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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1086.)
© 2006 American Heart Association, Inc.

Vascular Biology

Endothelial Dysfunction and Low-Grade Inflammation Explain Much of the Excess Cardiovascular Mortality in Individuals With Type 2 Diabetes

The Hoorn Study

Jolien de Jager; Jacqueline M. Dekker; Adriaan Kooy; Piet J. Kostense; Giel Nijpels; Rob J. Heine; Lex M. Bouter; Coen D.A. Stehouwer

From the Department of Internal Medicine, Bethesda General Hospital, Hoogeveen, the Netherlands (J.d.J., A.K); the Institute for Research in Extramural Medicine (J.M.D., P.J.K., G.N., R.J.H., L.M.B., C.D.A.S.), VU University Medical Center, Amsterdam, The Netherlands; and the Department of Internal Medicine, University Hospital Maastricht, The Netherlands (C.D.A.S.).

Correspondence to Coen D.A. Stehouwer, MD, Professor and Chair, Department of Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail csteh{at}sint.azm.nl

Objective— The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention.

Methods and Results— In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained 43% of the increase in cardiovascular mortality risk conferred by T2D.

Conclusions— These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.

Endothelial dysfunction and low-grade inflammation may explain, at least in part, the increased cardiovascular disease risk in type 2 diabetes (T2D). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic than in nondiabetic individuals (P interaction=0.06). T2D-associated endothelial dysfunction and low-grade inflammation explained 43% of the increase in cardiovascular mortality risk conferred by T2D.

Key Words: epidemiology • diabetes mellitus • endothelium • inflammation • mortality

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