American Journal of Hypertension最新文献

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.

Background: The relationship between childhood and adulthood obesity and the risk of gestational diabetes mellitus (GDM) remains unclear. To clarify the independent and joint effects of childhood and adulthood body size on GDM risk, and explore inflammation's role.

Methods: Using female-specific UK Biobank genome-wide association study data, genetic instruments for childhood/adult body size ("thinner," "about average," "plumper") and C-reactive protein (CRP) were identified. GDM variants came from FinnGen. Univariable and multivariable Mendelian randomization (MR) assessed causality and mediation.

Results: Univariable MR analyses provided strong evidence for genetically predicted effects of both childhood body size (odds ratio [OR] per category = 1.72, 95% CI: 1.42-2.09, P < 0.001) and adulthood body size (OR = 1.59, 95% CI: 1.42-1.79, P < 0.001) on GDM risk. However, in multivariable MR analysis, the effect of childhood body size was attenuated and no longer significant after adjusting for adulthood body size (OR = 1.19, 95% CI: 0.91-1.48, P = 0.221), whereas the effect of adulthood body size remained significant even after controlling for birth weight, childhood body size, and age at menarche (OR = 1.42, 95% CI: 1.15-1.68, P = 0.011). Further analysis indicated that CRP partially mediated the effect of adulthood body size on GDM risk.

Conclusions: Our findings suggest that childhood obesity increases the future risk of GDM primarily through its persistence into adulthood, and that inflammation, as indicated by elevated CRP levels, partially mediates the effect of adult obesity on GDM risk. These results highlight the importance of early obesity prevention and intervention, as well as inflammation control, to reduce the risk of GDM later in life.

Background: Nocturnal hypertension (NH) is associated with adverse cardiovascular outcomes beyond and even independent of daytime hypertension (DH). Although cohort studies have evaluated correlates of NH, there is comparably less data available from real-world clinical practice and for population subsets that tend to be under-represented in cohort studies.

Methods: This retrospective cohort study included all patients who underwent ambulatory blood pressure monitor (ABPM) testing at a large US academic medical center from 1 January 2013 to 31 December 2023. We used multivariable-adjusted logistic regression to assess DH as a correlate of NH, covariates related to the co-occurrence of DH and NH, and correlates of isolated NH.

Results: Of 1,566 patients, 812 (51.9%) had DH, 1,125 (71.8%) had NH, and 363 (23.2%) had isolated NH. A total of 762 (48.7%) patients had co-occurring daytime and NH. In multivariable analysis, significant correlates of NH included DH, male sex, age, Black race, and Hispanic ethnicity. By comparison, significant correlates of co-occurrent DH and NH included male sex, age, Asian race, Black race, and renal disease; coronary artery disease (CAD) was inversely associated with this co-occurrence. Among all covariates, only CAD was associated with isolated NH.

Conclusions: Our real-world study results highlight the generally under-recognized prominence of isolated NH, as well as the presence of NH among Hispanic and Asian-American populations. Further prospective investigations are needed to evaluate whether broader ABPM screening for NH is needed across all populations at risk, including but not limited to persons with more easily identified DH.

Background: The optimal blood pressure (BP) target for adults with type 2 diabetes (T2DM) remains a topic of debate. This systematic review and meta-analysis aimed to investigate the efficacy of intensive BP control strategies compared to standard or less intensive approaches in adults with T2DM.

Methods: We comprehensively searched databases for studies comparing intensive vs. less intensive BP targets in individuals with T2DM. In this study, the group with the most intensive target was compared to the group with the least intensive target. Also, studies were analyzed based on current guideline recommendations. Outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stroke, heart failure, retinopathy, neuropathy, nephropathy, and end-stage renal disease. Risk ratios with 95% confidence intervals were calculated.

Results: The meta-analysis included 21 studies (16 RCTs) with 290,907 participants (mean age 61.84 years, 55.03% male). Guideline-based analyses showed comparable clinical outcomes between groups with no significant differences. However, the most intensive targets vs. the least intensive targets revealed that the intensive BP control group experienced a significantly lower risk of MACE (RR = 0.75, 0.58; 0.98), nonfatal MI (RR = 0.61, 0.41; 0.91), nonfatal stroke (RR = 0.60, 0.39; 0.92), and total stroke (RR = 0.61, 0.39; 0.95). Other outcomes were similar between groups. Subgroup analysis of RCTs mirrored the overall findings.

Conclusions: In adults with T2DM, intensive BP control reduces the risk of cardiovascular events, such as MACE, stroke, and MI. Additionally, it demonstrates comparable diabetes-related complications to less intensive or standard controls.