Atherosclerosis

Micro- and nanoplastics (MNPs) are increasingly detected in human tissues, yet their causal contribution to cardiovascular disease remains poorly understood. Here we show that oral exposure to polyethylene (PE) and polyvinyl chloride (PVC) -- the most abundant polymers found in human atheromas -- accelerates atherosclerosis in ApoE-/-mice through distinct, polymer-specific molecular mechanisms. While both polymers increased plaque burden and reduced contractile smooth muscle cell (SMC) markers, ...

BackgroundCarbohydrate-restricted diets are gaining popularity, including among lean individuals. In these populations, a lipid phenotype often emerges comprising elevated LDL cholesterol (LDL-C), alongside elevated HDL-C and low triglycerides, termed the lean mass hyper-responder (LMHR). ObjectiveTo evaluate one-year coronary plaque progression in LMHRs and near-LMHRs. MethodsThis prospective study followed 100 participants who developed the triad of high LDL-C, high HDL-C, and low triglyceri...

BackgroundThe comparative roles of triglyceride-rich lipoproteins (TRLs) and low-density lipoproteins (LDLs) in abdominal aortic aneurysm (AAA) pathogenesis are unclear. ObjectivesTo evaluate the putative causal role of TRLs in AAA, quantify the relative effect on AAA risk ("aneurysmogenicity") of TRL vs LDL particles, and prioritize lipid-lowering drug targets for AAA prevention and treatment. MethodsWe performed summary-level and individual-level Mendelian randomization (MR) analyses. Geneti...

Apolipoprotein B (apoB) has emerged as a more accurate predictor of coronary artery disease risk relative to standard lipid measurements like low-density lipoprotein cholesterol (LDL-C). Here, we sought to characterize the clinical associations and genetics underlying apoB and LDL-C discordance. We derived a residualized-apoB phenotype, defined as observed minus expected apoB for an individual given their LDL-C level, in 239,144 individuals in the UK and Mass General Brigham Biobanks. Higher res...

BackgroundPlatelet morphological indices, such as mean platelet volume and distribution width, reflect platelet turnover and thrombo-inflammatory activity relevant to acute coronary syndrome (ACS), but their individual prognostic value remains inconsistent. This study aimed to derive an Integrated Platelet Index (IPI) using principal component analysis (PCA) to capture a multidimensional platelet morphological phenotype influenced by cardiometabolic and inflammatory stress and to examine its ass...

BackgroundThe pathways linking lipoprotein(a) (Lp[a]) to atherosclerotic cardiovascular disease (ASCVD) are unclear. This study aimed to discover Lp(a)-associated plasma proteins and estimate their associations with incident ASCVD. MethodsWe analyzed 48,859 UK Biobank participants with measured Lp(a) and proteomic profiles, with replication in 9,416 individuals in the Atherosclerosis Risk in Communities (ARIC) study cohort utilizing a separate proteomic platform. Linear models assessed associat...

BackgroundScreening criteria for abdominal aortic aneurysm (AAA) are based on clinical factors, such as age and smoking history, but do not include biological factors that may better reflect disease pathogenesis. ObjectivesWe sought to determine whether a proteomic risk score (ProRS) incorporating plasma protein abundance could improve prediction of AAA. MethodsWe performed a cross-sectional analysis of nearly 37,000 participants in the UK Biobank Pharma Proteomics Project with plasma protein ...

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease. Despite available lipid-lowering therapies (LLT), lipid control remains suboptimal. Bempedoic acid offers a non-statin oral treatment for hypercholesterolemia. However, real-world data in Asia are limited. The study aimed to investigate the effectiveness and safety of bempedoic acid in Taiwan. MethodsThis pragmatic phase IV study enrolled 180 patients with inadequately controlled hypercho...

BackgroundHDL particles can carry microRNAs (miRNAs), capable of regulating gene expression connected to HDL functions. Despite links to some cardiovascular risk factors, miRNA association with incident acute myocardial infarction (AMI) remains unclear. ObjectivesOur aim was to elucidate the association between HDL-bound miRNAs (HDL-miRNAs) and incident AMI using a non-targeted approach in a population-based study. MethodsWe conducted a case-cohort study including 247 participants from the REG...

BackgroundEvolocumab promotes coronary plaque regression in patients with coronary artery disease, but little is known regarding carotid plaques (CP). This study aimed to evaluate the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) compared to lipid-lowering therapy (LLT) alone. MethodsAsymptomatic patients with internal carotid stenosis[≥]50% and LDL-C[≥]100 mg/dL were randomized to ELLT or LLT and monito...

