Showing papers in "Hypertension in 2017"
TL;DR: Oxidative stress and inflammation, key mechanisms of endothelial dysfunction and arterial damage, link these risk factors to vascular disease, arterial stiffness, and aging.
Abstract: Age-related decline in function is a physiological phenomenon occurring in all organ systems. However, acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension.1,2 In the vascular system, this is characterized by progressive pathological remodeling with stiffening,3 typically associated with extracellular matrix (ECM) alterations in collagen and elastin.4 This is, in part, dependent on cellular senescence and growth arrest.5 Although hypertension and atherosclerosis are associated with accumulation of cellular senescence markers in the vascular wall, these conditions are often associated with vascular dysfunction rather than simple loss of proliferative capacity.6 For example, risk factors for cardiovascular disease, such as hypertension, smoking, hyperlipidaemia, or diabetes mellitus are associated with accelerated decline of vascular function.2 This is why vascular age determination has been introduced in key clinical guidelines for cardiovascular prevention, to indicate to the patient how their lifestyle contributes to the acceleration of vascular function deterioration.7
Oxidative stress and inflammation, key mechanisms of endothelial dysfunction and arterial damage, link these risk factors to vascular disease, arterial stiffness, and aging. These underlie macro- and microangiopathy, renal dysfunction, cardiac ischemia, and cognitive decline (Figure). Several novel pathways regulating these mechanisms of accelerated vascular aging have been elucidated in recent issues of Hypertension and are further discussed in the present Best Papers in Hypertension review.
Figure.
Central role of oxidative stress in accelerated vascular aging in hypertension. AT1R indicates angiotensin II receptor type 1; BH2, dihydrobiopterin; BH4, tetrahydrobiopterin; BMP, bone morphogenic protein; CypD, cyclophilin D; eNOS, endothelial NO synthase; ET1R, endothelin 1 receptor; H2O2, hydrogen peroxide; MMP, matrix metalloproteinase; Nox, NADPH oxidase; O2−., superoxide anion; RANTES, regulated on activation, normal T cell expressed and secreted chemokine; and SmgGDS, GTP-binding protein dissociation …
408 citations
TL;DR: Measurement of the baPWV could enhance the efficacy of prediction of the risk of development of CVD over that of the Framingham risk score, which is based on the traditional cardiovascular risk factors.
Abstract: An individual participant data meta-analysis was conducted in the data of 14 673 Japanese participants without a history of cardiovascular disease (CVD) to examine the association of the brachial-a...
319 citations
TL;DR: It is suggested that improved access to and engagement in medical care might improve hypertension control in young adults, particularly young adult men, and reduce life-time cardiovascular risk.
Abstract: Overall hypertension prevalence has not changed in the United States in recent decades although awareness, treatment, and control improved. However, hypertension epidemiology and its temporal trends may differ in younger adults compared with older adults. Our study included 41 331 participants ≥18 years of age from 8 National Health and Nutrition Examination Surveys (1999-2014) and estimated temporal trends of hypertension, awareness, treatment, and control among young adults (age, 18-39 years) compared with middle-age (age, 40-59 years) and older adults (age, ≥60 years). In 2013 to 2014, 7.3% of the US young adults had hypertension. During 1999 to 2014, young adults saw larger increases in hypertension awareness, treatment, and control than did older adults. However, all of these components of hypertension control were lower among young adults compared with middle-aged or older adults (74.7% younger versus 81.9% middle versus 88.4% older for awareness; 50.0% versus 70.3% versus 83.0% for treatment; and 40.2% versus 56.7% versus 54.4% for control). Worse hypertension awareness, treatment, and control in young adults overall were mostly driven by worse measures in young adult men compared with young adult women. More frequent healthcare visits by young adult women explained ≈28% of the sex-related difference in awareness, 60% of the difference in treatment, and 52% of the difference in control. These findings suggest that improved access to and engagement in medical care might improve hypertension control in young adults, particularly young adult men, and reduce life-time cardiovascular risk.
230 citations
TL;DR: It is suggested that long-term exposure to ambient PM2.5 might be an important risk factor of hypertension and is responsible for significant hypertension burden in adults in China and a higher consumption of fruit may mitigate, whereas overweight and obesity could enhance this effect.
