Genetics
Lp(a)'s heart attack risk is not explained by prothrombotic mechanisms, 410,177-person UK Biobank genetic study finds, and Lp(a) shows no link to venous thromboembolism at all (Eur J Intern Med 2025)
Original title: Lipoprotein(a) and prothrombotic effects: Evidence from a genetic association study
This genetic association study analysed 410,177 UK Biobank participants to test whether Lp(a)'s established link to myocardial infarction (MI) risk operates through prothrombotic mechanisms, by stratifying LPA genetic variants and observed Lp(a) concentrations against genetic scores for coagulation through the thrombin (F2/F5) and platelet (GUCY1A3) pathways. Neither LPA variants nor observed Lp(a) were associated with incident venous thromboembolism (HR per 100 nmol/L higher Lp(a) 1.02, 95% CI 1.00-1.04, P = 0.13), in contrast to a strong association with incident MI (HR per 100 nmol/L higher Lp(a) 1.31, 95% CI 1.29-1.33, P < 0.001). While the F2/F5 score reduced VTE risk stepwise and the GUCY1A3 score reduced MI risk stepwise, neither coagulation score modified the LPA-MI or Lp(a)-MI associations. The authors conclude Lp(a)'s excess MI risk is not explained by prothrombotic effects acting through the thrombin or platelet pathways, challenging a commonly assumed mechanism and pointing research toward Lp(a)'s other atherogenic and inflammatory properties instead.
Original abstract
Background: It is unknown whether lipoprotein(a) [Lp(a)] has prothrombotic effects contributing to its association with the risk of myocardial infarction (MI).
Methods: In 410,177 participants of UK Biobank, associations of LPA genetic variants and observed Lp(a) concentrations with the risk of venous thromboembolism (VTE) and MI were investigated, stratified by scores of genetic variants influencing coagulation through the thrombin and platelet pathways (denoted as F2/F5 and GUCY1A3 scores, respectively). Risk estimates are expressed as hazard ratio (HR) and 95% confidence interval (95% CI).
Results: Neither LPA genetic variants nor observed Lp(a) concentration were associated with the risk of incident VTE (HR per 100 nmol/L higher Lp(a) 1.02, 95% CI 1.00-1.04, p=0.13). In contrast, there was a strong association with the risk of incident MI (HR per 100 nmol/L higher Lp(a) 1.31, 95% CI 1.29-1.33, p<0.001). The F2/F5 score was associated with a stepwise decrease in the risk of VTE, and the GUCY1A3 score with a stepwise decrease in the risk of MI. However, the associations of LPA genetic variants and observed Lp(a) concentrations with the risk of MI were not modified by stratification for either of the coagulation scores.
Conclusion: The association between Lp(a) and MI was not modified by genetically determined levels of coagulation activity through the thrombin or platelet pathway. Our findings do not support the notion that the increased risk of MI caused by elevated Lp(a) is due to prothrombotic effects.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.