👤 Bharath Ambale-Venkatesh

Lp(a) (lipoprotein[a]) is a known cardiovascular risk factor; however, its role in cardiac remodeling and functional changes over time across diverse racial and ethnic groups remains underexplored. MESA is a prospective multi-ethnic cohort study of individuals without a history of cardiovascular disease on enrollment (2000-2002), conducted across 6 sites in the United States. Participants with baseline Lp(a) measurements and cardiac magnetic resonance imaging at both baseline and 10-year follow-up exam were included. Lp(a) was treated as both a log-transformed continuous variable (per SD log) and a categorical variable based on data-driven Lp(a) terciles. Multivariable regression models adjusted for sociodemographic, and cardiovascular risk factors, including coronary artery calcium and interim myocardial infarction, were used to assess associations between Lp(a) and longitudinal changes in left ventricular and atrial structure and function over a decade across different racial/ethnic groups. A total of 2366 participants were included. The average age at baseline was 60±9 with 53% women, 43% White, 24% Black, 21% Hispanic, and 12% Chinese. Each 1-SD increase in log-transformed Lp(a) was associated with an increase in left ventricular end-systolic volume index (β, 0.60 [95% CI, 0.02-1.18]), and left atrial minimum volume index (β, 0.81 [95% CI, 0.09-1.52]), and a decline in left ventricular ejection fraction (β, -0.75 [95% CI, -1.34 to -0.17]), and total left atrial emptying fraction (β, -1.17 [95% CI, -2.09 to -0.24]) in Hispanic subjects over a decade. No significant associations were seen in White, Black, or Chinese participants. The observed findings persisted after adjusting for coronary artery calcium, interim myocardial infarction, and atrioventricular decoupling, and when Lp(a) was treated as a categorical variable with race-specific terciles. Elevated Lp(a) levels were independently associated with maladaptive left ventricular and left atrial remodeling in Hispanic adults over a decade, while no statistically significant relationships were observed in White, Black, and Chinese participants. This suggests a unique susceptibility of Hispanic individuals to Lp(a)-mediated cardiovascular remodeling, independent of ischemic pathways. Show less

Rare pathogenic variants in cardiomyopathy (CM) genes can predispose to cardiac remodeling or fibrosis. We studied the carrier status for such variants in adults without clinical cardiovascular disease (CVD) in whom cardiac MRI (CMR)-derived measures of myocardial fibrosis were obtained in the Multi-Ethnic Study of Atherosclerosis (MESA). To identify CM-associated pathogenic variants and assess their relative prevalence in participants with extensive myocardial fibrosis by CMR. MESA whole-genome sequencing data was evaluated to capture variants in CM-associated genes ( A total of 1,135 MESA participants had available genetic data and phenotypic measures and were free of clinical CVD at the time of CMR. We identified 6,349 rare variants in CM-associated genes in the overall MESA population, of which six pathogenic/likely pathogenic (P/LP) variants were present in the phenotyped subpopulation. The genes harboring P/LP variants in the case group were We observed a higher prevalence of rare potentially pathogenic CM associated genetic variants in participants with significant myocardial fibrosis quantified in CMR as compared to controls without significant fibrosis. No cardiac structural or functional differences were found between participants with or without P/LP variants. Show less