Evidence of dependence of lipoprotein(a) on triglyceride and high-density lipoprotein metabolism

Abstract

Lipoprotein(a) [Lp(a)] is a complex lipoprotein consisting of a low-density lipoprotein (LDL)-like ApoB₁₀₀-containing core particle covalently bound to apo(a), a large functionally complex glycoprotein. The mechanisms of Lp(a) metabolism and its interactions with cell-surface lipoprotein receptors are incompletely understood. In this study, we investigated the relationship of Lp(a) to other lipoproteins at high and normal levels of serum triglycerides (TGs). We measured serum lipid and Lp(a) particle concentrations in 148 unselected primary- and secondary-prevention patients. Subjects with TG > 200 mg/dL were classified as having high TG in accordance with National Cholesterol Education Program Adult Treatment Panel III guidelines. Our analysis revealed mean TG levels of 100 and 270 mg/dL in the normal and high TG groups, respectively. Lp(a)-C, Lp(a)-P, and Lp(a) cholesterol content per particle [Lp(a)-C/Lp(a)-P] did not differ between groups. At normal TG levels, stepwise multiple linear regression revealed that Lp(a)-P correlated with Lp(a)-C (P < 10⁻⁶), ApoAI (P = .0001), the high-density lipoprotein cholesterol subfraction ratio (HDL₂-C/HDL₃-C; P = .002), and dense very-low-density lipoprotein cholesterol (VLDL₃-C; P = .04), overall model R = 0.74. At high TG levels, Lp(a)-P very strongly correlated primarily with HDL₂-C/HDL₃-C and TG-related variables with minimal dependence on Lp(a)-C (P = .09), overall model R = 0.96. These findings provide evidence of shared metabolic mechanisms for Lp(a), HDL, TG, and very low-density lipoprotein at high serum TG. Future studies are needed to elucidate common mechanisms, enzymes, and receptors involved in Lp(a) and HDL/TG metabolism with a focus on how these mechanisms are modified in the setting of hypertriglyceridemia.