Higher cystatin C level predicts long-term mortality in patients with peripheral arterial disease

Aims: Cystatin C and cathepsins could play a role in different processes and stages of the atherosclerotic disease. We aimed to investigate the relationship of cystatin C, and cathepsins L, and S, to lethal outcome in patients with peripheral arterial disease (PAD). Methods and results: We studied 378 patients with established PAD. Cox regression was used to assess relationships between serum cystatin C or cathepsins L and S, and time to lethal outcome. The role of cystatin for prognosis of cardiovascular death was assessed with c-statistic, and net reclassification improvement (NRI). Patients with cystatin C levels above 1 mg/l (fifth quintile) had a significantly increased adjusted risk for all-cause and cardiovascular mortality compared to patients with cystatin C levels below or equal to 1 mg/l (hazard ratios (HR) 2.2, 95% CI 1.22-4.12, and HR 3.2, 95% CI 1.39-7.59, respectively). Furthermore, high cystatin C levels were related with higher all-cause (adjusted HR 2.99, 95% CI 1.31-6.85) and cardiovascular mortality (adjusted HR 4.36, 95% CI 1.07-18.8) among PAD patients without renal impairment. Although the addition of cystatin C to conventional risk factors improved the accuracy of risk prediction model for cardiovascular mortality (0.72-0.79; p=0.03), it did not reclassify a substantial proportion of patients to risk categories (NRI = 0.12, p=0.128). Conclusions: Higher cystatin C levels independently predicted 5 years all-cause, and cardiovascular death in PAD patients. However, a small improvement in discrimination with the addition of cystatin C to conventional risk factors, and no improvement in reclassification of risk categories suggest that clinical usefulness of cystatin C for predicting cardiovascular mortality in PAD population might be modest. (C) 2011 Elsevier Ireland Ltd. All rights reserved.