Prevention of aortic valve stenosis: A realistic therapeutic target?

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• 作者：D.T. Ngo^a ; ^b ; ¹ ; A.L. Sverdlov^a ; ¹ ; J.D. Horowitz^a ; ^{john.horowitz@adelaide.edu.au}
• 关键词：5-HT ; serotonin ; ACE ; angiotensin-converting enzyme ; ADMA ; asymmetric dimethylarginine ; Ang II ; angiotensin II ; apo ; apolipoproteins ; AS ; aortic valve stenosis ; ASc ; aortic valve sclerosis ; ATP ; adenosine triphosphate ; AVA ; aortic valve area ; AVR ; aortic
• 刊名：Pharmacology and Therapeutics
• 出版年：2012
• 期刊代码：41_01637258
• 类别：pha
• 出版时间：July, 2012
• 卷：135
• 期：1
• 页码：78-93
• 文件大小：837 K

摘要

Aortic valve stenosis (AS) is the most common form of valvular heart disease in the Western world, affecting ~40%of the population over the age of 80; to date the only established treatment is valve replacement. However, AS progression occurs over many years, and is associated from its earliest stages with increased risk of coronary events.

Recent insight into the pathophysiology of AS has included central roles for angiotensin II, for diminished nitric oxide effect at the level of valve endothelium and matrix, and for inflammatory activation/redox stress culminating in activation of pro-calcific stimuli. Despite the presence of atheroma within the stenotic valve, hyperlipidemia per se does not play a critic role in the development of obstructive disease.

We review emerging options for pharmacotherapy of AS, including in particular retardation of disease progression. The various clinical evaluations of lipid-reducing therapy have been uniformly unsuccessful in slowing AS progression. However, recent studies in animal models and retrospective evaluations in humans suggest that ACE inhibitors and/or angiotensin receptor blockers may be effective in this regard. Furthermore, agents normally utilized to treat osteoporosis also offer promise in retarding AS. Given the considerable morbidity, mortality and health care costs associated with AS, such therapeutic developments should be expedited.