Journal of Hypertension

Background: Elevated blood pressure (BP) is common during hospitalization. Despite recommendations to avoid routine changes in antihypertensive therapy, clinical practice remains variable. Prospective data on whether elevated in-hospital BP identifies patients with hypertension after discharge are limited. Methods: Adults hospitalized for non-cardiac conditions with asymptomatic routine in-hospital BP ?140 and/or ?90 mmHg on at least two occasions separated by ?24 hours were prospectively enrolled. Antihypertensive therapy was managed at the discretion of treating physicians. Routine in-hospital BP, standardized research BP, and changes in antihypertensive therapy were recorded. Four weeks after discharge, participants underwent 24-hour ambulatory BP monitoring (ABPM). Results: Among 50 participants, 42 (84%; 95% CI, 70.9 ? 92.8) had hypertension on follow-up ABPM. Among 21 participants without known hypertension, 18 (86%) had previously unrecognized hypertension on follow-up ABPM; among 29 participants with known hypertension, 24 (83%) had uncontrolled hypertension. Antihypertensive therapy was changed during hospitalization in 26 participants (52%), with de-escalation more frequent than intensification. Hypertension on follow-up ABPM was present in 88.5% of participants with and 79.2% without in-hospital therapy changes. Standardized research BP, but not routine in-hospital BP, correlated with follow-up ABPM. Conclusion: Asymptomatic elevated routine in-hospital BP identified a population with a high prevalence of hypertension four weeks after discharge, including patients with and without previously diagnosed hypertension. These findings support structured post-discharge BP reassessment rather than assuming that elevated in-hospital BP is transient. URL: www.ClinicalTrials.gov; Unique identifier: NCT06132451

Introduction. Whether the arterial pressure waveform carries structural vascular information that brachial pressure does not, and whether its shape can be read from facial video, are both uncertain, and recording a continuous pressure reference with synchronised video in a hypertension clinic has not been reported. We sought to determine whether continuous finger arterial pressure recording with synchronised facial video, linked to existing coronary calcium imaging, is feasible in adults attending a hypertension clinic, whether a consumer camera recovers heart rate and pulse shape in that setting, and to generate exploratory estimates of association between waveform morphology and coronary calcium. Methods. BP-WAVE is a single-site prospective observational pilot study. The primary outcome was feasibility, pre-specified as recruitment, consent, completeness of waveform recording, imaging availability and data completeness. Secondary outcomes were waveform quality, device agreement, feature extraction, and recovery of heart rate and pulse shape from video. The exploratory outcome was the Spearman correlation of 14 waveform features with the Agatston calcium score, with exact permutation p values adjusted within each family of tests. Results. Nine of ten planned participants were recorded over 12 days (median age 55 years, range 40 to 74; five women); all nine completed the recording with video and had a calcium score (median 351, range 33 to 1816). Of 4,178 detected beats, 2,965 (71%) passed quality control. Video recovered heart rate within 0.4 to 4.1 beats per minute in eight of nine participants and pulse shape above a phase-randomised noise bound in six of nine (held-out r 0.48 to 0.76). Form factor had the strongest correlation with calcium (rho -0.68, exact p 0.050, q 0.68); no feature was associated with calcium after Benjamini-Hochberg adjustment within any of the nine families of 14 tests (126 tests in all; smallest q 0.17). Conclusion. In this single-site pilot of nine adults from a hypertension clinic, continuous finger arterial pressure recording with synchronised facial video and linkage to coronary calcium was feasible, a consumer camera recovered heart rate in eight and pulse shape in six participants, and no waveform feature was associated with coronary calcium after correction for multiple testing.

