Journal of Hypertension

1. Background: With the rising prevalence of hypertension, especially among younger populations, there is a critical need to better assess health status and predict associated complications. This study developed a biological age model ("hypertension age") for hypertensive patients to predict the risk and timing of major complications. 2. Methods: Using South Korea's NHIS-NHID data, researchers analyzed 4,535,041 hypertensive patients who underwent health examinations between 2009 and 2010. Patients were followed for an average of 12.40 years (until 2022). Principal Component Analysis (PCA) was used to develop the biological age (cBA) model. The risk and onset timing of complications were analyzed using Cox proportional hazards and multiple regression models, adjusting for variables like medication use and baseline diseases. 3. Results: A 1-standard deviation (SD) increase in the age gap?where biological age exceeds chronological age (cBA - CA)?was significantly associated with an elevated risk for all major complications in both sexes (p < 0.001). Furthermore, a 1-SD increase in this gap significantly accelerated the time to complication onset for nearly all conditions (p < 0.001), with the exception of dementia in women. The impacts of medication use, hypertension duration, and baseline comorbidities varied by specific complication. 4. Conclusions: Lowering "hypertension age" relative to chronological age can significantly reduce the risk and delay the onset of major cardiovascular and related complications. Quantifying this biological age gap serves as a powerful motivational tool for personalized health management and complication prevention in hypertensive patients.

Background: Primary aldosteronism (PA) testing is recommended for patients with resistant hypertension but remains underused, and evidence linking aldosterone-targeted therapy to improved cardiovascular and renal outcomes is limited. Methods: In a nationwide cohort of patients with resistant hypertension between 2001 and 2022, we assessed PA testing and subsequent mineralocorticoid receptor antagonist (MRA) use and adrenalectomy. Among tested patients, time-dependent Cox models were used to assess associations between treatment exposure and mortality, major adverse cardiovascular events (MACE) and renal outcomes. Results: Among 254,338 patients, only 2.0% were tested for PA. Tested patients had a higher prevalence of hypokalemia and cardiometabolic comorbidities. In the overall tested population, MRA use was not associated with lower risks of cardiovascular or renal outcomes. However, when testing resulted in an established PA diagnosis, the use of both MRA (hazard ratio [HR] 0.60, 95% CI 0.42-0.86) and adrenalectomy (HR 0.33, 95% CI 0.20-0.54) were associated with a reduced risk of MACE compared with no aldosterone-targeted therapy. Similar results were observed regarding mortality. Adrenalectomy was associated with lower risk of MACE (HR 0.55, 95% CI 0.30-0.99), all-cause mortality (HR 0.52, 95% CI 0.29-0.93) and renal outcomes (HR 0.37, 95% CI 0.17-0.80) compared with MRA in patients with a diagnosis of PA. Conclusions: PA remains markedly underrecognized in resistant hypertension. Among patients with resistant hypertension who did undergo PA testing with establishment of a PA diagnosis, aldosterone-targeted therapy resulted in lower risk of adverse cardiorenal outcomes and death when compared to conventional antihypertensive therapy.

BackgroundPredictors of arterial health impairment from childhood to adolescence remain largely unknown. We investigated associations of childhood cardiometabolic risk factors with several measures of arterial health in adolescence. MethodsAltogether, 222 children were examined at age 7-9 years and eight years later at age 15-17 years. Body fat percentage (BF%), glucose, insulin, lipids, blood pressure (BP), and inflammation biomarkers were measured and homeostatic model assessment for insulin resistance (HOMA-IR), a metabolic syndrome score (MetSscore), and an inflammation score were calculated at baseline. Pulse wave velocity (PWV) and cardio-ankle vascular index (CAVI) were assessed using impedance cardiography and carotid intima-media thickness (cIMT), carotid distensibility (cDIST), Youngs elastic modulus (YEM), and stiffness index (SI) using ultrasonography. Associations of childhood cardiometabolic risk factors with measures of arterial health were analyzed using linear regression models adjusted for childhood age and sex. ResultsBF% was positively associated with PWV (standardized regression coefficient {beta}=0.207, p=0.008), CAVI ({beta}=0.171, p=0.031), cIMT ({beta}=0.146, p=0.034), and YEM ({beta}=0.164, p=0.016). HOMA-IR was positively associated with PWV ({beta}=0.242, p=0.001) and CAVI ({beta}=0.216, p=0.004) and inversely with cDIST ({beta}=-0.162, p=0.015). MetSscore was positively associated with PWV ({beta}=0.266, p<0.001), CAVI ({beta}=0.219, p=0.004), and YEM ({beta}=0.141, p=0.032) and inversely with cDIST ({beta}=-0.140, p=0.035). SBP was positively associated with PWV ({beta}=0.257, p<0.001) and YEM ({beta}=0.156, p=0.018) and inversely with cDIST ({beta}=0.169, p=0.012). ConclusionIncreased adiposity, insulin resistance, elevated SBP, and cardiometabolic risk factor clustering in childhood association of arterial stiffness and reduced arterial distensibility in adolescence, emphasizing prevention of cardiovascular diseases since childhood.

