Relationship between plasma cathepsin S and cystatin C levels and coronary plaque morphology of mild to moderate lesions: an in vivo study using intravascular ultrasound

Background Cathepsin Sand its endogenous inhibitor cystatin Care implicated in the pathogenesis of atherosclerosis, especially in the plaque destabilization and rupture leading to acute coronary syndrome. However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet. Methods We recruited 98 patients with unstable angina (UA, n=56) or stable angina (SA, n=42) who had a segmental stenosis resulting in >20% and <70% diameter reduction in one major coronary artery on coronary angiography. Thirty-one healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate plaque morphology. Plasma cathepsin S and cystatin C were measured as well. Results At the culprit lesion site, plaque area ((7.85 +/- 2.83) mm(2) vs (6.53 +/- 2.92) mm(2), P=0.027), plaque burden ((60.92 +/- 11.04)% vs (53.87 +/- 17.52)%, P=0.025), remodeling index (0.93 +/- 0.16 vs 0.86 +/- 0.10, P=0.004) and eccentricity index (0.74 +/- 0.17 vs 0.66 +/- 0.21, P=0.038) were bigger in UA group than in SA group. Plasma cathepsin S and cystatin C were significantly higher in patients than in controls (P <0.01). Plasma cathepsin S was higher in UA group ((0.411 +/- 0.121) nmol/L) than in SA group ((0.355 +/- 0.099) nmol/L, P=0.007), so did the plasma cystatin C ((0.95 +/- 0.23) mg/L in UA group, (0.84 +/- 0.22) mg/L in SA group; P=0.009). Plasma cathepsin S positively correlated with remodeling index (r=0.402, P=0.002) and eccentricity index (r=0.441, P=0.001), and plasma cystatin C positively correlated with plaque area (r=0.467, P <0.001) and plaque burden (r=0.395, P=0.003) in UA group but not in SA group. Conclusions Plasma cathepsin S and cystatin C increased significantly in UA patients. In angina patients, higher plasma cathepsin S may suggest the presence of vulnerable plaque, and higher plasma cystatin C may be a clue for larger atherosclerotic coronary plaque. Chin Med J 2009;122(23):2820-2826