Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Across hs-CRP: A Systematic Review and Meta-Analysis.

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. The relationship between Lp(a) and major adverse cardiovascular events (MACE) in the context of high-sensitivity C-reactive protein (hs-CRP) levels remains controversial due to conflicting results from previous studies.

Objectives: This systematic review and meta-analysis aimed to clarify the association between Lp(a) and risk of MACE across different hs-CRP levels in both primary and secondary prevention settings.

Polygenic Prediction of Recurrent Events After Early-Onset Myocardial Infarction.

Background: Myocardial infarction (MI) is a complex disease caused by both lifestyle and genetic factors. This study aims to investigate the predictive value of genetic risk, in addition to traditional cardiovascular risk factors, for recurrent events following early-onset MI.

Methods: The Italian Genetic Study of Early-Onset Myocardial Infarction is a cohort study enrolling patients with MI before 45 years.

The breadth and impact of the Global Lipids Genetics Consortium.

Purpose Of Review: This review highlights contributions of the Global Lipids Genetics Consortium (GLGC) in advancing the understanding of the genetic etiology of blood lipid traits, including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-HDL cholesterol. We emphasize the consortium's collaborative efforts, discoveries related to lipid and lipoprotein biology, methodological advancements, and utilization in areas extending beyond lipid research.

Recent Findings: The GLGC has identified over 923 genomic loci associated with lipid traits through genome-wide association studies (GWASs), involving more than 1.

Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction.

Cardiac diseases represent common highly morbid conditions for which molecular mechanisms remain incompletely understood. Here we report the analysis of 1,459 protein measurements in 44,313 UK Biobank participants to characterize the circulating proteome associated with incident coronary artery disease, heart failure, atrial fibrillation and aortic stenosis. Multivariable-adjusted Cox regression identified 820 protein-disease associations-including 441 proteins-at Bonferroni-adjusted P < 8.

Aladyn Individual: Bayesian Hierarchical Dynamic Genetic Modeling of Comorbidity Progression.

Early identification of high-risk individuals through the analysis of their unique disease trajectories has a strong potential to support efficient prevention and clinical management across a range of chronic conditions. In this paper we present a novel approach for dynamic modeling of the evolution of chronic disease risks over time, incorporating individual genetic predispositions. Our approach uses a hierarchical Bayesian topic model including Gaussian Processes to capture age effects.

Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease.

Importance: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD.

Objective: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations.

Deep Learning-Based Detection of Carotid Plaques Informs Cardiovascular Risk Prediction and Reveals Genetic Drivers of Atherosclerosis.

Atherosclerotic cardiovascular disease, the leading cause of global mortality, is driven by lipid accumulation and plaque formation within arterial walls. Carotid plaques, detectable via ultrasound, are a well-established marker of subclinical atherosclerosis. In this study, we trained a deep learning model to detect plaques in 177,757 carotid ultrasound images from 19,499 UK Biobank (UKB) participants (aged 47-83 years) to assess the prevalence, risk factors, prognostic significance, and genetic architecture of carotid atherosclerosis in a large population-based cohort.

Multivariate genomic analysis of 5 million people elucidates the genetic architecture of shared components of the metabolic syndrome.

Metabolic syndrome (MetS) is a complex hereditary condition comprising various metabolic traits as risk factors. Although the genetics of individual MetS components have been investigated actively through large-scale genome-wide association studies, the conjoint genetic architecture has not been fully elucidated. Here, we performed the largest multivariate genome-wide association study of MetS in Europe (n = 4,947,860) by leveraging genetic correlation between MetS components.

Proteogenomic analysis integrated with electronic health records data reveals disease-associated variants in Black Americans.

BACKGROUNDMost GWAS of plasma proteomics have focused on White individuals of European ancestry, limiting biological insight from other ancestry-enriched protein quantitative loci (pQTL).METHODSWe conducted a discovery GWAS of approximately 3,000 plasma proteins measured by the antibody-based Olink platform in 1,054 Black adults from the Jackson Heart Study (JHS) and validated our findings in the Multi-Ethnic Study of Atherosclerosis (MESA). The genetic architecture of identified pQTLs was further explored through fine mapping and admixture association analysis.

Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery: a multi-ancestry study in 10 960 individuals from 9 biobanks.

Obesity is a significant public health concern. GLP-1 receptor agonists (GLP1-RA), predominantly in use as a type 2 diabetes treatment, are a promising pharmacological approach for weight loss, while bariatric surgery (BS) remains a durable, but invasive, intervention. Despite observed heterogeneity in weight loss effects, the genetic effects on weight loss from GLP1-RA and BS have not been extensively explored in large sample sizes, and most studies have focused on differences in race and ethnicity, rather than genetic ancestry.

Improving Cardiovascular Disease Primary Prevention Treatment Thresholds in a New England Health Care System.

Background: Atherosclerotic cardiovascular disease (ASCVD) risk estimation based on the pooled cohort equation (PCE) overestimates in population-based cohorts. Whether it performs equally across disaggregated demographics in health care populations is less known.

Objectives: The purpose of the study was to recalibrate PCE and rederive prevention thresholds in a contemporary health care system and evaluate its performance across sociodemographics.

Long-term longitudinal analysis of 4,187 participants reveals insights into determinants of clonal hematopoiesis.

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CHIP is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years.

Integration of observational and causal evidence for the association between adiposity and 17 gastrointestinal outcomes: An umbrella review and meta-analysis.

We systematically reviewed observational and Mendelian randomization (MR) articles that evaluated the association between obesity and 17 gastrointestinal (GI) diseases to integrate causal and observational evidence. A total of 594 observational studies from 26 systematic reviews and meta-analyses and nine MR articles were included. For every 5 kg/m increase in body mass index (BMI), there was an increased risk of GI diseases ranging from 2% for rectal cancer (relative risk [RR]: 1.

Colchicine prevents accelerated atherosclerosis in TET2-mutant clonal haematopoiesis.

Background And Aims: Somatic mutations in the TET2 gene that lead to clonal haematopoiesis (CH) are associated with accelerated atherosclerosis development in mice and a higher risk of atherosclerotic disease in humans. Mechanistically, these observations have been linked to exacerbated vascular inflammation. This study aimed to evaluate whether colchicine, a widely available and inexpensive anti-inflammatory drug, prevents the accelerated atherosclerosis associated with TET2-mutant CH.

Instability of high polygenic risk classification and mitigation by integrative scoring.

Polygenic risk scores (PRS) continue to improve with novel methods and expanding genome-wide association studies. Healthcare and commercial laboratories are increasingly deploying PRS reports to patients, but it is unknown how the classification of high polygenic risk changes across individual PRS. Here, we assessed association and classification performance of cataloged PRS for three complex traits.

Rare coding variant analysis for human diseases across biobanks and ancestries.

Large-scale sequencing has enabled unparalleled opportunities to investigate the role of rare coding variation in human phenotypic variability. Here, we present a pan-ancestry analysis of sequencing data from three large biobanks, including the All of Us research program. Using mixed-effects models, we performed gene-based rare variant testing for 601 diseases across 748,879 individuals, including 155,236 with ancestry dissimilar to European.