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Home > Vascular Annual Meeting > urbonaviciene_elevated_serum

Elevated Serum Cystatin C Is Associated with Increased Mortality in Patients with Peripheral Arterial Occlusive Disease

Grazina Urbonaviciene¹, Guo-Ping Shi², Eskild W Henneberg¹, Jes S Lindholt.^1
1Vascular Research Unit, Department of Vascular Surgery, Viborg Hospital, Viborg, Denmark;²Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

OBJECTIVES: Previous studies have shown that cysteine proteases and their inhibitor Cystatin C have been implicated in the development and progression of atherosclerosis. In addition, Cystatin C is becoming an increasingly known marker of elevated risk of death from cardiovascular (CV) causes, myocardial infarction and stroke. We look for associations between Cathepsins L, S and Cystatin C, and first CV event in patients with peripheral arterial occlusive disease (PAD).

METHODS: A cohort study of 376 patients with clinical evident PAD was enrolled at the Department of Vascular Surgery, Viborg Hospital. Follow-up was performed by nation wide registries concerning hospital admissions and death by all causes. The relationship between serum Cystatin C, Cathepsin L and S, time to first CV events and death was investigated by Cox regression, adjusted for potential confounders. After a median time of follow-up of 3.3±2.3 years, 166 first CV events and 84 deaths occurred.

RESULTS: Serum Cystatin C levels were significantly higher in patients dying during follow-up (1.04 vs. 0.75 mg/l, p<0.0001) compared to survived. Serum Cathepsin L levels tended to be higher in patients dying during follow-up (10.6 vs. 6.2 mg/l; p=0.065) contrary to Cathepsin S which was lower in patients dying later (18.5 vs. 21.6 mg/l, p<0.05. The unadjusted risk ratio of Cystatin C for death in the lower tertile, median, and upper tertile was 2.35 (95%CI, 1.37-4.01, p=0.002), 2.28 (95%CI, 1.4-3.58, p<0.0001), and 3.07 (95%CI, 1.99-4.73, p<0.0001), respectively. Consequently, patients in the upper third of Cystatin C-levels had more than three times increased risk of dying. After adjustment for age, gender, diabetes mellitus, current smoking, diastolic hypertension, body mass index and total cholesterol, this risk ratio remained significant at 2.08 (95%CI, 1.27-3.42; p=0.004). The unadjusted risk ratio for CV event in the lower tertile, median, and upper tertile was 0.99 (95%CI, 0.72-1.36), 0.96 (95%CI, 0.71-1.31), and 0.90 (95%CI, 0.65-1.24) respectively. These associations, however, did not reach statistical significance. We did not found any significant associations between Cathepsins L and S and risk of death or cardiovascular event.

CONCLUSIONS: Serum cystatin C seems to be a strong predictor of death in PAD patients.

AUTHOR DISCLOSURES: G. Urbonaviciene, None; G. Shi, None; E.W. Henneberg, None; J.S. Lindholt, None.