulmonary hypertension: 21 patient-specific fluid-structure interaction studies

    PubMed Central

    Su, Zhenbi; Hunter, Kendall S.; Shandas, Robin

    2011-01-01

    Recent clinical studies of pulmonary arterial hypertension (PAH) have found correlations between increased pulmonary vascular stiffness (PVS) and poorer disease outcomes. However, mechanistic questions remain about the relationships amongst PVS, RV power, and vascular hemodynamics in the setting of progressive PAH that are difficult or impossible to answer using direct measurements. Clinically-validated patient-specific computational modeling may allow exploration of these issues through perturbation-based predictive testing. Here we use a simple patient-specific model to answer four questions: how do hemodynamics change as PAH worsens? How does increasing PVS impact hemodynamics and RV power? For a patient with moderate PAH, what are the consequences if the pressures increase modestly yet sufficiently to engage collagen in those vessels? What impact does pressure-reducing vasodilator treatment have on hemodynamics? Twenty-one sets of model-predicted impedance and mean PA pressure (mPAP) show good agreement with clinical measurements, thereby validating the model. Worsening was modeled using data from three PAH outcomes groups; these show not only the expected increase in mPAP, but also an increase in pressure pulsatility. Interestingly, chronically increasing mPAP decreased WSS, suggesting that increased PA cross-sectional area affected WSS greater than increased PVS. For a patient with moderately high PVR (12.7 WU) with elastin-based upstream vascular remodeling, moving from elastin-dominant vessel behavior to collagen-dominant behavior caused substantial increases in mPAP, pressure and WSS pulsatility. For the same patient, reducing PVR through a simulated vasodilator to a value equivalent to mild PAH did not decrease pressure pulsatility and dramatically increased WSS pulsatility. Overall, these results suggest a close association between PVS and hemodynamics and that hemodynamics may play an important role in progressing PAH. These support the hypothesis that

  15. Pulmonary arterial hypertension in Saudi Arabia: Patients' clinical and physiological characteristics and hemodynamic parameters. A single center experience

    PubMed Central

    Idrees, MM; Al-Najashi, K; Khan, A; Al-Dammas, S; Al-Awwad, H; Batubara, E; Al Otai, A; Abdulhameed, J; Fayed, A; Kashour, T

    2014-01-01

    AIMS: The main objective of this study is to describe patients' clinical characteristics and physiological and hemodynamic parameters at the time of diagnosis in a pulmonary hypertension center in Saudi Arabia. MATERIALS AND METHODS: This study reports the results from a single pulmonary hypertension specialized center in Riyadh, Saudi Arabia, namely Prince Sultan Medical Military City/Cardiac Center (PSMMC & CC). Both newly diagnosed (incidence) and referred (prevalence) cases of pulmonary arterial hypertension are included. All characteristics, including clinical, physiological, and hemodynamic parameters at the time of diagnosis are described. RESULTS: A total of 107 patients were identified as having pulmonary arterial hypertension as diagnosed by right heart catheterization. The mean age at diagnosis was 36 (± 9) years, and there was a female preponderance of 62.6%. The mean duration between symptom onset and diagnosis was 27.8 (± 9.0) months. At the time of enrollment, 56.1% of patients were in functional class III and 16.8% were in functional class IV. Fifty five patients (51.4%) were diagnosed as idiopathic pulmonary arterial hypertension, 29 patients (27.1%) as congenital heart disease associated with pulmonary arterial hypertension, 16 patients (15.0%) as connective tissue diseases associated with pulmonary arterial hypertension, 4 patients (3.7%) as heritable pulmonary arterial hypertension, and 3 patients (2.8%) as portopulmonary hypertension. CONCLUSION: This data highlights the current situation of pulmonary arterial hypertension in Saudi Arabia. Our patients are much younger than patients described in other international registries but still detected as late in the course of the disease. A majority of patients displays severe functional and hemodynamic compromise. PMID:25276239

