Genomic and Precision Medicine Approaches in Atherosclerotic Cardiovascular Disease: From Risk Prediction to Therapy-A Review

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality, prompting significant interest in individualized prevention and treatment strategies. This review synthesizes recent advances in genomic and precision medicine approaches relevant to ASCVD, with a focus on genetic risk scores, lipid metabolism genes, and emerging gene editing techniques. A structured literature search was conducted across PubMed, Scopus, and Web of Science databases to identify key publications from the last decade addressing genomic mechanisms, therapeutic targets, and computational tools in ASCVD. Notable findings include the identification of causal genetic variants such as PCSK9 and LDLR, the development of polygenic risk scores for early prediction, and the use of deep learning algorithms for integrative multi-omics analysis. In addition, we highlight current and future therapeutic applications including PCSK9 inhibitors, RNA-based therapies, and CRISPR-based genome editing. Collectively, these advances underscore the promise of precision medicine in tailoring ASCVD prevention and treatment to individual genetic and molecular profiles.

Keywords: atherosclerosis; cardiovascular disease; genomics; personalized therapy; pharmacogenomics; polygenic risk score; precision medicine.

Figure 1

Overview of genomic approaches in ASCVD (monogenic forms), illustrating genetic risk stratification (e.g., PRS), key lipid-related genes (LDLR, PCSK9, APOE, ANGPTL3, Lp(a)), and precision therapies such as PCSK9 inhibitors, pharmacogenomics, and CRISPR-Cas9 gene editing for personalized treatment. ANGPTL3: Angiopoietin-like protein 3; ApoE: Apolipoprotein E; ASCVD: Atherosclerotic Cardiovascular Disease; CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats; DNA: Deoxyribonucleic Acid; LDLR: Low-Density Lipoprotein Receptor; Lp(a): Lipoprotein(a); PCSK9: Proprotein Convertase Subtilisin/Kexin Type 9; PRS: Polygenic Risk Score; SNP: Single Nucleotide Polymorphism.

Figure 2

Epigenomics and ASCVDs. Epigenetic mechanisms—including DNA methylation, histone modifications, and non-coding RNAs—mediate the impact of environmental stressors on gene regulation in ASCVD, influencing inflammation, endothelial dysfunction, and plaque progression. ABCA1, ATP-binding cassette transporter A1; ANRIL, antisense non-coding RNA in the INK4 locus; ASCVD, atherosclerotic cardiovascular disease; CDKN2A/B, cyclin-dependent kinase inhibitor 2A/B; circRNA, circular RNA; DNMT, DNA methyltransferase; miR, microRNA; TET, ten-eleven translocation enzymes.

Figure 3

CYP2C19 Genotype-Guided Therapy for Clopidogrel Use. Based on genotype, patients are classified into poor, intermediate, normal, rapid, or ultra-rapid metabolizers, guiding clopidogrel dosing or recommending alternative agents to optimize efficacy and minimize bleeding or thrombotic risk. CYP2C19: cytochrome P450 family 2 subfamily C member 19 enzyme.