Cystatin C deficiency linked to increased abdominal aortic aneurysm size

NEW YORK (Reuters Health) – Low levels of the cysteine protease inhibitor, cystatin C, are predictive of increasing size and expansion rate of abdominal aortic aneurysms in men, Danish researchers report.

Dr. J. S. Lindholt and colleagues from the Viborg-Kjellerup County Hospital, collected data on 151 men, 65 to 73 years of age with small abdominal aortic aneurysms. These patients were followed for a mean of 2.9 years. For 142 of the men, the researchers determined the serum levels of cystatin C, creatinine and C-reactive protein.

After adjusting for renal function, smoking, diastolic blood pressure, C-reactive protein, age and the size of the aneurysm, there was a negative correlation between levels of cystatin C and the increasing size (r = -0.22) and annual expansion rate (r = -0.24) of the aneurysm, Dr. Lindholt's team found.

During follow-up, 31 of the aneurysms expanded to over 50 mm, requiring surgery. Cystatin C levels predicted these events with a sensitivity of 61% and a specificity of 57%. However, the initial size of the aneurysm was more predictive of growth and expansion rate, with a sensitivity and specificity of 81%, according to the report in the November issue of the British Journal of Surgery.

Dr. Lindholt and colleagues conclude that "deficiency of cystatin C is associated with increased aneurysm expansion, possibly due to lack of inhibition of cysteine proteases involved in aneurysm degradation. Thus, several proteases and their inhibitors, including cystatin C, seem to be involved in the matrix degradation, in addition to metalloproteases."

"The findings in this study suggest two potential new pharmacological interventions for small abdominal aortic aneurysm," the investigators comment. One potential therapy is the administration of glucocorticoids to increase cystatin C levels, and the other is increasing cystatin production by giving transforming growth factor-beta-1.

Br J Surg 2001;88:1472-1475.

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