Clinical and Genetic Factors Associated with Multivessel Coronary Artery Disease: A Cross-Sectional Study of CYP2C19 Polymorphisms and Metabolic Comorbidities.

BACKGROUND

Multi-vessel coronary artery disease (MVCD), defined as stenosis affecting ≥2 major coronary arteries, confers poor clinical outcomes in patients with coronary artery disease (CAD). Cytochrome P450 2C19 (CYP2C19) CYP2C19 participates in lipid metabolism and inflammatory regulation, which may be associated with individual variations in the severity of coronary artery lesions. This study aimed to explore the clinical and genetic factors associated with MVCD focusing on CYP2C19 polymorphisms and chronic metabolic diseases.

METHODS

This single‑center cross‑sectional study enrolled 4124 patients with angiographically confirmed CAD, who were divided into single‑vessel CAD (n=846) and MVCD (n=3278) groups. Baseline clinical data and CYP2C19 genotypes were collected. The chi-square test, Hardy-Weinberg equilibrium test, and logistic regression analyses were performed for statistical evaluation.

RESULTS

Higher prevalences of hypertension, type 2 diabetes mellitus, and dyslipidemia were observed in MVCD patients. CYP2C19*2 (rs4244285, 681G>A) and *3 (rs4986893, 636G>A) allele frequencies were markedly elevated in the MVCD group. Logistic regression analysis confirmed that hypertension (odds ratio (OR)=1.485, 95% confidence interval (CI): 1.267‑1.740, p<0.001), T2DM (OR=2.441, 95% CI: 2.006‑2.970, p<0.001), dyslipidemia (OR=1.313, 95% CI: 1.097‑1.572, p=0.003), and CYP2C19 poor metabolizer (*2/*2, *2/*3 and *3/*3 genotypes) status (OR=1.744, 95% CI: 1.360‑2.237, p<0.001) was independently associated with MVCD. The combined impaired CYP2C19 metabolic phenotype (intermediate (*1/*2 and *1/*3 genotypes) plus poor metabolizers) was also independently correlated with MVCD (adjusted OR=1.285, 95% CI: 1.095-1.508, p=0.002).

CONCLUSION

Clinical metabolic comorbidities and the combined impaired CYP2C19 metabolic phenotype are associated with MVCD. These findings may provide valuable reference for risk assessment of severe CAD.