Physicians' Academy for Cardiovascular Education

Elevated levels of four inflammatory biomarkers associated with increased risk of stroke

Shoamanesh A et al., Neurology 2016

Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study

Shoamanesh A, Preis SR, Beiser AS, et al.
Neurology 2016; published online ahead of print


The Framingham Stroke Risk Profile score is used for the risk stratification of individuals at high risk of future vascular events. The risk score guides treatment strategies in these individuals.
The stroke pathogenesis is influenced by inflammatory processes. Therefore it is hypothesised that the inclusion of inflammatory biomarkers may strengthen the predictive ability of the Framingham Stroke Risk Profile score.
In this study, inflammatory biomarkers were evaluated in relation to the risk of incident ischemic stroke (IIS) in a community-based cohort of 3 224 Framingham off-spring participants. The inflammatory biomarkers included: CRP (C-reactive protein), tHcy (total homocysteine), TNFR2 (tumor necrosis factor receptor 2), and VEGF (vascular endothelial growth factor). During a mean follow-up of 9.3 years, 3% of the participants had an IIS.

Main results

Model 1 (including age and sex): These inflammatory biomarkers were associated with a risk of IIS:
  • CRP: HR: 1.28; 95% CI: 1.04–1.56
  • TNFR2: HR: 1.33; 95% CI: 1.09–1.63
  • tHcy: HR: 1.32; 95% CI: 1.11–1.58
  • VEGF: HR: 1.25; 95% CI 1.07–1.46
Model 2 (additional adjustment for SBP, hypertension treatment, current smoking, DM, CVD, AF): The following associations remained statistically significant: 
  • TNFR2: HR: 1.24; 95% CI: 1.02–1.51
  • tHcy: HR: 1.20; 95% CI: 1.01–1.43
  • VEGF: HR: 1.21; 95% CI: 1.04–1.42  
VEGF contributed the highest discriminatory ability to the Framingham Stroke Risk Profile score compared with the other biomarkers (NRI: 0.27; 95% CI: 0.03–0.50; P = 0.05).
The inclusion of all biomarkers led to the greatest improvement in the prediction of IIS (NRI: 0.34; 95% CI: 0.12–0.57; P = 0.05).


In community-dwelling individuals of the Framingham off-spring cohort, the predictive ability of the Framingham Stroke Risk Profile score for IIS was significantly improved by the addition of 4 inflammatory biomarkers, suggesting that these biomarkers should be further investigated as therapeutic targets for primary stroke prevention.
Find this article online at Neurology