  16. Cardiovascular design in fin whales: high-stiffness arteries protect against adverse pressure gradients at depth.

    PubMed

    Lillie, M A; Piscitelli, M A; Vogl, A W; Gosline, J M; Shadwick, R E

    2013-07-15

    Fin whales have an incompliant aorta, which, we hypothesize, represents an adaptation to large, depth-induced variations in arterial transmural pressures. We hypothesize these variations arise from a limited ability of tissues to respond to rapid changes in ambient ocean pressures during a dive. We tested this hypothesis by measuring arterial mechanics experimentally and modelling arterial transmural pressures mathematically. The mechanical properties of mammalian arteries reflect the physiological loads they experience, so we examined a wide range of fin whale arteries. All arteries had abundant adventitial collagen that was usually recruited at very low stretches and inflation pressures (2-3 kPa), making arterial diameter largely independent of transmural pressure. Arteries withstood significant negative transmural pressures (-7 to -50 kPa) before collapsing. Collapse was resisted by recruitment of adventitial collagen at very low stretches. These findings are compatible with the hypothesis of depth-induced variation of arterial transmural pressure. Because transmural pressures depend on thoracic pressures, we modelled the thorax of a diving fin whale to assess the likelihood of significant variation in transmural pressures. The model predicted that deformation of the thorax body wall and diaphragm could not always equalize thoracic and ambient pressures because of asymmetrical conditions on dive descent and ascent. Redistribution of blood could partially compensate for asymmetrical conditions, but inertial and viscoelastic lag necessarily limits tissue response rates. Without pressure equilibrium, particularly when ambient pressures change rapidly, internal pressure gradients will develop and expose arteries to transient pressure fluctuations, but with minimal hemodynamic consequence due to their low compliance.

  17. Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C.

    PubMed

    Barman, Scott A

    2007-08-01

    Although one of the common characteristics of pulmonary hypertension is abnormal sustained vasoconstriction, the signaling pathways that mediate this heightened pulmonary vascular response are still not well defined. Protein kinase C (PKC) and Rho-kinase are regulators of smooth muscle contraction induced by G protein-coupled receptor agonists including endothelin-1 (ET-1), which has been implicated as a signaling pathway in pulmonary hypertension. Toward this end, it was hypothesized that both Rho-kinase and PKC mediate the pulmonary vascular response to ET-1 in hypertensive pulmonary arterial smooth muscle, and therefore, the purpose of this study was to determine the role of PKC and Rho-kinase signaling in ET-1-induced vasoconstriction in both normotensive (Sprague-Dawley) and hypertensive (Fawn-Hooded) rat pulmonary arterial smooth muscle. Results indicate that ET-1 caused greater vasoconstriction in hypertensive pulmonary arteries compared with the normal vessels, and treatment with the PKC antagonists chelerythrine, rottlerin, and Gö 6983 inhibited the vasoconstrictor response to ET-1 in the hypertensive vessels. In addition, the specific Rho-kinase inhibitor Y-27632 significantly attenuated the effect of ET-1 in both normotensive and hypertensive phenotypes, with greater inhibition occurring in the hypertensive arteries. Furthermore, Western blot analysis revealed that ET-1 increased RhoA expression in both normotensive and hypertensive pulmonary arteries, with expression being greater in the hypertensive state. These results suggest that both PKC and Rho/Rho-kinase mediate the heightened pulmonary vascular response to ET-1 in hypertensive pulmonary arterial smooth muscle.

  18. A randomized trial of once-daily fluticasone furoate/vilanterol or vilanterol versus placebo to determine effects on arterial stiffness in COPD

    PubMed Central

    Bhatt, Surya P; Dransfield, Mark T; Cockcroft, John R; Wang-Jairaj, Jie; Midwinter, Dawn A; Rubin, David B; Scott-Wilson, Catherine A; Crim, Courtney

    2017-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD. Materials and methods The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial. Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70, and post-bronchodilator FEV1 ≤70% of predicted. Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded. Primary endpoint is change from baseline in aPWV after 24 weeks of treatment. Safety analyses included adverse events (AEs). Results The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141). Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV1 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening. At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo). AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients. Conclusion No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo. PMID:28176907

  19. [THE INFLUENCE OF ABDOMINAL OBESITY ON LEFT VENTRICULAR MYOCARDIALREMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION].

