Association of osteopontin, neopterin, and myeloperoxidase with stroke risk in patients with prior stroke or transient ischemic attacks results of an analysis of 13 biomarkers from the stroke prevention by aggressive reduction in cholesterol levels trial

Peter Ganz, Pierre Amarenco, Larry B. Goldstein, Henrik Sillesen, Weihang Bao, Gregory M. Preston, K. Michael A. Welch

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background and Purpose-Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. Methods-We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. Results-There was no association between time to stroke and lipoprotein-associated phospholipase A2, monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P<0.0001), neopterin (hazard ratio, 1.137; P=0.0107), myeloperoxidase (hazard ratio, 1.177; P=0.0022), and adiponectin (hazard ratio, 1.207; P=0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 (P=0.015) and yielded a continuous net reclassification improvement (29.1%; P<0.0001) and an integrated discrimination improvement (42.3%; P<0.0001). Conclusions-Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm. Clinical Trial Registration-URL: Http://www.clinicaltrials.gov. Unique Identifier: NCT00147602.

Original languageEnglish
Pages (from-to)3223-3231
Number of pages9
JournalStroke
Volume48
Issue number12
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2017 American Heart Association, Inc.

Keywords

  • Biomarkers
  • Hydroxymethylglutaryl-CoA reductase inhibitors
  • Proteomics
  • Risk factors
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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