Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds: JACC Review Topic of the Week

Abstract

This study reviews ancestral differences in the genetics of the LPA gene, risk categories of elevated lipoprotein(a) [Lp(a)] as defined by guidelines, ancestry-specific Lp(a) risk, absolute and proportional risk, predictive value of risk thresholds among different ancestries, and differences between laboratory vs clinical accuracy in Lp(a) assays. For clinical decision-making, the preponderance of evidence suggests that the predictive value of Lp(a) does not vary sufficiently to mandate the use of ancestry-specific risk thresholds. This paper interprets the literature on Lp(a) and ancestral risk to support: 1) clinicians on understanding cardiovascular disease risk in different ancestral groups; 2) trialists for the design of clinical trials to ensure adequate ancestral diversity to support broad conclusions of drug effects; 3) regulators in the evaluation of the design and interpretation of results of Lp(a)-lowering trials with different Lp(a) inclusion thresholds; and 4) clinical laboratories to measure Lp(a) by assays that discriminate risk thresholds appropriately.

Keywords: ancestry; aortic stenosis; atherosclerosis; lipoprotein(a); threshold.