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Sample records for arterial stiffness hypertension

  1. Elastin in large artery stiffness and hypertension.

    PubMed

    Wagenseil, Jessica E; Mecham, Robert P

    2012-06-01

    Large artery stiffness, as measured by pulse wave velocity, is correlated with high blood pressure and may be a causative factor in essential hypertension. The extracellular matrix components, specifically the mix of elastin and collagen in the vessel wall, determine the passive mechanical properties of the large arteries. Elastin is organized into elastic fibers in the wall during arterial development in a complex process that requires spatial and temporal coordination of numerous proteins. The elastic fibers last the lifetime of the organism but are subject to proteolytic degradation and chemical alterations that change their mechanical properties. This review discusses how alterations in the amount, assembly, organization, or chemical properties of the elastic fibers affect arterial stiffness and blood pressure. Strategies for encouraging or reversing alterations to the elastic fibers are addressed. Methods for determining the efficacy of these strategies, by measuring elastin amounts and arterial stiffness, are summarized. Therapies that have a direct effect on arterial stiffness through alterations to the elastic fibers in the wall may be an effective treatment for essential hypertension.

  2. 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.

  3. 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

  4. The Contribution of Osteoprogenitor Cells to Arterial Stiffness and Hypertension.

    PubMed

    Pikilidou, Maria; Yavropoulou, Maria; Antoniou, Maria; Yovos, John

    2015-01-01

    Hypertension, the major cause of cardiovascular disease, is bidirectionally linked to arterial stiffness. Evidence shows that vascular calcification, either medial or intimal, induces arterial stiffening further worsening hypertension parallel to substantially increasing cardiovascular risk. The disturbance in the bone-vascular axis that leads to the increase of calcium deposition in the arterial wall may be the result of a shift in the functionality of bone marrow-derived circulating stem cells with a calcifying potential, namely osteoprogenitor cells. These cells deposit bone matrix proteins in the vascular wall that can subsequently become mineralized. The current notion is that these cells derive from diverse cell lines. The present review summarizes the current knowledge on the role of progenitor cells with a calcifying potential on arterial calcification, stiffness and hypertension.

  5. An update on the role of adipokines in arterial stiffness and hypertension.

    PubMed

    Sabbatini, Andréa R; Fontana, Vanessa; Laurent, Stephane; Moreno, Heitor

    2015-03-01

    Adipokines are hormones produced by adipocytes and have been involved in multiple pathologic pathways, including inflammatory and cardiovascular complications in essential hypertension. Arterial stiffness is a frequent vascular complication that represents increased cardiovascular risk in hypertensive patients. Adipokines, such as adiponectin, leptin and resistin, might be implicated in hypertension, as well as in vascular alterations associated with this condition. Arterial stiffness has proven to be a predictor of cardiovascular events. Obesity and target-organ damage such as arterial stiffness are features associated with hypertension. This review aims to update the association between adipokines and arterial stiffness in essential and resistant hypertension (RHTN).

  6. 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

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

    PubMed

    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

  8. 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.

  9. 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. PMID:25251989

  10. Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

    PubMed Central

    Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

    2016-01-01

    Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

  11. 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.

  12. Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

    PubMed

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

    2016-09-01

    High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. PMID:27456526

  13. 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.

  14. Skinfold thickness as a predictor of arterial stiffness: obesity and fatness linked to higher stiffness measurements in hypertensive patients.

    PubMed

    Selcuk, Ali; Bulucu, Fatih; Kalafat, Firdevs; Cakar, Mustafa; Demirbas, Seref; Karaman, Murat; Ay, Seyid Ahmet; Saglam, Kenan; Balta, Sevket; Demirkol, Sait; Arslan, Erol

    2013-01-01

    Hypertensive patients have strong evidence of endothelial dysfunction. Some novel endothelial dysfunction parameters such as pulse wave velocity (PWV), augmentation index (AIx), and central aortic pressure (CAP) have been investigated as predictive markers of atherosclerosis. It is well known that obesity has relationships with endothelial dysfunction and atherosclerosis. We aimed to investigate relationships between anthropometric measurements and arterial stiffness parameters in essentially hypertensive patients. The study population included 100 patients (56 females, 44 males) newly or formerly diagnosed as essentially hypertensive in an outpatient clinic. Arterial stiffness measurements, including PWV, AIx, CAP, and body mass index (BMI); waist circumference, hip circumference; waist/hip ratio; and triceps, biceps, subscapular, and suprailiac skinfold thicknesses were also applied to all the study patients. Then, the relationships between BMI, anthropometric measurements, and arterial stiffness parameters were investigated. The mean systolic arterial blood pressure of the study population was 135.85 ± 15.27 mm Hg and the mean diastolic arterial blood pressure of the study population was 84.17 ± 9.58 mm Hg. The parameters such as PWV, AIx, and CAP measured for arterial stiffness had correlations between BMI and different anthropometric measurements. The statistically significant correlations were present between PWV and triceps skinfold thickness (TST) (r = 0.377, P < .001) and it was also seen when regression analysis was performed (PWV = 6.41 + [0.072 × TST]; R(2) = 0.142, F[1-98] = 16.23, P < .001). Triceps skinfold thickness among these correlations may be used to estimate the carotid-femoral PWV, which is an indicator of subclinical organ damage due to hypertension.

  15. Invited Commentary: Hypertension and Arterial Stiffness--Origins Remain a Dilemma.

    PubMed

    Jacobs, David R; Duprez, Daniel A; Shimbo, Daichi

    2016-04-01

    In this issue of the Journal, Chen et al. (Am J Epidemiol. 2016;183(7):599-608) present repeated measures of aorto-femoral pulse wave velocity, capacitive compliance (C1), and oscillatory compliance (C2) in the Bogalusa Heart Study, with the purpose of addressing which comes first: blood pressure elevation or arterial stiffening. After an average follow-up period of 7 years (2000-2010), the authors found that blood pressure at a mean age of 36 years predicted change in arterial stiffening by a mean age of 43 years, but not the reverse. Essential hypertension results from a mosaic of pathological mechanisms. It has been theorized that biological pathways involving increased sympathetic tone, insulin resistance, renin-angiotensin-aldosterone activation, and inflammation lead to hyperkinetic circulation, volume overload, and vascular remodeling. The resultant accelerated vascular aging may be assessed by determining the degree of arterial stiffness. The findings of Chen et al. add important empirical information to the literature but do not solve the dilemma regarding the origins of essential hypertension, partly because there are many techniques for estimating the many aspects of arterial stiffness which are not fully understood. Mathematical features of estimates might not be uniform across the age range. There is a need for tracking blood pressure and different aspects of arterial stiffness from childhood onward, with an aim of preventing hypertension in adult life.

  16. 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

  17. Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep

    PubMed Central

    Morgan, Matthew R.; Galambos, Csaba; Hunter, Kendall S.; Abman, Steven H.

    2014-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characterize main PA (MPA) stiffness in experimental PPHN and to determine the relationship of altered biomechanics of the MPA with changes in extracellular matrix (ECM) content and orientation of collagen and elastin fibers. MPAs were isolated from control and PPHN fetal sheep model and were tested by planar biaxial testing to measure stiffness in circumferential and axial vessel orientations. Test specimens were fixed for histological assessments of the vascular wall ECM constituents collagen and elastin. MPAs from PPHN sheep had increased mechanical stiffness (P < 0.05) and altered ECM remodeling compared with control MPA. A constitutive mathematical model and histology demonstrated that PPHN vessels have a smaller contribution of elastin and a greater role for collagen fiber engagement compared with the control arteries. We conclude that exposure to chronic hemodynamic stress in late-gestation fetal sheep increases proximal PA stiffness and alters ECM remodeling. We speculate that proximal PA stiffness further contributes to increased right ventricular impedance in experimental PPHN, which contributes to abnormal transition of the pulmonary circulation at birth. PMID:25326575

  18. Arterial Stiffness

    PubMed Central

    Avolio, Alberto

    2013-01-01

    Stiffness of large arteries has been long recognized as a significant determinant of pulse pressure. However, it is only in recent decades, with the accumulation of longitudinal data from large and varied epidemiological studies of morbidity and mortality associated with cardiovascular disease, that it has emerged as an independent predictor of cardiovascular risk. This has generated substantial interest in investigations related to intrinsic causative and associated factors responsible for the alteration of mechanical properties of the arterial wall, with the aim to uncover specific pathways that could be interrogated to prevent or reverse arterial stiffening. Much has been written on the haemodynamic relevance of arterial stiffness in terms of the quantification of pulsatile relationships of blood pressure and flow in conduit arteries. Indeed, much of this early work regarded blood vessels as passive elastic conduits, with the endothelial layer considered as an inactive lining of the lumen and as an interface to flowing blood. However, recent advances in molecular biology and increased technological sophistication for the detection of low concentrations of biochemical compounds have elucidated the highly important regulatory role of the endothelial cell affecting vascular function. These techniques have enabled research into the interaction of the underlying passive mechanical properties of the arterial wall with the active cellular and molecular processes that regulate the local environment of the load-bearing components. This review addresses these emerging concepts. PMID:26587425

  19. Abnormal structure and increased stiffness of the femoral arterial wall in young patients with sustained essential hypertension.

    PubMed

    Eiskjaer, H; Christensen, T; Pedersen, E B

    1989-10-01

    Thickness, elastic modulus, and stiffness of the common femoral arterial wall were estimated in 11 patients with essential hypertension and in 11 age-matched normotensive control subjects by use of an in vivo, non-invasive, ultrasound time-motion display technique (M-mode). Hypertensive patients had significantly higher levels than normotensive subjects with regard to arterial wall thickness (0.23 cm vs. 0.18 cm, medians; P less than 0.01), elastic modulus (10.6 x 10(7) Pa vs. 6.18 x 10(7) Pa, medians; P less than 0.05) and arterial wall stiffness (3.80 x 10(7) Pa vs. 2.07 +/- 10(7) Pa, medians; P less than 0.01). It is concluded that structural changes in the wall of the large arteries contribute to the increase in arterial wall stiffness in young patients with sustained essential hypertension.

  20. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension.

    PubMed

    Krasińska, Beata; Miazga, Angelika; Cofta, Szczepan; Szczepaniak-Chicheł, Ludwina; Trafas, Tomasz; Krasiński, Zbigniew; Pawlaczyk-Gabriel, Katarzyna; Tykarski, Andrzej

    2016-05-27

    INTRODUCTION    Obstructive sleep apnea (OSA) is considered to be one of the major causes of resistant arterial hypertension (RAH). Apnea episodes cause hypoxia, which triggers the activation of the renin-angiotensin-aldosterone system. This leads to water retention and swelling in the neck region, exacerbating OSA symptoms. It is assumed that the use of eplerenone may reduce the swelling and thus alleviate the severity of OSA. OBJECTIVES    We aimed to prospectively assess the impact of eplerenone on the severity of OSA and arterial stiffness in patients with RAH. PATIENTS AND METHODS    The study included 31 patients with RAH and OSA. The exclusion criteria were as follows: secondary hypertension, myocardial infarction, stroke 6 months prior to the study, congestive heart failure, chronic kidney failure, alcohol or drug addiction, and active cancer. In all patients, the following tests were performed: blood pressure (BP) measurement (traditionally and using ambulatory BP measuring [ABPM]), applanation tonometry, polysomnography, and the apnea-hypopnea index (AHI) calculation. The tests were done before and after 3 months of eplerenone therapy. Patients received 50 mg of oral eplerenone daily, along with other hypertensive drugs. RESULTS    The mean age of participants was 57.76 ±6.16 years. After 3 months of eplerenone therapy, we observed a significant reduction in the AHI, neck circumference, BP, aortic pulse wave, and arterial wall stiffness. There were significant correlations between the AHI and mean BP measured by ABPM and between the AHI and arterial stiffness parameters. CONCLUSIONS    Our results provide evidence for the clinical significance of eplerenone, not only as an antihypertensive medication but also as a drug that may reduce the severity of OSA and arterial stiffness in patients with RAH and OSA.

  1. Future Treatment of Hypertension: Shifting the Focus from Blood Pressure Lowering to Arterial Stiffness Modulation?

    PubMed

    Fok, Henry; Cruickshank, J Kennedy

    2015-08-01

    Isolated systolic hypertension is the commonest form of hypertension from middle age onwards. Achieving target systolic blood pressure (BP) control remains difficult in everyday clinical practice and even under clinical trial conditions. Most antihypertensive medicines were designed to lower peripheral vascular resistance, which was considered the haemodynamic determinant of hypertension; most are effective in reducing steady but not pulsatile components of BP. Arterial stiffness, defined via aortic length-specific pulse wave velocity (PWV), is thought to be an important determinant of pulse pressure widening through its effects on the timing and amplitude of pressure wave reflection, and/or the aorta's Windkessel function, or its excess 'reservoir' pressure. Whereas pulse pressure is neither an independent nor consistent cardiovascular risk factor, particularly below the age of about 60 years, PWV has become the most powerful predictor of cardiovascular outcomes including mortality, independent of systolic, pulse, mean or other BP components. PWV is therefore a more direct target for treatment. This review addresses the potential therapeutic options for targeting arterial stiffness and the role of pulse pressure.

  2. 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.

  3. 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

  4. 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

  5. A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

    PubMed Central

    2012-01-01

    Background Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. Methods A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2. Discussion The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders. PMID:23268774

  6. Aortic and Carotid Arterial Stiffness and Epigenetic Regulator Gene Expression Changes Precede Blood Pressure Rise in Stroke-Prone Dahl Salt-Sensitive Hypertensive Rats

    PubMed Central

    Herrera, Victoria L.; Decano, Julius L.; Giordano, Nicholas; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2014-01-01

    Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation. PMID:25229245

  7. 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.

  8. Arterial Stiffness Gradient

    PubMed Central

    Fortier, Catherine; Agharazii, Mohsen

    2016-01-01

    Background Aortic stiffness is a strong predictor of cardiovascular mortality in various clinical conditions. The aim of this review is to focus on the arterial stiffness gradient, to discuss the integrated role of medium-sized muscular conduit arteries in the regulation of pulsatile pressure and organ perfusion and to provide a rationale for integrating their mechanical properties into risk prediction. Summary The physiological arterial stiffness gradient results from a higher degree of vascular stiffness as the distance from the heart increases, creating multiple reflective sites and attenuating the pulsatile nature of the forward pressure wave along the arterial tree down to the microcirculation. The stiffness gradient hypothesis simultaneously explains its physiological beneficial effects from both cardiac and peripheral microcirculatory points of view. The loss or reversal of stiffness gradient leads to the transmission of a highly pulsatile pressure wave into the microcirculation. This suggests that a higher degree of stiffness of medium-sized conduit arteries may play a role in protecting the microcirculation from a highly pulsatile forward pressure wave. Using the ratio of carotid-femoral pulse wave velocity (PWV) to carotid-radial PWV, referred to as PWV ratio, a recent study in a dialysis cohort has shown that the PWV ratio is a better predictor of mortality than the classical carotid-femoral PWV. Key Messages Theoretically, the use of the PWV ratio seems more logical for risk determination than aortic stiffness as it provides a better estimation of the loss of stiffness gradient, which is the unifying hypothesis that explains the impact of aortic stiffness both on the myocardium and on peripheral organs. PMID:27195235

  9. 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.

  10. Arterial stiffness as a risk factor for coronary artery disease.

    PubMed

    Liao, Josh; Farmer, John

    2014-02-01

    Hypertension is a major modifiable risk factor, and clinical trials have demonstrated that successful reduction of elevated blood pressure to target levels translates into decreased risk for the development of coronary artery disease, stroke, heart failure, and renal failure. The arterial system had previously been regarded as a passive conduit for the transportation of arterial blood to peripheral tissues. The physiologic role the arterial system was greatly expanded by the recognition of the central role of the endothelial function in a variety of physiologic processes. The role of arterial function and structure in cardiovascular physiology was expanded with the development of a variety of parameters that evaluate arterial stiffness. Markers of arterial stiffness have been correlated with cardiovascular outcomes, and have been classified as an emerging risk factor that provides prognostic information beyond standard stratification strategies involving hypertension, diabetes, obesity, dyslipidemia and smoking. Multiple epidemiologic studies have correlated markers of arterial stiffness such as pulse-wave velocity, augmentation index and pulse pressure with risk for the development of fatal and nonfatal cardiovascular events. Additionally, measurements of arterial stiffness had clarified the results of clinical trials that demonstrated differing impacts on clinical outcomes, despite similar reductions in blood pressure, as measured by brachial and sphygmomanometry.

  11. Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.

    PubMed

    Baroni, Matteo; Nava, Stefano; Giupponi, Luca; Meani, Paolo; Panzeri, Francesco; Varrenti, Marisa; Maloberti, Alessandro; Soriano, Francesco; Agrati, Antonio Maria; Ferraro, Giovanni; Colombo, Fabrizio; Rampoldi, Antonio; Mancia, Giuseppe; Colombo, Paola; Klugmann, Silvio; Giannattasio, Cristina

    2015-12-01

    Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca' Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p < 0.05 versus baseline for all steps) as well as pulse wave velocity (p < 0.01 at 1 year versus baseline). Moreover, reduction in pulse wave velocity was higher than the expected value obtained only considering blood pressure drop. Conversely, no significant effect was observed on diastolic blood pressure as well as carotid intima-media thickness. In our study, renal denervation was a safe and effective procedure. The BP lowering effect was maintained during follow-up and a beneficial effect on arterial stiffness was observed, which implies that this effect can't passively originate from the BP fall but rather from an improvement of arterial mechanical properties, possibly related to a reduced sympathetic arterial drive.

  12. 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

  13. Arterial Stiffness in Children: Pediatric Measurement and Considerations

    PubMed Central

    Savant, Jonathan D.; Furth, Susan L.; Meyers, Kevin E.C.

    2014-01-01

    Background Arterial stiffness is a natural consequence of aging, accelerated in certain chronic conditions, and predictive of cardiovascular events in adults. Emerging research suggests the importance of arterial stiffness in pediatric populations. Methods There are different indices of arterial stiffness. The present manuscript focuses on carotid-femoral pulse wave velocity and pulse wave analysis, although other methodologies are discussed. Also reviewed are specific measurement considerations for pediatric populations and the literature describing arterial stiffness in children with certain chronic conditions (primary hypertension, obesity, diabetes, chronic kidney disease, hypercholesterolemia, genetic syndromes involving vasculopathy, and solid organ transplant recipients). Conclusions The measurement of arterial stiffness in children is feasible and, under controlled conditions, can give accurate information about the underlying state of the arteries. This potentially adds valuable information about the functionality of the cardiovascular system in children with a variety of chronic diseases well beyond that of the brachial artery blood pressure. PMID:26587447

  14. 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

  15. 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

  16. Arterial stiffness and its clinical implications in women.

    PubMed

    Coutinho, Thais

    2014-07-01

    The burden of cardiovascular disease (CVD) in women is increasing, and CVD presently kills more North American women than men, highlighting the need for sex-specific research aimed at disentangling the complex interactions between sex, aging, and cardiovascular health. In the past decade, arterial stiffness has emerged as an independent predictor of adverse cardiovascular events and mortality, and its noninvasive, safe evaluation makes it an attractive tool for a snapshot assessment of cardiovascular health. An increasing number of reports have documented greater aortic stiffness in older women than men, which appears to have close relationships with blood pressure control, diastolic dysfunction, impaired ventricular coupling, and left ventricular remodelling in women. Thus, arterial stiffness is thought to play a role in the female predominance of several diseases such as isolated systolic hypertension, refractory hypertension, heart failure with preserved ejection fraction, and paradoxical low-flow, low-gradient, normal ejection fraction severe aortic stenosis. Furthermore, greater arterial stiffness is a common characteristic of women who develop hypertensive complications of pregnancy. Thus, better understanding sex differences in arterial stiffness and aging might provide valuable insights into CVD in women, and help identify novel risk stratification tools and therapeutic targets. To this end, the present review aims at describing sex differences in arterial stiffness, exploring the potential role of sex hormones and menopause on arterial aging, and highlighting the role of arterial stiffness in specific CVDs that preferentially affect women.

  17. 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

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

    PubMed

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

    2015-11-26

    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.

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

    PubMed

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

    2015-11-26

    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

  20. Effects of amlodipine and candesartan on arterial stiffness estimated by cardio-ankle vascular index in patients with essential hypertension: A 24-week study

    PubMed Central

    Kurata, Mie; Okura, Takafumi; Watanabe, Sanae; Irita, Jun; Enomoto, Daijiro; Johtoku, Masanori; Miyoshi, Ken-ichi; Koresawa, Mitsuko; Fukuoka, Tomikazu; Higaki, Jitsuo

    2008-01-01

    Background: Aortic stiffness assessed by brachio-ankle pulse wave velocity (baPWV) can be used to predict cardiovascular events. However, baPWV is dependent on blood pressure. Antihypertensive drugs have been reported to reduce baPWV; but it is difficult to determine if this effect is associated with lowered blood pressure or reduced arterial stiffness. Objectives: The primary end point of this study was to assess whether antihypertensive drugs reduce arterial stiffness as estimated by cardio-ankle vascular index (CAVI). The secondary end point was to compare the effects of 2 widely used drugs, the calcium-channel blocker amlodipine and the angiotensin II receptor blocker candesartan, on arterial stiffness. Methods: Between October 2005 and September 2006, consecutive Japanese outpatients with essential hypertension (EHT) (defined as using antihypertensive drugs at screening, systolic blood pressure [SBP] > 140 mm Hg, or diastolic BP [DBP] >90 mm Hg) were assigned to treatment for 24 weeks with either amlodipine (5–10 mg/d) or candesartan (8–12 mg/d). Arterial stiffness was evaluated with CAVI before and after 24 weeks of treatment. Relative change in arterial stiffness from baseline was also compared. The evaluator was blinded to treatment. Results: Twenty patients (11 men, 9 women; mean [SD] age, 62 [10] years) were included in the study. There were no significant differences in clinical characteristics between the 2 groups. At baseline, mean (SD) CAVI was not significantly different in the amlodipine group compared with the candesartan group (8.93 [0.93] vs 8.46 [1.34], respectively). During the 24-week treatment period, mean SBP and DBP decreased significantly in both the amlodipine (14/10 mm Hg; P = 0.006 and P = 0.005) and the candesartan groups (13/11 mm Hg; P = 0.033 and P = 0.005). Amlodipine was associated with a significant change in CAVI from baseline (8.93 [0.93] vs 8.60 [1.50]; P = 0.017), whereas candesartan was not (8.46 [1.34] vs 8.81 [1

  1. Salt loading and potassium supplementation: effects on ambulatory arterial stiffness index and endothelin-1 levels in normotensive and mild hypertensive patients.

    PubMed

    Liu, Zhendong; Peng, Jie; Lu, Fanghong; Zhao, Yingxin; Wang, Shujian; Sun, Shangwen; Zhang, Hua; Diao, Yutao

    2013-07-01

    The authors investigated effects of excessive salt intake and potassium supplementation on ambulatory arterial stiffness index (AASI) and endothelin-1 (ET-1) in salt-sensitive and non-salt-sensitive individuals. AASI and symmetric AASI (s-AASI) were used as indicators of arterial stiffness. Plasma ET-1 levels were used as an index of endothelial function. Chronic salt-loading and potassium supplementation were studied in 155 normotensive to mild hypertensive patients from rural northern China. After 3 days of baseline investigation, participants were maintained sequentially for 7 days each on diets of low salt (51.3 mmol/d), high salt (307.7 mmol/d), and high salt+potassium (60 mmol/d). Ambulatory 24-hour blood pressure (BP) and plasma ET-1 were measured at baseline and on the last 2 days of each intervention. High-salt intervention significantly increased BP, AASI, s-AASI (all P<.001); potassium supplementation reversed increased plasma ET-1 levels. High-salt-induced changes in BP, s-AASI, and plasma ET-1 were greater in salt-sensitive individuals. Potassium supplementation decreased systolic BP and ET-1 to a significantly greater extent in salt-sensitive vs non-salt-sensitive individuals (P<.001). Significant correlations were identified between s-AASI and ET-1 change ratios in response to both high-salt intervention and potassium supplementation (P<.001). Reducing dietary salt and increasing daily potassium improves arterial compliance and ameliorates endothelial dysfunction.

  2. Arterial Stiffness and Chronic Kidney Disease

    PubMed Central

    Garnier, Anne-Sophie; Briet, Marie

    2016-01-01

    Chronic kidney disease (CKD) is a major public health concern due to the high prevalence of associated cardiovascular (CV) disease. CV mortality is 10-30 times higher in end-stage renal disease patients than in the age-adjusted general population. The last 20 years have been marked by a huge effort in the characterization of the vascular remodeling process associated with CKD and its consequences on the renal, CV and general prognosis. By comparison with patients with normal renal function, with or without hypertension, an increase in large artery stiffness has been described in end-stage renal disease as well as in CKD stages 2-5. Most clinical studies are consistent with the observation that damage to large arteries may contribute to the high incidence of CV disease. By contrast, the impact of large artery stiffening and remodeling on CKD progression is still a matter of debate. Concomitant exposure to other CV risk factors, including diabetes, seems to play a major role in the association between aortic stiffness and estimated GFR. The conflicting results obtained from longitudinal studies designed to evaluate the impact of baseline aortic stiffness on GFR progression are detailed in the present review. Only pulse pressure, central and peripheral, is almost constantly associated with incident CKD and GFR decline. Kidney transplantation improves patients’ CV prognosis, but its impact on arterial stiffness is still controversial. Donor age, living kidney donation and mean blood pressure appear to be the main determinants of improvement in aortic stiffness after kidney transplantation. PMID:27195244

  3. Arterial hypertension and cancer.

    PubMed

    Milan, Alberto; Puglisi, Elisabetta; Ferrari, Laura; Bruno, Giulia; Losano, Isabel; Veglio, Franco

    2014-05-15

    Arterial hypertension and cancer are two of the most important causes of mortality in the world; correlations between these two clinical entities are complex and various. Cancer therapy using old (e.g., mitotic spindle poisons) as well as new (e.g., monoclonal antibody) drugs may cause arterial hypertension through different mechanisms; sometimes the increase of blood pressure levels may be responsible for chemotherapy withdrawal. Among newer cancer therapies, drugs interacting with the VEGF (vascular endothelial growth factors) pathways are the most frequently involved in hypertension development. However, many retrospective studies have suggested a relationship between antihypertensive treatment and risk of cancer, raising vast public concern. The purposes of this brief review have then been to analyse the role of chemotherapy in the pathogenesis of hypertension, to summarize the general rules of arterial hypertension management in this field and finally to evaluate the effects of antihypertensive therapy on cancer disease.

  4. A review of genetics, arterial stiffness, and blood pressure in African Americans.

    PubMed

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

    2012-06-01

    The prevalence of hypertension in African Americans in the USA is among 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.

  5. Arterial Stiffness: A Novel Risk Factor for Kidney Injury Progression?

    PubMed

    Georgianos, Panagiotis I; Sarafidis, Pantelis A; Liakopoulos, Vassilios

    2015-08-01

    Arterial stiffness is typical feature of vascular remodeling in chronic kidney disease (CKD). Increased arterial stiffness raises flow and pressure pulsatility and is considered the principle pathogenic mechanism of isolated systolic hypertension, left ventricular hypertrophy, and congestive heart failure. Apart from the impact of arterial stiffness on left ventricular afterload, downstream transmission of pressure pulsatility to the level of microcirculation is suggested to promote injury of other susceptible organs. This may be of particular importance for kidney injury progression, since passive renal perfusion along with low resistance and input impedance in renal microvessels make kidneys particularly vulnerable to the damaging effect of systemic pulsatile pressure. Recent studies have provided evidence that arterial stiffness culminates in elevated pulsatility and resistance in renal microvasculature, promoting structural damage of small intra-renal arterioles. Further, prospective observational studies have shown that reduced aortic compliance is closely associated with the annual rate of renal function decline and represents independent predictor of kidney injury progression to end-stage renal disease among patients with CKD. This article provides insights into the cross-talk between macrocirculation and renal microcirculation and summarizes the currently available clinical evidence linking increased arterial stiffness with kidney disease progression.

  6. Aortic Compliance and Stiffness Among Severe Longstanding Hypertensive and Non-hypertensive

    PubMed Central

    Kamberi, Lulzim Selim; Gorani, Daut Rashit; Hoxha, Teuta Faik; Zahiti, Bedri Faik

    2013-01-01

    Introduction Abnormal aortic function in hypertension is generally attributed to accelerated breakdown of elastin in the aorta, leading to dilatation of the lumen and stiffening of the wall as elastin is replaced with stiffer collagen. Aortic stiffness is an independent predictor of cardiovascular risk and all-cause and cardiovascular mortality. Vascular stiffening can activate endothelium which in turn may promote atherogenesis. Modulation of arterial stiffness has been shown to be successfully managed via changes in lifestyle and put under control of hypertension pharmacologically with antihypertensive drugs and statins. Methods Hundred and forty four patients have been enrolled in this study. They have been divided in two groups, with hypertension and group of control. Groups were with no age difference. Results Group with hypertension were with reduced aortic strain, distensibility (compliance) and have higher stiffness than control group; GrHTA =9.3 compared to GC=5.4. After successful treatment of hypertension with antihypertensives and statins, for two years, these parameters showed improvement, but still remain out of normal range compared to control group; 7.6 vs. 5.38. Conclusions Hypertensive patients have reduced aortic elasticity and increased stiffness which can be stopped and improved after treatment with antihypertensive and statin. PMID:23572854

  7. Aortic stiffness and distensibility among hypertensives.

    PubMed

    Meenakshisundaram, R; Kamaraj, K; Murugan, S; Thirumalaikolundusubramanian, P

    2009-09-01

    Hypertension is one among many factors that contribute to aortic stiffness, which has repercussions mainly on the heart. To assess aortic stiffness among essential hypertensives of South India and its relationship with gender. An analytical study was designed to assess aortic stiffness among 60 nonobese, nonalcoholic, nonsmoking, and non-caffeine consuming essential hypertensives without any overt illness or infection, and compared with 30 healthy age- and sex-matched nonhypertensives. They were assessed clinically and also by laboratory means. Their left ventricular mass (LV) and left ventricular ejection fraction (LVEF) were measured using Transthoracic echocardiogram. Aortic systolic and diastolic diameters were measured by using M-mode echocardiography during consecutive beats and averaged for each case. Finally, aortic stiffness was calculated. The data were analyzed statistically. Hypertensives were divided into Group I, consisting of patients with hypertension at least for 5 years, who were not adherent to medication, and Group II, consisting of patients with hypertension of duration between 6 months and 1 year. There were 20 males and 10 females in each group. There was no significant difference between the hypertensive groups and a control, normotensive, group with regard to BMI or total cholesterol. The means of LV mass (in grams), systolic BP (in mmHg), diastolic BP (in mmHg), aortic systolic diameter (in mm), aortic diastolic diameter (in mm), aortic distensibility (in mm), and aortic stiffness found in Group I, Group II, and controls were 105.8 +/- 23.8, 101.5 +/- 21, and 84 +/- 9.8; 138 +/- 14.2, 153 +/- 17.1, and 120 +/- 8.3; 90.5 +/- 11.6, 101.7 +/- 17.1, and 76.5 +/- 5; 30.85 +/- 2.6, 28.7 +/- 2.6, and 27.7 +/- 2.4; 28.7 +/- 2.2, 25.8 +/- 2.5, and 24.2 +/- 2.5; 2.14 +/- 0.3, 2.84 +/- 0.5, and 3.5 +/- 0.6; and 1.31 +/- 0.09, 1.14 +/- 0.1, and 1.04 +/- 0.08, respectively. The differences between the hypertensive groups and the control group were

  8. The association between oxidative stress, activator protein-1, inflammatory, total antioxidant status and artery stiffness and the efficacy of olmesartan in elderly patients with mild-to-moderate essential hypertension.

    PubMed

    Liu, Qunwei; Han, Limin; Du, Qiufan; Zhang, Ming; Zhou, Shenghua; Shen, Xiangqian

    2016-01-01

    This study investigated the change of oxidative stress, activator protein-1 (AP-1), inflammatory, total antioxidant status (TAS) and artery stiffness, and explored the relationship between these characteristics and the efficacy of olmesartan intervention in elderly patients with mild-to-moderate essential hypertension (EH). In total, 386 elderly patients with EH and 353 normotensive controls were recruited. All study subjects had oxidative stress markers, AP-1, inflammatory factors, TAS and brancial-ankle artery pulse wave velocity (ba-PWV) measured. In total, 193 elderly patients with EH were randomized to olmesartan and were matched with 193 normotensive controls to observe the change of index above mentioned before and after the treatment. Compared with the controls, superoxide dismutase (SOD) and TAS were significantly reduced in patients with EH, and malondialdehyde (MDA), AP-1, high-sensitivity C-reactive protein (Hs-CRP), Monocyte Chemoattractant Protein-1 (MCP-1), heart rate, endothelin-1 (ET-1), TAS and ba-PWV were significantly increased (P < 0.01 for all). Pearson's correlation analysis showed that SOD and TAS were negatively related to AP-1 (P < 0.05 for all), and that blood pressure (BP), age, MDA, Hs-CRP, MCP-1, ET-1 were positively related to AP-1 (P < 0.01 for all). Multivariate linear regression analysis showed that BP, SOD, MDA, AP-1, Hs-CRP, MCP-1, ET-1, TAS, heart rate and age were independent risk factors for ba-PWV. After treatment with olmesartan, SOD and TAS were increased, while BP, heart rate, AP-1 and inflammatory factors were reduced with significant improvement in ba-PWV (P < 0.05 for all). More increase of arterial stiffness was reported in elderly hypertensive patients with greater oxidative stress, inflammatory, AP-1, heart rate, and lower TAS. Higher oxidative stress, AP-1 and inflammatory may predict higher arterial stiffness. Olmesartan may increase TAS, yet inhibit oxidative stress, AP-1, inflammatory, and heart rate with

  9. 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.

  10. The kidney and arterial hypertension.

    PubMed

    Ruilope, L M; Campo, C; Lahera, V

    1993-01-01

    It has been known for some time that a relationship exists between the kidney and blood pressure. The renal origin of arterial hypertension has been demonstrated in different animal models resembling human hypertension, with data from humans seeming to confirm this hypothesis. On the other hand, the renal vasculature also suffers the consequences of arterial hypertension, and renal insufficiency can develop as a result of elevated blood pressure levels. Antihypertensive therapy can prevent the development of renal damage secondary to hypertension. For example, calcium antagonists possess specific renal effects that not only facilitate their antihypertensive capacity but also protect the kidney from the development of renal failure.

  11. Review of ‘the potential role of arterial stiffness in the pathogenesis of Alzheimer’s disease’

    PubMed Central

    Hughes, Timothy M; Craft, Suzanne; Lopez, Oscar L

    2015-01-01

    SUMMARY Arterial stiffness is emerging as an important risk marker for poor brain aging and dementia through its associations with cerebral small vessel disease, stroke, β-amyloid deposition, brain atrophy and cognitive impairment. Arterial stiffness directly relates the detrimental effects of hypertension on peripheral organs with dire consequences for the extensive microvasculature structure of the kidneys and brain. In this review, we discuss the evidence linking arterial stiffness, hypertension and brain structural abnormalities in older adults. In particular, we discuss the potential mechanisms linking arterial stiffness to brain β-amyloid deposition and dementia and potential therapeutic strategies to prevent hypertension’s adverse effects on the brain. PMID:25894876

  12. 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 ...

  13. 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

  14. 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

    2013-01-01

    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

  15. Renal implications of arterial hypertension.

    PubMed

    Ruilope, L M

    1997-03-01

    Renal vascular damage caused by arterial hypertension participates in alterations of the systemic vascular function and structure. Nephrosclerosis seems to run in parallel with the systemic atherosclerosis that accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function must be considered in any stratification of cardiovascular risk in hypertensive patients.

  16. 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

  17. The conundrum of arterial stiffness, elevated blood pressure, and aging.

    PubMed

    AlGhatrif, Majd; Lakatta, Edward G

    2015-02-01

    Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naïve. The aorta's function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short- and long-term alterations in each other. Hence, it is impossible to detect an "initial insult" at an epidemiological level. Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of

  18. 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

  19. Immune Mechanisms in Arterial Hypertension.

    PubMed

    Wenzel, Ulrich; Turner, Jan Eric; Krebs, Christian; Kurts, Christian; Harrison, David G; Ehmke, Heimo

    2016-03-01

    Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

  20. 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.

  1. Secondary arterial hypertension linked to Freon exposure.

    PubMed

    Voge, V M

    1996-05-01

    Freons are generally considered to be minimally toxic. There are no reports in the literature of Freons causing secondary arterial hypertension. We report two cases of acute, massive Freon exposure that preceded secondary arterial hypertension. We hypothesize that the arterial hypertension was precipitated by renal proximal tubular damage, although several other mechanisms are possible.

  2. [PREDICTORS OF RESISTANT ARTERIAL HYPERTENSION].

    PubMed

    Lazutkina, A Y; Gorbunov, V V

    2016-01-01

    The paper reports results of 6 year prospective observation of 7959 members of locomotive crews engaged at the Transbaikal Railways. The study aimed to estimate the probability and time of development of resistant arterial hypertension under effect of predictors of this disease. The data obtained are of value for diagnostic, prophylactic, and therapeutic practice. PMID:27522725

  3. Long Sleep Duration Associated With a Higher Risk of Increased Arterial Stiffness in Males

    PubMed Central

    Tsai, Tsai-Chen; Wu, Jin-Shang; Yang, Yi-Ching; Huang, Ying-Hsiang; Lu, Feng-Hwa; Chang, Chih-Jen

    2014-01-01

    Study Objectives: We aimed to examine the association between sleep duration and arterial stiffness among adults of different ages, because to date there has been only one study on this relationship, which was confined to middle-aged civil servants. Design: Cross-sectional study. Setting: A health examination center in National Cheng Kung University Hospital, Taiwan. Participants: A total of 3,508 subjects, age 20–87 y, were enrolled after excluding those with a history of cerebrovascular events, coronary artery disease, peripheral artery disease, and taking lipid-lowering drugs, antihypertensives, hypoglycemic agents, and anti-inflammatory drugs, from October 2006 to August 2009. Interventions: N/A. Measurements and Results: Sleep duration was classified into three groups: short (< 6 h), normal (6–8 h) and long (> 8 h). Arterial stiffness was measured by brachial-ankle pulse-wave velocity (baPWV), and increased arterial stiffness was defined as baPWV ≥ 1400 cm/sec. The sleep duration was different for subjects with and without increased arterial stiffness in males, but not in females. In the multivariate analysis for males, long sleepers (odds ratio [OR] 1.75, P = 0.034) but not short sleepers (OR 0.98, P = 0.92) had a higher risk of increased arterial stiffness. In addition, age, estimated glomerular filtration rate, hypertension, diabetes, total cholesterol/high-density lipoprotein cholesterol ratio, cigarette smoking, and exercise were also independently associated factors. However, in females, neither short nor long sleep duration was associated with increased arterial stiffness. Conclusions: Long sleep duration was associated with a higher risk of increased arterial stiffness in males. Short sleepers did not exhibit a significant risk of increased arterial stiffness in either sex. Citation: Tsai TC, Wu JS, Yang YC, Huang YH, Lu FH, Chang CJ. Long sleep duration associated with a higher risk of increased arterial stiffness in males. SLEEP 2014

  4. Clinical assessment of arterial stiffness with cardio-ankle vascular index: theory and applications.

    PubMed

    Hayashi, Kozaburo; Yamamoto, Tomoyuki; Takahara, Akira; Shirai, Kohji

    2015-09-01

    Arterial stiffness is often assessed in clinical medicine, because it is not only an important factor in the pathophysiology of blood circulation but also a marker for the diagnosis and the prognosis of cardiovascular diseases. Many parameters have so far been proposed to quantitatively represent arterial stiffness and distensibility, such as pressure-strain elastic modulus (Ep), stiffness parameter (β), pulse wave velocity (PWV), and vascular compliance (Cv). Among these, PWV has been most frequently applied to clinical medicine. However, this is dependent on blood pressure at the time of measurement, and therefore it is not appropriate as a parameter for the clinical evaluation of arterial stiffness, especially for the studies on hypertension. On the contrary, stiffness parameter β is an index reflecting arterial stiffness without the influence of blood pressure. Recently, this parameter has been applied to develop a new arterial stiffness index called cardio-ankle vascular index (CAVI). Although this index is obtained from the PWV between the heart and the ankle, it is essentially similar to the stiffness parameter β, and therefore it does not depend on blood pressure changes during the measurements. CAVI is being extensively used in clinical medicine as a measure for the evaluation of cardiovascular diseases and risk factors related to arteriosclerosis. In the present article, we will explain the theoretical background of stiffness parameter β and the process to obtain CAVI. And then, the clinical utility of CAVI will be overviewed by reference to recent studies.

