American Journal of Hypertension最新文献

Background: Blood pressure (BP) variability and long-term BP exposure is associated with cardiorenal events. We investigated the associations of visit-to-visit BP variability and cumulative BP exposure with cardiorenal events in young adults with hypertension.

Methods: We identified adults aged 18-39 years with stage 1 or 2 hypertension between 2009-2019 from a large US integrated healthcare system. BP variability was assessed using coefficient of variation, and cumulative BP exposure was calculated as the time-weighted average over three years prior to the index date. Cox proportional hazards models assessed associations with incident cardiovascular and kidney events, adjusting for baseline BP and covariates.

Results: Among 151,692 young adults, 812 cardiovascular and 1,194 kidney events occurred over a median of 5.4 years. Both systolic BP (SBP) variability and time-weighted average SBP exhibited J-shaped or linear associations with cardiorenal events, especially among stage 1 hypertension. In this group, SBP variability at the 90th vs. 50th percentile was associated with increased risks of cardiovascular (HR = 1.25; 95%CI 1.07-1.46) and kidney events (HR = 1.24; 95%CI 1.09-1.41), after adjusting for baseline BP. Time-weighted average SBP of 140 vs. 120 mm Hg was associated with increased risks of cardiovascular (HR = 2.58; 95%CI 1.82-3.65) and kidney events (HR = 1.56; 95%CI 1.16-2.10). Time-weighted average diastolic BP of 90 vs. 80 mm Hg was associated with cardiovascular (HR = 3.65; 95%CI 2.18-6.14) and kidney events (HR = 1.53; 95%CI 0.96-2.42).

Conclusions: BP variability and cumulative BP exposure may be important prognostic markers for cardiorenal events in young adults, particularly those with stage 1 hypertension.

Background: Leucine-rich repeat-containing protein 8 A (LRRC8A) has been uncovered to play a role in pulmonary vascular remodeling during hypertension. The present study aims to investigate a novel mechanism involving LRRC8A in smooth muscle cell (SMC) phenotypic transformation under the hypertension context.

Methods: Angiotensin (Ang)-II-treated human aortic SMCs were established as the cell model under the hypertension context. Western blot and reverse-transcription quantitative polymerase chain reaction were used to detect the levels of target genes. Cell viability and proliferation were evaluated by cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays, and migration and invasion assays were applied to assess the abilities to migrate and invade of SMCs. The interaction between LRRC8A and ubiquitin-specific protein 8 (USP8) was predicted by the Ubibrowser database and verified by co-immunoprecipitation assay, respectively.

Results: LRRC8A was upregulated in Ang-II-treated SMCs, the silence of which reduced cell proliferation, migration, and invasion and increased the expression of contractile proteins (α-SMA, alpha-smooth muscle actin; SM22α, SM22 alpha). USP8 modulated the ubiquitination-modifying levels on LRRC8A protein, and USP8 promoted SMC phenotypic transformation depending on its deubiquitination function. LRRC8A overexpression reversed the repressed cell phenotypic transformation mediated by USP8 silence, and USP8 might accelerate vascular remodeling partly by activating the LRRC8A/PI3K/AKT axis during hypertension.

Conclusion: LRRC8A upregulation involves in SMC phenotypic transformation under the hypertension context; USP8 can modulate LRRC8A expression in a deubiquitination-dependent manner to further regulate the downstream PI3K/AKT axis during hypertension, which may provide novel therapeutic targets for hypertension management.

Background: Home blood pressure monitoring (HBPM) is an effective method for diagnosing and managing postpartum hypertension, a condition associated with increased health risks. A 5-min seated rest before home blood pressure (BP) measurement is recommended; however, compliance to this recommendation and its impact on HBPM reading in postpartum women is unknown.

Methods: A subset of participants enrolled in a pregnancy cohort were followed at 3 and 6 months postpartum. At each assessment, participants completed HBPM for seven days with an oscillometric device and concurrently wore an accelerometer on their thigh to assess postures. Mixed-effects models and intraclass correlation coefficients were utilized to analyze BP differences and measurement reliability between 5-min rest compliant and noncompliant readings, respectively.