BackgroundPsilocybin has increasingly been studied as a therapeutic for psychiatric and neurologic conditions, yet comprehensive cardiovascular safety data are limited. Current trials often exclude individuals with blood pressure [&ge;]140/90 mmHg, criteria established conservatively without robust empirical support. ObjectiveCharacterize the blood pressure and heart rate response to typical therapeutic doses of psilocybin and provide an evidence base for cardiovascular eligibility criteria and monitoring protocols for future clinical trials and emerging therapeutic practice. MethodsWe pooled data from 536 psilocybin sessions (oral doses 20-47 mg) among 368 participants across 14 studies at Johns Hopkins University since 1999. Blood pressure and heart rate were measured at baseline and at least hourly up to 360 minutes post-administration. We quantified peak changes, threshold excursions, and excursion duration. ResultsPsilocybin produced modest, transient blood pressure elevations. Median peak systolic blood pressure (SBP) was 145 mmHg (IQR 134-156), representing a median increase of 22 mmHg from baseline. Blood pressure peaked at approximately 90 minutes and returned to near-baseline by 300 minutes. SBP exceeded 170 mmHg in 32 sessions (6.0%; median duration 8.5 minutes) and 180 mmHg in 17 sessions (3.2%; median duration 10 minutes). Antihypertensive medication was administered in only 1 session (0.2%). Higher baseline blood pressure was associated with smaller increases, suggesting a ceiling effect rather than exaggerated response. ConclusionsPsilocybin produces modest, transient blood pressure elevations comparable to moderate exercise. Current exclusion criteria of [&ge;]140/90 mmHg are not supported by these data. We recommend broadening eligibility to <160/100 mmHg while maintaining exclusions for established cardiovascular disease.

Background Blood pressure (BP) regulation in individuals with sickle cell disease (SCD) is influenced by a complex interplay of genetic and physiological factors. While SCD has traditionally been associated with lower BP, there is an increased risk of hypertension. Emerging BP research suggests significant heterogeneity across genotypes, age groups, and sex. Objectives: This study investigated the longitudinal effects of population-level characteristics and continuous clinical and laboratory predictors on systolic (SBP) and diastolic blood pressure (DBP) in individuals with SCD, with emphasis on the interactions between baseline and predicted blood pressure slopes over time. Methods We retrospectively analyzed longitudinal data from a cohort of 2,739 patients with diverse SCD genotypes. Descriptive statistics were documented across sex, age range, genotype, health status and relative systemic hypertension risk categories (rHTN-risk). Linear mixed-effects models provided estimates of fixed- and random-effects of baseline BP and of time-related BP effects, respectively. Post-estimation margins provided contrasts of baseline-adjusted BP means and of pre-specified time effects on BP patterns. Results Males had significantly higher baseline SBP ({beta} = 6.64, p < 0.001) but lower baseline DBP ({beta} = -2.61, p < 0.001) compared with age-matched HbSS females. Baseline SBP was more unstable compared with baseline DBP and baseline DBP was more predictive of future BP trends than baseline SBP. Genotype was a consistent predictor of DBP (p < 0.05), but not of SBP. Similarly, we observed increased risks of relative diastolic hypertension across most genotypes, while the prevalence and magnitude of systolic hypertension was lower across all genotype compared with HbSS. Conclusions Blood pressure trajectories in SCD patients are not uniform and are significantly related to genotype, age group and sex over time. Baseline diastolic levels were less heterogenous and exhibited clear upward trajectories over time. These findings support the need for patient-specific BP surveillance in the care and management of SCD.

