BACKGROUND: Plasma 1-H nuclear magnetic resonance ( METHODS: Principal component analysis was performed on 168 RESULTS: The first six PCs collectively explaining 88% of the total variance were identified. For CAD, results from Cox and MR analyses were generally directionally consistent. The pooled odds ratios (ORs) [95% CI] for CAD per one-SD increase in genetically-influenced PC1 and PC3 (both characterized by distinct ApoB-associated lipoprotein profiles) were 1.04 [1.03, 1.05] and 0.94 [0.93, 0.96], respectively. Besides, the pooled OR [95% CI] for CAD per one-SD increase in genetically-influenced PC4, characterized by simultaneously decreased small HDL and increased large HDL, and independent of ApoB, was 1.05 [1.03, 1.07]. For ISTR, increases of PC3 and PC5 (characterized by increased amino acids) were associated with a lower risk and a higher risk, respectively. CONCLUSIONS: This study confirms associations of ApoB-associated lipoprotein profiles with CAD and ISTR, and highlights the possible existence of an ApoB-independent lipoprotein profile, characterized by a distinctive HDL sub-particle distribution, driving CAD.