Lipidomics Identified Novel Cholesterol-Independent Predictors for Risk of Incident Coronary Heart Disease: Mediation of Risk from Diabetes and Aggravation of Risk by Ambient Air Pollution.

•A panel of seven lipids increased c-statistic by an increment of 0.077, the greatest added value for prediction of incident CVD ever achieved by prospective lipidomics studies to the best of our knowledge.•Considerable mediations were observed through SM 41:1b, presumably SM(d18:1/23:0), in the associations between established cardiovascular risk factors and CHD risk, diabetes in particular.•CHD risk associated with increased levels of PC 36:0a, SM 41:1b, LPC 18:0 and LPC 20:3, and decreased levels of CE 18:2 were aggravated by long-term exposure to ambient air pollution.