Abstract 368: Serum Matrix Metalloproteinases 1, 2 and 9, Tissue Inhibitor of Metalloproteinases-1 and Inflammatory Markers in Patients with Aortic Valve Sclerosis

Abstract

Background: Valvular Aortic Sclerosis (AVS) and Calcified Degenerative Valvular Aortic Stenosis (AS) are important risk factors for cardiovascular events. Matrix Metalloproteinases (MMPs) and other inflammatory markers might play an important role in the mechanisms underlying endothelial dysfunction described in AS. The participation of MMPs in AVS is poorly studied as of yet. We evaluated the concentrations of MMPs 1,2 and 9 and tissue-1 inhibitor (TIMP-1) and inflammatory markers in AVS patients.

Methods: The research and the ethics committees of our institution approved the study. Samples were obtained from peripheral blood in a cohort of 107 subjects: 30 healthy blood donor controls, 47 with AS and 30 AVS. Serum concentrations of Interleukins (ILs) 1 and 6, Tumor Necrosis Factor (TNF-α) and MMPs 1, 2 and 9 and TIMP-1 were measured by quantitative immunoassay technique with commercial kits, while concentrations of C Reactive Protein (CRP) by nephelometry. In all patients endothelial function and carotid plaque, 256 slice coronary computed tomography and coronary calcium score were evaluated. A one way ANOVA nonparametric test (Kruskall-Wallis), Kaplan Meier and multivariate Cox regression model were performed.

Results: Serum concentrations of CRP, ILs 6 and 10, MMPs-1, 2, 9 and TIMP-1 were higher in AVS and AS patients than in healthy controls (p<0.001), while no differences between the two patients groups were found. However, the MMP-9/TIMP-1 ratio was higher in patients with AVS than the rest of the groups (p<0.05). Endothelial dysfunction (73.9%), carotid plaque (34.2%), coronary plaque (39.7%) and coronary calcium score >400 (14%) was similar in both patients groups. During follow-up of 19.96±14.51 months, 50.7% of AVS and AS patients developed cardiovascular events. Type 2 diabetes was the stronger predictors for cardiovascular events in ASV (RR= 2.67, IC95% de 1.027 - 6.926).

Conclusions: Our findings suggest an important inflammatory role of MMPs, TIMPs and cytokines in AVS disease, which could explain a higher prevalence of coronary artery disease in this patients.