Background: Primary aldosteronism (PA) is increasingly recognized as a common cause of hypertension. The 2025 Endocrine Society guideline introduced a simplified diagnostic framework, but its real-world clinical implications remain unclear. Methods: We conducted a multicenter retrospective cohort study of hypertensive patients undergoing PA testing in Taiwan. PA was defined biochemically according to the 2025 Endocrine Society criteria. Multivariable logistic regression identified factors associated with PA diagnosis and aldosterone-targeted therapy. Among patients with suppressed renin (?1 ng/mL/h), restricted cubic splines evaluated the adjusted association between renin and PA probability. Results: Among 18,766 patients undergoing PA testing, 6,760 (36.0%) met diagnostic criteria for PA. PA was associated with older age, female sex, lower potassium, resistant hypertension, and a higher antihypertensive medication burden. Among patients with suppressed renin, lower renin remained significantly associated with higher adjusted PA probability. However, only 39.0% of patients with PA received aldosterone-targeted therapy, including 28.2% who received mineralocorticoid receptor antagonist therapy within 6 months and 9.4% who underwent adrenalectomy during follow-up. Lower renin, higher aldosterone, lower potassium, and resistant hypertension were associated with aldosterone-targeted therapy, while younger patients with fewer comorbidities were more likely to undergo adrenalectomy. Conclusions: Using the updated diagnostic framework, PA was highly prevalent among hypertensive patients undergoing PA testing. Nevertheless, many patients who met these biochemical criteria did not receive aldosterone-targeted therapy in routine care. These findings highlight the potential treatment implications of broader PA recognition and support the development of practical pathways to guide MRA therapy, adrenalectomy referral, and individualized management.

Background As dementia prevalence rises globally, it is critical to find preventions that target modifiable risk factors like blood pressure. Pulse pressure (PP), a marker of arterial stiffness, contributes independently to cognitive impairment. Yet, clinically interpretable thresholds for PP for cognitive decline remain undefined. We examined the independent association between PP and domain-specific cognitive trajectories and identified PP thresholds associated with greater cognitive decline across ethnically diverse regional populations. Methods Data were harmonized across three longitudinal cohorts (54,878 participants with up to 20 years follow-ups and 266,144 observations). Linear mixed-effects models identified a nonlinear association between PP and cognition (memory, orientation, and executive function), whereby cognitive decline accelerated after around 50 mmHg of pulse pressure, despite controlling for mean arterial pressure and dementia risk factors. Stratification based on PP thresholds (Low: PP <30; Normal: 30 to <50; Borderline: [&ge;]50; and High: [&ge;]60 mmHg), and tested for differences in memory decline across groups. Stratified analyses were similarly conducted across other blood pressure measures, racial, age and sex groups. Findings Non-linear associations indicated that memory decline was particularly noticeable for pulse pressure [&ge;]60 mmHg. Compared with normal pulse pressure, [&ge;]60 mmHg was associated with worse memory performance (pooled {beta} -0.062 SD; 95% CI -0.107 to -0.016) and greater memory decline with age (-0.026 SD/year; -0.036 to -0.015), including among normotensive individuals. Findings were consistent across diverse regional cohorts (UK, US and China), racial groups, age strata and sexes. Interpretation Pulse pressure over 60 mmHg is associated with elevated cognitive risk, independent of blood pressure measures, even among normotensive individuals. These findings support pulse pressure thresholds as clinically interpretable and complementary markers of cognitive risk.

Background: Left atrial (LA) stiffness index is a non-invasive echocardiographic parameter reflecting left ventricular filling pressure; however, its prognostic significance in hypertension remains unclear. We aimed to assess the prognostic value of the longitudinal change in LA stiffness index in patients with hypertension. Methods: We analyzed 1,442 hypertensive patients from the STRATS-HHD registry who underwent echocardiography including LA and left ventricular (LV) strain at baseline and 6-18 months. Patients were categorized into four groups according to longitudinal changes in LA stiffness index: normal-normal, improved, aggravated, and persistently stiff. The primary outcome was a composite of hospitalization for heart failure (HHF) and cardiovascular death, and secondary outcomes included HHF and incident atrial fibrillation. Results: Among 1,442 patients, 996 (69.1%) were classified as normal-normal, 173 (12.0%) as improved, 91 (6.3%) as aggravated, and 182 (12.6%) as persistently stiff. Over 5 years, aggravated (adjusted hazard ratio [aHR] 2.175, 95% confidence interval [CI] 1.048-4.515, P=0.037) and persistently stiff (aHR 2.935, 95% CI 1.697-5.076, P<0.001) groups were associated with a higher risk of the primary outcome, whereas the improved group showed a similar risk to the normal-normal group. Similar trends were observed for HHF and for incident atrial fibrillation. Adding LA stiffness index into a model including clinical factors and LV mass index improved risk prediction for composite outcomes. Conclusions: LA stiffness index was associated with clinical outcomes in hypertensive patients, with longitudinal changes providing additional prognostic information. Assessment of its trajectory may further refine risk stratification in patients with hypertension.

BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs -0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [&le;]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention. Novelty and RelevanceO_ST_ABSWhat Is New?C_ST_ABSO_LIIn this nested case-control study, differences in hypertension care over time--including follow-up frequency, medication use, and treatment adjustments--were associated with incident ischemic stroke. C_LI What Is Relevant?O_LIVariations in hypertension care delivery over time may represent missed opportunities for stroke prevention regardless of baseline or average SBP levels during follow-up. C_LIO_LIImproving follow-up and timely treatment adjustments may offer actionable targets for primary prevention. C_LI Clinical/Pathophysiological ImplicationsO_LILongitudinal gaps in hypertension management may contribute to stroke risk beyond BP control, highlighting opportunities to improve prevention through more consistent care delivery. C_LI

Background: Hypertensive disorders of pregnancy (HDP) are a risk factor for early cardiovascular disease in women, perhaps related to adverse cardiovascular reactivity to physiologic stress. Objectives: To evaluate the association of HDP subtypes with exercise stress echocardiography parameters. Methods: This retrospective cohort study linked exercise stress echocardiograms with delivery records. HDP was classified as none, gestational hypertension (GH), and preeclampsia (PEC). We compared features of treadmill exercise stress echocardiography among HDP groups, adjusted for maternal demographic characteristics, time between delivery and stress testing, resting blood pressure (BP), and exercise duration. Results: Among 885 women with matching delivery and exercise echocardiography records (41.4plus-or-minus sign7.4 years at exercise exam), 92 (10.4%) experienced GH and 39 (4.4%) experienced PEC. Women with PEC were referred for exercise stress testing 3.1 years earlier following delivery (p<0.001) and had shorter exercise duration (lower case Greek beta]=-69.6 seconds [95% CI -115.9, -23.4], p=0.003) than those without HDP. Women with GH had higher peak exercise systolic BP (lower case Greek beta=8.96 mmHg [95% CI 4.89, 13.04], p<0.001), diastolic BP (lower case Greek beta=2.67 mmHg [95% CI 0.24, 5.10], p=0.031), and pulse pressure (lower case Greek beta=8.25 mmHg [95% CI 4.11, 12.39], p<0.001) than those without HDP. Women with GH and PEC were twice as likely to have concentric remodeling and more adverse diastolic parameters on echocardiography than those without HDP (p<0.05). Conclusions: Exercise stress echocardiography may detect subclinical cardiovascular dysfunction in midlife women following HDP, with adverse findings differing by subtype: GH was associated with higher peak exercise BP and PEC with lower exercise capacity.

Background Hypertension remains one of the most challenging healthcare problems in the community. It is a common, measurable, and treatable condition that is nonetheless responsible for millions of preventable deaths each year. Hypertension affects approximately 1.28 billion adults worldwide, yet fewer than half (46%) are aware of their condition. Undiagnosed hypertension is a critical public health gap, contributing to preventable cardiovascular morbidity through silent end-organ damage. Machine learning can enable community-level screening using routinely available, non-invasive data, without the requirement of laboratory investigations. Methods We conducted a cross-sectional ML study using the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle. Adults aged [&ge;]18 years were included; those with a self-reported prior hypertension diagnosis (n=1,930) were retained as negative controls. Probable undiagnosed hypertension was defined as mean blood pressure [&ge;]130/80 mmHg among participants reporting no prior hypertension diagnosis, consistent with the ACC/AHA 2017 threshold. Three classifiers: Logistic Regression (LR), Random Forest (RF), and Extreme Gradient Boosting (XGBoost) were trained on eight non-invasive predictor variables. Performance was assessed using AUC-ROC, sensitivity, specificity, and F1 score with bootstrap 95% confidence intervals (CIs). Stratified 5-fold cross-validation was applied. Results Of 9,254 NHANES 2017-2018 participants, 5,237 adults were included after exclusion criteria were applied; 1,072 (20.5%) had probable undiagnosed hypertension. LR achieved the highest test AUC of 0.611 (95% CI: 0.571-0.652), with sensitivity 0.535 (95% CI: 0.473-0.600) and specificity 0.594 (95% CI: 0.560-0.626). RF demonstrated near-absent sensitivity (0.047) despite adequate AUC (0.607), while XGBoost performed intermediately (AUC: 0.599; sensitivity: 0.279). Diabetes status, sex, and age were the most influential predictors by permutation feature importance. Conclusion ML classifiers trained on eight non-invasive variables demonstrated modest but consistent discrimination for identifying probable undiagnosed hypertension, supporting the feasibility of laboratory-free community screening. External validation in diverse populations is warranted before clinical implementation.

