Hypertension incidence increases with age, with its highest burden in elderly African Americans (AAs). But socio-biological aging pathways underlying this difference are not well characterized, with a substantial paucity of epigenetic studies on hypertension-related racial disparity in the elderly. We primarily examined epigenetic aging acceleration (aging accel) in the prospective development of hypertension and secondarily investigated the extent to which adverse social exposures mediated AAs' greater aging accel and, jointly with increased aging accel, explained their greater risk of hypertension outcomes. We obtained global-level DNA methylation and clinical data, social determinants of health (SDOH), and physiological data from > 1,500 postmenopausal women in the Women's Health Initiative. Hypertension outcomes were followed for 3-year short-term and a mean of 17-year longer-term periods. Levine's aging accel was estimated, and mediation analyses were performed with SDOH and aging accel via Sobel and Multiple Mediation Analysis. Greater epigenetic aging was associated with hypertension outcomes during the short-term follow-up. While the lower level of SDOH was related to greater aging accel, its influence on greater aging accel in AAs than whites varied by SDOH type and, in combination, was partial (range, 1-26%). Finally, a group of SDOH and aging accel, both separately and jointly, mediated AAs' greater incidence of hypertension to a limited extent during both short-term and longer-term follow-up periods. Our study contributes to better understanding of socio-biological hypertensive pathways shared by aging processes, which may inform risk stratification in the elderly in hypertension prevention and racial disparity.
This study examined the association of hypertension and obesity with incident heart failure (HF) and the feasibility of the clinical obesity definition proposed by The Lancet Diabetes & Endocrinology Commission. Data from the UK Biobank (n = 444,754) and Tongzhou Cohort (n = 10,459) were analyzed. Hypertension was defined as physician-diagnosed hypertension, blood pressure ≥140/90 mmHg, or antihypertensive treatment. Obesity was assessed as BMI-defined obesity, central obesity, a combined "BMI+central" anthropometric phenotype, and clinical obesity, defined as excess adiposity with obesity-related organ dysfunction and/or functional limitation. Participants were classified into four groups: neither hypertension nor obesity, obesity only, hypertension only, and coexisting hypertension and obesity. Kaplan-Meier curves and multivariable Cox models were used to estimate HF risk, and joint effects of elevated blood pressure and pre-obesity were evaluated. The two cohorts had similar mean ages: 58.15 ± 6.84 years in the UK Biobank and 59.42 ± 6.29 years in Tongzhou Cohort. Depending on the obesity definition, the prevalence of coexisting hypertension and obesity ranged from 18.0% to 25.9% in the UK Biobank and 23.1% to 37.3% in Tongzhou Cohort. Across BMI-defined obesity, central obesity, the combined "BMI+central" phenotype, and, in the UK Biobank, clinical obesity, coexistence of hypertension and obesity was consistently associated with the highest HF risk. Among individuals without hypertension or obesity, the combination of elevated blood pressure and pre-obesity was associated with increased risk of HF. Coexisting hypertension and obesity are associated with the highest HF risk across multiple adiposity definitions, and excess risk is evident even at preclinical stages.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Objective: This exploratory post hoc analysis examined the safety/efficacy of the aripiprazole once-monthly 400 mg (AOM 400) long-acting injectable (LAI) in Black/African American patients diagnosed with bipolar I disorder (BP-I). Methods: Data were from a 52-week, open-label trial of AOM 400 maintenance treatment in patients diagnosed with DSM-IV-TR-defined BP-I. Outcomes included treatment-emergent adverse events (TEAEs), clinician-rated extrapyramidal symptoms (EPS), patient stability, Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Bipolar Version-Severity (CGI-BP-S) scores, functioning, and quality of life (QoL). Data analyses comprised descriptive statistics and a mixed model for repeated measures. Results: Outcomes were analyzed in 464 patients (Black/African American, n=104; White, n=255; Asian, n=94; other racial groups, n=11). No notable increase in TEAEs, serious TEAEs, or TEAEs leading to discontinuation were observed in Black/African American patients vs those in other racial groups. Rates of akathisia, tremor, increased weight, or hypertension were lower/similar in Black/African American patients vs other racial groups; changes in EPS scores were minimal in all groups. At last visit, 90.1% of Black/African American patients were stable, similar to other racial groups. Small changes in YMRS total score occurred in all groups, with MADRS total score and CGI-BP-S scores largely unchanged. Functioning and QoL improved in Black/African American patients, to a similar/greater degree than other racial groups. Limitations include the open-label design, prior aripiprazole stabilization, and sparse metabolic laboratory data, constraining causal inference and metabolic conclusions. Conclusion: The safety and efficacy of AOM 400 is comparable between Black/African American and non-Black/African American patients with BP-I. The data provide valuable evidence supporting second-generation LAI antipsychotic use in these patients. Trial Registration: ClinicalTrials.gov identifier: NCT01710709.
