Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study

Abstract

Background and purpose: inflammatory markers may be associated with recurrent vascular events after stroke. We aimed to determine the association between IL-6, C-reactive protein, fibrinogen and white cell count, with recurrent vascular events after stroke, and to compare the association between circulating inflammatory markers with the risk of death from vascular vs nonvascular causes.

Methods: we prospectively recruited patients with acute stroke (n=817) and followed them for up to 4 years for the occurrence of fatal or nonfatal recurrent stroke, myocardial infarction or fatal vascular events, and death from any cause (n=159).

Results: the delay to assessment was a median of 10 days. The adjusted incidence of the outcome cluster recurrent stroke, myocardial infarction or vascular death after stroke was significantly higher with higher levels of IL-6 (75(th) to 25(th) percentile hazard ratio, 1.56; 95% CI, 1.37-1.77), C-reactive protein (75(th) to 25(th) percentile hazard ratio, 1.08; 95% CI, 1.04-1.11), and fibrinogen (75(th) to 25(th) percentile hazard ratio, 1.45; 95% CI, 1.24-1.72). The associations between inflammatory markers and death were stronger than with recurrent vascular events. The associations of inflammatory markers with vascular and nonvascular deaths were similar.

Conclusions: although inflammatory markers were associated with an increased risk of recurrent vascular events and vascular death after stroke, they were also associated with nonvascular causes of death, suggesting that inflammatory markers do not play a causal role specifically in the generation of recurrent vascular events after stroke. Future studies of the prediction of recurrent vascular events after stroke should concentrate on clinical variables or different blood markers.

Figure 1

Unadjusted Kaplan Meier survival curve and life table, for survival free from recurrent stroke, myocardial infarction or vascular death by third of interleukin 6.

Figure 2

Unadjusted cumulative incidence curves of (a) death from recurrent stroke, MI or other vascular causes, (b) death from the initial stroke with no evidence of recurrent stroke or (c) other non-vascular deaths, by thirds of interleukin 6, estimated from a competing risk analysis.