title: C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study.
abstract: OBJECTIVE
  Inflammatory 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.
  
  
  METHODS
  Levels 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.
  
  
  RESULTS
  Among 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.
  
  
  CONCLUSIONS
  Among 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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00059306.
authors: 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.).
authors: Mitchell S V
authors: MS
authors: Elkind
authors: Jorge M
authors: JM
authors: Luna
authors: Leslie A
authors: LA
authors: McClure
authors: Yu
authors: Y
authors: Zhang
authors: Christopher S
authors: CS
authors: Coffey
authors: Ana
authors: A
authors: Roldan
authors: Oscar H
authors: OH
authors: Del Brutto
authors: Edwin Javier
authors: EJ
authors: Pretell
authors: L Creed
authors: LC
authors: Pettigrew
authors: Brett C
authors: BC
authors: Meyer
authors: Jorge
authors: J
authors: Tapia
authors: Carole
authors: C
authors: White
authors: Oscar R
authors: OR
authors: Benavente
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis*; D000077144:Clopidogrel; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D018401:Sample Size; D059409:Stroke, Lacunar / Q000097:blood*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: C-reactive protein; inflammation; prognosis; stroke