Hypotension RSS : Gourt

Adrenergic Cardiovascular Control Before and After Removal of Stimulatory {alpha}-1 Adrenoreceptor Antibodies [Letters to the Editor]

Blood Pressure Threshold for Abnormal Ocular Fundus Findings Is Lower Than Expected [Letters to the Editor]

How Is Slow Wave Sleep Related to Hypertension? [Letters to the Editor]

Response to How Is Slow Wave Sleep Related to Hypertension? [Letters to the Editor]

Tetrahydrobiopterin and Endothelial Nitric Oxide Synthase Uncoupling [Letters to the Editor]

Response to Tetrahydrobiopterin and Endothelial Nitric Oxide Synthase Uncoupling [Letters to the Editor]

Pin1 as a Protector of Vascular Endothelial Homeostasis [Letters to the Editor]

Response to Pin1 as a Protector of Vascular Endothelial Homeostasis [Letters to the Editor]

Reactive Oxygen Species and Angiotensin II Response in Human Omental Arteries: What About Tachyphylaxis? [Letters to the Editor]

Response to Reactive Oxygen Species and Angiotensin II Response in Human Omental Arteries: What About Tachyphylaxis? [Letters to the Editor]

Eplerenone Use in Primary Aldosteronism During Pregnancy [Letters to the Editor]

Correction [Correction]

Unusual Hypertensive Phenotypes: What Is Their Significance? [Brief Review]

Severe Hypertension With Large-Vessel Arteritis [Hypertension Grand Rounds]

Above Which Blood Pressure Level Does the Risk of Atrial Fibrillation Increase? [Editorial Commentaries]

Breast Cancer, Age, and Hypertension: A Complex Issue [Editorial Commentaries]

Preterm Birth: A Novel Risk Factor for Higher Blood Pressure in Later Life [Editorial Commentaries]

Placenta Messages to the Mother: Not Just Debris [Editorial Commentaries]

Interventional Approaches to Reduce Sympathetic Activity in Resistant Hypertension: To Ablate or Stimulate? [Editorial Commentaries]

Mutations of the Potassium Channel KCNJ5 Causing Aldosterone-Producing Adenomas: One or Two Hits? [Editorial Commentaries]

Upper Normal Blood Pressures Predict Incident Atrial Fibrillation in Healthy Middle-Aged Men: A 35-Year Follow-Up Study [Epidemiology/Population Science]

Hypertension is the most prevalent risk factor for incident atrial fibrillation (AF). Recently, even high normal blood pressures (BPs) have been established as predictive of AF in women. We aimed to study the long-term impact of upper normal BP on incident AF in a population-based study of middle-aged men. From 1972 to 1975, 2014 healthy Norwegian men were included in a prospective cardiovascular survey and underwent a comprehensive clinical examination including standardized BP measurements. During up to 35 years of follow-up, 270 men were documented with AF by scrutinizing all hospital discharges. Risk estimations for incident AF were analyzed in quartiles of BP using multivariate adjusted Cox proportional hazards. Men with baseline systolic BP ≥140 mm Hg and upper normal BP 128 to 138 mm Hg had 1.60-fold (95% CI 1.15–2.21) and 1.50-fold (1.10–2.03) risk of AF, respectively, compared with men with BP <128 mm Hg. Baseline diastolic BP ≥80 mm Hg increased the risk of incident AF 1.79-fold (95% CI 1.28–2.59) compared with diastolic BP <80 mm Hg. When adjusting for the occurrence of diabetes mellitus or cardiovascular diseases before an AF event, the results still maintained significance. Additional analyses, on average 7 years after baseline, including men still healthy, showed that sustained upper normal systolic BP remained a significant predictor of subsequent AF. In conclusion, upper normal blood pressures are long-term predictors of incident AF in initially healthy middle-aged men.

