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 language | English |
|---|---|
| Pages (from-to) | 3223-3231 |
| Number of pages | 9 |
| Journal | Stroke |
| Volume | 48 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2017 |
Bibliographical note
Funding Information:Technical support in article preparation, but no assistance with content development or writing, was provided by Shirley Smith at Engage Scientific Solutions and was funded by Pfizer.
Funding Information:
This study was sponsored by Pfizer.
Funding Information:
Dr Ganz has received consulting fees from Pfizer and he consults for SomaLogic without payment. Dr Amarenco has received consulting or advisory board fees from Pfizer and Amgen; honoraria from AstraZeneca, Pfizer, KOWA, Bayer, Glaxo Smith Kline, Fibrogen, and ShingPoon; lecture fees from Bayer and Amgen; and grant support from French government, Pfizer, Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific. Dr Goldstein has received consulting fees and honoraria from Pfizer. Dr Sillesen has received consulting fees from Cardoz, Nycomed, and Pfizer. Dr Welch has received consulting fees, lecture fees, and grant support from Pfizer. Dr Bao is an employee of Pfizer; Dr Preston was an employee of Pfizer when this study was conducted.
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