HEARTS in the Americas is the regional adaptation of the WHO Global HEARTS Initiative. This paper presents Phase 3 of HEARTS 2.0, an evidence-informed process to prioritize clinical and health-system interventions to support the operationalization of integrated cardiovascular, kidney, and metabolic (CKM) care in primary health care (PHC) and to inform the update of the HEARTS Clinical Pathway. CKM conditions frequently coexist, sharing common risk factors and pathophysiological mechanisms that exacerbate cardiovascular disease burden. Despite their overlap, clinical practice often remains siloed due to condition-specific guidelines, and its integration remains limited. To prioritize evidence-informed clinical and health-system interventions that support the operationalization of integrated CKM care within PHC and inform the update of the HEARTS Clinical Pathway. Building on previous phases of HEARTS 2.0, a multidisciplinary panel evaluated 45 candidate interventions in different areas. The selection process utilized structured evidence appraisal, Evidence-to-Decision frameworks, and a modified RAND/UCLA appropriateness method involving anonymized rating rounds. A total of 38 interventions were prioritized for implementation. Although hypertension management remains the primary entry point, the resulting framework integrates early detection of diabetes and chronic kidney disease, lifestyle interventions, risk-based combination pharmacotherapy, task-sharing, and longitudinal follow-up. By translating dispersed guideline recommendations into implementable interventions, Phase 3 of HEARTS 2.0 provides an evidence-informed basis for advancing integrated CKM care at scale in PHC and guiding the forthcoming update of the HEARTS Clinical Pathway. The resulting framework offers a flexible, scalable approach for countries confronting similar epidemiological and health system challenges.
The 2025 American Heart Association/American College of Cardiology blood pressure guideline (2025-AHA/ACC-BP guideline) recommends out-of-office blood pressure (BP) assessment to exclude white-coat hypertension (WCH) in untreated and white-coat effect (WCE) in treated individuals among adults with office BP (OBP) ranging between 130/80-<160/100mmHg, but its real-world diagnostic performance remains incompletely characterized. We evaluated the performance of 2025-AHA/ACC-BP guideline-recommended OBP thresholds for screening WCH/WCE among 147,404 Brazilian adults with OBP ≥ 130/80mmHg, including 86,692 untreated (29.7% WCH) and 46,229 treated (29.2% WCE) individuals who underwent HBPM and 10,475 untreated (46.2% WCH) and 4,008 treated (49.4% WCE) individuals who underwent ABPM. OBP ranges combining ≥130/80mmHg with progressively lower upper limits (<160/100, <150/95, <150/90, and <140/90mmHg) were evaluated. The performance of OBP intervals to detect WCH/WCE was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). In the HBPM cohort, OBP ≥ 130/80-<160/100mmHg yielded sensitivity, specificity and AUC of 95%, 25% and 0.600 in untreated and 94%, 28% and 0.610 in treated participants. Narrower OBP ranges increased AUCs, peaking at OBP ≥ 130/80-<150/90mmHg (0.682 and 0.677 in untreated and treated, respectively). In the ABPM cohort, the corresponding values for OBP ≥ 130/80-<160/100mmHg were 94%, 34% and 0.641 (untreated) and 91%, 41% and 0.662 (treated), AUC's were highest at OBP ≥130/80-<150/90mmHg (0.722 in both groups). This real-world analysis shows that OBP thresholds recommended by the 2025-AHA/ACC-BP guideline for WCH/WCE screening are highly sensitive but have low specificity, resulting in referral of the majority of patients for out-of-office BP assessment.
