Lipoprotein(a) and prothrombotic effects: Evidence from a genetic association study: Prothrombotic effects of lipoprotein(a).

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.