Purpose: This study aimed to investigate the association between hypertension and anisometropia and determine whether interocular structural asymmetry mediates this relationship. Methods: In this cross-sectional study, nationally representative samples from the US (N = 12,749; NHANES 1999-2008) and Korea (N = 35,484; KNHANES 2008-2024) were analyzed. Associations between hypertension, blood pressure components (BPC), and anisometropia were examined using weighted multivariable logistic regression and restricted cubic splines. Mediation analysis assessed whether asymmetry in optical coherence tomography (OCT) structural parameters mediated the association between BPC and anisometropia. Results: Hypertensive individuals had higher odds of anisometropia in both cohorts (NHANES: OR = 1.32, 95% CI: 1.12-1.56, P = 0.001; KNHANES: OR = 1.12, 95% CI: 1.05-1.20, P < 0.001). Each 10 mmHg increase in systolic blood pressure (SBP) and pulse pressure (PP) was associated with 5% and 10% greater risk, respectively. Interocular differences in central macular and choroidal thickness partially mediated the association between BPCs and anisometropia. Time-course bulk RNA-seq identified Rock1 as a candidate gene downregulated under hypertensive conditions. Conclusions: Hypertension was associated with anisometropia across two national cohorts. Interocular differences in central macular and choroidal thickness partially mediated this association, suggesting a link between systemic hemodynamic alterations and ocular structural asymmetry. Translational Relevance: These findings suggest that interocular OCT structural asymmetry may serve as a clinically accessible imaging biomarker to identify individuals at increased risk of hypertension-associated anisometropia.

Arterial stiffness and endothelial dysfunction are non-traditional risk markers after stroke, yet reliability and minimal detectable change (MDC) of pulse wave velocity (PWV) and flow-mediated dilation (FMD) have not been established. We examined test-retest reliability and MDC of carotid-femoral (cfPWV), carotid-radial (crPWV), and femoral-dorsalis pedis PWV (ffPWV), and absolute and relative brachial artery FMD in people >12 months post-stroke. Seventeen individuals (n=4(24%) females; 63.9{+/-}8.6 years; 4.5{+/-}2.8 years post-stroke) completed two bilateral assessments of PWV via applanation tonometry and FMD via duplex ultrasound within one week. Intraclass correlation coefficients (ICC2,1) were calculated via two-way random-effects models, and MDC derived at 68%, 90%, and 95% confidence levels. We found good-to-excellent reliability for cfPWV in paretic (ICC2,1=0.85; 95%CI:0.59,0.95) and non-paretic (ICC2,1=0.94; 95%CI:0.82,0.98) limbs, with MDC95% values of 2.23 and 1.68 m/s, respectively. crPWV and ffPWV exhibited poor reliability bilaterally (ICC2,1=0.12-0.33). Relative FMD showed-moderate reliability for paretic (ICC2,1=0.50; 95%CI:-0.20,0.85) and non-paretic (ICC=0.59; 95%CI:0.04,0.84) limbs, with MDC95% values of 6.88% and 7.65%, respectively. Reliability for absolute FMD was poor (ICC2,1=0.11-0.44). These findings support cfPWV as a reliable vascular assessments in individuals >12 months post-stroke, and provide stroke-specific MDC values to guide interpretability in future trials.

Background: Hypertension prevalence rises sharply in females after menopause, exceeding that of age-matched males in later life, conferring greater relative cardiovascular disease risk in females than in males. However, the underlying mechanisms remain poorly understood. Method: We studied multi-tissue RNA-sequencing data from 193 CVD-free participants aged >55 years in the GTEx database and extended the findings to 1,605 age-matched Framingham Heart Study participants. Results: We identified a dominant female hypertension co-expression signature in blood, expressed at lower levels in females with uncontrolled high blood pressure than in males (sex-by-hypertension interaction) in both cohorts. Genes contributing to this signature were enriched for post-transcriptional modification and insulin signalling and regulated by ETS family transcription factors (TFs). Ten ETS TFs showed the same female-specific hypertension association and together explained the signature?s expression. Moreover, in females, but not males, lower blood signature scores were associated with a pro-inflammatory transcriptome in the artery and kidneys. Conclusions: Collectively, we identified the ETS-transcriptomic axis as a potential mechanism explaining sex differences in human hypertension.

