Statin therapy and levels of hemostatic factors in a healthy population: The Multi-Ethnic study of atherosclerosis

Background: HMG-CoA reductase inhibitors (statins) reduce the risk of venous thromboembolism (VTE) in healthy people. Statins reduce levels of inflammation biomarkers; however, the mechanism for the reduction in VTE risk is unknown. Aim: In a large cohort of healthy people, we studied associations of statin use with plasma hemostatic factors related to VTE risk. Methods: Cross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6814 healthy men and women aged 45-84 years, free of clinical cardiovascular disease at baseline; 1001 were using statins at baseline. Twenty-three warfarin users were excluded. Age, race and sex-adjusted mean hemostatic factor levels were compared between statin users and non-users, and multivariable linear regression models were used to assess associations of statin use with hemostatic factors, adjusted for age, race/ethnicity, education, income, aspirin use, hormone replacement therapy (in women), and major cardiovascular risk factors. Results: Participants using statins had lower adjusted levels of D-dimer (- 9%), C-reactive protein (- 21%) and factor VIII (- 3%) than non-users (P < 0.05). Homocysteine and von Willebrand factor levels were non-significantly lower with statin use. Higher fibrinogen (2%) and plasminogen activator inhibitor-1 (22%) levels were observed among statin users than among non-users (P < 0.05). Further adjustment for LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use. Conclusions: Findings of lower D-dimer, FVIII and C-reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk. A prospective study or clinical trial linking these biochemical differences to VTE outcomes in statin users and non-users is warranted.