Atherosclerosis

BACKGROUND: Coronary artery disease (CAD) and Impaired Cognitive (IC) disease share sociodemographic, genetic, and clinical factors, but the association of IC with statin use in CAD remains unclear. OBJECTIVES: To determine the association between IC and statin use in CAD based on APO (e) genotype, sex, and lipid levels. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective study of AllofUS (AoU) participants with CAD (Age [&ge;]60 yrs) enrolled from 2017 to 2023. We defined CAD as having a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC defined as mild cognitive impairment or all cause dementia, using ICD/SNOMED codes. MEASURES: We assessed the association between IC and statin use using logistic regression analysis, while adjusting for clinical factors, sociodemographics, and APO (e) genotypes before and after propensity score matching. We further performed stratified analysis by sex, and APO (e) genotypes. We finally assessed the association between IC and statin users, based magnitude on the change in lipid levels before CAD and after IC (TC: Total cholesterol, LDL: low density lipoprotein, HDL: High Density Lipoprotein). Significance was defined at p < 0.05. RESULTS: The cohort included 22,089 participants with CAD and 1343 with IC. Thirty-nine percent of participants were females, 77% were European, 13% were African American, and 9% were of Admixed American ancestry. The proportion of IC was higher (6.8% vs 3.5%, p<0.001) in statin users (n=17,191) vs non-statin users (n=4,898). IC was significantly associated with statin use (OR:1.70;1.40-2.10, p = 4.9e-7) after adjustment for clinical factors, sociodemographics, and APO (e) genotypes. After propensity-score matching between IC and CAD, we observed an association between IC and statin use (OR:1.55;1.24-1.94, p =1e-4). In stratified analysis, the association between IC and statin use was strongest in the APO e3/e3 group (OR:2.04;1.53-2.75, p = 1e-6), and in females (OR:2.20;1.60-3.06, p = 2.e-6) compared to males (OR:1.43;1.10-1.90, p = 0.01). We finally observed an increased magnitude of association between IC and statin users having higher HDL increase (> 10 mg/dl: OR:1.95;1.44-2.66, p=1e-5) as compared to statin users with lesser HDL increase (<=; 10mg/dl: OR:1.61;1.22-2.15, p=8e-4). CONCLUSION: In the AllofUS cohort, IC was significantly associated with statin use in CAD participants. We observed the strongest association in the APO e3/e3 group, among females, and with a greater increase in HDL levels in statin users.

Background: Treatment decisions for carotid atherosclerotic disease rely primarily on luminal stenosis, although plaque vulnerability and symptomatic status better reflect short-term cerebrovascular risk. A scalable CTA tool for automated phenotyping of symptomatic carotid disease is lacking. Materials & Methods: In this multi-institutional retrospective study, 689 patients (mean age, 67.9 {+/-} 7.7 years; 366 men) from four hospitals were analyzed after screening 705 CTA examinations. 423 patients from one center were used for five-fold development and internal validation, and 266 patients from three centers for independent external validation. CarotidMamba, a deep learning framework combining dual foundation-model encoders with Mamba-based sequence modeling, was developed and benchmarked against clinical, radiomics, clinic-radiomics, CNN, and transformer comparators. Results: In the development cohort, CarotidMamba achieved an AUC of 0.839 (95% CI, 0.799-0.879) and accuracy of 0.825 (95% CI, 0.793-0.857), outperforming the strongest comparator by 0.066 and 0.050, respectively. External validation yielded AUCs of 0.897 (95% CI, 0.835-0.959) in YCH, 0.809 (95% CI, 0.720-0.898) in DCH, and 0.762 (95% CI, 0.649-0.875) in GH-NTC. CarotidMamba showed the lowest Brier score and expected calibration error across cohorts, with calibration slopes near 1.0. Conclusion: CarotidMamba provides an interpretable, clinically oriented, and externally validated CTA framework for phenotyping symptomatic carotid plaques, supporting vulnerability-aware imaging assessment beyond stenosis alone.

