Lipoprotein(a) and Cardiovascular Risk: Emerging Therapeutic Perspectives with Implications for Chronic Kidney Disease
TL;DR
Chronic kidney disease (CKD) represents a clinically relevant setting in which Lp(a) levels may rise as renal function declines, contributing to the excess cardiovascular burden and residual risk left unaddressed by historical statin trials in the end-stage renal disease population.
Abstract
Abstract Background Lipoprotein(a) (Lp(a)) is an low-density lipoprotein (LDL)-like particle containing apolipoprotein B100 covalently bound to apolipoprotein(a). Elevated Lp(a) is now recognized as a genetically determined, independent, and likely causal risk factor for atherosclerotic cardiovascular disease, calcific aortic valve stenosis, and residual cardiovascular risk despite optimal LDL cholesterol control. Current European and North American recommendations support measuring Lp(a) at least once in adulthood, particularly for cardiovascular risk refinement. Lp(a) levels are predominantly inherited and are only modestly influenced by lifestyle or conventional lipid-lowering therapies. Summary Chronic kidney disease (CKD) represents a clinically relevant setting in which Lp(a) levels may rise as renal function declines, contributing to the excess cardiovascular burden and residual risk (including severe vascular calcification) left unaddressed by historical statin trials in the end-stage renal disease population. However, the causal role of Lp(a) in CKD-related cardiovascular disease remains incompletely defined. Key Messages Novel RNA-based and small molecule therapies, including pelacarsen, olpasiran, lepodisiran, zerlasiran, and muvalaplin, have shown marked Lp(a)-lowering effects, but definitive cardiovascular outcome data are still missing.