Abstract: Long-term exposure to ambient fine particulate pollution (PM 2.5 ) has been associated with cardiovascular diseases. Hypertension, a major risk factor for cardiovascular diseases, has also been hypothesized to be linked to PM 2.5 . However, epidemiological evidence has been mixed. We examined long-term association between ambient PM 2.5 and hypertension and blood pressure. We interviewed 12 665 participants aged 50 years and older and measured their blood pressures. Annual average PM 2.5 concentrations were estimated for each community using satellite data. We applied 2-level logistic regression models to examine the associations and estimated hypertension burden attributable to ambient PM 2.5 . For each 10 μg/m 3 increase in ambient PM 2.5 , the adjusted odds ratio of hypertension was 1.14 (95% confidence interval, 1.07–1.22). Stratified analyses found that overweight and obesity could enhance the association, and consumption of fruit was associated with lower risk. We further estimated that 11.75% (95% confidence interval, 5.82%–18.53%) of the hypertension cases (corresponding to 914, 95% confidence interval, 453–1442 cases) could be attributable to ambient PM 2.5 in the study population. Findings suggest that long-term exposure to ambient PM 2.5 might be an important risk factor of hypertension and is responsible for significant hypertension burden in adults in China. A higher consumption of fruit may mitigate, whereas overweight and obesity could enhance this effect.
151 citations
TL;DR: Asymptomatic hyperuricemia carries a significant risk for developing cardiometabolic conditions in Japanese individual without comorbidities.
Abstract: Whether asymptomatic hyperuricemia in the absence of comorbidities increases the risk for cardiometabolic disorders and chronic kidney disease remains controversial. This study was conducted to clarify the association between asymptomatic hyperuricemia and cardiometabolic conditions. Subjects consisting of Japanese adults between 30 and 85 years of age were enrolled in the study at Center for Preventive Medicine, St Luke’s International Hospital, Tokyo, and were available at enrollment (2004) and at 5-year follow-up (2009). Subjects were excluded if they were overweight or obese, hypertensive, diabetic, and dyslipidemic, had a history of gout or hyperuricemia on medications, or had chronic kidney disease as estimated glomerular filtration rate 2 . Linear and logistic regression analyses were used to examine the relationship between hyperuricemia and development of hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and overweight/obesity (unadjusted and adjusted for age, sex, smoking, drinking habits, baseline estimated glomerular filtration rate, and body mass index). Five thousand eight hundred and ninety-nine subjects without comorbidities (mean age of 47±10 years, 1864 men) were followed for 5 years. Hyperuricemia (defined as >7 mg/dL in men and ≥6 mg/dL in women) was associated with increased cumulative incidence of hypertension (14.9% versus 6.1%; P P P P P =0.087) showed a trend but did not reach statistical significance. In conclusion, asymptomatic hyperuricemia carries a significant risk for developing cardiometabolic conditions in Japanese individual without comorbidities.
151 citations
TL;DR: It is demonstrated that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure–lowering therapy and further development of discriminatory models incorporating these parameters might prove clinically useful in assessment ofnonadherence in countries where biochemical analysis is unavailable.
Abstract: Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence (P<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (P≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure-lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.
142 citations
TL;DR: The PARAMETER study as mentioned in this paper evaluated the effect of sacubitril/valsartan versus olmesartan in reducing clinic and ambulatory central aortic and brachial pressures in elderly patients with systolic hypertension and stiff arteries.