  5. 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

  6. [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.

  7. New therapies for arterial hypertension.

    PubMed

    Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

    2016-03-01

    Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures. PMID:26730462

  8. New therapies for arterial hypertension.

    PubMed

    Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

    2016-03-01

    Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures.

  9. [Update arterial hypertension 2015].

    PubMed

    Rickenbacher, Peter

    2015-04-22

    Hypertension, defined as office blood pressure of ≥140 mmHg systolic and/or ≥90 mmHg diastolic, is prevalent and one of the most important risk factors for disease and premature death. Diagnostic evaluation includes risk stratification regarding other cardiovascular risk factors, cardiovascular disease and asymptomatic organ damage. Currently, treatment is generally recommended with blood pressure ≥140/90 mmHg with the goal of reducing values below these limits also in high risk patients. Exceptions concern patients with advanced age or diabetes. Treatment involves lifestyle changes, anthypertensive drugs and in the future probably interventional techniques. This mini-review summarizes selected and practically relevant diagnostic and therapeutic aspects from recent international guidelines.

  10. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension

    PubMed Central

    Wang, Zhijie; Chesler, Naomi C.

    2011-01-01

    Pulmonary hypertension (PH) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload. These changes, characterized by narrowing and stiffening, occur in both proximal and distal pulmonary arteries (PAs). An important consequence of arterial narrowing is increased pulmonary vascular resistance (PVR). Arterial stiffening, which can occur in both the proximal and distal pulmonary arteries, is an important index of disease progression and is a significant contributor to increased RV afterload in PH. In particular, arterial narrowing and stiffening increase the RV afterload by increasing steady and oscillatory RV work, respectively. Here we review the current state of knowledge of the causes and consequences of pulmonary arterial stiffening in PH and its impact on RV function. We review direct and indirect techniques for measuring proximal and distal pulmonary arterial stiffness, measures of arterial stiffness including elastic modulus, incremental elastic modulus, stiffness coefficient β and others, the changes in cellular function and the extracellular matrix proteins that contribute to pulmonary arterial stiffening, the consequences of PA stiffening for RV function and the clinical implications of pulmonary vascular stiffening for PH progression. Future investigation of the relationship between PA stiffening and RV dysfunction may facilitate new therapies aimed at improving RV function and thus ultimately reducing mortality in PH. PMID:22034607

  11. Carotid intimal-medial thickness and stiffness are not affected by hypercholesterolemia in uncomplicated essential hypertension.

    PubMed

    Saba, P S; Roman, M J; Longhini, C; Scorzoni, D; Pini, R; Devereux, R B; Ganau, A

    1999-11-01

    The combined effects of hypertension and hypercholesterolemia on carotid anatomy and stiffness were studied in 62 normotensives, 141 uncomplicated essential hypertensives with a total cholesterol level <240 mg/dL, and 60 essential hypertensives with a total cholesterol level >/=240 mg/dL. Carotid ultrasonography was performed to evaluate intimal-medial thickness (IMT), relative wall thickness, and the presence of plaque. Carotid pressure waveforms were recorded by applanation tonometry to measure carotid stiffness (beta) and pressure wave reflection (ie, augmentation index). After adjusting for age, body mass index, and smoking habit by analysis of covariance, no significant differences were found between normocholesterolemic hypertensives and hypercholesterolemic hypertensives in terms of IMT (0.79+/-0.19 versus 0.81+/-0.19 mm), relative wall thickness (0.27+/-0.07 versus 0.28+/-0.07), carotid stiffness (6.1+/-3.2 versus 5.6+/-2.7), augmentation index (18. 7+/-12.9% versus 17.3+/-12.8%), and prevalence of plaque (30.8% versus 30.7%). In the whole population, carotid IMT was significantly related to age (r=0.43), systolic (r=0.35) and diastolic (r=0.35) blood pressures, body surface area (r=0.22), and cholesterol levels (r=0.22) (all P<0.05). Carotid stiffness was significantly related to age, blood pressure, body mass index, and body surface area but not to cholesterol levels. In multivariate analyses, age, body surface area, and systolic blood pressure, but not cholesterol, smoking habit, or sex, were independent correlates of IMT (multiple R=0.54, P<0.0001), whereas carotid stiffness was independently associated with age, body surface area, and sex (R=0. 38, P<0.0001). In conclusion, hypertension is a potent stimulus of vascular hypertrophy. The superimposition of hypercholesterolemia does not substantially augment these changes or further increase arterial stiffness in uncomplicated hypertensive subjects.

  12. [Management of arterial hypertension in the elderly].

    PubMed

    Xhignesse, P; Saint-Remy, A; Krzesinski, J M

    2014-01-01

    High blood pressure is very frequent in the elderly; it represents a real threat for the patient's health and a source of huge costs for the economic system. Systolic hypertension is the most frequent form observed in the old, due to large arteries stiffness. Antihypertensive therapy has proven effective to decrease significantly the cardiovascular morbi-mortality and total mortality in this population. A non pharmacological approach is also very useful, but should not be too restrictive. Blood pressure target in patients older than 65 (and, particularly, in octogenarians) is 150/80 mmHg. Blood pressure should be checked in the upright position before changing the drug dosage. The first line therapy in the old should generally be a calcium channel antagonist or a low dose diuretic.

  13. “Smooth Muscle Cell Stiffness Syndrome”—Revisiting the Structural Basis of Arterial Stiffness

    PubMed Central

    Sehgel, Nancy L.; Vatner, Stephen F.; Meininger, Gerald A.

    2015-01-01

    In recent decades, the pervasiveness of increased arterial stiffness in patients with cardiovascular disease has become increasingly apparent. Though, this phenomenon has been well documented in humans and animal models of disease for well over a century, there has been surprisingly limited development in a deeper mechanistic understanding of arterial stiffness. Much of the historical literature has focused on changes in extracellular matrix proteins—collagen and elastin. However, extracellular matrix changes alone appear insufficient to consistently account for observed changes in vascular stiffness, which we observed in our studies of aortic stiffness in aging monkeys. This led us to examine novel mechanisms operating at the level of the vascular smooth muscle cell (VSMC)—that include increased cell stiffness and adhesion to extracellular matrix—which that may be interrelated with other mechanisms contributing to arterial stiffness. We introduce these observations as a new concept—the Smooth Muscle Cell Stiffness Syndrome (SMCSS)—within the field of arterial stiffness and posit that stiffening of vascular cells impairs vascular function and may contribute stiffening to the vasculature with aging and cardiovascular disease. Importantly, this review article revisits the structural basis of arterial stiffness in light of these novel findings. Such classification of SMCSS and its contextualization into our current understanding of vascular mechanics may be useful in the development of strategic therapeutics to directly target arterial stiffness. PMID:26635621

  14. Impact of blood pressure perturbations on arterial stiffness.

    PubMed

    Lim, Jisok; Pearman, Miriam E; Park, Wonil; Alkatan, Mohammed; Machin, Daniel R; Tanaka, Hirofumi

    2015-12-15

    Although the associations between chronic levels of arterial stiffness and blood pressure (BP) have been fairly well studied, it is not clear whether and how much arterial stiffness is influenced by acute perturbations in BP. The primary aim of this study was to determine magnitudes of BP dependence of various measures of arterial stiffness during acute BP perturbation maneuvers. Fifty apparently healthy subjects, including 25 young (20-40 yr) and 25 older adults (60-80 yr), were studied. A variety of BP perturbations, including head-up tilt, head-down tilt, mental stress, isometric handgrip exercise, and cold pressor test, were used to encompass BP changes induced by physical, mental, and/or mechanical stimuli. When each index of arterial stiffness was plotted with mean BP, all arterial stiffness indices, including cardio-ankle vascular index or CAVI (r = 0.50), carotid-femoral pulse wave velocity or cfPWV (r = 0.51), brachial-ankle pulse wave velocity or baPWV (r = 0.61), arterial compliance (r = -0.42), elastic modulus (r = 0.52), arterial distensibility (r = -0.32), β-stiffness index (r = 0.19), and Young's modulus (r = 0.35) were related to mean BP (all P < 0.01). Changes in CAVI, cfPWV, baPWV, and elastic modulus were significantly associated with changes in mean BP in the pooled conditions, while changes in arterial compliance, arterial distensibility, β-stiffness index, and Young's modulus were not. In conclusion, this study demonstrated that BP changes in response to various forms of pressor stimuli were associated with the corresponding changes in arterial stiffness indices and that the strengths of associations with BP varied widely depending on what arterial stiffness indices were examined. PMID:26468262

  15. Impact of blood pressure perturbations on arterial stiffness.

    PubMed

    Lim, Jisok; Pearman, Miriam E; Park, Wonil; Alkatan, Mohammed; Machin, Daniel R; Tanaka, Hirofumi

    2015-12-15

    Although the associations between chronic levels of arterial stiffness and blood pressure (BP) have been fairly well studied, it is not clear whether and how much arterial stiffness is influenced by acute perturbations in BP. The primary aim of this study was to determine magnitudes of BP dependence of various measures of arterial stiffness during acute BP perturbation maneuvers. Fifty apparently healthy subjects, including 25 young (20-40 yr) and 25 older adults (60-80 yr), were studied. A variety of BP perturbations, including head-up tilt, head-down tilt, mental stress, isometric handgrip exercise, and cold pressor test, were used to encompass BP changes induced by physical, mental, and/or mechanical stimuli. When each index of arterial stiffness was plotted with mean BP, all arterial stiffness indices, including cardio-ankle vascular index or CAVI (r = 0.50), carotid-femoral pulse wave velocity or cfPWV (r = 0.51), brachial-ankle pulse wave velocity or baPWV (r = 0.61), arterial compliance (r = -0.42), elastic modulus (r = 0.52), arterial distensibility (r = -0.32), β-stiffness index (r = 0.19), and Young's modulus (r = 0.35) were related to mean BP (all P < 0.01). Changes in CAVI, cfPWV, baPWV, and elastic modulus were significantly associated with changes in mean BP in the pooled conditions, while changes in arterial compliance, arterial distensibility, β-stiffness index, and Young's modulus were not. In conclusion, this study demonstrated that BP changes in response to various forms of pressor stimuli were associated with the corresponding changes in arterial stiffness indices and that the strengths of associations with BP varied widely depending on what arterial stiffness indices were examined.

  16. 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

  17. Increased arterial stiffness and extracellular matrix reorganization in intrauterine growth–restricted fetal sheep

    PubMed Central

    Dodson, Reuben Blair; Rozance, Paul J.; Fleenor, Bradley S.; Petrash, Carson C.; Shoemaker, Lauren G.; Hunter, Kendall S.; Ferguson, Virginia L.

    2013-01-01

    BACKGROUND Fetal intrauterine growth restriction (IUGR) results in increased placental resistance to blood flow, fetal hypertension, and increased pulsatility stresses shown to lead to vascular remodeling. We tested our hypothesis that IUGR causes decreased compliance in the carotid and umbilical arteries due to altered extracellular matrix (ECM) composition and structure. METHODS A sheep model of placental insufficiency–induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Umbilical and carotid arteries from near-term fetuses were tested with pressure–diameter measurements to compare passive compliance in control and PI-IUGR tissues. ECM composition was measured via biochemical assay, and the organization was determined by using histology and second-harmonic generation imaging. RESULTS We found that PI-IUGR increased arterial stiffness with increased collagen engagement, or transition stretch. PI-IUGR carotid arteries exhibited increased collagen and elastin quantity, and PI-IUGR umbilical arteries exhibited increased sulfated glycosaminoglycans. Histomorphology showed altered collagen-to-elastin ratios with altered cellular proliferation. Increased stiffness indicates altered collagen-to-elastin ratios with less elastin contribution leading to increased collagen engagement. CONCLUSION Because vessel stiffness is a significant predictor in the development of hypertension, disrupted ECM deposition in IUGR provides a potential link between IUGR and adult hypertension. PMID:23154756

  18. Arterial stiffness estimation based photoplethysmographic pulse wave analysis

    NASA Astrophysics Data System (ADS)

    Huotari, Matti; Maatta, Kari; Kostamovaara, Juha

    2010-11-01

    Arterial stiffness is one of the indices of vascular healthiness. It is based on pulse wave analysis. In the case we decompose the pulse waveform for the estimation and determination of arterial elasticity. Firstly, optically measured with photoplethysmograph and then investigating means by four lognormal pulse waveforms for which we can find very good fit between the original and summed decomposed pulse wave. Several studies have demonstrated that these kinds of measures predict cardiovascular events. While dynamic factors, e.g., arterial stiffness, depend on fixed structural features of the vascular wall. Arterial stiffness is estimated based on pulse wave decomposition analysis in the radial and tibial arteries. Elucidation of the precise relationship between endothelial function and vascular stiffness awaits still further study.

  19. 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.

  20. 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.

  1. Pulmonary arterial hypertension and pregnancy

    PubMed Central

    Terek, Demet; Kayikcioglu, Meral; Kultursay, Hakan; Ergenoglu, Mete; Yalaz, Mehmet; Musayev, Oktay; Mogulkoc, Nesrin; Gunusen, Ilkben; Akisu, Mete; Kultursay, Nilgun

    2013-01-01

    This is the case report of a pregnant woman who refused pregnancy termination when diagnosed with pulmonary arterial hypertension (PAH) functional class 2–3 at the 24th week of gestation and of her newborn. A pregnant woman with PAH functional class 2–3 was treated with inhaled prostacyclin analog (iloprost), oral sildenafil, oxygen, and low molecular weight heparin. She delivered at 32nd week by Cesarean section. The infant required oxygen up to 36th week postconceptional age and had a short steroid treatment. The mother needed close cardiovascular monitorization, intensive oxygen and pulmonary vasodilator therapy for 2 months and was discharged with oxygen and oral iloprost treatment. A multidisciplinary approach together with pulmonary vasodilator therapy may be succesful in such a high-risk pregnant woman. PMID:23900530

  2. [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.

  3. Inflammation in pulmonary arterial hypertension.

    PubMed

    Price, Laura C; Wort, S John; Perros, Frédéric; Dorfmüller, Peter; Huertas, Alice; Montani, David; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2012-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study. PMID:22215829

  4. Drugs induced pulmonary arterial hypertension.

    PubMed

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  5. Changes in large pulmonary arterial viscoelasticity in chronic pulmonary hypertension.

    PubMed

    Wang, Zhijie; Lakes, Roderic S; Golob, Mark; Eickhoff, Jens C; Chesler, Naomi C

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

  6. Changes in Large Pulmonary Arterial Viscoelasticity in Chronic Pulmonary Hypertension

    PubMed Central

    Wang, Zhijie; Lakes, Roderic S.; Golob, Mark; Eickhoff, Jens C.; Chesler, Naomi C.

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01–20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

  7. [Arterial hypertension secondary to endocrine disorders].

    PubMed

    Minder, Anna; Zulewski, Henryk

    2015-06-01

    Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

  8. Pulmonary hypertension and pulmonary artery dissection

    PubMed Central

    Corrêa, Ricardo de Amorim; Silva, Luciana Cristina dos Santos; Rezende, Cláudia Juliana; Bernardes, Rodrigo Castro; Prata, Tarciane Aline; Silva, Henrique Lima

    2013-01-01

    Pulmonary artery dissection is a fatal complication of long-standing pulmonary hypertension, manifesting as acute, stabbing chest pain, progressive dyspnea, cardiogenic shock, or sudden death. Its incidence has been underestimated, and therapeutic options are still scarce. In patients with pulmonary hypertension, new chest pain, acute chest pain, or cardiogenic shock should raise the suspicion of pulmonary artery dissection, which can result in sudden death. PMID:23670510

  9. [Arterial hypertension and metabolic syndrome].

    PubMed

    Christ, Michael; Klima, Theresia; Maisch, Bernhard

    2003-12-01

    BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact

  10. 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.

  11. 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

  12. Pulmonary vascular stiffness: measurement, modeling, and implications in normal and hypertensive pulmonary circulations.

    PubMed

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

    2011-07-01

    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

  13. 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

  14. Severity of Osteoarthritis Is Associated with Increased Arterial Stiffness

    PubMed Central

    Kals, Jaak; Zilmer, Mihkel; Paapstel, Kaido; Märtson, Aare

    2016-01-01

    Objective. Osteoarthritis (OA) is associated with increased cardiovascular comorbidity and mortality. Evidence is lacking about whether arterial stiffness is involved in OA. The objective of our study was to find out associations between OA, arterial stiffness, and adipokines. Design. Seventy end-stage knee and hip OA patients (age 62 ± 7 years) and 70 asymptomatic controls (age 60 ± 7 years) were investigated using the applanation tonometry to determine their parameters of arterial stiffness. Serum adiponectin, leptin, and matrix metalloproteinase 3 (MMP-3) levels were determined using the ELISA method. Correlation between variables was determined using Spearman's rho. Multiple regression analysis with a stepwise selection procedure was employed. Results. Radiographic OA grade was positively associated with increased carotid-femoral pulse wave velocity (cf-PWV) (r = 0.272, p = 0.023). We found that OA grade was also associated with leptin and MMP-3 levels (rho = −0.246, p = 0.040 and rho = 0.235, p = 0.050, resp.). In addition, serum adiponectin level was positively associated with augmentation index and inversely with large artery elasticity index (rho = 0.293, p = 0.006 and rho = −0.249, p = 0.003, resp.). Conclusions. Our results suggest that OA severity is independently associated with increased arterial stiffness and is correlated with expression of adipokines. Thus, increased arterial stiffness and adipokines might play an important role in elevated cardiovascular risk in end-stage OA. PMID:27493667

  15. Arterial hypertension: A neglected risk for bleeding.

    PubMed

    Vogel, Birgit; Mehran, Roxana

    2016-08-01

    The impact of arterial hypertension, one of the most common comorbidities in CAD patients, on bleeding risk after PCI must not be underestimated. More rigorous control of blood pressure during PCI procedure, radial artery access and alternative anticoagulant strategy may be considered in these patients. Further investigation in a more contemporary setting of PCI procedure is warranted. PMID:27530190

  16. Serum Sclerostin as an Independent Marker of Peripheral Arterial Stiffness in Renal Transplantation Recipients

    PubMed Central

    Hsu, Bang-Gee; Liou, Hung-Hsiang; Lee, Chung-Jen; Chen, Yen-Cheng; Ho, Guan-Jin; Lee, Ming-Che

    2016-01-01

    Abstract Wnt/β-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. In this study, we applied automatic pulse wave analyzer (VaSera VS-1000) to measure brachial-ankle pulse wave velocity and either sides of brachial-ankle pulse wave velocity value, which greater than 14.0 m/s was determined as high arterial stiffness. Among 68 RT recipients, 30 patients (44.1%) were in the high arterial stiffness group. Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (β = 0.272, P = 0.014), phosphorus (β = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; β = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007–1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004–1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was

  17. Experimental exposure to diesel exhaust increases arterial stiffness in man

    PubMed Central

    Lundbäck, Magnus; Mills, Nicholas L; Lucking, Andrew; Barath, Stefan; Donaldson, Ken; Newby, David E; Sandström, Thomas; Blomberg, Anders

    2009-01-01

    Introduction Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness. Methods In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 μg/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated. Results Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure. Conclusion Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution. PMID:19284640

  18. Increased arterial stiffness in young adults with end-stage renal disease since childhood.

    PubMed

    Groothoff, Jaap W; Gruppen, Mariken P; Offringa, Martin; de Groot, Eric; Stok, Willem; Bos, Willem Jan; Davin, Jean Claude; Lilien, Marc R; Van de Kar, Nicole Caj; Wolff, Eric D; Heymans, Hugo S

    2002-12-01

    Increased arterial stiffness is a risk factor for mortality in adults over 40 yr of age with end-stage renal disease (ESRD). As no data exist on vascular changes in young adults with ESRD since childhood, a long-term outcome study was performed. All living Dutch adult patients with onset of ESRD between 1972 and 1992 at age 0 to 14 yr were invited for carotid artery and cardiac ultrasound and BP measurements. Data on clinical characteristics were collected by review of all medical charts. Carotid ultrasound data were compared with those of 48 age-matched and gender-matched healthy controls. Carotid artery and cardiac ultrasound was performed in 130 out of 187 eligible patients. Mean age was 29.0 (20.7 to 40.6) yr. Compared with controls, patients had a similar intima media thickness but a reduced mean arterial wall distensibility DC (40.0 versus 45.0 kPa(-1). 10(-3); 95% CI, -9.1 to -0.8; P < 0.001), an increased stiffness parameter beta (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P = 0.02), an increased elastic incremental modulus E(inc) (0.35 versus 0.27 kPa. 10(3); 95% CI, 0.02 to 0.12; P < 0.001). Multiple regression analyses in all subjects revealed that ESRD was associated with an increase in beta and E(inc). Arterial wall properties of patients currently on dialysis and transplanted patients were comparable. In all patients, current systolic hypertension was associated with increased E(inc) and decreased DC. In conclusion, carotid arterial wall stiffness is increased in young adult patients with pediatric ESRD. Hypertension is a main determinant and might be a target for treatment of these potentially lethal arterial wall changes.

  19. 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. PMID:27643106

  20. Modifiable Risk Factors for Increased Arterial Stiffness in Outpatient Nephrology

    PubMed Central

    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. PMID:25880081

  1. In vivo and in vitro measurements of pulmonary arterial stiffness: A brief review

    PubMed Central

    Tian, Lian; Chesler, Naomi C.

    2012-01-01

    During the progression of pulmonary hypertension (PH), proximal pulmonary arteries (PAs) undergo remodeling such that they become thicker and the elastic modulus increases. Both of these changes increase the vascular stiffness. The increase in pulmonary vascular stiffness contributes to increased right ventricular (RV) afterload, which causes RV hypertrophy and eventually failure. Studies have found that proximal PA stiffness or its inverse, compliance, is strongly related to morbidity and mortality in patients with PH. Therefore, accurate in vivo measurement of PA stiffness is useful for prognoses in patients with PH. It is also important to understand the structural changes in PAs that occur with PH that are responsible for stiffening. Here, we briefly review the most common parameters used to quantify stiffness and in vivo and in vitro methods for measuring PA stiffness in human and animal models. For in vivo approaches, we review invasive and noninvasive approaches that are based on measurements of pressure and inner or outer diameter or cross-sectional area. For in vitro techniques, we review several different testing methods that mimic one, two or several aspects of physiological loading (e.g., uniaxial and biaxial testing, dynamic inflation-force testing). Many in vivo and in vitro measurement methods exist in the literature, and it is important to carefully choose an appropriate method to measure PA stiffness accurately. Therefore, advantages and disadvantages of each approach are discussed. PMID:23372936

  2. Arterial stiffness of lifelong Japanese female pearl divers.

    PubMed

    Tanaka, Hirofumi; Tomoto, Tsubasa; Kosaki, Keisei; Sugawara, Jun

    2016-05-15

    Japanese female pearl divers called Ama specialize in free diving in the cold sea for collecting foods and pearls in oysters. Exercising in the water combined with marked bradycardia and pressor responses provides a circulatory challenge to properly buffer or cushion elevated cardiac pulsations. Because Ama perform repeated free dives throughout their lives, it is possible that they may have adapted similar arterial structure and function to those seen in diving mammals. We compared arterial stiffness of lifelong Japanese pearl divers with age-matched physically inactive adults living in the same fishing villages. A total of 115 Japanese female pearl divers were studied. Additionally, 50 physically inactive adults as well as 33 physically active adults (participating in community fitness programs) living in the same coastal villages were also studied. There were no differences in age (∼65 yr), body mass index, and brachial blood pressure between the groups. Measures of arterial stiffness, cardio-ankle vascular index and β-stiffness index were lower (P < 0.05) in pearl divers and physically active adults than in their physically inactive peers. Augmentation pressure and augmentation index adjusted for the heart rate of 75 beats/min were lower (P < 0.05) in pearl divers than in other groups. These results indicate that lifelong Japanese pearl divers demonstrate reduced arterial stiffness and arterial wave reflection compared with age-matched physically inactive peers living in the same fishing villages. PMID:26984889

  3. 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.

  4. Medical treatment update on pulmonary arterial hypertension

    PubMed Central

    Burger, Charles

    2015-01-01

    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. PMID:26336595

  5. 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

  6. 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.

  7. [Differential diagnosis of secondary arterial hypertension].

    PubMed

    Ruilope, L M

    1990-01-01

    The adequate performance of the differential diagnosis will permit us to classify any increase in blood pressure as due to primary or secondary causes. The data obtained in the clinical history and physical examination as well as those obtained through the minimal laboratory tests to be performed are the clues to identify secondary causes of arterial hypertension.

  8. Genetic impact dominates over environmental effects in development of carotid artery stiffness: a twin study.

    PubMed

    Horváth, Tamás; Osztovits, János; Pintér, Alexandra; Littvay, Levente; Cseh, Domonkos; Tárnoki, Adám D; Tárnoki, Dávid L; Jermendy, Adám L; Steinbach, Rita; Métneki, Júlia; Schillaci, Giuseppe; Kollai, Márk; Jermendy, György

    2014-01-01

    Arterial stiffness is an independent predictor of cardiovascular, cerebrovascular and all-cause mortality. Quantifying the genetic influence on the stiff arterial phenotype allows us to better predict the development of arterial stiffness. In this study, we aimed to determine the heritability of carotid artery stiffness in healthy twins. We studied 98 twin pairs of both sexes. We determined carotid artery stiffness locally using echo tracking and applanation tonometry. We estimated the heritability of stiffness parameters using structural equation modeling. The carotid distensibility coefficient showed the highest heritability (64%, 95% confidence interval 45-77%). The incremental elastic modulus, compliance and stiffness index β also showed substantial heritability (62%, 61% and 58%, respectively). The remaining 36-42% phenotypic variance was attributed to unshared environmental effects. Genetic influence appears to dominate over environmental factors in the development of carotid artery stiffness. Environmental factors may have an important role in favorably influencing the genetic predisposition for accelerated arterial stiffening.

  9. [Clinical value and measurement of arterial stiffness for the assessment of cardiovascular risk in light of recent results].

    PubMed

    Nemcsik, János; Tislér, András; Kiss, István

    2015-02-01

    Cardiovascular risk stratification is fundamental for the development of effective prevention and therapeutic strategies. Although there are numerous scores and risk tables available, a difference still exists between the estimated and real number of cardiovascular events. Measurement of arterial stiffness can provide additional information to risk stratification. The most widely accepted parameter of arterial stiffness is aortic pulse wave velocity, which has been included in the guideline of the European Society of Hypertension in 2007 and 2013, although American guidelines still omit it. In this review the authors summarize the evidence with regards to the different steps required for clinical application of arterial stiffness measurement and they also discuss the questions that evolved from the methodological variability of different measurement techniques.

  10. Role of Mineralocorticoid Receptors in Arterial Stiffness in Human Aging

    PubMed Central

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Nichols, Wilmer W.; Christou, Demetra D.

    2013-01-01

    Arterial stiffness, an independent predictor of cardiovascular disease, is increased in aging, but the underlying mechanisms are not completely understood. Mineralocorticoid receptors (MR) may contribute to oxidative stress and arterial stiffness in healthy older adults. To test the hypothesis that short-term MR blockade may reduce oxidative stress and improve arterial stiffness, we conducted a randomized, double blind, crossover study using the selective MR blocker Eplerenone or placebo in 23 older adults (age, 64±1 years; mean±SE) free from overt cardiovascular and other clinical disease (e.g, diabetes, renal and liver disease). In response to MR blockade, brachial and carotid blood pressure decreased (P≤0.01). However, MR blockade had no effect on oxidative stress (oxidized LDL, 61.2±6.8 vs. 62.4±7.4 U/L, P=0.9; placebo vs. Eplerenone) and arterial stiffness (aortic pulse wave velocity (PWV), 9.17±1.19 vs. 8.92±1.19 m/sec, P=0.5; leg PWV, 13.45±0.45 vs. 12.81±0.47 m/sec, P=0.3; arm PWV, 11.43±0.62 vs. 11.73±0.68 m/sec, P=0.7; carotid artery compliance, 0.150±0.013 vs. 0.149±0.014 mm2/mmHg, P=0.8; distensibility, 23.1±1.8 vs. 23.3±1.7 10−3/kPa, P=0.8; β stiffness index, 3.5±0.3 vs. 3.6±0.3, P=0.6; and augmentation index, 16.0±2.2 vs. 15.6±2.8 %, P=0.8). These results provide the first evidence that MR do not appear to contribute to oxidative stress in human aging and that short-term MR blockade does not result in reduced oxidative stress and improved arterial stiffness. PMID:23707930

  11. The Role of Monitoring Arterial Stiffness with Cardio-Ankle Vascular Index in the Control of Lifestyle-Related Diseases.

    PubMed

    Shirai, Kohji; Saiki, Atsuhito; Nagayama, Daiji; Tatsuno, Ichiro; Shimizu, Kazuhiro; Takahashi, Mao

    2015-09-01

    Arteriosclerosis is a major contributor to cardiovascular diseases. One of the difficulties in controlling those diseases is the lack of a suitable indicator of arteriosclerosis or arterial injury in routine clinical practice. Arterial stiffness was supposed to be one of the monitoring indexes of arteriosclerosis. Cardio-ankle vascular index (CAVI) is reflecting the stiffness of the arterial tree from the origin of the aorta to the ankle, and one of the features of CAVI is independency from blood pressure at a measuring time. When doxazosin, an α1-adrenergic blocker, was administered, CAVI decreased, indicating that arterial stiffness is composed of both organic stiffness and functional stiffness, which reflects the contraction of arterial smooth muscle. CAVI shows a high value with aging and in many arteriosclerotic diseases, and is also high in persons possessing main coronary risk factors such as diabetes mellitus, metabolic syndrome, hypertension and smoking. Furthermore, when the most of those risk factors were controlled by proper methods, CAVI improved. Furthermore, the co-relationship between CAVI and heart function was demonstrated during treatment of heart failure. This paper reviews the principle and rationale of CAVI, and discusses the meaning of monitoring CAVI in following up so-called lifestyle-related diseases and cardiac dysfunction in routine clinical practice. PMID:26587461

  12. PRESSOR SUBSTANCES IN ARTERIAL HYPERTENSION

    PubMed Central

    Schroeder, Henry A.; Perry, H. Mitchell; Dennis, Evie G.; Mahoney, Laura E.

    1955-01-01

    Some pharmacological and chemical qualities of pherentasin, a vasoconstrictor substance procured from human hypertensive blood, were studied by a new assay method using the spirally cut rabbit aorta. Of a number of drugs tested, six metal-binding agents including hydralazine inactivated the active principle. The material was stable in acid but not in alkali. It was destroyed by drying. Chemical analysis and inactivation procedures suggested the presence of primary amine and considerable sulfur; a peptide linkage was suspected because of inactivation by manganous ion and papain. The material was remarkably resistant to most pharmacological agents and appeared to act directly on smooth muscle. PMID:13252186

  13. Cystatin C Associates with Arterial Stiffness in Older Adults

    PubMed Central

    Madero, Magdalena; Wassel, Christina L.; Peralta, Carmen A.; Najjar, Samer S.; Sutton-Tyrrell, Kim; Fried, Linda; Canada, Robert; Newman, Anne; Shlipak, Michael G.; Sarnak, Mark J.

    2009-01-01

    Large arteries commonly become stiff in kidney failure, but few studies have investigated arterial stiffness in earlier stages of kidney disease. We evaluated the association between kidney function and aortic pulse wave velocity (aPWV) and its potential modification by race, diabetes, or coronary heart disease in older adults. We measured aPWV in 2468 participants in the Health Aging and Body Composition (Health ABC) study; mean age was 73.7 yr, 40% were black, and 24% had diabetes. After categorizing kidney function into three groups on the basis of cystatin C level, multivariable analysis revealed that the medium and high cystatin C groups associated with a 5.3% (95% confidence interval 0.8 to 10.0%) and 8.0% (95% confidence interval 2.2 to 14.1%) higher aPWV than the low cystatin C group; however, chronic kidney disease, as defined by estimated GFR <60 ml/min per 1.73 m2, did not significantly associate with aPWV. We did not identify interactions between cystatin C and race, diabetes, or coronary heart disease. In conclusion, stiffness of large arteries, a major risk factor for cardiovascular disease, may partially mediate the association between cystatin C and cardiovascular risk in older adults. PMID:19357259

  14. 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

  15. Immunity in arterial hypertension: associations or causalities?

    PubMed

    Anders, Hans-Joachim; Baumann, Marcus; Tripepi, Giovanni; Mallamaci, Francesca

    2015-12-01

    Numerous studies describe associations between markers of inflammation and arterial hypertension (aHT), but does that imply causality? Interventional studies that reduce blood pressure reduced also markers of inflammation, but does immunosuppression improve hypertension? Here, we review the available mechanistic data. Aberrant immunity can trigger endothelial dysfunction but is hardly ever the primary cause of aHT. Innate and adaptive immunity get involved once hypertension has caused vascular wall injury as immunity is a modifier of endothelial dysfunction and vascular wall remodelling. As vascular remodelling progresses, immunity-related mechanisms can become significant cofactors for cardiovascular (CV) disease progression; vice versa, suppressing immunity can improve hypertension and CV outcomes. Innate and adaptive immunity both contribute to vascular wall remodelling. Innate immunity is driven by danger signals that activate Toll-like receptors and other pattern-recognition receptors. Adaptive immunity is based on loss of tolerance against vascular autoantigens and includes autoreactive T-cell immunity as well as non-HLA angiotensin II type 1 receptor-activating autoantibodies. Such processes involve numerous other modulators such as regulatory T cells. Together, immunity is not causal for hypertension but rather an important secondary pathomechanism and a potential therapeutic target in hypertension.

  16. An Update on Pulmonary Arterial Hypertension

    PubMed Central

    Wapner, Joanna; Matura, Lea Ann

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. PAH is defined as a mean pulmonary arterial pressure ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg at rest. The diagnosis of PAH is one of exclusion; diagnostics include an extensive history, serology, chest radiograph, pulmonary function tests, ventilation/perfusion scan, transthoracic echocardiogram, and right heart catheterization. Treatment and care of patients with PAH can be complex. Therefore, the nurse practitioner is an integral member of the healthcare team caring for PAH patients, helping to ensure seamless care and support. PMID:25954140

  17. Hypertension and renal artery stenosis: a complex clinical scenario.

    PubMed

    Jaff, M R

    2000-10-01

    Hypertension remains the most common reason for patients to visit physicians in the United States. Although awareness of hypertension among patients continues to increase, adequate control of hypertension remains poor. In addition, as the population of patients with hypertension ages, atherosclerosis becomes increasingly prevalent. Atherosclerotic renal artery stenosis is the most common secondary cause of hypertension and can cause hypertension to be difficult to control. Atherosclerotic renal artery stenosis may also result in chronic renal insufficiency. The physician must be aware of the clinical scenarios in which renal artery stenosis may occur, methods of diagnosis, and indications for intervention.

  18. Management of pulmonary arterial hypertension.

    PubMed

    McLaughlin, Vallerie V; Shah, Sanjiv J; Souza, Rogerio; Humbert, Marc

    2015-05-12

    Pulmonary hypertension (PH) is common and may result from a number of disorders, including left heart disease, lung disease, and chronic thromboembolic disease. Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure. Over the past decades, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options has exploded. A thorough evaluation of a patient is critical to correctly characterize the PH. Cardiac studies, including echocardiography and right heart catheterization, are key elements in the assessment. Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management. This review also underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach.

  19. Pulmonary arterial hypertension: a clot in question.

    PubMed

    Patel, Bhavin; Pakala, Aneesh; Aronson, Willard; Magharyous, Hany; Brown, Brent

    2014-07-01

    Pulmonary arterial hypertension (PAH) is a group of disorders characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure and premature death. We present an unusual case of PAH diagnosed initially as Idiopathic PAH (IPAH) after secondary causes were excluded which was successfully managed for a number of years with vasodilators and anticoagulation. Over the months after stopping anticoagulation (because of recurring small bowel hemorrhaging) patient developed progressive findings of right heart failure, which failed to respond to escalating doses of prostacyclin. The patient died and an autopsy revealed the surprising finding of extensive organized central pulmonary artery thrombi as is seen in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We discuss the question of whether these thrombi are generally embolic or develop in situ and recommend that clinicians have a high index of suspicion for central thrombi in patients with IPAH were anticoagulation is contraindicated. PMID:25223151

  20. [Pathogenesis and epidemiology of arterial hypertension].

