Prognosis and Risk Factors in Patients With Asymptomatic Aortic Stenosis and Their Modulation by Atorvastatin (20 mg)

      The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 ± 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal–pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Grundy S.M.
        • Cleeman J.I.
        • Merz C.N.
        • Brewer Jr, H.B.
        • Clark L.T.
        • Hunninghake D.B.
        • Pasternak R.C.
        • Smith Jr, S.C.
        • Stone N.J.
        Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.
        J Am Coll Cardiol. 2004; 44: 720-732
        • 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
        • Otto C.M.
        • Burwash I.G.
        • Legget M.E.
        • Munt B.I.
        • Fujioka M.
        • Healy N.L.
        • Kraft C.D.
        • Miyake-Hull C.Y.
        • Schwaegler R.G.
        Prospective study of asymptomatic valvular aortic stenosis.
        Circulation. 1997; 95: 2262-2270
        • Rosenhek R.
        • Klaar U.
        • Schemper M.
        • Scholten C.
        • Heger M.
        • Gabriel H.
        • Binder T.
        • Maurer G.
        • Baumgartner H.
        Mild and moderate aortic stenosis.
        Eur Heart J. 2004; 25: 199-205
        • Rosenhek R.
        • Binder T.
        • Porenta G.
        • Lang I.
        • Christ G.
        • Schemper M.
        • Maurer G.
        • Baumgartner H.
        Predictors of outcome in severe, asymptomatic aortic stenosis.
        N Engl J Med. 2000; 343: 611-617
        • Pai R.G.
        • Kapoor N.
        • Bansal R.C.
        • Varadarajan P.
        Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement.
        Ann Thorac Surg. 2006; 82: 2116-2122
        • Galante A.
        • Pietroiusti A.
        • Vellini M.
        • Piccolo P.
        • Possati G.
        • De Bonis M.
        • Grillo R.L.
        • Fontana C.
        • Favalli C.
        C-reactive protein is increased in patients with degenerative aortic valvular stenosis.
        J Am Coll Cardiol. 2001; 38: 1078-1082
        • Bergler-Klein J.
        • Klaar U.
        • Heger M.
        • Rosenhek R.
        • Mundigler G.
        • Gabriel H.
        • Binder T.
        • Pacher R.
        • Maurer G.
        • Baumgartner H.
        Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis.
        Circulation. 2004; 109: 2302-2308
        • Novaro G.M.
        • Katz R.
        • Aviles R.J.
        • Gottdiener J.S.
        • Cushman M.
        • Psaty B.M.
        • Otto C.M.
        • Griffin B.P.
        Clinical factors, but not C-reactive protein, predict progression of calcified aortic-valve disease.
        J Am Coll Cardiol. 2007; 50: 1992-1999
        • Cowell S.J.
        • Newby D.E.
        • Prescott R.J.
        • Bloomfield P.
        • Reid J.
        • Northridge D.B.
        • Boon N.A.
        A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.
        N Engl J Med. 2005; 352: 2389-2397
        • Mohler III, E.R.
        • Wang H.
        • Medenilla E.
        • Scott C.
        Effect of statin treatment on aortic valve and coronary artery calcification.
        J Heart Valve Dis. 2007; 16: 378-386
        • Aronow W.S.
        • Ahn C.
        • Kronzon I.
        • Goldman M.E.
        Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons.
        Am J Cardiol. 2001; 88: 693-695
        • Novaro G.M.
        • Tiong I.Y.
        • Pearce G.L.
        • Lauer M.S.
        • Sprecher D.L.
        • Griffin B.P.
        Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis.
        Circulation. 2001; 104: 2205-2209
        • Bellamy M.F.
        • Pellikka P.A.
        • Klarich K.W.
        • Tajik A.J.
        • Enriquez-Sarano M.
        Association of cholesterol level, HMG-CoA reductase inhibitor treatment and progression of aortic stenosis in the community.
        J Am Coll Cardiol. 2002; 40: 1723-1730
        • Rosenhek R.
        • Rader F.
        • Loho N.
        • Gabriel H.
        • Heger M.
        • Klaar U.
        • Schemper M.
        • Binder T.
        • Maurer G.
        • Baumgartner H.
        Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis.
        Circulation. 2004; 110: 1291-1295
        • Moura L.M.
        • Ramos S.F.
        • Zamorano J.L.
        • Barros I.M.
        • Azevedo L.F.
        • Rocha-Goncalves F.
        • Rajamannan N.M.
        Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis.
        J Am Coll Cardiol. 2007; 49: 554-561