Abstract: Effective treatment of systolic hypertension in elderly patients remains a major therapeutic challenge. A multicenter, double-blind, randomized controlled trial with sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, was conducted to determine its effects versus olmesartan (angiotensin receptor blocker) on central aortic pressures, in elderly patients (aged ≥60 years) with systolic hypertension and pulse pressure >60 mm Hg, indicative of arterial stiffness. Patients (n=454; mean age, 67.7 years; mean seated systolic blood pressure, 158.6 mm Hg; mean seated pulse pressure, 69.7 mm Hg) were randomized to receive once-daily sacubitril/valsartan 200 mg or olmesartan 20 mg, force titrated to double the initial doses after 4 weeks, before primary assessment at 12 weeks. The study extended double-blind treatment for 12 to 52 weeks, during which amlodipine (2.5-5 mg) and subsequently hydrochlorothiazide (6.25-25 mg) were added-on for patients not achieving blood pressure target (<140/90). At week 12, sacubitril/valsartan reduced central aortic systolic pressure (primary assessment) greater than olmesartan by -3.7 mm Hg (P=0.010), further corroborated by secondary assessments at week 12 (central aortic pulse pressure, -2.4 mm Hg, P<0.012; mean 24-hour ambulatory brachial systolic blood pressure and central aortic systolic pressure, -4.1 mm Hg and -3.6 mm Hg, respectively, both P<0.001). Differences in 24-hour ambulatory pressures were pronounced during sleep. After 52 weeks, blood pressure parameters were similar between treatments (P<0.002); however, more patients required add-on antihypertensive therapy with olmesartan (47%) versus sacubitril/valsartan (32%; P<0.002). Both treatments were equally well tolerated. The PARAMETER study (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Measuring Arterial Stiffness in the Elderly), for the first time, demonstrated superiority of sacubitril/valsartan versus olmesartan in reducing clinic and ambulatory central aortic and brachial pressures in elderly patients with systolic hypertension and stiff arteries.
142 citations
TL;DR: In this article, the authors performed a meta-analysis, including dose-response analysis, to quantitatively evaluate the association between physical activity (PA) and incident hypertension, and found that additional benefits for hypertension prevention occur as the amount of PA increases.
Abstract: Despite the inverse association between physical activity (PA) and incident hypertension, a comprehensive assessment of the quantitative dose–response association between PA and hypertension has not been reported. We performed a meta-analysis, including dose–response analysis, to quantitatively evaluate this association. We searched PubMed and Embase databases for articles published up to November 1, 2016. Random effects generalized least squares regression models were used to assess the quantitative association between PA and hypertension risk across studies. Restricted cubic splines were used to model the dose–response association. We identified 22 articles (29 studies) investigating the risk of hypertension with leisure-time PA or total PA, including 330 222 individuals and 67 698 incident cases of hypertension. The risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92–0.96) with each 10 metabolic equivalent of task h/wk increment of leisure-time PA. We found no evidence of a nonlinear dose–response association of PA and hypertension ( P nonlinearity =0.094 for leisure-time PA and 0.771 for total PA). With the linear cubic spline model, when compared with inactive individuals, for those who met the guidelines recommended minimum level of moderate PA (10 metabolic equivalent of task h/wk), the risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92–0.97). This meta-analysis suggests that additional benefits for hypertension prevention occur as the amount of PA increases.
139 citations
University of Minnesota1, Wake Forest University2, Baylor College of Medicine3, Columbia University4, Veterans Health Administration5, Vanderbilt University6, National Institutes of Health7, Colorado School of Public Health8, Mayo Clinic9, Tulane University10, Carolinas Healthcare System11, University of California, San Diego12, University of Pennsylvania13, University of Tennessee Health Science Center14, Case Western Reserve University15
TL;DR: Targeting a systolic BP of <120 mm Hg, when compared with <140 mm’g, resulted in lower nighttime, daytime, and 24-hour systolics BP, but did not change the night/day syStolic BP ratio.
Abstract: The effect of clinic-based intensive hypertension treatment on ambulatory blood pressure (BP) is unknown. The goal of the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP ancillary...
137 citations
TL;DR: In this paper, a retrospective cohort study to review all women who gave birth at a tertiary hospital in Sydney between the years 1980 and 1989 (n=31 656) was conducted.
