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Ancestry, Lp(a) and cardiovascular risk thresholds (Tsimikas and Marcovina, JACC 2022)
Original title: Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds: JACC Review Topic of the Week
A JACC review of ancestral differences in LPA genetics, distributions and risk: distributions differ widely by ancestry, but the predictive value of a given Lp(a) concentration does not vary enough to justify ancestry-specific thresholds; the paper also separates laboratory from clinical accuracy of assays. Written for clinicians, trialists, regulators and laboratories alike, and the position most guidelines have since adopted.
Original 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.
ancestryguidelinestestingtherapy
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.