Lipoprotein(a) is not associated with venous thromboembolism risk

Objectives. Evidence from case-control studies as well as meta-analyses of these study designs suggest elevated lipoprotein(a) [Lp(a)] to be associated with an increased risk of venous thromboembolism (VTE). Prospective evidence on the association is limited, uncertain, and could be attributed to regression dilution bias. We aimed to assess the prospective association of Lp(a) with risk of VTE and correct for regression dilution. Design. We related plasma Lp(a) concentrations to the incidence of VTE in 2,180 men of the Kuopio Ischemic Heart Disease cohort study. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and repeat measurements of Lp(a) at 4 and 11 years from baseline, were used to correct for within-person variability. Results. After a median follow-up of 24.9 years, 110 validated VTE cases were recorded. The regression dilution ratio of loge Lp(a) adjusted for age was 0.85 (95% CI: 0.82-0.89). In analyses adjusted for several established risk factors and potential confounders, the HR (95% CI) for VTE per 1 SD (equivalent to 3.56-fold) higher baseline loge Lp(a) was 1.06 (0.87-1.30). In pooled analysis of five population-based cohort studies (including the current study) comprising 66,583 participants and 1,314 VTE cases, the fully-adjusted corresponding HR for VTE was 1.00 (95% CI: 0.94-1.07), with no evidence of heterogeneity between studies. Conclusions. Primary analysis as well as pooled evidence from previous studies suggest circulating Lp(a) is not prospectively associated with future VTE risk, indicating that evidence of associations demonstrated in case-control designs may be driven by biases such as selection bias.