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J Am Coll Cardiol, 2007; 49:554-561, doi:10.1016/j.jacc.2006.07.072 (Published online 19 January 2007).
© 2007 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: VALVULAR HEART DISEASE

Rosuvastatin Affecting Aortic Valve Endothelium to Slow the Progression of Aortic Stenosis

Luis M. Moura, MD*,{dagger}, Sandra F. Ramos, MSc{ddagger}, José L. Zamorano, MD, PhD{dagger}, Isabel M. Barros, MD*, Luis F. Azevedo, MD{ddagger}, Francisco Rocha-Gonçalves, MD, PhD{ddagger} and Nalini M. Rajamannan, MD§,1,*

* Hospital Pedro Hispano, Matosinhos, Portugal
{dagger} Hospital Clinico Universitário S. Carlos, Madrid, Spain
{ddagger} Oporto University Medical School, Oporto, Portugal
§ Northwestern University Feinberg School of Medicine, Chicago, Illinois

Manuscript received April 19, 2006; revised manuscript received July 20, 2006, accepted July 23, 2006.

* Reprint requests and correspondence: Dr. Nalini M. Rajamannan, Northwestern University Feinberg School of Medicine, Department of Medicine, Cardiology, 303 E Chicago, Tarry 12-717, Chicago, Illinois 60611. (Email: n-rajamannan{at}northwestern.edu).

OBJECTIVES: The objective of this study was to test the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor on the progression of moderate to severe aortic stenosis as measured by echocardiography.

BACKGROUND: Recent retrospective studies support the hypothesis that statins slow the progression of aortic stenosis.

METHODS: We performed an open-label, prospective study evaluating 121 consecutive patients with asymptomatic moderate to severe aortic stenosis (aortic valve area ≥ 1.0 cm2; mean age 73.7 ± 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months.

RESULTS: Sixty-one patients (50.4%) with elevated LDL (159.7 ± 33.4 mg/dl), aortic valve velocity (3.65 ± 0.64 m/s), and aortic valve area (1.23 ± 0.42 cm2) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 ± 37.4 mg/dl), aortic valve velocity (3.62 ± 0.61 m/s), and aortic valve area (1.20 ± 0.35 cm2) received no statin. During a mean follow-up of 73 ± 24 weeks, the change in aortic valve area in the control group was –0.10 ± 0.09 cm2/year versus –0.05 ± 0.12 cm2/year in the rosuvastatin group (p = 0.041). The increase in aortic valve velocity was 0.24 ± 0.30 m/s/year in the control group and 0.04 ± 0.38 m/s/year in the rosuvastatin group (p = 0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group.

CONCLUSIONS: Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/NCT00114491?order = 1; NCT0014491).

Abbreviations and Acronyms
  ANOVA = analysis of variance
  HMG CoA = 3-hydroxy-3-methylglutaryl coenzyme A
  hsCRP = high-sensitivity C-reactive protein
  IL = interleukin
  LDL = low-density lipoprotein


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J. Am. Coll. Cardiol. 2007 49: 562-564. [Full Text] [PDF]



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D. Mohty, P. Pibarot, J.-P. Despres, C. Cote, B. Arsenault, A. Cartier, P. Cosnay, C. Couture, and P. Mathieu
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Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 187 - 193.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
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]

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 Cardiovasc ResHome page
K.J. Grande-Allen, N. Osman, M.L. Ballinger, H. Dadlani, S. Marasco, and P.J. Little
Glycosaminoglycan synthesis and structure as targets for the prevention of calcific aortic valve disease
Cardiovasc Res, October 1, 2007; 76(1): 19 - 28.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
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]

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E. M. Tuzcu, R. C. Starling, and J. D. Thomas
ACC.07 and i2 Summit Highlights: A Conversation With the Experts
J. Am. Coll. Cardiol., August 21, 2007; 50(8_Suppl_C): C2 - C31.
[Full Text] [PDF]

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L. M. Moura, J. L. Zamorano, S. F. Ramos, I. M. Barros, L. F. Azevedo, F. Rocha-Goncalves, and N. M. Rajamannan
Reply
J. Am. Coll. Cardiol., July 17, 2007; 50(3): 290 - 290.
[Full Text] [PDF]

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M. B. Yilmaz
Statins and Aortic Stenosis in the Context of Ratio of Low- to High-Density Lipoprotein Cholesterol
J. Am. Coll. Cardiol., July 17, 2007; 50(3): 289 - 290.
[Full Text] [PDF]

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B. P. Griffin
Statins in Aortic Stenosis: New Data From a Prospective Clinical Trial
J. Am. Coll. Cardiol., February 6, 2007; 49(5): 562 - 564.
[Full Text] [PDF]


 
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