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.
Diabetes Care 28:1383-1389, 2005T here is increasing evidence that micro-and macrovascular complications of diabetes share certain pathophysiological mechanisms. This may explain why microangiopathy has been associated with macroangiopathy and with mortality (1-10). For example, microalbuminuria has strongly and independently been associated with the development of cardiovascular disease (CVD) and mortality in type 2 diabetic patients (1-3,10). Further, retinopathy has also been associated with increased cardiovascular and all-cause mortality risk, particularly in type 2 diabetes (4 -9). In type 1 diabetes, however, this association has been explored only in a limited fashion (4,11). Type 1 diabetes, though, offers a better opportunity to study the relationship between retinopathy and cardiovascular events than type 2 diabetes, because of a younger population with less confounding variables associated with the metabolic syndrome.The pathophysiology underlying the association of retinopathy with CVD and mortality is not well understood. Cardiovascular risk factors, such as hypertension, dyslipidemia, and elevated HbA 1c level are also known as risk factors for the developmen...