Results: A total of 45 participants (mean age: 30.5 years) provided HBPM data at 3 and/or 6 months postpartum, with 90.2% of requested BP measures taken. Approximately 33% of readings adhered to the 5-min rest protocol. Compliant readings averaged lower systolic and diastolic BP values than noncompliant readings (SBP: 105.9 mmHg vs. 107.1 mmHg; DBP: 72.6 mmHg vs. 73.2 mmHg), but differences were not clinically relevant. Compliant DBP ICCs fell within the good reliability range (ICCs: 0.785-0.817), while other ICCs indicated moderate reliability.

Conclusions: Despite low compliance with 5 mins of seated rest prior to HBPM, the minimal impact on BP values suggests HBPM remains a useful monitoring strategy in postpartum women, even if the premeasurement rest is not always possible. Future research could evaluate whether shorter premeasurement rest recommendations produce similar findings.

Hypertensive disorders of pregnancy (HDPs) are a leading cause of maternal and perinatal morbidity and mortality globally, affecting up to 10% of pregnancies. As rates of obesity, chronic hypertension, and advanced maternal age continue to rise, the burden of HDPs is expected to escalate. This review provides a comprehensive overview of HDPs, encompassing updated classification systems, risk factors, and diagnostic approaches, including emerging biomarkers and predictive imaging tools. We highlight the complex pathophysiology involving impaired placentation, angiogenic imbalance, immune dysregulation, oxidative stress, mitochondrial dysfunction, and epigenetic modifications. Current management strategies are discussed alongside evolving therapeutic interventions, including low-dose aspirin, statins, and novel agents such as hydrogen sulfide donors and C-type natriuretic peptide. Special emphasis is placed on racial, ethnic, and socioeconomic disparities that contribute to disproportionate outcomes, particularly among Black and Indigenous women. We also explore the role of personalized medicine, predictive models, and digital health tools in transforming HDP care. By integrating mechanistic insight with public health strategies and clinical innovation, this review aims to inform multidisciplinary approaches to reduce the burden of HDPs and promote equitable maternal and neonatal outcomes.

Background: Hypertension, a prevalent cardiovascular disorder, exerts detrimental effects on the respiratory system. However, the underlying mechanisms remain incompletely elucidated.

Methods: We conducted comparative transcriptomic profiling via RNA sequencing (RNA-seq) of lung tissues from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. Additionally, we assessed the effects of angiotensin receptor blocker (ARB) and angiotensin receptor-neprilysin inhibitor (ARNI) interventions on mRNA and protein expression profiles in SHR pulmonary tissue using integrated omics approaches.

Results: Core differentially expressed genes (DEGs) identified in SHR versus WKY comparisons included Nuf2 and Cenpa, with significant enrichment in the PI3K/AKT signaling pathway. In SHR versus ARB-treated cohorts, hub genes Ccnb2 and Mad2l1 demonstrated primary pathway enrichment in cell-cycle regulation and human T-cell leukemia virus 1 infection. ARNI intervention yielded distinct hub genes (Gzma, Icam1) enriched in PI3K/AKT signaling and extracellular matrix (ECM)-receptor interactions. Proteomic analysis confirmed concordant expression patterns for EGFR and JUN proteins with transcriptomic findings.

Conclusions: ARB and ARNI therapies mitigate hypertension-induced pulmonary damage through divergent molecular mechanisms, with PI3K/AKT signaling and ECM-receptor interactions serving as central regulatory hubs in this protective process.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce both systolic blood pressure (SBP) and diastolic blood pressure (DBP). The glucose-lowering effect of SGLT2i depends on baseline estimated glomerular filtration rate (eGFR), but whether the same is true for the blood-pressure-lowering effect is unknown.