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder frequently associated with non-dipper hypertension, with tolvaptan being the only currently approved treatment. However, the effects of tolvaptan on blood pressure (BP) in patients with ADPKD and hypertension remain unclear. This retrospective study examined the effect of tolvaptan on 24-hour ambulatory BP monitoring parameters. Changes in ambulatory BP-related parameters, including annual rate of change in total kidney volume (TKV), were assessed in 23 patients with ADPKD and hypertension before and after initiating tolvaptan. After initiation of tolvaptan, nocturnal systolic and diastolic BP dipping rates increased significantly, with systolic dipping rising from 9.61% to 14.0% (Δ  + 4.39%; P = .014) and diastolic dipping from 10.48% to 14.66% (Δ  + 4.18%; P = .023). The prevalence of a non-dipper BP profile decreased from 57% at baseline to 29% after treatment (P = .0339). In addition, the annual growth rate of TKV decreased from 13.6% to 1.61% (P < .0001), and the eGFR slope improved from -4.46 to - 2.26 mL/min/1.73 m2/year (P = .0431). Tolvaptan treatment was associated with improvements in nocturnal BP decline and diurnal BP patterns in patients with hypertension and ADPKD. In addition, a reduced rate of TKV growth and a slower decline in eGFR were observed. These findings provide further insight into the potential hemodynamic and renal effects of tolvaptan in this population.
The impact of the time target range of systolic blood pressure (SBP-TTR) on cardiovascular disease (CVD) and all-cause mortality has not yet been elucidated in the young and middle-aged adult subjects with hypertension. We detail the possible relationship between SBP-TTR and the risk of new-onset CVD and all-cause mortality among young and middle-aged adult subjects with hypertension. A longitudinal analysis was conducted within the Kailuan study, involving participants under 60 with hypertension per 2018 ESC/ESH guidelines, who underwent at least three health assessments from 2006 to 2016. The target range for SBP was defined as 120 to 140 mm Hg. SBP-TTR was determined through linear interpolation of systolic blood pressure (SBP) measurements during health exams until 2017. Primary outcomes included new-onset CVD and all-cause mortality through December 2022. The cohort included 21,855 participants (82.7% male) with an average SBP of 144.59 mmHg. The average SBP-TTR was 39%. 1,969 CVD events and 1,290 all-cause deaths were documented. Higher SBP-TTR correlated with younger age, greater education, and improved kidney function. Increased SBP-TTR was associated with diminished new-onset CVD and lower all-cause mortality rates. Specifically, risks for CVD decreased by 12%, 14%, and 31%, and for mortality by 9%, 12%, and 34% across increasing SBP-TTR groups. A near-linear dose-response relationship was noted (P for non-linearity = 0.303), confirmed by sensitivity analyses. The stricter SBP control was associated with a lower incidence of CVD. In middle-aged and younger adults with hypertension, a higher SBP time in target range is associated with progressively lower risks of new-onset CVD and all-cause mortality, underscoring the importance of sustained blood pressure control.
Regular physical activity (PA) is linked to improved health and hypertension management, yet many adults with hypertension do not meet aerobic guidelines, and limited research has examined the use of wearable devices in promoting activity in this population. This study aimed to examine the association between wearable device use and adherence to the aerobic PA guideline among individuals with hypertension. Adults with self-reported of hypertension in the 2017 Behavioral Risk Factor Surveillance System were included in the analysis. Participants were categorizing as either wearable device users or nonusers based on self-report. Participants were considered meeting the aerobic PA guidelines if they engaged in at least 150 minutes of moderate-to-vigorous PA per week. Otherwise, they were categorizing as not meeting the guideline. Associations between wearable device use and guideline adherence were evaluated using survey-weighted adjusted Poisson regression with a log link, adjusting for demographic characteristics. Among 1602 participants with hypertension, 18.1% (95% CI, 14.1-22.5) of participants reported using wearable devices. Among users, 79.3% (95% CI, 69.9-88.6) met the aerobic PA guideline, compared to 70.3% (95% CI, 64.7-76.0) of nonusers. Wearable users were more likely to meet the guideline than nonusers (prevalence ratio = 1.22 (95% CI, 1.06-1.40)). Wearable devices could be an effective tool in promoting PA among individuals with hypertension leading to adherence to the recommended aerobic PA guideline.
