• Mitchell S V Elkind, Jorge M Luna, Leslie A McClure, Yu Zhang, Christopher S Coffey, Ana Roldan, Oscar H Del Brutto, Edwin Javier Pretell, L Creed Pettigrew, Brett C Meyer, Jorge Tapia, Carole White, Oscar R Benavente, and LIMITS Investigators.
• From the Department of Neurology, College of Physicians and Surgeons (M.S.V.E., J.M.L.), Department of Epidemiology, Mailman School of Public Health (M.S.V.E., J.M.L.), and Gertrude H. Sergievsky Center (M.S.V.E.), Columbia University, New York, NY; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL (L.A.M., Y.Z.); Department of Biostatistics, University of Iowa, Iowa City, IA (C.S.C.); Department of Neurology, University of Texas at Houston, Houston, TX (A.R.); School of Medicine, Universidad Espíritu Santo-Ecuador, Guayaquil, Ecuador (O.H.D.B.); Department of Neurology, Hospital Alberto Sabogal, Lima, Peru (E.J.P.); Department of Neurology, University of Kentucky, Lexington, KY (L.C.P.); Department of Neurology, University of San Diego, San Diego, CA (B.C.M.); Department of Neurology, Pontificia Universidad Católica de Chile, Santiago, Chile (J.T.); School of Nursing and Secondary Prevention of Small Subcortical Strokes (SPS3) Coordinating Center, University of Texas Health Science Center at San Antonio, San Antonio, TX (C.W.); and Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada (O.R.B.).
• Stroke. 2014 Mar 1; 45 (3): 707-16.

Background And PurposeInflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke.MethodsLevels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use.ResultsAmong 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP>4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment.ConclusionsAmong recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets.Clinical Trial Registration Urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00059306.

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