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Abstract
Objective: We related a panel of inflammatory biomarkers to risk of incident ischemic stroke (IIS) in a community-dwelling sample.
Methods: Stroke-free Framingham offspring attending examination cycle 7 (1998–2001) had 15 circulating inflammatory biomarkers measured. Cox proportional hazard models were used to calculate the hazard ratios (HRs) of IIS per SD increment of each biomarker. Model 1 included age and sex. Model 2 additionally adjusted for systolic blood pressure, hypertension treatment, current smoking, diabetes, cardiovascular disease, and atrial fibrillation. The continuous net reclassification improvement was used to assess the improvement in IIS risk prediction of statistically significant biomarkers from our main analysis over traditional stroke risk factors.
Results: In 3,224 participants (mean age 61 ± 9 years, 54% women), 98 experienced IIS (mean follow-up of 9.8 [±2.2] years). In model 1, ln–C-reactive protein (ln-CRP) (HR 1.28, 95% confidence interval [CI] 1.04–1.56), ln–tumor necrosis factor receptor 2 (ln-TNFR2) (HR 1.33, 95% CI 1.09–1.63), ln–total homocysteine (ln-tHcy) (HR 1.32, 95% CI 1.11–1.58), and vascular endothelial growth factor (VEGF) (HR 1.25, 95% CI 1.07–1.46) were associated with risk of IIS. All associations, except for ln-CRP, remained significant in model 2 (ln-TNFR2: HR 1.24, 95% CI 1.02–1.51; ln-tHcy: HR 1.20, 95% CI 1.01–1.43; and VEGF: HR 1.21, 95% CI 1.04–1.42). The addition of these 4 biomarkers to the clinical Framingham Stroke Risk Profile score improved stroke risk prediction (net reclassification improvement: 0.34, 0.12–0.57; p < 0.05).
Conclusions: Higher levels of 4 biomarkers—CRP, tHcy, TNFR2, and VEGF—increased risk of IIS and improved the predictive ability of the Framingham Stroke Risk Profile score. Further research is warranted to explore their role as potential therapeutic targets.
GLOSSARY
- CE=
- cerebral embolus;
- CI=
- confidence interval;
- CRP=
- C-reactive protein;
- HR=
- hazard ratio;
- IIS=
- incident ischemic stroke;
- NRI=
- net reclassification improvement;
- tHcy=
- total homocysteine;
- TNFR2=
- tumor necrosis factor receptor 2;
- VEGF=
- vascular endothelial growth factor
Footnotes
↵* These authors contributed equally to this work as senior authors.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
Editorial, page 1194
- Received December 9, 2015.
- Accepted in final form May 17, 2016.
- © 2016 American Academy of Neurology
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