Fetuin-A, Type 2 Diabetes, and Risk of Cardiovascular Disease in Older Adults
The Cardiovascular Health Study
- Majken K. Jensen, PHD1⇓,
- Traci M. Bartz, MS2,
- Kenneth J. Mukamal, MD3,
- Luc Djoussé, DSC4,
- Jorge R. Kizer, MD5,
- Russell P. Tracy, PHD6,
- Susan J. Zieman, MD7,
- Eric B. Rimm, DSC1,8,
- David S. Siscovick, MD9,
- Michael Shlipak, MD10 and
- Joachim H. Ix, MD, MAS11
- 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- 2Department of Biostatistics, University of Washington, Seattle, Washington
- 3Beth Israel Deaconess Medical Center, Boston, Massachusetts
- 4Division of Aging, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts and Boston Veterans Affairs Healthcare System, Boston, Massachusetts
- 5Department of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
- 6Department of Pathology, Colchester Research Facility, University of Vermont, Colchester, Vermont
- 7National Institutes on Aging, National Institutes of Health, Bethesda, Maryland
- 8Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- 9Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington
- 10Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center and Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, California
- 11Nephrology Section, Veterans Affairs San Diego Healthcare System, and Divisions of Nephrology and Preventive Medicine, University of California San Diego, San Diego, California
- Corresponding author: Majken K. Jensen,
OBJECTIVE Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes.
RESEARCH DESIGN AND METHODS Prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008.
RESULTS Mean age was 75 years and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% CI, 0.88–0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93–1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85–0.97) and 0.87 (0.79–0.95), respectively].
CONCLUSIONS The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.
- Received August 7, 2012.
- Accepted October 28, 2012.
- © 2013 by the American Diabetes Association.
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