Lipid biomarkers, hormone therapy and the risk of venous thromboembolism in women

Summary.  Background: Published reports of a relationship between lipids and incident venous thromboembolism (VTE) are conflicting. Objectives: To clarify the relationship between lipids and VTE risk in healthy women, including potential effect modification by hormone therapy (HT). Patients/methods: Among 27 081 initially healthy women followed prospectively for incident VTE, we measured a full panel of lipid biomarkers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and apolipoproteins A-I (apo A-I) and B₁₀₀. Results: During a median follow-up of 11.4 years, VTE occurred in 355 women. We observed no relationship between any of the lipids and VTE risk. However, when unprovoked VTE was considered separately ( n  = 161), both HDL-C and apo A-I were positively associated with risk. Fully adjusted hazard ratios (HR) and 95% confidence intervals (CI) for extreme tertiles of HDL-C and apo A-I were 1.75 (1.13–2.73) and 1.70 (1.10–2.62), respectively. After stratifying by HT use, this relationship was present only among HT users; the HRs for unprovoked VTE for extreme tertiles of HDL-C and apo A-I were 3.58 (1.69–7.58) and 2.88 (1.29–6.42) among users, but only 0.79 (0.39–1.62) and 0.89 (0.50–1.57) among non-users. The interactions were statistically significant (each P _interaction <0.05). Conclusions: We observed little evidence that lipid levels predict risk of incident VTE among non-users of HT. High levels of HDL-C and apo A-I associate with unprovoked VTE risk among HT users. This observation likely reflects prothrombotic effects of HT that are concomitant with HDL-C and apo A-I levels, rather than direct effects of those lipids.