Journal of Hypertension

Abstract Background:Patients with hypertension commonly exhibit reduced exercise capacity. Impedance cardiography (ICG) enables continuous, non-invasive assessment of exercise-derived hemodynamic parameters; however, the relative associations of different ICG-derived parameters with exercise capacity remain unclear. Methods:In this retrospective cross-sectional study, 211 patients with hypertension who completed both ICG assessment and the six-minute walk test (6MWT) were enrolled. Exercise-derived hemodynamic parameters, including maximum heart rate (HRmax), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR), were continuously measured using the PhysioFlow(R) system. Univariable and multivariable linear regression analyses were performed to evaluate the associations between ICG-derived parameters and six-minute walk distance (6MWD). HRmax tertile and subgroup analyses were subsequently conducted. Results:In the final multivariable model, age ({beta} = -2.76, 95% CI, -3.85 to -1.67, P < 0.001), male sex ({beta} = 33.50, 95% CI, 8.40-58.60; P = 0.009), and HRmax ({beta} = 1.26, 95% CI, 0.69-1.83; P < 0.001) were independently associated with 6MWD. 6MWD increased progressively across HRmax tertiles (P for trend < 0.001). The positive association between HRmax and 6MWD remained consistent across all prespecified and exploratory subgroups. Conclusions:Among multiple exercise-derived ICG hemodynamic parameters, HRmax demonstrated the strongest and most consistent independent association with exercise capacity in patients with hypertension. These findings suggest that HRmax may represent the most informative dynamic hemodynamic parameter during exercise and that combining ICG with the 6MWT may provide a simple and accessible complementary approach for evaluating exercise capacity.

Background Randomized outcome trials have shown the benefit of antihypertensive treatment, but subgroup analyses exploring treatment responses in relation to patient characteristics are usually based on single factors rather than comprehensive patient profiles. We hypothesized that a combination of individual predictors better identifies patients who are more or less likely to achieve blood pressure (BP) control. Methods To test our hypothesis, we reanalysed the data from the double-blinded VALUE-outcome trial (n=15,313). The patient population was divided into an exploratory cohort (2/3) and a validation cohort (1/3). We constructed composite patient profiles by combining four proven predictors of BP control: age, severity of hypertension, comorbidity and previous treatment status. Logistic regression and Cox proportional hazard models were used to test whether BP control and cardiovascular event rates differed among these profiles, and whether profiling conferred additional predictive information beyond the individual factors alone. Results BP control rates differed significantly between patient profiles, regardless of treatment (likelihood ratio test, p<0.001). Results from the exploratory cohort were reproducible in the validation cohort. Profiling predicted BP control significantly better than any individual factor (p<0.001 for all comparisons). In addition, there were significant associations between profiles and the incidence of cardiovascular events. Adverse events, however, were not related to profiles. Conclusions We conclude that composite patient profiles may predict BP responses to antihypertensive treatment more accurately than single factors. These findings may help to better individualize antihypertensive therapy.

Background Hypertension is a major global health challenge with well-established cardiovascular risks, yet its relationship with bone mineral density and the skeletal relevance of antihypertensive-related targets remain unclear. Methods Based on individual-level data from 366,443 European-ancestry participants in the UK Biobank, this study adopted restricted cubic spline models to explore linear and nonlinear associations between systolic/diastolic blood pressure (SBP/DBP) and heel estimated bone mineral density (BMD). We stratified participants by median DBP to conduct systematic biomarker analyses covering renal, endocrine, inflammatory and metabolic indicators. Drug-target Mendelian randomization (MR) combined with colocalization and mediation analyses was further performed to identify and validate causal antihypertensive-related target genes associated with BMD. Results A significant inverted U-shaped association was identified between DBP and BMD (P non-linear=3.23e-9), with peak BMD observed at a DBP of 80-90 mmHg, while SBP showed a trend of nonlinear correlation. Biomarker analyses revealed that renal biomarker cystatin C and endocrine biomarker IGF-1 exhibited DBP-dependent associations with BMD, mediating the nonlinear DBP-bone density relationship. Drug-target MR demonstrated that genetically proxied MMP9 expression (ACE inhibitor-related) was negatively correlated with BMD (beta=-0.036, P=5.29e-6), whereas CACNA1G expression (T-type calcium channel blocker target) was positively associated with BMD (beta=0.042, P=1.57e-9). Conclusion The inverted U-shaped association between blood pressure and bone mass might partly reflected by renal dysfunction. Antihypertensive pathways mediated by MMP9 and CACNA1G exert opposing effects on bone mass, implying that skeletal health should be considered when selecting antihypertensive agents for vulnerable older populations.

