Association of urinary caffeine and caffeine metabolites with cardiovascular disease risk in adults

Abstract Background and aims : Studies have shown that the consumption of a moderate amount of caffeine is associated with a reduced risk of cardiovascular disease (CVD) and may even be protective against CVD. The purpose of the current study was to evaluate the association between urinary caffeine and its related metabolites and CVD risk in a national representative sample of United States (U.S.) adults. Methods : We analyzed cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2009-2010. The associations between the levels of urinary caffeine metabolites and self-reported CVD, including congestive heart failure, coronary heart disease, angina, heart attack and stroke, were examined separately in males and females using multivariable logistic regression models adjusted for covariates. Results : In total, 1,916 U.S. participants (910 males and 1,006 females) were included in the analysis. Among the females, the odds ratios (ORs) of CVD in the highest quartiles of 1,3-dimethylxanthine and 1,3,7-trimethylxanthine were 0.33 [95% confidence interval (CI): 0.12-0.92] and 0.35 (95% CI: 0.13-0.93), respectively, compared with the lowest quartiles. Each one-unit (µmol/L) increase in the theophylline concentration was associated with a 0.24 mg/dL increase in high density lipoprotein cholesterol (HDL-C) in the fully adjusted model. Among the males, no significant association between urinary caffeine metabolites and CVD was observed. Regarding the subtypes of CVD, compared with the females in the lowest quartiles of theophylline and caffeine, the odds of coronary heart disease decreased by 90% (95% CI: -99% to -11%) and 97% (95% CI: -99% to -47%) in those in the highest quartile, respectively. Conclusions : Urinary caffeine and theophylline excretion were significantly and inversely associated with CVDs in females. Additional studies are needed to further confirm the results of this study and explore the underlying mechanisms.