    PubMed

    Pardell, H; Armario, P; Hernández, R

    1998-01-01

    The pathogenesis of arterial hypertension is more clearly understood today because of the availability of data enabling identification of a certain number of precipitating factors. From a genetic standpoint, hypertension would appear to be a multifactorial polygenic disorder with a tendency to interact with certain environmental factors. The latter are mainly related to lifestyle and are potentially modifiable. Obesity during childhood and adolescence is the main predictive factor for hypertension. It has been suggested that the underlying mechanism could well be hyperinsulinaemia, which induces hyperactivity of the sympathetic nervous system. The mechanisms of the relationship between hypertension and alcohol are still unclear. However, in many countries, excessive alcohol consumption has been reported to be a significant factor in the development of arterial hypertension. The negative effect of a sedentary lifestyle on blood pressure has been widely demonstrated. In addition, it has also been shown that regular physical exercise under aerobic conditions leads to a reduction in blood pressure levels. An excessive sodium intake is also responsible for inducing arterial hypertension through increases in cardiac output and effects on vascular reactivity and contractility. Similarly, restricting sodium intake leads to a reduction in blood pressure levels. Smoking--namely, certain components of tobacco smoke--would appear to have both short and long term effects on blood pressure. These contributing factors all have specific effects on cardiac output and peripheral resistance in individuals. At the community level, the impact of hypertension is particularly significant. Prevalence is strongly influenced by the type of population studied, although it is generally estimated that this disease affects between 10 and 20% of the adult population and is responsible for 5.8% of all deaths worldwide. The direct and indirect costs of the disease are particularly high and are

  1. Vitamin D, arterial hypertension & cerebrovascular disease.

    PubMed

    Kienreich, Katharina; Grubler, Martin; Tomaschitz, Andreas; Schmid, Johannes; Verheyen, Nicolas; Rutters, Femke; Dekker, Jacqueline M; Pilz, Stefan

    2013-04-01

    Vitamin D is mainly derived from endogenous ultraviolet-B induced vitamin D synthesis in the skin, and the current high prevalence of vitamin D deficiency can, therefore, largely be attributed to lifestyle related low sunlight exposure. Regulation of bone and mineral metabolism is a classic vitamin D effect, but the identification of the vitamin D receptor (VDR) in almost all human cells suggests a role for vitamin D also in extra-skeletal diseases. Experimental studies demonstrated several antihypertensive and vascular protective effects of vitamin D, such as suppression of the renin angiotensin aldosterone system, beneficial modulation of classic cardiovascular risk factors, and anti-atherosclerotic properties including improvements of endothelial function. Additional neuroprotective actions of vitamin D have also been reported. In line with this, epidemiological studies have largely shown that vitamin D deficiency is an independent risk factor for arterial hypertension and strokes. Data from randomized controlled trials (RCTs) are, however, limited and less promising, with currently no confirmation that vitamin D reduces stroke incidence. Whereas some RCTs suggest that vitamin D supplementation might modestly reduce blood pressure, this has not been consistently observed in all studies. It is, therefore, premature to recommend vitamin D supplementation for the prevention and treatment of arterial hypertension and stroke. Nevertheless, the fact that patients with arterial hypertension and cerebrovascular disease are at a relatively high risk of vitamin D deficiency, and therewith associated musculoskeletal diseases can serve as a rationale for the evaluation, prevention and treatment of vitamin D deficiency in these patients.

  2. 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. PMID:25623500

  3. The physiological impact of the nonlinearity of arterial elasticity in the ambulatory arterial stiffness index.

    PubMed

    Craiem, Damian; Graf, Sebastian; Salvucci, Fernando; Chironi, Gilles; Megnien, Jean-Louis; Simon, Alain; Armentano, Ricardo L

    2010-07-01

    The ambulatory arterial stiffness index (AASI) is claimed to be a new estimator for arterial rigidity. It was recently defined as one minus the slope of the linear regression of systolic to diastolic ambulatory pressure during 24 h. Although several reports testify its clinical relevance, the explanation of how this new index is conceptually associated with arterial stiffness remains controversial. In this work we hypothesize that nonlinear arterial elasticity is behind AASI physiological principles. To that end, random number generators were used to emulate arterial cross-sectional area (CSA) during 24 h. Pressure values were calculated using linear and nonlinear elasticity models for rigid and compliant arteries. The AASI was calculated from simulated pressures and also analytically predicted for each model. Additionally, invasive aortic pressure and CSA were continuously measured in a conscious sheep during 24 h to test the nonlinear model. We found that analytical solutions agreed with simulation outcomes; for the nonlinear model, the AASI was higher in rigid arteries with respect to compliant arteries (0.51 versus 0.38) and the linear model systematically predicted AASI = 0. For in vivo pressure measurements, AASI was 0.31. Using the measured pulsatile CSA and an estimation of the elastic constant for the nonlinear model, the AASI was accurately predicted with errors below 5%. We conclude that the AASI is higher in stiffer arteries due to the nonlinear behavior of the arterial wall. With a nonlinear arterial function, the slope of the linear regression of diastolic to systolic pressures during 24 h depends on the product of an elastic constant by the pulsatile CSA. As the elastic constant dominates the product, the reported associations between the AASI and arterial stiffness indices now have a consistent explanation.

  4. Update on pulmonary arterial hypertension pharmacotherapy.

    PubMed

    Velayati, Arash; Valerio, Marcos G; Shen, Michael; Tariq, Sohaib; Lanier, Gregg M; Aronow, Wilbert S

    2016-06-01

    Pulmonary artery hypertension (PAH) refers to several subgroups of disease in which the mean pulmonary artery pressure (mPAP) is elevated to more than 25 mm Hg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR) > 3 Wood units as confirmed by right heart catheterization. The prevalence and geographic distribution of PAH vary depending on the type and etiology of the disease. Despite enormous efforts in the research and development of therapeutic agents in the last twenty years, the disease remains relatively incurable and the overall prognosis remains guarded. Median survival for an untreated patient is 2.8 years. In the last three decades, there have been dramatic advances in understanding the molecular mechanisms and signaling pathways involved in the disease, resulting in emerging new treatment strategies. In the following pages, we will review currently approved treatments for PAH, as well as a new generation of investigational drugs. PMID:27232660

  5. Targeted therapies in pulmonary arterial hypertension.

    PubMed

    Montani, David; Chaumais, Marie-Camille; Guignabert, Christophe; Günther, Sven; Girerd, Barbara; Jaïs, Xavier; Algalarrondo, Vincent; Price, Laura C; Savale, Laurent; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc

    2014-02-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies. PMID:24134901

  6. 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. PMID:26761621

  7. [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.

  8. Increased arterial wall stiffness and thickness in medium-sized arteries in patients with insulin-dependent diabetes mellitus.

    PubMed

    Christensen, T; Neubauer, B

    1988-01-01

    By means of ultrasonography, arterial wall stiffness, arterial wall thickness, and the elastic modulus of the common femoral artery were estimated in a group of 19 young insulin-dependent diabetics. The ultrasound technique for determination of these parameters is described as well as the echo-anatomy of the arterial wall. In accordance with a previous investigation a significant rise in arterial wall stiffness was found. Furthermore, there was a highly significant correlation between the stiffness and the thickness of the arterial wall. The elastic modulus also correlated to the stiffness. It is concluded that the diabetic macroangiopathy is characterized by an increased stiffness of the arterial wall caused by increased thickness as well as by progressive alterations of the elastic characteristics of the wall tissue. Possible pathogenetic reasons are discussed.

  9. 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

  10. 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

  11. [Serotonin hypothesis and pulmonary artery hypertension].

    PubMed

    Kloza, Monika; Baranowska-Kuczko, Marta; Pędzińska-Betiuk, Anna; Jackowski, Konrad; Kozłowska, Hanna

    2014-06-06

    Pulmonary arterial hypertension (PAH) is a progressive, complex disease leading to the right ventricular failure and premature death. PAH is characterized by increased pulmonary arterial pressure, increased vascular resistance, pulmonary vascular remodeling and endothelial dysfunction. Pathomechanism of this disease is still unknown. It has been suggested, that endothelial dysfunction is caused by unbalance between vasodilators and vasoconstrictors e.g. serotonin (5-HT). Previously, serotonin hypothesis was linked to the anorexigens, derivatives of fenfluramine, which are serotonin transporter (SERT) substrates. Nowadays, it has been proved that all elements of serotonergic system within pulmonary circulation participate in the developement of PAH. The tryptophan hydroxylase 1 (Tph-1) catalyses synthesis of 5-HT from tryptophan in the pulmonary arterial endothelial cells. 5-HT mediates contraction of pulmonary vessels via 5-HT1B and 5-HT2A receptors. 5-HT is also transported into pulmonary arterial smooth muscle cells via SERT and through activation of reactive oxygen species and Rho-kinase may contribute to contraction or/and, via stimulation of transcription factors, lead to proliferation and remodelling. There is also increasing number of evidence about functional interaction between 5-HT1B receptor and SERT in modulation of vasoconstriction and proliferation in pulmonary arteries. This review discusses the role of 5-HT in the development of PAH and highlights possible therapeutic targets within serotonergic system.

  12. Novel biomarkers for pulmonary arterial hypertension.

    PubMed

    Anwar, Anjum; Ruffenach, Gregoire; Mahajan, Aman; Eghbali, Mansoureh; Umar, Soban

    2016-01-01

    Pulmonary arterial hypertension is a deadly disease characterized by elevated pulmonary arterial pressures leading to right ventricular hypertrophy and failure. The confirmatory gold standard test is the invasive right heart catheterization. The disease course is monitored by pulmonary artery systolic pressure measurement via transthoracic echocardiography. A simple non-invasive test to frequently monitor the patients is much needed. Search for a novel biomarker that can be detected by a simple test is ongoing and many different options are being studied. Here we review some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. These biomarkers can be broadly categorized based on their association with endothelial cell dysfunction, inflammation, epigenetics, cardiac function, oxidative stress, metabolism,extracellular matrix, and volatile compounds in exhaled breath condensate. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes. PMID:27439993

  13. Exercise physiology and pulmonary arterial hypertension.

    PubMed

    Waxman, Aaron B

    2012-01-01

    The lungs are the only organ that receives the entire cardiac output with every stroke. The pulmonary circulation is normally a high-flow, low-resistance, low-pressure system that carries blood into the pulmonary microcirculation. In pulmonary artery hypertension (PAH)vascular remodeling contributes to a sustained elevation of pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) as a result of vascular remodeling characterized largely by vascular smooth muscle cell proliferation and medial hypertrophy, and endothelial cell proliferation resulting in lumen obliteration. The loss of pulmonary arterial compliance and development of elevated PVR puts an excessive burden on the right ventricle due to the increased workload necessary to overcome the downstream pressure, ultimately leading to right-sided heart failure. The functional status of the pulmonary circulation and the levels of PVR and PAP ultimately determine the outcome of patients with PAH. Study of the pressure-flow relationships in the pulmonary vascular bed will provide an improved appreciation of the pathophysiology of pulmonary hypertension.

  14. [Perinantal programming of arterial hypertension in child].

    PubMed

    Kovtun, O P; Tsyv'ian, P B

    2013-01-01

    There is a growing number of evidence linking fetal intrauterine malnutrition, other adverse events or exposures and arterial hypertension during the following life. After important epidemiological studiesfrom many countries, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements ofadverse perinatal conditions and normal development. This review focused on advances in comprehension of the influence of intrauterine malnutrition on developmental programming of hypertension. Significant decrease in nephrons number was demonstrated as a result of fetal asymmetrical growth restriction syndrome both in human and experimental animal model. The role of malnutrition and dexametasone induced rennin-angiotensin system inhibition in fetal and newborn nephrogenesis is discussed. Recent studies have revealed important mechanisms of altered vascular function and structure as well as sympathetic regulation of the cardiovascular system in perinatal hypertension models. Some of adverse effects on nephrogenesis and blood pressure regulation could be reversed by special diet and treatment during first two years of life. While the complexity of the interactions between antenatal and postnatal influences on blood pressure is increasingly recognized, the importance of early postnatal life in modulating developmental programming offers the hope of a critical 1000 days window of opportunity to reverse programming and prevent or reduce child hypertension.

  15. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

    PubMed

    Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

    2015-02-01

    Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.

  16. [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. PMID:21536178

  17. Hydration Status Is Associated with Aortic Stiffness, but Not with Peripheral Arterial Stiffness, in Chronically Hemodialysed Patients

    PubMed Central

    Bia, Daniel; Galli, Cintia; Valtuille, Rodolfo; Zócalo, Yanina; Wray, Sandra A.; Armentano, Ricardo L.; Cabrera Fischer, Edmundo I.

    2015-01-01

    Background. Adequate fluid management could be essential to minimize high arterial stiffness observed in chronically hemodialyzed patients (CHP). Aim. To determine the association between body fluid status and central and peripheral arterial stiffness levels. Methods. Arterial stiffness was assessed in 65 CHP by measuring the pulse wave velocity (PWV) in a central arterial pathway (carotid-femoral) and in a peripheral pathway (carotid-brachial). A blood pressure-independent regional arterial stiffness index was calculated using PWV. Volume status was assessed by whole-body multiple-frequency bioimpedance. Patients were first observed as an entire group and then divided into three different fluid status-related groups: normal, overhydration, and dehydration groups. Results. Only carotid-femoral stiffness was positively associated (P < 0.05) with the hydration status evaluated through extracellular/intracellular fluid, extracellular/Total Body Fluid, and absolute and relative overhydration. Conclusion. Volume status and overload are associated with central, but not peripheral, arterial stiffness levels with independence of the blood pressure level, in CHP. PMID:26167301

  18. Preeclampsia Is Associated with Increased Central Aortic Pressure, Elastic Arteries Stiffness and Wave Reflections, and Resting and Recruitable Endothelial Dysfunction

    PubMed Central

    Torrado, Juan; Farro, Ignacio; Zócalo, Yanina; Farro, Federico; Sosa, Claudio; Scasso, Santiago; Alonso, Justo; Bia, Daniel

    2015-01-01

    Introduction. An altered endothelial function (EF) could be associated with preeclampsia (PE). However, more specific and complementary analyses are required to confirm this topic. Flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and hyperemic-related changes in carotid-radial pulse wave velocity (PWVcr) offer complementary information about “recruitability” of EF. Objectives. To evaluate, in healthy and hypertensive pregnant women (with and without PE), central arterial parameters in conjunction with “basal and recruitable” EF. Methods. Nonhypertensive (HP) and hypertensive pregnant women (gestational hypertension, GH; preeclampsia, PE) were included. Aortic blood pressure (BP), wave reflection parameters (AIx@75), aortic pulse wave velocity (PWVcf) and PWVcr, and brachial and common carotid stiffness and intima-media thickness were measured. Brachial FMD and L-FMC and hyperemic-related change in PWVcr were measured. Results. Aortic BP and AIx@75 were elevated in PE. PE showed stiffer elastic but not muscular arteries. After cuff deflation, PWVcr decreased in HP, while GH showed a blunted PWVcr response and PE showed a tendency to increase. Maximal FMD and L-FMC were observed in HP followed by GH; PE did not reach significant arterial constriction. Conclusion. Aortic BP and wave reflections as well as elastic arteries stiffness are increased in PE. PE showed both “resting and recruitable” endothelial dysfunctions. PMID:26351578

  19. Preeclampsia Is Associated with Increased Central Aortic Pressure, Elastic Arteries Stiffness and Wave Reflections, and Resting and Recruitable Endothelial Dysfunction.

    PubMed

    Torrado, Juan; Farro, Ignacio; Zócalo, Yanina; Farro, Federico; Sosa, Claudio; Scasso, Santiago; Alonso, Justo; Bia, Daniel

    2015-01-01

    Introduction. An altered endothelial function (EF) could be associated with preeclampsia (PE). However, more specific and complementary analyses are required to confirm this topic. Flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and hyperemic-related changes in carotid-radial pulse wave velocity (PWVcr) offer complementary information about "recruitability" of EF. Objectives. To evaluate, in healthy and hypertensive pregnant women (with and without PE), central arterial parameters in conjunction with "basal and recruitable" EF. Methods. Nonhypertensive (HP) and hypertensive pregnant women (gestational hypertension, GH; preeclampsia, PE) were included. Aortic blood pressure (BP), wave reflection parameters (AIx@75), aortic pulse wave velocity (PWVcf) and PWVcr, and brachial and common carotid stiffness and intima-media thickness were measured. Brachial FMD and L-FMC and hyperemic-related change in PWVcr were measured. Results. Aortic BP and AIx@75 were elevated in PE. PE showed stiffer elastic but not muscular arteries. After cuff deflation, PWVcr decreased in HP, while GH showed a blunted PWVcr response and PE showed a tendency to increase. Maximal FMD and L-FMC were observed in HP followed by GH; PE did not reach significant arterial constriction. Conclusion. Aortic BP and wave reflections as well as elastic arteries stiffness are increased in PE. PE showed both "resting and recruitable" endothelial dysfunctions.

  20. 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.

  1. 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. PMID:26341985

  2. Linking systemic arterial stiffness among adolescents to adverse childhood experiences.

    PubMed

    Klassen, Stephen A; Chirico, Daniele; O'Leary, Deborah D; Cairney, John; Wade, Terrance J

    2016-06-01

    Adverse childhood experiences (ACEs) have been linked with cardiovascular disease and early mortality among adults. Most research examines this relationship retrospectively. Examining the association between ACEs and children's cardiovascular health is required to understand the time course of this association. We examined the relationship between ACEs exposure and ECG-to-toe pulse wave velocity (PWV), a measure of systemic arterial stiffness that is strongly related to cardiovascular mortality among adults. PWV (distance/transit time; m/s) was calculated using transit times from the ECG R-wave to the pulse wave contour at the toe. Transit times were collected over 15 heartbeats and the distance from the sternal notch to the left middle toe was used. A total of 221 children (119 females) aged 10-14 years participated in data collection of PWV, hemodynamic and anthropometric variables. Parents of these children completed a modified inventory of ACEs taken from the Childhood Trust Events Survey. Multivariable regression assessed the relationship between ACEs group (<4 ACEs versus ≥4 ACEs) and PWV. Analyses yielded an ACEs group by sex interaction, with males who experienced four or more ACEs having higher PWV (p<0.01). This association was independent of hemodynamic, anthropometric and sociodemographic variables (R(2)=0.346; p<0.01). Four or more ACEs is associated with greater arterial stiffness in male children aged 10-14 years. Addressing stress and trauma exposure in childhood is an important target for public health interventions to reduce early cardiovascular risk. PMID:27107504

  3. 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

  4. Arterial hypertension in liver transplant recipients.

    PubMed

    Hryniewiecka, E; Zegarska, J; Paczek, L

    2011-10-01

    Hypertension is an important cardiovascular risk factor that influences patient survival. This study sought to evaluate hypertension incidence and circadian rhythms of blood pressure (BP) among liver transplant recipients during the first posttransplant month. We also compared hypertension incidence according to clinical and automated blood pressure monitoring methods. BP was determined by clinical blood pressure monitoring (CBPM) methods and by automated blood pressure monitoring (ABPM) using the SpaceLabs device. We also assessed blood biochemistry, particularly kidney function parameters and immunosuppressive drug blood trough levels, among 32 white subjects (10 women and 22 men) of average age 47.58±14.19 years. The leading cause for transplantation was liver insufficiency due to viral hepatitis B and/or C infection (43.75%). The majority (93.75%) of patients was prescribed immunosuppressive treatment with tacrolimus. Although we observed hypertension in 28 patients (87.5%) by ABPM measurements and in 25 (78.12%) using CBPM method, the difference did not reach statistical significance. However, BP control was inadequate in 28 patients (87.5%) by ABPM assessment versus 3 (9.38%) according to CBPM readings (P=.025). The BP circadian rhythm was altered in 30 patients (93.75%) including 15 with higher nighttime BP readings. There was no correlation between tacrolimus blood levels and BP values or with kidney function as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We concluded that prevalence of arterial hypertension among liver transplant recipients within 1 month after transplantation is high. The majority of the patients show disturbed circadian rhythms in the early period after liver transplantation with loss or even reversal of the normal nocturnal decrease in BP. Owing to the fact that ABPM enables more adequate daily assessment of BP values, it is an optimal method to adjust antihypertensive therapy to optimal levels

  5. Can arterial stiffness parameters be measured in the sitting position?

    PubMed

    Nürnberger, Jens; Michalski, Rene; Türk, Tobias R; Opazo Saez, Anabelle; Witzke, Oliver; Kribben, Andreas

    2011-02-01

    Despite the introduction of arterial stiffness measurements in the European recommendation, pulse wave velocity (PWV) and augmentation index (AI) are still not used routinely in clinical practice. It would be of advantage if such measurements were done in the sitting position as is done for blood pressure. The aim of this study was to evaluate whether there is a difference in stiffness parameters in sitting vs. supine position. Arterial stiffness was measured in 24 healthy volunteers and 20 patients with cardiovascular disease using three different devices: SphygmoCor (Atcor Medical, Sydney, Australia), Arteriograph (TensioMed, Budapest, Hungary) and Vascular Explorer (Enverdis, Jena, Germany). Three measurements were performed in supine position followed by three measurements in sitting position. Methods were compared using correlation and Bland-Altman analysis. There was a significant correlation between PWV in supine and sitting position (Arteriograph: P<0.0001, r=0.93; Vascular Explorer; P<0.0001, r=0.87). There were significant correlations between AI sitting and AI supine using Arteriograph (P<0.0001, r=0.97), Vascular Explorer (P<0.0001, r=0.98) and SphygmoCor (P<0.0001, r=0.96). When analyzed by Bland-Altman, PWV and AI measurements in supine vs. sitting showed good agreement. There was no significant difference in PWV obtained with the three different devices (Arteriograph 7.5±1.6 m s(-1), Vascular Explorer 7.3±0.9 m s(-1), SphygmoCor 7.0±1.8 m s(-1)). AI was significantly higher using the Arteriograph (17.6±15.0%) than Vascular Explorer and SphygmoCor (10.2±15.1% and 10.3±18.1%, respectively). The close agreement between sitting and supine measurements suggests that both PWV and AI can be reliably measured in the sitting position.

  6. [Patterns, predictors, and personalization in pulmonary arterial hypertension].

    PubMed

    Kawut, Steven M

    2014-06-01

    Epidemiologic patterns of pulmonary arterial hypertension differ by era and region and may shed light on the pathophysiology and treatment of the disease. New efforts to target one or more of the recently studied therapies could establish personalized medicine as standard care in pulmonary arterial hypertension. PMID:25164214

  7. [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.

  8. 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

  9. Arterial stiffness & Sri Lankan chronic kidney disease of unknown origin

    PubMed Central

    Gifford, Fiona; Kimmitt, Robert; Herath, Chula; Webb, David J; Melville, Vanessa; Siribaddana, Sisira; Eddleston, Michael; Dhaun, Neeraj

    2016-01-01

    Chronic kidney disease (CKD) is common and independently associated with cardiovascular disease (CVD). Arterial stiffness contributes to CVD risk in CKD. In many developing countries a considerable proportion of CKD remains unexplained, termed CKDu. We assessed arterial stiffness in subjects with Sri Lankan CKDu, in matched controls without CKD and in those with defined CKD. Aortic blood pressure (BP), pulse wave velocity (PWV) and augmentation index (AIx) were assessed in 130 subjects (50 with CKDu, 45 with CKD and 35 without CKD) using the validated TensioMed™ Arteriograph monitor. Brachial and aortic BP was lower in controls than in CKDu and CKD subjects but no different between CKDu and CKD. Controls had a lower PWV compared to subjects with CKDu and CKD. Despite equivalent BP and renal dysfunction, CKDu subjects had a lower PWV than those with CKD (8.7 ± 1.5 vs. 9.9 ± 2.2 m/s, p < 0.01). Excluding diabetes accentuated the differences in PWV seen between groups (controls vs. CKDu vs. CKD: 6.7 ± 0.9 vs. 8.7 ± 1.5 vs. 10.4 ± 1.5 m/s, p < 0.001 for all). Sri Lankan CKDu is associated with less arterial stiffening than defined causes of CKD. Whether this translates to lower cardiovascular morbidity and mortality long term is unclear and should be the focus of future studies. PMID:27586642

  10. Arterial stiffness & Sri Lankan chronic kidney disease of unknown origin

    NASA Astrophysics Data System (ADS)

    Gifford, Fiona; Kimmitt, Robert; Herath, Chula; Webb, David J.; Melville, Vanessa; Siribaddana, Sisira; Eddleston, Michael; Dhaun, Neeraj

    2016-09-01

    Chronic kidney disease (CKD) is common and independently associated with cardiovascular disease (CVD). Arterial stiffness contributes to CVD risk in CKD. In many developing countries a considerable proportion of CKD remains unexplained, termed CKDu. We assessed arterial stiffness in subjects with Sri Lankan CKDu, in matched controls without CKD and in those with defined CKD. Aortic blood pressure (BP), pulse wave velocity (PWV) and augmentation index (AIx) were assessed in 130 subjects (50 with CKDu, 45 with CKD and 35 without CKD) using the validated TensioMed™ Arteriograph monitor. Brachial and aortic BP was lower in controls than in CKDu and CKD subjects but no different between CKDu and CKD. Controls had a lower PWV compared to subjects with CKDu and CKD. Despite equivalent BP and renal dysfunction, CKDu subjects had a lower PWV than those with CKD (8.7 ± 1.5 vs. 9.9 ± 2.2 m/s, p < 0.01). Excluding diabetes accentuated the differences in PWV seen between groups (controls vs. CKDu vs. CKD: 6.7 ± 0.9 vs. 8.7 ± 1.5 vs. 10.4 ± 1.5 m/s, p < 0.001 for all). Sri Lankan CKDu is associated with less arterial stiffening than defined causes of CKD. Whether this translates to lower cardiovascular morbidity and mortality long term is unclear and should be the focus of future studies.

  11. Arterial stiffness &Sri Lankan chronic kidney disease of unknown origin.

    PubMed

    Gifford, Fiona; Kimmitt, Robert; Herath, Chula; Webb, David J; Melville, Vanessa; Siribaddana, Sisira; Eddleston, Michael; Dhaun, Neeraj

    2016-01-01

    Chronic kidney disease (CKD) is common and independently associated with cardiovascular disease (CVD). Arterial stiffness contributes to CVD risk in CKD. In many developing countries a considerable proportion of CKD remains unexplained, termed CKDu. We assessed arterial stiffness in subjects with Sri Lankan CKDu, in matched controls without CKD and in those with defined CKD. Aortic blood pressure (BP), pulse wave velocity (PWV) and augmentation index (AIx) were assessed in 130 subjects (50 with CKDu, 45 with CKD and 35 without CKD) using the validated TensioMed™ Arteriograph monitor. Brachial and aortic BP was lower in controls than in CKDu and CKD subjects but no different between CKDu and CKD. Controls had a lower PWV compared to subjects with CKDu and CKD. Despite equivalent BP and renal dysfunction, CKDu subjects had a lower PWV than those with CKD (8.7 ± 1.5 vs. 9.9 ± 2.2 m/s, p < 0.01). Excluding diabetes accentuated the differences in PWV seen between groups (controls vs. CKDu vs. CKD: 6.7 ± 0.9 vs. 8.7 ± 1.5 vs. 10.4 ± 1.5 m/s, p < 0.001 for all). Sri Lankan CKDu is associated with less arterial stiffening than defined causes of CKD. Whether this translates to lower cardiovascular morbidity and mortality long term is unclear and should be the focus of future studies. PMID:27586642

  12. The structural factor of hypertension: large and small artery alterations.

    PubMed

    Laurent, Stéphane; Boutouyrie, Pierre

    2015-03-13

    Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.

  13. 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.

  14. 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. PMID:27590754

  15. Renin and aldosterone measurements in the management of arterial hypertension.

    PubMed

    Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

    2015-06-01

    Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy.

  16. Role of Elastin in Spontaneously Hypertensive Rat Small Mesenteric Artery Remodelling

    PubMed Central

    Briones, Ana M; González, José M; Somoza, Beatriz; Giraldo, Jesús; Daly, Craig J; Vila, Elisabet; Carmen González, M; McGrath, John C; Arribas, Silvia M

    2003-01-01

    Chronic hypertension is associated with resistance artery remodelling and mechanical alterations. However, the contribution of elastin has not been thoroughly studied. Our objective was to evaluate the role of elastin in vascular remodelling of mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR). MRA segments from Wistar Kyoto rats (WKY) and SHR were pressurised under passive conditions at a range of physiological pressures with pressure myography. Confocal microscopy was used to determine differences in the quantity and organisation of elastin in intact pressure-fixed arteries. To assess the contribution of elastin to MRA structure and mechanics, myograph-mounted vessels were studied before and after elastase incubation. When compared with WKY, MRA from SHR showed: (1) a smaller lumen, (2) decreased distensibility at low pressures, (3) a leftward shift of the stress-strain relationship, (4) redistribution of elastin within the internal elastic lamina (IEL) leading to smaller fenestrae but no change in fenestrae number or elastin amount. Elastase incubation (1) fragmented the structure of IEL in a concentration-dependent fashion, (2) abolished all the structural and mechanical differences between strains, and (3) decreased distensibility at low pressures. The study shows the overriding role of elastin in determining vascular dimensions and mechanical properties in a resistance artery. In addition, it informs hypertensive remodelling. MRA remodelling and increased stiffness are accompanied by elastin restructuring within the IEL and elastin degradation reverses structural and mechanical alterations of SHR MRA. Differences in elastin organisation are, therefore, a central element in small artery remodelling in hypertension. PMID:12844513

  17. The evolving definition of systemic arterial hypertension.

    PubMed

    Ram, C Venkata S; Giles, Thomas D

    2010-05-01

    Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

  18. Pulmonary arterial hypertension: a review in pharmacotherapy.

    PubMed

    Patel, Bhaumik B; Feng, Ying; Cheng-Lai, Angela

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that remains incurable. The past 2 decades have witnessed many advances in PAH-directed therapies. More recently, 3 new oral agents have become available in the United States within the past 2 years. Treprostinil is now available in extended-release oral tablets. Macitentan is the third endothelin receptor antagonist approved for use, demonstrating benefits on morbidity and mortality among patients with PAH in an event-driven study. Riociguat is the first soluble guanylate cyclase stimulator that has been approved for use in the United States. This article reviews the clinical efficacy and safety of these 3 agents and the roles they play in the management of PAH. Additionally, we review the limitations of using surrogate markers such as change in 6-minute walk distance to assess disease progression.

  19. [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. PMID:23859515

  20. 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.

  1. A Contemporary Approach to Pulmonary Arterial Hypertension.

    PubMed

    Krishnan, Udhay; Horn, Evelyn M

    2016-09-01

    In recent years, there have been major changes in the landscape of pulmonary arterial hypertension therapy with the introduction of novel agents and innovative treatment strategies for this progressive disease. The aim of this review is to discuss the evolution in trial design in this field and highlight the salient features of recently published studies. We also summarize our approach to therapy selection in this chronic disease and identify areas for future exploration. The therapeutic armamentarium now includes 13 approved therapies. While most of these agents have been studied in small, short-term trials using the 6-min walk distance as a primary endpoint, there has been a shift in recent years toward larger, long-term, event-driven trials that utilize combined morbidity and mortality endpoints. The SERAPHIN and GRIPHON trials were two such studies, which led to the approval of the dual endothelin-receptor antagonist macitentan and the selective prostacyclin receptor antagonist selexipag, respectively. Other event-driven trials, like AMBITION and COMPASS-2, have provided valuable insight into the use of combined oral therapies in symptomatic patients. In conclusion, despite being a more manageable disease in the modern treatment era, pulmonary hypertension is still associated with considerable morbidity and much more work remains to be done in this field. Important questions remain about the most optimal way to manage patients and conduct trials going forward. PMID:27491673

  2. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  3. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Primary pulmonary hypertension 2 Primary pulmonary hypertension 3 Primary pulmonary hypertension 4 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (4 links) ...

  4. 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. PMID:24582963

  5. Atherosclerotic Renal Artery Stenosis and Hypertension: Pragmatism, Pitfalls, and Perspectives.

    PubMed

    Bavishi, Chirag; de Leeuw, Peter W; Messerli, Franz H

    2016-06-01

    For many years and even decades, a diagnostic work-up to look for a secondary form of hypertension, particularly of renovascular origin, has been a central tenet in medicine. Atherosclerotic renal artery stenosis is considered the most common cause of renovascular hypertension. However, advances in understanding the complex pathophysiology of this condition and the recently documented futility of renal revascularization bring into question whether atherosclerotic renal artery stenosis truly causes "renovascular hypertension." From a clinical point of view, a clear distinction should be made between hypertension associated with atherosclerotic renal artery stenosis and hypertension caused by renal artery stenosis-induced activation of the renin-angiotensin-aldosterone system. Most patients with atherosclerotic renal artery stenosis do not have a form of hypertension that is remediable or improved by angioplasty; to expose them to the cost, inconvenience, and risk of a diagnostic work-up add up to little more than a wild goose chase. However, with very few exceptions, medical therapy with antihypertensives and statins remains the cornerstone for the management of patients with atherosclerotic renal artery stenosis and hypertension.

  6. 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

  7. Arterial stiffness is higher in older adults with increased perceived fatigue and fatigability during walking.

    PubMed

    Gonzales, Joaquin U; Wiberg, Matthew; Defferari, Elizabeth; Proctor, David N

    2015-01-01

    We investigated whether central and/or peripheral arterial stiffness contributes to increased perceived fatigue during walking in mobility-intact older adults. Arterial stiffness of the common carotid artery and superficial femoral artery (SFA) was measured using Doppler-ultrasound in 45 community-dwelling women and men (60-78yrs). The change in perceived fatigue was measured after a fast-pace 400meter walk test. Adults that rated feeling more tired after walking (n=10) had higher SFA stiffness (p<0.01), but not carotid artery stiffness, than adults that reported feeling more energetic after walking (n=22). The change in perceived fatigue rating was normalized to energy expenditure during walking to determine perceived fatigability. Adults were divided into lower and higher perceived fatigability groups (n=22 per group). Carotid artery stiffness was not different between perceived fatigability groups after adjusting for age, sex, body fat, systolic blood pressure, fasting blood glucose, daily physical activity levels, and resting diameter. However, SFA stiffness was significantly elevated in the higher as compared to lower perceived fatigability group (β-index: 20.7±1.3 vs. 15.3±1.4U; p=0.02) after adjusting for the abovementioned variables. Moreover, stepwise regression identified SFA β-index to be an independent predictor of perceived fatigability (r(2)=0.38, p<0.01). These results suggest that peripheral arterial stiffness is independently associated with perceived fatigue and fatigability in older adults. PMID:25482474

  8. [New guidelines 2007 for the management of arterial hypertension].

    PubMed

    Krzesinski, J M; Xhignesse, P

    2007-09-01

    New guidelines for the management of arterial hypertension have just been released by the European Societies of Cardiology and Arterial Hypertension. The global cardiovascular risk is again at the center of this management. The control of high blood pressure goes through an adequate use of antihypertensive agents and the application of healthy lifestyle and diet recommendations. Again, management of all the cardiovascular risk factors is stimulated.

  9. Secondary arterial hypertension: when, who, and how to screen?

    PubMed

    Rimoldi, Stefano F; Scherrer, Urs; Messerli, Franz H

    2014-05-14

    Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs.

  10. Epistatic interactions in idiopathic pulmonary arterial hypertension

    PubMed Central

    Vadapalli, Shivani; Satyanarayana, M. L.; Chaitra, K. L.; Rani, H. Surekh; Sastry, B.K.S.; Nallari, Pratibha

    2012-01-01

    BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR) analysis is a statistical method used to identify gene–gene interaction or epistasis and gene–environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes. AIM: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis. MATERIALS AND METHODS: A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2). MDR method was adopted to determine gene–gene interactions that increase the risk of IPAH. RESULTS: With MDR method, the single-locus model of 5HTT (L/S) polymorphism and the combination of 5HTT(L/S), EDN1(K198N), and NOS3(G894T) polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05. CONCLUSION: MDR method can be useful in understanding the role of epistatic and gene–environmental interactions in pathogenesis of IPAH. PMID:22754222

  11. Breath Analysis in Pulmonary Arterial Hypertension

    PubMed Central

    Cikach, Frank S.; Tonelli, Adriano R.; Barnes, Jarrod; Paschke, Kelly; Newman, Jennie; Grove, David; Dababneh, Luma; Wang, Sihe

    2014-01-01

    Background: Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath. Methods: We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n = 31) and from healthy control subjects (n = 34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts. Results: Patients with PAH were 51.5 ± 14 years old, and 27 were women (85%). Control subjects were 38 ± 13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P < .001) and was associated with right atrial pressure (ρ = 0.57, P < .001), mean pulmonary artery pressure (ρ = 0.43, P = .015), cardiac index by thermodilution (ρ = −0.39, P = .03), pulmonary vascular resistance (ρ = 0.40, P = .04), mixed venous oxygen (ρ = −0.59, P < .001), and right ventricular dilation (ρ = 0.42, P = .03). Conclusions: Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease. PMID:24091389

  12. 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.

  13. Definition, classification, and epidemiology of pulmonary arterial hypertension.

    PubMed

    Hoeper, Marius M

    2009-08-01

    Pulmonary arterial hypertension (PAH) is a distinct subgroup of pulmonary hypertension that comprises idiopathic PAH, familial/heritable forms, and PAH associated with connective tissue disease, congenital heart disease, portal hypertension, human immunodeficiency virus (HIV) infection, and some other conditions. The hemodynamic definition of PAH was recently revised: PAH is now defined by a mean pulmonary artery pressure at rest > or =25 mm Hg in the presence of a pulmonary capillary wedge pressure < or =15 mm Hg. The exercise criterion (mean pulmonary artery pressure > or =30 mm Hg during exercise) that was used in the old definition of PAH has been removed because there are no robust data that would allow defining an upper limit of normal for the pulmonary pressure during exercise. The revised classification of pulmonary hypertension still consists of five major groups: (1) PAH, (2) pulmonary hypertension due to left heart disease, (3) pulmonary hypertension due to chronic lung disease and/or hypoxia, (4) chronic thromboembolic pulmonary hypertension, and (5) miscellaneous forms. Modifications have been made in some of these groups, such as the addition of schistosomiasis-related pulmonary hypertension and pulmonary hypertension in patients with chronic hemolytic anemia to group 1.

  14. [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. PMID:27284843

  15. [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.

  16. CD133+ cells in pulmonary arterial hypertension.

    PubMed

    Foris, Vasile; Kovacs, Gabor; Marsh, Leigh M; Bálint, Zoltán; Tötsch, Martin; Avian, Alexander; Douschan, Philipp; Ghanim, Bahil; Klepetko, Walter; Olschewski, Andrea; Olschewski, Horst

    2016-08-01

    Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent.We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133(+) cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs).PAH patients were characterised by increased numbers of circulating CD133(+) cells and lymphopenia as compared with control. In PAH, CD133(+) subpopulations positive for CD117 or CD45 were significantly increased, whereas CD133(+)CD309(+), CD133(+)CXCR2(+) and CD133(+)CD31(+) cells were decreased. In CD133(+) cells, SOX2, Nanog, Ki67 and CXCR4 were not detected, but Oct3/4 mRNA was present in both PAH and controls. In the lung tissue, CD133(+) cells included three main populations: type 2 pneumocytes, monocytes and undifferentiated cells without significant differences between PAH and controls.In conclusion, circulating CD133(+) progenitor cells are elevated in PAH and consist of phenotypically different subpopulations that may be up- or downregulated. This may explain the inconsistent results in the literature. CD133(+) type 2 pneumocytes in the lung tissue are not associated with circulating CD133(+) mononuclear cells. PMID:27103380

  17. Updated treatment algorithm of pulmonary arterial hypertension.

    PubMed

    Galiè, Nazzareno; Corris, Paul A; Frost, Adaani; Girgis, Reda E; Granton, John; Jing, Zhi Cheng; Klepetko, Walter; McGoon, Michael D; McLaughlin, Vallerie V; Preston, Ioana R; Rubin, Lewis J; Sandoval, Julio; Seeger, Werner; Keogh, Anne

    2013-12-24

    The demands on a pulmonary arterial hypertension (PAH) treatment algorithm are multiple and in some ways conflicting. The treatment algorithm usually includes different types of recommendations with varying degrees of scientific evidence. In addition, the algorithm is required to be comprehensive but not too complex, informative yet simple and straightforward. The type of information in the treatment algorithm are heterogeneous including clinical, hemodynamic, medical, interventional, pharmacological and regulatory recommendations. Stakeholders (or users) including physicians from various specialties and with variable expertise in PAH, nurses, patients and patients' associations, healthcare providers, regulatory agencies and industry are often interested in the PAH treatment algorithm for different reasons. These are the considerable challenges faced when proposing appropriate updates to the current evidence-based treatment algorithm.The current treatment algorithm may be divided into 3 main areas: 1) general measures, supportive therapy, referral strategy, acute vasoreactivity testing and chronic treatment with calcium channel blockers; 2) initial therapy with approved PAH drugs; and 3) clinical response to the initial therapy, combination therapy, balloon atrial septostomy, and lung transplantation. All three sections will be revisited highlighting information newly available in the past 5 years and proposing updates where appropriate. The European Society of Cardiology grades of recommendation and levels of evidence will be adopted to rank the proposed treatments. PMID:24355643

  18. 17β-estradiol attenuates conduit pulmonary artery mechanical property changes with pulmonary arterial hypertension

    PubMed Central

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C.; Boston, Madison; Chesler, Naomi C.

