Abstract Background Whether estimated pulse wave velocity (ePWV) influences the effect of early antihypertensive treatment in acute ischemic stroke remains unclear. Methods This study was a post hoc analysis of the China Antihypertensive Trial in Acute Ischemic Stroke conducted in 2009–2013. ePWV was calculated using age and mean blood pressure on admission. The primary outcome was a composite of death or major disability at 14 days or hospital discharge and 3 months after stroke. We examined the association between ePWV and the primary outcome and tested for the interaction between ePWV and early blood pressure-lowering treatment. Results Among the 4058 and 3975 participants included in the 14-day or hospital discharge and 3-month analyses, respectively, 1364 (33.6%) and 1001 (25.2%) experienced the composite outcome of death or major disability. The multivariable-adjusted risk ratios (95% CIs) for the highest (≥12.7 m/s) versus lowest ePWV tertile (<11.1 m/s) were 1.23 (1.06–1.43) for the composite outcome of death or major disability and 2.87 (1.10–5.39) for death at 14 days or hospital discharge (P for trend<0.05). At 3 months, the adjusted risk ratios (95% CIs) were 1.41 (1.17–1.70), 3.91 (2.02–7.57), and 2.33 (1.33–4.07) for the composite outcome of death or major disability, death, and vascular events, respectively. There were no significant differences in clinical outcomes between the early antihypertensive treatment and control groups across ePWV tertiles. Conclusions : Higher ePWV was associated with worse clinical outcomes after acute ischemic stroke, and ePWV did not modify the effect of early antihypertensive treatment. Registration —URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.
Abstract BACKGROUND The association between a newly reported major diagnosis and subsequent self-reported hypertension-treatment status remains uncertain. METHODS We analyzed seven overlapping periods of three visits approximately 2 years apart in the Korean Longitudinal Study of Ageing (2006–2008–2010 through 2018–2020–2022). Eligibility required age ≥50 years, physician-diagnosed hypertension at Visit 1, and reported antihypertensive medication use or hypertension treatment at Visits 1 and 2. Newly reported diabetes, cancer, stroke, heart disease, or chronic lung disease was assessed at Visit 2. The Visit 3 outcome was a report of no current hypertension treatment, including no antihypertensive medication use. Modified-Poisson regression used participant-clustered standard errors. The adjusted absolute risk difference was defined as the standardized probability with a newly reported diagnosis minus that without one. RESULTS Among 13,579 observation periods from 3,581 participants, 932 included a newly reported diagnosis. Adjusted probabilities of no reported treatment were 7.5% with and 8.4% without a newly reported diagnosis. The adjusted risk ratio for not receiving treatment for hypertension, including antihypertensive medication, associated with a newly reported diagnosis was 0.89 (95% confidence interval 0.71–1.13); the adjusted absolute risk difference (newly reported diagnosis minus no newly reported diagnosis) was −0.90 percentage points (95% confidence interval −2.66 to 0.85). CONCLUSIONS A newly reported major diagnosis was not associated with self-reported antihypertensive medication use or hypertension treatment approximately 2 years later.
Abstract Background A Body Shape Index (ABSI) reflects abdominal adiposity independent of body size. Although the cardio-ankle vascular index (CAVI) is linked to ABSI, whether this association extends to innovative CAVI (iCAVI) remains unclear. We developed iCAVI, an arterial stiffness index measured from the aortic valve to the right brachial artery in the seated position and examined its association with ABSI. Methods This cross-sectional study included 117 individuals undergoing cardiovascular risk assessment. iCAVI, ABSI, body mass index (BMI), and waist circumference (WC) were evaluated. Associations were assessed using Spearman’s correlation and multivariable analyses adjusting for age and sex-adjusted analyses, with further adjustment for hypertension, diabetes mellitus, dyslipidemia, and coronary artery disease. Adjusted iCAVI values across anthropometric tertiles were compared. Results iCAVI was positively correlated with ABSI (ρ = 0.233, 95% CI [0.048, 0.402], p = 0.012), but not with WC (ρ = −0.054, 95% CI [−0.238, 0.134], p = 0.563) or BMI (ρ = −0.162, 95% CI [−0.339, 0.026], p = 0.081). Age- and sex-adjusted iCAVI increased across ABSI tertiles (2.79, 2.96, and 3.14; p for trend = 0.045). The linear contrast estimate was 0.25 (95% CI [0.01, 0.49]) and remained similar after further adjustment for hypertension, diabetes, dyslipidemia, and coronary artery disease (0.23, 95% CI [−0.02, 0.48]; p for trend = 0.067). Conclusions ABSI was positively associated with iCAVI, whereas BMI and WC were not, suggesting that ABSI may capture aspects of body shape associated with arterial stiffness that are not reflected by conventional anthropometric indices.
