CYP2C19 Poor Metabolizer Status and High System Inflammation Response Index are Independent Risk Factors for Premature Myocardial Infarction: A Hospital-Based Retrospective Study.

Objective: Atherosclerosis (AS) is a sustained chronic vascular inflammatory response caused by lipid metabolism disorders and immune response disorders and is the main cause of premature (men ≤ 55 years old, women ≤ 65 years old) myocardial infarction (PMI). Cytochrome P450 2C19 (CYP2C19) (related to vascular function and lipid metabolism) and peripheral immune cell levels and plays an important role in the course of AS. The association CYP2C19 polymorphisms, comprehensive immunoinflammatory indices with PMI susceptibility is unclear.

Methods: This study included 485 PMI patients, and 639 age-matched non-PMI individuals as controls, from January 2019 to March 2024. The relationship between CYP2C19 polymorphisms, peripheral immunoinflammatory indices (pan-immune inflammation value (PIV), systemic immune inflammation index (SII), and system inflammation response index (SIRI)) and PMI risk were analyzed.

Results: The inflammatory indices levels in PMI patients were higher than those in controls (all p<0.05). The frequencies of the CYP2C19 *1/*2 and *2/*2 genotypes were higher, while the frequency of the *1/*1 genotype was lower in the PMI patients than those in controls. The cut-off values of TC, TG, LDL-C, PIV, SII, and SIRI were 5.065, 1.305, 2.805, 410.485, 869.645, and 1.495 for distinguishing PMI, respectively. Logistic regression analysis showed that male (odds ratio (OR): 1.607, 95% confidence interval (CI): 1.134-2.277, p=0.008), history of smoking (OR: 7.108, 95% CI: 4.351-11.614, p<0.001), diabetes mellitus (OR: 4.906, 95% CI: 3.333-7.223, p<0.001), CYP2C19 poor metabolizer (PM) (*2/*2, *2/*3, and *3/*3) (OR: 2.147, 95% CI: 1.279-3.603, p=0.004), and high TG (≥1.305 vs <1.305, OR: 2.598, 95% CI: 1.864-3.623, p<0.001) and SIRI level (≥1.495 vs <1.495, OR: 2.495, 95% CI: 1.432-4.349, p=0.001) were independent risk factors for PMI.

Conclusion: CYP2C19 PM phenotype, high SIRI level (≥1.495) and TG level (≥1.305), male, history of smoking, and diabetes mellitus were independently associated with PMI susceptibility.