Low protein C and incidence of ischemic stroke and coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.
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.


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.
Folsom
A R
AR
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA. folso001@umn.edu
Ohira
T
T
Yamagishi
K
K
Cushman
M
M
D002545:Brain Ischemia / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011486:Protein C / Q000032:analysis*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology*
D011486:Protein C
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