Abstract 3612: Lipoprotein(a), Factor V Leiden Mutation and the Risk of Future Venous Thromboembolism in Women
Background: Venous thromboembolism (VTE) results from interactions of many risk factors, both genetic and environmental. Factor V Leiden (FVL) is a prevalent genetic risk factor for VTE. Lp(a), a heritable lipoprotein, is a known risk factor for arterial thrombosis but its contribution to venous thrombosis is less clear.
Methods: Lp(a) levels were measured by an apo(a)-isoform independent assay in 25,664 initially healthy women, free of prior VTE or cancer, in whom genotyping revealed that 1,282 carried FVL and 24,382 did not. The independent and joint effects of FVL and/or Lp(a) on the risk of first-ever VTE over an 11-year period were assessed in Cox-proportional hazard models and adjusted for potential confounding variables.
Results: There were 337 first VTE events over 282,644 person-years of follow-up. Women who were heterozygous or homozygous for FVL (5%) had 1.86 times higher risk of developing VTE in fully-adjusted models (95% CI [1.27, 2.73], P=0.0014), compared to noncarriers. In contrast, there was little evidence of a relationship between Lp(a) and VTE (P-trend for Lpa(a) quintiles 0.62). However, multiplicative interaction between Lp(a) quintiles and carriage of FVL was seen (P-interaction 0.018); in analyses evaluating potential joint effects, the highest risk of VTE was obtained among women who carried FVL and had elevated Lp(a) levels (Figure⇓). In contrast, women without FVL had similar overall risks for VTE regardless of Lp(a) status (P-trend 0.78).
Conclusion: In this prospective cohort of initially healthy women, we observed an interaction between the Factor V Leiden mutation and Lp(a) that results in high risk of incident VTE for jointly affected individuals.