A prospective study of serum metabolites and risk of ischemic stroke

Objective: To identify promising blood-based biomarkers and novel etiological pathways of disease risk, we applied an untargeted serum metabolomics profiling in a community-based prospective study of ischemic stroke (IS). Methods: In 3,904 men and women from the Atherosclerosis Risk In Communities (ARIC) study, Cox proportional hazard models were used to estimate the association of incident IS with the standardized level of 245 fasting serum metabolites individually, adjusting for age, sex, race, field center, batch, diabetes, hypertension, current smoking status, body mass index, and estimated glomerular filtration rate. Validation of results was carried out in an independent sample of 114 IS cases and 112 healthy controls. Results: Serum levels of two long-chain dicarboxylic acids, tetradecanedioate and hexadecanedioate, were strongly correlated (r=0.88) and were associated with incident IS after adjusting for covariates (Hazard Ratio [95% Confidence Interval (CI)] = 1.11 [1.06-1.16...