    2015-01-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Since proximal PA stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to RV function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia (SuHx). Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of SMC activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P < 0.05). 17β-estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via RV catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  19. [Arterial hypertension in special situations: mild, systolic and in pregnancy].

    PubMed

    Luque Otero, M; Fernández Pinilla, C

    1990-01-01

    Mild hypertension is very common, 50% of hypertensives being with their diastolic BP between 90 and 104 mmHg. Many large studies, especially HDFP, had shown not only the deleterious cardiovascular effects of mild hypertension but also the benefits obtained with the therapy. The non-pharmacological approach should be the first step in the treatment of mild hypertension. Isolated systolic hypertension have a high prevalence in the elderly, increasing the cardiovascular morbidity and mortality. Sodium restriction and, if necessary, vasodilators increasing the arterial compliance seem to be the logical approach to treat isolated systolic hypertension. Finally, eclampsia is the most serious complication of pregnancy - induced hypertension. The treatment with bed rest and either betablockers or methyldopa is beneficial. If eclampsia occurs hydralazine, magnesium sulphate or nifedipine should be used.

  20. 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.

  1. Therapeutic approaches of uncomplicated arterial hypertension in patients with COPD.

    PubMed

    Di Daniele, Nicola

    2015-12-01

    The concomitant presence of systemic arterial hypertension and chronic obstructive pulmonary disease (COPD) is frequent. Indeed, arterial hypertension is the most common comorbid disease in COPD patients. Since many antihypertensive drugs can act on airway function the treatment of arterial hypertension in COPD patients appears complex. Moreover, in these patients, a combined therapy is required for the adequate control of blood pressure. Currently, available data are inconsistent and not always comparable. Therefore the aim of this review is to analyze how antihypertensive drugs can affect airway function in order to improve the clinical management of hypertensive patients with COPD. Thiazide diuretics and calcium channel blockers appear the first-choice pharmacological treatment for these patients.

  2. Arterial stiffness: a novel cardiovascular risk factor in kidney disease patients.

    PubMed

    Georgianos, Panagiotis I; Sarafidis, Pantelis A; Lasaridis, Anastasios N

    2015-01-01

    Prospective observational studies have shown that arterial stiffness is a strong and independent predictor of cardiovascular disease in hemodialysis patients. Recent evidence further supports that arterial hardening predicts cardiovascular and all-cause mortality in peritoneal dialysis patients, renal transplant recipients and patients with chronic kidney disease (CKD) not on dialysis. Of note, dissociation of arterial stiffness with blood pressure reduction were related to worsened cardiovascular outcome in kidney disease patients, suggesting that arterial stiffness may not only be a predictor, but also a true risk factor, representing a specific and potentially reversible pattern of outward arterial remodeling in these individuals. On this basis, arterial stiffness has emerged as a novel therapeutic target for cardiovascular risk reduction in patients with CKD; specific interventions, such as renin-angiotensin-system blockade, use of statins, and decrease of calcium- phosphate product may delay the progression of arteriosclerotic process. This article summarizes the accumulated evidence from clinical and epidemiological studies regarding the prognostic significance of arterial stiffening on cardiovascular outcomes and provides insights on possible treatment strategies for arterial stiffness attenuation in patients with CKD.

  3. 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

  4. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.

    PubMed

    Rabinovitch, Marlene; Guignabert, Christophe; Humbert, Marc; Nicolls, Mark R

    2014-06-20

    This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. PMID:24951765

  5. Inflammation and Arterial Hypertension: From Pathophysiological Links to Risk Prediction.

    PubMed

    Pietri, Panagiota; Vlachopoulos, Charalambos; Tousoulis, Dimitris

    2015-01-01

    Over the last years, ample data have demonstrated the pivotal role of low-grade inflammation in the pathophysiology of atherosclerosis and cardiovascular disease. It is well established that inflammatory activation, serving either as a substrate, in the chronic phase of atherosclerotic disease, or as a trigger, in the acute phase, increases cardiovascular events. Considering hypertension, the inflammatory process is implicated in its pathophysiology through a bidirectional relationship since arterial hypertension may enhance inflammation and vice versa. Inflammatory biomarkers such as high-sensitivity C-reactive protein, have shown predictive value for both the incidence of hypertension and the clinical outcomes in hypertensive patients. In the present review, data on the association between arterial hypertension and low-grade inflammation will be reported and potential pathophysiological pathways and clinical implications underlying this association will be discussed.

  6. Diet and arterial hypertension: is the sodium ion alone important?

    PubMed

    Buemi, Michele; Senatore, Massimino; Corica, Francesco; Aloisi, Carmela; Romeo, Adolfo; Tramontana, Domenico; Frisina, Nicola

    2002-07-01

    Hypertension is a widespread phenomenon whose ultimate cause is still unknown. Many factors contribute to this disease, and partially for this reason, hypertension responds to different treatments in different individuals. It is difficult to generalize about therapies for general populations. In particular, the role of electrolytes in hypertension varies widely across individuals. This review focuses its attention on sodium, potassium, calcium, and magnesium ions in order to investigate whether these electrolytes play a role in the pathogenesis of arterial hypertension and its treatment. Some individuals are especially sensitive to sodium, and changing their intake of dietary sodium may lead to variations in the levels of the other electrolytes. These changes in electrolyte levels can complicate treatments for arterial hypertension in some patients.

  7. SFAs do not impair endothelial function and arterial stiffness123

    PubMed Central

    Sanders, Thomas AB; Lewis, Fiona J; Goff, Louise M; Chowienczyk, Philip J

    2013-01-01

    Background: It is uncertain whether saturated fatty acids (SFAs) impair endothelial function and contribute to arterial stiffening. Objective: We tested the effects of replacing SFAs with monounsaturated fatty acids (MUFAs) or carbohydrates on endothelial function and arterial stiffness. Design: With the use of a parallel-designed randomized controlled trial in 121 insulin-resistant men and women, we measured vascular function after 1 mo of consumption of a high-SFA (HS) diet and after 24 wk after random assignment to the HS diet or diets that contained <10% SFAs and were high in either MUFAs or carbohydrates. The primary outcome was a change in flow-mediated dilation (FMD), and secondary outcomes were changes in carotid to femoral pulse wave velocity (PWV) and plasma 8-isoprostane F2α-III concentrations. Results: For 112 participants with data available for analysis on the specified outcomes, no significant differences were shown. FMD with the HS reference diet was 6.7 ± 2.2%, and changes (95% CIs) after 6 mo of intervention were +0.3 (−0.4, 1.1), −0.2 (−0.8, 0.5), and −0.1 (−0.6, 0.7) with HS, high-MUFA (HM), and high-carbohydrate (HC) diets, respectively. After consumption of the HS reference diet, the geometric mean (±SD) PWV was 7.67 ± 1.62 m/s, and mean percentages of changes (95% CIs) were −1.0 (−6.2, 4.3) with the HS diet, 2.7 (−1.4, 6.9) with the HM diet, and −1.0 (−5.5, 3.4) with the HC diet. With the HS reference diet, the geometric mean (±SD) plasma 8-isoprostane F2α-III concentration was 176 ± 85 pmol/L, and mean percentage of changes (95% CIs) were 1 (−12, 14) with the HS diet, 6 (−5, 16) with the HM diet, and 4 (−7, 16) with the HC diet. Conclusion: The replacement of SFAs with MUFAs or carbohydrates in healthy subjects does not affect vascular function. This trial was registered at Current Controlled Trials (http://www.controlled-trials.com/ISRCTN) as ISRCTN 29111298. PMID:23964054

  8. Sublingual Microcirculation in Pulmonary Arterial Hypertension

    PubMed Central

    Dababneh, Luma; Cikach, Frank; Alkukhun, Laith; Dweik, Raed A.

    2014-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that leads to failure of the right ventricle and premature death. Objectives: To determine whether the sublingual microcirculation is affected in patients with PAH compared with healthy age- and sex-matched control subjects. Methods: Using the CapiScope Handheld Video Capillaroscope we measured the sublingual microvasculature density, flow index, tortuosity, and curvature. Videos were acquired immediately after right heart catheterization, and determinations were made off-line by investigators blinded to the group assignment or hemodynamics. Measurements and Main Results: In this cross-sectional pilot study, we included 26 patients with PAH (age, mean ± SD, 56.7 ± 10 yr; 77% women) and 14 healthy control subjects (age, 53.1 ± 12 yr; 71% women). Sublingual microvasculature flow index was lower (2 ± 0.66 vs. 2.7 ± 0.37, P < 0.001) with higher heterogeneity index (0.63 ± 0.63 vs. 0.25 ± 0.25, P = 0.04) in patients with PAH than control subjects. Microvasculature density was similar between the groups, but tortuosity was more pronounced in patients than control subjects (tort 0: 45 ± 19 vs. 23.6 ± 12, P = 0.001 and tort 1: 0.2 ± 0.16 vs. 0.06 ± 0.04, P < 0.001). Conclusions: Patients with PAH showed lower sublingual microvasculature flow index and higher tortuosity compared with healthy age- and sex-matched control subjects. Further investigations are needed to assess whether this methodology can provide information on disease prognosis and/or response to therapy in this condition. PMID:24601682

  9. 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.

  10. 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.

  11. [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. PMID:10517096

  12. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    SciTech Connect

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H. )

    1990-06-01

    Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with (111In)nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

  13. Correlates of carotid artery stiffness in young adults: The Bogalusa Heart Study.

    PubMed

    Urbina, E M; Srinivasan, S R; Kieltyka, R L; Tang, R; Bond, M G; Chen, W; Berenson, G S

    2004-09-01

    Decreased arterial elasticity, an independent risk factor for cardiovascular (C-V) disease, is associated with C-V risk factors in middle-aged and older individuals. However, information is limited in this regard in young adults. This aspect was examined in a community-based sample of 516 black and white subjects aged 25-38 years (71% white, 39% male). The common carotid artery elasticity was measured from M-mode ultrasonography as Peterson's elastic modulus (Ep) and relative wall thickness-adjusted Young's elastic modulus (YEM). Blacks and males had higher Ep (P < 0.05); males had higher YEM (P < 0.0001); and blacks had higher wall thickness (P < 0.01). For the entire sample adjusted for race and gender both Ep and YEM correlated significantly (P < 0.05-0.0001) with age, BMI, waist, systolic and diastolic blood pressures, heart rate, product of heart rate and pulse pressure, triglycerides, total cholesterol to HDL cholesterol ratio, insulin and glucose. In a multivariate regression model that included hemodynamic variables, systolic blood pressure, product of heart rate and pulse pressure, age, triglycerides, BMI, and male gender (for YEM only) were independent correlates of Ep (R2 = 0.38) and YEM (R2 = 0.25). When the hemodynamic variables were excluded from the model, age, triglycerides, BMI, black race (Ep only), male gender, parental history of hypertension, HDL cholesterol (inverse association), and insulin (marginal significance) remained independent correlates of Ep (R2 = 0.20) and YEM (R2 = 16). Both Ep and YEM increased (P for trend P < 0.0001) with increasing number of independent continuous risk factors (defined as values above or below the age, race, and gender-specific extreme quintiles) that were retained in the regression models. The observed increasing arterial stiffness (or decreased elasticity) with increasing number of risk factors related to insulin resistance syndrome in free-living, asymptomatic young adults has important implications for

  14. [Primary and secondary arterial hypertension - update 2016].

    PubMed

    Sanner, Bernd; Hausberg, Martin

    2016-06-01

    In patients with hypertension without diabetes and with an increased risk of cardiovascular complications a blood pressure of below 130 mmHg should be targeted. Hypertensive patients with an age above 80 years should be treated in the same way as younger hypertensive patients if they are otherwise healthy and functionally independent. On the other hand frail elderly patients could have an increased morbidity and mortality with intensive blood pressure control. In patients with resistant hypertension spironolactone was the most effective drug when given in addition to their baseline drugs (ACE-inhibitor/angiotensin receptor antagonist, calcium channel blocker and thiazide diuretic). PMID:27254628

  15. [Vascular damage in arterial hypertension: its noninvasive assessment].

    PubMed

    Novo, S; Failla, G; Liquori, M; Longo, B; Gennaro, C; Corda, M; Barbagallo, M; Abrignani, M G; Barbagallo Sangiorgi, G; Strano, A

    1991-12-01

    Arterial hypertension is a definite risk factor for the atherosclerotic disease and thus has a primary role in the genesis of cardiovascular diseases, but it acts also though a direct structural damage of great and small arteries and arterioles. Up to date, clinical research and technological advancements have made possible the development of instruments and methods for the evaluation of the vascular damage. Ultrasonographic methods are now the better non invasive tools for the study of arterial diseases, allowing a definition power comparable to angiography, and giving useful data on characters and composition of plaques, also minimal, at the level of the arterial district of lower limbs, epiaortic, renal, and abdominal vessels. These methods allow the study of the vascular lesion under the hemodynamic (CW or pulsed Doppler with spectral signal analysis) and the morphological profile (high resolution echotomography) or both echo-Doppler duplex scanning or color flow imaging). Arterial compliance of great vessels can be studied through the Doppler evaluation of pulsed wave velocity along the arterial tree. Other useful parameters are the aortic distensibility (ratio between % change in arterial volume and blood pressure), the elastic module, the index of arterial rigidity and the aortic index (ratio between pulse pressure and stroke volume). By using this latter parameter we demonstrated a significant decrease of arterial compliance that is proportional to the severity of blood pressure values. Small vessels may be studied through strain-gauge plethysmography, that allows to obtain the regional blood flows at the hand and forearm (skin circulation) and the calf (muscular circulation) both in basal conditions and after ischaemic stimulus. From the ratio between mean arterial pressure and post-ischemic blood flow it is possible to obtain minimal vascular resistances, expression of the maximal vasodilatation capacity in the arteriolar bed. With this method we showed

  16. [Arterial hypertension among oil-drilling workers exposed to noise].

    PubMed

    Souto Souza, N S; Carvalho, F M; de Cássia Pereira Fernandes, R

    2001-01-01

    A cross-sectional study with a retrospective component was conducted to evaluate occupational noise exposure as a potential risk factor for arterial hypertension among 775 workers from an oil-drilling industry. Hypertension was defined as >/= 140/90mmHg. Occupational noise exposure was measured as: (1) exposure to sound pressure levels >/= 85dbA for 10 years or more and (2) moderate-to-severe noise-induced hearing loss (NIHL). The effects of age, education, shift work, and obesity were evaluated by stratification and logistic regression analysis. A positive association between occupational noise exposure and hypertension was found, using both the level/duration of noise exposure (RP = 1.8; 95% CI: 1.3-2.4) and NIHL (RP = 1.5; 95% CI: 1.1-2.0) as exposure indicators. Considering the study limits, long-term occupational noise exposure thus appears to be a risk factor for arterial hypertension. PMID:11784909

  17. Pulmonary arterial hypertension: a current review of pharmacological management.

    PubMed

    Sahni, Sonu; Ojrzanowski, Marcin; Majewski, Sebastian; Talwar, Arunabh

    2016-01-01

    Pulmonary hypertension (PHTN) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance, which eventually leads to right ventricular failure and death. At present there is no cure for pulmonary arterial hypertension (PAH); however over the past decade targeted pharmaceutical options have become available for the treatment of PAH. Prior to evaluation for therapeutic options a definitive diagnosis of pulmonary arterial hypertension must be made via comprehensive physical exam and definitive diagnostic testing. Screening test of choice remains echocardiography and gold standard for definitive diagnosis is right heart catheterization. Once the establishment of a diagnosis of PAH is made therapeutic options may be a possibility based on a diagnostic algorithm and disease severity of the PAH patient. There are different classes of medications available with different mechanisms of actions which net a vasodilatory effect and improve exercise tolerance, quality of life as well and survival.

  18. [Arterial hypertension in gravidity - a risk factor for cardiovascular diseases].

    PubMed

    Kováčová, M; Kiňová, S

    2012-12-01

    Gravidity is a dynamic process and complications may occur at any stage and anytime during a thus far physiological gravidity. Such gravidity puts the mother, the foetus and, later, the newborn at a greater risk. The incidence of arterial hypertension is between 7 and 15% and is one of the 4 main causes of maternal and perinatal mortality. Cardiovascular stress test, such as gravidity, might help to identify women at a greater risk of cardiovascular diseases or with a subclinical vascular disease. Women with a history of preeclampsia are more likely to develop chronic arterial hypertension in the future either alone or associated with a cardiovascular disease. Arterial hypertension during gravidity should be considered as a risk factor for cardiovascular diseases during later stages of maternal life. Prevention of cardiovascular diseases should be a life-long aspiration.

  19. Hypercorticism--a risk factor in arterial hypertension and atherosclerosis.

    PubMed

    Berceanu-Gabrielescu, A; Mănciulescu, D; Marinescu, I; Popovici, D; Dinulescu, E; Juvină, E; Ioaniţiu, D; Tache, A; Cristoveanu, A; Ciocirdia, C; Bunea, M; Sooliuc, E; Panaitiu, G; Augustin, M

    1981-01-01

    The present work has attempted an analysis of the role hypercorticism as a risk factor in arterial hypertension and atherosclerosis. Our series consisted of 149 male and female patients of various ages. The incidence of cardiovascular disorders in relation to age and the glucidic lipidic metabolic disorders were also investigated. The results showed that hypercorticism may trigger in very young patients as well arterial hypertension (AH) and glucidic-lipid metabolic disorders both incriminated as risk factors in including atherosclerosis. Hypercorticism was proved to be an aggravating factor of pre-existing cardiopathy. Efficient management of adrenocortical hormones excess brings complete resolution of arterial hypertension and glucidic lipid metabolic disorders in young patients and most adult patients who had no cardiovascular complaints prior to the endocrine syndrome.

  20. 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.

  1. Notch3 signaling promotes the development of pulmonary arterial hypertension.

    PubMed

    Li, Xiaodong; Zhang, Xiaoxue; Leathers, Robin; Makino, Ayako; Huang, Chengqun; Parsa, Pouria; Macias, Jesus; Yuan, Jason X-J; Jamieson, Stuart W; Thistlethwaite, Patricia A

    2009-11-01

    Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevation of pulmonary vascular resistance, right ventricular failure and death. Here we show that human pulmonary hypertension is characterized by overexpression of NOTCH3 in small pulmonary artery smooth muscle cells and that the severity of disease in humans and rodents correlates with the amount of NOTCH3 protein in the lung. We further show that mice with homozygous deletion of Notch3 do not develop pulmonary hypertension in response to hypoxic stimulation and that pulmonary hypertension can be successfully treated in mice by administration of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a gamma-secretase inhibitor that blocks activation of Notch3 in smooth muscle cells. We show a mechanistic link from NOTCH3 receptor signaling through the Hairy and enhancer of Split-5 (HES-5) protein to smooth muscle cell proliferation and a shift to an undifferentiated smooth muscle cell phenotype. These results suggest that the NOTCH3-HES-5 signaling pathway is crucial for the development of pulmonary arterial hypertension and provide a target pathway for therapeutic intervention. PMID:19855400

  2. Macitentan in pulmonary arterial hypertension: The SERAPHIN trial.

    PubMed

    Said, Karim

    2014-01-01

    Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the history of clinical trials in PAH being the largest and longest clinical study conducted thus far in PAH patients with morbidity and mortality events as primary endpoint. SERAPHIN trial investigated whether long-term treatment with the new endothelin receptor antagonist macitentan would reduce the risk of mortality and morbidity in PAH patients.

  3. 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

  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. Non-dipping status in arterial hypertension: an overview.

    PubMed

    Sarigianni, Maria; Dimitrakopoulos, Konstantinos; Tsapas, Apostolos

    2014-05-01

    Non-dipping is a common pattern of arterial hypertension and it is associated with increased cardiovascular risk. Use of ambulatory blood pressure monitoring, as suggested in recent guidelines, could further increase its prevalence among subjects with hypertension. In this review we discuss assessment, relevance and associated factors. Non-dipping could be addressed through chronotherapy, the use of specific classes of anti-hypertensives, such as renin-angiotensin blockers, or modification of associated factors. However, more data are needed in order to comprehensively estimate factors associated with non-dipping and how they could be modified.

  6. Severe Pulmonary Arterial Hypertension: Comprehensive Evaluation by Magnetic Resonance Imaging

    PubMed Central

    Ibrahim, El-Sayed H.; Bajwa, Abubakr A.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery (PA) pressure, which negatively affects the right ventricular (RV) function. This report shows a patient with severe PAH, on whom a comprehensive MRI exam was performed to evaluate both PA and RV. New imaging sequences were implemented for obtaining additional parameters about the patient's condition. The results show the capabilities of the developed exam of providing complete picture of the cardiovascular system in PAH, which helps the physician optimize treatment. PMID:26435871

  7. The Warburg effect: A new story in pulmonary arterial hypertension.

    PubMed

    Peng, Hongyan; Xiao, Yunbin; Deng, Xicheng; Luo, Jingfei; Hong, Chenliang; Qin, Xuping

    2016-10-01

    Pulmonary arterial hypertension (PAH) is a rare yet fatal condition that is characterized by a continuous and notable elevation of pulmonary arterial pressure (PAP), resulting in right heart failure and death. Pulmonary arterial remodelling does not result from abnormal proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) but from pulmonary arterial endothelial cell (PAEC) dysfunction. However, the pathological mechanism of these two types of vascular cells in pulmonary artery remodelling is unclear. The Warburg effect describes aerobic glycolysis wherein cells commonly reprogram their energy metabolism to preferentially utilize glycolysis over oxidative phosphorylation for ATP production. Recent research has demonstrated that the Warburg effect plays a significant role in the development of PAH, which involves the abnormal proliferation of PASMCs and endothelial dysfunction. This review attempts to illustrate the functions of the Warburg effect in PAH, which may provide a new therapeutic target for PAH treatment.

  8. Arterial stiffness during acute and recovery phases of children with rheumatic fever.

    PubMed

    Ibrahim, N N I N; Jaafar, H; Rasool, A H; Wong, A R

    2016-02-01

    Acute rheumatic fever (ARF) is associated with systemic inflammation and arterial stiffness during the acute stage. It has not been reported if arterial stiffness remains after recovery. The aim of this study was to determine the arterial stiffness during acute stage and 6 months after recovery from ARF. Arterial stiffness was assessed by carotid femoral pulse wave velocity (PWV) in 23 ARF patients during the acute stage of ARF and 6 months later. Simultaneously, erythrocyte sedimentation rate (ESR) and other anthropometric measurements were taken during both stages. There was a significant reduction in PWV; 6.5 (6.0, 7.45) m/s to 5.9 (5.38, 6.48) m/s, p=0.003 6 months after the acute stage of ARF. Similarly, ESR was also significantly reduced from 92.0 (37.5, 110.50) mm/hr to 7.0 (5.0, 16.0) mm/hr, p=0.001. In conclusion, arterial stiffness improved 6 months after the acute stage with routine aspirin treatment; this correlates well with the reduction in systemic inflammation. PMID:27130739

  9. Lower Body vs. Upper Body Resistance Training and Arterial Stiffness in Young Men.

    PubMed

    Li, Y; Bopp, M; Botta, F; Nussbaumer, M; Schäfer, J; Roth, R; Schmidt-Trucksäss, A; Hanssen, H

    2015-11-01

    Resistance training has been shown to increase arterial stiffness. The purpose of the present study was to examine and compare the systemic arterial stiffness responses to acute lower body (LRT) and upper body (URT) resistance training. 20 healthy young men [median age: 26 years (interquartile range 23, 32)] underwent LRT, URT and whole body resistance training (WRT). Before and immediately after, as well as 20, 40 and 60 min after each training session, we measured the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) using VaSera VS-1500 N. We used mixed models for repeated measurements to estimate the post-exercise differences in CAVI and baPWV between the 3 resistance training modes. Immediately after exercise cessation, both CAVI and baPWV were lower for LRT compared with URT [CAVI: - 0.93 (95% confidence interval [CI] - 1.15, - 0.70); baPWV: - 2.08 m/s (95% CI - 2.48, - 1.67)]. Differences between LRT and URT gradually decreased during follow-up. Compared with WRT, LRT induced a decrease and URT an increase in arterial stiffness across all time points. In conclusion, LRT presents more favorable post-exercise arterial stiffness than URT. Our results suggest that LRT or WRT may be preferred over URT in individuals with impaired arterial stiffness. PMID:26212244

  10. Arterial Stiffness, Lipoprotein Particle Size, and Lipoprotein Particle Concentration in Children with Type 1 Diabetes

    PubMed Central

    Gallo, Lisa M; Silverstein, Janet H.; Shuster, Jonathan J; Haller, Michael J.

    2013-01-01

    OBJECTIVE To determine if lipoprotein particle abnormalities correlate with arterial stiffness in children with type 1 diabetes (T1D). STUDY DESIGN In this case-control study, we evaluated 70 children, 35 with T1D and 35 controls, ages 10–18 years, matched for age, sex, race, and BMI. Arterial stiffness was assessed by radial tonometry (AI75) and blood was collected for lipoprotein subclass analysis. RESULTS T1D subjects had increased AI75, decreased small LDL particle concentration (P=0.0067), increased large LDL particle concentration (P=0.007), increased large HDL particle concentration (P=0.0012), increased mean LDL particle size (P=0.0028), and increased mean HDL particle size (P<0.0001) compared to controls. No significant correlations were found between lipoprotein subclasses and arterial stiffness in T1D subjects. CONCLUSIONS T1D subjects have increased arterial stiffness when compared to controls, despite a less pro-atherogenic lipoprotein profile, indicating the need to identify other risk factors that correlate with arterial stiffness in T1D youth. PMID:20857838

  11. Hyperemia-Related Changes in Arterial Stiffness: Comparison between Pulse Wave Velocity and Stiffness Index in the Vascular Reactivity Assessment.

    PubMed

    Torrado, Juan; Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Farro, Federico; Armentano, Ricardo L

    2012-01-01

    Carotid-to-radial pulse wave velocity (PWV(cr)) has been proposed to evaluate endothelial function. However, the measurement of PWV(cr) is not without limitations. A new simple approach could have wide application. Stiffness index (SI) is obtained by analysis of the peripheral pulse wave and gives reproducible information about stiffness of large arteries. This study assessed the effects of hyperemia on SI and compared it with PWV(cr) in 14 healthy subjects. Both were measured at rest and during 8 minutes after ischemia. SI temporal course was determined. At 1 minute, SI and PWV(cr) decreased (5.58 ± 0.24 to 5.34 ± 0.23 m/s, P < 0.05; 7.8 ± 1.0 to 7.2 ± 0.9 m/s; P < 0.05, resp.). SI was positively related to PWV(cr) in baseline (r = 0.62 , P < 0.05), at 1 minute (r = 0.79, P < 0.05), and during the whole experimental session (r = 0.52, P < 0.05). Conclusion. Hyperemia significantly decreases SI in healthy subjects. SI was related to PWV(cr) and could be used to facilitate the evaluation of hyperemia-related changes in arterial stiffness.

  12. ISH PRE-1 REDUCTION OF CARDIOVASCULAR MORTALITY IN HYPERTENSIVES WITH COMORBIDITIES: BEYOND BLOOD PRESSURE LOWERING - THE ROLE OF ARTERIAL AGING.

    PubMed

    Safar, Michel E

    2016-09-01

    Mid-life elevated BP is classically associated with a raised systemic vascular resistance. A classical interpretation of the association between aortic stiffness and blood pressure (BP) invokes hypertension as a simple form of premature aging that increases stress on the arterial wall and accelerates age-related stiffening of the aorta. Recent clinical and experimental data have called into question the directionality of this sequence of events associating stiffness and hypertension.Therefore an initial abnormality in stiffness may antedate and contribute initially to the pathogenesis of hypertension, namely isolated systolic hypertension. This possibility is important to consider since it might affect the individual estimation of cardiovascular risk even in low risk prehypertensive subjects. Therefore, it might be essential to direct therapy of hypertension toward the reduction of both BP and aortic stiffness.Cardiovascular (CV) complications are dominant causes of death in severe hypertensive patients with comorbidities, especially diabetic hypertensive patients (DHS) and patients with end-stage renal disease (ESRD). Vascular calcifi cation and arterial stiffness are highly prevalent in such subjects, particularly in those with co-morbidities. Carotid-femoral pulse wave velocity (CFPWV) is the gold standard and simple, non-invasive and reproducible measure of large artery stiffness.This measurement have been frequently used as predictors for CV events and CV mortality in the general population, in specifi c populations such as in patients with DHS and ESRD. These fi ndings have been widely observed using conventional cross-sectional investigations. However, in such studies, it has been observed that the association between single measurements of CFPWV and CV events is frequently driven by the high incidence of late events, i.e. after 12 months of follow-up.New data from our prospective studies in DHS and ESRD evaluated the association between longitudinal changes

  13. [Health beliefs for the control of arterial hypertension].

    PubMed

    Pires, Cláudia Geovana da Silva; Mussi, Fernanda Carneiro

    2008-12-01

    Health beliefs can interfere with the adherence to arterial hypertension therapy. The aim of this descriptive-exploratory study that adopted the Model of Health Beliefs as a theoretical reference was to estimate percentages of health beliefs about the benefits of prevention and control measures of arterial hypertension and to identify the social-demographic factors associated with these beliefs. The study was conducted in a Health Center in the city of Salvador, with 106 adults self-declared as black, and with a medical diagnosis of arterial hypertension. For the interviews we used a "Scale of Health Beliefs" about 13 behaviors related to disease prevention and control measures. The data analysis was based on percentage rates, frequency of cases and scores and the social-demographic factors associated to these beliefs were analyzed based on the prevalence rate. The global analysis showed predominance in the category "beliefs about benefits" for 12 behaviors. Men and women realized different benefits from these behaviors. The socio-economically less favored strata, young adults and individuals living without a partner tended to perceive less benefits from the prevention and control measures of arterial hypertension.

  14. [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. PMID:25577549

  15. [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.

  16. [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.

  17. 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. PMID:18003349

  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. Extracellular matrix protein gene expression in atherosclerotic hypertensive pulmonary arteries.

    PubMed Central

    Botney, M. D.; Kaiser, L. R.; Cooper, J. D.; Mecham, R. P.; Parghi, D.; Roby, J.; Parks, W. C.

    1992-01-01

    Lobar pulmonary arteries from patients with unexplained pulmonary hypertension were obtained at the time of single-lung transplantation to determine the response of large elastic vessels to increased intraluminal pressure. Specifically, human pulmonary arteries were examined to determine if remodeling remained active at the time of surgery and whether remodeling was similar to previously reported remodeling observed in several animal models. Grossly, the hypertensive vessels appeared atherosclerotic. Histochemical stains revealed a thick, diffuse neointima in hypertensive vessels compared with normal vessels. Immunohistochemistry demonstrated elastin protein in the neointima and in situ hybridization studies demonstrated tropoelastin mRNA largely in the neointima. Similarly, immunohistochemistry and in situ hybridization detected cellular fibronectin, thrombospondin and type I collagen protein and mRNA within the thickened intima from hypertensive vessels. These studies provide evidence that hypertensive vessels in patients with severe chronic pulmonary hypertension are actively remodeling but that the pattern of remodeling is different from previously described animal models. Images Figure 1 Figure 2 Figure 3 PMID:1739129

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

    PubMed

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

    2008-10-01

    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. Prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension.

    PubMed

    Lee, Noel S; Blanchard, Daniel G; Knowlton, Kirk U; McDivit, Anna M; Pretorius, Victor; Madani, Michael M; Fedullo, Peter F; Kerr, Kim M; Kim, Nick H; Poch, David S; Auger, William R; Daniels, Lori B

    2015-06-01

    This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion. PMID:26064456

  2. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  3. Gene-environment interactions of selected pharmacogenes in arterial hypertension.

    PubMed

    Bochud, Murielle; Guessous, Idris

    2012-11-01

    Hypertension affects approximately 1 billion people worldwide. Owing to population aging, hypertension-related cardiovascular burden is expected to rise in the near future. In addition to genetic variants influencing the blood pressure response to antihypertensive drugs, several genes encoding for drug-metabolizing or -transporting enzymes have been associated with blood pressure and/or hypertension in humans (e.g., ACE, CYP1A2, CYP3A5, ABCB1 and MTHFR) regardless of drug treatment. These genes are also involved in the metabolism and transport of endogenous substances and their effects may be modified by selected environmental factors, such as diet or lifestyle. However, little is currently known on the complex interplay between environmental factors, endogenous factors, genetic variants and drugs on blood pressure control. This review will discuss the respective role of population-based primary prevention and personalized medicine for arterial hypertension, taking a pharmacogenomics' perspective focusing on selected pharmacogenes. PMID:23234325

  4. Arterial hypertension in diabetes mellitus: from theory to clinical practice.

    PubMed

    Sampanis, C; Zamboulis, C

    2008-04-01

    Diabetes mellitus and arterial hypertension are two common diseases that often coexist. Patients with diabetes have much higher rate of hypertension than that in general population. The co-existence of these disorders appears to accelerate microvascular and macrovascular complications and greatly increases the cardiovascular risk, risk of stroke and end stage renal disease. Arterial hypertension is clearly related to nephropathy in subjects with type 1 diabetes. In patients with type 2 diabetes insulin resistance seems to play a pivotal role in the pathogenesis of hypertension. Several well designed randomized controlled trials have provided evidence that patients with diabetes will benefit from a more aggressive treatment of hypertension. This benefit is seen at blood pressure level<130/80 mmHg. Moreover, most diabetic patients with hypertension require combination therapy to achieve optimal blood pressure goals. Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, diuretics, beta-adrenoreceptor blockers and calcium- channel blockers are all effective antihypertensive agents in type 2 diabetes mellitus and no comparative trial showed the superiority of any particular class in either lowering blood pressure or reducing cardiovascular morbidity and mortality. On the basis of experimental arguments and clinical observations that have shown their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers are preferred as the first choice alone or in combination with diuretics. Second choice should be long-acting calcium-channel blockers or cardioselective beta blockers. Clinicians should be aware of the need for aggressive treatment of hypertension and spend more time in order to provide maximal benefit to the treatment of diabetes mellitus and hypertension. PMID:18923653

  5. Arterial hypertension in diabetes mellitus: from theory to clinical practice

    PubMed Central

    Sampanis, C; Zamboulis, C

    2008-01-01

    Diabetes mellitus and arterial hypertension are two common diseases that often coexist. Patients with diabetes have much higher rate of hypertension than that in general population. The co-existence of these disorders appears to accelerate microvascular and macrovascular complications and greatly increases the cardiovascular risk, risk of stroke and end stage renal disease. Arterial hypertension is clearly related to nephropathy in subjects with type 1 diabetes. In patients with type 2 diabetes insulin resistance seems to play a pivotal role in the pathogenesis of hypertension. Several well designed randomized controlled trials have provided evidence that patients with diabetes will benefit from a more aggressive treatment of hypertension. This benefit is seen at blood pressure level < 130/80 mmHg. Mopreover, most diabetic patients with hypertension require combination therapy to achieve optimal blood pressure goals. Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, diuretics, β-adrenoreceptor blockers and calcium- channel blockers are all effective antihypertensive agents in type 2 diabetes mellitus and no comparative trial showed the superiority of any particular class in either lowering blood pressure or reducing cardiovascular morbidity and mortality. On the basis of experimental arguments and clinical observations that have shown their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers are preferred as the first choice alone or in combination with diuretics. Second choice should be long-acting calcium-channel blockers or cardioselective β blockers. Clinicians should be aware of the need for aggressive treatment of hypertension and spend more time in order to provide maximal benefit to the treatment of diabetes mellitus and hypertension. PMID:18923653

  6. Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

    PubMed

    Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

    2016-09-01

    The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. PMID:27456517

  7. [Heart failure and arterial hypertension disclosing amyloidosis].

    PubMed

    Habbal, R; Noureddine, M; Hachim, K; Zahraoui, M; Azzouzi, L; Fadouach, S; Zaid, D; Chraibi, N

    1997-01-01

    Amyloidosis results from protein infiltration of the extracellular space of organs and tissues. Several amyloidosis proteins have been identified. Protein AL, (deriving from immunoglobulin light chain), protein AA and prealbumin are the most involved in this disease. When AL amyloidosis involves the heart, the illness is often terminal. Most clinical symptoms are heart failure and arrhythmia or block conduction. This case was characterised by the unusual combination of hypertension and amyloidosis. The diagnosis suggested by the echocardiographic but was confirmed by the damaged organ's biopsy. The present case concerns a young woman, who has hypertension and a pulmonary oedema. The echocardiographic scan showed a septal hypertrophy with a shining and granite-like aspect which is compatible with heart amyloidosis. Systolic and diastolic disorder with mitral and aortic regurgitation were also revealed. The kidney and rectum biopsies confirmed amyloidosis AL of the Kappa dysglobulinemia type, without extraosseous plasmocytoma. The heart and kidney failure symptoms disappeared after treatment with diuretics and ACE inhibitors.

  8. Protein Changes Contributing to Right Ventricular Cardiomyocyte Diastolic Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rain, Silvia; Bos, Denielli da Silva Goncalves; Handoko, M. Louis; Westerhof, Nico; Stienen, Ger; Ottenheijm, Coen; Goebel, Max; Dorfmüller, Peter; Guignabert, Christophe; Humbert, Marc; Bogaard, Harm‐Jan; dos Remedios, Cris; Saripalli, Chandra; Hidalgo, Carlos G.; Granzier, Henk L.; Vonk‐Noordegraaf, Anton; van der Velden, Jolanda; de Man, Frances S.

