Abstract P277: Adherence to Time-Restricted Eating, Plasma Metabolomic Signatures, and Risk of Coronary Heart Disease

Abstract

Introduction: Early time-restricted eating (TRE) has been recently suggested as an effective dietary intervention strategy to improve risk factors of coronary heart disease (CHD), whereas late TRE may be related to poor cardiometabolic health. Metabolomic pathways linking the adherence to habitual TREs depending on the time of the day and CHD risk are unknown. Hypothesis: We tested whether adherence to early or late TRE was related to distinct metabolomic signatures (including those in pathways of energy/purine pyrimidine metabolism, lipids, carbohydrates, and acylcarnitines). We then tested whether TRE-related plasma metabolites were associated with the risk of incident CHD among women without prior CHD. Methods: This study included 674 women without cardiovascular disease who completed 7-day food records and measurements of untargeted plasma metabolomics in a sub-study of the Nurses’ Health Studies (NHS/NHSII). TRE was indicated by 4-12 hours of daily eating window. The adherence to TRE was assessed by summing up the TRE days in a week (0-7 days). We analyzed two TRE habits: early TRE (starting before 9 a.m./ending no later than 9 p.m.) and late TRE (beginning after 9 a.m.). Separately, plasma metabolites were measured in a prospective nested case-control of 762 incident cases of CHD and 762 matched controls identified over 10-14 years of follow-up in the NHS. A metabolomic risk score for predicting adherence to late TRE (MRS-TRE late ) was created based on metabolites selected through the elastic net procedure with a 10-fold cross-validation. Results: Adherence to late TRE was positively associated with greater adiposity, insulin/proinsulin, uric acid, and medium-chain fatty acids/acylcarnitines; the late TRE habit was inversely related to metabolites in the TCA cycle/pyruvate metabolism and specific PC species ( P FDR <0.05). On the other hand, metabolites in lipid pathways (including diglyceride DG 38:5) and glucose were inversely related to the adherence to early TRE. Individual levels of late-TRE-related metabolites in energy/phosphatidylcholine /acylcarnitine pathways were significantly associated with an increased risk of CHD. Every 1 SD increment of MRS-TRE late , based on 21 metabolites in various metabolic pathways, was associated with a relative risk (RR) of 1.24 (95% CI: 1.11, 1.38) for CHD in a model adjusted for matching factors, and a RR of 1.15 (1.02, 1.29) after adjusting for covariates, such as demographic factors, diet quality, alcohol, lifestyle factors, and BMI. Women in the top tertile of MRS-TRE late had a 1.44-fold (1.10, 1.89) increased risk of CHD as compared to those in the lowest tertile after adjusting for the covariates. Conclusions: TRE habit, depending on the timing, was related to distinct metabolomic pathways, and adherence to late TRE may be associated with metabolic reliance linked to the risk of incident CHD among women.