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

BackgroundHypertension, the persistent elevation of blood pressure (BP), is characterized by chronic low-grade inflammation and systemic cytokine release. Circulating cytokines contribute to the development of hypertension and end-organ damage. However, the specific immune profile associated with the progression of hypertension remains unclear. We hypothesize that a plasma cytokine signature reflects early BP changes in older adults. MethodsSeventy participants aged 57-81 years were categorized as normotensive (n = 17), elevated BP (n = 10), or hypertensive (n = 43) based on 24-hour ambulatory BP monitoring and antihypertensive treatment status. Plasma IL-1{beta}, IL-6, IL-10, IL-17A, IL-21, IL-22, IL-23, and TNF- were quantified using immunoassays. Partial Pearson correlations adjusted for demographic and biochemical covariates were used to assess associations between cytokines, BP, and cytokine-cytokine networks. ResultsIn untreated hypertensive individuals, plasma IL-23 was positively correlated with 24-hour diastolic BP. Antihypertensive treatment was associated with reduced IL-17A concentrations, which are negatively associated with 24-hour systolic BP. In the elevated BP group, IL-21 concentrations were higher than in normotensive individuals. To further characterize the cytokine signature, cytokine-cytokine correlations were examined. IL-23 and IL-17A were positively correlated with most interleukins, whereas TNF- showed few associations. IL-1{beta} exhibited strong correlations with both IL-23 and IL-17A, particularly in untreated participants. ConclusionIL-23 and IL-17A are associated with BP status and are broadly interconnected with other inflammatory cytokines, highlighting the potential importance of the IL-23/IL-17A axis in the hypertension of development. Early alterations in IL-21 in elevated BP may reflect immune changes that precede the onset of hypertension.

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.

Background. The imprecision of current metrics to capture the complex genetic admixture and racial identity among Hispanic/Latino individuals in the United States [US] is a concern. We examined the relationship of self-reported race and genetic ancestry with hypertension [HTN] among Hispanics/Latinos. Methods. Cross-sectional study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), including 10,586 Hispanic/Latino unrelated adults. Genetic ancestry: West African [AA], Amerindian [AI], and European [EA]. Self-reported race: White, Black, Native American, or Multiple/Missing (More than one race or Unknown/Not reported/Refused). HTN: systolic (SBP) [&ge;]130 mmHg, diastolic blood pressure (DBP) [&ge;]80 mmHg, and/or use of HTN medications. Age- and sex adjusted models were used. Results. Self-reported race was White (38{middle dot}6%), Black (3{middle dot}6%), Native American (4{middle dot}1%), and Multiple/Missing (53{middle dot}7%), with Unknown/Not reported/Refused representing 32{middle dot}7%. Black and White Hispanics/Latinos had the greatest AA (55{middle dot}7%) and EA (69{middle dot}3%) ancestries, respectively. Each 10% AA increase was associated with OR 1{middle dot}15, SBP beta +0{middle dot}9 mmHg, and DBP beta +0{middle dot}7 mmHg. Conversely, each 10% AI increase was associated with OR 0{middle dot}83, SBP beta -0{middle dot}4 mmHg, and DBP beta -0{middle dot}6 mmHg. HTN prevalence was highest among those with Black race or in the highest AA quantile (45{middle dot}6% and 48{middle dot}0%, respectively), and lowest among those with Native American race or in the highest AI quantile (37{middle dot}6% and 26{middle dot}7%, respectively). Conclusion. One-third of Hispanics/Latinos did not self-report race. Black or White self-reporting race did somewhat relate to AA or EA ancestry, respectively. HTN profiles were related to self-reported race and genetic ancestry in this admixed population.