Aims This multicenter study aims to compare outcomes of total aortic arch replacement (TAR) using the frozen elephant trunk (FET) technique in patients with and without heritable thoracic aortic disease (HTAD) and to assess whether HTAD influences postprocedural adverse aortic events (AAEs). Methods From 06/2007 to 05/2024, aortic databases from 13 European centers were screened for HTAD patients undergoing TAR with FET. All consecutive dissection and aneurysm non-HTAD patients from the four core centers served as comparator. The primary outcome was AAE, a composite of diameter progression, distal stent graft induced new entry (dSINE), malperfusion, rupture and pseudoaneurysm at 5 years after FET implantation. Results Of 2739 FET patients, 196 (7.2%) were diagnosed with HTAD. The control group consisted of 867 non-HTAD FET patients. Marfan syndrome was the most common condition (72%), followed by Loeys-Dietz syndrome (11%), vascular Ehlers-Danlos syndrome (5.6%) and Turner syndrome (2.0%). Seventeen (8.8%) patients were diagnosed with ns-HTAD. At 5 years 46 (24%) AAEs occurred in the HTAD group, 169 (20%) in the non-HTAD group (p=0.2). Diameter progression was the most common event (10% vs. 12%; p=0.6), followed by dSINE (5.8% vs. 4.5%; p=0.5), malperfusion (4.2% vs. 3.3%; p=0.5), rupture (2.1% vs. 0.7%; p=0.09) and pseudoaneurysm (0.5% vs. 0.2%; p=0.5). Conclusions The FET technique appears safe and effective for acute and chronic aortic disease in HTAD patients, with outcomes comparable to non-HTAD cases and no increase in graft-related complications, challenging traditional concerns about stent graft use in genetically mediated aortic disease.

Background: Chronic low-grade inflammation drives cardiovascular-kidney-metabolic (CKM) syndrome. Clonal hematopoiesis of indeterminate potential (CHIP), an age-related driver of systemic inflammation, is linked to several cardiometabolic disorders. However, whether CHIP modifies CKM progression and contributes to heterogeneity in cardiovascular disease (CVD) risk within the CKM framework remains uninvestigated. Methods: This cohort study included 307,025 UK Biobank participants at CKM stages 0-3 free of baseline CVD. CHIP status was identified via whole-exome sequencing (WES). The association between CHIP and baseline CKM severity was examined, along with the independent and joint effects of CHIP and CKM stages on incident CVD risk. The joint effects of CHIP and polygenic risk scores (PRS) were further assessed, and the incremental predictive value of incorporating CHIP into the AHA PREVENT equations was evaluated. Results: CHIP carriers were more likely to present with advanced CKM stages [OR 1.14 (1.09-1.20), P < 0.001] and exhibited higher incident CVD risk during follow-up [HR 1.13 (1.08-1.18), P < 0.001]. Significant joint effects between CHIP and CKM stages were observed, with the highest risk among CHIP carriers at CKM stage 3 [HR 1.63 (1.50-1.78), P < 0.001]. Large or multiple CHIP mutations conferred greater hazards, with distinct gene-specific effects observed. Moreover, CHIP and high genetic risk also jointly amplified CVD susceptibility. Most importantly, incorporating CHIP into AHA PREVENT significantly improved risk discrimination. Conclusions: CHIP is a significant risk factor associated with more advanced CKM stages and amplifies incident CVD risk. Integrating CHIP into existing prevention strategies may refine CVD risk stratification.

Background and Purpose: Hemorrhagic transformation (HT) is a serious complication of endovascular thrombectomy (EVT), yet dedicated prediction models for young adults are lacking. We aimed to develop and externally validate a simplified risk score for HT in young adults with acute ischemic stroke undergoing EVT. Methods: This multicenter retrospective study included patients aged 18 to 49 years with acute anterior circulation large vessel occlusion who underwent EVT. The primary outcome was any HT within 24 hours after EVT. Multivariable logistic regression was used to identify independent predictors of HT, from which the NO?PAIN Score was derived. External validation was performed in an independent cohort of 138 patients. Results: Among 598 patients in the derivation cohort, HT occurred in 176 (29.4%). Five independent predictors were identified: admission NIHSS, number of thrombectomy passes, atrial fibrillation, alcohol consumption, and mTICI grade. The mTICI grade demonstrated a non-linear, inverted U-shaped relationship with HT risk, peaking at partial recanalization. The NO-PAIN Score showed acceptable discrimination in both the derivation (C-index, 0.737; optimism-corrected C-index, 0.748) and external validation cohorts (C-index, 0.726), with satisfactory calibration. Conclusions: The NO-PAIN Score is a simple risk prediction tool for HT after EVT in young adults with acute anterior circulation large vessel occlusion. It may assist in individualized risk stratification in this population.

