Lipoprotein(a) and incident venous thromboembolism in pre- and postmenopausal women, and in men

Background and Aims Elevated lipoprotein(a) [Lp(a)] levels are an established risk factor for atherosclerotic cardiovascular disease, but the association between Lp(a) and venous thromboembolism (VTE) remains unclear. Sex and hormonal status may modify the relationship between Lp(a) and VTE. Methods The present study included participants from the UK Biobank with available baseline Lp(a) data. Individuals with a history of VTE or cancer, as well as those using anticoagulants, were excluded. Multivariable-adjusted Cox models were used to assess the association between Lp(a) levels ≥ 125 nmol/L and incident VTE in premenopausal women, postmenopausal women, and men. Subgroup analyses stratified premenopausal women by oral contraceptive (OCP) use and postmenopausal women by menopausal hormone therapy (MHT) use. Results Among 55 302 premenopausal women, 129 045 postmenopausal women, and 189 013 men, the proportions with Lp(a) ≥ 125 nmol/L were 14.0%, 19.0%, and 15.0%, respectively. Over a median (interquartile range) follow-up of 13.6 (12.9-14.4) years, 8186 VTE events occurred (cumulative incidence 2.2%). Lp(a) ≥ 125 nmol/L was associated with incident VTE in premenopausal women [adjusted hazard ratio (aHR) 1.32; 95% confidence interval (CI) 1.04-1.66; P = 0.02] but not in postmenopausal women (aHR 1.03; 95% CI 0.94-1.13; P = 0.47; Pinteraction = 0.03) or men (aHR 1.00; 95% CI 0.92-1.08; P = 0.94). OCP use did not modify the Lp(a)-VTE association among premenopausal women (Pinteraction = 0.61). However, among postmenopausal MHT users, Lp(a) ≥ 125 nmol/L was associated with higher VTE risk (aHR 1.48; 95% CI 1.03-2.12; P = 0.03; Pinteraction = 0.04). Conclusions Elevated Lp(a) was associated with VTE in premenopausal women and in postmenopausal MHT users, suggesting that hormonal context may influence Lp(a)- associated thrombotic risk.