Hypertension最新文献

It is now apparent that immune mediators including complement, cytokines, and cells of the innate and adaptive immune system contribute not only to blood pressure elevation but also to the target organ damage that occurs in response to stimuli like high salt, aldosterone, angiotensin II, and sympathetic outflow. Alterations of vascular hemodynamic factors, including microvascular pulsatility and shear forces, lead to vascular release of mediators that affect myeloid cells to become potent antigen-presenting cells and promote T-cell activation. Research in the past 2 decades has defined specific biochemical and molecular pathways that are engaged by these stimuli and an emerging paradigm is these not only lead to immune activation, but that products of immune cells, including cytokines, reactive oxygen species, and metalloproteinases act on target cells to further raise blood pressure in a feed-forward fashion. In this review, we will discuss these molecular and pathophysiological events and discuss clinical interventions that might prove effective in quelling this inflammatory process in hypertension and related cardiovascular diseases.

Background: The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown.

Methods: This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions.

Results: Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (β=-2.02; P=0.02) but not in girls (β=-0.49; P=0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; β_EAA=-2.95; β_IAA=-3.00; P<0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; P<0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; P<0.01). Significant sex differences were observed (P_{sex-interaction}<2×10^-16).

Conclusions: GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

Background: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored.

Methods: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension.

Results: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively.

Conclusions: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

Background: We investigated the potential impact of antihypertensive drugs for atrial fibrillation (AF) prevention through a drug target Mendelian randomization study to avoid the potential limitations of clinical studies.

Methods: Validated published single-nucleotide polymorphisms (SNPs) that mimic the action of 12 antihypertensive drug classes, including alpha-adrenoceptor blockers, adrenergic neuron blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta-adrenoceptor blockers, centrally acting antihypertensive drugs, calcium channel blockers, loop diuretics, potassium-sparing diuretics and mineralocorticoid receptor antagonists, renin inhibitors, thiazides and related diuretic agents, and vasodilators were used. We estimated, via their corresponding gene and protein targets, the downstream effect of these drug classes to prevent AF via systolic blood pressure using 2-sample Mendelian randomization analyses. The SNPs were extracted from 2 European genome-wide association studies for the drug classes (n=317 754; n=757 601) and 1 European genome-wide association study for AF (n=1 030 836).

Results: Drug target Mendelian randomization analyses supported the significant preventive causal effects of lowering systolic blood pressure per 10 mm Hg via alpha-adrenoceptor blockers (n=11 SNPs; odds ratio [OR], 0.34 [95% CI, 0.21-0.56]; P=2.74×10^-05), beta-adrenoceptor blockers (n=17 SNPs; OR, 0.52 [95% CI, 0.35-0.78]; P=1.62×10^-03), calcium channel blockers (n=49 SNPs; OR, 0.50 [95% CI, 0.36-0.70]; P=4.51×10^-05), vasodilators (n=19 SNPs; OR, 0.53 [95% CI, 0.34-0.84]; P=7.03×10^-03), and all 12 antihypertensive drug classes combined (n=158 SNPs; OR, 0.64 [95% CI, 0.54-0.77]; P=8.50×10^-07) on AF risk.

Conclusions: Our results indicated that lowering systolic blood pressure via protein targets of various antihypertensive drugs seems promising for AF prevention. Our findings inform future clinical trials and have implications for repurposing antihypertensive drugs for AF prevention.

Background: Metabolic and bariatric surgery (MBS) is the most effective and durable treatment for obesity. We aimed to compare the trajectories of antihypertensive medication (AHM) use among obese individuals treated and not treated with MBS.

Methods: Adults with a body mass index of ≥35 kg/m² were identified in the Merative Database (US employer-based claims database). Individuals treated with versus without MBS were matched 1:1 using baseline demographic and clinical characteristics as well as AHM utilization. Monthly AHM use was examined in the 3 years after the index date using generalized estimating equations. Subanalyses investigated rates of AHM discontinuation, AHM initiation, and apparent treatment-resistant hypertension.

