C-Reactive Protein Is a Determinant of First-Ever Stroke: Prospective Nested Case-Referent Study

Abstract

Background and Purpose: C-reactive protein (CRP) is a determinant of stroke, but there are no prospective studies on CRP and first ischemic stroke divided into etiologic subtypes. Our primary aim was to study CRP as a determinant of ischemic stroke, classified according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, and intracerebral hemorrhage (ICH) in a prospective study. A secondary aim was to study the relationship between the 1444C>T polymorphism, plasma levels of CRP and stroke. Methods: The study was a prospective population-based case-referent study nested within the Northern Sweden Cohorts. We defined 308 cases of ischemic stroke and 61 ICH. Two controls for each case were defined from the same cohort. Results: The OR for the highest (>3 mg/l) versus lowest group (<1 mg/l) of CRP was 2.58 (95% CI 1.74–3.84) for ischemic stroke and 1.63 (95% CI 0.67–3.93) for ICH. In a multivariate model including traditional risk factors, CRP remained associated with ischemic stroke (OR 2.06; 95% CI 1.29–3.29). Small-vessel disease was associated with CRP in the multivariate model (OR 3.88; 95% CI 1.10–13.7). The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP but neither with ischemic stroke nor with ICH. Conclusions: This prospective population-based study shows that CRP is significantly associated with the risk of having a first ischemic stroke, especially for small-vessel disease. No significant associations were found between the CRP 1444C>T polymorphism and any stroke subtype.