Association between NMR metabolomic signatures of healthy lifestyle and incident coronary artery disease

AIMS: To identify metabolites associated with a healthy lifestyle and explore the possible mechanisms of lifestyle in coronary artery disease (CAD). METHODS AND RESULTS: The nuclear magnetic resonance metabolomics platform was applied to perform metabolomic profiling of baseline plasma samples from a randomly selected subset of 121 733 UK Biobank participants. Cox proportional hazards models with covariate adjustments were used to investigate the associations between validated lifestyle-associated metabolites and incident CAD and to estimate the accuracy of the inclusion of metabolites to predict CAD compared with traditional prediction models. The discriminatory ability of each model was evaluated using Harrell's C statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI) indexes. During a median of 8.6 years of follow-up, 5513 incident CAD cases were documented. Among the 111 lifestyle-associated metabolites, 65 were significantly associated with incident CAD after multivariate adjustment (Bonferroni P < 3.11 × 10-04). The addition of these metabolites to classic risk prediction models [Framingham Risk Score (FRS) using lipids; FRS using body mass index] improved CAD prediction accuracy as assessed by the C statistic (increasing to 0.739 [95% CI, 0.731-0.747] and 0.752 [95% CI, 0.746-0.758]), respectively; continuous NRI (0.274 [0.227-0.325] and 0.266 [0.223-0.317]) and IDI (0.003 [0.002-0.004] and 0.003 [0.002-0.004]). CONCLUSION: Healthy lifestyle-associated metabolites are associated with the incidence of CAD and may help improve the prediction of CAD risk. The use of metabolite information combined with the FRS model warrants further investigation before clinical implementation.