Intrahepatic cholestasis of pregnancy (IHCP) is the most common pregnancy-specific liver disease. This study aimed to determine the prevalence of proteinuria in patients with IHCP and to evaluate its association with adverse pregnancy outcomes. This retrospective cohort study included pregnant patients with gestational age > 24 weeks who were diagnosed with IHCP and completed 24-hour urine protein collection at Haseki Training and Research Hospital (January 2018-December 2024). Proteinuria was defined as ≥300 mg/24-h urine collection. Patients were categorized into 3 groups: non-proteinuric, isolated proteinuria (proteinuria ≥ 300 mg/24 h in the absence of hypertension), and preeclampsia (defined according to the American College of Obstetricians and Gynecologists [ACOG] criteria). The primary outcome was a composite adverse pregnancy outcome, including preterm delivery at <34 weeks, umbilical artery pH < 7.1, and emergency cesarean delivery due to fetal distress. Group comparisons were performed using the Kruskal-Wallis test for continuous variables and the chi-square or Fisher exact test for categorical variables. Multivariate logistic regression was performed adjusting for maternal age, twin gestation, and in vitro fertilization conception. Among 341 patients, 207 (60.7%) had no proteinuria, 105 (30.8%) had isolated proteinuria, and 29 (8.5%) had preeclampsia. Overall, 39.3% of IHCP patients demonstrated proteinuria. The distribution of IHCP severity, as classified by maximum total bile acid (TBA) concentration, was comparable among the 3 groups (P = .976). The demographic parameters were comparable between the groups. The preeclampsia group exhibited significantly higher composite adverse outcome rates (P < .001). Multivariate logistic regression demonstrated that preeclampsia was independently associated with composite adverse outcomes (adjusted odds ratio: 6.96, 95% confidence interval: 2.69-18.01; P < .001), whereas isolated proteinuria showed no significant association (adjusted odds ratio: 1.54, 95% confidence interval: 0.95-2.50; P = .079). Approximately 39% of IHCP patients exhibited proteinuria. Isolated proteinuria without hypertension was not an independent predictor of adverse pregnancy outcomes. In the absence of hypertension or other features of preeclampsia, the presence of proteinuria alone may not warrant escalation of care or accelerated delivery decisions in IHCP. However, prospective validation of these findings is needed before definitive clinical recommendations can be established.
Arginine, as precursor of the antihypertensive metabolite nitric oxide, may influence blood pressure (BP) regulation and is therefore linked to hypertension, a serious global health issue. Thus, we investigated whether hypertension relates to alterations in arginine metabolism and examined the role of biological sex and body composition. We stratified 762 older adults (50-95yo) participating in the MEDIT-trial into four BP groups (normal, elevated, stage 1 and 2 hypertension) per 2025 ACC/AHA guidelines. Body composition was assessed by Dual-energy X-ray absorptiometry. After administering stable tracers of arginine, citrulline, and ornithine, blood samples were taken to measure postabsorptive plasma amino acid concentrations and tracer enrichments by LC-MS/MS. Compartmental modeling was applied to determine amino acid kinetics. Age and glucose, hs-CRP, and arginine levels were comparable across groups. Older adults with stage 1 and stage 2 hypertension had higher BMIs than those with normal BP (29.7 kg/m2 and 31.0 kg/m2 vs. 27.8 kg/m2). Whole-body and intracellular arginine production in stage 2 hypertension were increased by 10.4% and 10.7% compared to those with normotension (all: P < .05), particularly in females (whole-body: +13.7%; intracellular: +18.3%; all: P < .02). While females showed progressive increases in body composition parameters along BP groups, males displayed relatively stable values. Arginine metabolism in older adults is influenced by hypertension severity, with sex-specific differences in metabolic adaptation. Further research is warranted determining whether hypertension treatment for older adults should be individualized to disease severity, accounting for the upregulated arginine metabolism and sex-specific differences, which may lead to improved outcomes. www.clinicalTrials.gov, NCT01787682, NCT01871350, NCT01624792, NCT01890824, NCT02082418, NCT02157844, NCT06801964, NCT02065141, NCT03159390, NCT02770092, NCT02908425, NCT02780219, NCT02780206, NCT03327181, NCT06801951, NCT03796455, NCT04928872, NCT04461236, NCT05395390, NCT05240885, NCT06628349=.
