C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study

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; LIMITS Investigators

doi:10.1161/STROKEAHA.113.004562

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C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study

Journal article

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C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study

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, …

Stroke (1970), Vol.45(3), pp.707-716

03/2014

DOI: 10.1161/STROKEAHA.113.004562

PMCID: PMC4114338

PMID: 24523037

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Abstract

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. 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. 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. 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. http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Recurrence

Confidence Intervals

Prospective Studies

Ticlopidine - therapeutic use

Humans

Middle Aged

Stroke, Lacunar - blood

Inflammation Mediators - blood

Phlebotomy

Proportional Hazards Models

Male

Treatment Outcome

Biomarkers - blood

Antihypertensive Agents - therapeutic use

Ticlopidine - analogs & derivatives

Sample Size

Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use

Female

Aged

Aspirin - therapeutic use

Blood Pressure - drug effects

C-Reactive Protein - analysis

Platelet Aggregation Inhibitors - therapeutic use

Cohort Studies

Details

Title: Subtitle: C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study
Creators: Mitchell S V Elkind - 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.)
Jorge M Luna
Leslie A McClure
Yu Zhang - University of Alabama at Birmingham
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
LIMITS Investigators
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.45(3), pp.707-716
Publisher: United States
DOI: 10.1161/STROKEAHA.113.004562
PMID: 24523037
PMCID: PMC4114338
ISSN: 0039-2499
eISSN: 1524-4628
Grant note: R01 NS050724 / NINDS NIH HHS P30 DK079626 / NIDDK NIH HHS
Language: English
Date published: 03/2014
Academic Unit: Biostatistics
Record Identifier: 9983997324002771

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