    PubMed

    Poteklzin, N P; Sarkisov, K A; Orlov, F A; Alatortseva, I A; Starovoitova, L M; Drozdova, I N

    2015-01-01

    The obesity dependence of selected clinical and instrumental characteristics of 10 male patients with arterial hypertension (AH) was evaluated Group I included 79 patients with grade II hypertensive disease (HD), normal body weight and waist circumference. Group 2 comprised 61 patients with grade II HD and abdominal obesity. Patients of both groups showed high frequency of left ventricular (LV) hypertrophy (59.2 and 73.8% respectively). Concentric LV hypertrophy prevailed in group I and eccentric hypertrophy in group 2. 24 hr ECG monitoring showed that signs of relative coronary insufficiency were recorded more frequently in group 2 and cardiac rhythm disturbances in group I.

  20. Opiate Dependence as an Independent and Interactive Risk Factor for Arterial Stiffness and Cardiovascular Ageing - A Longitudinal Study in Females

    PubMed Central

    Reece, Albert Stuart; Hulse, Gary Kenneth

    2013-01-01

    Background Despite intriguing observational cross-sectional data there are no longitudinal studies of opiate related arterial disease. As opiates act via P16INK4A/CDKN2A, and vascular ageing has been thought to be a surrogate for organismal ageing, the subject has far-reaching implications. Methods Pulse Wave Analysis (PWA) by radial arterial tonometry (SphygmoCor) was performed on control and opiate dependent patients. Results A total of 37 controls were compared with 93 opiate dependents. They were studied on 117 and 275 occasions respectively up to 1,797 days. The mean (± S.E.M.) ages were 38.72 ± 2.64 and 33.78 ± 0.90 years (P = 0.0260), 91.4% and 10.8% smoked (P < 0.0001). Body mass index rose more in controls (P = 0.0185) and in interaction with time (P = 0.0025). When controlled for time and BMI, opiate dependency status was shown to be associated with vascular age and central arterial stiffness and pressure indices (all P < 0.05). When repeated measures multiple regression was performed on all traditional cardiovascular risk factors, the opiate dose-duration interaction was significant and appeared in 12 terms in the final model. It was also independently significant (P = 0.0153). Opiate dose or duration appeared in a further 15 terms. The model was shown to be significantly improved by the inclusion of terms for opiate dependency (A.I.C. 71.10 v 54.31, P < 0.0001). Conclusion These data confirm increased vascular stiffness and ageing in a longitudinal study, and thereby imply advanced organismal ageing. These multivariate studies are consistent with opiate dependency as an interactive and multivariate cardiovascular risk factor and emphasize the role of treatment duration. PMID:23976908

  1. Plasma Renin Activity Predicts the Improvement in Resistant Hypertension after Percutaneous Transluminal Renal Artery Angioplasty

    PubMed Central

    Daidoji, Hyuma; Tamada, Yoshiaki; Suzuki, Saya; Watanabe, Ken; Shikama, Taku; Kikuchi, Yoku; Kato, Shigehiko; Takahashi, Katsuaki; Fukui, Akio; Matsui, Motoyuki; Yahagi, Tomoyasu; Goto, Toshikazu

    2016-01-01

    Objective Percutaneous transluminal renal artery angioplasty (PTRA) has been recommended for the treatment of renovascular resistant hypertension. However, large randomized trials have reported that PTRA did not improve the outcomes compared with optimal medical therapy in patients with renal artery stenosis (RAS). It is important to identify patients with renovascular hypertension who are likely to respond to PTRA. We herein examined whether or not the plasma renin activity (PRA) could predict the improvement in resistant hypertension after PTRA for RAS. Methods and Results A total of 40 patients (mean age: 63±15 years) with unilateral RAS who received PTRA for resistant hypertension were enrolled in this study. Twenty-two (55%) patients experienced a significant reduction in their blood pressure while using few antihypertensive agents at the 3-month follow up. The median PRA was significantly higher in patients using few antihypertensive agents than in those using more [4.2 ng/mL/hr, interquartile range (IQR) 2.6-8.0 vs. 0.8 ng/mL/hr, IQR 0.4-1.7, p<0.001]. To predict the improvement in hypertension after PTRA, a receiver operating characteristic analysis determined the optimal cut-off value of PRA to be 2.4 ng/mL/hr. A multivariate logistic regression analysis showed that higher PRA (>2.4 ng/mL/hr) was an independent predictor of the improvement in hypertension after PTRA (odds ratio: 22.3, 95% confidence interval: 2.17 to 65.6, p<0.01). Conclusion These findings suggest that the evaluation of preoperative PRA may be a useful tool for predicting the improvement in resistant hypertension after PTRA for patients with RAS. PMID:27904103

  2. [The Course of Pregnancy in Women With Arterial Hypertension].