    2014-01-01

    Background Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. Methods and Results RV samples from PAH patients undergoing heart‐lung transplantation were compared to non‐failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western‐blot analyses using antibodies to protein‐kinase‐A (PKA), Cα (PKCα) and Ca2+/calmoduling‐dependent‐kinase (CamKIIδ) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCα sites were significantly less phosphorylated in PAH compared with donors (P<0.0001). To test the functional relevance of PKA‐, PKCα‐, and CamKIIδ‐mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKCα further increased stiffness while CamKIIδ had no major effect. CamKIIδ activation was determined indirectly by measuring PLN Thr17phosphorylation level. No significant changes were found between the groups. Myofilament Ca2+ sensitivity is mediated by sarcomeric troponin I (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P<0.05) and reduced PKA‐mediated cTnI phosphorylation (Ser22/23) (P<0.001). Finally, alterations in Ca2+‐handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca2+ clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P<0.05). Conclusions Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca2

  9. Does short-term whole-body vibration training affect arterial stiffness in chronic stroke? A preliminary study.

    PubMed

    Yule, Christie E; Stoner, Lee; Hodges, Lynette D; Cochrane, Darryl J

    2016-03-01

    [Purpose] Previous studies have shown that stroke is associated with increased arterial stiffness that can be diminished by a program of physical activity. A novel exercise intervention, whole-body vibration (WBV), is reported to significantly improve arterial stiffness in healthy men and older sedentary adults. However, little is known about its efficacy in reducing arterial stiffness in chronic stroke. [Subjects and Methods] Six participants with chronic stroke were randomly assigned to 4 weeks of WBV training or control followed by cross-over after a 2-week washout period. WBV intervention consisted of 3 sessions of 5 min intermittent WBV per week for 4 weeks. Arterial stiffness (carotid arterial stiffness, pulse wave velocity [PWV], pulse and wave analysis [PWA]) were measured before/after each intervention. [Results] No significant improvements were reported with respect to carotid arterial stiffness, PWV, and PWA between WBV and control. However, carotid arterial stiffness showed a decrease over time following WBV compared to control, but this was not significant. [Conclusion] Three days/week for 4 weeks of WBV seems too short to elicit appropriate changes in arterial stiffness in chronic stroke. However, no adverse effects were reported, indicating that WBV is a safe and acceptable exercise modality for people with chronic stroke.

  10. Does short-term whole-body vibration training affect arterial stiffness in chronic stroke? A preliminary study

    PubMed Central

    Yule, Christie E.; Stoner, Lee; Hodges, Lynette D.; Cochrane, Darryl J.

    2016-01-01

    [Purpose] Previous studies have shown that stroke is associated with increased arterial stiffness that can be diminished by a program of physical activity. A novel exercise intervention, whole-body vibration (WBV), is reported to significantly improve arterial stiffness in healthy men and older sedentary adults. However, little is known about its efficacy in reducing arterial stiffness in chronic stroke. [Subjects and Methods] Six participants with chronic stroke were randomly assigned to 4 weeks of WBV training or control followed by cross-over after a 2-week washout period. WBV intervention consisted of 3 sessions of 5 min intermittent WBV per week for 4 weeks. Arterial stiffness (carotid arterial stiffness, pulse wave velocity [PWV], pulse and wave analysis [PWA]) were measured before/after each intervention. [Results] No significant improvements were reported with respect to carotid arterial stiffness, PWV, and PWA between WBV and control. However, carotid arterial stiffness showed a decrease over time following WBV compared to control, but this was not significant. [Conclusion] Three days/week for 4 weeks of WBV seems too short to elicit appropriate changes in arterial stiffness in chronic stroke. However, no adverse effects were reported, indicating that WBV is a safe and acceptable exercise modality for people with chronic stroke. PMID:27134400

  11. Taking the pulse of a sick kidney: arterial stiffness in glomerulonephritis.

    PubMed

    Doyon, Anke; Schaefer, Franz

    2011-02-01

    Arterial stiffness is an increasingly recognized independent predictor of cardiovascular morbidity. Vessel volume and wall texture are the main determinants of pulse wave velocity (PWV), the most commonly used indicator of arterial elasticity. Hence, measurements of PWV will be affected by the site of measurement and the overall dimensions of the vascular tree as well as by alterations of vascular morphology. In children, methodological heterogeneity and the lack of pediatric reference values complicate the interpretation of PWV. Arterial elasticity is altered in numerous clinical conditions such as vasculitis, end-stage renal disease, and diabetes. Novel evidence suggests that acute postinfectious glomerulonephritis, but not pyelonephritis, is also associated with increased arterial stiffness, the persistence of which may predict the emergence of chronic kidney disease. We review the potential mechanisms underlying the link between acute and chronic kidney disease and impaired arterial elasticity. These might include activation of the renin-angiotensin system, sympathetic hyperactivation, and a subclinical state of inflammation. In view of the excessive cardiovascular comorbidity associated with kidney disease, the increasing evidence of the prognostic relevance of arterial stiffness should encourage further research investigating the usefulness of PWV as a biomarker in acute and chronic kidney disorders.

  12. 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.

  13. Acute Effect on Arterial Stiffness after Performing Resistance Exercise by Using the Valsalva Manoeuvre during Exertion

    PubMed Central

    Mak, Wai Yip Vincent; Lai, Wai Keung Christopher

    2015-01-01

    Background. Performing resistance exercise could lead to an increase in arterial stiffness. Objective. We investigate the acute effect on arterial stiffness by performing Valsalva manoeuvre during resistance exercise. Materials and Methods. Eighteen healthy young men were assigned to perform bicep curls by using two breathing techniques (exhalation and Valsalva manoeuvre during muscle contraction) on two separate study days. Carotid pulsed wave velocity (cPWV) was measured as an indicator to reflect the body central arterial stiffness using a high-resolution ultrasound system, and its value was monitored repeatedly at three predefined time intervals: before resistance exercise, immediately after exercise, and 15 minutes after exercise. Results. At the 0th minute after resistance exercise was performed using the Valsalva manoeuvre during exertion, a significant increase in cPWV (4.91 m/s ± 0.52) compared with the baseline value (4.67 m/s ± 0.32, P = 0.008) was observed, and then it nearly returned to its baseline value at the 15th minute after exercise (4.66 m/s ± 0.44, P = 0.010). These findings persisted after adjusting for age, body mass index, and systolic blood pressure. Conclusion. Our result suggests short duration of resistance exercise may provoke a transient increase in central arterial stiffness in healthy young men. PMID:26539481

  14. [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.

  15. Albuminuria as a marker of arterial stiffness in chronic kidney disease patients

    PubMed Central

    Kalaitzidis, Rigas G; Karasavvidou, Despina P; Tatsioni, Athina; Pappas, Kosmas; Katatsis, Giorgos; Liontos, Angelos; Elisaf, Moses S

    2015-01-01

    AIM: To access the association between albuminuria levels and arterial stiffness in non-diabetic patients with hypertension and chronic kidney disease (CKD) stages 1-2, treated with renin angiotensin blockade agents plus other hypertensive drugs when needed. METHODS: One hundred fifteen patients [median age 52 years (68% males)] were consequently enrolled in the study. For each patient, we recorded gender, age, body mass index (BMI), peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure, peripheral pulse pressure, central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), central pulse pressure (cPP), hematocrit, hemoglobin, hsCRP, total cholesterol triglycerides, high-density lipoprotein-C, low-density lipoprotein-C, calcium, phosphorus, parathormone, and albumin, as well as 24 h urine albumin excretion. According to 24-h urine albumin collection, patients were then classified as those with moderately increased albuminuria (formerly called macroalbuminuria) (≤ 300 mg/d) and those with severely increased albuminuria (formerly called macroaluminuria (> 300 mg/d). We considered aortic stiffness (AS) indices [carotid femoral pulse wave velocity (PWVc-f) and augmentation index (AIx)] as primary outcomes of the study. We explored potential correlations between severely increased albuminuria and AS indices using a multiple linear regression model. RESULTS: Fifty-eight patients were included in the moderately increased albuminuria group and 57 in the severely increased albuminuria. Blood pressure measurements of the study population were 138 ± 14/82 ± 1.3 mmHg (systolic/diastolic). There were no significant differences in age, sex, and BP measurements between the two groups. Patients with severely increased albuminuria had higher PWV and AIx than patients with moderately increased albuminuria (P < 0.02, P < 0.004, respectively). In addition these patients exhibited higher BMI (P < 0.03), hsCRP (P < 0.001), and fibrinogen

  16. 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

  17. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24303111

  19. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    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.

  20. 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

  1. [Relevance of arterial hypertension in primary open-angle glaucoma].

    PubMed

    Erb, C; Predel, H-G

    2014-02-01

    Primary open-angle glaucoma is a multifactorial disease with a lot of different risk factors. Beside the fact that intraocular pressure (IOP) is the most important risk factor, the reduction of IOP alone is in most cases not sufficient to stop the progression of glaucoma. Therefore, other risk factors play also an important role. One of them is arterial hypertension, the most common systemic disease in glaucoma patients. Arterial hypertension increases IOP slightly, but has an important negative effect on ocular perfusion. Especially the endothelial dysfunction with a disturbed retinal autoregulation plays an important role. Therefore, ischaemic and reperfusion effects alter the optic nerve head and have negative input to the glaucomatous optic neuropathy. In future glaucoma patients should be monitored by ophthalmologists as well as by general physicians/cardiologists to optimise their treatment and to stabilise their glaucoma as well as possible.

  2. Associations between bicycling and carotid arterial stiffness in adolescents: The European Youth Hearts Study.

    PubMed

    Ried-Larsen, M; Grøntved, A; Østergaard, L; Cooper, A R; Froberg, K; Andersen, L B; Møller, N C

    2015-10-01

    The aim of the study was to investigate the associations between bicycling and carotid arterial stiffness, independent of objectively measured moderate-and-vigorous physical activity. This cross-sectional study included 375 adolescents (age 15.7 ± 0.4 years) from the Danish site of the European Youth Heart Study. Total frequency of bicycle usage was assessed by self-report, and carotid arterial stiffness was assessed using B-mode ultrasound. After adjusting for pubertal status, body height, and objectively measured physical activity and other personal lifestyle and demographic factors, boys using their bicycle every day of the week displayed a higher carotid arterial compliance {standard beta 0.47 [95% confidence interval (CI) 0.07-0.87]} and distension [standard beta 0.38 (95% CI -0.04 to 0.81)]. Boys using their bicycle every day of the week furthermore displayed a lower Young's elastic modulus [standard beta -0.48 (95% CI -0.91 to -0.06)]. Similar trends were observed when investigating the association between commuter bicycling and carotid arterial stiffness. These associations were not observed in girls. Our observations suggest that increasing bicycling in adolescence may be beneficial to carotid arterial health among boys.

  3. Associations between bicycling and carotid arterial stiffness in adolescents: The European Youth Hearts Study.

    PubMed

    Ried-Larsen, M; Grøntved, A; Østergaard, L; Cooper, A R; Froberg, K; Andersen, L B; Møller, N C

    2015-10-01

    The aim of the study was to investigate the associations between bicycling and carotid arterial stiffness, independent of objectively measured moderate-and-vigorous physical activity. This cross-sectional study included 375 adolescents (age 15.7 ± 0.4 years) from the Danish site of the European Youth Heart Study. Total frequency of bicycle usage was assessed by self-report, and carotid arterial stiffness was assessed using B-mode ultrasound. After adjusting for pubertal status, body height, and objectively measured physical activity and other personal lifestyle and demographic factors, boys using their bicycle every day of the week displayed a higher carotid arterial compliance {standard beta 0.47 [95% confidence interval (CI) 0.07-0.87]} and distension [standard beta 0.38 (95% CI -0.04 to 0.81)]. Boys using their bicycle every day of the week furthermore displayed a lower Young's elastic modulus [standard beta -0.48 (95% CI -0.91 to -0.06)]. Similar trends were observed when investigating the association between commuter bicycling and carotid arterial stiffness. These associations were not observed in girls. Our observations suggest that increasing bicycling in adolescence may be beneficial to carotid arterial health among boys. PMID:25156494

  4. 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

  5. Depression as a risk factor for arterial hypertension.

    PubMed

    Vashadze, Sh

    2011-12-01

    The aim of the subject is to represents the connection of the Arterial Hypertension and thrombocyte number in blood and to find prevention ways. A clinical case of depression symptoms as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) is a disorder with both physical and mental characteristics that negatively disrupts an individual's ability to function day to day in social and work environments. According to the DSM, real depression is a condition of this nature that lasts for more than two weeks. The subject is actual because Arterial Hypertension according to WHO's data's is one the 1stplace, while Depression - one the 2nd.According to Georgian Disease Controlling and Medical Statistic National Centre data's, depression is characterized from 15% to 25% of people. We've searched for the clinical methods in Batumi Republic Hospital departments. 30 patient is studied by us - 15 women and 15 men. Among them, 20 patients was fallen ill with Arterial Hypertension, 5 with Ischemic insult and 5 - with Discirculating Encephalopathy. We've the question are of Beck. According to which we were able to ascertain the depression quality. The question are consists of 21 questions; by them it was possible to ascertain depression qualities light, medium and complex. The depression quality was defined as follows: the absence of depression in 13%; mild depression in 17%; medium - 30% and severe in 60%. Thus, Depression quality is very high in people with Arterial Hypertension. The number of thrombocyte is high also. Thrombocytes depression causes significant changes in the function, Thrombocytes Activation, Thrombosis increases the risk. So, it's necessary to treat this patient with Antithrombotic medicines and Antidepressants. That will contribute to solving the problem.

  6. [The cell immunity in patients with arterial hypertension and obesity].

    PubMed

    Trushina, É N; Mustafina, O K; Soto, S Kh; Bogdanov, A R; Sentsova, T B; Zaletova, T S; Kuznetsov, V D

    2012-01-01

    In the present study the relative quantity subpopulations of lymphocytes, activated T- lymphocytes and CD95-antigen (Fas/APO-1) expression on lymphocytes in the peripheral blood of patients with arterial hypertension and obesity in comparison with the healthy persons was determined. The cells were analyzed by the method of flow cytometry using Beckman Coulter FC 500 cytometer. The following of cells subsets: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD3+CD25+, CD3+HLA-DR+, CD45+CD95+ were investigated. In this research was establish the rise of immunoregulatory index (CD3+CD4+/CD3+CD8+) in consequence of increase the percentages of T-helper and decrease the cytotoxic T-lymphocytes in patients with arterial hypertension and obesity in comparison with the healthy persons. In the peripheral blood of patients with arterial hypertension and obesity were observed a greater level of activated T-lymphocytes (CD3+CD25+, CD3+HLA-DR+), that reflect the increase activity of T-cell immunity. In these patients a greater level of NKT-cells (CD3+CD16+CD56+) and lymphocytes expression of CD95-antigen in comparison with the healthy persons also was noted. The direct correlation between the increased quantity of T-helper lymphocytes, activated T-lymphocytes, NKT-cells, lymphocytes expression of CD95-antigen, and index of body mass in patients with arterial hypertension and obesity was found.

  7. [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and serotonin].

    PubMed

    Ayme-Dietrich, Estelle; Banas, Sophie M; Monassier, Laurent; Maroteaux, Luc

    2016-01-01

    Serotonin and bone-marrow-derived stem cells participate together in triggering pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors generates permanent changes in the composition of the blood and bone-marrow in the myeloid lineages, particularly in endothelial cell progenitors. The initial functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are restricted to bone-marrow cells. They contribute to the differentiation/proliferation/mobilization of endothelial progenitor cells from the bone-marrow. Those bone-marrow-derived cells have a critical role in the development of pulmonary hypertension and pulmonary vascular remodeling. These data indicate that bone-marrow derived endothelial progenitors play a key role in the pathogenesis of PAH and suggest that interactions involving serotonin and bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of the bone-marrow. PMID:27687599

  8. Sex Differences in Predictors of Longitudinal Changes in Carotid Artery Stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Stern, Rebecca; Tattersall, Matthew C.; Gepner, Adam D.; Korcarz, Claudia E.; Kaufman, Joel; Colangelo, Laura A.; Liu, Kiang; Stein, James H.

    2014-01-01

    Objective To identify sex differences in predictors of longitudinal changes in carotid arterial stiffness in a multi-ethnic cohort. Approach and Results Carotid artery distensibility coefficient (DC) and Young's Elastic Modulus (YEM) were measured in 2650 Multi-Ethnic Study of Atherosclerosis participants (45-84 years old and free of cardiovascular disease) at baseline and after a mean of 9.4 years. Predictors of changes in DC and YEM for each sex were evaluated using multivariable linear regression models. The 1236 men (46.6%) were 60.0 (standard deviation 9.3) years; 40% were White, 22% Black, 16% Chinese, and 22% Hispanic. The 1414 (53.4%) women were 59.8 (9.4) years old with a similar race distribution. Despite similar rates of change in DC and YEM, predictors of changes in distensibility markers differed by sex. In men, Chinese (p=0.002) and Black (p=0.003) race/ethnicity, systolic blood pressure (p=0.012), and diabetes mellitus (p=0.05) were associated with more rapidly decreasing DC (accelerated stiffening). Starting antihypertensive medication was associated with improved DC (p=0.03); stopping anti-hypertensives was associated with more rapid stiffening (increased YEM, p=0.05). In women, higher education was associated with slower stiffening (DC p=0.041; YEM p<0.001) as was use of lipid-lowering medication (p=0.03), whereas baseline use of antihypertensive medications (YEM p=0.01) and systolic blood pressure (DC p=0.02; p=0.04) predicted increasing stiffening in women. Conclusions Longitudinal changes in carotid artery stiffness are associated with systolic blood pressure and antihypertensive therapy in both sexes; however, race/ethnicity (in men) and level of education (in women) may have different contributions between the sexes. PMID:25477347

  9. [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. PMID:27284844

  10. [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.

  11. Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring.

    PubMed

    Li, Yan; Wang, Ji-Guang; Dolan, Eamon; Gao, Ping-Jin; Guo, Hui-Feng; Nawrot, Tim; Stanton, Alice V; Zhu, Ding-Liang; O'Brien, Eoin; Staessen, Jan A

    2006-03-01

    We hypothesized that 1 minus the slope of diastolic on systolic pressure during 24-hour ambulatory monitoring (ambulatory arterial stiffness index [AASI]) might reflect arterial stiffness. We compared AASI with established measures of arterial stiffness and studied its distribution in Chinese and European populations. We used 90207 SpaceLabs monitors and the SphygmoCor device to measure AASI, central and peripheral pulse pressures, the central (CAIx) and peripheral (PAIx) systolic augmentation indexes, and aortic pulse wave velocity. In 166 volunteers, the correlation coefficient between AASI and pulse wave velocity was 0.51 (P<0.0001). In 348 randomly recruited Chinese subjects, AASI correlated (P<0.0001) with CAIx (r=0.48), PAIx (r=0.50), and central pulse pressure (r=0.50). AASI increased with age and mean arterial pressure but decreased with body height. Both before and after adjustment for arterial wave reflections by considering height and heart rate as covariates, AASI correlated more (P<0.0001) closely with CAIx and PAIx than 24-hour pulse pressure. Among normotensive subjects, the 95th percentile of AASI was 0.55 in Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of AASI in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In conclusion, AASI is a new index of arterial stiffness that can be easily measured under ambulatory conditions. Pending additional validation in outcome studies, normal values of AASI are probably <0.50 and 0.70 in young and older subjects, respectively. PMID:16432048

  12. 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

  13. Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness.

    PubMed

    Nguy, Lisa; Johansson, Maria E; Grimberg, Elisabeth; Lundgren, Jaana; Teerlink, Tom; Carlström, Mattias; Lundberg, Jon O; Nilsson, Holger; Guron, Gregor

    2013-05-01

    Rats with adenine-induced chronic renal failure (A-CRF) develop metabolic and cardiovascular abnormalities resembling those in patients with chronic kidney disease. The aim of this study was to investigate the mechanisms of hypertension in this model and to assess aortic stiffness in vivo. Male Sprague-Dawley rats were equipped with radiotelemetry probes for arterial pressure recordings and received either chow containing adenine or normal control diet. At 7 to 11 wk after study start, blood pressure responses to high NaCl (4%) diet and different pharmacological interventions were analyzed. Aortic pulse wave velocity was measured under isoflurane anesthesia. Baseline 24-h mean arterial pressure (MAP) was 101 ± 10 and 119 ± 9 mmHg in controls and A-CRF animals, respectively (P < 0.01). After 5 days of a high-NaCl diet, MAP had increased by 24 ± 6 mmHg in A-CRF animals vs. 2 ± 1 mmHg in controls (P < 0.001). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (-12 ± 3 vs. -5 ± 5 mmHg, P < 0.05). Aortic pulse wave velocity was elevated in A-CRF rats (5.10 ± 0.51 vs. 4.58 ± 0.17 m/s, P < 0.05). Plasma levels of creatinine were markedly elevated in A-CRF animals (259 ± 46 vs. 31 ± 2 μM, P < 0.001), whereas plasma renin activity was suppressed (0.6 ± 0.5 vs. 12.3 ± 7.3 μg·l(-1)·h(-1), P < 0.001). In conclusion, hypertension in A-CRF animals is characterized by low plasma renin activity and is aggravated by high-NaCl diet, suggesting a pathogenic role for sodium retention and hypervolemia probably secondary to renal insufficiency. Additionally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic pulse wave velocity.

  14. 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

  15. 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

  16. 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

  17. A Novel Echocardiographic Method for Assessing Arterial Stiffness in Obstructive Sleep Apnea Syndrome

    PubMed Central

    Akyol, Aytac; Cakmak, Huseyin Altug; Gunbatar, Hulya; Asker, Muntecep; Babat, Naci; Tosu, Aydin Rodi; Yaman, Mehmet; Gumrukcuoglu, Hasan Ali

    2015-01-01

    Background and Objectives Obstructive sleep apnea syndrome (OSAS) is associated with increased arterial stiffness and cardiovascular complications. The objective of this study was to assess whether the color M-mode-derived propagation velocity of the descending thoracic aorta (aortic velocity propagation, AVP) was an echocardiographic marker for arterial stiffness in OSAS. Subjects and Methods The study population included 116 patients with OSAS and 90 age and gender-matched control subjects. The patients with OSAS were categorized according to their apnea hypopnea index (AHI) as follows: mild to moderate degree (AHI 5-30) and severe degree (AHI≥30). Aortofemoral pulse wave velocity (PWV), carotid intima-media thickness (CIMT), brachial artery flow-mediated dilatation (FMD), and AVP were measured to assess arterial stiffness. Results AVP and FMD were significantly decreased in patients with OSAS compared to controls (p<0.001). PWV and CIMT were increased in the OSAS group compared to controls (p<0.001). Moreover, AVP and FMD were significantly decreased in the severe OSAS group compared to the mild to moderate OSAS group (p<0.001). PWV and CIMT were significantly increased in the severe group compared to the mild to moderate group (p<0.001). AVP was significantly positively correlated with FMD (r=0.564, p<0.001). However, it was found to be significantly inversely related to PWV (r=-0.580, p<0.001) and CIMT (r=-0.251, p<0.001). Conclusion The measurement of AVP is a novel and practical echocardiographic method, which may be used to identify arterial stiffness in OSAS. PMID:26617653

  18. 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

  19. Glycated Albumin is Independently Associated With Arterial Stiffness in Non-Diabetic Chronic Kidney Disease Patients

    PubMed Central

    Choi, Hoon Young; Park, Seung Kyo; Yun, Gi Young; Choi, Ah Ran; Lee, Jung Eun; Ha, Sung Kyu; Park, Hyeong Cheon

    2016-01-01

    Abstract Glycated albumin (GA) exhibits atherogenic effects and increased serum GA levels are associated with the development of cardiovascular complications in diabetic patients. GA production also increases with aging, oxidative stress, and renal dysfunction. We performed this study to further ascertain the association between GA and arterial stiffness in nondiabetic chronic kidney disease (CKD) patients. We enrolled 129 nondiabetic CKD patients. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) using a volume plethysmographic instrument along with simultaneous measurements of GA. Insulin resistance was determined with the homeostatic model assessment. The estimated glomerular filtration rate was calculated using serum creatinine and cystatin C according to the CKD-EPI Creatinine-Cystatin C equation adjusted for age, sex, and race (eGFRcr-cys). Nondiabetic CKD patients with arterial stiffness (baPWV ≥1400 cm/s) showed higher GA levels than those without arterial stiffness (14.2 [8.7–20.2]% vs 13.0 [8.8–18.9]%, P = 0.004). In the subgroup analysis, the patients who had both a higher GA level and a lower eGFRcr-cys, showed the highest baPWV compared with patients with a higher GA or a lower GFR alone. By Spearman's correlation analysis, GA correlated significantly with baPWV (r = +0.291, P = 0.001) and fasting serum glucose level (r = +0.191, P = 0.030), whereas The homeostatic model assessment of insulin resistance did not show any significant correlation with baPWV. Systolic blood pressure (r = +0.401 P < 0.001), age (r = +0.574, P < 0.001), high-density lipoprotein (HDL)-cholesterol level (r = −0.317, P < 0.001), and eGFRcr-cys (r = −0.285, P = 0.002) had a significant correlation with baPWV. According to multivariable logistic regression analysis, higher GA and systolic blood pressure were the independent risk factors affecting arterial stiffness. Our results suggest

  20. 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.

  1. Glycated Albumin is Independently Associated With Arterial Stiffness in Non-Diabetic Chronic Kidney Disease Patients.

    PubMed

    Choi, Hoon Young; Park, Seung Kyo; Yun, Gi Young; Choi, Ah Ran; Lee, Jung Eun; Ha, Sung Kyu; Park, Hyeong Cheon

    2016-04-01

    Glycated albumin (GA) exhibits atherogenic effects and increased serum GA levels are associated with the development of cardiovascular complications in diabetic patients. GA production also increases with aging, oxidative stress, and renal dysfunction. We performed this study to further ascertain the association between GA and arterial stiffness in nondiabetic chronic kidney disease (CKD) patients. We enrolled 129 nondiabetic CKD patients. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) using a volume plethysmographic instrument along with simultaneous measurements of GA. Insulin resistance was determined with the homeostatic model assessment. The estimated glomerular filtration rate was calculated using serum creatinine and cystatin C according to the CKD-EPI Creatinine-Cystatin C equation adjusted for age, sex, and race (eGFRcr-cys). Nondiabetic CKD patients with arterial stiffness (baPWV ≥1400 cm/s) showed higher GA levels than those without arterial stiffness (14.2 [8.7-20.2]% vs 13.0 [8.8-18.9]%, P = 0.004). In the subgroup analysis, the patients who had both a higher GA level and a lower eGFRcr-cys, showed the highest baPWV compared with patients with a higher GA or a lower GFR alone. By Spearman's correlation analysis, GA correlated significantly with baPWV (r = +0.291, P = 0.001) and fasting serum glucose level (r = +0.191, P = 0.030), whereas The homeostatic model assessment of insulin resistance did not show any significant correlation with baPWV. Systolic blood pressure (r = +0.401 P < 0.001), age (r = +0.574, P < 0.001), high-density lipoprotein (HDL)-cholesterol level (r = -0.317, P < 0.001), and eGFRcr-cys (r = -0.285, P = 0.002) had a significant correlation with baPWV. According to multivariable logistic regression analysis, higher GA and systolic blood pressure were the independent risk factors affecting arterial stiffness. Our results suggest that serum GA is a

  2. 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

  3. 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

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

    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.

  4. The Effect of High Dose Cholecalciferol on Arterial Stiffness and Peripheral and Central Blood Pressure in Healthy Humans: A Randomized Controlled Trial

    PubMed Central

    Bressendorff, Iain; Brandi, Lisbet; Schou, Morten; Nygaard, Birgitte; Frandsen, Niels Erik; Rasmussen, Knud; Ødum, Lars; Østergaard, Ove Vyff; Hansen, Ditte

    2016-01-01

    Background Low levels of serum 25-hydroxy vitamin D are associated with increased arterial stiffness and hypertension. Supplementation with vitamin D precursors has been proposed as a treatment option for these conditions. We examined the effect of oral cholecalciferol on arterial stiffness and blood pressure in healthy normotensive adults. Methods 40 healthy adults were randomised in this double-blinded study to either oral cholecalciferol 3000 IU/day or matching placebo and were followed for 16 weeks to examine any effects on pulse wave velocity (PWV), augmentation index (AIx), peripheral and central blood pressure and 24-hour ambulatory blood pressure. Results 22 subjects in the cholecalciferol arm and 18 subjects in the placebo arm completed the 16 weeks of follow-up. There was no difference in changes in PWV, AIx corrected for heart rate or central or peripheral blood pressure between the two groups. There was no correlation between serum 25-hydroxy vitamin D and any of these parameters. Conclusions Oral cholecalciferol 3000 IU/day does not affect arterial stiffness or blood pressure after 16 weeks of treatment in healthy normotensive adults. Trial Registration ClinicalTrials.gov NCT00952562 PMID:27509187

  5. 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

  6. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension.

    PubMed

    Bertero, Thomas; Oldham, William M; Cottrill, Katherine A; Pisano, Sabrina; Vanderpool, Rebecca R; Yu, Qiujun; Zhao, Jingsi; Tai, Yiyin; Tang, Ying; Zhang, Ying-Yi; Rehman, Sofiya; Sugahara, Masataka; Qi, Zhi; Gorcsan, John; Vargas, Sara O; Saggar, Rajan; Saggar, Rajeev; Wallace, W Dean; Ross, David J; Haley, Kathleen J; Waxman, Aaron B; Parikh, Victoria N; De Marco, Teresa; Hsue, Priscilla Y; Morris, Alison; Simon, Marc A; Norris, Karen A; Gaggioli, Cedric; Loscalzo, Joseph; Fessel, Joshua; Chan, Stephen Y

    2016-09-01

    Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus-infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ-GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH.

  7. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension.

    PubMed

    Bertero, Thomas; Oldham, William M; Cottrill, Katherine A; Pisano, Sabrina; Vanderpool, Rebecca R; Yu, Qiujun; Zhao, Jingsi; Tai, Yiyin; Tang, Ying; Zhang, Ying-Yi; Rehman, Sofiya; Sugahara, Masataka; Qi, Zhi; Gorcsan, John; Vargas, Sara O; Saggar, Rajan; Saggar, Rajeev; Wallace, W Dean; Ross, David J; Haley, Kathleen J; Waxman, Aaron B; Parikh, Victoria N; De Marco, Teresa; Hsue, Priscilla Y; Morris, Alison; Simon, Marc A; Norris, Karen A; Gaggioli, Cedric; Loscalzo, Joseph; Fessel, Joshua; Chan, Stephen Y

    2016-09-01

    Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus-infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ-GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH. PMID:27548520

  8. 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.

  9. Right Ventricular Dysfunction in Systemic Sclerosis Associated Pulmonary Arterial Hypertension

    PubMed Central

    Tedford, Ryan J.; Mudd, James O.; Girgis, Reda E.; Mathai, Stephen C.; Zaiman, Ari L.; Housten-Harris, Traci; Boyce, Danielle; Kelemen, Benjamin W.; Bacher, Anita C.; Shah, Ami A.; Hummers, Laura K.; Wigley, Fredrick M.; Russell, Stuart D.; Saggar, Rajeev; Saggar, Rajan; Maughan, W. Lowell; Hassoun, Paul M.; Kass, David A.

    2013-01-01

    Background Systemic sclerosis associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared to idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often due to right ventricular (RV) failure. We tested if SScPAH or systemic sclerosis related pulmonary hypertension with interstitial lung disease (SSc-ILD-PH) imposes a greater pulmonary vascular load than IPAH and/or leads to worse RV contractile function. Methods and Results We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 SSc-ILD-PH, 67 IPAH). An inverse relation between pulmonary resistance (RPA) and compliance (CPA) was similar for all three groups, with a near constant resistance × compliance product. RV pressure-volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7) as well as SSc without PH (SSc-no-PH, n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of right ventricular load (arterial elastance [Ea]), and RV-pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (RPA=7.0±4.5 vs. 7.9±4.3 Wood units; Ea=0.9±0.4 vs. 1.2±0.5 mmHg/mL; CPA=2.4±1.5 vs. 1.7±1.1 mL/mmHg; p>0.3 for each). Though SScPAH did not have greater vascular stiffening compared to IPAH, RV contractility was more depressed (Ees=0.8±0.3 vs. 2.3±1.1, p<0.01; Msw=21±11 vs. 45±16, p=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 vs. 2.1±1.0, p=.03). This ratio was higher in SSc-no-PH (Ees/Ea = 2.3±1.2, p=0.02 vs. SScPAH). Conclusions RV dysfunction is worse in SScPAH compared to IPAH at similar afterload, and may be due to intrinsic systolic function rather than enhanced pulmonary vascular resistive and/or pulsatile loading. PMID:23797369

  10. Pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction in dogs.

    PubMed

    Stepien, Rebecca L

    2009-09-01

    Pulmonary arterial hypertension is a description of a physiological finding rather than a diagnosis. Pulmonary arterial pressure is the result of interactions among pulmonary blood flow (right ventricular cardiac output), pulmonary vascular impedance and post-capillary pressure (typically reflecting left atrial pressure). When elevations in pulmonary arterial pressure (systolic/diastolic pulmonary arterial pressure > approximately 30/19 mmHg at rest) are accompanied by increased left atrial pressure, pulmonary arterial hypertension may be considered secondary to left-heart failure. Introduction of Doppler methods to diagnose pulmonary arterial hypertension has increased the awareness of the prevalence and importance of pulmonary arterial hypertension dogs with left-heart failure. Increasing understanding of the mechanism of development of pulmonary venous hypertension and reactive pulmonary arterial hypertension in dogs with left-heart disease has led to the development of successful additive therapies for progressive clinical signs in the setting of chronic therapy for congestive heart failure due to left-sided valvular and myocardial dysfunction. Because effective therapies for pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction are now available, screening for pulmonary arterial hypertension should be a regular part of the Doppler echocardiographic examination in a clinical setting of chronic therapy for left-sided congestive heart failure due to valvular or myocardial disease.

  11. Pulse Wave Analysis by Applanation Tonometry for the Measurement of Arterial Stiffness

    PubMed Central

    Doupis, John; Papanas, Nikolaos; Cohen, Alison; McFarlan, Lyndsay; Horton, Edward

    2016-01-01

    The aim of our study was to investigate the association between pulse wave velocity (PWV) and pulse wave analysis (PWA)-derived measurements for the evaluation of arterial stiffness. A total of 20 (7 male and 13 female) healthy, non-smoking individuals, with mean age 31 ± 12years were included. PWV and PWA measurements were performed using a SphygmoCor apparatus (Atcor Medical Blood Pressure Analysis System, Sydney Australia). PWV significantly correlated with all central aortic haemodynamic parameters, especially with pulse pressure (PP) (p < 0.0001), augmentation index corrected for 75 pulses/min (AI75) (p = 0.035) and augmentation pressure (AP) (p = 0.005). Male subjects presented significantly higher PWV compared with females (p = 0.03), while there were no differences in PP, AP and AI75. In conclusion, PWA is strongly correlated with PWV as a method for the evaluation of arterial stiffness.

  12. Pulse Wave Analysis by Applanation Tonometry for the Measurement of Arterial Stiffness.

    PubMed

    Doupis, John; Papanas, Nikolaos; Cohen, Alison; McFarlan, Lyndsay; Horton, Edward

    2016-01-01

    The aim of our study was to investigate the association between pulse wave velocity (PWV) and pulse wave analysis (PWA)-derived measurements for the evaluation of arterial stiffness. A total of 20 (7 male and 13 female) healthy, non-smoking individuals, with mean age 31 ± 12years were included. PWV and PWA measurements were performed using a SphygmoCor apparatus (Atcor Medical Blood Pressure Analysis System, Sydney Australia). PWV significantly correlated with all central aortic haemodynamic parameters, especially with pulse pressure (PP) (p < 0.0001), augmentation index corrected for 75 pulses/min (AI75) (p = 0.035) and augmentation pressure (AP) (p = 0.005). Male subjects presented significantly higher PWV compared with females (p = 0.03), while there were no differences in PP, AP and AI75. In conclusion, PWA is strongly correlated with PWV as a method for the evaluation of arterial stiffness. PMID:27651842

  13. Pulse Wave Analysis by Applanation Tonometry for the Measurement of Arterial Stiffness

    PubMed Central

    Doupis, John; Papanas, Nikolaos; Cohen, Alison; McFarlan, Lyndsay; Horton, Edward

    2016-01-01

    The aim of our study was to investigate the association between pulse wave velocity (PWV) and pulse wave analysis (PWA)-derived measurements for the evaluation of arterial stiffness. A total of 20 (7 male and 13 female) healthy, non-smoking individuals, with mean age 31 ± 12years were included. PWV and PWA measurements were performed using a SphygmoCor apparatus (Atcor Medical Blood Pressure Analysis System, Sydney Australia). PWV significantly correlated with all central aortic haemodynamic parameters, especially with pulse pressure (PP) (p < 0.0001), augmentation index corrected for 75 pulses/min (AI75) (p = 0.035) and augmentation pressure (AP) (p = 0.005). Male subjects presented significantly higher PWV compared with females (p = 0.03), while there were no differences in PP, AP and AI75. In conclusion, PWA is strongly correlated with PWV as a method for the evaluation of arterial stiffness. PMID:27651842

  14. Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

    PubMed

    Langleben, D; Szarek, J L; Coflesky, J T; Jones, R C; Reid, L M; Evans, J N

    1988-11-01

    Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model. PMID:3145283

  15. Arterial stiffness after glucose ingestion in exercise-trained versus untrained men.

    PubMed

    Kobayashi, Ryota; Yoshida, Shou; Okamoto, Takanobu

    2015-11-01

    Postprandial hyperglycemia increases arterial stiffness. Arterial stiffness and insulin resistance are lower in exercise-trained humans than in untrained humans. However, the effect of exercise on arterial stiffness after glucose ingestion in young adults remains unknown. The present study investigates the effect of regular aerobic exercise on arterial stiffness after glucose ingestion in young males. Ten exercise-trained males (age, 20.8 ± 0.2 years; ETR) and 9 healthy untrained males (age, 22.2 ± 0.7 years; UTR) participated in this study. Carotid-femoral (aortic) pulse wave velocity (PWV), femoral-ankle (leg) PWV, carotid augmentation index (AIx) (applanation tonometry), brachial and ankle blood pressure (BP), heart rate (oscillometric device and electrocardiography), and blood glucose (glucose oxidase method) were measured at 30 min before (baseline) and 30, 60, and 120 min after a 75-g oral glucose tolerance test. Leg PWV at 30 min after glucose ingestion was significantly higher (P < 0.01) in the UTR group than in the ETR group. Ankle systolic BP at 30 min after glucose ingestion was also significantly higher in the UTR group than in the ETR group (P < 0.05). Blood glucose increased from baseline at 30 min (P < 0.01) and 60 min (P < 0.05) after glucose ingestion in both groups. Aortic PWV, carotid AIx, and brachial systolic BP did not change from baseline after glucose ingestion in both groups. The present findings indicate that leg PWV and ankle systolic BP after glucose ingestion were significantly lower in the ETR group than in the UTR group. PMID:26444929

  16. Effects of Allopurinol on Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Deng, Gang; Qiu, Zhandong; Li, Dayong; Fang, Yu; Zhang, Suming

    2016-01-01

    Background Several studies have tested the effects of allopurinol on arterial stiffness, but the results have been inconclusive. We aimed to conduct a meta-analysis to investigate the impacts of allopurinol treatment on arterial stiffness, as measured by pulse wave velocity (PWV) and augmentation index (AIx). Material/Methods Randomized controlled trials (RCTs) assessing the effects of allopurinol on arterial stiffness were identified through searching PubMed, Web of Science, EMBASE, the Cochrane Library for Central Register of Clinical Trials, and China National Knowledge Infrastructure up to December 2015. The primary endpoints were the change of PWV and AIx after allopurinol treatment. The weighted mean difference (WMD) or standardized mean difference (SMD) and the 95% confidence interval (CI) of each study were pooled for meta-analysis. Results A total of 11 RCTs met the inclusion criteria and were included in the final meta-analysis. Eight RCTs with 1,111 patients were pooled for PWV; eight RCTs with 397 patients were pooled for PWV. Allopurinol administration did not significantly change PWV (WMD=−0.19 m/s, 95% CI: −0.49 to 0.12, Z=1.21, p=0.23), but significantly reduced AIx (SMD=−0.34, 95% CI: −0.54 to −0.14, Z=3.35, p=0.0008). Conclusions Although our meta-analysis showed some favorable effects of allopurinol treatment on improving AIx, its impact on arterial stiffness must be tested in more large-scale RCTs. PMID:27110924

  17. Longitudinal perspective on the conundrum of central arterial stiffness, blood pressure, and aging.

    PubMed

    Scuteri, Angelo; Morrell, Christopher H; Orrù, Marco; Strait, James B; Tarasov, Kirill V; Ferreli, Liana Anna Pina; Loi, Francesco; Pilia, Maria Grazia; Delitala, Alessandro; Spurgeon, Harold; Najjar, Samer S; AlGhatrif, Majd; Lakatta, Edward G

    2014-12-01

    The age-associated increase in arterial stiffness has long been considered to parallel or to cause the age-associated increase in blood pressure (BP). Yet, the rates at which pulse wave velocity (PWV), a measure of arterial stiffness, and BP trajectories change over time within individuals who differ by age and sex have not been assessed and compared. This study determined the evolution of BP and aortic PWV trajectories during a 9.4-year follow-up in >4000 community-dwelling men and women of 20 to 100 years of age at entry into the SardiNIA Study. Linear mixed effects model analyses revealed that PWV accelerates with time during the observation period, at about the same rate over the entire age range in both men and women. In men, the longitudinal rate at which BP changed over time, however, did not generally parallel that of PWV acceleration: at ages>40 years the rates of change in systolic BP (SBP) and pulse pressure (PP) increase plateaued and then declined so that SBP, itself, also declined at older ages, whereas PP plateaued. In women, SBP, diastolic BP, and mean BP increased at constant rates across all ages, producing an increasing rate of increase in PP. Therefore, increased aortic stiffness is implicated in the age-associated increase in SBP and PP. These findings indicate that PWV is not a surrogate for BP and that arterial properties other than arterial wall stiffness that vary by age and sex also modulate the BP trajectories during aging and lead to the dissociation of PWV, PP, and SBP trajectories in men.

