Effects of Caffeine and Coffee on Incident Heart Failure in General Population. Role of the CYP1A2 -163C>A Polymorphism

This study investigates in epidemiological setting the effects of chronic caffeine and coffee intake on incident heart failure (HF) across the –163C>A polymorphism of CYP1A2 gene, mediating caffeine metabolism. We studied 1,475 unselected subjects from general population aged 60.0±16.7 years, genotyped for CYP1A2 –163C>A polymorphism and divided into fast (AA homozygous) and slow (C-carriers) caffeine metabolizers. Daily caffeine intake was calculated from a questionnaire and a dietary diary. Events due to HF were recorded during a 12-year follow-up. Multivariate Cox regression adjusted for confounders was used for statistical analysis. In the whole cohort, HF incidence decreased with increasing caffeine intake (hazard ratio, HR, 0.998, 95% confidence intervals, CI, 0.996-0.999, p=0.02). After stratifying by sex and genotype, this effect was still detectable in C-carrier men only (OR 0.994, CI 0.990-0.998, p=0.01). No effect was observed in women and in AA men. Cox estimates were significantly higher for coffee than for caffeine both in the whole cohort and in C-carrier men. At a population level, caffeine intake is protective against HF occurrence in slow-metabolizer men, and innocuous in other subjects. The protective effect of coffee is greater than that of mere caffeine.