Familial Hypercholesterolemia and Elevated Lipoprotein(a): Cascade Testing and Other Implications for Contextual Models of Care

Abstract

Elevated lipoprotein(a) [Lp(a)], a predominantly genetic disorder, is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valvular disease, particularly in patients with familial hypercholesterolemia (FH), a Tier I genomic condition. The combination from birth of the cumulative exposure to elevated plasma concentrations of both Lp(a) and low-density lipoprotein is particularly detrimental and explains the enhanced morbidity and mortality risk observed in patients with both conditions. An excellent opportunity to identify at-risk patients with hyper-Lp(a) at increased risk of ASCVD is to test for hyper-Lp(a) during cascade testing for FH. With probands having FH and hyper-Lp(a), the yield of detection of hyper-Lp(a) is 1 individual for every 2.1-2.4 relatives tested, whereas the yield of detection of both conditions is 1 individual for every 3-3.4 relatives tested. In this article, we discuss the incorporation of assessment of Lp(a) in the cascade testing in FH as a feasible and crucial part of models of care for FH. We also propose a simple management tool to help physicians identify and manage elevated Lp(a) in FH, with implications for the care of Lp(a) beyond FH, noting that the clinical use of RNA therapeutics for specifically targeting the overproduction of Lp(a) in at risk patients is still under investigation.

Keywords: FH model of care; Lp(a); cascade testing; familial hypercholesterolemia; hyper-Lp(a); inherited hypercholesterolemia; lipoprotein (a).