Abstract: Hypertensive disorders of pregnancy are associated with vascular dysfunction in the pregnancy and an increased risk of long-term cardiovascular disease (CVD) in the mother. What remains to be understood is whether the length, severity of the disease, the treatment of hypertension in pregnancy, or the subtype of hypertensive disorders of pregnancy are significant predictors of future CVD. We undertook a retrospective cohort study to review all women who gave birth at a tertiary hospital in Sydney between the years 1980 and 1989 (n=31 656). A cohort of women was further defined by having hypertension during the antenatal, intrapartum, or postnatal periods (n=4387). Randomly selected records of women (n=1158) with a hypertensive disorder of pregnancy were individually reviewed to collect data on their pregnancy and pregnancy outcomes. The entire cohort then underwent linkage analysis to future CVDs. Women who presented with gestational hypertension were at greater risk of future hypertension and ischemic heart disease compared with the women who were diagnosed with preeclampsia. There was no significant difference between the women who were treated with antihypertensive medication and the women who did not receive antihypertensive medication or the duration of hypertensive disorders of pregnancy and future admission for CVD, although severity of hypertension tracked with increased risk of future hypertension in all groups. This study demonstrated that all women who present with any of the subtypes of hypertensive disorders in pregnancy are at significant risk of future CVD compared with women who remain normotensive during their pregnancy.
134 citations
TL;DR: In this paper, the authors conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention.
Abstract: Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention.
TL;DR: Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies, and their siblings, born after anormotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association.
Abstract: Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring’s cardiovascular risk profile in young adulthood and their siblin...
TL;DR: Data show that nonadherent hypertensive patients respond to liquid chromatography–tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop, and such repeated biochemical analyses should be considered as a therapeutic approach in nonadherence hypertensive Patients.
Abstract: We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.
TL;DR: 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources are identified and these robustly implicated genes may provide new leads for therapeutic innovation.
Abstract: Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
TL;DR: The first observation of functional eNOS expressed on STBEV from NP and preeclampsia placentae, as well as in plasma is observed, contributing to the decreased NO bioavailability in this disease.
Abstract: Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age–matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N G -nitro-l-arginine methyl ester (eNOS inhibitor; P N -(3-(aminomethyl) bezyl) acetamidine) (inducible nitric oxide synthase inhibitor). STBEV-eNOS catalytic activity was confirmed by visualizing eNOS dimerization. STBEV-eNOS was more abundant in uterine vein compared with peripheral blood, indicating placental origin. STBEV isolated from preeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; P P P
TL;DR: A continuum of renin-independent aldosteronism and mineralocorticoid receptor activity in normotension that ranges from subtle to overtly dysregulated and autonomous is indicated.
Abstract: Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity ( 12 μg/24 hours with urinary sodium excretion >200 mmol/24 hours. Across the population, there were strong and significant associations between higher aldosterone excretion rate and higher urinary potassium excretion, higher angiotensin II-stimulated aldosterone, and lower plasma renin activity, suggesting a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity. Autonomous aldosterone secretion that fulfilled confirmatory criteria for primary aldosteronism was detected in 29 participants (14%). Normotensives with evidence suggestive of confirmed primary aldosteronism had higher 24-hour urinary aldosterone excretion rate (20.2±12.2 versus 6.2±2.9 μg/24 hours; P<0.001) as expected, but also higher angiotensin II-stimulated aldosterone (12.4±8.6 versus 6.6±4.3 ng/dL; P<0.001) and lower 24-hour urinary sodium-to-potassium excretion (2.69±0.65 versus 3.69±1.50 mmol/mmol; P=0.001); however, there were no differences in age, aldosterone-to-renin ratio, blood pressure, or renal plasma flow between the 2 groups. These findings indicate a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity in normotension that ranges from subtle to overtly dysregulated and autonomous. Longitudinal studies are needed to determine whether this spectrum of autonomous aldosterone secretion contributes to hypertension and cardiovascular disease.
TL;DR: Functional studies on primary human tissues and animal models have found that proton pump inhibitors decrease sFlt-1 and soluble endoglin secretion and endothelial dysfunction, dilate blood vessels, decrease blood pressure, and have antioxidant and anti-inflammatory properties.
