A Novel Triglyceride- and Cholesterol-Enriched Lipoprotein(a) Phenotype in Moderate Hypertriglyceridemia

In moderate hypertriglyceridemia, lipoprotein(a) (Lp[a]) particles were enriched in triglycerides and cholesterol, accounting for about 16% to 21% of plasma triglycerides and about 9% to 11% of plasma cholesterol. In a phase 2 trial, apolipoprotein C-III inhibition with olezarsen reduced Lp(a)-associated triglycerides and cholesterol by about 56% to 70%, with no consistent reduction in plasma Lp(a). Oxidized phospholipid measures tracked more closely with Lp(a) particle concentration than with Lp(a)-associated lipid content, supporting partially distinct dimensions of Lp(a) biology. These findings identify Lp(a) lipid composition as a dynamic, therapeutically modifiable feature in hypertriglyceridemia. (Study of ISIS 678354 [AKCEA-APOCIII-LRx] in Participants With Hypertriglyceridemia and Established Cardiovascular Disease [CVD]; NCT03385239).