on August 30, 2004
Circulation. 2004
Published online before print August 30, 2004, doi: 10.1161/01.CIR.0000140723.15274.53
Published online before print August 30, 2004, doi: 10.1161/01.CIR.0000140723.15274.53
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 26, 2004
From the Department of Cardiology (R.R., F.R., N.L., H.G., M.H., U.K., T.B., G.M., H.B.), Vienna General Hospital and the Ludwig Boltzmann Institute for Cardiovascular Research and the Department of Medical Computer Sciences (M.S.), Medical University of Vienna, Vienna, Austria. * To whom correspondence should be addressed. E-mail: raphael.rosenhek{at}meduniwien.ac.at.
Background--Recently, statins and angiotensin-converting enzyme inhibitors (ACEIs) have been shown to slow aortic valve calcium accumulation. Although several studies also suggest that statins may reduce the hemodynamic progression of aortic stenosis (AS), no data are available for ACEIs or the combination of both. Methods and Results--A total of 211 consecutive patients (aged 70±10 years, 104 females) with native AS, defined by a peak velocity >2.5 m/s (valve area 0.84±0.23 cm2, mean gradient 42±19 mm Hg), with normal left ventricular function and no other significant valvular lesion who were examined between 2000 and 2002 and who had 2 echocardiograms separated by at least 6 months were included. Of these, 102 patients were treated with ACEIs, 50 patients received statins, and 32 patients received both. Hemodynamic progression of AS was assessed and related to medical treatment. Annualized increase in peak aortic jet velocity for the entire study group was 0.32±0.44 m · s-1 · y-1. Progression was significantly lower in patients treated with statins (0.10±0.41 m · s-1 · y-1) than in those who were not (0.39±0.42 m · s-1 · y-1; P<0.0001). This effect was observed both in mild-to-moderate and severe AS. ACEI use, however, did not significantly affect hemodynamic progression (P=0.29). Furthermore, ACEIs had no additional effect on AS progression when given in combination with statins (0.11±0.42 versus 0.08±0.43 m · s-1 · y-1 for combination versus statin only; P=0.81). Cholesterol levels did not correlate with hemodynamic progression either in the group receiving statins or in the group that did not. Conclusions--ACEIs do not appear to slow AS progression. However, statins significantly reduce the hemodynamic progression of both mild-to-moderate and severe AS, an effect that may not be related to cholesterol lowering.
Revised on May 24, 2004
Accepted on May 25, 2004
Statins but Not Angiotensin-Converting Enzyme Inhibitors Delay Progression of Aortic Stenosis
Raphael Rosenhek MD*,
Key words: stenosis • statins • inhibitors • values
Related Article:
Circulation 2004 110: 1180-1182.
This article has been cited by other articles:
 |
|
 |
|
  J. A. Benton, H. B. Kern, L. A. Leinwand, P. D. Mariner, and K. S. Anseth Statins Block Calcific Nodule Formation of Valvular Interstitial Cells by Inhibiting {alpha}-Smooth Muscle Actin Expression Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1950 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Antonini-Canterin, E. Leiballi, M. Capanna, C. Burelli, M. Cassin, F. Macor, U. Grandis, and G. L. Nicolosi Association Between Carotid and Coronary Artery Disease in Patients With Aortic Valve Stenosis: An Angiographic Study Angiology, October 1, 2009; 60(5): 596 - 600. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Baumgartner and C. M. Otto Aortic stenosis severity: do we need a new concept? J. Am. Coll. Cardiol., September 8, 2009; 54(11): 1012 - 1013. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Schenke-Layland, U. A. Stock, A. Nsair, J. Xie, E. Angelis, C. G. Fonseca, R. Larbig, A. Mahajan, K. Shivkumar, M. C. Fishbein, et al. Cardiomyopathy is associated with structural remodelling of heart valve extracellular matrix Eur. Heart J., September 2, 2009; 30(18): 2254 - 2265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Stritzke, P. Linsel-Nitschke, M. R. P. Markus, B. Mayer, W. Lieb, A. Luchner, A. Doring, W. Koenig, U. Keil, H.-W. Hense, et al. Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey Eur. Heart J., August 2, 2009; 30(16): 2044 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Helske and C. M. Otto Lipid Lowering in Aortic Stenosis: Still Some Light at the End of the Tunnel? Circulation, May 26, 2009; 119(20): 2653 - 2655. [Full Text] [PDF]