Results: The primary cohort included 43 206 adults who underwent MBS matched with 43 206 who did not. Compared with no MBS, those treated with MBS had sustained, markedly lower rates of AHM use (31% versus 15% at 12 months; 32% versus 17% at 36 months). Among patients on AHM at baseline, 42% of patients treated with MBS versus 7% treated medically discontinued AHM use (P<0.01). The risk of apparent treatment-resistant hypertension was 3.41× higher (95% CI, 2.91-4.01; P<0.01) 2 years after the index date in patients who did not undergo MBS. Among those without hypertension treated with MBS versus no MBS, 7% versus 21% required AHM at 2 years.

Conclusions: MBS is associated with lower rates of AHM use, higher rates of AHM discontinuation, and lower rates of AHM initiation among patients not taking AHM. These findings suggest that MBS is both an effective treatment and a preventative measure for hypertension.

Background: Although smoking cigarettes has been shown to have a protective effect on preeclampsia, quitting smoking also results in weight gain. Weight gain leading to an obese body mass index is a risk factor for hypertensive disorders of pregnancy (HDP).

Methods: The objective of this study was to explore the relationship between smoking status, body mass index, and gestational weight gain on the risk of HDP. A cross-sectional analysis was performed utilizing US birth certificate data. We examined HDP risks in relation to maternal smoking, body mass index, and gestational weight gain. Associations were expressed as rate ratios with 95% CIs and adjusted for potential confounders. Clinically important outcomes of smoking throughout pregnancy were also evaluated.

Results: Of the 22 191 568 women studied, HDP rates among nonsmokers, those who quit smoking, and persistent smokers were 6.8%, 8.6%, and 7.0%, respectively. The rate ratio of HDP was higher for women who quit smoking, especially evident among those with excessive gestational weight gain. Corrections for exposure misclassification and unmeasured confounding strengthened the associations among women who quit smoking. There was an almost 6-fold increase in the rate of stillbirth for persistent smokers (2.3%) compared with those who quit smoking (0.4%) and nonsmokers (0.4%).

Conclusions: Women who quit smoking during pregnancy were more likely to gain excessive weight and develop HDP. Although quitting smoking during pregnancy may be associated with an increase in the risk of HDP, it is also associated with a reduced risk of stillbirth. Pregnant women counseled to quit smoking should also receive counseling on nutrition and exercise to prevent excessive gestational weight gain.

Background: Treatment of chronic hypertension during pregnancy has been shown to reduce the risk of adverse perinatal outcomes. In this study, we examined the prevalence and treatment of chronic hypertension during pregnancy and assessed changes in these outcomes following the release of the updated 2017 hypertension guidelines of the American College of Cardiology and American Heart Association.

Methods: We analyzed the Merative^TM Marketscan^® Research Database of United States commercial insurance claims from 2007 to 2021. We assessed the prevalence of chronic hypertension during pregnancy and oral antihypertensive medication use over time. We then performed interrupted time series analyses to evaluate changes in these outcomes.

Results: The prevalence of chronic hypertension steadily increased from 1.8% to 3.7% among 1 900 196 pregnancies between 2008 and 2021. Antihypertensive medication use among pregnant individuals with chronic hypertension was relatively stable (57%-60%) over the study period. The proportion of pregnant individuals with chronic hypertension treated with methyldopa or hydrochlorothiazide decreased (from 29% to 2% and from 11% to 5%, respectively), while the proportion treated with labetalol or nifedipine increased (from 19% to 42% and from 9% to 17%, respectively). The prevalence or treatment of chronic hypertension during pregnancy did not change following the 2017 American College of Cardiology and American Heart Association hypertension guidelines.

Conclusions: The prevalence of chronic hypertension during pregnancy doubled between 2008 and 2021 in a nationwide cohort of individuals with commercial insurance. Labetalol replaced methyldopa as the most commonly used antihypertensive during pregnancy. However, only about 60% of individuals with chronic hypertension in pregnancy were treated with antihypertensive medications.

Background: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial).

Methods: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events.

Results: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease.

Conclusions: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.