Cigarette smoking might weaken the prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction patients

Abstract

Prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction is still not well investigated. The aim of the study was to determine the relationship between the genetic polymorphism and the outcome of the acute myocardial infarction patients, and to further clarify the impact of smoking on such relationship. Six hundred acute myocardial infarction patients were enrolled. All of them provided blood samples and underwent clopidogrel treatment. The genetic polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism analysis, and the platelet function was assessed using conventional aggregometry. Of the included patients, 287 carried GG wild‐type genotypes, 225 carried GA genotypes and 88 carried AA genotypes. The platelet aggregation rate was significantly elevated in the AA genotype patients, mainly in the non‐smoking patients (P < 0.001) and the former‐smoking patients (P < 0.001). During 5‐year follow‐up period, after adjusted for multiple confounding factors, AA genotypes were associated with the increase in 5‐year mortalities in the non‐smoking patients [OR: 7.06, 95% confidence interval (CI): 2.16–11.49] and the former‐smoking patients (OR: 4.38, 95% CI: 1.05–9.40), but not in the current‐smoking patients (OR: 1.12, 95% CI: 0.60–2.31). In conclusion, the study suggested a potential role of P450 2C19*2 polymorphism as a prognostic indicator in acute myocardial infarction patients. We had also obtained some evidence that current smoking might weaken the prognostic significance of the genetic polymorphism in patients.

CAMI-NSTEMI Score ― China Acute Myocardial Infarction Registry-Derived Novel Tool to Predict In-Hospital Death in Non-ST Segment Elevation Myocardial Infarction Patients ―

“…25 Similarly, evidence for smoker's paradox was also seen in the present study after adjustment for age and comorbidity, consistent with previous studies. 26 Possible mechanisms include greater clopidogrel-induced platelet suppression, 27,28 and lower risk of adverse LV remodeling after infarction. 29 Because it is well-established that obesity and smoking are associated with long-term adverse event risk, we still recommend that patients maintain a BMI between 18.5 and 24.9 kg/m 2 and stop smoking after AMI, in accordance with the guideline.…”

Influence of CYP2C19 genetic variants and smoking on dual antiplatelet efficacy in patients with coronary artery disease

“…Some studies have revealed that smoking could enhance the efficacy of clopidogrel and improve prognosis in patients with stroke or ACS ( 13 – 16 ). Other studies have shown that cigarettes may lower platelet activity during treatment, and weaken the outcomes significance of CYP2C19*2 in patients with ACS ( 16 , 17 ). Our study extended previous findings.…”

Association between smoking and in-hospital mortality in patients with acute myocardial infarction: results from a prospective, multicentre, observational study in China

“…First, some studies showed that a suppressive effect of clopidogrel on platelets was greater in smokers than in non-smokers 27–29. A potential explanation for this finding is that smoking can enhance in-vivo bioactivation of clopidogrel via increasing induction of cytochrome P450 (CYP1A2 and CYP2B6) and increased active metabolite concentrations of clopidogrel 30 31.…”