Abstract: Preeclampsia is a severe complication of pregnancy. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. Oxidative stress and vascular inflammation exacerbate the endothelial injury. A drug that can block these pathophysiological steps would be an attractive treatment option. Proton pump inhibitors (PPIs) are safe in pregnancy where they are prescribed for gastric reflux. We performed functional studies on primary human tissues and animal models to examine the effects of PPIs on sFlt-1 and soluble endoglin secretion, vessel dilatation, blood pressure, and endothelial dysfunction. PPIs decreased sFlt-1 and soluble endoglin secretion from trophoblast, placental explants from preeclamptic pregnancies, and endothelial cells. They also mitigated tumor necrosis factor-α-induced endothelial dysfunction: PPIs blocked endothelial vascular cell adhesion molecule-1 expression, leukocyte adhesion to endothelium, and disruption of endothelial tube formation. PPIs decreased endothelin-1 secretion and enhanced endothelial cell migration. Interestingly, the PPI esomeprazole vasodilated maternal blood vessels from normal pregnancies and cases of preterm preeclampsia, but its vasodilatory effects were lost when the vessels were denuded of their endothelium. Esomeprazole decreased blood pressure in a transgenic mouse model where human sFlt-1 was overexpressed in placenta. PPIs upregulated endogenous antioxidant defenses and decreased cytokine secretion from placental tissue and endothelial cells. We have found that PPIs decrease sFlt-1 and soluble endoglin secretion and endothelial dysfunction, dilate blood vessels, decrease blood pressure, and have antioxidant and anti-inflammatory properties. They have therapeutic potential for preeclampsia and other diseases where endothelial dysfunction is involved.
TL;DR: A substantial body of clinical data on elevated blood pressure (BP) in children and adolescents have been published during the past decade, and the American Academy of Pediatrics supported development and publication of a new clinical practice guideline on high BP in childhood.
Abstract: A substantial body of clinical data on elevated blood pressure (BP) in children and adolescents have been published during the past decade. In response to the need to update management guidelines on pediatric hypertension, the American Academy of Pediatrics (AAP) supported development and publication of a new clinical practice guideline on high BP in childhood. Before 1977, there was no consistent definition of hypertension in childhood, and BP was not commonly measured in asymptomatic children or adolescents. Consequently, childhood hypertension had been considered rare and, if detected, the assumption was that it would be secondary to an underlying disorder. In the mid-1970s, the National High Blood Pressure Education (NHBPEP) of the National Heart Lung and Blood Institute (NHLBI) convened a task force to examine available BP data on healthy children to determine the normal BP distribution in children and define the upper limits of BP according to age. Although available BP data at that time were limited by current standards, it was clear that BP levels in children were related to age, with a progressive increase from early childhood through adolescence. In the absence of long-term outcome data, it was not possible to link a level of childhood BP to risk of later cardiovascular events. Therefore, the task force defined hypertension as the BP level that exceeded the 95th percentile on age-related BP distribution curves. The recommendations of this task force on detection, evaluation, and management of hypertension in children and adolescents were published in 1977.1 In addition to providing a framework on diagnosis of hypertension, the publication included information on proper BP measurement in children, diagnostic evaluation for children with elevated BP, and management of BP in hypertensive children.
That report of that NHBPEP Task Force1 constituted the first clinical practice guideline (CPG) for childhood hypertension. Major …
TL;DR: It is concluded that FMD is a systemic arterial disease and RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation and bilateral RA lesions.
Abstract: Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associate...
TL;DR: The prevalence of prehypertension has decreased modestly since 1999–2000 and risk factors for cardiovascular disease and incident hypertension increased during this time period, including prediabetes, overweight, and obesity.
