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

Summary

In 410,177 UK Biobank participants, higher Lp(a) strongly increased MI risk (HR 1.31 per 100 nmol/L) but was not associated with VTE. The MI association was not modified by genetic scores for thrombin or platelet pathway activity, arguing against a prothrombotic mechanism.

Key Findings

• Higher Lp(a) was not associated with incident VTE (HR 1.02 per 100 nmol/L; p=0.13).
• Higher Lp(a) was strongly associated with incident MI (HR 1.31 per 100 nmol/L; p<0.001).
• Associations of LPA variants/Lp(a) with MI were not modified by F2/F5 (thrombin) or GUCY1A3 (platelet) genetic scores.

Clinical Implications

Lp(a)-driven MI risk likely reflects atherosclerotic mechanisms; intensifying antithrombotic therapy alone is unlikely to mitigate risk. These data support prioritizing Lp(a)-lowering therapies and do not support anticoagulation solely for elevated Lp(a).

Limitations

• Observational design cannot fully exclude residual confounding
• Generalizability may be limited by UK Biobank demographics and ancestry composition

Future Directions

Evaluate whether Lp(a)-lowering therapies reduce MI independent of antithrombotic strategies and clarify atherogenic pathways (e.g., oxidized phospholipids) mediating risk.