Hypertension最新文献

Background: To understand the role of hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension (GH), in brain health earlier in life, we investigated the association of HDP with midlife cognition and brain health.

Methods: We studied a prospective cohort of women, baseline age 18 to 30 years, who were assessed at study years 25 and 30 with a cognitive battery and a subset with brain magnetic resonance imaging. A history of HDP was defined based on self-report. We conducted linear regression to assess the association of a history of preeclampsia, GH, or no HDP with cognition and brain magnetic resonance imaging white matter hyperintensities.

Results: Among 1441 women (mean age, 55.2±3.6 years), 202 reported preeclampsia and 112 reported GH. GH was associated with worse cognitive performance: global cognition (mean score, 23.2 versus 24.0; P=0.018), processing speed (67.5 versus 71.3; P=0.01), verbal fluency (29.5 versus 31.1; P=0.033), and a trend for executive function (24.3 versus 22.6; P=0.09), after multivariable adjustment. GH was associated with a greater 5-year decline in processing speed (mean change, -4.9 versus -2.7; P=0.049) and executive function (-1.7 versus 0.3; P=0.047); preeclampsia was associated with a greater 5-year decline on delayed verbal memory (-0.3 versus 0.1; P=0.041). GH and preeclampsia were associated with greater white matter hyperintensities in the parietal and frontal lobes, respectively.

Conclusions: GH and preeclampsia are associated with cognition and white matter hyperintensities during midlife, with differences in cognitive domains and brain lobes. Women with HDP may need to be closely monitored for adverse brain outcomes starting in midlife.

Several microRNAs (miRNAs) strongly influence blood pressure and the development of hypertension by modulating vascular, renal, and other physiological mechanisms. In addition, miRNAs may contribute to the genetic regulation of blood pressure. Future research should focus on investigating select miRNAs with potent physiological effects, understanding cellular context-dependent mechanisms conferring specificity to miRNA action, and integrating miRNAs as powerful modulators into the molecular system that underlies the regulation of blood pressure and the development of hypertension.

Background: Dietary Approaches to Stop Hypertension (DASH) is a recommended first-line treatment for adults with hypertension, yet adherence to DASH is low. To evaluate the efficacy of a digital health intervention (DHI), compared with attention control, on changes in DASH adherence and blood pressure among adults with hypertension.

Methods: Nourish was a 12-month, parallel, 2-arm, randomized controlled trial of a virtually delivered DHI. Participants had a previous diagnosis of hypertension. The primary outcome was a 6-month change in DASH adherence. The secondary outcome was a change in blood pressure. We used linear mixed models to compare 6 and 12-month changes in DASH adherence, systolic blood pressure, and diastolic blood pressure.

Results: Nourish randomized 301 adults who averaged 54.4 (SD, 13.4) years and predominately identified as female (65%), White (53%), or Black (31%). Adjusted mean baseline DASH score was 2.30 (95% CI, 2.03-2.58). The adjusted mean baseline systolic blood pressure and diastolic blood pressure were 123.2 (95% CI, 119.5-126.9) and 77.1 (95% CI, 74.6-79.6) mm Hg. DASH score change was not significantly different between arms at 6 months (M_diff, 0.02 [95% CI, -0.37 to 0.40]). Yet, DHI participants had significantly greater 12-month changes in DASH score, relative to control (M_diff, 0.62 [95% CI, 0.16-1.08]). Between-group differences in 6-month changes were insignificant for systolic blood pressure and marginally significant for diastolic blood pressure, despite the DHI group showing significant blood pressure reductions from baseline.

Conclusions: A DHI led to modest improvements in DASH and blood pressure among adults with hypertension but did not outperform the attention control. Further research is needed to understand the utility of DHIs to promote DASH and identify intervention components that support long-term behavior change.

Background: Epigenetic changes can be shaped by a wide array of environmental cues, maternal health, and behaviors. One of the most detrimental behaviors to the developing fetus is nicotine exposure. Perinatal nicotine exposure remains a significant risk factor for cardiovascular health and, in particular, hypertension. Increased basal carotid body (CB) activity and excitation are significant contributors to hypertension. This study investigated the epigenetic changes to CB activity induced by perinatal nicotine exposure resulting in CB-mediated hypertension.

Methods: We used a rodent model of perinatal nicotine exposure and cell culture methods.

Results: We show that the AgtR1 (angiotensin II type 1 receptor) is upregulated in the carotid bodies of nicotine-exposed offspring. These changes were attributed to an upregulation of genetic promotion as DNA methylation of AgtR1 occurred within intron regions, exemplifying an upregulation of genetic transcription for this gene. Nicotine increased angiotensin signaling in vitro. CB reactivity to angiotensin was increased in perinatal nicotine-exposed offspring compared with control offspring. Furthermore, CB denervation reduced arterial pressure because of suppressed efferent sympathetic activity in perinatal nicotine-exposed offspring.