Background: In atrial fibrillation (AF), cerebral microbleed (CMB) burden guides anticoagulation decisions, yet AF is itself inconsistently associated with CMBs, a paradox unexplained by frameworks that treat CMBs as a unitary marker of small vessel disease. We hypothesized that the white matter hyperintensity (WMH) context in which CMBs arise modifies their vascular meaning, and that this context-dependence underlies the inconsistent AF-CMB association. Methods: From a multicenter Korean stroke registry, we analyzed 5,735 first-ever ischemic stroke patients imaged at nine centers using susceptibility-weighted MRI. WMH volume and CMB count were extracted by validated deep learning pipelines. Patients were cross-classified by age-adjusted WMH residual (median split) and CMB count (2) into four groups. The AF-CMB association was estimated by multivariable logistic regression within each WMH stratum with formal interaction testing. Spatial CMB distribution was analyzed against the Automated Anatomical Labeling atlas. Results: In the full cohort (mean age 69.5 years; 57.7% male), AF was not associated with CMBs (OR 1.04; 95% CI 0.87-1.25). Stratification yielded divergent estimates: the adjusted AF OR was 1.46 (1.11-1.93; P = 0.007) in the WMH-low stratum and 0.95 (0.73-1.22; P = 0.665) in the WMH-high stratum, with significant interaction (OR 0.56; P < 0.001). The discordant phenotype (low WMH, high CMB; 8.9%) was enriched for AF (28.0%) and showed fronto-temporal cortical predominance with deep structure sparing. AF independently reduced the proportion of deep CMBs (IRR 0.80; P = 0.040). The interaction was preserved across prespecified sensitivity analyses. Conclusions: The AF-CMB association is confined to patients with low WMH burden relative to age and is accompanied by a topographically distinct CMB distribution. Clinical assessment of small vessel disease based on WMH alone may overlook a CMB phenotype linked to AF.

Introduction: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality, and low-dose aspirin (LDA) prophylaxis is the cornerstone of evidence-based prevention. Despite guideline recommendations, LDA adherence remains poor, with 10-25% of moderate-risk patients taking aspirin. Objective personalized risk stratification using biomarkers has been shown to motivate behavior change in other disease contexts. Survey data suggest that patients are more motivated to take aspirin if informed by an objective predictive test. Here, we report real-world LDA adherence among patients who received a high-risk result from a cell-free RNA (cfRNA) PE risk prediction test. Methods: This retrospective, observational survey study included asymptomatic patients of advanced maternal age (AMA; [&ge;] 35 years at delivery) with singleton pregnancies without USPSTF-defined preexisting high-risk conditions for PE who received the cfRNA PE risk prediction test. Patients who opted in to receive text message surveys were asked about LDA use following receipt of test results. High adherence was defined as reporting LDA use on at least 6 of 7 days per week at least 85% of the time surveyed. The primary analysis included patients with a high-risk test result and at least one LDA frequency survey response following receipt of test result. The observed proportion of adherent patients was compared to a baseline estimate of 25% using an exact binomial test. Results: Of 166 patients who received a cfRNA PE risk prediction test result, 48 (28.9%) received a high-risk result. Of these, 29 (60%) opted in and responded to at least one survey, constituting the primary analysis population. Twenty-seven of the 29 (93.1%; 95% CI: 78.0-98.1%) were classified as highly adherent, significantly higher than the 25% baseline adherence estimate for moderate-risk patients (p < 0.0001). Conclusion: Among surveyed patients who received a high-risk cfRNA PE test result, the proportion classified as highly adherent to LDA (93%) substantially exceeded published estimates of adherence in a similar patient population and met the clinically meaningful threshold of [&ge;] 80% associated with reduced risk of preterm preeclampsia. These findings indicate that objective and personalized biomarker risk testing may be a powerful driver of behavior change that current guidelines have failed to produce.

