Skin Sodium and Hypertension: a Paradigm Shift?

PURPOSE OF REVIEW: Dietary sodium is an important trigger for hypertension and humans show a heterogeneous blood pressure response to salt intake. The precise mechanisms for this have not been fully explained although renal sodium handling has traditionally been considered to play a central role. RECENT FINDINGS: Animal studies have shown that dietary salt loading results in non-osmotic sodium accumulation via glycosaminoglycans and lymphangiogenesis in skin mediated by vascular endothelial growth factor-C, both processes attenuating the rise in BP. Studies in humans have shown that skin could be a buffer for sodium and that skin sodium could be a marker of hypertension and salt sensitivity. Skin sodium storage could represent an additional system influencing the response to salt load and blood pressure in humans.British Heart Foundation NIHR Addenbrookes Charitable Trus

Feeling the pressure: (patho) physiological mechanisms of weight gain and weight loss in humans.

Obesity is an ongoing global epidemic and has adverse consequences for cardiovascular health. Obesity is often associated with hypertension, which is, itself, a common condition and an important cause of morbidity and mortality worldwide. Although animal models of obesity have provided extensive data on the links between obesity and hypertension, a greater understanding of the pathways linking obesity and hypertension in humans is likely to assist translation of animal data, and may, itself, identify important treatment strategies. Ultimately, this could have a substantial impact on human health, both at an individual and population level. The current review will focus specifically on studies of experimental weight gain and weight loss in humans and the following key areas, which are strongly related to blood pressure: cardiovascular function, autonomic nervous system function, metabolic function and the impact of cardiorespiratory fitness.National Institute for Health Research Cambridge Biomedical Research CentreThis is the author accepted manuscript. The final version is available from Nature Publishing via http://dx.doi.org/10.1038/hr.2016.14

Endothelin-1 regulates arterial pulse wave velocity in vivo

AbstractObjectivesThe aim of this study was to investigate whether endothelin-1, acting locally, regulates arterial distensibility, assessed by measuring pulse-wave velocity in vivo.BackgroundArterial stiffness is a key determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. However, the role of endothelin-1 (ET-1) in the regulation of arterial stiffness has not been investigated.MethodsAll studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated using the foot-to-foot methodology from two pressure waveforms simultaneously recorded with a high-fidelity, dual pressure-sensing catheter placed in the common iliac artery.ResultsIntra-arterial infusion of ET-1 significantly increased iliac PWV by 12 ± 5% (mean ± STD; p < 0.001), whereas infusion of the endothelin-A (ETA) receptor antagonist BQ-123 significantly reduced PWV by 12 ± 4% (p < 0.001). After BQ-123 infusion, exogenously infused ET-1 did not significantly change PWV compared with infusion of saline (change of −0.08 ± 0.11% vs. −0.01 ± 0.07%; p = 0.53). Importantly, infusion of BQ-123 or ET-1 distal to the common iliac artery did not affect PWV.ConclusionsThese results demonstrate, for the first time, that endogenous ET-1 production directly regulates large artery PWV in vivo. In addition, exogenous ET-1 increases PWV, and this can be blunted by ETAreceptor blockade. These observations explain, in part, why conditions that exhibit up-regulation of ET-1 are also associated with arterial stiffening. Therefore, drugs that block ETAreceptors may be effective in reducing large artery stiffness in humans, and thus cardiovascular risk