Methods: We performed a systematic literature review in PubMed (Study 1) and analyzed data from a clinical study (Study 2) to investigate if the blood-pressure-lowering effect of SGLT2i depends on baseline eGFR. In the literature review, we performed a weighted regression analysis with mean change in SBP and DBP as dependent variables and mean eGFR as an independent variable. Furthermore, we analyzed data from a cohort of 48 patients with either type 2 diabetes mellitus with and without chronic kidney disease (CKD) or non-diabetic CKD with varying degrees of kidney function.

Results: In total, 2,069 articles were identified, of which 27 articles met the inclusion criteria. Analysis revealed a mean weighted reduction in SBP -4.7 mmHg compared to baseline and -3.5 mmHg compared to placebo. The weighted regression analysis showed no correlation between change in SBP and baseline eGFR. Data analysis of 48 patients revealed an SBP reduction of 5.5 mmHg, and the simple linear regression revealed no correlation between the decrease in blood pressure and baseline eGFR.

Conclusions: The blood-pressure-lowering effect of SGLT2i does not depend on baseline eGFR.

Background: Racial/ethnic disparities in sleep outcomes may compound cardiovascular health (CVH) risks, particularly among adults with hypertension (HTN). This study examines differences in sleep health across racial/ethnic groups, with a primary focus on adults with HTN.

Methods: We analyzed NHANES data (2011-2023) for adults aged ≥20 years. Sleep outcomes included daytime sleepiness (2015-2020), sleep duration (2011-2023), and sleep quality (2011-2020). HTN was defined as blood pressure ≥130/80 mmHg, self-reported diagnosis, or antihypertensive use. Regression models assessed associations between race/ethnicity and each sleep outcome, adjusting for relevant covariates. Analyses were stratified by HTN status to examine differences among adults with and without HTN. All models incorporated NHANES sampling weights and accounted for the complex survey design.

Results: Among ~201.7 million US adults (mean age: 48.0 ± 17.1 years), 52.6% had HTN. Among adults with HTN, NH Black and NH Asian adults had higher odds of short sleep (<7 hours) compared to NH White adults (aOR: 1.86, 95% CI: 1.58-2.21; aOR: 1.58, 95% CI: 1.29-1.93). Odds of poor sleep quality were elevated in NH Asian (aOR: 2.45, 95% CI: 2.09-2.89), NH Black (aOR: 1.47, 95% CI: 1.29-1.67), and Mexican-American/Hispanic adults (aOR: 1.57, 95% CI: 1.34-1.83). In contrast, excessive daytime sleepiness was less common among NH Asian (aOR: 0.17, 95% CI: 0.11-0.25), NH Black (aOR: 0.49, 95% CI: 0.34-0.72), and Hispanic adults (aOR: 0.38, 95% CI: 0.27-0.53) than NH White adults.

Conclusions: Racial/ethnic disparities in sleep health are more pronounced among adults with HTN, compounding their overall cardiovascular health risk.

Background: Hypertension is caused by a combination of genetic and environmental factors. Angiotensinogen (AGT) is a component of renin-angiotensin-aldosterone system, which regulates blood pressure. Genome-wide association studies have shown that two A/G polymorphisms (rs2493134 and rs2004776), located at +507 and +1164 in intron I of the human AGT (hAGT) gene, are linked to hypertension. AGT polymorphisms result in two haplotypes, Hap-I a pro-hypertensive, whereas Hap-II is normotensive. Previous studies support the role of epigenetics in blood pressure regulation. In this study, we generated transgenic mice (TG) with hAGT containing Hap-I and Hap-II variants to investigate the effect of high salt diet (HSD) on epigenetics and transcriptional regulation.

Methods: We treated Hap-I and Hap-II TG mice with 4% HSD and identified DNA methylation patterns. We measured hAGT mRNA and protein by qPCR and immunoblot, respectively. Chromatin immunoprecipitation assay and RNA sequencing were performed.