Hypertension affects almost half of US adults and is a major cause of cardiovascular morbidity and mortality. Although expert guidelines recommend screening for secondary hypertension in patients with treatment-resistant hypertension and other high-risk groups, screening is conducted in <2% of candidates. This study aimed to determine barriers for secondary hypertension screening across US practices. Primary care physicians, cardiologists, nephrologists, and endocrinologists, randomly selected from active members of the American Medical Association, were surveyed on barriers for secondary hypertension screening. Response rate was 67% (425 of 633 response-eligible physicians). The leading reported barriers preventing secondary hypertension screening included visit time constraints (43.5%), poor ancillary support (29.4%), and testing-related logistics (27.5%). Primary care physicians were 10- to 17-fold less likely to be familiar with testing interpretation and subsequent steps than nephrologists and endocrinologists. Physicians in practices covered largely by Medicare were twice more likely to report poor ancillary support than physicians in practices covered primarily by private health insurance. Private practice physicians were more likely to report reimbursement concerns (adjusted odds ratio, 3.4 [95% CI, 1.6-7.7]) and poor ancillary support (adjusted odds ratio, 2.1 [95% CI, 1.3-3.6]) but also more likely to have access to specialists (adjusted odds ratio, 4.0 [95% CI, 1.2-13.5]) than physicians practicing in large medical groups. Our findings call for measures to address critical barriers in secondary hypertension screening. Strategies needed to facilitate personalized hypertension care include optimization of clinic visit duration, ancillary support, education initiatives, and timely access to specialists.
The hemoglobin-albumin-lymphocyte-platelet (HALP) score integrates pathways of anemia, malnutrition, inflammation, and thrombosis that are central to hypertensive organ damage. We therefore hypothesized that HALP would serve as a robust predictor of all-cause and cardiovascular mortality, specifically in adults with hypertension. This cohort study included 23,564 U.S. adults from NHANES (2005-2018), comprising 12,319 with hypertension and 11,245 without, linked to mortality data through 2019. Hypertension was defined as self-reported diagnosis, antihypertensive medication use, or measured blood pressure ≥130/80 mmHg. Multivariable Cox models and restricted cubic spline analysis were used to assess HALP-mortality associations. Effect modification by hypertension status was formally tested. During a mean follow-up of 7.4 years, 1,738 all-cause deaths and 451 cardiovascular deaths occurred among adults with hypertension. In this group, each one-SD higher HALP score was associated with a lower risk of all-cause mortality (HR, 0.89; 95% CI, 0.83-0.94) and cardiovascular mortality (HR, 0.74; 95% CI, 0.65-0.83). In contrast, no association was observed in adults without hypertension (all-cause mortality HR, 0.96; 95% CI, 0.83-1.13; cardiovascular mortality HR, 0.85; 95% CI, 0.65-1.15). An interaction was observed between HALP score and hypertension status for both all-cause (p for interaction = 0.008) and cardiovascular mortality (p for interaction < 0.001). Furthermore, restricted cubic spline analysis within the cohort with hypertension revealed L-shaped nonlinear relationships between the HALP score and mortality risks. A higher HALP score was associated with lower mortality risk among adults with hypertension but not among those without hypertension.