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.

Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefit in type 2 diabetes and obesity, with recent observational data suggesting favorable associations after transcatheter aortic valve replacement. Whether similar associations exist after surgical aortic valve replacement (SAVR) is unknown. Methods: Retrospective propensity-matched cohort analysis using the TriNetX U.S. Collaborative Network. Adults with type 2 diabetes or obesity (BMI [&ge;]30 kg/m2) undergoing SAVR were categorized by GLP-1 RA exposure (any use within 3 months before through 1 year after SAVR) versus no use. One-to-one matching was performed on 44 covariates. Primary outcomes were 1-year all-cause mortality, heart failure, acute kidney injury, acute myocardial infarction, cerebral infarction, and atrial fibrillation. Sensitivity analyses included 30-day landmark restriction and falsification outcomes. Results: After matching, 1,984 patients were retained per cohort. GLP-1 RA use was associated with lower 1-year risks of all-cause mortality (4.8% vs 10.4%; HR, 0.44; 95% CI, 0.34-0.56), acute kidney injury (6.9% vs 10.1%; HR, 0.65; 95% CI, 0.49-0.85), myocardial infarction (3.0% vs 5.1%; HR, 0.57; 95% CI, (0.40-0.82), heart failure (11.3% vs 15.7%; HR, 0.68; 95% CI, (0.51-0.90), and atrial fibrillation or flutter (10.1% vs 13.9%; HR, 0.69; 95% CI, 0.54-0.90; all P[&le;]006). Cerebral infarction did not differ. In landmark analysis, mortality, heart failure, and acute kidney injury associations persisted; myocardial infarction and atrial fibrillation associations were attenuated. Falsification outcomes were null. Conclusions: Perioperative GLP-1 RA use was associated with lower 1-year cardiovascular event rates after SAVR. These hypothesis-generating findings support prospective randomized investigation.

