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Major cardiovascular events in first-degree relatives of individuals with elevated plasma lipoprotein(a): a

Gustav Kindborg1, Daniel Eriksson Hogling1, Henrike Häbel2

  • 1Department of Medicine Huddinge, Karolinska Institutet, Endokrinexpeditionerna C2:94, Karolinska Universitetssjukhuset Huddinge, 141 86 Stockholm, Sweden.

European Heart Journal
|August 31, 2025
PubMed

Insights

First-degree relatives of individuals with high lipoprotein(a) [Lp(a)] levels face increased cardiovascular disease risk. Cascade screening can identify these at-risk relatives for early intervention.

Area of Science:

  • Cardiovascular Science
  • Genetics
  • Epidemiology

Background:

  • Lipoprotein(a) [Lp(a)] is genetically determined and causally linked to atherosclerotic cardiovascular disease.
  • The cardiovascular risk in first-degree relatives (FDR) of individuals with elevated Lp(a) (≥80th percentile) is not well understood.

Purpose of the Study:

  • To investigate the association between parental elevated lipoprotein(a) levels and the risk of major adverse cardiovascular events (MACE) in their first-degree relatives.
  • To assess the concordance of Lp(a) levels within families.

Main Methods:

  • Utilized the Swedish STRIREG cohort, including 41,304 index individuals with Lp(a) measurements and 61,715 FDR (aged 35-69).
  • Stratified FDR based on index Lp(a) percentile (<50th, 50-<80th, 80-<95th, ≥95th) and analyzed MACE incidence using competing risk-adjusted cumulative incidence and Cox regression.
  • Examined Lp(a) concordance in a nested analysis of 4243 related index individuals.

Main Results:

  • Over a median 19-year follow-up, FDR of individuals with elevated Lp(a) showed a progressively higher risk of MACE.
  • Cumulative incidence of MACE by age 65 increased with parental Lp(a) strata (6.2% to 8.1%, P<0.001).
  • Hazard ratios for MACE increased significantly with higher parental Lp(a) strata (e.g., 1.30 for 80-<95th percentile).

Conclusions:

  • First-degree relatives of individuals with elevated Lp(a) have a significantly higher incidence of major adverse cardiovascular events.
  • Cascade screening of FDR is a potentially effective strategy for identifying individuals at heightened cardiovascular risk due to inherited high Lp(a).
Abstract

Keywords:
Atherosclerotic cardiovascular diseaseLipoprotein(a)Major adverse cardiovascular eventPrimary preventionScreening

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