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 Goldstein;Henrik Sillesen;Weihang Bao;Gregory Preston;K. Michael Welch;
From Division of Cardiology, San Francisco General Hospital and University of California (P.G.); Paris-Diderot, Sorbonne University, France (P.A.); Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France (P.A.); Department of Neurology, University of Kentucky, Lexington (L.B.G.); Department of Vascular Surgery, University of Copenhagen, Denmark (H.S.); Pfizer Inc, New York, NY (W.B., G.M.P.); and Rosalind Franklin University of Medicine and Science, North Chicago, IL (K.M.A.W.).
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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.