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(Circulation. 2009;119:2653-2655.)
© 2009 American Heart Association, Inc.

Editorial

Lipid Lowering in Aortic Stenosis

Still Some Light at the End of the Tunnel?

Satu Helske, MD, PhD; Catherine M. Otto, MD

From the Wihuri Research Institute, Helsinki, Finland (S.H.); and the Department of Medicine, Division of Cardiology, University of Washington, Seattle (C.M.O.).

Correspondence to Catherine M. Otto, MD, University of Washington, Division of Cardiology, Box 356422, 1959 NE Pacific St, AA510, Seattle, WA. E-mail cmotto@u.washington.edu

Key Words: Editorials • angiotensin • calcium • hypercholesterolemia • inflammation • stenosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

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

Article see p 2693

Inspired by these observations and epidemiological studies revealing an association between AS and hypercholesterolemia,¹ several prospective trials of statins in patients with AS have been conducted. The prospective but not randomized Rosuvastatin Affecting Aortic Valve Endothelium (RAAVE) trial (n=121) showed a smaller decline in valve area in AS patients receiving rosuvastatin. However, only patients with elevated serum low-density lipoprotein received the investigated drug.⁶ In contrast, 2 prospective randomized lipid-lowering trials both failed to show a decrease in hemodynamic progression of AS or a . . . [Full Text of this Article]

Related Article:

Lowering Plasma Cholesterol Levels Halts Progression of Aortic Valve Disease in Mice

Jordan D. Miller, Robert M. Weiss, Kristine M. Serrano, Robert M. Brooks, II, Christopher J. Berry, Kathy Zimmerman, Stephen G. Young, and Donald D. Heistad
Circulation 2009 119: 2693-2701. [Abstract] [Full Text]