Clinical Research
Cardiovascular Risk
The Association of Fetuin-A With Cardiovascular Disease Mortality in Older Community-Dwelling Adults: The Rancho Bernardo Study

https://doi.org/10.1016/j.jacc.2012.01.038Get rights and content
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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.

Key Words

cardiovascular disease
diabetes mellitus
epidemiology
fetuin-A
mortality

Abbreviations and Acronyms

BMI
body mass index
CI
confidence interval
CVD
cardiovascular disease
eGFR
estimated glomerular filtration rate
HDL
high-density lipoprotein
HOMA-IR
homeostasis model assessment for insulin resistance
HR
hazard ratio
LDL
low-density lipoprotein

Cited by (0)

This study was sponsored by a grant from the National Heart, Lung, and Blood Institute (R01HL096851) supporting Drs. Laughlin, Wassel, and Ix. The Rancho Bernardo Study was funded by research grants AG028507 and AG018339 from the National Institute on Aging and grant DK31801 from the National Institute of Diabetes and Digestive and Kidney Diseases. Drs. Laughlin and Daniels were also supported by grants from the American Heart Association.

All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. JoAnn Manson, MD, served as Guest Editor for this paper.