Plasma CXCL12 Levels as a Predictor of Future Stroke

Abstract

Background and Purpose— The chemokine ligand CXCL12 is constitutively expressed in the bone marrow and other tissues including the brain endothelium and is responsible for regulating the trafficking of bone marrow progenitor cells. CXCL12 has been shown to play a significant role in animal models of ischemic stroke but its role in human stroke is unclear. The aim of this study was to test the hypothesis that elevated circulating baseline CXCL12 levels are associated with subsequent stroke. Methods— We prospectively collected demographic and angiographic data from consecutive patients referred for elective coronary angiography. Before coronary angiography a peripheral blood sample was collected for subsequent measurement of CXCL12. One-year stroke risk was calculated using the Framingham Risk Profile. Clinical follow-up was performed at 6 months and 1 year. Results— Of 206 subjects enrolled, 10 (4.9%) sustained an ischemic stroke over the 1year follow-up. There were no significant differences in baseline clinical characteristics or angiographic findings. However, median CXCL12 levels were significantly higher in those who sustained an ischemic stroke compared with those who did not (10 856 pg/mL versus 2241 pg/mL, P =0.007). The time to stroke distribution between subjects with baseline CXCL12 levels ≥10 421 pg/mL and those with baseline CXCL12 levels <10 421 pg/mL was significantly different (log rank P <0.001). The weighted Cox proportional hazard model demonstrated that baseline CXCL12 levels ≥10 421 pg/mL were significantly associated with ischemic stroke at follow-up (hazard ratio, 15.29; 95% CI, 3.05–76.71). Conclusions— Plasma CXCL12 levels may represent a novel biomarker of future ischemic stroke.