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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:815.)
© 2005 American Heart Association, Inc.

Atherosclerosis & Lipoproteins

High Serum Levels of Advanced Glycation End Products Predict Increased Coronary Heart Disease Mortality in Nondiabetic Women but not in Nondiabetic Men

A Population-Based 18-Year Follow-Up Study

Bente K. Kilhovd; Auni Juutilainen; Seppo Lehto; Tapani Rönnemaa; Peter A. Torjesen; Kåre I. Birkeland; Tore J. Berg; Kristian F. Hanssen; Markku Laakso

From the Diabetes Research Centre, Aker and Ullevål University Hospitals and Department of Medicine (B.K.K., T.J.B., K.F.H.) and the Hormone Laboratory (P.A.T., K.I.B.), Aker University Hospital HF, Oslo; the Department of Medicine (A.J., S.L., M.L.), University of Kuopio and Kuopio University Hospital; and the Department of Medicine (T.R.), University of Turku, Finland.

Correspondence to Markku Laakso, MD, Professor, University of Kuopio, Department of Medicine, 70210 Kuopio, Finland. E-mail markku.laakso{at}kuh.fi

Background— Advanced glycation end products (AGEs), modification products of glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes as well as in nondiabetic subjects.

Methods and Results— Serum levels of AGEs were measured with an immunoassay in samples obtained at baseline examination of a random sample of 1141 nondiabetic individuals (535 men and 606 women), aged 45 to 64 years, living in Kuopio, East Finland, or Turku, West Finland in 1982 to 1984. After 18 years of follow-up, all-cause mortality, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality were registered on the basis of copies of death certificates. Multivariate Cox regression model showed a significant association of serum AGEs with all-cause (P=0.012), CVD (P=0.018), and CHD (P=0.008) mortality in women but not in men. Fasting serum AGEs in the highest quartile were an independent risk factor for all-cause (hazards ratio [HR], 1.90; 95% CI, 1.16 to 3.11; P=0.011) and CHD (HR, 6.51; 95% CI, 1.78 to 23.79; P=0.005) mortality in women, even after the adjustment for confounding factors, including highly sensitive C-reactive protein.

Conclusions— The present study is the first to show that serum levels of AGEs can predict total, CVD, and CHD mortality in nondiabetic women.

Serum levels of advanced glycation end products measured at baseline in a random sample of 1141 Finnish middle-aged nondiabetic individuals (535 men and 606 women) predicted all-cause mortality, cardiovascular, and coronary heart disease mortality after 18 years of follow-up in women but not in men.

Key Words: advanced glycation end products • coronary heart disease • cardiovascular disease • mortality

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