Abstract

Introduction: CD14 is a co-receptor for bacterial lipopolysaccharide and promotes an inflammatory response. CD14 is expressed on the surface of several innate immune cell subpopulations and also circulates in blood as a soluble form (sCD14). Despite its potential role in cardiovascular disease risk, prospective studies evaluating sCD14 with ischemic stroke outcomes are limited, especially among those of non-European ancestry. We examined the associations between sCD14 levels with incident ischemic stroke risk in REGARDS. Methods: REGARDS recruited 30,239 participants across the contiguous U.S. in 2003-07. By design, 55% of participants were female, 41% were black, and 56% lived in the southeast. With 5.8 years follow up, baseline plasma sCD14 was measured by ELISA in 548 incident cases of ischemic stroke and in a stroke-free cohort random sample ( n =1,039). Cox proportional hazards models were used to estimate the hazard ratio (HR) of incident ischemic stroke adjusted for Framingham stroke risk factors. We tested for a sCD14-by-race interaction. Results: Soluble CD14 levels were higher with older age, in women, and lower among blacks. Each 1-standard deviation (SD) higher sCD14 (447 ng/mL) was associated with an increased risk of incident ischemic stroke following adjustment for demographic variables (HR: 1.22; 95% confidence interval (CI): 1.07, 1.40) and stroke risk factors (HR: 1.19; 95% CI: 1.01, 1.40). In analyses stratified by race, the association of sCD14 with stroke was stronger in blacks (HR: 1.42; 95% CI: 1.12, 1.80) and not present in whites (HR: 1.02; 95% CI: 0.82, 1.27) (sCD14 x race interaction p-value = 0.04). Conclusions: These results show that higher sCD14 is associated with risk of ischemic stroke in blacks but not whites, and thus may be a risk factor unique to blacks.

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