Retinopathy predicts stroke but not myocardial infarction in type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: Microangiopathy in type 2 diabetes (T2D) is associated with cardiovascular disease (CVD), but most relevant studies were performed > 10 years ago. CVD risk factor management has since improved. The aim of this study was to determine whether diabetic retinopathy (DR) and its severity increases stroke and myocardial infarction (MI) risk in a contemporary cohort. METHODS: Fremantle Diabetes Study Phase II participants with T2D had DR graded from fundus photography at baseline between 2008 and 2011. Subsequent hospitalizations and mortality for MI or stroke were ascertained through validated data linkage to end-2016. Cox regression modelling identified predictors of first stroke and MI including DR presence and severity. RESULTS: The 1521 participants with T2D and known DR status (mean age 65.6 years, 52.1% males, median diabetes duration 9.0 years) were followed for a mean of 6.6 years. After excluding those with prior MI/stroke, there were 126 incident MIs among 1393 eligible participants and 53 incident strokes in 1473 eligible participants, respectively. Moderate non-proliferative DR (NPDR) or worse was significantly and independently associated with an increased risk of incident stroke (adjusted hazard ratio 2.55 (95% CI 1.19, 5.47), p = 0.016). Retinopathy presence and severity increased the risk of incident MI in unadjusted models (p ≤ 0.001), but these associations were no longer statistically significant after adjusting for other risk factors. CONCLUSIONS: Moderate NPDR or worse was associated with an increased risk of first stroke in Australians with T2D. Intensified CVD risk factor management should be considered for patients with at least moderate NPDR.

Contemporary Cardiovascular Risk Assessment for Type 2 Diabetes Including Heart Failure as an Outcome: The Fremantle Diabetes Study Phase II.

Background: Type 2 diabetes (T2D) cardiovascular disease (CVD) risk assessment has limitations. The aim of this study was to develop a risk equation adding heart failure (HF) to conventional major adverse cardiovascular events (MACE, myocardial infarction, stroke, and CVD death) and allowing for non-CVD death. Methods: 1551 community-based people with T2D (mean age 66 years, 52% males) were followed from baseline in 2008-2011 for five years to the first CVD event/death. Cox and competing risk regression identified predictors of three-point MACE and four-point MACE (including HF). Discrimination was assessed by the area under the receiver-operating characteristic curve (AUC) and calibration by the Hosmer-Lemeshow test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for a 10% five-year CVD risk cut-off. Results: 143 participants (9.2%) experienced a three-point MACE during 7,111 person-years of follow-up and 245 (15.8%) a four-point MACE during 6,896 person-years. The best model was the competing risk four-point MACE (221 predicted events (14.3%), AUC 0.82 (95% CI: 0.79-0.85), Hosmer-Lemeshow test, p = 0.17, sensitivity 79.2%, specificity 68.1%, PPV 31.8%, NPV 94.6%) with validation in 177 adults with T2D from an independent population (AUC 0.81 (0.74-0.89). Conclusions: A validated four-point MACE competing risk model reliably predicts key T2D CVD outcomes.