  18. Arterial stiffness after glucose ingestion in exercise-trained versus untrained men.

    PubMed

    Kobayashi, Ryota; Yoshida, Shou; Okamoto, Takanobu

    2015-11-01

    Postprandial hyperglycemia increases arterial stiffness. Arterial stiffness and insulin resistance are lower in exercise-trained humans than in untrained humans. However, the effect of exercise on arterial stiffness after glucose ingestion in young adults remains unknown. The present study investigates the effect of regular aerobic exercise on arterial stiffness after glucose ingestion in young males. Ten exercise-trained males (age, 20.8 ± 0.2 years; ETR) and 9 healthy untrained males (age, 22.2 ± 0.7 years; UTR) participated in this study. Carotid-femoral (aortic) pulse wave velocity (PWV), femoral-ankle (leg) PWV, carotid augmentation index (AIx) (applanation tonometry), brachial and ankle blood pressure (BP), heart rate (oscillometric device and electrocardiography), and blood glucose (glucose oxidase method) were measured at 30 min before (baseline) and 30, 60, and 120 min after a 75-g oral glucose tolerance test. Leg PWV at 30 min after glucose ingestion was significantly higher (P < 0.01) in the UTR group than in the ETR group. Ankle systolic BP at 30 min after glucose ingestion was also significantly higher in the UTR group than in the ETR group (P < 0.05). Blood glucose increased from baseline at 30 min (P < 0.01) and 60 min (P < 0.05) after glucose ingestion in both groups. Aortic PWV, carotid AIx, and brachial systolic BP did not change from baseline after glucose ingestion in both groups. The present findings indicate that leg PWV and ankle systolic BP after glucose ingestion were significantly lower in the ETR group than in the UTR group.

  19. Differences in arterial stiffness at rest and after acute exercise between young men and women.

    PubMed

    Doonan, Robert J; Mutter, Andrew; Egiziano, Giordano; Gomez, Yessica-Haydee; Daskalopoulou, Stella S

    2013-03-01

    There is controversy as to whether there are sex differences in arterial stiffness. Acute physical stress can elicit vascular abnormalities not present at rest. Our objective was to assess sex differences in arterial stiffness at rest and in response to acute physical stress. Healthy young men (n=67) and women (n=55) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest and 2, 5, 10 and 15 min following an exercise test to exhaustion. At rest, aortic systolic, diastolic, pulse and mean pressures were all significantly higher in men as was aortic pulse pressure at 10 and 15 min post exercise and aortic systolic pressure at 15 min. Carotid-femoral pulse wave velocity was significantly higher in men (6.0±0.7 m s(-1) vs. 5.6±0.6 m s(-1), P=0.03) at rest and at all time points post exercise. Heart rate-adjusted augmentation index was significantly lower (-10.7±10.2% vs. -4.0±10.9, P<0.0001) and subendocardial viability ratio was significantly higher (176.2±43.8% vs. 163.4±40.9, P=0.04) in men at rest. To our knowledge, this is the first study to assess sex differences in the arterial stiffness response to acute physical stress in young men and women. Although we were not able to elicit differences in vascular function after adjustment, which were not present at rest, we found that young men and women exhibit differences in arterial stiffness at rest and after acute physical stress.

  20. Arterial hypertension and cardiovascular risk in HIV-infected patients.

    PubMed

    Calò, Lorenzo A; Caielli, Paola; Maiolino, Giuseppe; Rossi, Gianpaolo

    2013-08-01

    The dramatic change of the natural history of HIV-infected patients by highly active antiretroviral therapy (HAART) has exposed these patients to cardiovascular risk, including cardiovascular disease and hypertension. In HIV-infected patients, the development of arterial hypertension, at least in the medium-long term is an established feature, although recognized predictors of its development have not been clearly identified. In addition, conflicting data regarding the influence of antiretroviral therapy (ART) are reported. The presence of a proinflammatory state and oxidative stress-mediated endothelial dysfunction seem, however, to play a pathophysiologic role. In this review, we examine and provide a comprehensive, literature based, consideration of the pathophysiologic aspects of hypertension in these patients. HIV-infected patients, independently of the presence of hypertension, remain at very high cardiovascular risk due to the presence of the same cardiovascular risk factors recognized for the general population with, in addition, the indirect influence of the ART, essentially via its effect on lipid metabolism. This review based on the evidence from the literature, concludes that the management of HIV-infected patients in terms of cardiovascular prevention emerges as a priority. The consideration of cardiovascular risk in these patients should receive the same emphasis given for the general population at high cardiovascular risk, including adequate blood pressure control according to international guidelines.

  1. Arterial Stiffening Provides Sufficient Explanation for Primary Hypertension

    PubMed Central

    Pettersen, Klas H.; Bugenhagen, Scott M.; Nauman, Javaid; Beard, Daniel A.; Omholt, Stig W.

    2014-01-01

    Hypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Its etiology remains enigmatic despite intense research efforts over many decades. By use of empirically well-constrained computer models describing the coupled function of the baroreceptor reflex and mechanics of the circulatory system, we demonstrate quantitatively that arterial stiffening seems sufficient to explain age-related emergence of hypertension. Specifically, the empirically observed chronic changes in pulse pressure with age and the impaired capacity of hypertensive individuals to regulate short-term changes in blood pressure arise as emergent properties of the integrated system. The results are consistent with available experimental data from chemical and surgical manipulation of the cardio-vascular system. In contrast to widely held opinions, the results suggest that primary hypertension can be attributed to a mechanogenic etiology without challenging current conceptions of renal and sympathetic nervous system function. PMID:24853828

  2. 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

  3. 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

  4. Biomarkers and prognostic indicators in pulmonary arterial hypertension.

    PubMed

    Jardim, Carlos; Souza, Rogerio

    2015-06-01

    Our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) has increased substantially in the past decades. More accurate diagnosis and increased options for treatment have given researchers the opportunity to better explore the response to medical therapy and prognosis. As a result, the use of biomarkers and prognostic indicators for this devastating disease has been widely investigated. Biomarkers and prognostic indicators have also been more frequently incorporated into the design of new clinical trials. This approach has helped the pulmonary hypertension (PH) community step forward in the search for effective treatments for PAH. However, no single biomarker has shown significant superiority in predicting prognosis or patient response and an integrative approach is necessary to understand which combination of markers should be used in each of the clinical scenarios that characterize the management of PAH.

  5. [Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology].

    PubMed

    Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

    2014-10-01

    Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the uderlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. (J Am Coll Cardiol 2013;62:D22-33) a 2013 by the American College of Cardiology Foundation).

  6. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology.

    PubMed

    Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

    2013-12-24

    Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation.

  7. Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women

    PubMed Central

    Meditz, Amie; Deane, Kevin D.; Kohrt, Wendy M.

    2012-01-01

    The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH4), a critical cofactor for endothelial nitric oxide synthase to produce nitric oxide, would increase vascular endothelial-dependent vasodilatory tone and decrease arterial stiffness in estrogen-deficient postmenopausal women. Additionally, we examined whether the beneficial effects of estrogen on vascular function were possibly related to BH4. Arterial stiffness (carotid artery compliance) and endothelial-dependent vasodilation [brachial artery flow-mediated dilation (FMD)] were measured in postmenopausal (n = 24; 57 ± 1 yr, mean ± SE) and eumenorrheic premenopausal (n = 9; 33 ± 2 yr) women before and 3 h after the oral administration of BH4. Subsequently, in postmenopausal women, vascular testing (before and after BH4) was repeated following randomization to either 2 days of transdermal estradiol or placebo. Baseline carotid artery compliance and brachial artery FMD were lower in postmenopausal than in premenopausal women (P < 0.0001). BH4 administration increased carotid artery compliance (0.61 ± 0.05 to 0.73 ± 0.04 mm2·mmHg−1·10−1 vs. baseline, P < 0.0001) and brachial artery FMD (P < 0.001) in postmenopausal women but had no effect in premenopausal women (P = 0.62). Carotid artery compliance (0.59 ± 0.05 to 0.78 ± 0.06 mm2·mmHg−1·10−1, P < 0.001) and FMD increased in postmenopausal women in response to estradiol (P = 0.02) but were not further improved with the coadministration of BH4, possibly because estrogen increased BH4 bioavailability. Carotid artery compliance and FMD increased with BH4 in the placebo group (P = 0.02). Although speculative, these results suggest that reduced vascular BH4 may be an important contributor to arterial stiffening in estrogen-deficient postmenopausal women, related in part to reduced endothelial-dependent vasodilatory tone. PMID:22245769

  8. Non-dipping blood pressure patterns and arterial stiffness parameters in patients with Behcet's disease.

    PubMed

    Celik, Gulperi; Yilmaz, Sema; Ergulu Esmen, Serpil

    2015-12-01

    Behcet's disease is a multisystemic vasculitis involving veins and arteries of various sizes. Non-dipping status, augmentation index and pulse wave velocity are important determinants of cardiovascular mortality and morbidity. We investigated the non-dipping status and arterial stiffness in patients with Behcet's disease. In this cross-sectional study, we examined the vascular parameters of 96 patients with Behcet's disease (53% female) and 60 age- and sex-matched control subjects. The non-dipping status and arterial distensibility were assessed using a Mobil-O-Graph Arteriograph, an automatic oscillometric device. In total, 65.6% of 96 patients were systolic non-dippers, and 34.4% exhibited high augmentation indices. Ten percent of the control subjects were systolic non-dippers, and 11.7% exhibited high augmentation indices. Nocturnal decreases in systolic blood pressure correlated with central systolic blood pressure and diastolic blood pressure, as well as nocturnal decreases in diastolic blood pressure. Furthermore, non-dipper patients with Behcet's disease exhibited higher nocturnal cardiac outputs than did dipper patients with Behcet's disease. Augmentation index correlated negatively with C-reactive protein and correlated positively with both 24 h and nocturnal peripheral resistance, as well as 24 h pulse wave velocity. The patients with high augmentation indices exhibited lower creatinine clearance, as well as lower nocturnal cardiac outputs, higher 24 h peripheral resistance and higher 24 h pulse wave velocities. Non-dipping status and arterial stiffness may exacerbate the harmful cardiovascular effects of the other. In addition to conventional risk factors, non-dipping status and arterial stiffness should be examined during the follow-up evaluations of patients with Behcet's disease.

  9. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension.

    PubMed

    Limoges, Maude; Langleben, David; Fox, Benjamin D; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G; Hirsch, Andrew M; Schlesinger, Robert D; Lesenko, Lyda

    2016-09-01

    It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615

  10. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Spikes, L; Williamson, T; Satterwhite, L

    2014-06-01

    Macitentan is a novel, dual endothelin receptor antagonist recently approved for the treatment of WHO Group I pulmonary arterial hypertension. Its pharmacologic mechanism of action as well as the pharmacokinetics, pharmacodynamics and potential drug-drug interactions have been demonstrated in multiple phase I and II trials. The pivotal randomized, placebo-controlled, event-driven clinical trial revealed a significant reduction in morbidity. The most common adverse events were rarely clinically significant, nor did they result in a high rate of discontinuation. Of note, macitentan is contraindicated in pregnant women due to embryo-fetal toxicity.

  11. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension

    PubMed Central

    Langleben, David; Fox, Benjamin D.; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G.; Hirsch, Andrew M.; Schlesinger, Robert D.; Lesenko, Lyda

    2016-01-01

    Abstract It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615

  12. 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. PMID:27598071

  13. Pulmonary arterial hypertension associated with neurofibromatosis type 1.

    PubMed

    Carrascosa, Miguel F; Larroque, Isabel Celemín; Rivero, Juan-Luis García; García, José-Antonio Saiz-Quevedo; Hoz, Marta Cano; Ares, Miguel Ares; López, Xabier Arrastio; Caviedes, José-Ramón Salcines

    2010-01-01

    The authors report a case of severe pulmonary arterial hypertension (PAH) in a 75-year-old woman who had received a diagnosis of neurofibromatosis type 1 (NF1) 23 years before. She presented with progressive dyspnoea and recurrent syncope. Even though the patient initially improved after starting supportive and specific treatment for PAH, she then deteriorated and died from respiratory failure 11 months after the diagnosis of PAH. Prompt recognition of such an unusual association between PAH and NF1 and appropriate therapeutic intervention could ameliorate quality of life and prolong survival in this patient population. PMID:22798089

  14. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension

    PubMed Central

    Langleben, David; Fox, Benjamin D.; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G.; Hirsch, Andrew M.; Schlesinger, Robert D.; Lesenko, Lyda

    2016-01-01

    Abstract It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease.

  15. Depression in pulmonary arterial hypertension: An undertreated comorbidity

    PubMed Central

    Verma, Sameer; Sahni, Sonu; Vijayan, Vannan K; Talwar, Arunabh

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a debilitating condition leading to progressive decline in functional capacity. As a result, PAH can lead to psychological impairment that can impact the overall disease status. The medical community has developed several screening questionnaires in order to assess depression in their patients allowing physicians to be at the forefront of recognizing clinical depression. There is a suggestion that depression symptomatology is more prevalent in the PAH population. The aim of this article is to review the current thought process about diagnosis and management of depression in PAH patients. PMID:26933309

  16. Cardiac Autonomic Drive during Arterial Hypertension and Metabolic Disturbances.

    PubMed

    Kseneva, S I; Borodulina, E V; Trifonova, O Yu; Udut, V V

    2016-06-01

    ANS support of the cardiac work was assessed with analysis of heart rate variability in representative samples of patients with arterial hypertension and metabolic disturbances manifested by overweight, classes I-II obesity, compromised glucose tolerance, and type II diabetes. Initially enhanced sympathetic effects on the heart rate demonstrated no further increase during the orthostatic test in contrast to suprasegmentary influences enhanced by this test. The pronouncedness of revealed peculiarities in ANS drive to the heart correlated with metabolic disturbances, and these peculiarities attained maximum in patients with type II diabetes. PMID:27383176

  17. 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

  18. 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

  19. Relation of pulse pressure and arterial stiffness to concentric left ventricular hypertrophy in young men (from the Bogalusa Heart Study).

    PubMed

    Toprak, Ahmet; Reddy, Jagadeesh; Chen, Wei; Srinivasan, Sathanur; Berenson, Gerald

    2009-04-01

    Differences in geometric adaptation of the left ventricle and associated cardiovascular risk may reflect the differential effects of classic risk factors and arterial stiffness on the left ventricle. In the present study, the influence of cardiovascular risk factors and arterial stiffness indexes on left ventricular (LV) geometry types were studied in a large community-based cohort of young adults. As part of the Bogalusa Heart Study, echocardiographic examinations of the heart were performed on 786 black and white adults (age range 24 to 43 years, average 36; 42% men, 70% white). Arterial stiffness indexes of the study cohort included aorta-femoral pulse wave velocity, carotid artery elastic modulus, and arterial compliance using tonometry. Pulse pressure in young adults with concentric LV hypertrophy (47 +/- 11 mm Hg) was significantly higher than in those with eccentric LV hypertrophy (40 +/- 8 mm Hg) and normal geometry (37 +/- 7 mm Hg). Multinomial logistic regression analysis showed that widened pulse pressure, the presence of diabetes mellitus, and increased body mass index were associated with concentric LV hypertrophy compared with normal geometry. Similarly, higher Peterson's and Young's elastic modulus of the carotid arteries and lower large- and small-artery compliance, in addition to increased body mass index, diabetes mellitus, and black race, were associated with concentric LV hypertrophy in young adults. In conclusion these data suggested that concentric LV hypertrophy was associated with widened pulse pressure, increased arterial stiffness, and decreased arterial compliance in young adults.

  20. Severe pulmonary arterial hypertension due to Angiostrongylosus vasorum in a dog.

    PubMed

    Nicolle, Audrey P; Chetboul, Valérie; Tessier-Vetzel, Dominique; Carlos Sampedrano, Carolina; Aletti, Edouard; Pouchelon, Jean-Louis

    2006-08-01

    A dog was presented with a history of dyspnea, coughing, and ascites. Angiostrongylosis and severe pulmonary arterial hypertension (PAH) were found, as well as a marked discordance between the electrical and mechanical events of the heart. Pulmonary arterial hypertension related to Angiostrongylus vasorum has rarely been reported.

  1. Role of oxidized lipids in pulmonary arterial hypertension.

    PubMed

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

    2016-09-01

    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

  2. Role of oxidized lipids in pulmonary arterial hypertension.

    PubMed

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

    2016-09-01

    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.

  3. 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

  4. 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.

  5. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    PubMed

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed; Erzurum, Serpil C; Aldred, Micheala A

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  6. Pulmonary arterial hypertension: a comparison between children and adults.

    PubMed

    Barst, R J; Ertel, S I; Beghetti, M; Ivy, D D

    2011-03-01

    The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).

  7. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension

    PubMed Central

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  8. 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.

  9. Arterial stiffness and wave reflections in patients with sickle cell disease.

    PubMed

    Lemogoum, Daniel; Van Bortel, Luc; Najem, Boutaina; Dzudie, Anasthase; Teutcha, Charles; Madu, Ernest; Leeman, Marc; Degaute, Jean-Paul; van de Borne, Philippe

    2004-12-01

    We tested the hypothesis that lower blood pressure and increased vasodilatation reported in sickle cell disease (SCD) patients with hemoglobin SS genotype (SS) are translated by lower arterial stiffness determined by pulse wave velocity (PWV) and wave reflections assessed by augmentation index (AI). We enrolled 20 SS (8 females; 12 male) patients closely matched for age, gender, height, and body mass index to 20 subjects with hemoglobin AA genotype (AA). Carotid-femoral PWV (PWV(CF)) and carotid-radial PWV (PWV(CR)) were recorded with the Complior device. Aortic AI was derived from pressure wave analysis (SphygmocoR). PWV(CF) and PWV(CR) were lower in SS than in AA (4.5+/-0.7 m/s versus 6.9+/-0.9 m/s, P<0.0001 and 6.6+/-1.2 m/s versus 9.5+/-1.4 m/s, P<0.0001, respectively). AI was lower in SS than in AA (2+/-14% versus 11+/-8%, P=0.02). Multivariate analysis revealed that both PWV(CF) and PWV(CR) were negatively associated with hemoglobin SS type and positively related to mean arterial pressure (MAP), whereas AI was positively associated with MAP and total cholesterol (all P<0.0001). Multivariate analysis restricted to SS indicated a positive association between PWV(CF) and PWV(CR) with age but a negative association with MAP (R2=0.57 and 0.51, respectively, both P<0.001), whereas MAP and heart rate were independently associated with AI (R2=0.65, P<0.001). This study provides the first evidence that SCD is associated with both lower arterial stiffness and wave reflections. SS patients have a paradoxical negative association between PWV and MAP, suggesting that low MAP does not protect them against arterial stiffness impairment.

  10. Arterial hypertension: which targets in over-75-year people?

    PubMed

    Mureddu, Gian Francesco

    2016-01-01

    Arterial hypertension has always been considered the main risk factor in cardiovascular prevention. However, the goals of anti-hypertensive treatment (targets) in the elderly has long been under discussion. The results of the studies in favor of the hypothesis "the lower the better" than those that argue against the existence of the phenomenon of the J-curve, that is, the hypothesis according to which mortality increases to too low pressure values lower than 115/75 mmHg, are still controversial. However, in elderly patients the association between blood pressure lowering and increased cardiovascular events seems to depend on the general health status, that means the presence of comorbidity, frailty and / or disability. Recent data from the SPRINT study show that the benefit of an intensive blood pressure target (SBP <120 mmHg) compared to a usual target (SBP <140 mmHg), appears to be greater in the oldest hypertensive patients (≥75 years). The cardio-geriatric functional assessment can provide useful information to better stratify the elderly and to define more accurately the pressure targets, the choice is individual. PMID:27374038

  11. Arterial lesions and hypertension induced by saline, unilateral nephrectomy, and deoxycorticosterone in spontaneously hypertensive SHR rats.

    PubMed

    Wexler, B C

    1979-07-01

    Male and female, 100 days old, spontaneously hypertensive rats (SHR) were divided into two major groups: intact and uninephrectomized, given either no treatment, 1p.100 saline drinking water, 1p.100 saline + Deoxycorticosterone (DOC), or DOC alone. The DOC (Percorten pivalate) was given subcutaneously 2 times weekly, at a dose level of 2 mg/rat for 8 weeks. At autopsy, the combination of DOC + saline caused: the greatest exacerbation of blood pressure, marked catabolism, adrenal hypertrophy and thymic involution, little increase in heart weight, but a marked increase in kidney weight, elevated triglyceride and free fatty acids, cerebral and myocardial necrosis, fibrinous hyalinization of the cerebral, coronary, mesenteric, renal, testicular and ovarian arteries, foci of aortic cartilaginous metaplasia, PAN, foci of hepatic necrosis, and extensive lipid depletion from the zonae glomerulosa. Circulating corticosterone levels were suppressed to below normal levels. Excursion of circulating CPK levels coincided with the finding of myocardial necrosis and cerebral damage. It is suggested that the genetically-mediated hypertension of SHR is programmed through abnormal activity of the hypothalamic-pituitary axis and the specific morphologic make-up of arterial lesions is dependent upon the variety of adrenal or gonadal steroids secreted and their conditioning effect on the arterial wall.

  12. Arterial Stiffness Is Increased in Patients With Type 1 Diabetes Without Cardiovascular Disease

    PubMed Central

    Llauradó, Gemma; Ceperuelo-Mallafré, Victòria; Vilardell, Carme; Simó, Rafael; Freixenet, Núria; Vendrell, Joan; González-Clemente, José Miguel

    2012-01-01

    OBJECTIVE To investigate the relationship between arterial stiffness and low-grade inflammation in subjects with type 1 diabetes without clinical cardiovascular disease. RESEARCH DESIGN AND METHODS Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFαR1 and sTNFαR2, respectively) were measured. All statistical analyses were stratified by sex. RESULTS Subjects with diabetes had a higher aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001; women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after adjusting for cardiovascular risk factors. Men with diabetes had higher concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P = 0.002), sTNFαR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFαR2 (2,774 vs. 2,060 pg/mL; P < 0.001). Women with diabetes only had higher concentrations of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008), whereas in women with diabetes no significant correlation was found. In men, multiple linear regression analysis showed that the following variables were associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade inflammation (R2 = 0.543). In women, these variables were age, BMI, mean arterial pressure, and type 1 diabetes (R2 = 0.550). CONCLUSIONS Arterial stiffness assessed as aPWV is increased in patients with type 1 diabetes without clinical cardiovascular disease, independently of classical cardiovascular risk factors. In men with type 1 diabetes, low-grade inflammation is independently associated with arterial stiffness. PMID:22357186

  13. [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.

  14. [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. PMID:27172721

  15. [Role of arterial hypertension in the cardiac involvement of acromegaly].

    PubMed

    Morvan, D; Komajda, M; Grimaldi, A; Turpin, G; Grosgogeat, Y

    1990-09-01

    Cardiac disease is common in acromegaly. Several mechanisms have been implicated: hypertension, coronary artery disease, valvular heart disease, endocrinopathies including "acromegalic cardiomyopathy". Fifteen consecutive patients with acromegaly, aged 48 +/- 13 years and treated for 4 +/- 5 years, underwent Doppler echocardiography. The patients had no cardiovascular symptoms: 6 had hypertension for 10 +/- 7 years and were compared with a group of 10 control subjects of the same age (48 +/- 17 years). The myocardial mass index (MMI) was higher in acromegaly (110 +/- 32 vs 82 +/- 12 g/m2, p = 0.02), left ventricular enddiastolic dimensions where comparable (48 +/- 7 vs 48 +/- 5 mm, NS) fractional shortening was slightly greater (0.37 +/- 0.04 vs 0.34 +/- 0.04, p = 0.07) as was velocity of shortening (NS) and the ratio of systolic time intervals (NS). The mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 ms; p less than 0.02); the ratio of the amplitudes of the E and A waves was a little decreased and the isovolumic relaxation phase was increased (92 +/- 13 vs 69 +/- 16 ms; p less than 0.01). Hypertensives (N = 6) had higher MMI (133 +/- 27 vs 94 +/- 24 g/m2, p = 0.02). Normotensive patients had larger isovolumic relaxation periods than control subjects (90 +/- 11 vs 69 +/- 16 ms, p less than 0.05). These results show that in the infraclinical phase, the heart in acromegaly is hypertrophied, not dilated. Hypertension plays a significant role in the development of this hypertrophy. Left ventricular systolic function is normal but diastolic function is impaired.

  16. 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.

  17. 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. PMID:26084306

  18. ARTERIAL STIFFNESS AND INFLUENCES OF THE METABOLIC SYNDROME: A CROSS-COUNTRIES STUDY

    PubMed Central

    Scuteri, Angelo; Cunha, Pedro Guimaraes; Cucca, Francesco; Cockcroft, John; Raso, Francesco U Mattace; Muiesan, Maria Lorenza; Ryliškytė, Ligita; Rietzschel, Ernst; Strait, James; Vlachopoulos, Charalambos; Laurent, Stephane; Nilsson, Peter M; Lakatta, Edward G

    2015-01-01

    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% (4,985 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). PMID:24561493

  19. Causal estimation of neural and overall baroreflex sensitivity in relation to carotid artery stiffness.

    PubMed

    Lipponen, Jukka A; Tarvainen, Mika P; Laitinen, Tomi; Karjalainen, Pasi A; Vanninen, Joonas; Koponen, Timo; Laitinen, Tiina M

    2013-12-01

    Continuous electrocardiogram, blood pressure and carotid artery ultrasound video were analyzed from 15 diabetics and 28 healthy controls. By using these measurements artery elasticity, overall baroreflex sensitivity (BRS) assessed between RR and systolic blood pressure variation, and neural BRS assessed between RR and artery diameter variation were estimated. In addition, BRS was estimated using traditional and causal methods which enable separation of feedforward and feedback variation. The aim of this study was to analyze overall and neural BRS in relation to artery stiffness and to validate the causal BRS estimation method in assessing these two types of BRS within the study population. The most significant difference between the healthy and diabetic groups (p < 0.0007) was found for the overall BRS estimated using the causal method. The difference between the groups was also significant for neural BRS (p < 0.0018). However neural BRS was normal in some old diabetics, which indicates normal functioning of autonomic nervous system (ANS), even though the elasticity in arteries of these subjects was reduced. The noncausal method overestimated neural BRS in low BRS values when compared to causal BRS. In conclusion, neural BRS estimated using the causal method is proposed as the best marker of ANS functioning. PMID:24168896

  20. 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

  1. Effects of smoking cessation on central blood pressure and arterial stiffness

    PubMed Central

    Takami, Takeshi; Saito, Yoshihiko

    2011-01-01

    Purpose: Smoking affects arterial stiffness, thus causing an elevation in central blood pressure (CBP). The present study was designed to examine whether smoking cessation treatment improved CBP and arterial stiffness. Patients and methods: We conducted an observational study of 70 patients receiving smoking cessation treatment. Before and 60 weeks after the start of a 12-week varenicline treatment, we measured brachial blood pressure, CBP, brachial-ankle pulse wave velocity (baPWV), normalized radial augmentation index (rAIx@75), left ventricular weight, and left ventricular diastolic function of each patient. The data were compared between the patients who succeeded in quitting smoking (smoking cessation group; n = 37) and those who failed to quit smoking (smoking group; n = 33). Results: Baseline characteristics were similar in both groups. Brachial blood pressure remained unchanged in both groups. CBP, baPWV, and rAIx@75 decreased significantly in the smoking cessation group, while these parameters showed no significant change in the smoking group. Thus, CBP, baPWV, and rAIx@75 showed greater decrease in the smoking cessation group than in the smoking group (CBP, −7.1 ± 1.4 mmHg vs 1.2 ± 2.7 mmHg; P < 0.01; baPWV, −204 ± 64 cm/s vs −43 ± 72 cm/s; P < 0.01; rAIx@75, −6.4 ± 2.8% vs −1.0 ± 3.9%; P < 0.01). Left ventricular weight and left ventricular diastolic function remained unchanged in both groups. Conclusion: Patients in the smoking cessation group showed significant improvement in CBP, baPWV, and rAIx@75. These results indicate that smoking cessation can improve arterial stiffness and CBP. PMID:22102787

  2. 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.

  3. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Reusser, Mark; Stenmark, Kurt R; Hunter, Kendall S; Qi, H Jerry; Shandas, Robin

    2011-11-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics. PMID:21856906

  4. Liver and spleen stiffness and other noninvasive methods to assess portal hypertension in cirrhotic patients: a review of the literature.

    PubMed

    Colecchia, Antonio; Marasco, Giovanni; Taddia, Martina; Montrone, Lucia; Eusebi, Leonardo H; Mandolesi, Daniele; Schiumerini, Ramona; Di Biase, Anna R; Festi, Davide

    2015-09-01

    Portal hypertension (PH) is one of the most important causes of morbidity and mortality in patients with chronic liver disease. PH measurement is crucial to stage and predict the clinical outcome of liver cirrhosis. Measurement of hepatic vein pressure gradient is considered the gold standard for assessment of the degree of PH; however, it is an invasive method and has not been used widely. Thus, noninvasive methods have been proposed recently. We critically evaluated serum markers, abdominal ultrasonography, and particularly liver and spleen stiffness measurement, which represent the more promising methods to stage PH degree and to assess the presence/absence of esophageal varices (EV). A literature search was carried out on MEDLINE, EMBASE, Web of Science, and Scopus for articles and abstracts. The search terms used included 'liver cirrhosis', 'portal hypertension', 'liver stiffness', 'spleen stiffness', 'ultrasonography', and 'portal hypertension serum biomarker'. The articles cited were selected on the basis of their relevance to the objective of the review. The results of available studies indicate that individually, these methods have a mild accuracy in predicting the presence of EV, and thus they cannot substitute endoscopy to predict EV. When these tests were used in combination, their accuracy increased. In addition to the PH staging, several serum markers and spleen stiffness measurement can predict the clinical outcome of liver cirrhosis with a good accuracy, comparable to that of hepatic vein pressure gradient. In the future, noninvasive methods could be used to select patients requiring further investigations to identify the best tailored clinical management.

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

    PubMed

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

    2016-02-01

    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 CyA therapy, time on

  6. Versican accumulates in vascular lesions in pulmonary arterial hypertension.

    PubMed

    Chang, Ya-Ting; 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

    2016-09-01

    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 [(35)S]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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists.

  12. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    DuBrock, Hilary M; Channick, Richard N

    2014-08-01

    Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of symptomatic pulmonary arterial hypertension (PAH). Compared to other endothelin receptor antagonists, in vitro and in vivo studies have demonstrated that macitentan has improved tissue targeting, a longer duration of action and an improved safety profile. Macitentan is available as a once daily oral medication and has been well tolerated in clinical trials. The recently published Study with an Endothelin Receptor Antagonist in PAH to Improve cliNical Outcomes (SERAPHIN), which was the first event-driven trial ever done in PAH, also demonstrated the benefit of macitentan on reducing the likelihood of a composite endpoint of morbidity and mortality events without a significant difference in mortality.

  13. Macitentan (Opsumit) for the treatment of pulmonary arterial hypertension.

    PubMed

    Clarke, Megan; Walter, Claire; Agarwal, Richa; Kanwar, Manreet; Benza, Raymond L

    2014-07-01

    The endothelin pathway is a key pathway for the pathogenesis of pulmonary arterial hypertension (PAH). Antagonism of this pathway is recommended as initial therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and inflammation caused by endothelin. Prior to October 2013, ambrisentan, a selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were the only currently available agents for PAH targeting the endothelin pathway. Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit®), a new ETA/ETB antagonist, has been US FDA approved to delay disease progression and reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event-driven strategy with a composite primary end point of morbidity or mortality. Previous trials have focused on short-term outcomes, such as improved 6-min walk distance and WHO functional class.

  14. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH.

  15. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH. PMID:27421214

  16. Novel Strategies in the Treatment of Pulmonary Arterial Hypertension.

    PubMed

    Madonna, Rosalinda; Cocco, Nino

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by increased pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and remodeling of pulmonary microcirculation during PAH. In responders patients, classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo-controlled trials have shown that ERAs improves haemodynamic parameters of the pulmonary circulation, functional capacity and clinical outcome in patients affected by PAH. Here, we will review the definition, classification and pathophysiology of PH. Furthermore, we will provide an up-to-date overview of currently recommended diagnostic and therapeutic work-up in PAH. PMID:26201488

  17. New trial designs and potential therapies for pulmonary artery hypertension.

    PubMed

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2013-12-24

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH.

  18. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists. PMID:27159936

  19. Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

    PubMed

    Tantawy, Azza A G; Adly, Amira A M; Ismail, Eman A R; Habeeb, Nevin M

    2013-06-01

    Heart disease is the leading cause of mortality and morbidity in β-thalassemia major (β-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young β-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 μg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

  20. The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults.

    PubMed

    Melo, Xavier; Fernhall, Bo; Santos, Diana A; Pinto, Rita; Pimenta, Nuno M; Sardinha, Luís B; Santa-Clara, Helena

    2016-03-01

    This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index α and β (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 ± 0.38 years) and 45 young adults (25.22 ± 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; η(2) = 0.394) increased more in adults after exercise (p < 0.05). Compliance (η(2) = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index α and β. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (η(2) = 0.115) but apparently only in those with small MAP changes (η(2) = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults. PMID:26842667

  1. Arterial stiffness and blood flow adaptations following eight weeks of resistance exercise training in young and older women.

    PubMed

    Rossow, Lindy M; Fahs, Christopher A; Thiebaud, Robert S; Loenneke, Jeremy P; Kim, Daeyeol; Mouser, James G; Shore, Erin A; Beck, Travis W; Bemben, Debra A; Bemben, Michael G

    2014-05-01

    Resistance training is recommended for all adults of both sexes. The arterial stiffness and limb blood flow responses to resistance training in young and older women have not been well-studied. The purpose of this study was to examine arterial stiffness and blood flow adaptations to high-intensity resistance exercise training in young and older women. Young (aged 18-25) and older (aged 50-64) women performed full-body high-intensity resistance exercise three times per week for eight weeks. The following measurements were performed twice prior to training and once following training: carotid to femoral and femoral to tibialis posterior pulse wave velocity (PWV), blood pressure, heart rate, resting forearm blood flow and forearm reactive hyperemia. Data was analyzed by ANOVAs with alpha set at 0.05. Correlations were also examined between changes in arterial stiffness and baseline arterial stiffness values. Older subjects had higher carotid-femoral PWV than younger subjects. No significant effects were found for femoral-tibialis posterior PWV or for resting forearm blood flow. Changes in carotid-femoral and femoral-tibialis posterior PWV correlated significantly with their respective baseline values. Older subjects increased peak forearm blood flow while young subjects showed no change. Total hyperemia increased significantly in both groups. In conclusion, in both young and older women, eight weeks of high-intensity resistance training appeared to improve microvascular forearm function while not changing carotid-femoral or femoral-tibialis posterior arterial stiffness. However, a large degree of individual variation was found and arterial stiffness adaptations appeared positively related to the initial stiffness values. PMID:24566193

  2. Associations of Triiodothyronine Levels with Carotid Atherosclerosis and Arterial Stiffness in Hemodialysis Patients

    PubMed Central

    Kircelli, Fatih; Asci, Gulay; Carrero, Juan Jesus; Gungor, Ozkan; Demirci, Meltem Sezis; Ozbek, Suha Sureyya; Ceylan, Naim; Ozkahya, Mehmet; Toz, Huseyin; Ok, Ercan

    2011-01-01

    Summary Background and objectives End-stage renal disease is linked to alterations in thyroid hormone levels and/or metabolism, resulting in a high prevalence of subclinical hypothyroidism and low triiodothyronine (T3) levels. These alterations are involved in endothelial damage, cardiac abnormalities, and inflammation, but the exact mechanisms are unclear. In this study, we investigated the relationship between serum free-T3 (fT3) and carotid artery atherosclerosis, arterial stiffness, and vascular calcification in prevalent patients on conventional hemodialysis. Design, setting, participants, & measurements 137 patients were included. Thyroid-hormone levels were determined by chemiluminescent immunoassay, carotid artery–intima media thickness (CA-IMT) by Doppler ultrasonography, carotid-femoral pulse wave velocity (c-f PWV), and augmentation index by Sphygmocor device, and coronary artery calcification (CAC) scores by multi-slice computerized tomography. Results Mean fT3 level was 3.70 ± 1.23 pmol/L. Across decreasing fT3 tertiles, c-f PWV and CA-IMT values were incrementally higher, whereas CACs were not different. In adjusted ordinal logistic regression analysis, fT3 level (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97), age, and interdialytic weight gain were significantly associated with CA-IMT. fT3 level was associated with c-f PWV in nondiabetics but not in diabetics. In nondiabetics (n = 113), c-f PWV was positively associated with age and systolic BP but negatively with fT3 levels (odds ratio = 0.57, 95% confidence interval 0.39 to 0.83). Conclusions fT3 levels are inversely associated with carotid atherosclerosis but not with CAC in hemodialysis patients. Also, fT3 levels are inversely associated with surrogates of arterial stiffness in nondiabetics. PMID:21836150

  3. 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.