|
|
|
|
|
|
J. D. Miller, R. M. Weiss, K. M. Serrano, R. M. Brooks II, C. J. Berry, K. Zimmerman, S. G. Young, and D. D. Heistad Lowering Plasma Cholesterol Levels Halts Progression of Aortic Valve Disease in Mice Circulation, May 26, 2009; 119(20): 2693 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Antonini-Canterin, E. Leiballi, R. Enache, B. A. Popescu, M. Rosca, E. Cervesato, R. Piazza, C. Ginghina, and G. L. Nicolosi Hydroxymethylglutaryl Coenzyme-A Reductase Inhibitors Delay the Progression of Rheumatic Aortic Valve Stenosis: A Long-Term Echocardiographic Study J. Am. Coll. Cardiol., May 19, 2009; 53(20): 1874 - 1879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Akat, M Borggrefe, and J J Kaden Aortic valve calcification: basic science to clinical practice Heart, April 1, 2009; 95(8): 616 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Katz, M. J. Budoff, J. Takasu, D. M. Shavelle, A. Bertoni, R. S. Blumenthal, P. Ouyang, N. D. Wong, and K. D. O'Brien Relationship of Metabolic Syndrome With Incident Aortic Valve Calcium and Aortic Valve Calcium Progression: The Multi-Ethnic Study of Atherosclerosis (MESA) Diabetes, April 1, 2009; 58(4): 813 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Parolari, C. Loardi, L. Mussoni, L. Cavallotti, M. Camera, P. Biglioli, E. Tremoli, and F. Alamanni Nonrheumatic calcific aortic stenosis: an overview from basic science to pharmacological prevention Eur. J. Cardiothorac. Surg., March 1, 2009; 35(3): 493 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Matsumoto, V. Adams, C. Walther, C. Kleinecke, P. Brugger, A. Linke, T. Walther, F. W. Mohr, and G. Schuler Reduced number and function of endothelial progenitor cells in patients with aortic valve stenosis: a novel concept for valvular endothelial cell repair Eur. Heart J., February 1, 2009; 30(3): 346 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Monzack, X. Gu, and K. S. Masters Efficacy of Simvastatin Treatment of Valvular Interstitial Cells Varies With the Extracellular Environment Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 246 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ramaraj An elderly man who suddenly lost consciousness BMJ, January 7, 2009; 338(jan07_2): a3009 - a3009. [Full Text]
|
|
|
|
 |
|
 H. Takagi, N. Kawai, and T. Umemoto Do statins delay the progression of aortic stenosis? J. Thorac. Cardiovasc. Surg., January 1, 2009; 137(1): e6 - e9. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Dal-Bianco, B. K. Khandheria, F. Mookadam, F. Gentile, and P. P. Sengupta Management of Asymptomatic Severe Aortic Stenosis J. Am. Coll. Cardiol., October 14, 2008; 52(16): 1279 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
2006 WRITING COMMITTEE MEMBERS, R. O. Bonow, B. A. Carabello, K. Chatterjee, A. C. de Leon Jr, D. P. Faxon, M. D. Freed, W. H. Gaasch, B. W. Lytle, R. A. Nishimura, et al. 2008 Focused Update Incorporated Into the 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): Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Circulation, October 7, 2008; 118(15): e523 - e661. [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Rossebo, T. R. Pedersen, K. Boman, P. Brudi, J. B. Chambers, K. Egstrup, E. Gerdts, C. Gohlke-Barwolf, I. Holme, Y. A. Kesaniemi, et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis N. Engl. J. Med., September 25, 2008; 359(13): 1343 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O. Bonow, B. A. Carabello, K. Chatterjee, A. C. de Leon Jr, D. P. Faxon, M. D. Freed, W. H. Gaasch, B. W. Lytle, R. A. Nishimura, P. T. O'Gara, et al. 2008 Focused Update Incorporated Into the 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) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J. Am. Coll. Cardiol., September 23, 2008; 52(13): e1 - e142. [Full Text] [PDF]
|
|
|
|
|
|
