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June 1, 2026Journal of the American College of Cardiology147 citations

Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds

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STSotirios TsimikasSMSantica M. Marcovina

Key Points

  • The study aims to understand how genetics of lipoprotein(a) varies by ancestry and its impact on cardiovascular risk assessment.
  • Reviewed literature on ancestral differences in LPA gene and lipoprotein(a) risk categories.
  • Analyzed predictive value of risk thresholds across different ancestries.
  • Evaluated laboratory versus clinical accuracy in lipoprotein(a) assays.
  • The predictive value of lipoprotein(a) does not significantly vary by ancestry, suggesting standardized risk thresholds are sufficient.
  • Evidence supports understanding cardiovascular disease risk in diverse populations without requiring ancestry-specific adjustments.
  • Clinical and laboratory measures of lipoprotein(a) should efficiently discriminate risk thresholds.

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.

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Cite This Study

Tsimikas et al. (2022) studied this question.

synapsesocial.com/papers/6a1df74c48189dc8301a4221https://doi.org/10.1016/j.jacc.2022.06.019
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