Background: Cardio-kidney-metabolic (CKM) diseases share risk factors, but their shared and distinct risk factors for disease progression remain unclear. We examined whether classical risk factors predict baseline CKM indicators and their longitudinal changes in a population-based German National Cohort (NAKO) sample. Methods: In 2,650 NAKO-IMMEDIATE participants selected for deep-phenotyping, baseline values and 5-year changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), pulse wave velocity (PWV), and estimated glomerular filtration rate (eGFR) were linearly regressed on age, sex, education, alcohol and tobacco consumption, body mass index (BMI), and residuals of BMI-adjusted waist circumference (WC) with mutual adjustment. Results: Baseline values for HbA1c were 34.6{+/-}5.8 mmol/mol, for PWV 8.3{+/-}1.5 m/s, for SBP 128.0{+/-}15.7 mmHg and for eGFR 96.0{+/-}14.6 ml/min/1.73 m2. Cross-sectionally, all risk factors were associated with one or more of the CKM indicators, with age and BMI being associated with all four indicators. Over 5 years, HbA1c (1.2{+/-}4.2 mmol/mol), PWV (0.5{+/-}1.2 m/s) and SBP (0.6{+/-}14.2 mmHg) increased, whereas eGFR (-2.3{+/-}9.5 ml/min/1.73 m2) decreased. Age (0.03 m/s per 5 year, 95% CI 0.01, 0.06 m/s) was associated with higher and BMI (-0.02 m/s per 1kg/m2, -0.03, -0.01) with lower PWV changes. No other risk factors were associated with CKM indicator changes. Conclusion: Classical risk factors were more frequently related to baseline CKM indicators than to their 5-year changes. Within longitudinal analyses, only age and BMI were related to PWV 5-year changes. Keywords: Cardio-kidney-metabolic function, risk factors, longitudinal studies

Objectives: To describe associations between peripheral arterial disease (PAD) and bladder health (BH) and lower urinary tract symptoms (LUTS) among a subset of women in the Coronary Artery Risk Development In Young Adults (CARDIA) study. Methods: Women from CARDIA at Birmingham, AL and Minneapolis, MN were eligible if they completed a questionnaire about bladder symptoms in 2022-23, an ancillary study post-year 35 called CARDIA-PLUS, including the global BH scale (possible range, 0-100) and the LURN-SI 10 (0-38) and the AUASI (0-35). A subset (n=216) completed an in-person examination, including the ankle brachial index (ABI) procedure (n=194). ABI scores were clinically categorized as normal (1.00-1.40), borderline abnormal (0.91-0.99), and abnormal (</=;0.90; evidence of PAD). Continuous BH and LUTS variables were regressed on ABI category, adjusting for sociodemographics, obstetric/gynecologic variables, co-morbidities, and physical activity. Key Results: Among women who completed BH/LUTS questionnaires and the ABI (n=192), the mean age was 63+/-4 years and racial composition was 47% Black and 53% White. ABI results were normal (74%), borderline abnormal (20%), and abnormal (6%). After adjusting for covariates, women with abnormal ABI scores had higher LURN-SI scores (4.1 points, 95% CI 0.7, 7.5) and did not have higher AUASI scores (1.4 points, 95% CI -3.1, 5.7) or lower BH scores (-9.6 points, 95% CI -24.0, 4.9) compared to women with normal ABI scores. Borderline abnormal ABI was not associated with BH or LUTS. Discussion/Conclusion: In this cohort, PAD was associated with greater LUTS severity. PAD and LUTS may share common etiologies and risk factors that need additional research.

Current evidence supports resistance training for stroke recovery but autonomic dysregulation following stroke can lead to exaggerated fluctuations in blood pressure (BP) in response to exercise, thus challenging perceptions about safety and feasibility of resistance exercise. This study compared the post-exercise BP response following a single bout of leg-press exercise between people with and without stroke. Data from 11 individuals with chronic stroke (age 39-76 years, 5 female, 1-9 years post-stroke) and 19 recreationally active controls (age 18-33 years, 11 female) were included. Brachial artery BP was measured before exercise and immediately following a single set of leg-press (8 repetitions, target rating of perceived exertion 5-7/10). The difference between pre- and post-exercise BP was calculated and compared between groups using an independent t-test of equal variance. Additionally, a two-way analysis of covariance was used to examine potential cofounding effects of activity level and baseline BP on between group differences in BP response. No group differences were observed in post-exercise change in systolic (mean difference=3.61 mmHg, 95%CI:-8.36, 15.57, p=0.54); and diastolic (mean difference=5.38 mmHg, 95%CI:-6.11, 16.86, p=0.35) BP. Results were unchanged after controlling for baseline BP, and activity levels. Our work suggests that individuals with and without chronic stroke experience similar acute BP responses immediately following resistance exercise; however, work with more appropriately matched controls and greater sample sizes is needed to support these findings. Future studies may elucidate mechanisms related to the acute cardiovascular response to resistance exercise in individuals with stroke.