    PubMed

    V Brytkova, Ya; Stryuk, R I

    2017-01-01

    We included in this study 69 women with hypertension in the II trimester of pregnancy, of whom 52 (75%) had normal weight gain during the period of gestation, and 17 (25%) had abnormal weight gain. Comprehensive clinical and instrumental examination included calculation of body mass index before and during gestation, 24-hour ambulatory blood pressure (BP) monitoring, assessment of activity of sympathetic-adrenal system by quantification of -adrenoreception of erythrocytes cell membranes. Women with excessive weight gain during gestation were older, more often had increased body weight before pregnancy. They also more often had insufficient nocturnal BP lowering, hypersympathicotonia, premature labor, pre-eclampsia, and lower anthropometric parameters of newborns.

  3. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

    PubMed

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease.

  4. [Social perception of arterial hypertension from a transcultural perspective].

    PubMed

    Fouraste, R F

    1984-01-01

    From ethnological and psychological inquiries, during an ordinary elaboration of methodology (between France and West Africa that took place in Ivory Coast) the author emphasizes the differential value of the terms hypertension or hypotension with a systematic claim of a take of blood pressure in Europe. This uncommon fact in West Africa becomes integrated into the notion of a medical technology and raises the problem of evolution of society (non migration, new forms of alimentation, work and urbanization...). While in France the inquiry is dependent on an image of an hypertensive, his body, his personality, his problems; in Ivory Coast people refer to a body language, the psychosomatic damage including the existential malaise politics, cultural confrontations, stress pathology ... all this with periods of high or low tension internal or external pressures, getting out of the medical act consisting in a take of blood pressure or a particular psychic state testing, the nervous break down or anxiety for example. In a methodological field, the author from different levels of view points (sociological, statistical, ethnological and clinical) is in search of an adapted synthetic formula in anthropology for situations of substitution and social differences.

  5. [Radionuclide evaluation of the cardiovascular system in arterial hypertension].

    PubMed

    Oganesian, N M; Babaian, A S; Mikaelian, R S; Mnatsakanian, E L

    1986-08-01

    Proceeding from a study of the nature of changes in hemodynamics during development of hypertensive disease (HD) at its different stages it was shown that hemodynamic changes in 42.1% of the patients with Stage I-IIA HD were of hypertensive type, in the patients with Stage IIB-III HD normal and hypokinetic types of the blood circulation prevailed. After bicycle ergometry exercise the reactivity of the cardiovascular system was revealed more completely. The transition of one hemodynamic type into another and its detection acquired a great importance. The definition of the types of hemodynamics at rest and of effort was very important in terms of adequate antihypertensive therapy and the prediction of a subsequent course of disease. The most complete information on function of the cardiovascular system and myocardial contractility can be obtained with the help of radio-angiocardiography and radionuclide ventriculography. However in the absence of a gamma-chamber radiocardiography can provide necessary information on function of the cardiovascular system in case it is used in one and the same patient over time using bicycle ergometry testing.

  6. [Sodium and arterial hypertension --one hundred years of controversies].

    PubMed

    Krzesinski, J M

    2009-01-01

    Sodium chloride (salt) plays a role in the development and maintenance of high blood pressure (25% of the normotensive population are called sodium sensitive and 50% of the hypertensive people would present a significative decrease either of their blood pressure when low salt diet is applied) or of cardiovascular complications, but also of other diseases (obesity, osteoporosis, kidney stones, cancer,...) The regulation of salt balance is played by the kidneys, the function of which can be genetically (more rarely) or secondarily acquired (most often) disturbed. Salt restriction (maximum 5-6 g/d) with higher potassium intake, is now recommended. This can easier allow the lowering of the blood pressure, especially in resistant forms of hypertension. Proposed to everybody, even normotensive, it could be beneficial reducing the trend of blood pressure increase with age, but also the burden of cardiovascular complications and promoting general health. For reaching these objectives, this reduction in salt consumption needs motivated and well educated people, well labelled food products about salt content and the apprppriate help of food industries.

