Genetics
Is Lp(a) a real risk multiplier in familial hypercholesterolaemia, or just along for the ride? A review calls for direct drug-based proof (Curr Opin Lipidol 2022)
Original title: Lipoprotein (a) in familial hypercholesterolaemia
This review by Durrington, Bashir, Bhatnagar and Soran examines the long-disputed question of whether Lp(a) is genuinely elevated in familial hypercholesterolaemia (FH) and whether it adds to the already high cardiovascular risk in this condition. The authors conclude that FH does raise Lp(a), likely through increased hepatic production mediated by PCSK9 and augmented by apolipoprotein E, though whether this elevated Lp(a) meaningfully adds to FH already substantial cardiovascular risk remains controversial. Since emerging Lp(a)-specific drugs are expected to work best in people with the highest Lp(a) levels, unlike statins which work across the LDL spectrum, the authors argue FH patients could be among the first to benefit, and that this question can only be definitively answered using drugs designed specifically to lower Lp(a).
Original abstract
Purpose Of Review: The role of lipoprotein (a) in atherogenesis has been the subject of argument for many years. Evidence that it is raised in familial hypercholesterolaemia has been disputed not least because a mechanism related to low density lipoprotein (LDL) receptor mediated catabolism has been lacking. Whether lipoprotein (a) increases the already raised atherosclerotic cardiovascular disease (ASCVD) risk in familial hypercholesterolaemia is also more dubious than is often stated. We review the evidence in an attempt to provide greater clarity.
Recent Findings: Lipoprotein (a) levels are raised as a consequence of inheriting familial hypercholesterolaemia. The mechanism for this is likely to involve increased hepatic production, probably mediated by PCSK9 augmented by apolipoprotein E. The extent to which raised lipoprotein (a) contributes to the increased ASCVD risk in familial hypercholesterolaemia remains controversial.Unlike, for example, statins which are effective across the whole spectrum of LDL concentrations, drugs in development to specifically lower lipoprotein (a) are likely to be most effective in people with the highest levels of lipoprotein (a). People with familial hypercholesterolaemia may therefore be in the vanguard of those in whom theses agents should be exhibited.
Summary: Inheritance of familial hypercholesterolaemia undoubtedly increases the likelihood that lipoprotein (a) will be raised. However, in familial hypercholesterolaemia when ASCVD incidence is already greatly increased due to high LDL cholesterol, whether lipoprotein (a) contributes further to this risk cogently needs to be tested with drugs designed to specifically lower lipoprotein (a).
familial hypercholesterolaemiagenetics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.