Elevated Serum Cystatin C and Decreased Cathepsin S/Cystatin C Ratio Are Associated with Severe Peripheral Arterial Disease and Polyvascular Involvement.

Peripheral arterial disease (PAD) is frequently associated with atherosclerotic manifestations of the carotids and coronaries. Polyvascular involvement and low ankle−brachial index predict major cardiovascular events and high mortality. Cathepsin S (Cat S) promotes the inflammatory pathways of the arterial wall, while Cystatin C (Cys C) functions as its inhibitor; therefore, Cys C was proposed to be a biomarker of progression in PAD. In a single-center observational study, we investigated the correlations of serum Cys C and Cat S/Cys C ratio in a group of 90 PAD patients, predominantly with polyvascular involvement. Cys C and Cat S/Cys C were associated with ankle−brachial index (ABI) scores <0.4 in univariate and multiple regression models. Furthermore, both markers correlated positively with the plasma Von Willebrand Factor Antigen (VWF: Ag) and Von Willebrand Factor collagen-binding activity (VWF: CB). In addition, Cat S/Cys C was significantly decreased, whereas Cys C increased in subjects with three-bed atherosclerotic involvement. According to our results, high serum Cys C and low Cat S/Cys C ratios may indicate severe peripheral arterial disease and polyvascular atherosclerotic involvement.

High circulating osteoprotegerin levels are associated with non-zero blood groups.

BACKGROUND: Osteoprotegerin (OPG) and von Willebrand factor (VWF) form complex within endothelial cells and following secretion. The nature of blood group antigens strongly influences the levels of circulating VWF, but there is no available data concerning its ascendancy on OPG levels. We aimed to assess the relationship of AB0 blood groups with OPG, VWF levels (VWF: Ag) and collagen binding activity (VWF: CB) in peripheral arterial disease (PAD) patients. METHODS: Functional and laboratory parameters of 105 PAD patients and 109 controls were examined. Results of OPG, VWF: Ag, VWF: CB (ELISA-s) were analysed by comparative statistics, together with clinical data. RESULTS: OPG levels were higher in patients than in controls (4.64 ng/mL vs. 3.68 ng/mL, p < 0.001). Among patients elevation was marked in the presence of critical limb ischemia (5.19 ng/mL vs. 4.20 ng/mL, p = 0.011). The OPG in patients correlated positively with VWF: Ag and VWF: CB (r = 0.26, p = 0.008; r = 0.33, p = 0.001) and negatively with ankle-brachial pressure index (r = -0.22, p = 0.023). Furthermore, OPG was significantly elevated in non-0 blood groups compared to 0-groups both in patients and controls (4.95 ng/mL vs. 3.90 ng/mL, p = 0.012 and 4.09 ng/mL vs. 3.40 ng/mL, p = 0.002). CONCLUSIONS: OPG levels are associated to blood group phenotypes and higher in non-0 individuals. Increased OPG levels in PAD characterize disease severity. The significant correlation between OPG and VWF:CB might have functional importance in an atherothrombosis-prone biological environment.