Objectives: To compare real-world cardiovascular outcomes and safety events in patients with resistant hypertension following initiation of transdermal clonidine (TC) or spironolactone. Methods: A retrospective analysis was performed using Merative MarketScan(R) Databases in the USA to identify cohorts with resistant hypertension initiating TC or spironolactone as a fourth-line agent between January 2012 and September 2024. Major Adverse Cardiovascular Events (MACE) and safety events were assessed during variable follow-up periods. Inverse probability of treatment weighting (IPTW) was applied to adjust for differences in baseline characteristics. Cox proportional hazard models were used to adjust for post-index beta-blocker utilization as a time-varying covariate for MACE outcomes. Results: The analysis included 3,113 patients in the TC cohort and 30,640 in the spironolactone cohort. After IPTW, baseline characteristics were well balanced between cohorts (standardized mean differences <0.10; mean age 60 years, 54% male). Mean follow-up was 7.1 and 10.5 months for the TC and spironolactone cohorts, respectively. After IPTW no differences in MACE outcomes were observed between the two cohorts (weighted rate ratio 1.27 [0.79-2.06]). Results were consistent after adjusting for post-index beta-blocker use. The risk of hyperkalemia was significantly lower in the TC cohort (weighted rate ratio, 0.48 [0.33-0.70]. Conclusions: In this real-world analysis, patients with resistant hypertension treated with TC have similar risk for MACE outcomes as with spironolactone, but with significantly lower risk of hyperkalemia. Thus, in patients with resistant hypertension TC appears to provide similar cardiovascular protection, with a more favorable safety profile.

Background: Comprehensive assessment of hypertension-mediated organ damage (HMOD) across multiple organ systems in sub-Saharan Africa is limited. We assessed the prevalence and correlates of multidomain HMOD in a geographically diverse population in Ghanaian adult. Methods: This cross-sectional secondary analysis of the Ghana Heart Study, which included 1,106 adults aged [&ge;]18 years from four Ghanaian regions between September 2016 and March 2017. Multidomain HMOD was determined using a pre-specified 9-domain composite score [&ge;]2, using an ESH/ESC 2018 guideline-informed selection of HMOD domain with baPWV instead of carotid-femoral PWV (cfPWV), due to device unavailability, and a threshold of [&ge;]14 m/s which was derived from analysis within the cohort. LODO sensitivity analyses were used to address issues of predictor-outcome circularity. We used logistic regression models to examine association between each predictor and multidomain HMOD, adjusted for age, systolic blood pressure, body mass index, presence of dyslipidaemia and smoking status. We also performed receiver operating characteristic (ROC) analysis to determine correlates of multidomain HMOD and compare the discriminative ability of each predictor against the others. Results: The mean age of participants was 46.9{+/-}17.2 years of which 58% were females. Multidomain HMOD was observed in 21.3% (235/1,106; zero-imputation lower bound 21.2%) of participants studied. There was a marked increase in the prevalence of multidomain HMOD with advancing age. Thus, while 8.6% (44/ 511) of adults<45years had multidomain HMOD, 20.6% (63/306) of 45- to 59-yr-olds and 44.4% (128/ 288) of individuals [&ge;]60 years had multidomain HMOD. HMOD-positive adults were older (59.1{+/-}8.4 vs 43.6{+/-}13.4y, p<0.001), had higher systolic BP (147{+/-}22 vs 123{+/-}21 mmHg, p<0.001), and had higher prevalence of hypertension (73% vs 28%, p<0.001) than their HMOD-negative counterparts. Using the primary (circular) specification, the strongest co-occurrence among all domains of HMOD was observed between peripheral artery disease and other HMOD (OR 41.2, 95% CI 20.7-81.6; p<0.001) followed by valvular burden and other HMOD (OR 14.4, 95% CI 4.8-43.8; p<0.001) and between ECG-LVH and other HMOD (OR 9.0, 95% CI 5.9-13.8; p<0.001) (S2 Table). After LODO correction to remove the self-inclusive co-occurrence between each predictor domain and the outcome (all p-values calculated in S2 Table), there was no significant association between the remaining 8 HMOD domains and the prevalence of multidomain HMOD (all p-values>0.05; S2 Table). This was not the case for baPWV, however. Thus, whereas the AUC of the best performing non-self-inclusive HMOD domain (ECG-CMD) only reached 0.688{+/-}0.016 (vs 0.827{+/-}0.008 for self-inclusive AUC calculated for the sake of interest only and provided as supplementary material), baPWV demonstrated good discriminative capacity (LODO-adjusted AUC = 0.702, 95% CI 0.654-0.751; S3 Fig). However, this AUC did not significantly exceed that for age alone (AUC = 0.752; {Delta}AUC = -0.050, 95% CI ?0.103 to 0.03; p=0.106; S3 Fig). Most importantly, after adjustment for SBP (a direct mediator in this pathway), the LODO AUC for baPWV did not exceed that for the single variable age (S3 Fig), indicating that baPWV does not possess independent discriminative power for multidomain HMOD above and beyond the information provided by SBP and age. Importantly, however, the adjusted OR for baPWV did not reach statistical significance (OR 1.094, 95% CI 0.986-1.213; p=0.091), suggesting that while circularity prevented validation of biological association, it did not prove the absence of association altogether. Sensitivity analysis (estimating total as opposed to direct effect) in which SBP was excluded from the regression model to estimate the total effect of baPWV on the prevalence of HMOD showed that, indeed, the OR for baPWV was significantly elevated (OR 1.261; 95% CI 1.150-1.382; p<0.001) in this specification. The effect of SBP, a direct mediator in this pathway, therefore apparently accounted for the non-significance in the original model entirely. Formal mediation analysis using the aforementioned specification yielded that SBP indeed mediated 69.9% (95% CI 41.3-128.8%) of the effect of baPWV on the prevalence of HMOD. Conclusions: One in five Ghanaian adults has hypertension-mediated organ damage in multiple HMOD domains. baPWV has good discriminative power for HMOD risk prediction in a Ghanaian adult population under the non-circular LODO estimand (LODO- adjusted AUC = 0.702; 95% CI: 0.654, 0.751) than the PCE (AUC = 0.496; 95% CI: 0.438, 0.555; {Delta}AUC = +0.206; p < 0.001). However, baPWV LODO AUC (0.702) was not statistically significantly greater than age alone (AUC = 0.752; 95% CI: 0.730, 0.774; {Delta}AUC = -0.050, p = 0.106). AUC for self- inclusive model was provided in supplementary materials for the reader's perusal, and that AUC (0.827; 95% CI: 0.794, 0.860) is circular. The prevalence of ECG-LVH was substantially higher (42%) than that of echocardiographic- LVH (5.9%) in this Black African population. These findings support further research on the role of baPWV for HMOD risk prediction in a Ghanaian adult population. Prospective validation of baPWV would be needed before clinical use.