J. D. Miller, Y. Chu, R. M. Brooks, W. E. Richenbacher, R. Pena-Silva, and D. D. Heistad Dysregulation of Antioxidant Mechanisms Contributes to Increased Oxidative Stress in Calcific Aortic Valvular Stenosis in Humans J. Am. Coll. Cardiol., September 2, 2008; 52(10): 843 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Tourmousoglou, S. Lalos, and T. Psarros Do statins slow the progression of aortic valve stenosis? Interactive CardioVascular and Thoracic Surgery, August 1, 2008; 7(4): 684 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Helske, T. Miettinen, H. Gylling, M. Mayranpaa, J. Lommi, H. Turto, K. Werkkala, M. Kupari, and P. T. Kovanen Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves J. Lipid Res., July 1, 2008; 49(7): 1511 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Pedersen Overview of clinical trials on calcific aortic stenosis Eur. Heart J. Suppl., July 1, 2008; 10(suppl_E): E31 - E40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Owens, R. Katz, E. Johnson, D. M. Shavelle, J. L. Probstfield, J. Takasu, J. R. Crouse, J. J. Carr, R. Kronmal, M. J. Budoff, et al. Interaction of Age With Lipoproteins as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis Arch Intern Med, June 9, 2008; 168(11): 1200 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Jassal, J. W. Tam, K. M. Bhagirath, I. Gaboury, R. A. Sochowski, J. G. Dumesnil, P. J. Giannoccaro, J. Jue, A. S. Pandey, C. D. Joyner, et al. Association of mitral annular calcification and aortic valve morphology: a substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study Eur. Heart J., June 2, 2008; 29(12): 1542 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pachon and J. Zamorano Mitral annular calcifications and aortic valve stenosis Eur. Heart J., June 2, 2008; 29(12): 1478 - 1480. [Full Text] [PDF]
|
|
|
|
|
|
K. Linhartova Impact of blood pressure on the Doppler echocardiographic assessment of severity of aortic stenosis Heart, April 1, 2008; 94(4): 508 - 508. [Full Text] [PDF]
|
|
|
|
|
|
M. Liberman, E. Bassi, M. K. Martinatti, F. C. Lario, J. Wosniak Jr, P. M.A. Pomerantzeff, and F. R.M. Laurindo Oxidant Generation Predominates Around Calcifying Foci and Enhances Progression of Aortic Valve Calcification Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mihaljevic, M. R. Sayeed, S. C. Stamou, and S. Paul Pathophysiology of Aortic Valve Disease Card. Surg. Adult, January 1, 2008; 3(2008): 825 - 840. [Full Text]
|
|
|
|
|
|
D. Mohty, P. Pibarot, J.-P. Despres, C. Cote, B. Arsenault, A. Cartier, P. Cosnay, C. Couture, and P. Mathieu Association Between Plasma LDL Particle Size, Valvular Accumulation of Oxidized LDL, and Inflammation in Patients With Aortic Stenosis Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 187 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Stone C-Reactive Protein to Identify Early Risk for Development of Calcific Aortic Stenosis: Right Marker? Wrong Time? J. Am. Coll. Cardiol., November 13, 2007; 50(20): 1999 - 2001. [Full Text] [PDF]
|
|
|
|
|
|
S. H. Goldbarg, S. Elmariah, M. A. Miller, and V. Fuster Insights Into Degenerative Aortic Valve Disease J. Am. Coll. Cardiol., September 25, 2007; 50(13): 1205 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Kaden Towards medical therapy of calcific aortic stenosis lessons from molecular biology Eur. Heart J., August 1, 2007; 28(15): 1795 - 1796. [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Ertas, T. Hasan, C. Ozdol, S. Gulec, Y. Atmaca, C. Tulunay, H. Karabulut, H. T. Kocum, I. Dincer, K. S. Kose, et al. Relationship Between Angiotensin-Converting Enzyme Gene Polymorphism and Severity of Aortic Valve Calcification Mayo Clin. Proc., August 1, 2007; 82(8): 944 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Arishiro, M. Hoshiga, N. Negoro, D. Jin, S. Takai, M. Miyazaki, T. Ishihara, and T. Hanafusa Angiotensin Receptor-1 Blocker Inhibits Atherosclerotic Changes and Endothelial Disruption of the Aortic Valve in Hypercholesterolemic Rabbits J. Am. Coll. Cardiol., April 3, 2007; 49(13): 1482 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Johnson, J. A. Leopold, and J. Loscalzo Vascular Calcification: Pathobiological Mechanisms and Clinical Implications Circ. Res., November 10, 2006; 99(10): 1044 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Weiss, M. Ohashi, J. D. Miller, S. G. Young, and D. D. Heistad Calcific Aortic Valve Stenosis in Old Hypercholesterolemic Mice Circulation, November 7, 2006; 114(19): 2065 - 2069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O. Bonow, B. A. Carabello, K. Chatterjee, A. C. de Leon Jr, D. P. Faxon, M. D. Freed, W. H. Gaasch, B. W. Lytle, R. A. Nishimura, P. T. O'Gara, 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., August 1, 2006; 48(3): e1 - e148. [Full Text] [PDF]
