Fetuin-A, Type 2 Diabetes, and Risk of Cardiovascular Disease in Older Adults

The Cardiovascular Health Study

  1. Joachim H. Ix, MD, MAS11
  1. 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  2. 2Department of Biostatistics, University of Washington, Seattle, Washington
  3. 3Beth Israel Deaconess Medical Center, Boston, Massachusetts
  4. 4Division of Aging, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts and Boston Veterans Affairs Healthcare System, Boston, Massachusetts
  5. 5Department of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
  6. 6Department of Pathology, Colchester Research Facility, University of Vermont, Colchester, Vermont
  7. 7National Institutes on Aging, National Institutes of Health, Bethesda, Maryland
  8. 8Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  9. 9Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington
  10. 10Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center and Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, California
  11. 11Nephrology Section, Veterans Affairs San Diego Healthcare System, and Divisions of Nephrology and Preventive Medicine, University of California San Diego, San Diego, California
  1. Corresponding author: Majken K. Jensen, mkjensen{at}


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.

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