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CLINICAL RESEARCH: VALVULAR HEART DISEASE

Clinical Factors, But Not C-Reactive Protein, Predict Progression of Calcific Aortic-Valve Disease

The Cardiovascular Health Study

Gian M. Novaro, MD^_*,_*, Ronit Katz, PhD, Ronnier J. Aviles, MD, John S. Gottdiener, MD, Mary Cushman, MD, MSc^||, Bruce M. Psaty, MD, PhD^¶, Catherine M. Otto, MD^# and Brian P. Griffin, MD^_**

^_* Department of Cardiology, Cleveland Clinic Florida, Weston, Florida
Department of Biostatistics, University of Washington, Seattle, Washington
Overlake Hospital Medical Center, Bellevue, Washington
Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland
^|| Department of Medicine, University of Vermont and Fletcher Allen Health Care, Colchester, Vermont
^¶ Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington
^# Department of Cardiology, University of Washington, Seattle, Washington
^_** Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.

Manuscript received May 25, 2007; revised manuscript received July 30, 2007, accepted July 30, 2007.

^_* Reprint requests and correspondence: Dr. Gian M. Novaro, Department of Cardiology, Desk A23, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, Florida 33331. (Email: novarog{at}ccf.org).

Objectives: The purpose of this study was to examine the relationship between C-reactive protein (CRP) and calcific aortic valve disease in a large, randomly selected, population-based cohort.

Background: The pathobiology of calcific aortic stenosis involves an active inflammatory, atheromatous, osteogenic process. Elevations in CRP, a measure of systemic inflammation, have been associated with aortic stenosis.

Methods: Two-dimensional and Doppler echocardiography and CRP measurement were performed at baseline in 5,621 participants in the Cardiovascular Health Study. Multivariable analysis was used to identify CRP as a predictor of baseline and incident aortic stenosis.

Results: At a mean echocardiographic follow-up of 5 years, 9% of subjects with aortic sclerosis progressed to some degree of aortic stenosis. Increasing age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.16; p < 0.001) and male gender (OR 3.05, 95% CI 1.76 to 5.27; p < 0.001) were related to risk of incident aortic stenosis, whereas increasing height (OR 0.96, 95% CI 0.94 to 0.99; p = 0.013) and African-American ethnicity conveyed a lower risk (OR 0.49, 95% CI 0.25 to 0.95; p = 0.035). C-reactive protein, treated as a continuous variable, was not associated with baseline aortic stenosis, progression to aortic sclerosis (adjusted OR 0.93, 95% CI 0.85 to 1.02; p = 0.107), or progression to aortic stenosis (adjusted OR 0.85, 95% CI 0.70 to 1.03; p = 0.092).

Conclusions: In this large population-based cohort, approximately 9% of subjects with aortic sclerosis progressed to aortic stenosis over a 5-year follow-up period. There was no association between CRP levels and the presence of calcific aortic-valve disease or incident aortic stenosis. C-reactive protein appears to be a poor predictor of subclinical calcific aortic-valve disease.

Abbreviations and Acronyms   CI = confidence interval   CRP = C-reactive protein   OR = odds ratio

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