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Aortic Valve Sclerosis and Clinical Outcomes: Moving Toward a Definition

      Abstract

      The presence of aortic valve sclerosis has been suggested as a marker of increased cardiovascular risk, including increased mortality. However, it remains unclear whether aortic valve sclerosis is independently associated with risk or merely a marker of coexistent cardiovascular risk factors. Aortic valve sclerosis is usually diagnosed on transthoracic echocardiography, the most widely used imaging modality in observational and natural history studies of aortic valve disease. Defining aortic valve sclerosis has remained challenging due to the variable and qualitative nature of its description by ultrasound techniques. Importantly, artifacts common to ultrasound imaging and awareness of demographic and clinical history information may bias the diagnosis of aortic valve sclerosis. Because clinicians may alter treatment recommendations or follow-up based on echocardiographic reporting of aortic valve sclerosis, highlighting pitfalls of the subjective nature by which aortic valve sclerosis is identified and establishing diagnostic criteria are necessary. This review describes the diagnostic criteria for aortic valve sclerosis used in outcome studies, summarizes the epidemiological findings reporting the relationship between aortic valve sclerosis and clinical outcome, and proposes a definition of aortic valve sclerosis based on the literature.

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      References

        • Otto C.M.
        • Lind B.K.
        • Kitzman D.W.
        • Gersh B.J.
        • Siscovick D.S.
        Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly.
        N Engl J Med. 1999; 341: 142-147
        • Volzke H.
        • Haring R.
        • Lorbeer R.
        • et al.
        Heart valve sclerosis predicts all-cause and cardiovascular mortality.
        Atherosclerosis. 2010; 209: 606-610
        • Conte L.
        • Rossi A.
        • Cicoira M.
        • et al.
        Aortic valve sclerosis: a marker of significant obstructive coronary artery disease in patients with chest pain?.
        J Am Soc Echocardiogr. 2007; 20: 703-708
        • Otto C.M.
        Why is aortic sclerosis associated with adverse clinical outcomes?.
        J Am Coll Cardiol. 2004; 43: 176-178
        • Carabello B.A.
        Aortic sclerosis—a window to the coronary arteries?.
        N Engl J Med. 1999; 341: 193-195
        • Chandra H.R.
        • Goldstein J.A.
        • Choudhary N.
        • et al.
        Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation.
        J Am Coll Cardiol. 2004; 43: 169-175
        • Baumgartner H.
        • Hung J.
        • Bermejo J.
        • et al.
        Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice.
        J Am Soc Echocardiogr. 2009; 22 (quiz 101-102): 1-23
        • Bonow R.O.
        • Carabello B.A.
        • Chatterjee K.
        • et al.
        ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.
        J Am Coll Cardiol. 2006; 48: e1-e148
        • Stewart B.F.
        • Siscovick D.
        • Lind B.K.
        • et al.
        Clinical factors associated with calcific aortic valve disease.
        J Am Coll Cardiol. 1997; 29: 630-634
        • Lindroos M.
        • Kupari M.
        • Heikkila J.
        • Tilvis R.
        Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample.
        J Am Coll Cardiol. 1993; 21: 1220-1225
        • Cosmi J.E.
        • Kort S.
        • Tunick P.A.
        • et al.
        The risk of the development of aortic stenosis in patients with “benign” aortic valve thickening.
        Arch Intern Med. 2002; 162: 2345-2347
        • Agmon Y.
        • Khandheria B.K.
        • Meissner I.
        • et al.
        Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease?.
        J Am Coll Cardiol. 2001; 38: 827-834
        • Palmiero P.
        • Maiello M.
        • Passantino A.
        • Wasson S.
        • Reddy H.K.
        Aortic valve sclerosis: is it a cardiovascular risk factor or a cardiac disease marker?.
        Echocardiography. 2007; 24: 217-221
        • Rajamannan N.M.
        • Subramaniam M.
        • Rickard D.
        • et al.
        Human aortic valve calcification is associated with an osteoblast phenotype.
        Circulation. 2003; 107: 2181-2184
        • Otto C.M.
        • Kuusisto J.
        • Reichenbach D.D.
        • Gown A.M.
        • O'Brien K.D.
        Characterization of the early lesion of 'degenerative' valvular aortic stenosis.
        Circulation. 1994; 90: 844-853
        • Olsson M.
        • Rosenqvist M.
        • Nilsson J.
        Expression of HLA-DR antigen and smooth muscle cell differentiation markers by valvular fibroblasts in degenerative aortic stenosis.
        J Am Coll Cardiol. 1994; 24: 1664-1671
        • Miller J.D.
        • Chu Y.
        • Brooks R.M.
        • Richenbacher W.E.
        • Pena-Silva R.
        • Heistad D.D.
        Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans.
        J Am Coll Cardiol. 2008; 52: 843-850
        • Shah S.J.
        • Ristow B.
        • Ali S.
        • Na B.Y.
