Diabetic Retinopathy Is Associated With Mortality and Cardiovascular Disease Incidence

Abstract

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...

Diabetic Retinopathy and the Risk of Coronary Heart Disease

“…Studies in Finland (10,16) and Milan (11) have reported an increased CHD risk among diabetic individuals with retinopathy, while controlling for cardiovascular risk factors. Other studies, however, suggest that the association of diabetic retinopathy with CHD is largely due to shared risk factors (12,13,15). A recent study of 824 type 2 diabetic patients, using fundoscopic examinations to evaluate retinopathy, showed a sex difference in the association of background diabetic retinopathy with CHD death, raising the possibility that microvascular disease might be more important in the development of CHD in women than in men (16).…”

Proliferative Diabetic Retinopathy in Type 2 Diabetes Is Related to Coronary Artery Calcium in the Veterans Affairs Diabetes Trial (VADT)

“…In fact, substantial evidence now exists that both microalbuminuria and retinopathy are independent risk factors for CVD events and mortality (2)(3)(4)(5)(7)(8)(9)(10)(11)30). Although the studies in type 1 diabetes are limited in number (9,31), this relationship between retinopathy and CVD is present in both type 1 and type 2 diabetic populations and appears strongest for proliferative retinopathy (4,5,7-11).…”

“…This relationship appears to be present in both type 1 and type 2 diabetes (4 -11). Importantly, most (4,5,(7)(8)(9)(10)(11), but not all (9), of these studies have indicated that retinopathy may be independently associated with CVD events or mortality even after taking into account standard cardiovascular risk factors, diabetes duration, and/or glycemic control. Results from these studies suggest that there may be shared risk factors or mechanisms underlying both retinopathy and clinical CVD and that the relationship does not appear to be explained by standard cardiovascular risk factors or glycemic control.…”

Risk factors for development and progression of nonproliferative retinopathy in normoalbuminuric patients with type 1 diabetes

“…Diabetic retinopathy is also associated with mortality and cardiovascular disease incidence in diabetes [2]. Prospective studies identified poor glycemic control, duration of diabetes and blood pressure as most important risk factors for development of retinopathy [3][4][5][6][7].…”