Inflammatory Markers and Outcomes After Lacunar Stroke: Levels of Inflammatory Markers in Treatment of Stroke Study.

Abstract

BACKGROUND AND PURPOSE:

We hypothesized that concentrations of interleukin 6 (IL-6), serum amyloid A, tumor necrosis factor-α receptor 1, CD40 ligand, and monocyte chemoattractant protein 1 would predict recurrent ischemic stroke and major vascular events after recent lacunar stroke.

METHODS:

Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) study, a Phase III trial in patients with recent lacunar stroke. Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for recurrence risks.

RESULTS:

Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), there were 115 major vascular events (stroke, myocardial infarction, and vascular death). The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-α receptor 1 (adjusted HR per SD, 1.21; 95% CI, 1.05-1.41; P=0.01) and IL-6 (adjusted HR per SD, 1.10; 95% CI, 1.02-1.19; P=0.008). Compared with the bottom quartile (tumor necrosis factor-α receptor 1 <2.24 ng/L), those in the top quartile of tumor necrosis factor-α receptor 1 (>3.63 ng/L) were at twice the risk of major vascular events after adjusting for demographics (partially adjusted HR, 1.98; 95% CI, 1.11-3.52), though the effect attenuated after adjusting for other risk factors and statin use (adjusted HR, 1.68; 95% CI, 0.93-3.04). Serum amyloid A, CD40 ligand, and monocyte chemoattractant protein 1 were not associated with prognosis.

CONCLUSIONS:

Among recent lacunar stroke patients, IL-6 and TNF receptor concentrations predict risk of recurrent vascular events, and they are associated with the effect of antiplatelet therapies.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

• Authors: Amelia K Boehme, Leslie A McClure, Yu Zhang, Jorge M Luna, Oscar H Del Brutto, Oscar R Benavente, Mitchell S V Elkind
• Journal: Stroke (Stroke) Vol. 47 Issue 3 Pg. 659-67 (Mar 2016) ISSN: 1524-4628 [Electronic] United States
• PMID: 26888535 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Observational Study)
• Copyright: © 2016 American Heart Association, Inc.

Chemical References

• Biomarkers
• IL6 protein, human
• Inflammation Mediators
• Interleukin-6
• Platelet Aggregation Inhibitors
• Receptors, Tumor Necrosis Factor, Type I

Topics

• Aged
• Biomarkers (blood)
• Female
• Humans
• Inflammation Mediators (blood)
• Interleukin-6 (blood)
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (administration & dosage)
• Prospective Studies
• Receptors, Tumor Necrosis Factor, Type I (blood)
• Risk Factors
• Stroke, Lacunar (blood, diagnosis, drug therapy)
• Treatment Outcome