Low protein C and incidence of ischemic stroke and coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.
    Folsom AR， Ohira T， Yamagishi K， Cushman M.
    Division of Epidemiology & Community Health， School of Public Health， University of Minnesota， Minneapolis， MN 55454， USA. folso001@umn.edu
Abstract
    BACKGROUND: Protein C is an important plasma natural anticoagulant. Although protein C deficiency increases risk of venous thrombosis， it remains uncertain whether low protein C increases risk of atherothrombosis.
    OBJECTIVE: To examine whether low protein C may be a risk factor for ischemic stroke or coronary events in a prospective population-based study.
    PATIENTS/METHODS: The Atherosclerosis Risk in Communities Study assessed protein C antigen by ELISA at baseline in 1987-89 and followed participants (n = 13 879) for incident ischemic stroke or coronary events through 2005.
RESULTS: Over a median of 16.9 years of follow-up， 613 ischemic strokes and 1257 coronary heart disease events occurred. Protein C was inversely associated with incidence of ischemic stroke. Adjusted for multiple risk factors， the rate ratios (95% CIs) from highest to lowest quintiles were 1.0， 1.16 (0.90-1.50)， 1.22 (0.94-1.58)， 1.18 (0.90-1.55) and 1.52 (1.17-1.98). This inverse association was stronger for non-lacunar and cardioembolic stroke than for lacunar stroke. In contrast， there was a positive association between protein C and coronary heart disease in incompletely adjusted models， but no association after adjustment for plasma lipids.
    CONCLUSIONS: In this cohort study， low protein C was a risk factor for incident ischemic stroke but not coronary heart disease. Levels of protein C associated with stroke risk were not restricted to the traditional ’deficient’ range for protein C (< 0.5 percentile)， suggesting that other etiologies for a lower protein C， or genetic variants associated with more subtle changes in protein C， are playing a role in disease pathogenesis.
 

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