Aims: The risks of dementia, stroke, and mortality increase from normoglycemia to prediabetes and type 2 diabetes (T2D). Blood pressure variability (BPV) is associated with adverse vascular and neurological outcomes, but its role in glycemia-associated risks remains unclear. We examined the interplay between glycemia, BPV, and these outcomes. Methods and Results: In a large prospective cohort, visit-to-visit BPV was quantified using absolute and directional measures of systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP). Glycemic status was defined as normoglycemia, prediabetes, and T2D. Time-updated Cox models estimated outcome associations, adjusting for confounders and mean blood pressure. We evaluated the joint and independent associations of BPV and glycemic status with outcomes, effect modification, and attenuation of glycemia-associated risks after BPV adjustment. Among 57,611 participants (median follow-up, 5.1 years; IQR, 3.3-9.5 years), compared with normoglycemia and low BPV, T2D with high SBP variability was associated with higher risks of all-cause mortality (HR 2.80, 95% CI 2.12-3.69) and nominally higher risk of all-cause dementia (HR 2.46, 95% CI 1.37-4.42). All absolute BPV measures were independently associated with mortality, while DBP and MAP variability were associated with overall stroke after FDR correction. Additional adjustment for BPV minimally attenuated glycemia-associated risk, and no multiplicative interaction remained significant after multiple-testing correction. Conclusions: Absolute BPV was associated with mortality, and DBP and MAP variability with overall stroke, after accounting for glycemic status and mean blood pressure. Additional BPV adjustment changed the glycemic association only minimally.

Background: Data from National Health and Nutrition Examination Survey (NHANES) cycles 1988-1994 and 1999-2004 show a declining trend in the adherence to Dietary Approaches to Stop Hypertension (DASH) among adults. Since then, DASH evidence, dietary guidelines, and public-facing dietary resources have advanced, but whether national DASH adherence has improved is uncertain. Methods: We extended the Mellen et al. NHANES analysis among 14,163 adults with self-reported hypertension (N=6,914, 2003-2010, N=7,249, 2011-2018). DASH score included 9 nutrient components: total fat, saturated fat, protein, cholesterol, fiber, calcium, magnesium, potassium, and sodium, with adherence defined as a score 4.5. Survey-weighted multivariable models compared DASH score, adherence, and nutrient-threshold attainment across periods. Results: In 2011-2018, U.S. adults with self-reported hypertension represented 76.2 million individuals (33.8%). Multivariable-adjusted DASH adherence declined from 22.1% in 2003-2010 to 18.6% in 2011-2018 (p=0.003), and mean DASH score declined from 2.98 to 2.85 (p=0.007). Adjusted odds of adherence were lower in 2011-2018 compared with 2003-2010 (OR, 0.78; 95% CI, 0.67-0.91; p=0.002). Adherence was lower among non-Hispanic Black adults (OR, 0.70; 95% CI, 0.59-0.84), adults with BMI 30 kg/m2 (OR, 0.61; 95% CI, 0.51-0.73), and adults with prior stroke (OR, 0.71; 95% CI, 0.56-0.89). Total fat and sodium threshold attainment declined from 20.9% to 18.7% and 13.8% to 11.8%, respectively. Conclusions: DASH adherence among U.S. adults with self-reported hypertension declined from 2003-2011 to 2011-2018. Implementation strategies should identify barriers to adoption and address the full DASH dietary pattern.

