Toward Precision Medicine in Atherosclerotic Cardiovascular Disease: Insights from Omics Data into Sex Differences

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide. Although there is increasing recognition of sex differences in ASCVD epidemiology, pathogenesis, and clinical outcomes, the underlying biological mechanisms are still insufficiently understood. Women often present with distinct disease phenotypes, such as a higher prevalence of fibrous plaques and microvascular dysfunction, compared with the lipid-rich, inflammatory plaques more typical in men. This review examines recent omics research to clarify the molecular basis of these sex-specific patterns and explores their implications for precision cardiovascular medicine.

Advances in genomics, epigenomics, transcriptomics, proteomics, and metabolomics have shown that sex differences in ASCVD arise from complex hormonal, genetic, epigenetic, and molecular interactions. The variety of available omics approaches offers the potential to discover sex-specific regulatory networks and therapeutic targets, thereby addressing persistent knowledge gaps. However, significant challenges remain, including integrating these diverse omics layers, harmonising datasets across platforms, managing substantial computational demands, and navigating ethical constraints related to data sharing. Multiomics technologies provide unprecedented opportunities to dissect sex-specific mechanisms in ASCVD and to refine individualised risk stratification and therapeutic strategies. Overcoming current analytical and infrastructural barriers through collaborative efforts, standardised methodologies, and responsible data governance will be critical to unlocking the full potential of multiomics in precision cardiovascular medicine. This review synthesises recent evidence across omics domains and underscores their potential to improve ASCVD prevention and treatment.