Although the Y chromosome represents roughly 2% of the male genome, it is often ignored in genome-wide association studies (GWAS). Subsequently, the potential health impacts of Y-chromosomal genetic variation remain incompletely understood. To fill this gap, we performed a phenome-wide association study (PheWAS) in FinnGen across 1,426 binary and quantitative traits using Y-chromosomal variation (frequency [&ge;] 1%) in 104,334 genotyped men. As Y chromosome variation is prone to population stratification, we performed carefully adjusted association analyses and further examined these through kin-based validation in 19,275 female and 24,712 male 1st degree relatives. We found 121 suggestive (p < 5.6x10-3) phenotypic associations in the Y chromosome, yet none of these were strong enough to reach phenome-wide significance (p < 3.9x10-6). While only 38 associations were supported in the kin-based validation, intriguingly we found support for a previously suggested link between haplogroup I1 and coronary heart disease (CHD; OR=1.06, 95%CI=1.02-1.11, p=3.7x10-3; male validation OR=1.05; female validation OR=0.97). The I1-CHD association was detected across distinct geographical areas within Finland and was independent from Loss of Y (LOY) and the autosomal risk to CHD, proposing a link between germline Y-chromosomal variation and heart disease risk. Overall, this study presents a comprehensive phenome-wide analysis of Y-chromosomal associations, highlighting the potential relevance of Y-chromosomal variation beyond sex determination. Our findings further emphasize the need for improved capture of Y-chromosomal variants and further analyses in biobank-scale data to allow for deeper exploration of male-specific genetic architecture of complex diseases.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome is a leading driver of cardiovascular morbidity and mortality. Whole-body molecular imaging is well-positioned to phenotype such syndromes, yet no imaging biomarker quantifies cumulative CKM burden. Bone scintigraphy with 99mTc-labeled bisphosphonates is widely performed and expanding with transthyretin amyloidosis assessment, under which Perugini grade 0 (absent cardiac uptake) is considered clinically benign. Objective: We hypothesized that the soft tissue-to-bone ratio (STBR) on these scans captures CKM burden and is an independent prognostic biomarker. Methods: We retrospectively analyzed 8,769 consecutive patients without cardiac uptake on 99mTc-DPD whole-body planar scintigraphy. The primary endpoint was all-cause mortality. Secondary endpoints were major adverse cardiovascular events (MACE) and heart failure hospitalization. Cox models were adjusted for ten established cardiovascular risk factors. Imaging-phenotype association (IPA) analysis mapped STBR to 1,210 clinical traits. STBR distribution across CKM stages was assessed in four prespecified analyses, including a non-cancer subgroup. Results: During a median follow-up of 5.1 years (IQR 2.5-8.2), 2,418 deaths occurred. Patients with prespecified STBR >0.5 (n=772, 8.8%) had significantly higher mortality (adjHR 1.73, 95% CI 1.54-1.94, p<0.0001) with an adjHR of up to 3.42 at higher thresholds (95% CI 2.05-5.42, p<0.0001). Hazard increased monotonically with STBR. STBR >0.5 was independently associated with MACE (adjHR 1.51, 95% CI 1.11-2.05, p=0.008) and heart failure hospitalization (adjHR 1.31, 95% CI 1.02-1.67, p=0.03). The association was robust across all prespecified subgroups and sensitivity analyses, including continuous STBR and patients without renal insufficiency. IPA analysis identified significant associations with type 2 diabetes, chronic kidney disease, chronic ischaemic heart disease, heart failure, atrial fibrillation, liver disease, amyloidosis, and hypertension among binary traits, as well as with CRP, NT-proBNP, BUN, cholesterol (inverse), and hemoglobin (inverse) among continuous parameters. STBR increased monotonically across CKM stages in all sensitivity analyses (all p<0.0001). Conclusions: STBR derived from routine 99mTc-DPD bone scintigraphy in patients without cardiac uptake is an independent prognostic imaging biomarker associated with cumulative cardiovascular-kidney-metabolic burden. As an opportunistic measure from scans already acquired at scale, STBR could refine CKM risk stratification at no additional cost, radiation, or acquisition time.

Background. Blood-based biomarkers are increasingly proposed for identifying high-risk individuals before clinical disease and for making prevention-oriented trials more efficient. Prognostic enrichment can increase event rates, but trial efficiency also depends on whether the intervention effect is preserved in the enriched population. Methods. Using the UK Biobank Pharma Proteomics Project, we trained disease-specific proteomic risk scores (ProRS) from 2,916 plasma proteins with elastic-net Cox models. We compared ProRS, polygenic risk scores (PRS), and combined PRS--ProRS scores across ten incident diseases. We estimated cumulative incidence and theoretical two-arm time-to-event trial sample sizes across risk strata. To evaluate effect preservation, we examined six intervention-analogue exposure--outcome pairs spanning genetic (PCSK9/coronary artery disease, APOE/Alzheimer's disease, PPARG/type 2 diabetes, IL23R/Crohn's disease), behavioural (physical activity/all-cause mortality), and pharmacological (RAAS inhibitors versus calcium channel blockers/coronary artery disease) examples. Results. ProRS outperformed PRS for 9 of 10 diseases (median C-index 0.75 versus 0.61). ProRS and PRS were weakly correlated (median Pearson |r| = 0.04), and joint PRS--ProRS stratification identified groups with higher observed incidence than either score alone for several endpoints. In the top risk quartile, combined-score enrichment reduced theoretical required sample sizes by 32--74\% under a fixed 20\% relative hazard reduction. These gains were not always preserved when stratum-specific intervention-analogue effects were used. Effects were broadly preserved for APOE/Alzheimer's disease and physical activity/mortality. The PPARG/type 2 diabetes effect attenuated toward the null under all three score types, showing that event-rate enrichment does not guarantee effect preservation. For IL23R/Crohn's disease and the antihypertensive comparison, point estimates differed across score types -- preserved under polygenic but attenuated under proteomic enrichment -- but confidence intervals were wide and overlapping. Conclusions. Proteomic risk scores can identify high-event-rate populations for prevention-oriented trials, but event-rate enrichment alone is insufficient for trial design. Biomarker-guided enrichment should evaluate mechanism-specific effect preservation and may be preferable as a stratification or adaptive-design variable rather than as a restrictive eligibility criterion.