Elevated systolic blood pressure (SBP) is a major modifiable driver of cardiovascular morbidity. Digital food-as-medicine and home-blood-pressure-monitoring programs increasingly support its management outside the clinic, but most published evaluations are single-arm, pre/post designs; because enrolment is conditioned on an elevated baseline reading, regression to the mean (RTM) is expected to inflate any observed improvement, and this is rarely checked against an internal comparator. We conducted a retrospective, single-arm cohort study of home blood-pressure monitoring within a commercial digital food-as-medicine program serving a US employer-sponsored population with obesity. Of 329 members included, 136 were at-goal (<130/80 mmHg), 74 at Stage 1 (130-134/80-84 mmHg) and 119 at Stage 2 ([&ge;]135/85 mmHg) at baseline; follow-up SBP was evaluable for 128, 68 and 112 members in these strata at 3 months and for 62, 34 and 53 at 6 months, respectively. The primary estimand was the unadjusted within-member change in home SBP at 6 months among members with Stage-1 and Stage-2 blood pressure at baseline; a secondary estimand corrected for RTM using an ANCOVA linear mixed model with the at-goal stratum as an internal negative-control population. Among Stage-1 members (n = 34), unadjusted SBP change was -4.36 mmHg (95% CI -7.43 to -1.28; p = 0.0069), paired with an RTM-corrected secondary change of -3.33 mmHg (-6.40 to -0.26; p = 0.033). Among Stage-2 members (n = 53), unadjusted change was -10.17 mmHg (-12.94 to -7.40; p < 0.001), paired with an RTM-corrected secondary change of -5.50 mmHg (95% CI -8.50 to -2.50; p = 0.00037); RTM accounted for ~24% and ~46% of the unadjusted decline in Stage-1 and Stage-2, respectively. RTM-corrected estimates were robust to sensitivity analyses on measurement modality, seasonality, covariates and model specification, with no evidence of attrition bias. Program participation was associated with a decline in home SBP among Stage-1 and Stage-2 members that remained significant, though smaller, after RTM correction, supporting RTM-adjusted SBP change as the appropriate metric for evaluating food-as-medicine interventions.

BackgroundMacitentan is a dual endothelin receptor antagonist used in pulmonary arterial hypertension (PAH) and has also been studied in other forms of pulmonary hypertension (PH). Evidence across PH phenotypes has been heterogeneous. This study aims to evaluate the efficacy and safety of macitentan compared with concurrent control therapies across PH phenotypes and to explore whether treatment effects differ according to PH classification. MethodsPubMed, Embase, and the Cochrane database were searched from inception through June 2026. Randomized and non-randomized comparative studies of patients with PH receiving macitentan were eligible. Prespecified efficacy outcomes were 6-minute walk distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), and cardiac index; prespecified safety outcomes included mortality and adverse events. Random-effects meta-analyses were performed using mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. ResultsFourteen studies met the eligibility criteria. Macitentan was associated with a greater reduction in PVR (MD, -134.50 dyn.s.cm; 95% CI, -226.10 to -42.86) and an increase in cardiac index (MD, 0.44 L/min/m; 95% CI, 0.22 to 0.67). No statistically significant difference was observed for 6MWD (MD, 5.04 m; 95% CI, -15.06 to 25.14) or mPAP (MD, -2.70 mmHg; 95% CI, -6.46 to 1.05). In pooled safety analyses, mortality was lower and risks of anemia, peripheral edema, and discontinuation due to adverse events were higher with macitentan. Heterogeneity and the small number of studies within several phenotype-specific analyses limited the precision of subgroup findings. ConclusionsMacitentan-containing therapy was associated with favorable changes in selected hemodynamic outcomes but not with a statistically significant improvement in 6MWD or mPAP. The safety findings were characterized by higher risks of anemia, peripheral edema, and treatment discontinuation. These results should be interpreted in the context of differences in PH phenotype, dose, comparator, study design, and outcome measurement.

Purpose We examined whether drinking a small volume of cold water during orthostatic stress attenuates the fall in systolic blood pressure (SBP). Methods In a randomized crossover study, 19 healthy young adults underwent 15 min of 60 degree head-up tilt under three conditions on separate days: no water, 200 mL of body-temperature water (37 degrees Celsius), and 200 mL of cold water (4 degrees Celsius). Drinking began 5 min after tilting and lasted 1 min. Hemodynamics and tympanic temperature were analyzed using covariate-adjusted linear mixed models with within- and between-condition comparisons. Results During drinking, SBP increased from pre-drinking values by 9.54 mmHg (95% confidence interval [CI] 5.58 to 13.50) with body-temperature water and 14.70 mmHg (10.74 to 18.66) with cold water. After cold water ingestion, SBP remained higher by 5.95 mmHg (95% CI 1.99 to 9.91) over the first 4 min and 4.84 mmHg (0.88 to 8.80) over the subsequent 5 min. No clear post-drinking increases occurred with body-temperature water. SBP was higher with cold water than with both other conditions during the first 4 min after drinking, and higher than with body-temperature water during the subsequent 5 min. After cold water ingestion, stroke volume was higher and heart rate lower than before drinking, and tympanic temperature declined between the two post-drinking periods. Conclusion Drinking 200 mL of cold water after blood pressure had fallen attenuated the reduction in SBP during continued orthostatic stress in healthy young adults.

