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Review
. 2022 Aug 30;80(9):934-946.
doi: 10.1016/j.jacc.2022.06.019.

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

Sotirios Tsimikas  1 , Santica M Marcovina  2
Affiliations
Free article
Review

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

Sotirios Tsimikas et al. J Am Coll Cardiol. .
Free article

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.

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Conflict of interest statement

Funding Support and Author Disclosures This study was supported in part by the National Institutes of Health, National Heart, Lung, and Blood Institute (R01HL159156, Dr Tsimikas). Dr Tsimikas is a co-inventor and receives royalties from patents owned by the University of California San Diego and is a co-founder and has an equity interest in Oxitope, Inc and its affiliates, Kleanthi Diagnostics, LLC and Covicept Therapeutics, Inc; and has a dual appointment at the University of California San Diego and Ionis Pharmaceuticals. Dr Marcovina is a consultant for Roche Diagnostics, Denka Seiken, and Novartis; and receives research support from contracts between Amgen and Medpace.

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