Lipid biomarkers, hormone therapy and the risk of venous thromboembolism in women.
BACKGROUND
Published reports of a relationship between lipids and incident venous thromboembolism (VTE) are conflicting.


OBJECTIVE
To clarify the relationship between lipids and VTE risk in healthy women, including potential effect modification by hormone therapy (HT).


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 B(100).


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 Pinteraction<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.
Everett
B M
BM
The Center for Cardiovascular Disease Prevention, Harvard Medical School, and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA. beverett@partners.org
Glynn
R J
RJ
Buring
J E
JE
Ridker
P M
PM
D016632:Apolipoprotein A-I / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012306:Risk; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology*
D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D008055:Lipids