Background: Dietary sodium intake is a modifiable determinant of blood pressure, and impaired renal sodium handling is implicated in the pathogenesis of hypertension. Whether dietary sodium intake modulates renal tubular sodium transporter abundance among normotensive adults at risk for hypertension is unknown. Methods: Forty-six normotensive adults with normal kidney function at risk of developing hypertension were prospectively enrolled to complete a very low sodium (LS) diet followed by a high sodium (HS) diet. Urinary extracellular vesicle (uEV) proteins were quantified from a 24-hour urine collection at the end of each diet. We compared normalized uEV protein concentrations between diets and tested whether diet modified uEV protein associations with serum aldosterone, urinary aldosterone, and serum cortisol-cortisone ratio under either diet using Wilcoxon rank sums and linear mixed effects models, respectively. Results: Participants achieved median [IQR] urine sodium 13.2 [7.7-19.9] mEq/24h on the LS diet and 244.0 [197.1-297.0] mEq/24h on the HS diet. LS intake induced greater renin activity, greater plasma and urinary aldosterone, and lower urinary cortisol, when compared to HS intake. In parallel, NCC, ENaC, SGLT2, OXSR1, and Pendrin uEV concentrations were significantly higher during LS intake than HS intake (p<0.05 for all), whereas TRPV5 and AQP2 uEV concentrations were lower during LS intake than HS intake (p<0.001 for both). Conclusions: Controlled dietary sodium modulation induced nephron-segment specific changes in uEV protein abundance. These findings demonstrate the ability of uEVs to serve as a non-invasive tool to probe in vivo renal sodium, water, and electrolyte handling.

Abstract Background: Conventional cuff based methods report single systolic and diastolic pressure values and depend either on Korotkoff sounds or on empirical oscillometric algorithms. Methods: We developed a patented cuff based method, termed plethysmometry, that simultaneously records cuff pressure and finger photoplethysmograms from the cuffed and contralateral arms. The contralateral photoplethysmogram serves as an internal physiological reference for pulse amplitude. Following an initial pressure ramp, 16 cuff pressure plateaus are applied. Absolute and normalized pulse amplitudes in the cuffed arm are related to cuff pressure to estimate lower and upper systolic and diastolic pressures. Mean arterial pressure is estimated independently from cuff pressure oscillation amplitude. The estimations are done by automated algorithms developed in MATLAB. Results: The method reports lower and upper systolic, diastolic and mean arterial pressure ranges (during the recording period), together with their average values. Average pulse pressure is also reported. Graphs are provided for reference to check the accuracy of reported pressures. Conclusion: Plethysmometry provides an objective digital record of the cuff pressure and pulse traces and estimates systolic and diastolic pressure ranges from the pulse response of the individual subject to graded cuff pressure. It also reports mean arterial pressure. Comparison of plethysmometric systolic and diastolic pressures with sphygmomanometrically derived pressures and diagnostic agreement are reported in a companion paper.

