Petershahn5645

Antihypertensive drug treatment is cost-effective for adults at high risk of developing cardiovascular disease (CVD). However, the cost-effectiveness in people with stage 1 hypertension (140-159 mm Hg systolic blood pressure) at lower CVD risk remains unclear. The objective was to establish the 10-year CVD risk threshold where initiating antihypertensive drug treatment for primary prevention in adults, with stage 1 hypertension, becomes cost-effective. A lifetime horizon Markov model compared antihypertensive drug versus no treatment, using a UK National Health Service perspective. Analyses were conducted for groups ranging between 5% and 20% 10-year CVD risk. Health states included no CVD event, CVD and non-CVD death, and 6 nonfatal CVD morbidities. Interventions were compared using cost-per-quality-adjusted life-years. The base-case age was 60, with analyses repeated between ages 40 and 75. The model was run separately for men and women, and threshold CVD risk assessed against the minimum plausible risk for each group. Treatment was cost-effective at 10% CVD risk for both sexes (incremental cost-effectiveness ratio £10 017/quality-adjusted life-year [$14 542] men, £8635/QALY [$12 536] women) in the base-case. The result was robust in probabilistic and deterministic sensitivity analyses but was sensitive to treatment effects. Treatment was cost-effective for men regardless of age and women aged >60. Initiating treatment in stage 1 hypertension for people aged 60 is cost-effective regardless of 10-year CVD risk. For other age groups, it is also cost-effective to treat regardless of risk, except in younger women.Hypertension is a major risk factor for cardiovascular disease (CVD), but previous studies have mostly been limited to a single exam, a single cohort, a short follow-up period, or a limited number of outcomes. This study aimed to assess the association of 10-year cumulative systolic blood pressure (BP) in middle age with long-term risk of any CVD, coronary heart disease, stroke, heart failure, all-cause mortality, and healthy longevity. Individuals (11 502) from 5 racially/ethnically diverse US community-based cohorts were included in this study once they met all the inclusion criteria ≥10 year of observation in the included cohort, aged 45 to 60 years, free of CVD, and had ≥3 visits with BP exams over the preceding 10 years. For each participant, systolic BP level was predicted for each year of the 10-year prior inclusion, based on the available exams (median of 4.0; spread over, 9.1 [range, 7.2-10] years). Lower 10-year cumulative systolic BP was associated with 4.1 years longer survival and 5.4 years later onset of CVD, resulting in living longer life with a shorter period with morbidity. Models adjusted for sociodemographic characteristics, cardiovascular risk factors, and index systolic BP demonstrated associations of 10-year cumulative systolic BP (per 130 mm Hg×year change, the threshold for stage-1 hypertension) with CVD (hazard ratio [HR], 1.28 [95% CI, 1.20-1.36]), coronary heart disease (HR, 1.29 [95% CI, 1.19-1.40]), stroke (HR, 1.33 [95% CI, 1.20-1.47]), heart failure (HR, 1.12 [95% CI, 1.02-1.23]), and all-cause mortality (HR, 1.21 [95% CI, 1.14-1.29]). These findings emphasize the importance of 10-year cumulative systolic BP as a risk factor to CVD, above and beyond current systolic BP.Animal studies have revealed gut microbial and metabolic pathways of blood pressure (BP) regulation, yet few epidemiological studies have collected microbiota and metabolomics data in the same individuals. In a population-based, Chinese cohort who did not report antihypertension medication use (30-69 years, 54% women), thus minimizing BP treatment effects, we examined multivariable-adjusted (eg, diet, physical activity, smoking, kidney function), cross-sectional associations between measures of gut microbiota (16S rRNA [ribosomal ribonucleic acid], N=1003), and plasma metabolome (liquid chromatography-mass spectrometry, N=434) with systolic (SBP, mean [SD]=126.0 [17.4] mm Hg) and diastolic BP (DBP [80.7 (10.7) mm Hg]). We found that the overall microbial community assessed by principal coordinate analysis varied by SBP and DBP (permutational multivariate ANOVA P less then 0.05). To account for strong correlations across metabolites, we first examined metabolite patterns derived from principal component analysis and found that a lipid pattern was positively associated with SBP (linear regression coefficient [95% CI] per 1 SD pattern score 2.23 [0.72-3.74] mm Hg) and DBP (1.72 [0.81-2.63] mm Hg). Among 1104 individual metabolites, 34 and 39 metabolites were positively associated with SBP and DBP (false discovery rate-adjusted linear model P less then 0.05), respectively, including linoleate, palmitate, dihomolinolenate, 8 sphingomyelins, 4 acyl-carnitines, and 2 phosphatidylinositols. Subsequent pathway analysis showed that metabolic pathways of long-chain saturated acylcarnitine, phosphatidylinositol, and sphingomyelins were associated with SBP and DBP (false discovery rate-adjusted Fisher exact test P less then 0.05). Our results suggest potential roles of microbiota and metabolites in BP regulation to be followed up in prospective and clinical studies.As the most common clinical stress during mid and late pregnancy, antenatal hypoxia has profound adverse effects on individual's vascular health later in life, but the underlying mechanisms are still not understood. Cyclopamine antagonist The purpose of this study was to reveal the mechanisms of the acquired vascular dysfunction in offspring imposed by antenatal hypoxia. Pregnant rats were housed in a normoxic or hypoxic (10.5% oxygen) chamber from gestation day 10 to 21. Male offspring were euthanized at gestational day 21 (fetus) or postnatal 16 weeks old (adult offspring). Mesenteric arteries were collected for examining Ang II (angiotensin II)-mediated vascular contractility, gene expression, and promoter methylation. Antenatal hypoxia increased vascular sensitivity to Ang II, which was resulted by an upregulated AT1R (angiotensin II type 1 receptor). The increased AT1R was correlated with a hypomethylation-mediated activated transcription of Agtr1a (alpha subtype of AT1R). In addition, we presented evidences that there was an AT1R-Egr1 (early growth response gene 1)-PKCε (ε isoform of protein kinase C) axis in vasculature; AT1R could modulate PKCε expression via upregulating Egr1; Egr1 mediated transcription activation of PKCε via Egr1 binding sites in PKCε gene promoter.