BackgroundCardiovascular-Kidney-Metabolic (CKM) syndrome is a progressive spectrum where patients often struggle with daily exercise. The "Weekend Warrior" (WW) pattern offers a flexible alternative, but its efficacy across CKM stages remains unclear. We evaluated the association of accelerometer-derived WW activity with cardiovascular outcomes across CKM Stages 0-3. MethodsThis prospective study included 88,832 UK Biobank participants (CKM Stages 0-3). Physical activity was objectively measure...

Background/ObjectivesCoronary artery disease (CAD) remains the leading cause of mortality worldwide, with South Asia bearing a disproportionately high and rising burden, particularly at younger ages. This pilot study aimed to investigate genetic variants associated with premature coronary artery disease (PCAD) using whole genome sequencing (WGS). MethodsWGS was conducted on 12 people (5 PCAD cases, 7 matched controls) to assess feasibility and methodology for future large-scale research. High-q...

BackgroundClonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) in the general population and is more common among people with HIV (PWH). The mechanisms by which CHIP contributes to atherosclerosis in PWH are unknown. We hypothesized that CHIP is associated with carotid atherosclerosis, arterial inflammation, and hematopoietic activity among PWH. MethodsIn a cohort study, we studied PWH ages 31-74 years. CHIP mutations were detected with a valida...

BackgroundChronic inflammation predicts adverse cardiovascular outcomes, but mechanisms linking systemic inflammation to cardiac remodeling remain incompletely understood. We investigated associations between circulating inflammatory biomarkers and cardiac phenotypes in a population-based cohort and examined how environmental exposures and genetic susceptibility influence inflammatory responses. MethodsWe analyzed subsets of 488,079 UK Biobank participants with metabolomic and proteomic profili...

BackgroundEpigenetic mechanism underlying susceptibility to abdominal aortic aneurysm (AAA) remain poorly understood. Identifying causal DNA methylation markers for AAA can elucidate the regulatory processes that drive aneurysm formation and would accelerate translational applications. We leveraged the VA Million Veteran Program (MVP) to identify methylation biomarkers and delineate underlying pathways. MethodsWe first conducted an epigenome-wide association study (EWAS) of incident AAA (1,324 ...

BackgroundArterial calcification is increasingly recognized as a deep-rooted biological process, observed not only in modern patients but also in ancient human remains. While atherosclerosis has been widely studied, medial arterial calcification (MAC), a distinct entity associated with chronic kidney disease (CKD), diabetes, and aging, remains largely unexplored in early populations. This gap limits our understanding of MACs historical prevalence and etiologic drivers. During a paleopathological...

ObjectiveDiabetes mellitus (DM) approximately doubles the risk of atherosclerotic cardiovascular disease (ASCVD) events, but the molecular basis is poorly understood. We aimed to define arterial differentially expressed genes (DEGs) associated with DM, validate hits as plasma proteins, and ascertain whether these complement ASCVD risk prediction tools. Research design and methodsRNA-sequencing data from the Genotype-Tissue Expression (GTEx) cohort was used to define DEGs associated with DM in t...

BackgroundSex hormone alterations, such as estrogen deficiency or testosterone excess, substantially increase cardiovascular disease (CVD) risk in females. Dietary fibre and its microbial by-products, short-chain fatty acids (SCFAs), have cardioprotective effects, but it remains unclear whether these benefits extend to females with an altered sex hormone profile. In this study, we aim to investigate whether dietary fibre intake, measured via plasma acetate--the most abundant SCFA--is associated ...

ImportanceGenetic factors only explain [~]50% of an individuals lifetime CAD risk. Workplace pollution exposure likely represents a significant, under-recognized, and modifiable contributor. Clarifying its independent effect - distinct from residential air pollution - could inform targeted prevention, clinical risk assessment, and policy strategies. ObjectiveTo quantify the independent association between workplace pollution exposure and incident CAD, rigorously adjusting for canonical risk fac...

BackgroundPatients with myocardial infarction (MI) often exhibit neuropsychiatric symptoms, but the underlying pathophysiological mechanisms remain elusive. This study examines the roles of the tryptophan catabolite (TRYCAT) pathway, systemic inflammation, and adverse metabolic remodeling in this comorbidity, both before and after percutaneous coronary intervention (PCI). MethodsWe assessed depression, anxiety, and chronic-fatigue syndrome (CFS)-like rating scales, blood levels of TRYCATs, infl...