Purpose: To determine whether the velocity reflection index (VRI) is the carotid Doppler waveform feature most strongly associated with chronological age after adjustment for sex and exercise habit, and whether its feature ranking remains stable across cross-validated and cohort-sensitivity analyses. Methods: Eight waveform-derived features were analysed in 197 participants meeting the study eligibility criteria and measured using a validated continuous-wave carotid Doppler system. Pearson and partial correlations and multivariable regression evaluated associations with chronological age. Random Forest regression with repeated 10-fold cross-validation, held-out permutation importance and bootstrap resampling assessed feature ranking. Sensitivity analysis evaluated the influence of cohort construction. Results: VRI showed the strongest association with chronological age (r = 0.738, 95% CI [0.667, 0.796]) and remained strongly associated after adjustment for sex and exercise habit (partial r = 0.798). VRI ranked first by both impurity-based (0.536) and held-out permutation (0.765) importance; repeated cross-validation yielded MAE = 6.87 +/- 1.26 years and R^2 = 0.572 +/- 0.153. Its leading ranking was stable in 85.3% of bootstrap resamples and the age-VRI correlation was essentially unchanged in the cohort-sensitivity analysis. The exercise association was significant after age adjustment (B = -0.043, p = 0.018) but attenuated after additional adjustment for sex (B = -0.026, p = 0.098). The sex association remained significant after adjustment for age and height. Conclusion: VRI was robustly associated with chronological age and retained the leading feature-importance ranking across adjusted statistical and cross-validated machine-learning analyses. Validation against an established arterial-stiffness measure in an independent cohort is required before VRI can be considered a clinical vascular-aging biomarker.

Background: Electrocardiographic (ECG) markers of atrial cardiopathy (AC) are associated with stroke mortality, but whether this association is modified by blood pressure (BP) is unknown. Methods: We analyzed 7,191 adults free of cardiovascular disease from the Third National Health and Nutrition Examination Survey who underwent baseline ECG. AC was defined by three ECG markers: prolonged P-wave duration 120 ms), abnormal P-wave axis (<0{degrees} or >75{degrees}), and deep terminal negativity of the P wave in V1 (<100 V). AC burden (per additional AC marker) and AC presence (1 vs. 0 markers) were examined in relation to stroke mortality using Cox proportional hazards models. Participants were stratified by BP as normal/elevated (<130/80 mmHg), stage 1-2 hypertension (130-159/80-99 mmHg), or severe hypertension (160/100 mmHg). Interaction by BP category was assessed. Results: During a median follow-up of 13.8 years, 183 stroke deaths occurred. In multivariable adjusted model, AC burden was associated with a 41% higher risk of stroke mortality (HR (95%CI): 1.41 (1.13-1.77)). This association was significantly modified by BP (interaction P=0.003). The HRs (95% CIs) per additional AC marker were 0.88 (0.52-1.49), 1.39 (1.03-1.88), and 2.94 (1.82-4.75) for normal/elevated BP, stage 1-2 hypertension, and severe hypertension, respectively. A similar pattern of associations was observed for AC presence, although the interaction with BP was not statistically significant. Conclusions: ECG-defined AC burden was independently associated with stroke mortality, with substantially stronger associations among individuals with severe hypertension, supporting BP as an important modifier of its prognostic significance.

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.

Ambulatory blood pressure monitoring (ABPM) is recommended for confirming hypertension and assessing out-of-office blood pressure (BP). However, patient burden and device tolerability may limit broader implementation. We compared participant experience with a traditional oscillometric ABPM device and a compact cuff-integrated ABPM. The PRO-BP Study was a pilot randomized crossover study of 20 adults in New York City. Participants completed two 24-hour ABPM periods over 7 days using the SpaceLabs 90227 and SOMNOmedics ABPM Pro devices. After each period, participants rated comfort, pain, sleep interference, embarrassment, noise, skin irritation, and interference with daytime activities. Both devices achieved guideline-based recording-quality thresholds. Compared with SpaceLabs, ABPM Pro was associated with greater comfort (median 7.0 [IQR, 5.0-8.5] vs 3.5 [IQR, 2.0-6.5]; P=0.004), less pain (1.5 [0-3.5] vs 5.0 [0.5-7.0]; P=0.003), and less embarrassment (0.5 [0-3.5] vs 3.0 [0-6.0]; P=0.01). Other experience ratings did not differ significantly. Participant experience should be considered alongside recording quality when evaluating validated ambulatory BP monitoring technologies.