Background Totally endoscopic aortic root (AR) surgery via right anterior minithoracotomy (RAMT) may reduce surgical trauma and accelerate recovery compared with full sternotomy (FS). However, the approach is technically demanding due to limited access and anatomical complexity. This study compares early clinical outcomes and quality of life (QoL) after RAMT versus FS to evaluate the feasibility and safety of the totally endoscopic approach. Methods This single-center, retrospective study included 149 patients underwent AR surgery via RAMT (n=74) or FS (n=75) between January 2021 and March 2026. Patients with aortic dissection, infective endocarditis, redo surgery, concomitant procedures, or arch replacement were excluded. Operative outcomes, postoperative recovery, 30-day and 1-year mortality were analyzed. QoL was assessed using the Short Form-8 (SF-8) questionnaire. Results The median age was 60.0 years, and 79.9% of patients were male. Bentall procedure was performed in 84.6% of patients, 15.4% underwent a David procedure. Compared with FS-AR, RAMT-AR was associated with shorter median operative time (147.0 vs. 178.0 min; p<0.001), lower median chest drainage volume (650.0 vs. 850.0 mL; p<0.001), and shorter median ICU stay (24.0 vs. 25.0 h; p=0.008) and hospital stay (6.0 vs. 8.0 days; p=0.028). Overall, 30-day and 1-year mortality was 0.7%. SF-8 analysis demonstrated significantly higher physical and mental component scores in RAMT-AR patients. Conclusion In specialized centers, totally endoscopic AR surgery via RAMT is a safe and feasible minimally invasive approach associated with favorable early outcomes and a potential benefit in postoperative physical and mental QoL by reducing surgical trauma.

Cardiovascular diseases (CVDs) are highly heritable, but pathogenesis at the organ and physiological level is still poorly defined. Polygenic risk scores (PRSs), which estimate individual genetic susceptibility to a disease, may allow for the identification of associated abnormal organ structures. Ultimately, identifying where cardiovascular polygenic risk manifests can guide early interventions, shape mechanistic hypotheses, and motivate prevention trials for cardiac remodelling. This study investigated the association between PRSs for five common CVDs [heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), abdominal aortic aneurysm (AAA) and ischaemic stroke (IS)] and 28 imaging-derived phenotypes (IDPs) from cardiac magnetic resonance imaging of ~62,000 participants in UK Biobank. To investigate the cardiac features associated with elevated polygenic risk of CVDs, we tested CVD PRSs against cardiac IDPs and identified 97 significant associations (FDR [&le;] 0.05). We further identified 32 significant putative mediators between CVD PRSs and incident disease events, revealing that across CVDs, polygenic risk manifested as distinct patterns in cardiac structures. HF implicated all cardiac chambers, including left ventricular and left atrial dysfunction alongside enlarged aorta. AF was characterised by biatrial enlargement and reduced ejection fractions, most prominently in the left atrium but also involving left ventricular wall thickness. IS exhibited left ventricular hypertrophy and left atrial dysfunction, while CAD predominantly involved left ventricular hypertrophy. AAA was primarily characterised by enlarged descending aorta. Overall, cardiac IDPs mediated a substantial proportion of polygenic risk for CVDs, in particular for HF. Taken together, our results show that cardiac structure and function lie on the pathway between polygenic risk and cardiovascular events.