Background and Aims In SELECT, subcutaneous semaglutide (target dose 2.4 mg) weekly in adults with pre-existing cardiovascular disease and body mass index >= 27 kg/m(2) without diabetes significantly reduced major adverse cardiovascular events (MACE) by 20% vs placebo. This analysis explored potential mediators of this cardiovascular benefit. Methods Changes from randomization to 24 months in body weight, waist circumference, plasma high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA(1c)), lipids, blood pressure, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio were examined individually, and in combination, as potential mediators of MACE risk reduction, using the Vansteelandt repeated regression method (a counterfactual approach). Results Semaglutide significantly (P < .05) improved all potential mediators investigated. Point estimates for % mediation were largest for waist circumference (64.0% [95% confidence interval (CI) 27.5, 179.6]), hsCRP (42.1% [17.9, 110.5]), HbA(1c) (29.0% [-20.7, 120.5]), and body weight (19.5% [-33.0, 110.7]), examined separately, but all had wide CIs. Supplementary analyses suggested unreliability of estimates for body weight and waist circumference, potentially due to differing relationship of body weight and waist change to MACE between treatment arms. Multivariable analysis estimated joint mediation for all potential mediators combined to be 31.4% (95% CI -30.1, 143.6). When variables other than body weight and waist circumference were considered, % mediation was 46.0% (95% CI -6.0, 161.0). Conclusions Mediation analyses could not fully ascribe the effects of semaglutide on MACE to known risk factors in SELECT with any certainty. Further investigation of potential additional biomarkers and mediators of semaglutide's cardiovascular protective effect are of interest. [GRAPHICS] .
Background and Aims A major component of long QT syndrome (LQTS) is LQT2 due to pathogenic variants in KCNH2, which frequently cause trafficking defects. Despite progress in therapeutic management, there is an unmet clinical need for mechanism-targeted therapies. It has been previously shown, using patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), that lumacaftor (LUM), currently used for cystic fibrosis, can partially correct hERG trafficking. A single-arm phase 2 study was conducted to determine whether LUM could shorten QTc in LQT2 patients with trafficking defects. Methods Sixteen adult patients with genetically confirmed trafficking-defective KCNH2 variants were enrolled. Participants were admitted to hospital and received LUM for 7 days under continuous telemetry. QTc was quantified on serial electrocardiograms and 12-lead Holter recordings. For mechanistic correlation, hiPSC-CMs were generated from the first five participants with distinct genetic variants and assessed for hERG maturation and trafficking. Results Overall, lumacaftor produced a significant QTc shortening (P < .001). The per-patient change averaged 31 +/- 21 ms. Patients with baseline QTc >= 500 ms exhibited the most substantial effect, with 75% achieving reductions >= 40 ms. No ventricular arrhythmias occurred, and adverse effects were primarily gastrointestinal and self-limited. In hiPSC-CMs, LUM restored hERG trafficking in three out of five variants, mirroring the clinical observations. Conclusions Short-term LUM therapy is safe and yields a significant QTc shortening in LQT2 patients with a trafficking defect. Concordance between cellular and clinical findings reinforces the value of a mechanism-based, variant-informed approach and supports the feasibility of trafficking-correction strategies within a precision-medicine framework for inherited arrhythmia syndromes.