Background: Atrial fibrillation (AF) may increase susceptibility to falls, but its association with injurious falls among adults with hypertension and whether intensive blood pressure (BP) lowering modifies this association are uncertain. Methods: We analyzed 8,807 SPRINT participants with a baseline electrocardiogram and postrandomization follow-up for injurious falls. AF was evaluated at baseline and as a time-updated exposure incorporating AF identified during follow-up. Cox models estimated hazard ratios (HRs) and 95% CIs for the first injurious fall and assessed effect modification by randomized BP treatment assignment. Results: Among 8,807 participants, 163 had baseline AF, 142 developed AF during follow-up, and 637 experienced an injurious fall. In fully adjusted analyses, baseline AF (HR, 1.79 [95% CI, 1.18-2.70]) and time-updated AF (HR, 1.89 [95% CI, 1.32-2.71]) were associated with higher fall risk. The association with time-updated AF was similar with standard and intensive BP treatment (HR, 1.91 [95% CI, 1.12-3.26] and 1.94 [95% CI, 1.18-3.19], respectively; P for interaction=0.964) and across prespecified subgroups. Results were robust in competing-risk and temporal-lag sensitivity analyses. Conclusions: Among adults with hypertension and elevated cardiovascular risk, AF was independently associated with higher injurious-fall risk. The association was observed with baseline and time-updated AF and was not modified by intensive BP lowering, suggesting that AF identifies patients at increased fall risk without evidence that intensive BP treatment amplifies this risk.

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: Vascular calcification (VC) is prevalent among patients with atherosclerosis, hypertension, diabetes, elderly individuals, and those with chronic kidney disease. However, effective diagnostic and therapeutic strategies are lacking. Plasma and urinary biomarkers are commonly used in clinical settings to assess disease progression. Objective: This study investigates causal relationships between plasma/urinary biomarkers and VC using Mendelian randomization (MR), aiming to identify potential targets for VC intervention, and to assess whether biomarkers mediate the effects of modifiable risk factors on VC. Methods: We performed two-sample bidirectional MR using large-scale genome-wide association study data (n=363,228 for biomarkers, n=28,654 for VC) to investigate the causal effects of plasma/urinary biomarkers on VC. Then, a literature review was performed to identify common VC risk factors, followed by univariate MR to select risk factors associated with both VC and biomarkers. Finally, mediation analysis was conducted to explored whether biomarkers mediate the effects of modifiable risk factors on VC. Results: MR analysis identified 7 plasma biomarkers linked to VC, 5 of which were positively correlated. A literature review revealed 856 VC risk factors, with 28 identified through univariate MR analysis, 11 of which correlated with identified biomarkers. Mediation analysis showed that 5 biomarkers (TRIG, GGT, CA, BILD, SHBG) partially mediated the effects of 4 modifiable risk factors on VC. Conclusion: This study identifies several clinically common used biomarkers for diagnosing and treating VC, suggesting that modulating these biomarkers through lifestyle changes, such as controlling smoking, intake of milk, blood pressure and diabetes, may slow VC progression in patients.

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 Sedentary behaviour independently contributes to cardiovascular disease risk. In healthy adults, prolonged uninterrupted sitting acutely elevates blood pressure, whereas light-activity breaks attenuate this response. Whether such strategies confer similar benefits in high-risk populations, such as chronic stroke survivors, remains unanswered. OBJECTIVES To determine whether non-ambulatory, seated heel-raise interruptions every 10 minutes would attenuate central systolic blood pressure (cSBP) during 3 hours of prolonged sitting in individuals with chronic stroke. We hypothesized that the experimental (heel-raise interruption) condition (EXP) would significantly mitigate the cSBP response relative to uninterrupted sitting (CON). METHODS Using a randomized crossover design, 15 chronic stroke patients (X = 69.3; SD = 10.8 y; 10 male) completed two 3-hour conditions: CON and EXP (10 seated bi-lateral heel raises at 1 rep per second every 10 minutes). Central and peripheral blood pressures were assessed pre- and post-each condition using the SphygmoCor XCEL. Condition by Time interactions were tested using repeated-measures ANOVA. RESULTS The primary hypothesis was confirmed: a significant Condition by Time interaction was detected for cSBP (p < 0.05; partial eta squared = 0.28), with EXP eliciting a smaller increase than CON (5.6 mmHg [95% CI;6.4, 17.6] vs. 9.6 mmHg [95%CI; 2.4, 21.6]). CONCLUSIONS Heel-raise interruptions every 10 minutes attenuate the cSBP response to prolonged sitting in chronic stroke patients and reduce cardiac workload. Frequent, non-ambulatory activity breaks represent a practical secondary prevention strategy for this population, though higher intensity or frequency may be required to fully protect vascular function.