Abstract Background Peripheral artery disease (PAD) is a major contributor to morbidity and mortality, particularly among individuals with diabetes mellitus (DM), in whom its prevalence is markedly increased. PAD is often asymptomatic and under-diagnosed, especially in low-resource settings. This study aimed to determine the prevalence of PAD and associated factors among adults with DM in Eastern Uganda. Methods We conducted a hospital-based cross-sectional study at Mbale Regional Referral Hospital from 10th/12/ 2024 to 30th/4/2025. A total of 300 adult patients with DM were consecutively enrolled. Data on sociodemographic characteristics, clinical characteristics, comorbidities, and behavioural risk factors were collected using an interviewer-administered data tool. PAD was assessed using the ankle-brachial index (ABI), defined as [&le;] 0.90. Modified Poisson regression was used to identify factors associated with PAD. As a secondary measure for PAD, we administered the Edinburgh Claudication Questionnaire (ECQ) to capture symptomatic PAD. Results The majority of the participants had a low fruit intake (68%), physical inactivity (54%), and elevated low-density lipoprotein (60%). The prevalence of PAD as measured by ABI was 42.3% (127/300; 95% CI 0.38-0.48), while the magnitude of PAD as measured by ECQ, combining participants with possible claudication and definite claudication was 37.3% 95% CI 31.9 - 42.8). Out of participants with PAD, 15.8% (20/127) were classified as having severe PAD (ABI <0.4). Socio-demographic and clinical factors were assessed for association with PAD. We found no evidence of association between the examined factors such as age (aPR 1.24 95% CI 0.73 - 2.09), sex (aPR 1.46 95% CI 0.84 - 2.55), cholesterol level (aPR 1.39 95% CI 0.86 - 2.25), glycemic control (aPR 1.35 95% CI 0.72 - 2.53), and sedentary behaviour (aPR 1.28 95% CI 0.79-2.08) and PAD. Conclusion The prevalence of PAD was high among adults with DM in Eastern Uganda. Routine health education, and ABI screening of PAD should be done for patients living with DM. The absence of significant associations despite high prevalence of PAD may reflect unmeasured factors e.g. chronic inflammation that may be unique to this population, future prospective studies with larger sample size and more detailed objective measures e.g. inflammatory markers are needed to determine locally relevant modifiable risk factors.

Background: Two-thirds of Dutch cardiovascular risk management (CVRM) for patients at risk of cardiovascular disease is delivered in primary care practices. While individual risk scores are increasingly used during consultation, a population-level structure for risk-based patient outreach is not currently available. We therefore developed the PROSPERA programme, a multilevel intervention comprising population-level risk stratification and individual-level support tools. Aim: To assess anticipated and experienced barriers and facilitators among healthcare professionals (HCPs) to inform implementation in primary care. Methods: We conducted four focus groups and six interviews with nine primary care HCPs to explore anticipated and experienced barriers and facilitators. Inductive codes were thematically analysed and assigned to corresponding domains of the Theoretical Domains Framework (TDF) and the related Capability, Opportunity, Motivation model of Behaviour. Results: Barriers and facilitators were identified in 11 TDF domains. Population-level barriers included altered professional roles and limitations in technological infrastructure. Individual-level barriers were limited skills in interpreting risk calculations and difficulty integrating tools into clinical routine. Facilitators were related to beliefs on the importance of providing proactive care (population level), the use of U-Prevent for risk communication (individual level) and positive patient responses to the Lifestylecheck questionnaire (individual level). Conclusion: Addressing barriers and facilitators identified at both the population and individual levels can support implementation of the PROSPERA programme. Opportunities exist in education and training of HCPs in risk communication, as well as support in restructuring the physical and digital environment.

