Abstract P076: Genetic Factors Modify the Triggering of Acute Myocardial Infarction by Transient Exposure to Coffee Intake

Abstract

Introduction: Caffeinated coffee increases sympathetic nervous activity that may adversely affect a vulnerable atherosclerotic plaque and therefore trigger an acute myocardial infarction (AMI). Additionally, it is possible that genetic variation alter the susceptibility to the acute effects of coffee. Hypothesis: We assessed the hypothesis that genetic factors associated to AMI can modify the triggering of AMI by acute coffee intake. Methods: We collected information on intake of coffee during the 24 hours and days before the myocardial infarction and habitual intake of coffee in 1,234 incident cases of non-fatal AMI from 1994–2004. Data was analyzed as a case-crossover design assuming a hazard period of 1 hour. We used a genetic score with 3 loci from AMI GWAS that has been validated in this population. People with a higher score have a greater risk for AMI. In addition, we also evaluated one polymorphism in the cytochrome P450 1A2 candidate gene that decreases the enzyme inducibility, resulting in impaired caffeine metabolism. Carriers of the variant CYP1A2*1F allele are slow caffeine metabolizers, whereas individuals who are homozygous for the CYP1A2*1A allele are rapid metabolizers. Results: Participants were classified as low AMI genetic risk (1 to 3 alleles) or high genetic risk (4 to 6 alleles) according to the genetic risk score. RR for the association between coffee and AMI were 1.72 (95%CI:1.22, 2.43) and 1.06 (95%CI:0.85, 1.31) for the low and high genetic risk groups respectively (test of homogeneity p-value=0.02). RR were 1.38 (95%CI:1.07, 1.76) and 0.99 (95%CI:0.77, 1.28) for homozygous carriers of the rapid CYP1A2*1A allele and carriers of the slow CYP1A2*1F allele, respectively (test of homogeneity p-value =0.067). Because we have shown previously that coffee intake is not associated with AMI among heavy drinkers (≥ 4 cups/d), we repeated the analysis among light/occasional and moderate drinkers. RR were 1.69 (95%CI:1.28, 2.23) and 1.09 (95%CI:0.80, 1.48) for rapid and slow metabolizers, respectively (test of homogeneity p-value=0.038). Conclusions: In conclusion, people with lower genetic risk seem to be more susceptible to coffee. It is possible that the effect of environmental factors (including triggers like coffee intake) is higher among people who are not at risk because of genetic factors. Light and moderate drinkers who are rapid caffeine metabolizers are also more susceptible to coffee. It is possible that light/moderate drinkers who are slow metabolizers develop more tolerance to caffeine than rapid metabolizers.