  4. 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

  5. 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).

  6. [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.

  7. 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

  8. An international physician survey of pulmonary arterial hypertension management.

    PubMed

    Preston, Ioana R; Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H; Lang, Irene

    2016-09-01

    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.

  9. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension

    PubMed Central

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  10. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension.

    PubMed

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  11. 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.

  12. An international physician survey of pulmonary arterial hypertension management.

    PubMed

    Preston, Ioana R; Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H; Lang, Irene

    2016-09-01

    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

  13. [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. PMID:27303586

  14. [Drug therapy of pulmonary arterial hypertension in 2014].

    PubMed

    Aschermann, Michael; Jansa, Pavel

    2014-04-01

    Pulmonary arterial hypertension (PAH) is a primary pulmonary arteriolar disease, characterized by a progressive increase in pulmonary vascular resistance and pressure in the pulmonary circulation. It progressively leads to hypertrophy of the right ventricle and with no treatment to its failure and patient´s death. Etiology of pulmonary hypertension (PH) has been reclassified repeatedly, most recently during the 4th World Symposium on Pulmonary Hypertension held in 2008 [1]. Currently, the first group contains PAH with either unknown or known cause (systemic connective tissue disease, liver disease, congenital heart disease, HIV infection, abuse of anorexic agents). Current drug therapy of PAH is divided into conventional (anticoagulant therapy, calcium channel blockers, therapy of chronic heart failure) and specific (prostanoids, endothelium receptor antagonists, phosphodiesterase 5 inhibitors). Patients with positive vasodilator test are indicated for the high doses treatment of calcium channel blockers. Patients with negative vasodilator test are indicated for chronic anticoagulant therapy and specific drug therapy either as mono-therapy, or as combined therapy. Recent years have brought a wide range of new treatments modalities, especially in the field of pharmacotherapy. In addition, other treatment modalities have been tested, for example application of stem cells. Drugs in research include several groups: 1. vasodilators: fasudil, adrenonedullin, activators and stimulators of guanylate cyclase, vasoactive intestinal peptide (VIP); 2. Anti-inflammatory agents: inhibitor of elastase, antagonist of B cells, immunosuppressive agents, inhibitor of HDAC1; 3. agents affecting metabolism: nitrites, PPAR antagonists, antioxidants, serotonin receptor antagonist and serotonin transporter blockers, statins, inhibitors of Rho-kinase; 4. apoptosis inductors of smooth muscle cells: tyrosine-kinase inhibitors, elastase inhibitors; 5. agents influencing vascular regeneration

  15. 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.

  16. Increased aortic stiffness and related factors in patients with peripheral arterial disease.

    PubMed

    Catalano, Mariella; Scandale, Giovanni; Carzaniga, Gianni; Cinquini, Michela; Minola, Marzio; Dimitrov, Gabriel; Carotta, Maria

    2013-10-01

    A number of conditions have been associated with functional changes of large arteries. The aim of this study was to evaluate the factors associated with aortic stiffness in patients with peripheral arterial disease (PAD). The authors studied 86 patients with PAD (ankle-brachial pressure index [ABPI] ≤0.9) and 86 controls. Aortic stiffness was determined by pulse wave velocity (aPWV) using applanation tonometry. In PAD patients, aPWV was higher compared with controls (11 ± 3 vs 9.8 ± 1.8; P=.002). In multiple regression analysis, aPWV was independently associated with pulse pressure (β=0.05, P=.01) in the PAD patients and with age in the control group (β=0.08, P=.0005). The results of this study confirm an aPWV increase in patients with PAD and emphasize the association between blood pressure and aPWV. Further studies are necessary to assess whether higher aortic stiffening adds prognostic value to ABPI, which is the most powerful prognostic indicator in PAD. PMID:24088278

  17. Different Contributions of Physical Activity on Arterial Stiffness between Diabetics and Non-Diabetics

    PubMed Central

    Ando, Jiro; Watanabe, Masafumi; Murasawa, Takahide; Komuro, Issei

    2016-01-01

    Background We compared the contribution of physical activity to the change in arterial stiffness between patients with and without diabetes in ischemic heart disease. Methods We studied 96 (diabetes) and 109 (without diabetes) patients with ischemic heart disease treated by percutaneous coronary intervention (PCI). Arterial stiffness was assessed by cardio-ankle vascular index (CAVI) at the first diagnosis of significant coronary ischemia and 6 months after PCI and optimal medical therapy. Physical activity was evaluated using the long form of the International Physical Activity Questionnaire (IPAQ). Results CAVI values increased more for diabetic patients than for non-diabetic. The IPAQ scores did not differ between the two groups. During follow-up, CAVI values did not significantly change in either group. In diabetic patients, the CAVI score for 48 patients did not change (NC-group) and 48 patients improved (Improved-group). Physical activity scores were 937.9 ± 923.2 and 1524.6 ± 1166.2 in the NC- and Improved-groups, respectively. IPAQ scores and uric acid levels significantly affect CAVI improvement after adjusting for age, sex, baseline CAVI, total cholesterol, and estimated glomerular filtration rate. Conclusion Determining factors influencing CAVI improvement during follow-up were significantly different between patients with and without diabetes. IPAQ scores and uric acid levels were significantly correlated with CAVI changes. PMID:27508936

  18. 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

  19. Arterial stiffness, endothelial function and microcirculatory reactivity in healthy young males.

    PubMed

    Wright, C I; Scholten, H J; Schilder, J C M; Elsen, B M; Hanselaar, W; Kroner, C I; Draijer, R; Kastelein, J J P; Stok, W; Karemaker, J; de Groot, E

    2008-09-01

    Large (C1) and small (C2) arterial stiffness has been suggested to parallel endothelial reactivity and has led researchers to suggest parameters of arterial stiffness may be alternative measures to brachial sonographic assessments of flow-mediated dilatation (FMD). However, past studies comparing these measures can be criticized. In addition to %FMD responses, we recorded concurrent hyperaemic responses of the microcirculation and both were compared with C1 and C2. Twenty-nine subjects 18-30 years of age were investigated. Radial blood pressure was recorded with a tonometer. Pulse waveform analysis was performed to calculate C1 and C2. These were compared with %FMD responses and responses of finger flux measured by laser Doppler fluxmetry (LDF); pulsatile finger volume measured by photoplethysmography (PPG); and palm skin temperature measured by infrared thermography (Tpalm) (i.e. microcirculatory responses). Responses were determined as % changes from control. We only found weak relationships between C1 and %FMD (r=0.4, P=0.04); C2 and %PPG (r=0.38, P=0.07); and C2 and %LDFdorsal (r=-0.38; P=0.04). Responses of %FMD weakly parallel those of C1. Neither C2 nor C1 are viable indicators of endothelial or microcirculatory reactivity (i.e. hyperaemic or venous constriction) in healthy, resting young males. These findings refute the claims that C1 and C2 are substitute measures to sonographic assessments of brachial FMD. PMID:18445071

  20. 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. PMID:6839814

  1. The limits of oral therapy in pulmonary arterial hypertension management

    PubMed Central

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  2. 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

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

    PubMed

    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

  4. 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

  5. Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension.

    PubMed

    Igarashi, Ataru; Inoue, Sachie; Ishii, Tomonori; Tsutani, Kiichiro; Watanabe, Hiroshi

    2016-07-27

    Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC. PMID:27385603

  6. Drug-induced pulmonary arterial hypertension: a recent outbreak.

    PubMed

    Montani, David; Seferian, Andrei; Savale, Laurent; Simonneau, Gérald; Humbert, Marc

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH. PMID:23997051

  7. The limits of oral therapy in pulmonary arterial hypertension management.

    PubMed

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  8. Imatinib in pulmonary arterial hypertension: c-Kit inhibition.

    PubMed

    Farha, Samar; Dweik, Raed; Rahaghi, Franck; Benza, Raymond; Hassoun, Paul; Frantz, Robert; Torres, Fernando; Quinn, Deborah A; Comhair, Suzy; Erzurum, Serpil; Asosingh, Kewal

    2014-09-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterized by severe remodeling of the pulmonary artery resulting in increased pulmonary artery pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow-derived progenitor cells play a critical role in vascular homeostasis and have been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit(+) hematopoietic progenitors and mast cells has been noted in the remodeled vessels in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. As a corollary to the phase 3 study using imatinib in PAH, blood samples were collected from 12 patients prior to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight were randomized to imatinib and 4 to placebo. Circulating c-Kit(+) and CD34(+)CD133(+) hematopoietic progenitors as well as biomarkers of mast cell numbers and activation were measured. Circulating CD34(+)CD133(+) and c-Kit(+) progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib therapy (all P < 0.05). In addition, total tryptase, a marker of mast cell load, dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a potential mechanism of action of imatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy. PMID:25621158

  9. Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

    PubMed Central

    Chitalia, Nihil; Ismail, Tuan; Tooth, Laura; Boa, Frances; Hampson, Geeta; Goldsmith, David; Kaski, Juan Carlos; Banerjee, Debasish

    2014-01-01

    Background Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results Clinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration ClinicalTrials.gov NCT02005718 PMID:24646518

  10. Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension.

    PubMed

    Sakao, Seiichiro; Voelkel, Norbert F; Tanabe, Nobuhiro; Tatsumi, Koichiro

    2015-01-01

    Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

  11. Is epistaxis associated with arterial hypertension? A systematic review of the literature.

    PubMed

    Kikidis, D; Tsioufis, K; Papanikolaou, V; Zerva, K; Hantzakos, A

    2014-02-01

    Both epistaxis and hypertension are frequent problems in the adult population. The relationship between the level of arterial pressure and incidence of epistaxis in a patient with hypertension is a question that appears frequently in the clinical practice. A systematic review of the literature regarding the relation of arterial hypertension with epistaxis was performed through MEDLINE and EMBASE. All studies, whether examining the correlation of arterial pressure at presentation of a patient with nasal bleeding or the repercussion of episodes of epistaxis in hypertensive patients, were included in this review. Studies were evaluated independently by two reviewers according to a standard evaluation form. Overall, nine studies fulfilled our inclusion criteria. Five of them were single-group (patient) studies, while the remaining four included a control group. In eight studies, the patient group included patients with epistaxis, while one focused on hypertensive patients. Six out of nine studies agree that arterial pressure is higher at the time of epistaxis, as compared to the control group or to the general population. Seven out of nine studies conclude that there is cross-correlation between arterial pressure and the actual incident of epistaxis. The presence of high arterial blood pressure during the actual episode of nasal bleeding cannot establish a causative relationship with epistaxis, because of confounding stress and possible white coat phenomenon, but may lead to initial diagnosis of an already installed arterial hypertension.

  12. The role of pulse transit time as an index of arterial stiffness during exercise.

    PubMed

    Kounalakis, S N; Geladas, N D

    2009-09-01

    The aim of the present study was to investigate, whether pulse transit time (PTT), a popular index of arterial stiffness at rest, can be also used as such, during steady state exercise. For this purpose, twelve male volunteers exercised on a cycle ergometer for 70 min on three separate occasions whereas, cycling cadence and workload were manipulated in order to produce diverse cardiorespiratory responses. PTT, blood pressure, cardiac output and respiratory frequency were measured during exercise. Resistance to systole and total peripheral resistance were calculated by the ratio of systolic pressure, and mean arterial pressure over cardiac output, respectively. All subjects across all conditions, showed a negative linear correlation (P < 0.01) between changes in PTT and systolic pressure (SP) (r = -0.66), changes in cardiac output (r = -0.76), and respiratory frequency (r = -0.40), whereas PTT was positively correlated (P < 0.05) with total peripheral resistance (r = 0.31), the SP to cardiac output ratio (r = 0.30) and plasma volume changes (r = 0.29). However, forward stepwise multiple regression analysis revealed that 71% (P < 0.001) of PTT changes from rest (DeltaPTT) variability was attributed to changes in cardiac output, SP and SP to cardiac output ratio. In the same model, total peripheral resistance did not exert significant influence on DeltaPTT variability. In conclusion, PTT is a reflection not only of SP but also of cardiac output changes per se and in combination with cardiac output (SP to cardiac output ratio) and should not be used as a pure marker of arterial stiffness under marked exercise cardiovascular and respiratory perturbations.

  13. Determinants of the ambulatory arterial stiffness index in 7604 subjects from 6 populations.

    PubMed

    Adiyaman, Ahmet; Dechering, Dirk G; Boggia, José; Li, Yan; Hansen, Tine W; Kikuya, Masahiro; Björklund-Bodegård, Kristina; Richart, Tom; Thijs, Lutgarde; Torp-Pedersen, Christian; Ohkubo, Takayoshi; Dolan, Eamon; Imai, Yutaka; Sandoya, Edgardo; Ibsen, Hans; Wang, Jiguang; Lind, Lars; O'Brien, Eoin; Thien, Theo; Staessen, Jan A

    2008-12-01

    The ambulatory arterial stiffness index (AASI) is derived from 24-hour ambulatory blood pressure recordings. We investigated whether the goodness-of-fit of the AASI regression line in individual subjects (r(2)) impacts on the association of AASI with established determinants of the relation between diastolic and systolic blood pressures. We constructed the International Database on the Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (7604 participants from 6 countries). AASI was unity minus the regression slope of diastolic on systolic blood pressure in individual 24-hour ambulatory recordings. AASI correlated positively with age and 24-hour mean arterial pressure and negatively with body height and 24-hour heart rate. The single correlation coefficients and the mutually adjusted partial regression coefficients of AASI with age, height, 24-hour mean pressure, and 24-hour heart rate increased from the lowest to the highest quartile of r(2). These findings were consistent in dippers and nondippers (night:day ratio of systolic pressure >or=0.90), women and men, and in Europeans, Asians, and South Americans. The cumulative z score for the association of AASI with these determinants of the relation between diastolic and systolic blood pressures increased curvilinearly with r(2), with most of the improvement in the association occurring above the 20th percentile of r(2) (0.36). In conclusion, a better fit of the AASI regression line enhances the statistical power of analyses involving AASI as marker of arterial stiffness. An r(2) value of 0.36 might be a threshold in sensitivity analyses to improve the stratification of cardiovascular risk.

  14. Arterial stiffness in kidney transplantation: a single center case-control study comparing belatacept versus calcineurin inhibitor immunosuppressive based regimen.

    PubMed

    Melilli, Edoardo; Bestard-Matamoros, Oriol; Manonelles-Montero, Anna; Sala-Bassa, Neus; Mast, Richard; Grinyó-Boira, Josep M; Cruzado, Josep M

    2015-01-01

    Arterial stiffness is nowadays a well-accepted predictor of cardiovascular mortality in general population; as well as in kidney transplant recipient population. The femoral-carotid pulse wave velocity (cf-PWV) is the widest used method to assess the arterial stiffness. The aim of this study was to test whether CNI-free immunosuppression based on belatacept was associated with lower cf-PWV, as a surrogate marker of arterial stiffness, than CNI. This was a retrospective case-control study. We included all the cases treated with belatacept as a maintenance immunosuppression in our center (n=20). An appropriate control group of patients (n=20) treated with CNI was selected to achieve match for key factors associated with arterial stiffness. After a follow-up of 5 years after transplantation, the Belatacept group had a reduced prevalence of patients with a cf-PWV higher than 8.1m/s (50% in BLC vs. 25% in CNI, p=0.08). At multivariate logistic regression analysis, the risk of high cf-PWV was correlated with age (OR 1.24; p<0.03) and renal resistive index (OR 1.25; p<0.05). Belatacept treatment was associated with a significant reduction in risk of cf-PWV (OR 0.008; P=0.045). Belatacept-based maintenance immunosuppression could improve kidney transplant recipient’s survival by reducing cardiovascular events related to stiffness. PMID:25611834

  15. 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.

  16. 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. PMID:26747504

  17. [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. PMID:12852007

  18. Hagen-Poiseuille's law: The link between cirrhosis, liver stiffness, portal hypertension and hepatic decompensation.

    PubMed

    Lake-Bakaar, Gerond; Ahmed, Muneeb; Evenson, Amy; Bonder, Alan; Faintuch, Salomao; Sundaram, Vinay

    2015-01-27

    The onset of hepatic decompensation in cirrhosis heralds an accelerated downhill course with poor outcome. The sole predictor of this decompensation in cirrhosis is increased hepatic vein to portal vein gradient hepatic venous pressure gradient (HVPG). Surrogate markers of liver function or hepatic reserve appear to be less relevant. The hepatic sinusoids become less elastic and more rigid as liver fibrosis and cirrhosis progress. We propose that the Hagen-Poiseuille's law, which applies to rigid, but not elastic vessels, determines the pressure-flow characteristics in the sinusoids. In the rigid cirrhotic liver, HVPG rises dramatically with any change in net surface area or radius, r(4) of the vasculature that follows surgical resection. This review relates liver stiffness to the risk of decompensation in patients with cirrhosis. The liver has a unique dual blood supply comprising a low pressure portal vein and high pressure hepatic artery. We compare the complexity of autoregulation in the normal elastic liver with that in the rigid cirrhotic liver. Therapeutic modalities to reduce portal pressure may reduce the risk of hepatic decompensation and improve outcomes in cirrhosis.

  19. Hagen-Poiseuille’s law: The link between cirrhosis, liver stiffness, portal hypertension and hepatic decompensation

    PubMed Central

    Lake-Bakaar, Gerond; Ahmed, Muneeb; Evenson, Amy; Bonder, Alan; Faintuch, Salomao; Sundaram, Vinay

    2015-01-01

    The onset of hepatic decompensation in cirrhosis heralds an accelerated downhill course with poor outcome. The sole predictor of this decompensation in cirrhosis is increased hepatic vein to portal vein gradient hepatic venous pressure gradient (HVPG). Surrogate markers of liver function or hepatic reserve appear to be less relevant. The hepatic sinusoids become less elastic and more rigid as liver fibrosis and cirrhosis progress. We propose that the Hagen-Poiseuille’s law, which applies to rigid, but not elastic vessels, determines the pressure-flow characteristics in the sinusoids. In the rigid cirrhotic liver, HVPG rises dramatically with any change in net surface area or radius, r4 of the vasculature that follows surgical resection. This review relates liver stiffness to the risk of decompensation in patients with cirrhosis. The liver has a unique dual blood supply comprising a low pressure portal vein and high pressure hepatic artery. We compare the complexity of autoregulation in the normal elastic liver with that in the rigid cirrhotic liver. Therapeutic modalities to reduce portal pressure may reduce the risk of hepatic decompensation and improve outcomes in cirrhosis. PMID:25624993

  20. 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

  1. Step Monitoring to improve ARTERial health (SMARTER) through step count prescription in type 2 diabetes and hypertension: trial design and methods

    PubMed Central

    2014-01-01

    Background With increasing numbers of type 2 diabetes (DM2) and hypertension patients, there is a pressing need for effective, time-efficient and sustainable strategies to help physicians support their patients to achieve higher physical activity levels. SMARTER will determine whether physician-delivered step count prescriptions reduce arterial stiffness over a one-year period, compared with usual care, in sedentary overweight/obese adults with DM2/hypertension. Design Randomized, allocation-concealed, assessor-blind, multisite clinical trial. The primary outcome is change in arterial stiffness over one year. The secondary outcomes include changes in physical activity, individual vascular risk factors, medication use, and anthropometric parameters. Assessments are at baseline and one year. Methods Participants are sedentary/low active adults with 25 ≤ BMI < 40 kg/m2 followed for DM2/hypertension by a collaborating physician. The active arm uses pedometers to track daily step counts and review logs with their physicians at 3 to 4-month intervals. A written step count prescription is provided at each visit, aiming to increase counts by ≥3,000 steps/day over one year, with an individualized rate increase. The control arm visits physicians at the same frequency and receives advice to engage in physical activity 30-60 minutes/day. SMARTER will enroll 364 individuals to detect a 10 ± 5% difference in arterial stiffness change between arms. Arterial stiffness is assessed noninvasively with carotid femoral pulse wave velocity using applanation tonometry. Discussion The importance of SMARTER lies not simply in the use of pedometer-based monitoring but also on its integration into a prescription-based intervention delivered by the treating physician. Equally important is the measurement of impact of this approach on a summative indicator of arterial health, arterial stiffness. If effectiveness is demonstrated, this strategy has strong potential for widespread

  2. Soluble Guanylate Cyclase: A new therapeutic target for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

    PubMed Central

    Das Gupta, Asish; Bowman, Lindsay; D’Arsigny, Christine L.; Archer, Stephen L.

    2014-01-01

    Nitric oxide (NO) activates soluble guanylate cyclase (sGC) by binding its prosthetic heme group, thereby catalyzing cyclic guanosine monophosphate (cGMP) synthesis. cGMP causes vasodilation and may inhibit smooth muscle cell proliferation and platelet aggregation. The NO-sGC-cGMP pathway is disordered in pulmonary arterial hypertension (PAH), a syndrome in which pulmonary vascular obstruction, inflammation, thrombosis, and constriction ultimately lead to death from right heart failure. Expression of sGC is increased in PAH but its function is reduced by decreased NO bioavailability, sGC oxidation and the related loss of sGC’s heme group. Two classes of sGC modulators offer promise in PAH. sGC stimulators (e.g. riociguat) require heme-containing sGC to catalyze cGMP production, whereas sGC activators (e.g. cinaciguat) activate heme-free sGC. Riociguat is approved for PAH and yields functional and hemodynamic benefits similar to other therapies. Its main serious adverse effect is dose-dependent hypotension Riociguat is also approved for inoperable chronic thromboembolic pulmonary hypertension. PMID:25670386

  3. Information experiences and needs in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

    PubMed

    Ivarsson, Bodil; Ekmehag, Björn; Sjöberg, Trygve

    2014-01-01

    Background. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal, noncurable, but treatable diseases that strongly affect the patients. Objective. To describe patients' experience of information relating to PAH or CTEPH. Methods. A qualitative method using content analysis was applied. Seventeen patients (thirteen women and four men) aged 28-73 years from a regional PAH centre were individually interviewed. Results. Three categories that describe patients' experiences of information emerged: handling of information, struggling with feelings that also affect others, and vulnerability associated with uncertainty. The patients would have welcomed more information to relatives from the healthcare professionals. Shortcomings on communicating a prognosis were experienced. The mediated information and knowledge gave the patients insight into physical or psychosocial problems. Mutual exchange of information between patients and healthcare professionals were marred by different experiences of attitudes, behaviour, and ownership. Conclusions. In the future, healthcare organizations must struggle to achieve a holistic healthcare by making it more person-centred, and they must also promote cooperation between PAH centres and local healthcare providers. It is essential to determine the most appropriate and valuable path of information and communication and, thereby, the most cost-effective management of PAH or CTEPH. PMID:25197567

  4. Copper Dependence of Angioproliferation in Pulmonary Arterial Hypertension in Rats and Humans

    PubMed Central

    Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A.; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C.; Humbert, Marc; Noordegraaf, Anton Vonk; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F.

    2012-01-01

    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. PMID:22162909

  5. 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

  6. Increased Mutagen Sensitivity and DNA Damage in Pulmonary Arterial Hypertension

    PubMed Central

    Federici, Chiara; Drake, Kylie M.; Rigelsky, Christina M.; McNelly, Lauren N.; Meade, Sirena L.; Comhair, Suzy A. A.; Erzurum, Serpil C.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a serious lung condition characterized by vascular remodeling in the precapillary pulmonary arterioles. We and others have demonstrated chromosomal abnormalities and increased DNA damage in PAH lung vascular cells, but their timing and role in disease pathogenesis is unknown. Objectives: We hypothesized that if DNA damage predates PAH, it might be an intrinsic cell property that is present outside the diseased lung. Methods: We measured DNA damage, mutagen sensitivity, and reactive oxygen species (ROS) in lung and blood cells from patients with Group 1 PAH, their relatives, and unrelated control subjects. Measurements and Main Results: Baseline DNA damage was significantly elevated in PAH, both in pulmonary artery endothelial cells (P < 0.05) and peripheral blood mononuclear cells (PBMC) (P < 0.001). Remarkably, PBMC from unaffected relatives showed similar increases, indicating this is not related to PAH treatments. ROS levels were also higher (P < 0.01). DNA damage correlated with ROS production and was suppressed by antioxidants (P < 0.001). PBMC from patients and relatives also showed markedly increased sensitivity to two chemotherapeutic drugs, bleomycin and etoposide (P < 0.001). Results were consistent across idiopathic, heritable, and associated PAH groups. Conclusions: Levels of baseline and mutagen-induced DNA damage are intrinsically higher in PAH cells. Similar results in PBMC from unaffected relatives suggest this may be a genetically determined trait that predates disease onset and may act as a risk factor contributing to lung vascular remodeling following endothelial cell injury. Further studies are required to fully characterize mutagen sensitivity, which could have important implications for clinical management. PMID:25918951

  7. Nitric oxide synthase gene polymorphism (G894T) influences arterial stiffness in adults: The Bogalusa Heart Study.

    PubMed

    Chen, Wei; Srinivasan, Sathanur R; Bond, M Gene; Tang, Rong; Urbina, Elaine M; Li, Shengxu; Boerwinkle, Eric; Berenson, Gerald S

    2004-07-01

    The endothelial nitric oxide synthase (eNOS) gene is known to influence the regulation of blood pressure (BP) levels. However, whether the eNOS gene locus influences arterial stiffness independently of BP is unknown. This study examines the independent effect of the eNOS gene polymorphism (G894T) on arterial stiffness in 118 African American and 285 white young adults, aged 25 to 37 years. Arterial stiffness was measured from M-mode ultrasounds of common carotid artery using Peterson's (Ep) and Young's (YEM) elastic modulus. African Americans displayed a lower frequency of the T allele than did whites (0.131 v 0.321, P <.001). The T allele was associated with lower systolic BP in African Americans (P =.04) but not in whites. African Americans showed significantly higher values of Ep (that is, increased stiffness) than did whites (49.9 kPa vs 45.5 kPa, P =.003), whereas no such difference in ethnicity was found for YEM, a measure of elasticity adjusted for relative wall thickness. After controlling for sex, age, body mass index, insulin, heart rate, and mean arterial pressure, the T allele was associated with significantly lower values of Ep (P =.037) and YEM (P =.068) in African Americans. Although the genotype effect on Ep and YEM was not significant in whites, trends were similar to those in African Americans. In the total sample, including ethnicity as an additional covariate, the G894T genotype was significantly associated with Ep (P =.046) and YEM (P =.035). These results suggest that the allelic variation (G894T) of the eNOS gene or a locus closely linked to it is associated with lower arterial wall stiffness, adjusting for BP levels, in young adults.

  8. 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.

  9. Do arterial stiffness and wave reflection underlie cardiovascular risk in ethnic minorities?

    PubMed Central

    Nanino, Elisa; Mills, Charlotte E; Cruickshank, Kennedy J

    2016-01-01

    Increasing evidence indicates that remarkable differences in cardiovascular risk between ethnic groups cannot be fully explained by traditional risk factors such as hypertension, diabetes or dislipidemia measured in midlife. Therefore, the underlying pathophysiology leading to this “excess risk” in ethnic minority groups is still poorly understood, and one way to address this issue is to shift the focus from “risk” to examine target organs, particularly blood vessels and their arterial properties more directly. In fact, structural and functional changes of the vascular system may be identifiable at very early stages of life when traditional factors are not yet developed. Arterial stiffening, measured as aortic pulse wave velocity, and wave reflection parameters, especially augmentation index, seem to be an important pathophysiological mechanism for the development of cardiovascular disease and predict mortality independent of other risk factors. However, data regarding these arterial indices in ethnic minorities are relatively rare and the heterogeneity between populations, techniques and statistical methods make it difficult to fully understand their role. PMID:27540482

  10. Do arterial stiffness and wave reflection underlie cardiovascular risk in ethnic minorities?

    PubMed

    Faconti, Luca; Nanino, Elisa; Mills, Charlotte E; Cruickshank, Kennedy J

    2016-01-01

    Increasing evidence indicates that remarkable differences in cardiovascular risk between ethnic groups cannot be fully explained by traditional risk factors such as hypertension, diabetes or dislipidemia measured in midlife. Therefore, the underlying pathophysiology leading to this "excess risk" in ethnic minority groups is still poorly understood, and one way to address this issue is to shift the focus from "risk" to examine target organs, particularly blood vessels and their arterial properties more directly. In fact, structural and functional changes of the vascular system may be identifiable at very early stages of life when traditional factors are not yet developed. Arterial stiffening, measured as aortic pulse wave velocity, and wave reflection parameters, especially augmentation index, seem to be an important pathophysiological mechanism for the development of cardiovascular disease and predict mortality independent of other risk factors. However, data regarding these arterial indices in ethnic minorities are relatively rare and the heterogeneity between populations, techniques and statistical methods make it difficult to fully understand their role. PMID:27540482

  11. Do arterial stiffness and wave reflection underlie cardiovascular risk in ethnic minorities?

    PubMed

    Faconti, Luca; Nanino, Elisa; Mills, Charlotte E; Cruickshank, Kennedy J

    2016-01-01

    Increasing evidence indicates that remarkable differences in cardiovascular risk between ethnic groups cannot be fully explained by traditional risk factors such as hypertension, diabetes or dislipidemia measured in midlife. Therefore, the underlying pathophysiology leading to this "excess risk" in ethnic minority groups is still poorly understood, and one way to address this issue is to shift the focus from "risk" to examine target organs, particularly blood vessels and their arterial properties more directly. In fact, structural and functional changes of the vascular system may be identifiable at very early stages of life when traditional factors are not yet developed. Arterial stiffening, measured as aortic pulse wave velocity, and wave reflection parameters, especially augmentation index, seem to be an important pathophysiological mechanism for the development of cardiovascular disease and predict mortality independent of other risk factors. However, data regarding these arterial indices in ethnic minorities are relatively rare and the heterogeneity between populations, techniques and statistical methods make it difficult to fully understand their role.

  12. Alterations in structure of elastic laminae of rat pulmonary arteries in hypoxic hypertension.

    PubMed

    Liu, S Q

    1996-11-01

    The effect of hypoxic hypertension on the remodeling process of the elastic laminae of the rat hilar pulmonary arteries (PAs) was studied by electron microscopy. Rats were exposed to hypoxia (10% O2) for periods of 0.5, 2,6,12,48,96,144, and 240 h. Changes in the structure of the PA elastic laminae were examined and analyzed with respect to changes in the PA wall tensile stress. The PA blood pressure increased rapidly within the first several hours of hypoxia and reached a stable level within 2 days, whereas the PA wall tensile stress increased initially due to elevated blood pressure and then decreased after 48 h due to vessel wall thickening and returned to the control level after 4 days. In association with these changes, the elastic laminae, which appeared homogeneous in normal control rats, changed into structures composed of randomly oriented filaments and edematous contents with an increase in the volume during the early period of hypoxia and regained their homogeneous appearance and normal volume after 4 days. The changes in the elastic laminae were correlated with changes in the tensile stress. These changes were associated with a transient decrease in the stiffness of the PAs. In hypoxic rats given nifedipine, no change was found in the blood pressure, the tensile stress, or the structure of the elastic laminae of the PAs despite continuous exposure to hypoxia. These results suggested that altered tensile stress in the PA wall played a critical role in the initiation and regulation of structural changes in the elastic laminae and that these changes might contribute to alterations in the mechanical properties of the PA in hypoxic hypertension. PMID:8941540

  13. 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

  14. Racial and socioeconomic disparities in arterial stiffness and intima media thickness among adolescents.

    PubMed

    Thurston, Rebecca C; Matthews, Karen A

    2009-03-01

    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 life.

  15. Updated Evidence-Based Treatment Algorithm in Pulmonary Arterial Hypertension

    PubMed Central

    Barst, Robyn J.; Gibbs, J. Simon; Ghofrani, Hossein A.; Hoeper, Marius M.; McLaughlin, Vallerie V.; Rubin, Lewis J.; Sitbon, Olivier; Tapson, Victor; Galiè, Nazzareno

    2009-01-01

    Uncontrolled and controlled clinical trials with different compounds and procedures are reviewed to define the risk-benefit profiles for therapeutic options in pulmonary arterial hypertension (PAH). A grading system for the level of evidence of treatments based on the controlled clinical trials performed with each compound is used to propose an evidence-based treatment algorithm. The algorithm includes drugs approved by regulatory agencies for the treatment of PAH and/or drugs available for other indications. The different treatments have been evaluated mainly in idiopathic PAH, heritable PAH, and in PAH associated with the scleroderma spectrum of diseases or with anorexigen use. Extrapolation of these recommendations to other PAH subgroups should be done with caution. Oral anticoagulation is proposed for most patients; diuretic treatment and supplemental oxygen are indicated in cases of fluid retention and hypoxemia, respectively. High doses of calcium channel blockers are indicated only in the minority of patients who respond to acute vasoreactivity testing. Nonresponders to acute vasoreactivity testing, or responders who remain in World Health Organization (WHO) functional class III, should be considered candidates for treatment with either an oral phosphodiesterase-5 inhibitor or an oral endothelin-receptor antagonist. Continuous intravenous administration of epoprostenol remains the treatment of choice in WHO functional class IV patients. Combination therapy is recommended for patients treated with PAH monotherapy who remain in New York Heart Association functional class III. Atrial septostomy and lung transplantation are indicated for refractory patients or where medical treatment is unavailable. PMID:19555861

  16. Development of macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Selej, Mona; Romero, Alain J; Channick, Richard N; Clozel, Martine

    2015-11-01

    Pulmonary arterial hypertension (PAH) is a serious, chronic condition that, without early recognition and treatment, leads to progressive right heart failure and death. The dual endothelin receptor antagonist macitentan was designed through a deliberate discovery process to maximize endothelin-axis blockade while improving adverse-effect profiles compared with previous compounds. Macitentan's efficacy was demonstrated in an event-driven morbidity and mortality study of treatment-naive and background PAH therapy-treated symptomatic patients. Compared to placebo, 10 mg of macitentan significantly reduced the relative risk of morbidity and mortality by 45%, primarily by delaying PAH worsening, most prominently in World Health Organization (WHO) functional class II and III PAH patients. Macitentan reduced the incidence of the composite end point of PAH-related hospitalizations and mortality and improved WHO FC and exercise capacity (6-min walk distance). Furthermore, it significantly improved cardiopulmonary hemodynamics and quality of life, and had a favorable safety and tolerability profile. To date, this was the largest and longest prospective trial for PAH. Macitentan, currently the only approved oral PAH treatment shown to be safe and effective in delaying long-term progression and reducing PAH-related hospitalizations, has changed treatment paradigms from goal-directed to long-term outcome-oriented therapy.

  17. 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

  18. 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

  19. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

    Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

  20. Apoptosis-based therapy to treat pulmonary arterial hypertension

    PubMed Central

    Suzuki, Yuichiro J.; Ibrahim, Yasmine F.; Shults, Nataliia V.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is rare, but patients who are diagnosed with this disease still suffer from a lack of satisfactory treatment strategies to prolong survival. While currently approved drugs for PAH have some benefits, these vasodilators only have limited efficacy for eliminating pulmonary vascular remodeling and reducing mortality. Thus, our laboratory has been exploring the use of aggressive drugs, which are capable of causing apoptotic cell death, to treat PAH. We have so far found that three classes of anti-tumor agents, including anthracyclines, taxanes, and proteasome inhibitors, are capable of reducing pulmonary vascular thickness in rats with PAH. These drugs kill cells in remodeled pulmonary vessels without affecting the normal, healthy pulmonary vasculature, revealing that proliferating vascular cells in PAH patients are more sensitive to drug-induced apoptosis compared to the differentiated phenotype that is physiologically important for smooth muscle contraction. Since many apoptosis-inducing drugs cause cardiotoxicity in cancer patients, and because PAH patients already have a weakened heart, we focus on finding biological mechanisms that may reverse pulmonary vascular remodeling without promoting cardiotoxicity. We found two agents, dexrazoxane and pifithrin-α, that selectively inhibit cardiac muscle apoptosis without affecting the drug-induced apoptosis of the proliferating pulmonary vascular cells. Thus, we propose that the addition of apoptosis-inducing drugs and cardioprotectants to PAH therapies may be effective in treating patients and preventing right heart failure.

  1. 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

  2. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series)

    PubMed Central

    2015-01-01

    Abstract Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively. PMID:26697167

  3. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series).

    PubMed

    Fessel, Joshua P; West, James D

    2015-12-01

    Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively.

  4. 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

  5. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario.

    PubMed

    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

  6. [Early digitalisation of patients with arterial hypertension (author's transl)].

    PubMed

    Nechwatal, W; König, E; Eversmann, A; Lehnert, J

    1977-07-01

    Haemodynamic tests were performed at rest and during exercise in 41 patients with arterial hypertension and early impairment of left-ventricular function, before and after administration of a single dose of 0.6 mg beta-methyl-digoxin. After clinical, ECG and coronary-angiographic studies, the patients were assigned to two groups. Group I: 17 patients with transmural infarcts in the chronic stage or with angina. Cardiac output was within normal limits at rest and on exercise and was not significantly altered by administration of beta-methyl-digoxin. There was no significant fall during exercise of the abnormally elevated pulmonary "wedge" pressure or of other pressures in the lesser circulation after digitalis. Group II: 24 patients without signs of coronary heart disease. They, too, had a normal cardiac output at rest and on exercise, not significantly changed by digitalisation with beta-methyl-digoxin. But pulmonary "wedge" pressure and right-atrial mean pressure were significantly reduced during exercise. Before beta-methyl-digoxin the mean "wedge" pressure rose on exercise to an average of 27.3 +/- 5.4 mm Hg, but after beta-methyl-digoxin to only 21.7 +/- 5.1 mm Hg (P less than 0.001). The mean right atrial pressure changed similar. These results indicate that acute digitalisation at the stated dosage in general has an effect on abnormal myocardial function only if there is no additional coronary heart disease. PMID:880903

  7. [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. PMID:26047999

  8. Initial dual oral combination therapy in pulmonary arterial hypertension.

    PubMed

    Sitbon, Olivier; Sattler, Caroline; Bertoletti, Laurent; Savale, Laurent; Cottin, Vincent; Jaïs, Xavier; De Groote, Pascal; Chaouat, Ari; Chabannes, Céline; Bergot, Emmanuel; Bouvaist, Hélène; Dauphin, Claire; Bourdin, Arnaud; Bauer, Fabrice; Montani, David; Humbert, Marc; Simonneau, Gérald

    2016-06-01

    Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment. PMID:26989105

  9. 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.