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: The manifestations of cardiovascular disease (CVD) among people with HIV (PWH) differ by region globally. While HIV disease is associated with increased atherosclerotic CVD risk in the global North, non-ischemic heart failure (HF) is more common in sub-Saharan Africa, the global HIV epicenter. We estimated the effect of treated HIV on the frequency and phenotype of HF and its cardiac precursors in South Africa (SA). Methods: In an observational study, we recruited PWH on antiretroviral therapy (ART), age [&ge;]40 years and people without HIV (PWoH) with similar distributions of age, sex, ethnicity, and hypertension, from a community clinic in Khayelitsha (Cape Town, SA). Procedures included a clinical assessment, echocardiography (Echo), and b-type natriuretic peptide (BNP) measure. Echo parameters defined structural abnormalities, left ventricle (LV) filling pressure, and LV systolic and diastolic dysfunction (DD). HF was defined by symptoms and/or BNP [&ge;]35pg/mL and LV dysfunction, subcategorized as reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, and HFpEF). Comparisons by HIV status were adjusted for age, sex, hypertension, smoking, obesity, diabetes, elevated LDL-cholesterol, and hazardous alcohol use. Results: Between September 2022 and August 2025, we enrolled 1008 PWH and 500 controls [median (Q1-Q3) age 48 years (43-53), 77% female]. Among PWH and controls respectively, 37% and 39% had hypertension, 21% and 25% were current smokers, 40% and 45% were obese, and 9% and 17% had diabetes. LV systolic dysfunction (1%) and HFrEF (1%) were rare, and undiagnosed HFpEF (8%) was the predominant HF phenotype. Compared to controls, PWH had higher odds of elevated LV mass index (LVMI) (OR 2.1; 95%CI 1.5-3.0) and DD (OR 1.4; 95%CI 1.0-2.0). Risk for elevated LVMI and DD was greatest among women with HIV, who also had an increased risk for undiagnosed HFpEF (OR 1.9; 95%CI 1.2-3.2), compared to women without HIV; effects which were not seen among men (p=0.051 for HIV*Sex interaction). Conclusions: In a peri-urban SA community with a high burden of cardiometabolic risk factors, the frequency of abnormal structural and functional cardiac precursors of HFpEF was greater amongst ART-treated PWH. This was most pronounced amongst women with HIV, who also had increased risk of undiagnosed HFpEF.

Background and Aims: MASLD has become the most prevalent chronic liver disease globally. Although MVPA and plasma fatty acids have been individually studied in relation to metabolic health, their independent and combined associations with MASLD incidence remain unclear. We aimed to investigate these associations. Methods: This study included 51,717 UK Biobank participants free of liver disease at baseline, with MVPA measured using wrist-worn accelerometers and plasma fatty acids quantified via NMR. Multivariable-adjusted Cox models and restricted cubic splines were used. Results: Over a median follow-up of 7.8 years, 472 incident cases were identified. In fully adjusted models, meeting recommended MVPA levels together with higher n-6 PUFA concentrations was associated with a 71% lower risk (HR 0.29, 95% CI 0.18-0.45). The MVPA-MASLD association was nonlinear, with risk reduction plateauing at approximately 189 minutes per week. Higher n-6 PUFA was associated with reduced risk, whereas n-3 PUFA showed no significant association. Conclusions: These findings suggest that behavioral and metabolic factors may jointly influence MASLD risk. Further studies in diverse populations are needed to confirm these associations.

This cross-sectional study aimed to examine the prevalence of alcohol use and its sociodemographic correlates among adults with cardiovascular disease (CVD). We analyzed data from two large US cohorts: the All of Us Research Program (2017-2023) and the National Health and Nutrition Examination Survey (NHANES, 1999-2016). Both CVD diagnosis and past-year alcohol consumption were self-reported. Risky drinking was defined as exceeding moderate drinking or binge drinking (All of Us), or moderate/heavy drinking (NHANES). Multivariable logistic regression was used to exam associations with sociodemographic and lifestyle factors. Among 32,788 current drinkers with CVD in the All of Us cohort, 15% exceeded moderate drinking thresholds and 26% reported binge drinking. Older age, female sex, and higher socioeconomic status were inversely associated with risky drinking, while smoking was positively associated. In NHANES, moderate drinking rose from 47.3% to 57.2% and heavy drinking from 6.7% to 7.2%. Moderate/heavy drinking was positively associated with age <65 but inversely with age [&ge;]65. Higher education and income were linked to moderate drinking, while current smoking was strongly associated with heavy drinking. These results highlight the need to integrate holistic screening for alcohol use, tobacco use, and social context into routine cardiovascular care.