Abstract 123: Role of Valsartan (V) Alone or in Combination with Simvastatin (S) in Reducing Inflammation of Thin Cap Fibroatheromas

Abstract

Objectives: We investigated the role of V alone or in combination with S on the histomorphologic characteristics of thin cap fibroatheromas (TCFAs), and tested the hypothesis that V or VS attenuate the proinflammatory effect of low endothelial shear stress (ESS). We used vascular profiling of swine coronary arteries for in vivo assessment of ESS to prospectively identify these low ESS areas that are prone to develop TCFAs. Methods: 12 diabetic hyperlipidemic swine were allocated into 3 treatment groups: placebo (P, n=4), V (n=4) and VS (n=4). Blood pressure, serum cholesterol and glucose were similar between the treatment groups. IVUS-based geometrically correct 3D reconstruction of the coronary arteries was performed at baseline (wk 23) and follow up (wk 30). Baseline ESS was calculated using computational fluid dynamics and plaque-free subsegments of interest were identified (n=109). Coronary arteries (n=31) were harvested at follow up, cryosectioned at the subsegments of interest and stained histologically. Intima/media ratio and inflammation (CD45) were quantified. Lesions were classified into atheromas without evidence of fibrous cap (n=82) and TCFAs (n=60). Results: V alone or in combination with S reduced the amount of plaque inflammation, particularly in TCFAs (Fig A ). V and VS attenuated the proinflammatory effect of local low ESS compared to P (Fig B ). Conclusion: V alone or in combination with S exerts a stabilizing effect of reducing plaque inflammation, even in high-risk regions with low ESS. These results suggest a mechanism of regional atheroprotection associated with V or VS.