Cystatin C is an Independent Risk Factor and Therapeutic Target for Acute Ischemic Stroke

Cystatin C (CysC) has been used as a renal function indicator and a strong predictor of cardiovascular events. In this study, we determined the prognostic value of serum CysC in patients with acute ischemic stroke (AIS) and examined its protective role on ischemic brain injury. First-ever stroke patients (601 cases) and control subjects (325 cases) were recruited. Serum CysC level in patients with AIS were significantly higher than that in controls. Multivariate logistic regression analyses showed that elevated CysC is an independent risk factor of AIS; the odds ratio (95 % confidence interval) was 9.80 (3.12-30.83). The integrated population was divided into quintiles according to serum CysC. Compared with the first quintile, the odds ratios of risk for AIS in fourth quintile and fifth quintile were 1.92 (1.08-3.40) and 2.88 (1.49-5.54), respectively. Serum CysC was not associated with neurological deficits and the location of ischemic area; however, serum CysC in patients decreased after one-week therapy. This was consistent with CysC expression after ischemia/reperfusion injury in a mouse focal ischemia/reperfusion injury model. Exogenous CysC exerted neuroprotective effects by reducing infarct volume in this animal stroke model. Therefore, serum CysC is highly associated with AIS and is an independent prediction marker for AIS. Since our findings demonstrated the protection of exogenous CysC on ischemic brain injury, CysC is a novel and promising therapeutic target for AIS.