TY - JOUR

T1 - Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks

T2 - Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial

AU - Ganz, Peter

AU - Amarenco, Pierre

AU - Goldstein, Larry B

AU - Sillesen, Henrik

AU - Bao, Weihang

AU - Preston, Gregory M

AU - Welch, K Michael A

AU - SPARCL Steering Committee

N1 - © 2017 American Heart Association, Inc.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Aged

KW - Anticholesteremic Agents/therapeutic use

KW - Biomarkers/blood

KW - Cohort Studies

KW - Female

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Ischemic Attack, Transient/epidemiology

KW - Male

KW - Middle Aged

KW - Neopterin/blood

KW - Osteopontin/blood

KW - Peroxidase/blood

KW - Prognosis

KW - ROC Curve

KW - Recurrence

KW - Risk Factors

KW - Stroke/epidemiology

U2 - 10.1161/STROKEAHA.117.017965

DO - 10.1161/STROKEAHA.117.017965

M3 - Journal article

C2 - 29114094

VL - 48

SP - 3223

EP - 3231

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 12

ER -