Fourteen Biomarkers and Subsequent Disability in Patients with Stroke Recurrence: Results from the SPARCL Trial

INTRODUCTION: In patients enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial levels of osteopontin, neopterin, N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), myeloperoxidase, monocyte chemoattractant protein-1 (MCP-1), resistin, matrix metalloproteinase-9 (MMP-9), adiponectin, high-sensitive C-reactive protein (hsCRP), lipoprotein-associated phospholipase-A2 (Lp-PLA2), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble CD40-ligand (sCD40L), and HDL cholesterol (HDL-c) were measured 1-6 months after the qualifying stroke or TIA. We determined whether any of these biomarkers were associated with disability in case of recurrence.

METHODS: Among 463 recurrent strokes, the associations of these biomarkers with the National Institutes of Health-Stroke Scale (NIHSS), Barthel Index, and modified Rankin Score (mRS) measured after 90 days were assessed. Using adjusted logistic regression analysis, biomarker levels were compared between unfavorable versus favorable outcome (NIHSS ≥2 versus 0-1; Barthel Index <95 versus 95-100; and mRS 2-6 versus 0-1).

RESULTS: Higher baseline levels of osteopontin (OR: 1.166; 95% CI: 1.01-1.347, p = 0.0367) and neopterin (OR: 1.531; 95% CI: 1.07-2.188, p = 0.0195) predicted poorer outcomes after recurrent stroke. For participants with ischemic stroke, higher levels of neopterin (OR: 1.488; 95% CI: 1.022-2.167, p = 0.0384) and NT-proBNP, (OR: 1.399; 95% CI: 1.035-1.891, p = 0.0289) were predictor of unfavorable mRS. Analyses including stroke and TIA showed that lower HDL-c levels were associated with an unfavorable mRS (OR: 0.564; 95% CI: 0.328-0.971, p = 0.0387).

CONCLUSIONS: Higher levels of osteopontin, neopterin and NT-ProBNP and lower levels of HDL-c after stroke were independently associated with greater disability in case of recurrent stroke.