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

Background Hypertension is the leading modifiable risk factor for cardiovascular disease (CVD). Despite availability of blood pressure (BP)-lowering therapies, BP control rates remain suboptimal. Reluctance to initiate treatment with combination therapy and delayed treatment intensification contribute to poor control. Early use of single-pill combinations (SPCs) within standardised treatment protocols (STPs) may improve outcomes, but evidence from India is limited. Objective To evaluate the effectiveness and safety of a new STP incorporating initial or early use of SPCs compared with usual care among adults with hypertension. Methods The New Standardised TrEatment Protocol (NewSTeP) trial is a pragmatic, multicentre, randomized, parallel-group, open-label trial conducted in tertiary healthcare centres in India. Adults with hypertension who are untreated or receiving one BP-lowering drug and require treatment initiation or intensification (n = 300) will be randomized 1:1 to either a new STP incorporating early SPC therapy or usual care. Participants will be followed for 6 months. The primary effectiveness outcome is change in home-measured mean systolic BP from randomization to month 6. The primary safety outcome is discontinuation of trial drug due to adverse events. Secondary outcomes include proportion of participants achieving BP control, change in diastolic BP, incidence of adverse events of special interest, treatment adherence, treatment modification, and time to BP control. A process evaluation will assess reach, implementation, acceptability, and sustainability, while an economic evaluation will assess cost-effectiveness of the intervention. Results Between October 2025 and March 2026, 300 participants were randomized across nine sites (150 to New STP; 150 usual care) from 360 screened individuals. Final follow-up is expected in September 2026, with results anticipated in October 2026. Conclusions The NewSTeP trial will provide evidence on the effectiveness, safety, implementation, and cost-effectiveness of an SPC-based STP for hypertension management in India and inform future hypertension control strategies and policies.

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.

Background: Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Historically, male sex was considered a cardiovascular risk factor however recent accumulating data suggest complex interaction between sex and CVD leading to specific inequalities affecting both males and females with specific cardiometabolic features. Methods: Data from a large nationwide screening cohort were used to assess the cardiometabolic burden among males vs females in Algeria. The prevalence and adjusted Odds Ratio (aOR) of major CVD diseases were compared across the study cohorts. Records of systolic (SBP) and diastolic blood pressure (DBP), as well as findings of clinical examination, ECG, and echocardiography were collected and reviewed for analysis. Results: A total of 21,522 patients were included among them 12,015 were females and 9,507 were males. The latter group had higher age (median age: 60 [51.00-68.00] vs 57 [49.00-65.00] years; p< 0.001), sitting DBP (83 [76.00-92.00] vs 80 [75.00-90.00]; p< 0.001), standing SBP (142 [130.00-160.00] vs 140 [124.00-154.00] mmHg; p< 0.001), smoking (22.1% vs 0.9%; p<0.001) and unknown diabetes (15.2% vs 13.2%; p< 0.001) rates. Moreover, females showed an overall worse cardiometabolic profile while males had a greater burden of ischemic heart disease, arrhythmia, conduction abnormalities, and left ventricular dysfunction. On multivariate analysis, female sex was correlated with higher aOR for known hypertension (aOR:1.55; 95%CI:1.40-1.72; p<0.001) and known dyslipidaemia (aOR: 1.23; 95%CI:1.09-1.39; p=0.001). On the other hand, female sex predicted lower risk of any CVD (aOR:0.84; 95%CI:0.72-0.98; p=0.028) and known cardiovascular disease (aOR: 0.79; 95%CI: 0.67-0.94; p=0.007). Conclusion: CVD affect males and females differently which reflects multifaceted biological, cardiometabolic, and sociodemographic disparities. These findings highlight the need to reduce the sex gap in the prevention and management of CVD. Keywords: Cardiovascular disease; Sex; Management disparities; Sex Gap; North Africa; Algeria