Lipoprotein subfractions in cardiovascular disease risk prediction and therapeutic targeting: Current landscape and future directions

Dyslipidemia is a well-established driver of atherosclerotic cardiovascular disease (ASCVD).However, substantial residual risk persists despite aggressive lowering of low-density lipoprotein cholesterol (LDL-C).Advances in analytical techniques have strengthened the scientific consensus that specific lipoprotein subfractions contribute to this residual risk. 1 LIPOPROTEIN SUBFRACTIONS ASSOCIATED WITH ASCVD LDL SubfractionsCurrent research has increasingly focused on LDL subfractions such as particle size, particle concentration, and oxidative modification.As for LDL size, pathological researches indicate that small dense LDL (sdLDL) particles may exhibit heightened atherogenicity, attributed to their enhanced ability to infiltrate the arterial intima, increased susceptibility to oxidation, and prolonged circulation time.Nevertheless, in clinical researches, the association between sdLDL and ASCVD risk is substantially attenuated or nullified after adjustment for conventional risk factors, 2 And the Mendelian randomization (MR) analysis revealed that, after adjusting for triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and LDL-C, sdLDL had no significant impact on myocardial infarction (MI).Thus, the evidence regarding the connection between LDL size and cardiovascular events remains inconclusive. 3As for LDL particle (LDL-P)