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

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.