Objectives: To investigate whether genetic predisposition to hypertensive disorders of pregnancy (HDP), measured using polygenic risk scores (PRS), is associated with subsequent cardiovascular disease (CVD) outcomes in analyses stratified by HDP history. Study design and main outcome measures: This population-based cohort included 1,284 women from the 1994-95 Busselton Health Study with genotype data, pregnancy history, cardiovascular risk factors, and linked hospitalisation and death records to 2022. Four HDP-related PRS were assessed: two for preeclampsia, one for gestational hypertension, and one for broad HDP phenotype. Outcomes were incident first CVD events classified into categories. Fine-Gray competing-risk models adjusted for age, cardiovascular risk factors, and genetic principal components estimated subdistribution hazard ratios (sHR) per standard deviation increase in PRS. Results: Of 1,284 women, 309 reported a history of HDP and 651 experienced an incident CVD event during follow-up. In analyses stratified by HDP history, the largest estimates were observed for first cerebrovascular disease, although event numbers were small. The PGS003586 preeclampsia PRS showed the largest estimate (sHR 3.41, 95% confidence interval (CI) 1.54-7.58, p = 0.003), while PGS004593, another preeclampsia-related score, was also positively associated with cerebrovascular disease (sHR 1.86, 95% CI 1.05-3.30, p = 0.035). The gestational hypertension and broad HDP scores also showed positive estimates, but CI included 1.0, indicating inconclusive evidence. Conclusions: Among women with a history of HDP, preeclampsia-related PRS showed preliminary evidence of an association with incident cerebrovascular disease. Given the small number of events, findings should be interpreted cautiously and validated in larger, multi-ancestry cohorts.

Background Attentional control declines with normal aging, yet the role of modifiable lifestyle factors in accelerating this decline remains incompletely characterised in large, diverse populations. We examined associations between four modifiable risk factors (smoking intensity, alcohol binge drinking, social satisfaction and blood pressure) and sustained attention performance in 13,866 adults drawn from the All of Us Research Program. Methods Cognitive performance was assessed using the Gradual-Onset Continuous Performance Task (GradCPT). A composite cognitive efficiency score was derived via principal component analysis of four GradCPT metrics: d' (perceptual sensitivity), response criterion, median reaction time and reaction time variability. Associations between cognitive efficiency and each risk factor were examined using multiple linear regression adjusted for age, sex and race/ethnicity. Effect sizes were expressed as age-equivalent years of cognitive aging (age-equivalent years = regression coefficient for the risk factor divided by the regression coefficient for age) to aid clinical interpretation. Results GradCPT performance declined progressively with age (p < 0.001). Social satisfaction emerged as the strongest lifestyle predictor: low social satisfaction was associated with approximately 5.8 additional age-equivalent years of cognitive aging relative to high social satisfaction. Smoking showed a dose-response pattern, with heavy smokers (> 20 cigarettes/day) exhibiting an approximately 5-year age-equivalent deficit versus never-smokers. Stage 2 hypertension showed a modest, non-significant negative association. Binge drinking showed limited significant associations, likely complicated by survivor and abstainer biases. Bootstrapped analyses of combined exposures showed that combinations of risk factors, particularly those involving low social satisfaction, produced larger cognitive deficits than expected under an additive model. Conclusions These findings support an interactive rather than a purely additive model of lifestyle-related cognitive vulnerability and highlight the GradCPT as a subclinical measure of attention-based cognitive risk in non-clinical populations. Keywords Cognitive aging, Sustained attention, GradCPT, Modifiable risk factors, Social isolation, Smoking, Hypertension, All of Us Research Program

Background Pediatric nephrotic syndrome (NS) significantly increases cardiovascular risk, primarily through activation of the renin-angiotensin-aldosterone system (RAAS) and chronic inflammation. This study aimed to evaluate the relationship between serum aldosterone and interleukin 6 (IL-6) levels with carotid intima-media thickness (CIMT) in children with steroid-sensitive (SSNS) and steroid-resistant NS (SRNS), both before and after combined treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Materials and methods A prospective cohort study enrolled 32 children aged 2-18 years with idiopathic NS at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia (May-June 2024). Participants received lisinopril (ACEI) or valsartan (ARB) for 12 weeks. Serum aldosterone was quantified via liquid chromatography-tandem mass spectrometry, IL-6 via electrochemiluminescence immunoassay, and CIMT via high-resolution B-mode Doppler ultrasound. Data were analyzed using SPSS version 26.0, including Shapiro Wilk normality testing, Pearson/Spearman correlations, and multivariate linear regression (enter method, R2=0.022), with statistical significance set at p<0.05. Results CIMT decreased significantly post-treatment (0.13{+/-}0.04 cm to 0.06{+/-}0.01 cm; p<0.001). Serum aldosterone remained stable (5.15 to 4.0 ng/dL; p=0.933), as did IL-6 (3.5 pg/mL; p=0.156). Univariate analyses revealed weak correlations (aldosterone-CIMT: R2=0.075; IL-6-CIMT: R2=0.215). Multivariate regression (R2=0.022) identified SRNS as positively associated with CIMT change (p=0.047), while aldosterone and IL-6 showed no significant independent effects. Conclusion This study highlights that ACEI and ARB therapy improved CIMT regardless of steroid sensitivity, suggesting vascular benefits may occur through pathways independent of aldosterone and IL-6 modulation.

