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Background  Human abdominal aortic aneurysm (AAA) lesions contain high levels of cathepsin S (CatS), but are deficient in its inhibitor, cystatin C. Whether plasma CatS and cystatin C levels are also altered in AAA patients remains unknown.    Methods and Results  Plasma samples were collected from 476 male AAA patients and 200 age–matched male controls to determine CatS and cystatin C levels by ELISA. Student's  t  test demonstrated higher plasma levels of total, active, and pro–CatS in AAA patients than in controls ( P <0.001). ROC curve analysis confirmed higher plasma total, active, and pro–CatS levels in AAA patients than in controls ( P <0.001). Logistic regression suggested that plasma total (odds ratio [OR] = 1.332), active (OR = 1.21), and pro–CatS (OR = 1.25) levels were independent AAA risk factors that associated positively with AAA ( P <0.001). Plasma cystatin C levels associated significantly, but negatively, with AAA (OR = 0.356,  P <0.001). Univariate correlation demonstrated that plasma total and active CatS levels correlated positively with body–mass index, diastolic blood pressure, and aortic diameter, but negatively with the lowest ankle–brachial index (ABI). Plasma cystatin C levels also correlated negatively with the lowest ABI. Multivariate linear regression showed that plasma total, active, and pro–CatS levels correlated positively with aortic diameter and negatively with the lowest ABI, whereas plasma cystatin C levels correlated negatively with aortic diameter and the lowest ABI, after adjusting for common AAA risk factors.    Conclusions  Correlation of plasma CatS and cystatin C with aortic diameter and the lowest ABI suggest these serological parameters as biomarkers for human peripheral arterial diseases and AAA.

Plasma Cathepsin S and Cystatin C Levels and Risk of Abdominal Aortic Aneurysm: A Randomized Population–Based Study