Published Online
on March 27, 2006

A more recent version of this article appeared on April 11, 2006

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Submitted on May 20, 2005
Revised on January 26, 2006
Accepted on February 3, 2006

Association Between Human Fetuin-A and the Metabolic Syndrome. Data From the Heart and Soul Study

Joachim H. Ix MD^*, Michael G. Shlipak MD, MPH, Vincent M. Brandenburg MD, Sadia Ali MD, MPH, Markus Ketteler MD, and Mary A. Whooley MD

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

^* To whom correspondence should be addressed. E-mail: jix{at}medicine.ucsf.edu.

Background--Fetuin-A is a multifunctional hepatic secretory protein that inhibits the action of insulin in experimental animals. We evaluated the association between human serum fetuin-A and the metabolic syndrome (MetS) in a cohort of persons with coronary artery disease.

Methods and Results--We defined MetS by the National Cholesterol Education Program criteria among 711 nondiabetic outpatients with coronary artery disease. The mean age was 67 years, and 82% were male. We divided participants into quartiles by serum fetuin-A concentrations. A total of 45% of participants (80 of 177) in the highest quartile of fetuin-A had MetS compared with 24% of participants (42 of 177) in the lowest quartile (odds ratio, 2.7; 95% confidence interval, 1.7 to 4.2; P<0.001). This association persisted after adjustment for potential confounding variables, including hypertension, body mass index, and inflammatory biomarkers (adjusted odds ratio, 2.0; 95% confidence interval, 1.1 to 3.5; P=0.02). Higher fetuin-A quartiles were also strongly and independently associated with higher low-density lipoprotein, non-high-density lipoprotein (HDL), and triglyceride concentrations and lower HDL concentrations (all P<0.01).

Conclusions--Higher human fetuin-A concentrations are strongly associated with MetS and an atherogenic lipid profile. Future studies should evaluate whether fetuin-A predicts coronary artery disease risk.

Key words: alpha2HS-glycoprotein • hypercholesterolemia • insulin • lipids • metabolism

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