Hypertension is a recognized risk factor for acute coronary syndrome and major adverse cardiovascular events, yet its influence on high sensitivity cardiac troponin (hscTn) concentrations and on the prognostic value of intermediate hscTnI results remains uncertain. We assessed whether blood pressure category confounds the relationship between intermediate hscTnI values (4-18 nanograms per liter [ng/L]) and 30-day major adverse cardiovascular events. We performed a secondary analysis of the Rapid Acute Coronary Syndrome Evaluation-Implementation Trial (steppedwedge randomized trial across nine Michigan emergency departments [ED] (July 2020-April 2021). From 32,609 patients in the primary trial, we analyzed only those with available hs-cTnI values reported to be in the intermediate range (4-18 ng/L). The first recorded ED blood pressure-determined category: normotensive (< 140/< 90 millimeters of mercury [mm Hg] moderate [140-179/90-109 mm Hg]; or severe [≥ 180/≥ 110 mm Hg]. Generalized linear models and penalized logistic regression examined associations with hscTnI and 30-day major adverse cardiovascular events (allcause death, myocardial infarction, or urgent revascularization), respectively, adjusting for confounders. Analysis included 23,803 patients. Mean age was 57.5 ± 17.9 years; 57.5% were women and 32.7% Black. Blood pressure categories were normotensive 40.9%, moderate 46.5%, and severe 12.6%. After adjustment, severe blood pressure was associated with a 16% higher mean hscTnI (calculated as %change= 10β - 1; β = 0.064, 95%, CI 0.047-0.082). Major adverse cardiovascular events at 30-days occurred in 148 patients (0.6%), 47 of them normotensive (0.5%), 77 with moderate hypertension (0.7%), and 24 with severe hypertension (0.8%). Compared with normotension, moderate blood pressure independently increased 30-day major adverse cardiovascular events risk (adjusted odds ratio [AOR] 1.47, 95% CI, 1.02-2.13; absolute risk difference +0.25%, 95% CI, 0.01-0.49), whereas severe blood pressure showed no clear association (AOR 1.32, 95% CI, 0.80-2.18; absolute risk difference +0.17%, 95 % CI, -0.09 to 0.43). Estimates were similar in sensitivity analyses limited to patients without coronary artery disease. Among ED patients with intermediate hscTnI, blood pressure ≥ 140/90 mm Hg confers modestly higher short term risk of major adverse cardiovascular events, but incremental severity beyond this threshold does not add prognostic value. Elevated hscTnI in the context of severely elevated blood pressure likely reflects myocardial stress rather than additional ischemic risk. Clinicians should interpret intermediate troponin results in hypertensive patients cautiously, integrating clinical presentation and established risk factors.
A deeper understanding of the association between blood pressure (BP) control and neighborhood-level social determinants of health (SDOH) may help elucidate nonclinical factors that contribute to hypertension disparities. We sought to evaluate patterns of BP elevations by neighborhood-level SDOH domains. In this single-center retrospective cohort study at Cedars-Sinai Medical Center, adults with ≥2 outpatient visits/year in at least 2 consecutive years (each consecutive 2-year period forms a dyad) from 2018-2023 were linked to the Healthy Places Index (HPI), a measure of neighborhood SDOH. Among patients with normotensive BP (BP < 130/80 mmHg) in the first year of at least 1 dyad, we assessed for the development of high BP (systolic BP ≥ 130 or diastolic BP ≥ 80 mmHg) in the following year. A total of 94,276 adults (median age 56.4 ± 18.8 years; 37.2% male) with BP < 130/80 mmHg, of whom 38,719 (41.1%) developed high BP. In analyses adjusting for demographic, clinical, and SDOH factors, risk of developing high BP was associated with living in a neighborhood with a HPI score in the lowest vs highest quartile (Prevalence Ratio [PR] 1.07, 95% CI 1.05-1.10). This finding was primarily associated with the economic (1.04, 1.00-1.07) and educational attainment (1.05, 1.02-1.08) domains, captured as part of the HPI score. In a cohort of > 94,000 adults starting with BP < 130/80 mmHg, an increase in BP above this threshold in the following year was associated with neighborhood-level SDOH status, particularly variations in economic and educational attainment.