Results: hAGT gene expression is increased by HSD in both Hap-I and Hap-II TG mice. In the liver and kidney, we observed significantly higher DNA demethylation (less CpG's) and stronger binding of transcription factors in the promoter of Hap-I TG mice as compared to Hap-II post HSD. RNA-Seq identified differentially expressed genes, novel target genes, canonical pathways, and upstream regulators associated with hypertension.

Conclusions: Our findings identified a novel high salt-sensitive risk haplotype, novel CpG sites and DNA methylation patterns, potential gene targets, and pathways implicated in hypertension. Combining epigenetic and transcriptional analysis allows for a more holistic understanding of the regulatory mechanisms that govern the hAGT gene.

Background: Recent studies show that cardiovascular disease (CVD) risk increases from a lower nadir of systolic blood pressure (SBP) in women than men, and increases thereafter at a greater rate. This has led to a suggestion that sex-based SBP thresholds are required. We investigated sex differences in the associations of SBP and incident atherosclerotic CVD.

Methods: This prospective study included 420,649 UK Biobank participants with no prior history of CVD. Age-adjusted sex-specific risks, relative risks (RRs), and risk differences (RDs) relating SBP to CVD were estimated using Poisson and Cox regression.

Results: Over 13.6 years of follow-up, there were 28,628 CVD events. CVD risks across BP levels showed a "J-shape," and were higher in men than women at all BP levels. The lowest risks were at SBP 100-<105 mmHg (events per 10,000 person-years [95% CI]: 15.6 [11.8-19.4]) and 110-<115 (47.2 [41.4-53.0]) among women and men, respectively. Compared with SBP 100-<110, sex-specific RRs at above 120 were higher in women than men, but RDs were higher in men than women at all levels of SBP. Compared to men at 110-<115 (ie, the men with least risk), risks in women were lower at all levels of SBP below 170.

Conclusions: CVD risk is lowest for women at a slightly lower SBP than men and RRs for CVD increase with SBP at a slightly steeper rate in women. However, both risks and RDs in women are never greater than in men. This evidence does not support lower thresholds for diagnosis of hypertension in women.

Background: Excess aldosterone of >15 ng/dL, in the presence of low renin, is linked to hypertension (HTN) and chronic kidney disease (CKD). This study investigated the association of aldosterone dysregulation at lower plasma aldosterone levels (≥5 ng/dL) with the risk of uncontrolled HTN and CKD prevalence.

Methods: Patient plasma aldosterone measurements obtained during 2013-2023 were identified in the TriNetX Dataworks-USA Network of electronic medical records. Eligible patients (≥18 years) had a plasma renin activity measurement of ≤1 ng/mL/h within 12 months before, and a systolic blood pressure (SBP) measurement within 12 months following, the index aldosterone measurement. The primary outcome was uncontrolled HTN (SBP ≥130 mmHg) prevalence. The secondary outcome was CKD prevalence (CKD diagnosis or eGFR measurement of <60 mL/min/1.73 m2). The adjusted odds ratio (aOR) of uncontrolled HTN during a 12-month follow-up was calculated among plasma aldosterone groups (≥5 vs <5 ng/dL, ≥10 vs <10 ng/dL, and ≥15 vs <15 ng/dL).

Results: Patients (N = 1334) had a mean age of 59 years, and 55.9% were female. Patients with plasma aldosterone of ≥5 ng/dL (N = 903) had a higher risk (aOR [95% CI]) of uncontrolled HTN (2.01 [1.38-2.92]; P < .001) versus <5 ng/dL (N = 431). Similar findings were observed for plasma aldosterone levels of ≥10 ng/dL and ≥15 ng/dL. Patients with plasma aldosterone of ≥10 ng/dL (N = 514) had a higher risk of CKD (1.49 [1.15-1.92]; P < .001) versus <10 ng/dL (N = 820). Similar findings were observed for plasma aldosterone levels of ≥15 ng/dL.

Conclusions: Clinically relevant aldosterone dysregulation, in the presence of low renin, occurs at lower aldosterone levels than previously thought, and remains significantly associated with uncontrolled HTN and CKD prevalence.