Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: a systematic review and meta-analysis of randomized controlled trials Background: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin–angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. Methods: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. Results: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by −24.55% (95% CI −29.57 to −19.53%), urine protein-to-creatinine ratio (UPCR) by −53.93% (95% CI −79% to −28.86%) and 24 h albumin excretion by −32.47% (95% CI −41.1 to −23.85%). MRAs also reduced UACR by −22.48% (95% CI −24.51 to −20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of −2.38 ml/min per 1.73 m2 (95% CI −3.51 to −1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16–0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69–4.08) compared with placebo/active control. Conclusion: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels.

Prehypertension and risk of cardiovascular diseases: a meta-analysis of 47 cohort studies Objective: To assess the association of prehypertension (SBP 120–139 mmHg and/or DBP 80–89 mmHg) and total cardiovascular diseases (CVDs), coronary heart disease (CHD), myocardial infarction (MI), and stroke. Methods: PubMed, Embase, and Web of Science were searched for articles published up to 7 November 2018. Normal range BP was considered SBP less than 120 mmHg and DBP less than 80 mmHg. RRs and 95% CIs were pooled using fixed-effects models. Meta-regression was conducted to estimate the heterogeneity among subgroups. Results: We included 27 articles (47 studies including 491 666 study participants) in the analysis. Prehypertension was associated with total CVDs (RR 1.40, 95% CI 1.34–1.46), CHD (1.40, 1.28–1.52), MI (1.86, 1.50–2.32), and stroke (1.66, 1.56–1.76). Risk of total CVDs, MI, and stroke was increased with low-range prehypertension (low-range: SBP 120–129 mmHg and/or DBP 80–84 mmHg) versus normal BP – RR 1.42 (95% CI 1.29–1.55), 1.43 (1.10–1.86), and 1.52 (1.27–1.81), respectively – and risk of total CVDs, CHD, MI, and stroke was increased with high-range prehypertension (high-range: SBP 130–139 mmHg and/or DBP 85–89 mmHg) – RR 1.81 (95% CI 1.56–2.10), 1.65 (1.13–2.39), 1.99 (1.59–2.50), and 1.99 (1.68–2.36), respectively. The population-attributable risk for the association of total CVDs, CHD, MI, and stroke with prehypertension was 12.09, 13.26, 24.60, and 19.15%, respectively. Conclusion: Prehypertension, particularly high-range, is associated with increased risk of total CVDs, CHD, MI, and stroke. Effective control of prehypertension could prevent more than 10% of CVD cases.

Consequences of the evolutionary cardiovascular challenge of human bipedalism: orthostatic intolerance syndromes, orthostatic hypertension In quadrupeds, the arterial baroreflex has dominance in the reflex homeostatic responses, which protect against haemorrhage. In humans, it is the low pressure cardiopulmonary reflex, which protects against the analogous cardiovascular challenge of gravity-dependent venous pooling with standing. To preserve orthostatic cardiovascular homeostasis with the emergence of bipedalism in humans the low pressure reflex, a minor, subsidiary reflex in quadripeds, was co-opted. Mirroring the imperfect skeletal evolution to bipedalism, this cardiovascular development has been problematic, with dysregulation manifesting as disabling orthostatic intolerance syndromes and, paradoxically, an orthostatic hypertensive response that appears to play a role in the development of essential hypertension in some people. Improved understanding of these evolutionary faults provides new options for postural and pharmacological treatments.