  10. [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.

  11. Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

    PubMed Central

    Papathanasiou, Athanasios; Nakos, George

    2015-01-01

    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

  12. 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. PMID:24570273

  13. Association between plasma sLOX-1 concentration and arterial stiffness in middle-aged and older individuals.

    PubMed

    Otsuki, Takeshi; Maeda, Seiji; Mukai, Jun; Ohki, Makoto; Nakanishi, Mamoru; Yoshikawa, Toshikazu

    2015-09-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is implicated in vascular endothelial function. Vascular endothelial function is a potent regulator of arterial stiffness, an independent risk factor for cardiovascular disease. However, it is unknown whether LOX-1 is associated with arterial stiffness. Plasma concentrations of soluble LOX-1 (sLOX-1) and brachial-ankle pulse wave velocity (baPWV, an index of arterial stiffness) were measured in 143 individuals between 51 and 83 years of age. Plasma sLOX-1 concentration was correlated with baPWV (r = 0.288, p = 0.0005). In stepwise regression analysis, plasma sLOX-1 concentration was associated with baPWV, after adjusting for age; body mass index; blood pressure; heart rate; blood levels of cholesterol, triglycerides, glucose, hemoglobin A1c, and insulin; sex; and use of antihypertensives, lipid-lowering agents, and other medications (R (2) = 0.575, p<0.0001). Multiple logistic regression demonstrated that plasma sLOX-1 concentration was independently associated with elevated baPWV (≥14.0 m/s; odds ratio, 1.01; 95% confidence interval, 1.00-1.03; p = 0.03). These results suggest that LOX-1 is associated with arterial stiffness. PMID:26388674

  14. 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.

  15. 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

  16. Influence of metabolic syndrome on arterial stiffness and its age-related change in young adults: the Bogalusa Heart Study.

    PubMed

    Li, Shengxu; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S

    2005-06-01

    Increased arterial stiffness is associated with risk variables of metabolic syndrome in middle-aged and older adults. However, information regarding the influence of the metabolic syndrome on arterial stiffness and its rate of change with age in young adults is limited. These aspects were examined in a sample of 806 asymptomatic, healthy young adults aged 24-44 years from a black-white community. Brachial to ankle pulse wave velocity (baPWV) measured by an oscillometric method was used as an index of arterial stiffness. baPWV increased with the increasing number of metabolic syndrome components, defined by National Cholesterol Education Program Adult Treatment Panel III (1256, 1314, and 1422 cm/s for those with 0, 1-2, and 3-5 components, respectively, P for trend <0.001). Furthermore, the rate of change (slope) of baPWV with age increased as the number of metabolic syndrome components increased (4.1, 10.7, and 18.7 cm/s per year for those with 0, 1-2, and 3-5 components, respectively; P for comparison of slopes <0.001). These findings by showing the deleterious effects of metabolic syndrome on arterial stiffness and its age-related increase in young adults underscore the importance of this syndrome in cardiovascular risk assessment even in a younger population. Further longitudinal studies are needed to confirm the current cross-sectional findings.

  17. 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

  18. Pulmonary artery endothelium resident endothelial colony-forming cells in pulmonary arterial hypertension

    PubMed Central

    Duong, Heng T.; Comhair, Suzy A.; Aldred, Micheala A.; Mavrakis, Lori; Savasky, Benjamin M.; Erzurum, Serpil C.; Asosingh, Kewal

    2011-01-01

    Proliferative pulmonary vascular remodeling is the pathologic hallmark of pulmonary arterial hypertension (PAH) that ultimately leads to right heart failure and death. Highly proliferative endothelial cells known as endothelial colony-forming cells (ECFC) participate in vascular homeostasis in health as well as in pathological angiogenic remodeling in disease. ECFC are distinguished by the capacity to clonally proliferate from a single cell. The presence of ECFC in the human pulmonary arteries and their role in PAH pathogenesis is largely unknown. In this study, we established a simple technique for isolating and growing ECFC from cultured pulmonary artery endothelial cells (PAEC) to test the hypothesis that ECFC reside in human pulmonary arteries and that the proliferative vasculopathy of PAH is related to greater numbers and/or more proliferative ECFC in the pulmonary vascular wall. Flow cytometric forward and side scatter properties and aggregate correction were utilized to sort unmanipulated, single PAEC to enumerate ECFC in primary PAEC cultures derived from PAH and healthy lungs. After 2 weeks, wells were assessed for ECFC formation. ECFC derived from PAH PAEC were more proliferative than control. A greater proportion of PAH ECFC formed colonies following subculturing, demonstrating the presence of more ECFC with high proliferative potential among PAH PAEC. Human androgen receptor assay showed clonality of progeny, confirming that proliferative colonies were single cell-derived. ECFC expressed CD31, von Willebrand factor, endothelial nitric oxide synthase, caveolin-1 and CD34, consistent with an endothelial cell phenotype. We established a simple flow cytometry method that allows ECFC quantification using unmanipulated cells. We conclude that ECFC reside among PAEC and that PAH PAEC contain ECFC that are more proliferative than ECFC in control cultures, which likely contributes to the proliferative angiopathic process in PAH. PMID:22530103

  19. [Cardiovascular risk factors in young adults with arterial hypertension and/or diabetes mellitus].

    PubMed

    Moreira, Thereza Maria Magalhães; Gomes, Emiliana Bezerra; dos Santos, Jênifa Cavalcante

    2010-12-01

    In this study we aimed to investigate the risk factors associated with arterial hypertension and diabetes mellitus in young adults assisted in six Family Health Units (UBASF), of Fortaleza, Ceará, Brazil. This is a descriptive and documental study, based on the records of the Care Program to Arterial Hypertension and Diabetes Mellitus (HIPERDIA). The sample was composed of 60 records, including hypertensive, diabetics and patients with the two diagnoses. The results showed prevalence of young female adults (78%). Regarding the risk factors, arterial hypertension (n=45), family history (n=33), overweight (n=33) and sedentary lifestyle (n=27) stood out. Regarding the cardiovascular risk stratification, most presented Medium additional risk for cardiovascular disease. We concluded that the individualized evaluation of risk factors supports an action addressed for possible events, being necessary investments in prevention and also in training and maintenance of the HIPERDIA system.

  20. 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.

  1. Maraviroc Reduces Arterial Stiffness in PI-Treated HIV-infected Patients

    PubMed Central

    Piconi, Stefania; Pocaterra, Daria; Rainone, Veronica; Cossu, Maria; Masetti, Michela; Rizzardini, Giuliano; Clerici, Mario; Trabattoni, Daria

    2016-01-01

    The Δ32-CCR5 deletion of the CCR5 receptor is protective toward coronary artery pathology and myocardial infarction. Maraviroc (MVC), a CCR5 antagonist, was recently introduced in the therapy of HIV infection; we evaluated whether this drug could modulate the atherosclerotic burden in aviremic PI-treated HIV-positive individuals who underwent MVC intensification. Thus, the effect of MVC on intima media thickness, arterial stiffness, metabolic parameters, pro-inflammatory cytokines, endothelial dysfunction, and microbial traslocation markers was analyzed in 6 aviremic PI-treated HIV-positive individuals and were compared to those obtained in 9 additional aviremic PI-treated subjects that were enrolled retrospectively from our outpatients cohort. MVC intensification resulted in a significant reduction in intima media thickness, pulse wave velocity and triglycerides compared to baseline. Notably, MVC was also associated with a significant reduction of IL-6, microbial translocation indexes, sICAM and sVCAM; these changes were maintained throughout the 6 months of MVC intensification. No significant modifications were observed in CD4 counts, HIV viral load, and cholesterolemia. Results herein support a role of CCR5 antagonists in reducing the cardiovascular risk in HIV-infection. The hampering of inflammation, microbial translocation and the improvement of endothelial function could justify the protective role of CCR5 antagonists on atherosclerotic burden. PMID:27352838

  2. 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. PMID:26737764

  3. Effect of probe contact pressure on the photoplethysmographic assessment of conduit artery stiffness

    NASA Astrophysics Data System (ADS)

    Grabovskis, Andris; Marcinkevics, Zbignevs; Rubins, Uldis; Kviesis-Kipge, Edgars

    2013-02-01

    Currently, photoplethysmography (PPG) is a frequently studied optical blood pulsation detection technique among biophotonic and biomedical researchers due to the fact that it shows high potential for estimating the arterial stiffness (AS). The extraction of diagnostically useful information requires standardized measurement procedure with good repeatability. However, the effects of a crucially important factor-the optimal contact pressure (CP) of the probe-are often ignored. Also, CP values are not reported to evaluate those effects. It is hypothesized that AS estimated from PPG pulse wave 2nd derivative parameter b/a is strongly inconsistent when recorded at nonoptimal probe CP. Our pilot study confirmed this during in vivo PPG recordings from conduit artery sites on five healthy subjects at variable probe CP (0 to 15 kPa) by using 880 nm reflectance type sensor, force transducer, and PPG alternating current (AC) signal pulse area derived optimal CP criterion. The b/a values, calculated from PPG with variable CP, showed variation >300 percent. In contrast, at the optimal CP, the b/a showed high repeatability (coefficient of variability <5 percent). The effect has been explained with exponential pulse pressure-volume relationship model which indicates the optimal CP range.

  4. 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.

  5. Effect of whole-body vibration for 3 months on arterial stiffness in the middle-aged and elderly

    PubMed Central

    Lai, Chung-Liang; Chen, Han-Yu; Tseng, Shiuan-Yu; Liao, Wan-Chun; Liu, Bing-Tang; Lee, Meng-Chih; Chen, Hsin-Shui

    2014-01-01

    Background Cardiovascular disease (CVD) is a common problem of middle-aged and older adults. Increased arterial stiffness is a CVD risk factor. Whole-body vibration (WBV) is a simple and convenient exercise for middle-aged and older adults; however, there have been few studies investigating the effect of WBV on arterial stiffness. This study mainly investigated the effect of WBV on arterial stiffness in middle-aged and older adults. Methods A total of 38 (21 women and 17 men) middle-aged and elderly subjects (average age, 61.9 years) were randomly divided into the WBV group and the control group for a 3-month trial. The WBV group received an intervention of 30 Hz and 3.2 g WBV in a natural full standing posture at a sports center. The brachial–ankle pulse wave velocity (baPWV), a marker of systemic arterial stiffness, and blood pressure and heart rate were measured before and after the intervention. Results After 3 months, there were no significant changes in blood pressure or heart rate in both groups. However, the bilateral baPWV was significantly reduced in the WBV group (decreased by 0.65 m/second [P=0.014]; 0.63 m/second [P=0.041] in either side), but not in the control group. The comparison between the two groups was not statistically significant. Conclusion This study found that 3 months of WBV had a positive effect on arterial stiffness in middle-aged and older adults and could therefore be regarded as a supplementary exercise. Larger-scale studies are needed to confirm the effects of WBV in the future. PMID:24872684

  6. Association between arterial stiffness, disease activity and functional impairment in ankylosing spondylitis patients: a cross-sectional study.

    PubMed

    Avram, Claudiu; Drăgoi, Răzvan Gabriel; Popoviciu, Horațiu; Drăgoi, Mihai; Avram, Adina; Amaricăi, Elena

    2016-08-01

    Cardiovascular risk is an important factor for increased morbidity and mortality in patients with ankylosing spondylitis. The aim of this study is to assess arterial stiffness in relation to the disease activity and functional limitation in patients with ankylosing spondylitis. Twenty-four patients (mean age 45.8 ± 11.7 years) suffering of ankylosing spondylitis (disease duration 11.1 ± 5.1 years) and 24 gender and age-matched healthy controls were included in the study. Clinical, biological, and functional status of ankylosing spondylitis patients was recorded. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) and pulse wave analysis (PWA) was performed using applanation tonometry. We found significant differences between ankylosing spondylitis patients and healthy controls in regard to PWV (p = 0.047), aortic augmentation pressure-AP (p = 0.028), augmentation index-AIx (p = 0.038) and aortic augmentation index adjusted for heart rate-AIx75 (p = 0.011). PWV and AIx75 were significantly associated with the disease functioning score-BASFI (p = 0.012, r = 0.504; p = 0.041, r = 0.421). Aortic AP and augmentation indexes (AIx and AIx75) were all associated to ASDAS score (p = 0.028, r = 0.448; p = 0.005, r = 0.549; p = 0.025, r = 0.455). Our study showed that ankylosing spondylitis patients have a higher arterial stiffness than the age-matched controls, leading to an increased cardiovascular risk. We found that arterial stiffness is positively associated with disease activity and functional impairment. Chronic spondiloarthropaties should be screened for arterial stiffness, even in the absence of traditional cardiovascular risk factors, in order to benefit from primary prevention measures.

  7. Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling

    PubMed Central

    Sumida, Tomokazu; Naito, Atsuhiko T.; Nomura, Seitaro; Nakagawa, Akito; Higo, Tomoaki; Hashimoto, Akihito; Okada, Katsuki; Sakai, Taku; Ito, Masamichi; Yamaguchi, Toshihiro; Oka, Toru; Akazawa, Hiroshi; Lee, Jong-Kook; Minamino, Tohru; Offermanns, Stefan; Noda, Tetsuo; Botto, Marina; Kobayashi, Yoshio; Morita, Hiroyuki; Manabe, Ichiro; Nagai, Toshio; Shiojima, Ichiro; Komuro, Issei

    2015-01-01

    Hypertension induces structural remodelling of arteries, which leads to arteriosclerosis and end-organ damage. Hyperplasia of vascular smooth muscle cells (VSMCs) and infiltration of immune cells are the hallmark of hypertensive arterial remodelling. However, the precise molecular mechanisms of arterial remodelling remain elusive. We have recently reported that complement C1q activates β-catenin signalling independent of Wnts. Here, we show a critical role of complement C1-induced activation of β-catenin signalling in hypertensive arterial remodelling. Activation of β-catenin and proliferation of VSMCs were observed after blood-pressure elevation, which were prevented by genetic and chemical inhibition of β-catenin signalling. Macrophage depletion and C1qa gene deletion attenuated the hypertension-induced β-catenin signalling, proliferation of VSMCs and pathological arterial remodelling. Our findings unveil the link between complement C1 and arterial remodelling and suggest that C1-induced activation of β-catenin signalling becomes a novel therapeutic target to prevent arteriosclerosis in patients with hypertension. PMID:25716000

  8. 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.

  9. 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

  10. Arterial Stiffness Is Associated With Cardiovascular, Renal, Retinal, and Autonomic Disease in Type 1 Diabetes

    PubMed Central

    Theilade, Simone; Lajer, Maria; Persson, Frederik; Joergensen, Christel; Rossing, Peter

    2013-01-01

    OBJECTIVE In patients with type 1 diabetes, we investigated the association between arterial stiffness and diabetes complications. RESEARCH DESIGN AND METHODS This was a cross-sectional study including 676 Caucasian patients with type 1 diabetes (374 [55%] men, aged 54 ± 13 years [mean ± SD]) and 51 nondiabetic controls (28 [55%] men, aged 47 ± 13 years). Aortic pulse wave velocity (PWV) was measured with SphygmoCor (AtCor Medical, Sydney, Australia) for 635 patients and all 51 controls. RESULTS PWVs (mean ± SD) in patients and controls were 10.4 ± 3.4 and 7.6 ± 1.9 m/s, respectively (P < 0.001). After multivariate adjustment, PWV correlated with age, diabetes duration, urinary albumin excretion rate, heart rate, and blood pressure (P < 0.05 for all). ANCOVA was used for comparisons between groups and adjusted for gender, age, estimated glomerular filtration rate, heart rate, HbA1c, and 24-h mean arterial pressure. PWVs in normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 9.5 ± 3.2, 11.0 ± 3.6, and 11.4 ± 3.0 m/s, respectively (adjusted P < 0.001). PWV in patients with previous cardiovascular disease, versus patients without, was 12.1 ± 3.5 vs. 10.0 ± 3.2 m/s, respectively (adjusted P < 0.001). PWVs in patients with high (≥140/90 mmHg) versus intermediate (130–40/80–89 mmHg) and low (<130/80 mmHg) blood pressure were 11.8 ± 3.6, 10.0 ± 3.0, and 9.8 ± 3.3 m/s, respectively (adjusted P < 0.001). Furthermore, PWV increased with increasing degree of retinopathy: 8.0 ± 2.5 m/s (nil), 10.0 ± 2.8 m/s (simplex), 12.1 ± 3.5 m/s (proliferative), and 12.7 ± 2.4 m/s (blind), respectively (adjusted P < 0.001). Finally, PWV increased with abnormal heart rate variability: 11.5 ± 3.3 m/s vs. 10.1 ± 3.1 m/s (borderline) and 8.1 ± 2.1 m/s (normal) (adjusted P = 0.027). CONCLUSIONS Arterial stiffness increased with presence and duration of type 1 diabetes. Furthermore, PWV increased with all the investigated diabetes complications

  11. Altered Arterial Stiffness and Subendocardial Viability Ratio in Young Healthy Light Smokers after Acute Exercise

    PubMed Central

    Doonan, Robert J.; Scheffler, Patrick; Yu, Alice; Egiziano, Giordano; Mutter, Andrew; Bacon, Simon; Carli, Franco; Daskalopoulos, Marios E.; Daskalopoulou, Stella S.

    2011-01-01

    Background Studies showed that long-standing smokers have stiffer arteries at rest. However, the effect of smoking on the ability of the vascular system to respond to increased demands (physical stress) has not been studied. The purpose of this study was to estimate the effect of smoking on arterial stiffness and subendocardial viability ratio, at rest and after acute exercise in young healthy individuals. Methods/Results Healthy light smokers (n = 24, pack-years = 2.9) and non-smokers (n = 53) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest, and 2, 5, 10, and 15 minutes following an exercise test to exhaustion. Smokers were tested, 1) after 12h abstinence from smoking (chronic condition) and 2) immediately after smoking one cigarette (acute condition). At rest, chronic smokers had higher augmentation index and lower aortic pulse pressure than non-smokers, while subendocardial viability ratio was not significantly different. Acute smoking increased resting augmentation index and decreased subendocardial viability ratio compared with non-smokers, and decreased subendocardial viability ratio compared with the chronic condition. After exercise, subendocardial viability ratio was lower, and augmentation index and aortic pulse pressure were higher in non-smokers than smokers in the chronic and acute conditions. cfPWV rate of recovery of was greater in non-smokers than chronic smokers after exercise. Non-smokers were also able to achieve higher workloads than smokers in both conditions. Conclusion Chronic and acute smoking appears to diminish the vascular response to physical stress. This can be seen as an impaired ‘vascular reserve’ or a blunted ability of the blood vessels to accommodate the changes required to achieve higher workloads. These changes were noted before changes in arterial stiffness or subendocardial viability ratio occurred at rest. Even light smoking in young healthy individuals appears to have

  12. [Anesthetic Management for Non-cardiac Surgery in a Patient with Severe Pulmonary Arterial Hypertension].

    PubMed

    Ohno, Sho; Niiyama, Yukitoshi; Murouchi, Takeshi; Yamakage, Michiaki

    2016-05-01

    Severe pulmonary arterial hypertension is a significant risk factor for anesthetic management in patients undergoing even non-cardiac surgery. A 64-year-old female patient with severe pulmonary arterial hypertension was scheduled to undergo inguinal hernioplasty. Preoperative systolic pulmonary arterial pressure was 115 mmHg. We selected monitored anesthesia care with 0.2-0.5 μg x kg(-1) x hr(-1) dexmedetomidine and ultrasound-guided iliohypogastric block. Thereafter, LiDCOrapid was used to acquire the hemodynamic responses during surgery. Continuous iliohypogastric block produced postoperative pain relief and the supplemental analgesic was not needed. The monitored anesthesia care by dexmedetomidine and ultrasound guided continuous iliohypogastric block would be a safe procedure for patients with severe pulmonary arterial hypertension undergoing non-cardiac surgery. LiDCO rapid could be low invasive and useful as a hemodaynamic monitor in such a case. PMID:27319099

  13. [Metabolic syndrome with vascular risk and arterial hypertension].

    PubMed

    Wassermann, A O; Grosso, C P

    1996-01-01

    Hypertension is associated with metabolic disturbances that may be related to hyperinsulinemia, both resulting from our lifestyle. Insulin resistance generated by central obesity, and complex relations with sympathetic activity, dyslipemia, atherosclerosis, sodium retention, altered vascular reactivity and hypertension, lead to pathophysiological connections, that are still to be understood. Even if obesity and hypertension were not related through hyperinsulinemia, the metabolic syndrome increases either vascular risk or hypertension, and it has to be re-evaluated whether essential hypertension is an adequate diagnosis for these patients.

  14. [Metabolic syndrome with vascular risk and arterial hypertension].

    PubMed

    Wassermann, A O; Grosso, C P

    1996-01-01

    Hypertension is associated with metabolic disturbances that may be related to hyperinsulinemia, both resulting from our lifestyle. Insulin resistance generated by central obesity, and complex relations with sympathetic activity, dyslipemia, atherosclerosis, sodium retention, altered vascular reactivity and hypertension, lead to pathophysiological connections, that are still to be understood. Even if obesity and hypertension were not related through hyperinsulinemia, the metabolic syndrome increases either vascular risk or hypertension, and it has to be re-evaluated whether essential hypertension is an adequate diagnosis for these patients. PMID:8935572

  15. Effects of portal hypertension on responsiveness of rat mesenteric artery and aorta.

    PubMed Central

    Cawley, T; Geraghty, J; Osborne, H; Docherty, J R

    1995-01-01

    1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle. PMID:7773539

  16. Effects of collagen deposition on passive and active mechanical properties of large pulmonary arteries in hypoxic pulmonary hypertension.

    PubMed

    Wang, Zhijie; Lakes, Roderic S; Eickhoff, Jens C; Chesler, Naomi C

    2013-11-01

    Proximal pulmonary artery (PA) stiffening is a strong predictor of mortality in pulmonary hypertension. Collagen accumulation is mainly responsible for PA stiffening in hypoxia-induced pulmonary hypertension (HPH) in mouse models. We hypothesized that collagen cross-linking and the type I isoform are the main determinants of large PA mechanical changes during HPH, which we tested by exposing mice that resist type I collagen degradation (Col1a1[Formula: see text] and littermate controls (Col1a1[Formula: see text] to hypoxia for 10 days with or without [Formula: see text]-aminopropionitrile (BAPN) treatment to prevent cross-link formation. Static and dynamic mechanical tests were performed on isolated PAs with smooth muscle cells (SMC) in passive and active states. Percentages of type I and III collagen were quantified by histology; total collagen content and cross-linking were measured biochemically. In the SMC passive state, for both genotypes, hypoxia tended to increase PA stiffness and damping capacity, and BAPN treatment limited these increases. These changes were correlated with collagen cross-linking ([Formula: see text]). In the SMC active state, hypoxia increased PA dynamic stiffness and BAPN had no effect in Col1a1[Formula: see text] mice ([Formula: see text]). PA stiffness did not change in Col1a1[Formula: see text] mice. Similarly, damping capacity did not change for either genotype. Type I collagen accumulated more in Col1a1[Formula: see text] mice, whereas type III collagen increased more in Col1a1[Formula: see text] mice during HPH. In summary, PA passive mechanical properties (both static and dynamic) are related to collagen cross-linking. Type I collagen turnover is critical to large PA remodeling during HPH when collagen metabolism is not mutated and type III collagen may serve as a reserve. PMID:23377784

  17. Relations of Digital Vascular Function, Cardiovascular Risk Factors, and Arterial Stiffness: The Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) Cohort Study

    PubMed Central

    Brant, Luisa C. C.; Hamburg, Naomi M.; Barreto, Sandhi M.; Benjamin, Emelia J.; Ribeiro, Antonio L. P.

    2014-01-01

    Background Vascular dysfunction is an early expression of atherosclerosis and predicts cardiovascular (CV) events. Peripheral arterial tonometry (PAT) evaluates basal pulse amplitude (BPA), endothelial function (PAT ratio), and wave reflection (PAT‐AIx) in the digital microvessels. In Brazilian adults, we investigated the correlations of PAT responses to CV risk factors and to carotid‐femoral pulse wave velocity (PWV), a measure of arterial stiffness. Methods and Results In a cross‐sectional study, 1535 participants of the ELSA‐Brasil cohort underwent PAT testing (52±9 years; 44% women). In multivariable analyses, more‐impaired BPA and PAT ratios were associated with male sex, higher body mass index (BMI), and total cholesterol/high‐density lipoprotein. Higher age and triglycerides were related to higher BPA, whereas lower systolic blood pressure, hypertension (HTN) treatment, and prevalent CV disease (CVD) were associated with lower PAT ratio. PAT‐AIx correlated positively with female sex, advancing age, systolic and diastolic blood pressures, and smoking and inversely to heart rate, height, BMI, and prevalent CVD. Black race was associated with lower BPA, higher PAT ratio, and PAT‐AIx. Microvessel vasodilator function was not associated with PWV. Higher PAT‐AIx was modestly correlated to higher PWV and PAT ratio and inversely correlated to BPA. Conclusion Metabolic risk factors are related to impaired microvessel vasodilator function in Brazil. However, in contrast to studies from the United States, black race was not associated with an impaired microvessel vasodilator response, implying that vascular function may vary by race across populations. PAT‐AIx relates to HTN, may be a valid measure of wave reflection, and provides distinct information from arterial stiffness. PMID:25510401

  18. 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

  19. Clinical Implications of Hemoptysis in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Cantu, Jose; Wang, Degang; Safdar, Zeenat

    2013-01-01

    Introduction Pulmonary arterial hypertension (PAH) is a disabling disease that may result in haemoptysis. Patients with congenital heart disease associated PAH (CHD-APAH) may have a survival advantage when compared with patients with other types of PAH presenting with haemoptysis. The effects of aetiology and sub-sequent management choice of haemoptysis in PAH patients is not well-defined. Methods We conducted outcome analysis in CHD-APAH vs. all other subtypes of PAH patients presenting with haemoptysis to The Methodist Hospital. Twenty-one patients were identified, thirteen patients in the CHD-APAH group and eight patients in the non-CHD group. We evaluated outcomes related to treatment (bronchial artery embolization vs. conservative management), hospital length of stay, mortality rates and survival in this cohort. Results The CHD-APAH and non-CHD groups had similar baseline demographic, haemodynamic and laboratory values except BMI was higher in the non-CHD group and haematocrit was higher in the CHD-APAH group. Twenty-eight-day mortality (0% vs. 31%) and 1-year mortality (0% vs. 54%) was lower in the CHD-APAH patients as compared with non-CHD group. A statistically significant difference was found in the survival rate in favour of CHD-APAH group for the total follow-up period (p = 0.02). Although not statistically significant, patients treated with BAE had shorter length of stay (4.0 days ± 4.0 vs. 13.7 days ± 22.5; p = 0.26). There was recurrent haemoptysis in 43% of patients treated with BAE. Conclusion Haemoptysis in PAH patients is a serious event with a high mortality rate. CHD-APAH seems to confer a survival advantage, independent of therapy utilised. Termination of haemoptysis with BAE is rapid with relatively few complications except for frequent re-bleeding episodes. Further studies are needed to determine the risk factors that may predispose PAH patients to excessive mortality from haemoptysis and to identify an optimal therapeutic modality. PMID

  20. Novel biomarkers for risk stratification in pulmonary arterial hypertension

    PubMed Central

    Zelniker, Thomas; Uhlmann, Lorenz; Spaich, Sebastian; Friedrich, Jörg; Preusch, Michael R.; Meyer, Franz J.; Katus, Hugo A.

    2015-01-01

    Risk stratification in pulmonary arterial hypertension (PAH) is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT), pro-atrial natriuretic peptide (proANP), growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4%) patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR) 1.91), hsTnT (HR 1.41), echocardiographic right ventricular impairment (HR 1.30) and 6-min walk test (HR 0.97 per 10 m) remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

  1. The heart and pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Vandecasteele, Els H; De Pauw, Michel; Brusselle, Guy; Decuman, Saskia; Piette, Yves; De Keyser, Filip; Smith, V

    2016-02-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials. PMID:27075793

  2. Phase I safety study of ranolazine in pulmonary arterial hypertension

    PubMed Central

    Schilz, Robert; Mediratta, Anuj; Addetia, Karima; Coslet, Sandra; Thomeas, Vasiliki; Gillies, Hunter; Oudiz, Ronald J.

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swan-Ganz catheter. All patients received 500-mg doses, uptitrated to 1,000 mg at week 4, monthly evaluations, and a complete objective assessment after 12 weeks, followed by an open-label extension. Thirteen patients were randomized and 12 enrolled (6 ranolazine, 6 placebo). All patients completed the acute phase; 10 completed the 12-week study. There were no acute changes in invasive hemodynamics. At 12 weeks ranolazine was well tolerated. Only 1 of the 5 patients on ranolazine had a serum concentration considered to be in the therapeutic range. Two serious adverse events required early withdrawal (both in the ranolazine group); gastrointestinal complaints were the most common adverse event. Efficacy measures did not demonstrate any differences between treatment groups. During the open-label trial, 2 additional patients reached a therapeutic concentration. Ranolazine in PAH appears safe, without acute hemodynamic effects after a 500-mg dose. Ranolazine administrated to PAH patients receiving background PAH therapies did not consistently reach therapeutic levels. Future studies should first perform PK analysis in PAH patients receiving PAH therapies and explore the safety and tolerability of the higher doses perhaps necessary to achieve therapeutic levels in PAH patients. (Trial registration: Clinicaltrials.gov identifier NCT01757808.) PMID:26697176

  3. Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study.

    PubMed

    van Campen, Jasmijn S J A; de Boer, Karin; van de Veerdonk, Mariëlle C; van der Bruggen, Cathelijne E E; Allaart, Cor P; Raijmakers, Pieter G; Heymans, Martijn W; Marcus, J Tim; Harms, Hendrik J; Handoko, M Louis; de Man, Frances S; Vonk Noordegraaf, Anton; Bogaard, Harm-Jan

    2016-09-01

    While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min(-1)·m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients. PMID:27390285

  4. Pulmonary arterial hypertension among Filipino patients with connective tissue diseases.

    PubMed

    Santos Estrella, Paul V; Lin, Yih Chang; Navarra, Sandra V

    2007-01-01

    We describe the clinical features, therapies, and clinical course of pulmonary arterial hypertension (PAH) in a group of Filipinos with connective tissue diseases (CTDs). We retrospectively reviewed the records of patients diagnosed with PAH by a two-dimensional echocardiogram as a tricuspid regurgitant jet of more than 25 mmHg. All patients had underlying CTDs, defined by the American College of Rheumatology criteria, and were seen at the rheumatology clinics of the University of Santo Tomas Hospital and the St. Luke's Medical Center, Philippines. Of the 33 patients (32 women) included in the analysis, there were 14 patients with systemic lupus erythematosus (SLE), 12 with scleroderma, 5 with mixed connective tissue disease (MCTD), 1 with primary antiphospholipid syndrome (APS), and 1 with dermatomyositis. The average age at PAH diagnosis was 38 +/- 14 years (mean +/- SD), and the mean duration of illness from CTD to PAH diagnosis was 53 +/- 52 months. Twelve patients had died at the time of this report, with a median duration of 15 months (range 1-57 months) from PAH diagnosis to mortality: six of these had scleroderma, five with SLE, and one with APS. The following therapies were used in this group of patients: low molecular weight heparin, warfarin, calcium-channel blockers, aspirin, cyclophosphamide, bosentan, iloprost, and sildenafil. We have described the clinical profile of PAH in a group of Filipino patients with CTDs, most commonly SLE. Various forms of pharmacologic therapies were used among these patients. Mortality remains high, particularly among those with underlying scleroderma. Early recognition and treatment are crucial in order to provide a better outcome for these patients.

  5. Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension.

    PubMed

    Quail, Michael A; Knight, Daniel S; Steeden, Jennifer A; Taelman, Liesbeth; Moledina, Shahin; Taylor, Andrew M; Segers, Patrick; Coghlan, Gerry J; Muthurangu, Vivek

    2015-06-15

    Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e(-8)). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63-100%] and specificity of 91% (95% CI 75-98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH. PMID:25659483

  6. Predictors and outcomes of resistant hypertension among patients with coronary artery disease and hypertension

    PubMed Central

    Smith, Steven M.; Gong, Yan; Handberg, Eileen; Messerli, Franz H.; Bakris, George L.; Ahmed, Ali; Bavry, Anthony A.; Pepine, Carl J.; Cooper-DeHoff, Rhonda M.

    2014-01-01

    Objective Resistant hypertension (res-HTN) is a challenging problem, but little is known of res-HTN in patients with coronary artery disease (CAD). In this post-hoc INternational VErapamil SR-Trandolapril STudy (INVEST) analysis, we assessed prevalence, predictors, and impact on outcomes of res-HTN in CAD patients with hypertension. Methods Participants (n=17 190) were divided into three groups according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three or fewer drugs); uncontrolled (BP ≥140/90mmHg on two or fewer drugs); or resistant (BP ≥140/90 mmHg on three drugs or any patient on at least four drugs). Results The prevalence of res-HTN was 38%: significant predictors of res-HTN included heart failure [odds ratio (OR) 1.73], diabetes (OR 1.63), Black race (OR 1.50), and US residence (OR 1.50). Compared with controlled HTN, res-HTN had multivariate-adjusted association with higher risk of adverse outcomes {first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke [hazard ratio 1.27, 95% confidence interval (CI) 1.13–1.43], and individual outcomes of all-cause death (hazard ratio 1.29, 95% CI 1.13–1.48), cardiovascular mortality (hazard ratio 1.47, 95% CI 1.21–1.78), and nonfatal stroke (hazard ratio 1.61, 95% CI 1.17–2.22), but not nonfatal myocardial infarction (hazard ratio 0.98, 95% CI 0.72–1.34)}. Adverse outcomes, except nonfatal stroke, did not differ in patients with res-HTN compared to uncontrolled HTN. Conclusions Res-HTN is common in patients with CAD and hypertension, associated with poor prognosis, and linked with a number of conditions. Emphasis should be placed on recognizing those at risk for res-HTN and future studies should examine whether more aggressive treatment of res-HTN improves outcomes. PMID:24299915

  7. 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.

  8. Macular circulation in patients with diabetes mellitus with and without arterial hypertension

    PubMed Central

    Arend, O; Ruffer, M; Remky, A

    2000-01-01

    BACKGROUND—Previous fluorescein angiographic studies have shown alterations in the macular microcirculation in patients with diabetes mellitus and arterial hypertension. In both diseases capillary blood velocity was reduced and capillary density decreased. These changes were more pronounced in diabetic patients. We have examined the influence of arterial hypertension in combination with diabetes mellitus.
METHODS—62 patients with diabetes mellitus and arterial hypertension (group 1) were matched with patients with diabetes mellitus but without arterial hypertension (group 2, match criteria: ETDRS stage of retinopathy). In all subjects fluorescein angiograms were performed with a scanning laser ophthalmoscope. Macular capillary blood velocity (CBV), perifoveal intercapillary area (PIA), the coefficient of variation of both parameters, the area of the foveal avascular zone (FAZ), and the arteriovenous passage time (AVP) were assessed by digital image analysis.
RESULTS—Systolic and diastolic blood pressures were significantly increased in the patients with arterial hypertension (systolic p=0.0008; diastolic p=0.03). Neither dynamic measures (AVP: 1.64 (0.49) seconds (group 1), 1.72 (0.58) seconds (group 2); CBV: 1.98 (0.39) mm/s (group 1), 2.09 (0.43) mm/s (group 2)) nor morphological measures (PIA: 7985 (3137) µm2 (group 1), 8338 (3376) µm2 (group 2); FAZ: 0.319 (0.206) mm2 (group 1), 0.363 (0.237) mm2 (group 2)) were significantly different between the two groups of diabetic patients.
CONCLUSION—Arterial hypertension did not result in more severe macular capillary dropout than diabetes without hypertension. This might be explained by the fact that most of the patients were being treated with antihypertensive drugs.

 PMID:11090480

  9. Arterial wall metabolism in experimental hypertension of coarctation of the aorta of short duration

    PubMed Central

    Hollander, William; Kramsch, Dieter M.; Farmelant, Melvin; Madoff, Irving M.

    1968-01-01

    Coarctation of the mid-thoracic aorata was surgically produced in mongrel dogs which were sacrificed from 4-12 wk after the operation. As compared to the findings in control animals, the sodium, chloride, and water content of the hypetensive portion of the coarcted thoracic aorta was significantly elevated, whereas the electrolyte and water content of the relatively normotensive portion of the coarcted aorta was normal. The sodium, potassium, and water content of the pulmonary artery, skeletal muscle, and cardiac muscle of the coarcted dog was not altered. These observations suggest that an elevated arterial pressure may influence the electrolyte and water composition of the arteries. The arterial pressure also may influence the content and synthesis of acid mucopolysaccharides (MPS) in the arteries since the content of sulfated MPS and the incorporation of injected radiosulfate into sulfated MPS were significantly increased in the hypertensive portion of the coarcted thoracic aorta but were significantly reduced in the relatively normotensive (“hypotensive”) portion of the coarcted aorta. The observed increase in MPS may have been a factor directly responsible for the increase in the sodium content of the hypertensive aorta since MPS can act as polyelectrolytes and bind cations. Although the arterial pressure may influence certain metabolic functions in the arteries, it did not appear to have a direct effect on the arterial lipids since the lipid content of the hypertensive and of the relatively normotensive portions of the coarcted aorta were comparable to the values found in the normal aorta. Images PMID:5645864

  10. Arterial stiffness is regulated by nitric oxide and endothelium-derived hyperpolarizing factor during changes in blood flow in humans.

    PubMed

    Bellien, Jeremy; Favre, Julie; Iacob, Michele; Gao, Ji; Thuillez, Christian; Richard, Vincent; Joannidès, Robinson

    2010-03-01

    Cytochrome-derived epoxyeicosatrienoic acids may be important endothelium-derived hyperpolarizing factors, opening calcium-activated potassium channels, but their involvement in the regulation of arterial stiffness during changes in blood flow in humans is unknown. In healthy volunteers, we measured arterial pressure, radial artery diameter, wall thickness, and flow (NIUS02) during hand skin heating in the presence of saline or inhibitors of NO synthase (N(G)-monomethyl-L-arginine), calcium-activated potassium channels (tetraethylammonium), and cytochrome epoxygenases (fluconazole). Arterial compliance and elastic modulus were calculated and fitted as functions of midwall stress to suppress the confounding influence of geometric changes. Under saline infusion, heating induced an upward shift of the compliance-midwall stress curve and a downward shift of the modulus-midwall stress curve demonstrating a decrease in arterial tone and stiffness when blood flow increases. These shifts were reduced by N(G)-monomethyl-L-arginine and abolished by the combinations of N(G)-monomethyl-L-arginine+tetraethylammonium and N(G)-monomethyl arginine+fluconazole. In parallel, in isolated mice coronary arteries