  7. Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.

    PubMed

    Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J

    2015-12-01

    Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.

  8. Association of hypertension with coronary artery disease onset in the Lebanese population.

    PubMed

    Milane, Aline; Abdallah, Jad; Kanbar, Roy; Khazen, Georges; Ghassibe-Sabbagh, Michella; Salloum, Angelique K; Youhanna, Sonia; Saad, Aline; El Bayeh, Hamid; Chammas, Elie; Platt, Daniel E; Hager, Jörg; Gauguier, Dominique; Zalloua, Pierre; Abchee, Antoine

    2014-01-01

    The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

  9. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Medical and surgical management for pulmonary arterial hypertension

    PubMed Central

    Idrees, Majdy M.; Swiston, John; Nizami, Imran; Al Dalaan, Abdullah; Levy, Robert D.

    2014-01-01

    Prior to the availability of the pulmonary arterial hypertension (PAH)-specific therapy, PAH was a dreadful disease with a very poor prognosis. Better understanding of the complex pathobiology of PAH has led to a major therapeutic evolution. International regulatory agencies have approved many specific drugs with different pharmacologic pathways and routes of administration. In the year 2013, two new drugs with great potentials in managing PAH have been added to the treatment options, macitentan and riociguat. Additional drugs are expected to come in the near future. A substantial body of evidence has confirmed the effectiveness of pulmonary arterial hypertension (PAH)-specific therapies in improving the patients’ symptomatic status and slowing down the rate of clinical deterioration. Although the newer modern medications have significantly improved the survival of patients with PAH, it remains a non-curable and fatal disease. Lung transplantation (LT) remains the only therapeutic option for selected patients with advanced disease who continue to deteriorate despite optimal therapy. PMID:25077002

  10. Age and cigarette smoking modulate the relationship between pulmonary function and arterial stiffness in heart failure patients

    PubMed Central

    Li, Li; Hu, Bangchuan; Gong, Shijin; Yu, Yihua; Yan, Jing

    2017-01-01

    Abstract The aim of this study was to assess the relationship between arterial stiffness and pulmonary function in chronic heart failure (CHF). Outpatients previously diagnosed as CHF were enrolled between April 2008 and March 2010, and submitted to arterial stiffness measurement and lung function assessment. Spirometry was performed by measuring forced vital capacity (FVC), the fraction of predicted FVC, forced expiratory volume in 1 second (FEV1), the percentage of predicted FEV1 in 1 second, FEV1 to FVC ratio, and the percentage of predicted FEV1/FVC. Cardio-ankle vascular index (CAVI) was considered for the estimation of arterial stiffness. The 354 patients assessed included 315 nonsmokers, and were 68.2 ± 7.2 years’ old. Unadjusted correlation analyses demonstrated CAVI was positively related to age (r = 0.3664, P < 0.0001), and negatively related to body mass index (BMI, r = −0.2040, P = 0.0001), E/A ratio (r = −0.1759, P = 0.0010), and FEV1 (r = −0.2987, P < 0.0001). Stepwise multivariate regression analyses showed age (r2 = 0.2391, P < 0.0001), BMI (r2 = −0.2139, P < 0.0001), smoking (r2 = 0.1211, P = 0.0130), E/A ratio (r2 = −0.1082, P = 0.0386), and FEV1 (r2 = −0.2550, P < 0.0001) were independent determinants of CAVI. In addition, there is a significant interaction between CAVI and forced expiratory volume in 1 second (FEV1) in relation to age (Pint < 0.0001) and smoking (Pint = 0.0001). Meanwhile, pulmonary function was not associated with BMI or E/A ratio. These findings demonstrated that reduced pulmonary function is associated with the increased CAVI, and had an interactive effect with age and smoking on CAVI in patients with CHF. PMID:28272233

  11. Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

    PubMed

    Hirashiki, Akihiro; Adachi, Shiro; Nakano, Yoshihisa; Kamimura, Yoshihiro; Shimokata, Shigetake; Takeshita, Kyosuke; Murohara, Toyoaki; Kondo, Takahisa