|
|
|
|
|
|
R. O. Bonow, B. A. Carabello, K. Chatterjee, A. C. de Leon Jr, D. P. Faxon, M. D. Freed, W. H. Gaasch, B. W. Lytle, R. A. Nishimura, P. T. O'Gara, et al. ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive Summary: 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., August 1, 2006; 48(3): 598 - 675. [Full Text] [PDF]
|
|
|
|
|
|
K. D. O'Brien Pathogenesis of Calcific Aortic Valve Disease: A Disease Process Comes of Age (and a Good Deal More) Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1721 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Briand, I. Lemieux, J. G. Dumesnil, P. Mathieu, A. Cartier, J.-P. Despres, M. Arsenault, J. Couet, and P. Pibarot Metabolic Syndrome Negatively Influences Disease Progression and Prognosis in Aortic Stenosis J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2229 - 2236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D E Newby, S J Cowell, and N A Boon Emerging medical treatments for aortic stenosis: statins, angiotensin converting enzyme inhibitors, or both? Heart, June 1, 2006; 92(6): 729 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Katz, N. D. Wong, R. Kronmal, J. Takasu, D. M. Shavelle, J. L. Probstfield, A. G. Bertoni, M. J. Budoff, and K. D. O'Brien Features of the Metabolic Syndrome and Diabetes Mellitus as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis Circulation, May 2, 2006; 113(17): 2113 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Liebe, M. Brueckmann, M. Borggrefe, and J. J. Kaden Statin therapy of calcific aortic stenosis: hype or hope? Eur. Heart J., April 1, 2006; 27(7): 773 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Skowasch, S Schrempf, C J Preusse, J A Likungu, A Welz, B Luderitz, and G Bauriedel Tissue resident C reactive protein in degenerative aortic valves: correlation with serum C reactive protein concentrations and modification by statins Heart, April 1, 2006; 92(4): 495 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Rahimtoola The Year in Valvular Heart Disease J. Am. Coll. Cardiol., January 17, 2006; 47(2): 427 - 439. [Full Text] [PDF]
|
|
|
|
|
|
D. Skowasch, S. Schrempf, N. Wernert, M. Steinmetz, A. Jabs, I. Tuleta, U. Welsch, C. J. Preusse, J. A. Likungu, A. Welz, et al. Cells of primarily extravalvular origin in degenerative aortic valves and bioprostheses Eur. Heart J., December 1, 2005; 26(23): 2576 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Baumgartner Aortic stenosis: medical and surgical management Heart, November 1, 2005; 91(11): 1483 - 1488. [Full Text] [PDF]
|
|
|
|
|
|
R. V. Freeman and C. M. Otto Spectrum of Calcific Aortic Valve Disease: Pathogenesis, Disease Progression, and Treatment Strategies Circulation, June 21, 2005; 111(24): 3316 - 3326. [Full Text] [PDF]
|
|
|
|
|
|
S. J. Cowell, D. E. Newby, R. J. Prescott, P. Bloomfield, J. Reid, D. B. Northridge, N. A. Boon, and the Scottish Aortic Stenosis and Lipid Lowering Tr A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis N. Engl. J. Med., June 9, 2005; 352(23): 2389 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rosenhek Statins for Aortic Stenosis N. Engl. J. Med., June 9, 2005; 352(23): 2441 - 2443. [Full Text] [PDF]
|
|
|
|
|
|
H. C. Routledge, J. N. Townend, R. Rosenhek, F. Rader, N. Loho, H. Gabriel, M. Heger, U. Klaar, T. Binder, G. Maurer, et al. Letter Regarding Article by Rosenhek et al, "Statins but Not Angiotensin-Converting Enzyme Inhibitors Delay Progression of Aortic Stenosis" * Response Circulation, May 3, 2005; 111(17): e274 - e275. [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Quinn Jr. and S. A. Spinler Efficacy of statins in preventing progression of aortic stenosis Am. J. Health Syst. Pharm., May 1, 2005; 62(9): 979 - 981. [Full Text] [PDF]
|
|
|
|
|
|
J. S. Borer Aortic Stenosis and Statins: More Evidence of "Pleotropy"? Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 476 - 477. [Full Text] [PDF]
|
|
|
|
 |
|
 Aortic Stenosis Slowed by Statins -- But Not ACE Inhibitors Journal Watch Cardiology, December 3, 2004; 2004(1203): 6 - 6. [Full Text]
|
|
|
|
|
|
N. M. Rajamannan and C. M. Otto Targeted Therapy to Prevent Progression of Calcific Aortic Stenosis Circulation, September 7, 2004; 110(10): 1180 - 1182. [Full Text] [PDF]
|
|