The association of fetuin-A with cardiovascular disease mortality in older community-dwelling adults: the Rancho Bernardo study

Objectives: The goal of this study was to evaluate the prospective association of fetuin-A levels with cardiovascular disease (CVD) mortality.

Background: Fetuin-A is a circulating inhibitor of calcium deposition in the vasculature and of insulin action in muscle and fat, and may be involved in the pathogenesis of CVD.

Methods: This is a population-based prospective study of 633 men and 1,025 women (median age = 73 years) who had fetuin-A levels and CVD risk factors evaluated in 1992 to 1996 and were followed for vital status through 2010.

Results: Plasma fetuin-A (g/l ± SD) was highest in women using oral estrogens (0.55 ± 0.12), intermediate for women not using oral estrogens (0.51 ± 0.10), and lowest for men (0.50 ± 0.10), p < 0.001. Lower fetuin-A levels were associated with older age, but with lower levels of other CVD risk factors including adiposity, blood pressure, lipids, triglycerides, and insulin resistance (all p < 0.01). During the median 12-year follow-up, 273 deaths were attributed to CVD. The association of fetuin-A with CVD mortality differed by diabetes status (p for interaction = 0.003). Adjusting for age, sex, oral estrogens, and lifestyle, the hazard ratio for CVD mortality comparing the lowest fetuin-A quartile with all higher values was 1.76 (95% confidence interval [CI]: 1.34 to 2.31; p < 0.001) for participants without diabetes and 0.43 (95% CI: 0.19 to 0.98; p = 0.046) for participants with diabetes.

Conclusions: Low fetuin-A levels predicted greater risk for CVD mortality in older adults without diabetes, but were associated with reduced risk of CVD death in those with diabetes. Fetuin-A may provide novel insight into mechanisms leading to CVD death in those with versus without diabetes.