Conclusions: Our data demonstrate that perinatal nicotine exposure adversely affects CB afferent sensing, which augments efferent sympathetic activity to increase vasoconstrictor signaling and induce hypertension. Targeting angiotensin signaling in the carotid bodies may provide a way to alleviate hypertension acquired by adverse maternal uterine environments in general and perinatal nicotine exposure in particular.

Background: Postpartum hypertension is a key factor in racial-ethnic inequities in maternal mortality. Emerging evidence suggests that experiences of racism, both structural and interpersonal, may contribute to disparities. We examined associations between gendered racial microaggressions (GRMs) during obstetric care with postpartum blood pressure (BP).

Methods: We conducted a prospective postpartum cohort of 373 Asian, Black, and Hispanic people in New York City and Philadelphia. At delivery, we administered the GRM in obstetrics scale. We measured BP for 3 months using text-based monitoring. We estimated place-based structural racism with the Structural Racism Effect Index. We used mixed models to estimate associations between GRM and mean postpartum systolic BP and diastolic BP. We adjusted for race-ethnicity, education, body mass index, chronic hypertension (diagnosed at <20 weeks of gestation), age, and the Structural Racism Effect Index. We examined effect modification by hypertensive disorder of pregnancy and place-based structural racism.

Results: A total of 4.6% of participants had chronic hypertension, 20.9% had pregnancy hypertension, and 13.4% had preeclampsia, comprising a hypertensive disorder of pregnancy subgroup (n=117). A total of 37.5% of participants experienced ≥1 GRM. Participants who experienced ≥1 GRM versus none had 1.88 mm Hg higher systolic BP from days 1 to 10 (95% CI, -0.19 to 3.95) and 2.19 mm Hg higher systolic BP from days 11 to 85 (95% CI, 0.17-4.22). Associations followed a similar pattern for diastolic BP and were stronger among the hypertensive disorder of pregnancy subgroup. Participants experiencing GRM and a high Structural Racism Effect Index had systolic BP 7.55 mm Hg (95% CI, 3.41-11.69) and diastolic BP 6.03 mm Hg (95% CI, 2.66-9.41) higher than those with neither.

Conclusions: Structural racism and interpersonal racism are associated with increased postpartum BP, potentially contributing to inequities in postpartum morbidity and mortality and lifecourse cardiovascular disease.

Background: Increased blood pressure (BP) variability is linked to dementia risk, but the relationship between baroreflex sensitivity (BRS), a fundamental mechanism for maintaining stable BP, and dementia risk is undetermined.

Methods: We tested the hypothesis that impaired BRS is associated with increased dementia risk in 1819 older adults (63% women; age, 71.0±6.3 years) from the community-based Rotterdam Study. Cardiac BRS was determined from a 5-minute beat-to-beat BP recording at supine rest between 1997 and 1999. Cardiac BRS measures the correlation between changes in consecutive beat-to-beat systolic BP and subsequent responses in heartbeat intervals, with a higher value indicating better BRS. The primary outcome was incident dementia ascertained from baseline through January 1, 2020; the secondary outcome was all-cause mortality.

Results: During a median follow-up of 14.8 years, 421 participants developed dementia. The association of cardiac BRS with dementia risk differed by antihypertensive medication use (P_interaction=0.03) and was only observed in participants not taking antihypertensives. Specifically, in those not taking antihypertensive medication, reduced BRS was associated with a higher risk of dementia (adjusted hazard ratio comparing bottom versus top quintiles, 1.60 [95% CI, 1.07-2.40]; P_trend=0.02). Reduced BRS was also associated with an increased risk of death (corresponding hazard ratio, 1.76 [95% CI, 1.32-2.35]). The association remained after adjusting for average BP and BP variability.

Conclusions: Impaired BRS partly explains hypertension-related brain damage and excessive dementia risk beyond conventional BP measures, making it a potential novel biomarker for the early detection and prevention of dementia.

Background: Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults.

Methods: We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004). Caregiving stress over the past 12 months was assessed via a single item in the global perceived stress scale. Caregiving for a high-needs dependent status was assessed via a question on hours per week spent caregiving for children (≤5 years or disabled) or older adults. Incident hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-report of taking antihypertensive medication at follow-up exams in 2005 to 2008 and 2009 to 2013.

Results: Over a median follow-up of 7.4 years, 43.5% of participants developed hypertension. Participants with moderate/high versus no/low caregiving stress had a higher incidence of hypertension (51.7% versus 40.6%). Higher caregiving stress was associated with incident hypertension after adjustment for sociodemographic and clinical factors, health behaviors, and depressive symptoms (hazard ratio, 1.39 [95% CI, 1.01-1.94]). Being a caregiver for a high-needs dependent was not associated with incident hypertension (adjusted hazard ratio, 0.88 [95% CI, 0.64-1.21]).

Conclusions: Higher caregiving stress among reproductive-age Black women was associated with incident hypertension. Hypertension prevention approaches for this high-risk population may include caregiving stress management strategies.