        • Schiller N.B.
        • Whooley M.A.
        Acute myocardial infarction in patients with versus without aortic valve sclerosis and effect of statin therapy (from the Heart and Soul Study).
        Am J Cardiol. 2007; 99: 1128-1133
        • Aronow W.S.
        • Ahn C.
        • Shirani J.
        • Kronzon I.
        Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis.
        Am J Cardiol. 1999; 83 (A598): 599-600
        • Kizer J.R.
        • Wiebers D.O.
        • Whisnant J.P.
        • et al.
        Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study.
        Stroke. 2005; 36: 2533-2537
        • Olsen M.H.
        • Wachtell K.
        • Bella J.N.
        • et al.
        Aortic valve sclerosis and albuminuria predict cardiovascular events independently in hypertension: a losartan intervention for endpoint-reduction in hypertension (LIFE) substudy.
        Am J Hypertens. 2005; 18: 1430-1436
        • Taylor Jr, H.A.
        • Clark B.L.
        • Garrison R.J.
        • et al.
        Relation of aortic valve sclerosis to risk of coronary heart disease in African-Americans.
        Am J Cardiol. 2005; 95: 401-404
        • da Rosa E.M.
        • Sant'anna J.R.
        • Oppermann L.P.
        • Castro I.
        Prognosis of aortic valve sclerosis in cardiovascular mortality of patients seen at the cardiology institute of Rio Grande do Sul.
        Arq Bras Cardiol. 2007; 88: 234-239
        • Barasch E.
        • Gottdiener J.S.
        • Marino Larsen E.K.
        • Chaves P.H.
        • Newman A.B.
        Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study).
        Am J Cardiol. 2006; 97: 1281-1286
        • Fox C.S.
        • Larson M.G.
        • Vasan R.S.
        • et al.
        Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study.
        J Am Soc Nephrol. 2006; 17: 521-527
        • Barasch E.
        • Gottdiener J.S.
        • Larsen E.K.
        • Chaves P.H.
        • Newman A.B.
        • Manolio T.A.
        Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly.
        Am Heart J. 2006; 151: 39-47
        • Gardin J.M.
        • Wong N.D.
        • Bommer W.
        • et al.
        Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study.
        J Am Soc Echocardiogr. 1992; 5: 63-72
        • Hawkins K.
        • Henry J.S.
        • Krasuski R.A.
        Tissue harmonic imaging in echocardiography: better valve imaging, but at what cost?.
        Echocardiography. 2008; 25: 119-123
      1. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Moura L.M.
        • Ramos S.F.
        • Zamorano J.L.
        • et al.
        Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis.
        J Am Coll Cardiol. 2007; 49: 554-561
        • Cowell S.J.
        • Newby D.E.
        • Prescott R.J.
        • et al.
        A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.
        N Engl J Med. 2005; 352: 2389-2397
        • Chan K.L.
        • Teo K.
        • Dumesnil J.G.
        • Ni A.
        • Tam J.
        Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial.
        Circulation. 2010; 121: 306-314
        • Rossebo A.B.
        • Pedersen T.R.
        • Boman K.
        • et al.
        Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.
        N Engl J Med. 2008; 359: 1343-1356
        • Carabello B.A.
        The SEAS Trial.
        Curr Cardiol Rep. 2010; 12: 122-124
        • Caira F.C.
        • Stock S.R.
        • Gleason T.G.
        • et al.
        Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation.
        J Am Coll Cardiol. 2006; 47: 1707-1712
        • Ngo D.T.
        • Wuttke R.D.
        • Turner S.
        • Marwick T.H.
        • Horowitz J.D.
        Quantitative assessment of aortic sclerosis using ultrasonic backscatter.
        J Am Soc Echocardiogr. 2004; 17: 1123-1130
        • Ngo D.T.
        • Sverdlov A.L.
        • Willoughby S.R.
        • et al.
        Determinants of occurrence of aortic sclerosis in an aging population.
        JACC Cardiovasc Imaging. 2009; 2: 919-927
        • Jeon D.S.
        • Atar S.
        • Brasch A.V.
        • et al.
        Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age<or =65 years old.
        J Am Coll Cardiol. 2001; 38: 1988-1993
        • Morgan-Hughes G.J.
        • Roobottom C.A.
        • Marshall A.J.
        Aortic valve imaging with computed tomography: a review.
        J Heart Valve Dis. 2002; 11: 604-611
        • Markl M.
        • Harloff A.
        • Foll D.
        • Langer M.
        • Hennig J.
        • Frydrychowicz A.
        Sclerotic aortic valve: flow-sensitive 4-dimensional magnetic resonance imaging reveals 3 distinct flow-pattern changes.
        Circulation. 2007; 116: e336-e337
        • Mitchell L.
        • Jenkins J.P.
        • Watson Y.
        • Rowlands D.J.
        • Isherwood I.
        Diagnosis and assessment of mitral and aortic valve disease by cine-flow magnetic resonance imaging.
        Magn Reson Med. 1989; 12: 181-197
        • Hamilton A.M.
        • Rogers K.A.
        • Belisle A.J.
        • et al.
        Early identification of aortic valve sclerosis using iron oxide enhanced MRI.
        J Magn Reson Imaging. 2010; 31: 110-116