The Association of Severe Diabetic Retinopathy With Cardiovascular Outcomes in Long-standing Type 1 Diabetes: A Longitudinal Follow-up

Abstract

Objective: It is well established that diabetic nephropathy increases the risk of cardiovascular disease (CVD), but how severe diabetic retinopathy (SDR) impacts this risk has yet to be determined.

Research design and methods: The cumulative incidence of various CVD events, including coronary heart disease (CHD), peripheral artery disease (PAD), and stroke, retrieved from registries, was evaluated in 1,683 individuals with at least a 30-year duration of type 1 diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). The individuals were divided into four groups according to the presence of diabetic kidney disease (DKD) and/or SDR (+DKD/+SDR, +DKD/-SDR, -DKD/+SDR, and -DKD/-SDR) at baseline visit. Furthermore, age-specific incidences were compared with 4,016 control subjects without diabetes. SDR was defined as laser photocoagulation and DKD as estimated glomerular filtration rate <60 mL/min/1.73 m².

Results: During 12,872 person-years of follow-up, 416 incident CVD events occurred. Even in the absence of DKD, SDR increased the risk of any CVD (hazard ratio 1.46 [95% CI 1.11-1.92]; P < 0.01), after adjustment for diabetes duration, age at diabetes onset, sex, smoking, blood pressure, waist-to-hip ratio, history of hypoglycemia, and serum lipids. In particular, SDR alone was associated with the risk of PAD (1.90 [1.13-3.17]; P < 0.05) and CHD (1.50 [1.09-2.07; P < 0.05) but not with any stroke. Moreover, DKD increased the CVD risk further (2.85 [2.13-3.81]; P < 0.001). However, the risk was above that of the control subjects without diabetes also in patients without microvascular complications, until the patients reached their seventies.

Conclusions: SDR alone, even without DKD, increases cardiovascular risk, particularly for PAD, independently of common cardiovascular risk factors in long-standing type 1 diabetes. More remains to be done to fully understand the link between SDR and CVD. This knowledge could help combat the enhanced cardiovascular risk beyond currently available regimens.

Figure 1

A: Cumulative incidence of CVD events from baseline, divided by the DKD/SDR status. All P values for the log-rank test with the group −DKD/−SDR as a reference <0.001. B: Cumulative incidence of CVD events from baseline, divided by the ALB/SDR status. All P values for the log-rank test with the group −ALB/−SDR as a reference <0.001. +ALB defined as having micro- or macroalbuminuria or end-stage renal disease and −ALB as normoalbuminuria.

Figure 2

A: Age-specific incidences of overall CVD depending on the DKD/SDR status. Comparison with the matched control group of patients without diabetes is added. Age-specific incidences: age-groups 20–29, 30–39, 40–49, 50–59, 60–69, and 70–79 years. *The upper limit of the 95% CI is 399. #The upper limit of the 95% CI is 199. B: Duration-specific incidence of overall CVD depending on the DKD/SDR status; duration groups: 0–19, 20–29, 30–39, 40–49, and ≥50 years.