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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1018.)
© 2002 American Heart Association, Inc.

Thrombosis

Protein C, Antithrombin, and Venous Thromboembolism Incidence

A Prospective Population-Based Study

Aaron R. Folsom; Nena Aleksic; Lu Wang; Mary Cushman; Kenneth K. Wu; Richard H. White

From the Division of Epidemiology (A.R.F., L.W.), School of Public Health, University of Minnesota, Minneapolis; the Division of Hematology (N.A., K.K.W.), University of Texas Medical School, Houston; the Department of Medicine (M.C.), University of Vermont, Burlington; and the Division of General Medicine (R.H.W.), University of California-Davis, Sacramento.

Correspondence to Aaron R. Folsom, MD, Division of Epidemiology, School of Public Health, University of Minnesota, Suite 300, 1300 South Second St, Minneapolis, MN 55454-1015. E-mail folsom{at}epi.umn.edu

Abstract— Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95% CI 1.24 to 9.11) in the 1.1% of subjects with protein C values <2.0 mg/L compared with subjects with higher values. In contrast, in the ARIC Study and the CHS, there was no association between low plasma antithrombin and venous thromboembolism. In conclusion, in this population-based study, a low protein C, but not antithrombin, level has been determined to be associated with an increased incidence of venous thromboembolism. Attributable risk estimates suggest that low protein C levels account for 2.5% of venous thromboembolic events in the ARIC population.

Key Words: antithrombin • protein C • prospective study • venous thrombosis • pulmonary embolus

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