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Recent studies described an association between elevated levels of C-reactive protein (CRP) and outcome after ischemic stroke. We investigated the impact of early serial CRP measurements in hyperacute ischemic stroke on long-term outcome.One hundred twenty-seven consecutive patients without thrombolysis with a first ischemic stroke no more than 12 hours after symptom onset were examined. Serial CRP measurements were done at admission (CRP 1), within 24 hours (CRP 2), and within 48 hours (CRP 3) after symptom onset. In addition to several cerebrovascular risk factors, the 1-year outcome and the lesion volumes of initial diffusion-weighted images were determined.The CRP concentration increased significantly during the first 48 hours after symptom onset (CRP 1, 0.86 mg/dL [95% CI, 0.69 to 1.02]; CRP 2, 1.22 mg/dL [95% CI, 0.88 to 1.55]; CRP 3, 1.75 mg/dL [95% CI, 1.25 to 2.25];P =0.003). Multiple logistic regression analysis identified Barthel Index score at admission and CRP 2 and 3 as independent predictors of an unfavorable outcome. Kaplan-Meier analysis revealed a significantly higher rate of end point events (adjusted odds ratio, 3.9 [95% CI, 1.4 to 10.7];P =0.008) only in patients with elevated CRP 2 concentrations.The CRP level measured within 12 hours after symptom onset of an acute ischemic stroke is not independently related to long-term prognosis. In contrast, a CRP increase between 12 and 24 hours after symptom onset predicts an unfavorable outcome and is associated with an increased incidence of cerebrovascular and cardiovascular events.