Abstract: Prehypertension is associated with increased risk for hypertension and cardiovascular disease. Data are limited on the temporal changes in the prevalence of prehypertension and risk factors for hypertension and cardiovascular disease among US adults with prehypertension. We analyzed data from 30 958 US adults ≥20 years of age who participated in the National Health and Nutrition Examination Surveys between 1999 and 2012. Using the mean of 3 blood pressure (BP) measurements from a study examination, prehypertension was defined as systolic BP of 120 to 139 mm Hg and diastolic BP <90 mm Hg or diastolic BP of 80 to 89 mm Hg and systolic BP <140 mm Hg among participants not taking antihypertensive medication. Between 1999-2000 and 2011-2012, the percentage of US adults with prehypertension decreased from 31.2% to 28.2% (P trend=0.007). During this time period, the prevalence of several risk factors for cardiovascular disease and incident hypertension increased among US adults with prehypertension, including prediabetes (9.6% to 21.6%), diabetes mellitus (6.0% to 8.5%), overweight (33.5% to 37.3%), and obesity (30.6% to 35.2%). There was a nonstatistically significant increase in no weekly leisure-time physical activity (40.0% to 43.9%). Also, the prevalence of adhering to the Dietary Approaches to Stop Hypertension eating pattern decreased (18.4% to 11.9%). In contrast, there was a nonstatistically significant decline in current smoking (25.9% to 23.2%). In conclusion, the prevalence of prehypertension has decreased modestly since 1999-2000. Population-level approaches directed at adults with prehypertension are needed to improve risk factors to prevent hypertension and cardiovascular disease.
TL;DR: BP trajectories were associated with the risk of stroke and increasing BP trajectories within the currently designated normal range may still increase the risk for stroke.
Abstract: The association between long-term blood pressure (BP) patterns in community-dwelling adults and risk of intracerebral hemorrhage and cerebral infarction is not well characterized. This prospective study included 79 385 participants, free of stroke, myocardial infarction, and cancer in or before 2010 (baseline). Systolic BP trajectories were identified using latent mixture modeling with data from 2006, 2008, and 2010. Incident cases of intracerebral hemorrhage and cerebral infarction occurred during 2010 to 2014, confirmed by review of medical records, by 3 physicians. We identified 5 distinct systolic BP trajectories during 2006 to 2010. Each of the trajectories was labeled according to their BP range and pattern over time: normotensive-stable (n=26 740), prehypertension-stable (n=35 674), stage 1 hypertension-increasing (n=8215), stage 1 hypertension-decreasing (n=6422), and stage 2 hypertension-stable (n=2334). We documented 1034 incident cases of cerebral infarction and 187 cases of intracerebral hemorrhage. Although the prehypertension-stable trajectory exhibited systolic BP range within the normal range (120-140 mm Hg) during 2006 to 2010, this group had higher stroke risk relative to the normotensive-stable group (<120 mm Hg) (adjusted hazard ratio was 3.11 for intracerebral hemorrhage and 1.99 for cerebral infarction; P<0.001 for both), after adjusting for possible confounders. Individuals in the stage 2 hypertension-stable systolic BP trajectory (175-179 mm Hg) had the highest risk of intracerebral hemorrhage (adjusted hazard ratio was 12.4) and cerebral infarction (adjusted hazard ratio was 5.07), relative to the normotensive-stable group (P<0.001 for both). BP trajectories were associated with the risk of stroke and increasing BP trajectories within the currently designated normal range may still increase the risk for stroke.
TL;DR: A novel mechanism for TIMP1 action is identified whereby, independent from its matrix metalloproteinase–inhibitory function, it mediates an association between CD63 and integrin on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and &bgr;-catenin, leading to de novo collagen synthesis.
Abstract: Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1-deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies.
TL;DR: Indicators of frailty, but not BP or number of antihypertensive medication classes, were associated with increased risk for serious fall injuries among older adults taking antihyertensive medication.
Abstract: Antihypertensive medication and low systolic blood pressure (BP) and diastolic BP have been associated with an increased falls risk in some studies. Many older adults have indicators of frailty, which may increase their risk for falls. We contrasted the association of systolic BP, diastolic BP, number of antihypertensive medication classes taken, and indicators of frailty with risk for serious fall injuries among 5236 REGARDS study (Reasons for Geographic and Racial Difference in Stroke) participants ≥65 years taking antihypertensive medication at baseline with Medicare fee-for-service coverage. Systolic BP and diastolic BP were measured, and antihypertensive medication classes being taken assessed through a pill bottle review during a study visit. Indicators of frailty included low body mass index, cognitive impairment, depressive symptoms, exhaustion, impaired mobility, and history of falls. Serious fall injuries were defined as fall-related fractures, brain injuries, or joint dislocations using Medicare claims through December 31, 2014. Over a median of 6.4 years, 802 (15.3%) participants had a serious fall injury. The multivariable-adjusted hazard ratio for a serious fall injury among participants with 1, 2, or ≥3 indicators of frailty versus no frailty indicators was 1.18 (95% confidence interval, 0.99-1.40), 1.49 (95% confidence interval, 1.19-1.87), and 2.04 (95% confidence interval, 1.56-2.67), respectively. Systolic BP, diastolic BP, and number of antihypertensive medication classes being taken at baseline were not associated with risk for serious fall injuries after multivariable adjustment. In conclusion, indicators of frailty, but not BP or number of antihypertensive medication classes, were associated with increased risk for serious fall injuries among older adults taking antihypertensive medication.