Social determinants of health (SDOH) affect cardiovascular disease (CVD) risk in Black adults, but there is limited knowledge on how SDOH dimensions are linked to CVD risk factors across different Black groups. The study examined differences in SDOH dimensions and CVD risk factors among Black ethnic groups, hypothesizing stronger associations for US-born adults. Using the National Health Interview Surveys 2013 to 2018, we categorized 24 380 non-Hispanic Black adults by birthplace into 3 groups: US born, Caribbean born, and African born. Thirteen SDOH variables were reduced to 4 indices (standard of living, neighborhood cohesion, socioeconomic advantage, and health care access) using principal component analysis. Associations between these indices and the prevalence of 3 self-reported CVD risk factors (hypertension, diabetes, and high cholesterol) were assessed using modified Poisson regression models. Among US-born Black adults, all SDOH indices were significantly associated with hypertension, diabetes, and high cholesterol (P<0.05), except for low standard of living and poor neighborhood cohesion with high cholesterol. For Caribbean-born Black adults, a low standard of living was associated with a higher prevalence of hypertension (prevalence ratio, 1.10 [95% CI, 1.1-1.21]) and diabetes (prevalence ratio, 1.24 [95% CI, 1.11-1.38]). Among African-born Black adults, only socioeconomic disadvantage was significantly associated with hypertension (prevalence ratio, 1.15 [95% CI, 1.05-1.26]). The relationship between CVD risk factors and SDOH indices varied across different Black groups and was not consistent for all indices and risk factors. These distinct associations underscore the importance of tailored interventions to address context-specific CVD risk factors and social determinants to protect cardiovascular health.
Hypertension is a leading global cause of cardiovascular, renal, and cerebrovascular morbidity. Beyond classical genetic and environmental determinants, accumulating evidence highlights epigenetic regulation as a key contributor to blood pressure control and vascular pathology. Epigenetic mechanisms including DNA methylation, histone post-translational modifications, and non-coding RNAs govern gene expression without altering the underlying DNA sequence, thereby linking environmental and physiological stimuli to stable transcriptional changes. Aberrant epigenetic signatures have been identified in vascular, renal, and endocrine tissues integral to blood pressure regulation, influencing pathways that mediate vascular tone, sodium handling, oxidative stress, and inflammation. Among these, differential methylation and histone modification of renin angiotensin aldosterone system (RAAS) genes, including AGT, REN, ACE, and AT1R, have been shown to promote sustained activation of vasoconstrictive and sodium-retentive signaling cascades. Chronic exposure to a high-salt diet (HSD) represents a potent environmental modifier of this epigenetic landscape. Excess dietary sodium can alter CpG methylation patterns, histone acetylation states, and microRNA profiles across multiple tissues, leading to enhanced RAAS activity and vascular dysfunction. These HSD-induced alterations often persist despite subsequent sodium normalization, reflecting an enduring "epigenetic memory" of dietary stress that contributes to salt-sensitive hypertension. Understanding how HSD and other environmental factors reprogram RAAS-related gene networks through epigenetic mechanisms provides critical insight into the molecular basis of hypertension. Moreover, these findings open new avenues for therapeutic intervention utilizing DNA methyltransferase and histone deacetylase inhibitors, as well as RNA-based precision therapies aimed at reversing the maladaptive epigenetic imprint underlying chronic blood pressure elevation.