Background: Comprehensive assessment of hypertension-mediated organ damage (HMOD) across multiple organ systems remains limited in sub-Saharan Africa. We aimed to determine the prevalence and predictors of multidomain HMOD in a geographically diverse Ghanaian adult population. Methods: This secondary analysis of the Ghana Heart Study included 1,106 adults from four regions. Multidomain HMOD was defined as a pre-specified 9-domain TOD composite score ?2, based on the ESH/ESC 2018 guidelines framework. Logistic regression and ROC analysis were used to identify predictors and compare discriminative performance. Results: Mean age was 46.9 (17.2) years and 58% were female. Multidomain HMOD prevalence was 21.2% (235/1,106) and increased steeply with age: 8.6% (<45 years), 20.6% (45?59 years), and 44.4% (?60 years). Hypertension prevalence was 73% in the HMOD group versus 28% in those without HMOD (p < 0.001). The strongest independent associations were peripheral artery disease (OR 41.2), valvular burden (OR 14.4), and ECG-LVH (OR 9.0). baPWV showed superior discriminative performance (AUC 0.827, 95% CI 0.794?0.860) compared with the ASCVD Pooled Cohort Equations (AUC 0.466; ?AUC +0.351, DeLong test p < 0.001). Conclusions: One in five Ghanaian adults has hypertension-mediated organ damage in ?2 organ systems. baPWV is the strongest predictor and substantially improves risk stratification beyond conventional scores. These findings support the use of baPWV to guide hypertension management and HMOD assessment in West Africa.