Background: Cardiometabolic disease is a leading cause of death, and most therapies suppress established pathology rather than restore functional capacity. Pulsed electromagnetic field (PEMF) therapy is a non-invasive stimulus touted as a potential complementary approach that may engage adaptive responses, with practical potential for home-based use. We systematically reviewed and meta-analysed PEMF effects on cardiometabolic outcomes. Methods: We searched seven electronic databases and Google Scholar from inception to 31 August 2026 for studies of PEMF in adults, healthy or with cardiometabolic conditions. Between-group differences were rescaled into minimal clinically important difference (MCID) units to facilitate comparison across diverse outcomes. Established anchor-based MCIDs were used where available; otherwise, 0.5 pooled within-arm SD was used. Effects were pooled using multilevel random-effects models with study-clustered robust variance, with subgroup, sensitivity, and exploratory dose-response analyses. The review was registered with PROSPERO (CRD420261404575). Results: Ten studies (353 participants) were included. PEMF was associated with an overall benefit of 0.54 MCID units (95% CI 0.08-1.00). Effects were largest in hypertension (1.24 MCID units, 0.52-1.96), with no observed heterogeneity across two double-blind trials (I2=0%). Exploratory multivariable meta-regression associated greater cumulative exposure and lower frequency with larger effects. Conclusions: PEMF therapy may offer a non-invasive, non-pharmacological adjunct for improving cardiometabolic outcomes, with potential for home-based use. The most compelling signal was observed in hypertension, where the pooled effect exceeded one clinically important difference, although confirmation in larger trials is required.

Background Cardiovascular prevention is organized around target metrics. Blood pressure, LDL cholesterol, and A1c define treatment targets, quality metrics, and, implicitly, who is considered safe. Yet a value below a cutoff is a correlative measurement, not an outcome. We tested whether social context recorded before the measurement separated subsequent cardiovascular events among people whose numbers already met the cutoff. Methods In this retrospective cohort study, we analyzed All of Us participants without recorded cardiovascular disease and with low comorbidity in three separately indexed cohorts: systolic blood pressure (SBP), LDL cholesterol, and A1c. A preindex score combined household income, education, food security, physical activity, and ZIP-linked deprivation, standardized against a fixed pooled reference of 325,652 eligible people. The outcome was first myocardial infarction, ischemic stroke, or heart failure. A sensitivity analysis indexed participants at only events recorded in inpatient or emergency settings. Results The SBP, LDL, and A1c cohorts included 19,525, 16,578, and 18,539 participants with 144, 129, and 191 events. Each one-SD more favorable score was associated with lower hazard: HR 0.611 (95% CI 0.498-0.749), 0.631 (0.512-0.778), and 0.544 (0.457-0.648), respectively. Below each study cutoff (SBP <140 mmHg, LDL <100 mg/dL, A1c <8%), less favorable context had event rates of 3.39 versus 1.68, 7.16 versus 2.05, and 8.67 versus 2.34 per 1,000 person-years. In a one-year analysis restricted to 2019-2023 index dates, the corresponding adjusted HRs were 0.530, 0.336, and 0.365. In the sensitivity cohorts (54,338, 41,451, and 33,607 participants; 493, 288, and 316 events), HRs were 0.732 (0.657-0.815), 0.660 (0.573-0.761), and 0.631 (0.552-0.722). Conclusions A biomarker below the study cutoff did not identify a uniform, low-risk population. Social context recorded before the measurement separated cardiovascular events after adjustment for the measured value and clinical factors. Risk assessment that stops at the number misses this variation.