Genomic and Molecular Pathways in Cardiovascular Disease: A Translational Perspective
Author(s):
Cardiovascular disease (CVD) pathogenesis is being redefined through advances in genomic medicine and molecular biology. This review synthesizes current knowledge across five key areas: (1) polygenic risk stratification, (2) inflammatory pathways in atherosclerosis, (3) cardiomyopathy genetics, (4) pharmacogenomics, and (5) emerging gene therapies. Analysis of 120 studies reveals that genome-wide association studies (GWAS) have identified >300 CVD-associated loci, while single-cell RNA sequencing has uncovered 17 distinct macrophage phenotypes in atherosclerotic plaques. Clinically, polygenic risk scores (PRS) now stratify coronary artery disease (CAD) risk with AUC 0.65-0.71, and PCSK9 inhibitors demonstrate genotype-dependent efficacy (LDL reduction: 58% in PCSK9 loss-of-function carriers vs 42% non-carriers). We evaluate challenges in implementing genomic medicine, including variant interpretation (20% of TTN truncations are benign) and health disparities (80% of GWAS data derive from European populations). The review concludes with a translational roadmap featuring: (i) functional validation pipelines for non-coding variants, (ii) clonal hematopoiesis screening protocols, and (iii) CRISPR-based therapies for familial hypercholesterolemia.