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(Circulation. 2007;115:2533-2539.)
© 2007 American Heart Association, Inc.

Valvular Heart Disease

Association of Fetuin-A With Mitral Annular Calcification and Aortic Stenosis Among Persons With Coronary Heart Disease

Data From the Heart and Soul Study

Joachim H. Ix, MD; Glenn M. Chertow, MD, MPH; Michael G. Shlipak, MD, MPH; Vincent M. Brandenburg, MD; Markus Ketteler, MD; Mary A. Whooley, MD

From the Division of Nephrology (J.H.I., G.M.C.), Department of Medicine (J.H.I., G.M.C., M.G.S., M.A.W.), and Department of Epidemiology and Biostatistics (G.M.C., M.G.S., M.A.W.), University of California, San Francisco; Section of General Internal Medicine (M.G.S., M.A.W.), VA Medical Center, San Francisco, Calif; and Department of Nephrology and Clinical Immunology (V.M.B., M.K.), University Hospital of the RWTH Aachen, Aachen, Germany.

Correspondence to Joachim H. Ix, MD, Division of Nephrology, Department of Medicine, Box 0532, HSE 672, University of California, San Francisco, San Francisco, CA 94143–0532. E-mail jix{at}medicine.ucsf.edu

Received December 5, 2006; accepted February 16, 2007.

Background— Fetuin-A is a multifunctional hepatic secretory protein that inhibits dystrophic vascular and valvular calcification. Lower serum fetuin-A concentrations are associated with valvular calcification in persons with end-stage renal disease. Whether fetuin-A is associated with valvular calcification in other patient populations is unknown.

Methods and Results— We evaluated the associations among serum fetuin-A concentrations, mitral annular calcification, and aortic stenosis in 970 ambulatory persons with coronary heart disease and without severe kidney disease. The presence or absence of mitral annular calcification and aortic stenosis was determined by transthoracic echocardiography. The subjects’ mean age was 66 years; 81% were men; 189 (20%) had mitral annular calcification; and 79 (8%) had aortic stenosis. Participants were categorized by tertiles of fetuin-A concentrations. Those within the highest fetuin-A tertile had significantly lower odds of mitral annular calcification compared with the lowest tertile (adjusted odds ratio, 0.47; 95% confidence interval, 0.29 to 0.77; P=0.002); this association was similar regardless of diabetes status (P for interaction=0.34). In contrast, the association of fetuin-A with aortic stenosis was modified by the presence or absence of diabetes mellitus (P for interaction=0.03). Among participants without diabetes, the highest fetuin-A tertile had a significantly lower odds of aortic stenosis compared with the lowest tertile (adjusted odds ratio, 0.37; 95% confidence interval, 0.15 to 0.92; P=0.03), whereas among participants with diabetes, no statistically significant association was observed between fetuin-A and aortic stenosis (adjusted odds ratio, 1.49; 95% confidence interval, 0.48 to 4.63; P=0.49).

Conclusions— Among persons with coronary heart disease, we observed an inverse association of fetuin-A and mitral annular calcification. An inverse association also was observed between fetuin-A and aortic stenosis among participants without diabetes mellitus. Fetuin-A may represent an important inhibitor of dystrophic calcification in persons with coronary heart disease.

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