Mohammedi K, et al. – The objective of this study was to assess the respective impacts of prior microvascular and macrovascular disease on the risk of major outcomes, including microvascular events, in these patients. The evidence suggested that microvascular and macrovascular disease are independently correlated with the 10–year risk of death, major macrovascular events (MACE), and major clinical microvascular events in patients with type 2 diabetes. The coexistence of these conditions was correlated with the highest risks.

Methods

• Participants in the Action in Diabetes and Vascular Disease: Researchers classified PreterAx and DiamicroN Modified–Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and the ADVANCE–ON post–trial study (n = 8494) into 4 groups at baseline: dual absence of microvascular or macrovascular disease (n = 6789), presence of microvascular disease alone (n = 761), macrovascular disease alone (n = 3196), and both (n = 394).
• All–cause mortality, major macrovascular events (MACE), and major clinical microvascular events were considered as outcomes.

Results

• They found that all–cause mortality, MACE, and major clinical microvascular events occurred in 2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median follow–up of 9.9 (inter–quartile interval 5.6–10.9) years.
• The data indicated that the adjusted hazard ratios [95% CI] of death, MACE, and major clinical microvascular events were each greater in patients with baseline microvascular disease (1.43 [1.20–1.71], 1.64 [1.37–1.97], and 4.74 [3.86–5.82], respectively), macrovascular disease (1.43 [1.30–1.57], 2.04 [1.86–2.25], and 1.26 [1.06–1.51]) or both (2.01 [1.65–2.45], 2.92 [2.40–3.55], and 6.30 [4.93–8.06]) compared with those without these conditions.
• There were no interaction between baseline microvascular and macrovascular disease for these events.
• In context of the findings, the addition of microvascular disease (change in c–statistic [95% CI] 0.005 [0.002–0.008], p = 0.02) or macrovascular disease (0.005 [0.002–0.007], p < 0.0001) considered separately or together (0.011 [0.007–0.014], p < 0.0001) enhanced the discrimination and the classification (integrated discrimination improvement (IDI): 0.013 [0.010–0.016], p < 0.001; net reclassification improvement (NRI): 0.021 [0.011–0.032], p < 0.001) of the risk of all–cause mortality.
• The data suggested that microvascular disease improved discrimination (0.009 [0.003–0.014]) and classification (IDI: 0.008 [0.006–0.010]; NRI: 0.011 [0.001–0.020]) of MACE.
• Remarkably, baseline macrovascular disease modestly enhanced IDI (0.002 [0.001–0.002]) and NRI (0.041 [0.002–0.087]), but not discri–ination, of major clinical microvascular events.