Lipoprotein(a) does not have a clinically significant arterial or venous prothrombotic effect

Presented at EAS 2022 by Elena Olmastroni (Milan, Italy)

Introduction and methods

Epidemiological meta-analysis, mendelian randomization and genome-wide association studies have demonstrated that lipoprotein(a) [Lp(a)] is an independent and causal contributor to ASCVD events. On the other hand, studies investigating a possible link between Lp(a) and VTE have reported conflicting results. The current study aimed to clarify the relation between Lp(a) and VTE by investigating whether Lp(a) has genetically and clinically meaningful venous or arterial prothrombotic effects.

The study used data from 445,774 participants (mean age 57.3 years, 54% female) from the UK Biobank. Exposure to Lp(a) was characterized from a clinical point of view by a measurement at the time of enrolment in the UK Biobank, and from a genetical point of view as an additive genetic score including two genetic variants.

Outcomes were major coronary events (MCE, defined as first occurrence of fatal or non-fatal MI, or coronary revascularization) and VTE (defined as a composite of DVT and PE). Stratified analyses were performed where the association between Lp(a) and MCE was stratified by genetic scores that mimic the effect of antiplatelet and antithrombin therapies.

Main results

• Median Lp(a) concentration was 18.7 nmol/L (IQR 7.4-72.9) in the overall cohort. Stratified by Lp(a) genetic score, median Lp(a) concentration was 13.6 (6.2-35.0) for a score of 0, 146.3 (104.8-200.2) for a score of 1 and 261.8 (190.2-336) for a score of 2.
• 100 nmol/L higher Lp(a) was associated with a 35% higher risk of MCE (HR 1.35, 95% CI 1.32-1.38). Risk for MCE increased with increasing Lp(a) genetic score (score of 0 = reference; score of 1: HR 1.47, 95% CI 1.43-1.52; score of 2: HR 1.89, 95% CI 1.70-2.10).
• There was no statistically significant evidence of an association between Lp(a) and VTE (effect of 100 nmol/L higher Lp(a): OR 0.99, 95% CI 0.96-1.02; Lp(a) genetic score of 1: OR 0.99, 95% CI 0.95-1.03; Lp(a) genetic score of 2: OR 1.00, 95% CI 0.85-1.18).
• In stratified analyses, the antiplatelet score was associated with a dose-dependent step-wise reduction in MCE risk, and the antithrombin score was associated with a dose-dependent step-wise reduction in VTE risk. However, the effects of Lp(a) on MCE risk were not attenuated by either genetically determined platelet or thrombin inhibition.

Conclusion

This study found that Lp(a) concentrations are not associated with thrombotic events. Elena Olmastroni further concluded that the increased risk of MCE caused by elevated Lp(a) is unlikely to be decreased by antiplatelet or antithrombin therapy. Therapies specially aimed at lowering Lp(a) are therefore needed.

– Our coverage of EAS 2022 is based on the information provided during the congress –