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Nat Rev Dis Primers. 2016 Mar 3;2:16006. doi: 10.1038/nrdp.2016.6.

Calcific aortic stenosis.

Author information

Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.
Québec Heart and Lung Institute, Department of Medicine, Laval University, 2725 Chemin Sainte-Foy, Québec City, Québec G1V 4G5, Canada.
Cardiology Department, AP-HP, Bichat Hospital, Paris, France.
Paris-Diderot University, DHU Fire, Paris, France.
University of Liège Hospital, GIGA Cardiovascular Sciences, Department of Cardiology, Heart Valve Clinic and CHU Sart Tilman, Liège, Belgium.
Grupo Villa Maria Care and Research, Anthea Hospital, Bari, Italy.
Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, USA.


Calcific aortic stenosis (AS) is the most prevalent heart valve disorder in developed countries. It is characterized by progressive fibro-calcific remodelling and thickening of the aortic valve leaflets that, over years, evolve to cause severe obstruction to cardiac outflow. In developed countries, AS is the third-most frequent cardiovascular disease after coronary artery disease and systemic arterial hypertension, with a prevalence of 0.4% in the general population and 1.7% in the population >65 years old. Congenital abnormality (bicuspid valve) and older age are powerful risk factors for calcific AS. Metabolic syndrome and an elevated plasma level of lipoprotein(a) have also been associated with increased risk of calcific AS. The pathobiology of calcific AS is complex and involves genetic factors, lipoprotein deposition and oxidation, chronic inflammation, osteoblastic transition of cardiac valve interstitial cells and active leaflet calcification. Although no pharmacotherapy has proved to be effective in reducing the progression of AS, promising therapeutic targets include lipoprotein(a), the renin-angiotensin system, receptor activator of NF-κB ligand (RANKL; also known as TNFSF11) and ectonucleotidases. Currently, aortic valve replacement (AVR) remains the only effective treatment for severe AS. The diagnosis and staging of AS are based on the assessment of stenosis severity and left ventricular systolic function by Doppler echocardiography, and the presence of symptoms. The introduction of transcatheter AVR in the past decade has been a transformative therapeutic innovation for patients at high or prohibitive risk for surgical valve replacement, and this new technology might extend to lower-risk patients in the near future.

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