585 TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP1, TIMP2) ARE RELATED TO HYPERTENSION AND AORTIC STENOSIS?

Background: Aortic stenosis (AS) and hypertension (HT) are both associated with chronic pressure overload and left vetricular hyperthrophy. Matrix metalloproteinases (MMPs), specific tissue inhibitors of metalloproteinases (TIMPs) and inflammatory cytokines are involved in left ventricular remodeling. Local expression of TIMP-1 and TIMP-2 was found to be related to cardiac interstitial fibrosis and left ventricular overload. Objectives: The aim of study was to compare the serum level of metalloproteinase inhibitors (TIMP1, TIMP2) and selected mediators of inflammation and tissue remodeling (IL-1b, IL-6, monocyte chemoattractant protein 1 (MCP-1), TNFα, osteoprotegerin (OPG), osteopontin (OPN), NT-proBNP) in hypertensive and non-hypertensive stenotic patients and to evaluate the relationship of examined clinical and biochemical parameters to hypertension. Patients and Methods: Sixty six patients accepted for surgical aortic valve replacement with moderate (n=27) and severe (n=39) aortic stenosis were included. There were fifty two (78,8%) cases with concomitant arterial hypertension. In all patients we performed transthoracal echo with thypical projections, severe AS in 33 (50,0%) patients wtih mean gradient ≥ 50mmHg with left ventricular ejection fraction LVEF ≥50%, moderate AS 27 (40,9%) patients with mean gradient <50mmHg with LVEF < 50%. The panel of serum biomarkers: IL-1b, IL-6, TIMP1, 2 TIMP2, MCP-1, TNFα, OPG, OPN, NT-proBNP was measured using multiplex method based on Luminex technology (Flexmap 3D analyser). The data were analyzed with Mann-Whitney test, chi-squared/Fisher's exact test. Variables were also tested in multivariate logistic regression models. Results: The comparison of hypertensive and non-hypertensive patients disclosed the following significant differences: age (years) 67 (61-73) [median (inter-quartile range)] vs 57 (53-72); body mass index (BMI) 29,1 (26,9-32,1) vs 25,3 (22,8-29,6); IL-6 (pg/ml) 1,291 (0,82-2,872) vs 0,802 (0,563-1,17); TIMP2 (ng/ml) 113,6 (98,95-128,35) vs 95,73 (83,34-105,85) respectively. There were no significant differences in severity (moderate/severe) of aortic stenosis between hypertensive and non-hypertensive patients. In multivariate logistic regression analysis TIMP2 was the only factor significantly contributed to hypertension (OR=1.05, 95% CI=1.001-1.09, P=0.046). Conclusions: In our study the level of TIMP2 is related with arterial hypertension in patients with moderate to severe aortic stenosis influencing on pressure overload of the left ventricle.