TL;DR: In this article, the authors identify subgroups of individuals with similar trajectories in blood pressure from childhood to young adulthood and determine the relationship of BP trajectories with carotid intima-media thickness (IMT) and left ventricular mass index (LVMI).
Abstract: The purpose of this study is to identify subgroups of individuals with similar trajectories in blood pressure (BP) from childhood to young adulthood and to determine the relationship of BP trajectories with carotid intima-media thickness (IMT) and left ventricular mass index (LVMI). BP was measured ≤16 times during a 23-year period in 683 participants from childhood to young adulthood. IMT and LVMI were measured in 551 participants and 546 participants, respectively. Using latent class models, 3 trajectory groups in BP from childhood to young adulthood were identified, including high-increasing, moderate-increasing, and low-increasing groups. We found that trajectory of systolic BP was a significant predictor of both IMT and LVMI with increased rate of growth in systolic BP associated with higher levels of IMT and LVMI (Pfor trend <0.001). Similar to the BP trajectory groups from childhood to young adulthood, 3 trajectory groups in BP during childhood (≤18 years) were identified, and participants in the high-increasing group had thicker IMT (P<0.001) and increased LVMI (P=0.043) in comparison with those in the low-increasing group. Results were similar for mid-BP trajectories but not for diastolic BP trajectories. Our results suggested that different BP trajectories exist from childhood to young adulthood, and the trajectories were independently associated with IMT and LVMI. We, for the first time, reported the association between systolic BP trajectories derived from childhood with subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BP from childhood may help identify a high cardiovascular risk population in early life.
TL;DR: The sFlt-1:PlGF ratio provided clinically useful prediction of the risk of the most important manifestations of preeclampsia in a cohort of unselected nulliparous women with a singleton pregnancy.
Abstract: We sought to assess the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) in maternal serum as a screening test for preeclampsia in unselected nulliparous women with a singleton pregnancy. We studied 4099 women recruited to the POP study (Pregnancy Outcome Prediction) (Cambridge, United Kingdom). The sFlt-1:PlGF ratio was measured using the Roche Cobas e411 platform at ≈20, ≈28, and ≈36 weeks of gestational age (wkGA). Screen positive was defined as an sFlt-1:PlGF ratio >38, but higher thresholds were also studied. At 28 wkGA, an sFlt-1:PlGF ratio >38 had a positive predictive value (PPV) of 32% for preeclampsia and preterm birth, and the PPV was similar comparing women with low and high prior risk of disease. At 36 wkGA, an sFlt-1:PlGF ratio >38 had a PPV for severe preeclampsia of 20% in high-risk women and 6.4% in low-risk women. At 36 wkGA, an sFlt-1:PlGF ratio >110 had a PPV of 30% for severe preeclampsia, and the PPV was similar comparing low- and high-risk women. Overall, at 36 wkGA, 195 (5.2%) women either had an sFlt-1:PlGF ratio of >110 or an sFlt-1:PlGF ratio >38 plus maternal risk factors: 43% of these women developed preeclampsia, about half with severe features. Among low-risk women at 36 wkGA, an sFlt-1:PlGF ratio ≤38 had a negative predictive value for severe preeclampsia of 99.2%. The sFlt-1:PlGF ratio provided clinically useful prediction of the risk of the most important manifestations of preeclampsia in a cohort of unselected nulliparous women.
TL;DR: It is found that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis and Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not.