BackgroundRisk stratification in hypertension remains challenging. The prognostic value of plasma renin in guiding therapy for hypertension is not well established. MethodsIn this multicenter retrospective cohort of 16,600 people with hypertension, we evaluated the association between plasma renin activity and major adverse cardiovascular events (MACE) defined as stroke, myocardial infarction, and all-cause death. Plasma renin was analyzed as a continuous variable using restricted cubic splines. A 6-month landmark analysis assessed treatment effects of mineralocorticoid receptor antagonists (MRA) as opposed to baseline renin-angiotensin system inhibitors. ResultsContinuous renin level showed a U-shaped association with MACE, with the lowest risk at 1.17ng/mL/h. In categorical analyses, low renin (<0.3 ng/mL/h; adjusted hazard ratio [HR]=1.29, 95% CI 1.15-1.45) and high renin (>3.0ng/mL/h; HR=1.19, 95% CI 1.06-1.33) were both associated with higher MACE risk. Initiation of MRA therapy after renin measurement was associated with a graded reduction in MACE risk where patients with low renin had the lowest risk (HR=0.75, 95%CI 0.60-0.92), and patients with high-renin had the highest risk (HR=1.41, 95%CI 1.03-1.94). In contrast, baseline use of renin-angiotensin system inhibitors was associated with a graded reduction in MACE risk where patients with high-renin had the lowest risk (HR=0.76, 95%CI 0.63-0.92) but those with low renin did not benefit (HR=0.87, 95%CI 0.72-1.04). ConclusionsPlasma renin is a prognostic biomarker for MACE and may serve as a guide for treatment selection. A renin-guided strategy that favors MRAs in patients with low renin may reduce MACE and support individualized hypertension care. Clinical PerspectiveO_ST_ABSWhat is News?C_ST_ABSO_LIIn this large multicenter cohort of 16,600 patients with hypertension, plasma renin activity demonstrated a U-shaped association with major adverse cardiovascular events, with increased risk observed at both suppressed and elevated renin levels. C_LIO_LIRenin-defined hypertensive phenotypes were associated with differential treatment responses that mineralocorticoid receptor antagonist initiation was associated with lower cardiovascular risk in patients with low renin, whereas baseline renin-angiotensin system inhibitor use was associated with lower risk in patients with higher renin. C_LIO_LIThese findings extend the clinical role of renin beyond screening for primary aldosteronism, suggesting that renin may serve as an accessible marker that links hypertension pathophysiology, cardiovascular risk, and treatment responsiveness. C_LI What Are the Clinical Implications?O_LIPlasma renin may help clinicians move beyond blood pressure levels alone and recognize biologically distinct forms of hypertension that may require different therapeutic strategies. C_LIO_LISuppressed renin may identify a broader phenotype of renin-independent aldosteronism or mineralocorticoid receptor activation, in which earlier consideration of mineralocorticoid receptor antagonist therapy may be appropriate even without a formal diagnosis of primary aldosteronism. C_LIO_LIA renin-guided treatment strategy may provide a practical framework for mechanism-based hypertension care, while prospective studies are needed to determine whether this approach improves long-term cardiovascular outcomes. C_LI

We evaluated the blood pressure (BP) lowering efficacy and safety of triple vs dual therapy of antihypertensive drug (AHTD) combinations, among adults with hypertension. Seventeen randomized, double-blind trials (41 comparisons and 13,461 participants) comparing triple versus dual therapy for 3 weeks identified by multiple literature databases searches including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) until October 2024 were included in the meta-analysis. Triple therapy achieved a greater reduction in systolic BP (SBP) compared with dual therapy (26.9 vs. 21.7 mmHg, mean difference 5.4 mmHg [95% CI, 4.7 to 6.2]). Among patients receiving dual therapy at submaximal and maximal doses, the addition of a third drug further reduced SBP by 7.5 and 3.6 mmHg, respectively. BP control was significantly better with triple therapy (60% vs. 47%, RR=1.34 [1.27 to 1.41]). Withdrawal due to adverse events was slightly higher in the triple therapy group (4% vs. 3%, RR=1.5 [1.2 to 1.8]). Triple AHTD therapy provides superior BP reduction and is well-tolerated compared to dual therapy.

This study enrolled 152 hypertensive patients with an ARR > 3.7 to assess the relationship between the traditional hypokalemia cutoff (3.5 mmol/L) and primary aldosteronism (PA) screening, and to establish a new cutoff. Under the traditional cutoff, only 35.7% of PA patients presented with hypokalemia. ROC curve analysis identified a new cutoff of 4.22 mmol/L, which increased sensitivity from 35.7% to 77.5%, with a specificity of 91.1% and an AUC of 0.897. The findings indicate that the traditional cutoff is insufficiently sensitive, while the new cutoff markedly improves screening sensitivity and facilitates early detection of PA.