The smoothness index: an ‘all purposes’ approach to the assessment of the homogeneity of 24-h blood pressure control? No abstract available

Prognostic significance of acute hypertensive response in ischemic stroke or transient ischemic attack patients and its relationship with left ventricular myocardial function Objectives: Acute hypertensive response (AHR) in acute stroke is associated with adverse outcomes; however, the underlying pathophysiology of the association is poorly understood and its prognostic impact in ischemic stroke remains unclear. We aimed to investigate the prognostic significance of AHR in patients with ischemic stroke or transient ischemic attack (TIA), and further examined the relationship between AHR and myocardial function, using two-dimensional speckle-tracking echocardiography (2D-STE). Methods: A total of 244 consecutive patients with acute ischemic stroke (AIS) (n = 192) or TIA (n = 52), who were evaluated with 2D-STE within 7 days from admission, were retrospectively analysed. The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infraction or recurrent ischemic stroke. Results: Among the study population, AHR was observed in 161 (66%) patients. During a mean follow-up of 21.0 ± 12.5 months, 29 patients (11.9%) [25 (15.5%) AHR vs. 4 (4.8%) No AHR, P = 0.014] reached the primary endpoint. A Kaplan–Meier curve revealed that patients with AHR had a significantly higher incidence of MACCE than those without AHR (log-rank P = 0.013). Multivariate Cox regression analysis demonstrated that AHR [adjusted hazard ratio 4.60, 95% confidence interval (95% CI) 1.31–16.15] was a strong predictor of MACCE. In multivariate logistic regression analysis, left ventricular global longitudinal strain (per 1% decrease) showed a significant relationship with AHR (adjusted odds ratio 1.17, 95% CI 1.02–1.35). Conclusion: AHR in patients with AIS or TIA may be an important poor prognostic marker related to myocardial dysfunction.

Association of hypertriglyceridemic waist-to-height ratio and its dynamic status with incident hypertension: the Rural Chinese Cohort Study Objective: We aimed to evaluate whether hypertriglyceridemic waist-to-height ratio (HWHtR) and its dynamic status was associated with hypertension (HTN). Methods: We examined data for 10 312 nonhypertensive participants aged at least 18 years from the Rural Chinese Cohort Study at the baseline examination who were followed until 2014 with a median follow-up of 6 years. HWHtR was defined by combined triglyceride level and waist-to-height ratio (WHtR). Multiple logistic regression models were used to examine the probability of incident HTN according to HWHtR and its transformation, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 127 men and 225 women with high triglyceride level and high WHtR (HTHWH) had incident HTN during follow-up. After adjusting for potential confounders, the probability of HTN was increased with HTHWH for men [OR 1.49 (95% CI 1.01–2.20)] but this association was not significant for women [1.21 (0.88–1.66)]. The results of the sensitivity analyses were robust for men and women. The ORs were generally consistent on subgroup analysis by age,BMI, SBP and DBP for men. As compared with persistent normal triglyceride level and normal WHtR (NTNWH), the transformation from baseline NTNWH to follow-up HTHWH was associated with increased probability of HTN for men [OR 4.16 (95% CI 2.21–7.84)]. However, for women, the association of changed HWHtR from baseline to follow-up with probability of HTN was not significant for almost all transformation groups. Conclusion: HWHtR and its dynamic status was associated with incident HTN for rural Chinese men. From this cohort study, HWHtR may be an indicator for interventions aiming to reduce HTN among these men.

Plasminogen activator inhibitor-1 activity and the 4G/5G polymorphism are prospectively associated with blood pressure and hypertension status Objectives: Plasminogen activator inhibitor-1 (PAI-1) has consistently shown positive associations with blood pressure (BP). Whether elevations in PAI-1 levels precede or result from raised BP is still under debate and data on prospective studies are limited. Hence, we investigated the prospective associations of PAI-1 and the 4G/5G polymorphism with brachial and central BP and pulse pressure (PP) over a 10-year period. Methods: Black South Africans aged 30 years and older were included. Baseline data collection commenced in 2005 (n = 2010) with follow-up data collection in 2010 (n = 1288) and 2015 (n = 926). Plasma PAI-1 activity (PAI-1act), 4G/5G polymorphism genotyping, waist circumference and BP measurements were performed and analysed using sequential regression and mixed models. Results: In multivariable adjusted analyses, PAI-1act and the 4G/4G (vs. the 5G/5G) genotype increased the odds of developing hypertension in the total group [1.04 (1.01; 1.08) and 1.82 (1.07; 3.12) respectively]. Furthermore, PAI-1act was prospectively associated with brachial SBP (r = 0.0815) and PP (r = 0.0832) in the total group, and with central PP in women (r = 0.1125; all P < 0.05). Addition of waist circumference to the models either decreased or nullified the contribution of PAI-1act to BP and hypertension development. Conclusion: PAI-1act and the 4G/4G (vs. the 5G/5G) genotype increased the odds of developing hypertension. Furthermore, PAI-1act associated prospectively with both brachial and central BP. These associations were mediated in part by central adiposity. The study supports the hypothesis that PAI-1 also contributes to hypertension development rather than solely being a consequence thereof.

