Lipid Lowering in Aortic Stenosis

Aortic valve stenosis (AS) is the end stage of an active fibrocalcific process with local inflammation, lipid deposition, fibrosis, and calcification as its key features.1 Adverse remodeling of a stenotic valve includes collagen deposition and elastin degradation, resulting from myofibroblast proliferation and activation, recruitment of inflammatory cells, and expression of proinflammatory cytokines.2 Activation of local calcific mediators results in massive calcification and even bone formation in the affected leaflets.1 In addition, oxidative stress is increased and neovascularization occurs in the normally avascular valve tissue.3,4 Lipid accumulation and oxidation may further contribute a proinflammatory impetus toward calcification and ossification.5 Moreover, valvular myofibroblasts undergo phenotypic transdifferentiation into osteoblastic cells, which spontaneously form calcific nodules, a process accelerated by inflammatory cytokines and oxidized cholesterol.2,5 Furthermore, in experimental animal models, hypercholesterolemia increases aortic valve cholesterol content and results in osteoblastic differentiation and bone formation; these adverse changes can be prevented by atorvastatin.5 Indeed, several experimental and retrospective clinical studies have suggested that statins may retard AS development.1,5