This study assessed the impact of non-communicable diseases (NCDs) on health-related quality of life (HRQoL) in nursing home residents in Armenia. We used a structured interviewer-administered questionnaire to collect data on socio-demographic characteristics, NCDs, sleeping disorders, smoking status, visual impairment (VI), and HRQoL in a sample of 313 participants from nursing homes in Armenia. The Short-Form Health Survey (SF-36) questionnaire was used to measure the Physical Component Summary (PCS) and Mental Component Summary (MCS) of HRQoL. An ophthalmic examination was conducted to assess VI. The participants' mean age was 72.45 years. The most common NCDs in the sample were bone/joint diseases (30.7%), hypertension (27.5%), and heart diseases (18.5%). In the adjusted analysis, those with more than one NCD reported significantly lower PCS and MCS scores. After adjusting for potential confounders, only kidney disease was significantly associated with both PCS and MCS scores. Heart disease, respiratory diseases/asthma, and bone/joint diseases were significantly associated with only PCS score. The assessment of the influence of each NCD on specific SF-36 domains showed that, after adjusting for confounders, heart and kidney diseases were significantly associated with "pain" and "general health" domains of PCS. Bone/joint diseases were negatively associated with all domains of PCS. Kidney diseases were found to be associated with "vitality" and "mental health". NCDs significantly impaired HRQoL, with kidney and bone/joint diseases having the broadest impact on HRQoL domains. Strategies should be developed for the adequate management of NCDs, prioritizing the residents of nursing homes with multiple conditions.
Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) arises from chronic left-to-right shunting and high-flow exposure, leading to pulmonary vascular remodelling and right-heart dysfunction. Whether high-flow shunting induces branch-selective unfolded protein response (UPR) activation and endoplasmic reticulum (ER) structural adaptation in pulmonary vascular smooth muscle remains incompletely defined. Rats underwent right pulmonary artery ligation combined with left common carotid artery-external jugular vein shunting (RPAL/LCS), with or without 4-phenylbutyric acid (4-PBA) treatment. Hemodynamics, right-heart function, vascular remodeling, UPR signaling, transcriptomic profiles, apoptosis, and ER ultrastructure were assessed in vivo or in HPASMC gain- and loss-of-function experiments. RPAL/LCS increased RVSP from 22.46 ± 1.68 to 59.66 ± 7.06 mmHg, whereas 4-PBA reduced RVSP to 38.24 ± 1.71 mmHg. The wall area/total vessel area ratio increased from 46.88 ± 1.69% to 77.89 ± 3.08% after RPAL/LCS and decreased to 47.19 ± 2.00% after 4-PBA treatment. Lung immunoblotting showed increased p-IRE1α/IRE1α, whereas p-PERK/PERK and ATF6N/ATF6 did not differ significantly; these proximal UPR markers were not reduced by 4-PBA at the endpoint. In HPASMCs, ATF4 and ATF6N overexpression enriched apoptosis-related programs and induced ER swelling and fragmentation, whereas XBP-1s overexpression maintained organized ER cisternae and XBP-1s knockdown disrupted ER ultrastructure with increased Annexin V-positive apoptotic cells. This study suggests that the IRE1α-XBP1s axis supports adaptive ER proteostasis and structural organization in shunt-driven pulmonary hypertension, whereas 4-PBA improves disease features without measurable suppression of canonical UPR branch activation markers.
Pulse wave velocity (PWV) is a well-established marker of arterial stiffness and cardiovascular risk, but most assessments rely on a single value. We aimed to determine whether visit-to-visit variability in brachial-ankle PWV (baPWV) provides additional prognostic information for long-term cardiovascular outcomes. In this single-center prospective study, participants underwent baPWV measurements at baseline and at 1, 6, and 12 months. PWV variability was assessed using the coefficient of variation (CV) of baPWV. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE), including cardiac death, non-fatal myocardial infarction, non-fatal ischemic stroke, and coronary revascularization. A total of 794 participants were analyzed. The mean age was 62.6 ± 10.6 years, and 40.9% of the study population were female. During a median follow-up period of 6.31 years (interquartile range: 5.42-6.72 years), 66 cases of MACE (8.31%) were observed. Participants who experienced MACE had higher baPWV CV compared with those without events (11.25% ± 6.87% vs. 7.45% ± 5.16%). Kaplan-Meier analyses demonstrated progressively lower MACE-free survival across increasing baPWV CV tertiles. In multivariable Cox proportional hazards models, higher baPWV CV was associated with an increased risk of MACE (hazard ratio 2.38, 95% confidence interval 1.18-4.79) after adjustment for potential confounders. Longitudinal fluctuations in arterial stiffness may provide additional prognostic value beyond a single PWV measurement. This indicates the potential importance of monitoring PWV over time rather than relying solely on a single measurement.