Inflammation, Hemostatic Markers, and Antithrombotic Agents in Relation to Long-Term Risk of New Cardiovascular Events in First-Ever Ischemic Stroke Patients

Abstract

The measurement of markers of inflammation or thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. We evaluated the usefulness of these markers as predictors of cardiovascular events in ischemic stroke patients. We analyzed levels of C-reactive protein (CRP), fibrinogen, and D-dimer within the first 24 hours after stroke onset in 473 first-ever ischemic stroke patients and determined the cumulative survival curves free of cardiovascular events in relation to the level of each of these markers according to the Kaplan-Meier method. We adjusted for possible confounding variables using a multivariate Cox proportional-hazards model. Patients in the highest tertiles of D-dimer, fibrinogen, and CRP were associated with an excess risk of new cardiovascular events of 36% (P=0.0134), 63% (P<0.0001), and 72% (P<0.0001), respectively, compared with patients in the lowest tertile. The patients in the highest tertile of CRP had 4 times the risk (hazard ratio, 4.04; P<0.0001) of a new cardiovascular event. Smoking, age, sex, and body mass index did not modify risk, and risk was independent of other confounding variables and of D-dimer and fibrinogen levels. The use of ticlopidine was associated with a significant risk reduction among patients with lower (86%, P=0.0159) and middle (69%, P<0.0001) levels of CRP, whereas a nonsignificant excess risk (27%, P=0.3896) was evident among those with the highest levels. Elevated levels of CRP, more than of D-dimer and fibrinogen, are related to the risk of new cardiovascular events after ischemic stroke. The efficacy of antiplatelet therapy in secondary prevention appears to be directly related to level of inflammatory and thrombotic markers.