Abstract: Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate-adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank P=0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank P<0.001]), and AIx(75) (88.4%, 66.7%, 69.0%, 62.8% [log-rank P=0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187-2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis.
TL;DR: The findings support prevention strategies targeting modifiable factors and behaviors and obesity, in particular, to prevent or delay vascular aging and the associated risk of CVD.
Abstract: Hypertension and increased vascular stiffness are viewed as inevitable parts of aging. To elucidate whether the age-related decrease in vascular function is avoidable, we assessed the prevalence, c...
TL;DR: In this article, the authors evaluated the long-term efficacy and safety of baroreflex activation therapy in patients with resistant hypertension and found that office systolic blood pressure fell from 179±24 mm ǫ hg to 144±28 mm hg after a follow-up of 6 years.
Abstract: Baroreflex activation therapy is a novel technique for treating patients with resistant hypertension. Although short-term studies have demonstrated that it lowers blood pressure, long-term results have not yet been reported. The aim of the present study is to assess the long-term efficacy and safety of baroreflex activation therapy. Long-term follow-up data were analyzed from all patients who had been included in 1 of the 3 trials that focused on treatment-resistant hypertensive patients. Altogether, 383 patients were available for analysis: 143 of these had completed 5 years of follow-up and 48 patients had completed 6 years of follow-up. In the entire cohort, office systolic blood pressure fell from 179±24 mm Hg to 144±28 mm Hg ( P P P After a follow-up of 6 years, baroreflex activation therapy maintains its efficacy for persistent reduction of office blood pressure in patients with resistant hypertension without major safety issues.
TL;DR: In this article, the role of pyr1-apelin-13 peptide pathway in angiotensin (Ang) II-mediated heart disease was investigated in young apelin-deficient (APLN/y) and apolipoprotein E knockout mice.
Abstract: The apelin pathway has emerged as a critical regulator of cardiovascular homeostasis and disease. However, the exact role of pyr1-apelin-13 in angiotensin (Ang) II-mediated heart disease remains unclear. We used apelin-deficient (APLN-/y) and apolipoprotein E knockout mice to evaluate the regulatory roles of pyr1-apelin-13. The 1-year aged APLN-/y mice developed myocardial hypertrophy and dysfunction with reduced angiotensin-converting enzyme 2 levels. Ang II infusion (1.5 mg kg-1 d-1) for 4 weeks potentiated oxidative stress, pathological hypertrophy, and myocardial fibrosis in young APLN-/y hearts resulting in exacerbation of cardiac dysfunction. Importantly, daily administration of 100 μg/kg pyr1-apelin-13 resulted in upregulated angiotensin-converting enzyme 2 levels, decreased superoxide production and expression of hypertrophy- and fibrosis-related genes leading to attenuated myocardial hypertrophy, fibrosis, and dysfunction in the Ang II-infused apolipoprotein E knockout mice. In addition, pyr1-apelin-13 treatment largely attenuated Ang II-induced apoptosis and ultrastructural injury in the apolipoprotein E knockout mice by activating Akt and endothelial nitric oxide synthase phosphorylation signaling. In cultured neonatal rat cardiomyocytes and cardiofibroblasts, exposure of Ang II decreased angiotensin-converting enzyme 2 protein and increased superoxide generation, cellular proliferation, and migration, which were rescued by pyr1-apelin-13, and Akt and endothelial nitric oxide synthase agonist stimulation. The increased superoxide generation and apoptosis in cultured cardiofibroblasts in response to Ang II were strikingly prevented by pyr1-apelin-13 which was partially reversed by cotreatment with the Akt inhibitor MK2206. In conclusion, pyr1-apelin-13 peptide pathway is a negative regulator of aging-mediated and Ang II-mediated adverse myocardial remodeling and dysfunction and represents a potential candidate to prevent and treat heart disease.
TL;DR: Sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH.
Abstract: Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P <0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P <0.001; 356.4 mL/24 hours, P =0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: −20%; P =0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH.
Clinical Trial Registration— URL: . Unique identifier: [NCT01681576][1].
# Novelty and Significance {#article-title-41}
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01681576&atom=%2Fhypertensionaha%2F69%2F1%2F32.atom