The Association of Fetuin-A With Cardiovascular Disease Mortality in Older Community-Dwelling Adults

Objectives 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 1025 women (median age=73 years) who had fetuin-A levels and CVD risk factors evaluated in 1992-96 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 hazards ratio for CVD mortality comparing the lowest fetuin-A quartile with all higher values was 1.76 (95% CI 1.34, 2.31; P<0.001) for participants without diabetes and 0.43 (95% CI 0.19, 0.98; P=.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.