Association between dietary carotenoid intakes and hypertension in adults: National Health and Nutrition Examination Survey 2007–2014 Objective: Few epidemiological studies concentrated on dietary carotenoids and hypertension since new hypertension guideline released in 2017. Thus, this study was aimed to evaluate their association. Methods: Data from National Health and Nutrition Examination Survey (NHANES) 2007–2014 were used in this cross-sectional study. Dietary carotenoids data were obtained from 24-h dietary recall interviews. Hypertension was defined as SBP at least 130 mmHg or DBP at least 80 mmHg, taking antihypertensive medicine or self-report. Logistic regression models and restricted cubic spline models were applied to explore the associations between α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein with zeaxanthin, and total carotenoids from diet and supplements and hypertension. Total carotenoids showed significant reductive risk of hypertension at 100 μg/kg per day and over. Results: A total of 17 398 adults aged 20 years and over were identified. High dose of β-carotene, lycopene, lutein with zeaxanthin, and total carotenoids were significantly associated with decreased risk of hypertension in crude results. After multivariate-adjustment in model 2, the odds ratios (OR) with 95% confidence intervals (CI) of β-cryptoxanthin, lycopene, lutein with zeaxanthin and total carotenoids for hypertension were 0.79 (0.67–0.93), 0.85 (0.73–0.98), 0.69 (0.58–0.83), 0.73 (0.62–0.86) for the highest versus lowest quartile intakes, respectively. Dose–response analyses showed that all of the carotenoids were inversely associated with hypertension in a linear manner. Total carotenoids showed significant effect of lower risk of hypertension at 100 μg/kg per day. Conclusion: Intakes of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein with zeaxanthin, and total carotenoids were inversely associated with hypertension in US adults. The intake of total carotenoids was suggested at least 100 μg/kg per day for general adult population.

Sex differences in masked hypertension: the Coronary Artery Risk Development in Young Adults study Objective: To evaluate the association of sex with masked hypertension, defined by out-of-clinic hypertension based on ambulatory blood pressure monitoring (ABPM) among adults without hypertension based on blood pressure (BP) measured in the clinic, after adjusting for potential confounders. Methods: We evaluated sex differences in the prevalence of masked hypertension and the difference between awake, or alternatively 24-h, ambulatory BP and clinic BP using multivariable adjusted models among 658 participants who underwent 24-h ABPM and had clinic SBP/DBP less than 140/90 mmHg during the Year 30 Exam of the Coronary Artery Risk Development in Young Adults study. Results: The mean age ± standard deviation (SD) of the participants was 54.8 ± 3.7 years, 58.4% were women, and 58.2% were black. The prevalence of any masked hypertension was 37.5% among women and 60.6% among men. In a model including adjustment for demographics, cardiovascular risk factors, antihypertensive medication, and clinic BP, the prevalence ratios (95% confidence intervals) comparing men versus women were 1.39 (1.18–1.63) for any masked hypertension, and 1.60 (1.28–1.99), 1.71 (1.36–2.15), and 1.40 (1.13–1.73) for masked awake, 24-h and asleep hypertension, respectively. In a fully adjusted model, the differences between mean awake ambulatory BP and clinic BP were 2.75 [standard error (SE) 0.92] mmHg higher for SBP and 3.61 (SE 0.58) mmHg higher for DBP among men compared with women. Conclusion: The prevalence of masked hypertension on ABPM was high in both men and women. Male sex was an independent predictor of masked hypertension.