Risks of adverse perinatal and maternal outcomes among women with hypertensive disorders of pregnancy in southwestern Uganda.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are a leading cause of global perinatal (fetal and neonatal) and maternal morbidity and mortality. We sought to describe HDP and determine the magnitude and risk factors for adverse perinatal and maternal outcomes among women with HDP in southwestern Uganda. METHODS: We prospectively enrolled pregnant women admitted for delivery and diagnosed with HDP at a tertiary referral hospital in southwestern Uganda from January 2019 to November 2019, excluding women with pre-existing hypertension. The participants were observed and adverse perinatal and maternal outcomes were documented. We used multivariable logistic regression models to determine independent risk factors associated with adverse perinatal and maternal outcomes. RESULTS: A total of 103 pregnant women with a new-onset HDP were enrolled. Almost all women, 93.2% (n = 96) had either pre-eclampsia with severe features or eclampsia. The majority, 58% (n = 60) of the participants had an adverse perinatal outcome (36.9% admitted to the neonatal intensive care unit (ICU), 20.3% stillbirths, and 1.1% neonatal deaths). Fewer participants, 19.4% (n = 20) had an adverse maternal outcome HELLP syndrome (7.8%), ICU admission (3%), and postpartum hemorrhage (3%). In adjusted analyses, gestational age of < 34 weeks at delivery and birth weight <2.5kg were independent risk factors for adverse perinatal outcomes while referral from another health facility and eclampsia were independent risk factors for adverse maternal outcomes. CONCLUSION: Among women with HDP at our institution, majority had preeclampsia with severe symptoms or eclampsia and an unacceptably high rate of adverse perinatal and maternal outcomes; over a fifth of the mothers experiencing stillbirth. This calls for improved antenatal surveillance of women with HDP and in particular improved neonatal and maternal critical care expertise at delivering facilities. Earlier detection and referral, as well as improvement in initial management at lower level health units and on arrival at the referral site is imperative

Socioeconomic status, education, and aortic stiffness progression over 5 years: the Whitehall II prospective cohort study.

OBJECTIVE: The inverse association between socioeconomic status (SES) and cardiovascular disease (CVD) risk is well documented. Aortic stiffness assessed by aortic pulse wave velocity (PWV) is a strong predictor of CVD events. However, no previous study has examined the effect of SES on arterial stiffening over time. The present study examines this association, using several measures of SES, and attained education level in a large ageing cohort of British men and women. METHODS: Participants were drawn from the Whitehall II study. The sample was composed of 3836 men and 1406 women who attended the 2008-2009 clinical examination (mean age = 65.5 years). Aortic PWV was measured in 2008-2009 and in 2012-2013 by applanation tonometry. A total of 3484 participants provided PWV measurements on both occasions. The mean difference in 5-year PWV change was examined according to household income, education, employment grade, and father's social class, using linear mixed models. RESULTS: PWV increase [mean: confidence interval (m/s)] over 5 years was higher among participants with lower employment grade (0.38: 0.11-0.65), household income (0.58, 95%: 0.32-0.85), and education (0.30: 0.01, 0.58), after adjusting for sociodemographic variables, BMI, alcohol consumption, smoking, and other cardiovascular risk factors, namely SBP, mean arterial pressure, heart rate, cholesterol, diabetes, and antihypertensive use. CONCLUSION: The present study supports the presence of robust socioeconomic disparities in aortic stiffness progression. Our findings suggest that arterial aging could be an important pathophysiological pathway explaining the impact of lower SES on CVD risk

Maternal Cardiovascular Dysfunction is Associated with Hypoxic Cerebral and Umbilical Doppler Changes.

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention

Aortic Pulse Wave Velocity as Adjunct Risk Marker for Assessing Cardiovascular Disease Risk : Prospective Study

Peer reviewe

Validation of a Non-invasive Inverse Problem-Solving Method for Stroke Volume.

Stroke volume (SV) is a major biomarker of cardiac function, reflecting ventricular-vascular coupling. Despite this, hemodynamic monitoring and management seldomly includes assessments of SV and remains predominantly guided by brachial cuff blood pressure (BP). Recently, we proposed a mathematical inverse-problem solving method for acquiring non-invasive estimates of mean aortic flow and SV using age, weight, height and measurements of brachial BP and carotid-femoral pulse wave velocity (cfPWV). This approach relies on the adjustment of a validated one-dimensional model of the systemic circulation and applies an optimization process for deriving a quasi-personalized profile of an individual's arterial hemodynamics. Following the promising results of our initial validation, our first aim was to validate our method against measurements of SV derived from magnetic resonance imaging (MRI) in healthy individuals covering a wide range of ages (n = 144; age range 18-85 years). Our second aim was to investigate whether the performance of the inverse problem-solving method for estimating SV is superior to traditional statistical approaches using multilinear regression models. We showed that the inverse method yielded higher agreement between estimated and reference data (r = 0.83, P < 0.001) in comparison to the agreement achieved using a traditional regression model (r = 0.74, P < 0.001) across a wide range of age decades. Our findings further verify the utility of the inverse method in the clinical setting and highlight the importance of physics-based mathematical modeling in improving predictive tools for hemodynamic monitoring