Genetics
Lp(a) concentrations vary more than 100-fold by ancestry, yet the relative ASCVD risk per unit is universal, review of ancestral variation finds (Curr Atheroscler Rep 2025)
Original title: Ancestral Variation in Lp(a): Epidemiology, Isoform Diversity, and Testing
This review examines how Lp(a)'s structural and genetic determinants vary across ancestry groups. Plasma concentrations vary more than 100-fold between individuals, driven mainly by LPA gene polymorphisms and the number of kringle-IV type 2 repeats that set apolipoprotein(a) isoform size; individuals of African descent have the highest median concentrations, followed by South Asians, with Hispanic/Latino and East Asian populations showing lower levels, and admixed populations reflecting heterogeneous ancestry. Despite these large differences in absolute levels, the relative ASCVD risk per unit increase in Lp(a) is consistent across groups, underscoring elevated Lp(a)'s universal atherogenicity. Small apo(a) isoforms track with both higher Lp(a) and higher risk, though isoform size mainly proxies for Lp(a) burden itself. The authors note that despite this strong genetic basis and disproportionate burden in some populations, ancestry-specific testing guidelines remain limited and testing rates stay low, and call for integrating ancestry-informed perspectives with universal risk principles as one-time Lp(a) testing and Lp(a)-directed therapies mature.
Original abstract
Purpose Of Review: This review aims to explore the epidemiology of lipoprotein(a) [Lp(a)] by its structural and genetic make-up variation amongst ancestry groups.
Recent Findings: Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle, causally implicated in atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Given its genetic basis, studies have shown marked ancestry-related differences in different races and ethnicities. Lp(a) plasma concentrations vary by more than 100-fold among individuals, primarily due to LPA gene polymorphisms and the number of kringle-IV type 2 (KIV2) repeats, which define apolipoprotein(a) [apo(a)] isoform size. Individuals of African descent have the highest median concentrations, followed by South Asians, with Hispanics/Latinos and East Asians having lower levels. Admixed populations display heterogeneity reflecting genetic ancestry. Despite differences in absolute levels, the relative ASCVD risk per unit increase in Lp(a) is consistent across groups, highlighting the universal atherogenicity of elevated Lp(a). Small apo(a) isoforms are associated with higher Lp(a) concentrations and risk, though isoform size is mainly a surrogate for Lp(a) burden. Despite a strong genetic basis and disproportionate burden in some populations, ancestry-specific testing guidelines are limited and testing rates remain low. Therapies targeting LPA transcription are in development, with outcome trials underway. Integrating ancestry-informed perspectives with universal risk principles is essential for equitable prevention and treatment. Routine, one-time Lp(a) testing enables cost-effective early risk stratification as Lp(a)-directed therapies emerge.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.