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Diabetes Care 28:1383-1389, 2005
© 2005 by the American Diabetes Association, Inc.


Pathophysiology/Complications
Original Article

Diabetic Retinopathy Is Associated With Mortality and Cardiovascular Disease Incidence

The EURODIAB Prospective Complications Study

Manon V. van Hecke, MD1,2, Jacqueline M. Dekker, PHD2, Coen D.A. Stehouwer, MD, PHD2,3, Bettine C.P. Polak, MD, PHD1,2, John H. Fuller, FRCP4, Anne Katrin Sjolie, DSCI5, Athanasios Kofinis, MD6, Raoul Rottiers, MD7, Massimo Porta, MD, PHD8 and Nish Chaturvedi, MRCP9

1 Department of Ophthalmology, VU University Medical Center, Amsterdam, the Netherlands
2 Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, the Netherlands
3 Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, the Netherlands
4 Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, U.K.
5 Department of Ophthalmology, Odense University Hospital, Odense, Denmark
6 Diabetic Centre, Hippokration Hospital, Athens, Greece
7 Department of Endocrinology, University Hospital Gent, Gent, Belgium
8 Department of Internal Medicine, University of Turin, Turin, Italy
9 International Centre for Circulatory Health & National Heart & Lung Institute, Imperial College London, London, U.K.

Address correspondence and reprint requests to Manon V. van Hecke, MD, Department of Ophthalmology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. E-mail: m.vanhecke{at}vumc.nl

OBJECTIVE—To study the relationship of nonproliferative and proliferative retinopathy with all-cause mortality and cardiovascular disease (CVD) incidence in type 1 diabetic patients and, additionally, the role of cardiovascular risk factors in these associations.

RESEARCH DESIGN AND METHODS—This prospective study included 2,237 type 1 diabetic patients from 31 centers in 16 European countries at baseline, aged 15–60 years, who were examined for retinopathy by taking two-field 45° fundus photographs, which were centrally graded. Mortality and cardiovascular morbidity follow-up was assessed 6–8 years after baseline examination according to a standardized protocol.

RESULTS—After 7.9 years of follow-up, 64 patients had died and 128 patients had incident CVD. The age- and sex-adjusted hazard ratios (HRs) of all-cause mortality were 1.45 (95% CI 0.71–2.96) and 4.16 (1.96–8.84) in patients with nonproliferative and proliferative retinopathy at baseline, respectively. Adjustments for cardiovascular risk factors completely obliterated the association with nonproliferative retinopathy, whereas the association with proliferative retinopathy remained twofold increased, although nonsignificant. The age- and sex-adjusted HRs of incident CVD were 1.73 (1.15–2.60) and 2.05 (1.22–3.45) in patients with nonproliferative and proliferative retinopathy, respectively. After adjustments for cardiovascular risk factors, both associations were attenuated and lost statistical significance.

CONCLUSIONS—This study shows that type 1 diabetic patients with nonproliferative or proliferative retinopathy have an increased risk for all-cause mortality and incident CVD. The presence of cardiovascular risk factors explained the associations to a large extent, except for the associations with proliferative retinopathy, which suggests that other shared mechanisms may be involved.

Abbreviations: AER, albumin excretion rate • CVD, cardiovascular disease • ECG, electrocardiogram


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Find additional patient-related information at:

Connections Between Retinopathy and Cardiovascular Disease in Patients With Type 1 Diabetes


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