    2016-06-01

    Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 patients with PAH and 8 with CTEPH were treated with bosentan. All patients underwent FMD assessment before and after 3 months of bosentan treatment. Whereas FMD increased from 6.01% ± 2.42% at baseline to 8.07% ± 3.18% after 3 months (P < 0.0001) in patients with PAH, those with CTEPH showed no change in FMD after bosentan therapy. In addition, FMD at baseline showed no correlation with pulmonary vascular resistance (r = 0.09) or plasma brain natriuretic peptide levels (r = -0.23) in patients with PAH. Bosentan treatment ameliorated PED in patients with PAH but not in those with inoperable CTEPH. In addition, FMD did not correlate with PAH severity.

  12. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with connective tissue diseases

    PubMed Central

    Boueiz, Adel; Hassoun, Paul M.

    2014-01-01

    The explosive growth of medical literature on pulmonary hypertension (PH) has led to a steady increase in awareness of this disease within the medical community during the past decade. The recent revision of the classification of PH is presented in in the main guidelines. Group 1 PH or pulmonary arterial hypertension (PAH) is a heterogeneous group and includes PH due to inheritable, drug-induced, and toxin-induced causes and to such underlying systemic causes as connective tissue diseases, human immunodeficiency viral infection, portal hypertension, congenital heart disease, and schistosomiasis. Systemic sclerosis (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per million in the United States.[1] Its manifestations are not confined to the skin but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal system, gastrointestinal tract, and heart. The outcome of PAH associated with SSc is worse when compared to other subtypes of PAH. In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection. PMID:25076994

  13. [Modern approaches to the use of neurotropic physical therapy in arterial hypertension].

    PubMed

    Orekhova, E M; Konchugova, T V; Kul'chitskaya, D B; Korchazhkina, N B; Egorova, L A; Chuich, N G

    2016-01-01

    The development and introduction into clinical practice of non-pharmacological methods for the prevention and treatment of arterial hypertension is a primary objective of modern physical therapy, especially as regards the neurotropic influences. This article was designed to report the results of the investigation into the hypotensive effect of transcerebral magnetic therapy obtained during the treatment of 60 patients presenting with arterial hypertension. The study included the comparative examination of two randomly formed groups containing 30 patients each. The patients of the main group received transcerebral magnetic therapy (to the frontal region) while those in the group of comparison were given magnetotherapy at the collar region. The study has demonstrated that transcerebral magnetic therapy given to the patients of the main group was a more efficient treatment than magnetotherapy at the collar region since it produced a more pronounced hypotensive effect irrespective of the initial hemodynamic type.

  14. Role of vasopressin and aldosterone in pulmonary arterial hypertension: A pilot study.

    PubMed

    Bansal, Shweta; Badesch, David; Bull, Todd; Schrier, Robert W

    2009-09-01

    Much has been learned about the pathophysiological state that underlies the development of increased total body volume and edema in left ventricular failure. Very little, however, is known about the mechanism underlying systemic hypervolemia in patients with isolated right ventricular dysfunction. In this manuscript, we describe our randomized clinical trial to assess the relationship between severity of pulmonary arterial hypertension and neurohormonal activation, total plasma volume and renal function. We assess the role of aldosterone and vasopressin in volume retention in patients with pulmonary arterial hypertension with right ventricular failure. As understanding of the pathogenesis of left ventricular failure has been associated with improved therapies, the better understanding of the mechanisms of isolated right ventricular cardiac failure will also lead to improved patient care.

  15. Role of vasopressin and aldosterone in pulmonary arterial hypertension: A pilot study

    PubMed Central

    Bansal, Shweta; Badesch, David; Bull, Todd; Schrier, Robert W.

    2009-01-01

    Much has been learned about the pathophysiological state that underlies the development of increased total body volume and edema in left ventricular failure. Very little, however, is known about the mechanism underlying systemic hypervolemia in patients with isolated right ventricular dysfunction. In this manuscript, we describe our randomized clinical trial to assess the relationship between severity of pulmonary arterial hypertension and neurohormonal activation, total plasma volume and renal function. We assess the