Comorbidity as a Mediator of Survival Disparity Between Younger and Older Women Diagnosed With Metastatic Breast Cancer [Epidemiology/Population Science]

The presence of comorbidity becomes increasingly important for its prognostic effect on survival in breast cancer patients with advancing age. This study aimed to evaluate the role of comorbidities including hypertension as a mediator of disparity in survival after metastasis diagnosis between younger (≤51 years) and older (>51 years) patients. A total of 553 patients 26–88 years of age with breast cancer metastasis diagnosis from 1 large urban practice were followed between January 1, 1999, and June 30, 2008. Comorbidity variables and survival were analyzed using Cox regression model. To assess comorbidity variables as a mediator of age-survival relationship, 2 approaches have been applied: (1) Baron Kenny approach and (2) alternative assessment to compute the percentage change in the hazard ratios (HRs). The median survival was 40 months, with 265 (47.9%) alive and 288 (52.1%) dead. Older patients had worse survival than younger patients (HR, 1.43; 95% confidence interval [CI], 1.11–1.84). Hypertension was related to survival (HR, 1.45; 95% CI, 1.12–1.89) when age and other covariates were controlled. The effect of age on survival was no longer significant after adjustment for hypertension (HR, 1.26; 95%, CI 0.97–1.65) or hypertension-augmented Charlson comorbidity score (HR, 1.24; 95% CI, 0.95–1.63). Hypertension-augmented Charlson comorbidity score or hypertension was a strong mediator of age-survival relationship among metastatic breast cancer patients, explaining survival disparity between younger and older patients by 44% and 40%, respectively. The study findings suggest that hypertension should be included in the comorbidity information for decision-making support programs.

Prognostic Value of the Variability in Home-Measured Blood Pressure and Heart Rate: The Finn-Home Study [Epidemiology/Population Science]

The objective of the study was to assess the prognostic value of variability in home-measured blood pressure (BP) and heart rate (HR) in a general population. We studied a representative sample of the Finnish adult population with 1866 study subjects aged 45–74 years. BP and HR self-measurements were performed on 7 consecutive days. The variabilities of BP and HR were defined as the SDs of morning minus evening, day-by-day, and first minus second measurements. The primary end point was incidence of a cardiovascular event. The secondary end point was total mortality. During a follow-up of 7.8 years, 179 subjects had experienced a cardiovascular event, and 130 subjects had died. In Cox proportional hazard models adjusted for age, sex, BP/HR, and other cardiovascular risk factors, morning-evening home BP variability (systolic/diastolic relative hazard: 1.04/1.10 [95% CI: 1.01–1.07/1.05–1.15] per 1-mm Hg increase in BP variability) and morning day-by-day home BP variability (relative hazard: 1.04/1.10 [95% CI: 1.00–1.07/1.04–1.16] per 1-mm Hg increase in BP variability) were predictive of cardiovascular events. Morning-evening home HR variability (relative hazard: 1.07 [95% CI: 1.02–1.12] per 1-bpm increase in HR variability) and morning day-by-day home HR variability (relative hazard: 1.11 [95% CI: 1.05–1.17] per 1-bpm increase in HR variability) were also independent predictors of cardiovascular events. Greater variabilities of morning home BP and HR are independent predictors of cardiovascular events. Because the variabilities of home BP and HR are easily acquired in conjunction with home BP and HR level, they should be used as the additive information in the assessment of cardiovascular risk.

Rate of Decline of Forced Vital Capacity Predicts Future Arterial Hypertension: The Coronary Artery Risk Development in Young Adults Study [Epidemiology/Population Science]

Lung function studies in middle-aged subjects predict cardiovascular disease mortality. We studied whether greater loss of forced vital capacity (FVC) early in life predicted incident hypertension. The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults Study examined between 1985 and 1986 (Coronary Artery Risk Development in Young Adults year 0, ages 18–30 years) and 2005–2006 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios and linear regression models predicted incident hypertension at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 – peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5, and 10). Covariates included demographics, center, systolic blood pressure, FVC maximum, smoking, physical activity, asthma, and body mass index. Unadjusted cumulative incident hypertension was 25% in the lowest FVC loss quartile (Q1; median loss: 370 mL) compared with 12% cumulative incident hypertension in those who achieved peak FVC at year 10 (Q4). Minimally adjusted hazard ratio for Q1 versus Q4 was 2.21 (95% CI: 1.73–2.83), and this association remained significant in the fully adjusted model (1.37; 95% CI: 1.05–1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45 years. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality.