Background: Pediatric hypertension (HTN) remains underdiagnosed despite established guidelines. Prior studies evaluating social drivers of health (SDOH) relied on diagnostic codes or single-visit blood pressure (BP) measurements, limiting identification of persistent BP elevation. We evaluated longitudinal BP patterns and associated SDOH among children with continuity of care. Methods: We conducted a retrospective cohort study of children aged 6-17 years with [&ge;]3 primary care visits between 2017 and 2024 within a large healthcare network. BP was classified according to guidelines. Multivariable logistic regression evaluated associations between persistent abnormal BP ([&ge;]3 abnormal readings, would meet guideline-based diagnosis for HTN) and stage 1/2 HTN with demographic, clinical, and neighborhood-level factors, including Area Deprivation Index (ADI), Child Opportunity Index (COI), and insurance instability. Results: Among 71,683 children, 2,911 (4.2%) had persistent abnormal BP, whereas only 848 (1.2%) had a documented HTN diagnosis. Obesity, age [&ge;]13 years, male sex, prematurity, and insurance instability were associated with abnormal BP and stage 1/2 HTN. Higher ADI quartiles were associated with increased odds of abnormal BP (Q3: OR 2.48) and stage 1/2 HTN (Q3: OR 4.89). Higher COI socioeconomic opportunity was associated with lower odds of abnormal BP, whereas higher educational opportunity was associated with higher odds; these associations were not observed for stage 1/2 HTN. Conclusions: Among children with continuity of care, substantial gaps in HTN recognition persist despite repeated opportunities for diagnosis. SDOH factors remained associated with BP abnormalities, supporting the need for system-level and community-based strategies to improve HTN detection.

Intro: Characteristics of the pulse wave transmitted through the carotid arteries are predictive of cognitive decline and cerebrovascular health in humans. This study aimed to identify risk factor trajectories in childhood, adolescence and early adulthood that are associated with forward compression wave intensity (FCWI) in the common carotid artery in adults aged 28 years. Methods: Systolic blood pressure (SBP), body mass index (BMI) and fasting blood glucose (FBG) measured at multiple time-points when participants were aged between 8-20 years were included in a trajectory analysis. At age 28 years, FCWI was measured in 402 (M=206, F=196) participants who underwent a Duplex ultrasound assessment of the common carotid artery. Statistical analysis assessed differences in FCWI between each trajectory group for males and females separately. Results: In males, four trajectory groups were identified for BMI, three for SBP, and two for FBG. In females, three trajectory groups were identified for BMI, SBP, and FG. In males, having higher BMI (P=0.006), SBP (P=0.021) and FBG (P=0.002) from ages 8-20 years was associated with greater FCWI at age 28 years. In females, no associations were found between FCWI at age 28-years and trajectory groups for BMI (P=0.185), SBP (P=0.289) or FBG (P=0.070). Conclusion: Having high BMI, SBP and FBG throughout childhood, adolescence and early adulthood was associated with higher FCWI in the carotid artery at age 28 years in males, but not females. This may have a direct impact on the etiology of cognitive decline and cerebrovascular disease in later life.

The purposes of this study were to determine whether adverse childhood family environment (ACFE) exposure is associated with altered hemodynamic responses to graded exercise in young adulthood, and whether this association was modified by sex and race in a large, population-based cohort. We hypothesized that ACFE exposure would be associated with an exaggerated exercise pressor response in young adulthood, independent of resting BP. We further hypothesized that the association between ACFE and the hemodynamic response to exercise would be stronger in females than males, and in Black versus White participants. MethodsExercising blood pressure (BP) and heart rate (HR) responses were recorded during graded exercise testing and ACFE exposure was assessed among 3,417 young adults (mean age = 25 {+/-} 4 y; 44% female; 46% Black). Linear mixed-effects models that included participant-specific random intercepts and random slopes were used to assess the relation between ACFE exposure and exercising systolic (SBP), diastolic, and mean BP, pulse pressure (PP), pulse pressure index (PPI), heart rate (HR), and rate pressure product (RPP). All models were adjusted for resting values of the hemodynamic outcome, as well as age, sex, race, study center, body mass index, current hypertension medication use, smoking status, and alcohol consumption. ResultsGraded exercise hemodynamic responses were analyzed in 3,346-3,417 participants in the final models, providing 15,372-17,481 observations. Higher ACFE exposure was associated with lower SBP ({beta} = -0.304 mmHg/ACFE, p = 0.033), HR ({beta} = -0.485 bpm/ACFE, p<0.001), and RPP ({beta} = -83.404 bpm{middle dot}mmHg/ACFE, p=0.002) at the lowest workload, but steeper workload-related increases in SBP (interaction {beta} = 0.044 mmHg{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.029), HR ({beta} = 0.061 bpm{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p<0.001), RPP ({beta} = 10.16 bpm{middle dot}mmHg{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.025), and PP ({beta} = 0.052 mmHg{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.038) and PPI ({beta} = 0.000232 units{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.018). These findings were robust to additional adjustment for central adiposity, exercise capacity, and maximal heart rate and heart rate recovery. ConclusionOur findings add nuanced evidence revealing that early adversity is associated with a demand-dependent shift in cardiovascular regulation, with attenuated responses at low demand, but more dramatic increases in pulsatile and myocardial load responses during progressive physiological stress.