Background: Ang-(1-7) (angiotensin (1-7)) via MasR (Mas receptor) opposes vaso-injurious actions of Ang II (angiotensin II) as shown in models of pulmonary hypertension. The underlying mechanisms remain unclear. We hypothesized cross talk between Ang-(1-7) and the protective arm of the ET-1 (endothelin-1) system involving MasR and ET_BR (endothelin receptor type B).

Methods: To address this, we studied multiple models: in vivo, in a mouse model of ET-1-associated vascular injury (hypoxia-induced pulmonary hypertension); ex vivo, in isolated mouse arteries; and in vitro, in human endothelial cells.

Results: Pulmonary hypertension mice exhibited pulmonary vascular remodeling, endothelial dysfunction, and ET-1-induced hypercontractility. Ang-(1-7) treatment (14 days) ameliorated these effects and increased the expression of vascular ET_BR. In human endothelial cells, Ang-(1-7)-induced activation of eNOS (endothelial NO synthase)/NO was attenuated by A779 (MasR antagonist) and BQ788 (ET_BR antagonist). A779 inhibited ET-1-induced signaling. Coimmunoprecipitation and peptide array experiments demonstrated the interaction between MasR and ET_BR. Binding sites for ET_BR were mapped to MasR (amino acids 290-314). Binding sites for MasR on ET_BR were identified (amino acids 176-200). Peptides that disrupt MasR:ET_BR prevented Ang-(1-7) and ET-1 signaling. Using high-throughput screening, we identified compounds that enhance MasR:ET_BR interaction, which we termed enhancers. Enhancers increased Ang-(1-7)-induced eNOS activity, NO production, and Ang-(1-7)-mediated vasorelaxation, and reduced contractile responses.

Conclusions: We identify cross talk between Ang-(1-7) and ET-1 through MasR:ET_BR interaction as a novel network that is vasoprotective. Promoting coactivity between these systems amplifies Ang-(1-7) signaling, increases ET-1/ET_BR-mediated vascular actions, and attenuates the injurious effects of ET-1. Enhancing Ang-(1-7)/MasR:ET-1/ET_BR signaling may have therapeutic potential in conditions associated with vascular damage.

cGMP plays a central role in cardiovascular regulation in health and disease. It is synthesized by NO or natriuretic peptide activated cyclases and hydrolyzed to 5'GMP by select members of the PDEs (phosphodiesterase) superfamily. The primary downstream effector is cGMP-dependent protein kinase, primarily cGK-1a (cyclic GMP-dependent protein kinase 1 alpha) also known as protein kinase G 1a in the heart and vasculature. cGMP signaling is controlled in intracellular nanodomains to regulate myocyte growth, survival, metabolism, protein homeostasis, G-protein-coupled receptor signaling, and other critical functions. The vascular effects of cGMP signaling have been dominated by its lowering of smooth muscle tone, but other cellular processes are also engaged. Localization of cyclases and corresponding PDEs within intracellular domains, along with their varying expression across different cell types, adds multiorgan complexity to cGMP signaling. This diversity can be leveraged therapeutically by targeting selective pathway components to impact some but not other cGMP signaling effects. Here, we review the generation and regulation of cGMP by PDEs and cyclases, focusing mainly on their role in cardiac physiology and pathophysiology. Current therapeutic uses of cGMP modulation and ongoing trials testing new potential applications are discussed.

Background: Aldosterone-producing adenomas (APAs) are a common cause of primary aldosteronism that can lead to cardiovascular complications if left untreated. Machine learning-based bioinformatics approaches have emerged as powerful tools for identifying potential disease markers, gaining widespread recognition in biomedical research. We aimed to use machine learning to discover novel biomarkers of APAs to identify new pathophysiological mechanisms.

Methods: We applied 2 machine learning algorithms to published RNA sequencing data to identify APA feature genes. Validation was performed using APA tissue samples, spatial transcriptomics, pig adrenal glands, and in vitro assays in a human adrenocortical cell line.

Results: Machine learning identified ATP2A3 as a key feature gene in APA, and its upregulation in APAs compared with the adjacent cortex was confirmed by spatial transcriptomics. In human adrenocortical cells, angiotensin II treatment increased ATP2A3 gene expression 9.15-fold. Silencing ATP2A3 decreased basal CYP11B2 expression and aldosterone secretion by 3.51-fold and 1.46-fold, respectively, and by 1.77-fold and 1.94-fold under angiotensin II stimulation. Dietary sodium restriction in pigs significantly increased ATP2A3 mRNA and protein levels. Spatial transcriptomics showed that APA cells exhibited higher ATP2A3 gene expression compared with all other adrenal cell types. The suppressive effect of ATP2A3 silencing on CYP11B2 expression was further enhanced by Ca²⁺ inhibitors.

Conclusions: The ATP2A3 gene is highly expressed in APA and is a key regulator of CYP11B2 expression and aldosterone production.