Systematic Review and Meta-Analysis of Preterm Birth and Later Systolic Blood Pressure [Epidemiology/Population Science]

Lower birth weight because of fetal growth restriction is associated with higher blood pressure later in life, but the extent to which preterm birth (<37 completed weeks' gestation) or very low birth weight (<1500 g) predicts higher blood pressure is less clear. We performed a systematic review of 27 observational studies that compared the resting or ambulatory systolic blood pressure or diagnosis of hypertension among children, adolescents, and adults born preterm or very low birth weight with those born at term. We performed a meta-analysis with the subset of 10 studies that reported the resting systolic blood pressure difference in millimeters of mercury with 95% CIs or SEs. We assessed methodologic quality with a modified Newcastle-Ottawa Scale. The 10 studies were composed of 1342 preterm or very low birth weight and 1738 term participants from 8 countries. The mean gestational age at birth of the preterm participants was 30.2 weeks (range: 28.8–34.1 weeks), birth weight was 1280 g (range: 1098–1958 g), and age at systolic blood pressure measurement was 17.8 years (range: 6.3–22.4 years). Former preterm or very low birth weight infants had higher systolic blood pressure than term infants (pooled estimate: 2.5 mm Hg [95% CI: 1.7–3.3 mm Hg]). For the 5 highest quality studies, the systolic blood pressure difference was slightly greater, at 3.8 mm Hg (95% CI: 2.6–5.0 mm Hg). We conclude that infants who are born preterm or very low birth weight have modestly higher systolic blood pressure later in life and may be at increased risk for developing hypertension and its sequelae.

KCNJ5 Mutations in European Families With Nonglucocorticoid Remediable Familial Hyperaldosteronism [Genetics]

Primary aldosteronism is the most frequent cause of endocrine hypertension. Three forms of familial hyperaldosteronism (FH) have been described, named FH-I to -III. Recently, a mutation of KCNJ5 has been shown to be associated with FH-III, whereas the cause of FH-II is still unknown. In this study we searched for mutations in KCNJ5 in 46 patients from 21 families with FH, in which FH-I was excluded. We identified a new germline G151E mutation in 2 primary aldosteronism–affected subjects from an Italian family and 3 somatic mutations in aldosterone-producing adenomas, T158A described previously as a germline mutation associated with FH-III, and G151R and L168R both described as somatic mutations in aldosterone-producing adenoma. The phenotype of the family with the G151E mutation was remarkably milder compared with the previously described American family, in terms of both clinical and biochemical parameters. Furthermore, patients with somatic KCNJ5 mutations displayed a phenotype indistinguishable from that of sporadic primary aldosteronism. The functional characterization of the effects of the G151E mutation in vitro showed a profound alteration of the channel function, with loss of K+ selectivity, Na+ influx, and membrane depolarization. These alterations have been postulated to be responsible for voltage gate Ca2+ channel activation, increase in cytosolic calcium, and stimulation of aldosterone production and adrenal cell proliferation. In conclusion, we describe herein a new mutation in the KCNJ5 potassium channel associated with FH-III, responsible for marked alterations of channel function but associated with a mild clinical and hormonal phenotype.

Genome-Wide Profiling of Blood Pressure in Adults and Children [Genetics]

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms. Subsequently, genetic risk scores for systolic blood pressure and diastolic blood pressure were calculated in an independent adult population (n=2072) and a child population (n=1034). The explained variance of the genetic risk scores was evaluated using linear regression models, including sex, age, and body mass index. Genetic risk scores, including also many nongenome-wide significant single nucleotide polymorphisms, explained more of the variance than scores based only on very significant single nucleotide polymorphisms in adults and children. Genetic risk scores significantly explained ≤1.2% (P=9.6*10–8) of the variance in adult systolic blood pressure and 0.8% (P=0.004) in children. For diastolic blood pressure, the variance explained was similar in adults and children (1.7% [P=8.9*10–10] and 1.4% [P=3.3*10–5], respectively). These findings suggest the presence of many genetic loci with small effects on blood pressure regulation both in adults and children, indicating also a (partly) common polygenic regulation of blood pressure throughout different periods of life.

Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase [Genetics]

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37–1.73]; combined P=2.58 · 10–13). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25–1.44; P=1.032 · 10–14). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16–3.66) for systolic and 1.40 (95% CI: 0.25–2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

Transcriptionally Active Syncytial Aggregates in the Maternal Circulation May Contribute to Circulating Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia [Pregnancy/Preeclampsia]

The cardinal manifestations of the pregnancy-specific disorder preeclampsia, new-onset hypertension, and proteinuria that resolve with placental delivery have been linked to an extracellular protein made by the placenta, soluble fms-like tyrosine kinase 1 (sFlt1), that injures the maternal vasculature. However, the mechanisms by which sFlt1, which is heavily matrix bound, gain access to the systemic circulation remain unclear. Here we report that the preeclamptic placenta's outermost layer, the syncytiotrophoblast, forms abundant "knots" that are enriched with sFlt1 protein. These syncytial knots easily detach from the syncytiotrophoblast, resulting in free, multinucleated aggregates (50–150 μm diameter) that are loaded with sFlt1 protein and mRNA, are metabolically active, and are capable of de novo gene transcription and translation. At least 25% of the measurable sFlt1 in the third-trimester maternal plasma is bound to circulating placental microparticles. We conclude that detachment of syncytial knots from the placenta results in free, transcriptionally active syncytial aggregates that represent an autonomous source of sFlt1 delivery into the maternal circulation. The process of syncytial knot formation, shedding of syncytial aggregates, and appearance of placental microparticles in the maternal circulation appears to be greatly accelerated in preeclampsia and may contribute to the maternal vascular injury that characterizes this disorder.

Hydroxysteroid (17-{beta}) Dehydrogenase 1 Is Dysregulated by Mir-210 and Mir-518c That Are Aberrantly Expressed in Preeclamptic Placentas: A Novel Marker for Predicting Preeclampsia [Pregnancy/Preeclampsia]

In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff value=21.9 ng/mL) and 0.88/0.51 (cutoff value=30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35–15.77) and 7.83 (95% CI: 1.70–36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE.

Glycogen Phosphorylase Isoenzyme BB Plasma Concentration Is Elevated in Pregnancy and Preterm Preeclampsia [Pregnancy/Preeclampsia]

Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from 6 groups (n=396) were studied: nonpregnant and pregnant women with normal term delivery, term and preterm preeclampsia, and term and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term delivery were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in nonpregnant women (38.7 versus 9.2 ng/mL; P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Cases of preterm (but not term) preeclampsia had higher median plasma GPBB concentrations than gestational age-matched normal pregnancy cases (72.6 versus 26.0 ng/mL; P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiological elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin.

Increased Angiotensin II-Induced Hypertension and Inflammatory Cytokines in Mice Lacking Angiotensin-Converting Enzyme N Domain Activity [Renin-Angiotensin-Aldosterone System]

—Angiotensin-converting enzyme (ACE) is composed of the N- and C-terminal catalytic domains. To study the role of the ACE domains in the inflammatory response, N-knockout (KO) and C-KO mice, models lacking 1 of the 2 ACE domains, were analyzed during angiotensin II–induced hypertension. At 2 weeks, N-KO mice have systolic blood pressures that averaged 173±4.6 mm Hg, which is more than 25 mm Hg higher than the blood pressures observed in wild-type or C-KO mice (146±3.2 and 147±4.2 mm Hg). After 3 weeks, blood pressure differences between N-KO, C-KO, and wild-type were even more pronounced. Macrophages from N-KO mice have increased expression of tumor necrosis factor α after stimulation with either lipopolysaccharide (about 4-fold) or angiotensin II (about 2-fold), as compared with C-KO or wild-type mice. Inhibition of the enzyme prolyl oligopeptidase, responsible for the formation of acetyl-SerAspLysPro and other peptides, eliminated the blood pressure difference and the difference in tumor necrosis factor α expression between angiotensin II–treated N-KO and wild-type mice. However, this appears independent of acetyl-SerAspLysPro. These data establish significant differences in the inflammatory response as a function of ACE N- or C-domain catalytic activity. They also indicate a novel role of prolyl oligopeptidase in the cytokine regulation and in the blood pressure response to experimental hypertension.