Aims/hypothesis: The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial. Methods: Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n=8,689), 24-27 ('mild dysfunction', n=2,231) and <24 ('severe dysfunction', n=212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis. Results: Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99; both p<0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46; both p≤0.05) and all-cause death (1.33, 95% CI 1.16-1.54 and 1.50, 95% CI 1.06-2.12; both p<0.03). Severe, but not mild, cognitive dysfunction increased the risk of severe hypoglycaemia (HR 2.10, 95% CI 1.14-3.87; p=0.018). There was no evidence of heterogeneity of treatment effects on cardiovascular outcomes in subgroups defined by cognitive function at baseline. Conclusions/interpretation: Cognitive dysfunction is an independent predictor of clinical outcomes in patients with type 2 diabetes, but does not modify the effects of BP lowering or glucose control on the risks of major cardiovascular events. Trial registration:: ClinicalTrials.gov NCT00145925 Funding:: Supported by grants from Servier and from the National Health and Medical Research Council of Australia. © 2009 Springer-Verlag.
De Galan, B., Zoungas, S., Chalmers, J., Anderson, C., Dufouil, C., Pillai, A., et al. (2009). Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: The action in diabetes and vascular disease: Preterax and diamicron modified release controlled evaluation (ADVANCE) trial. DIABETOLOGIA, 52, 2328-2336 [10.1007/s00125-009-1484-7].
Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: The action in diabetes and vascular disease: Preterax and diamicron modified release controlled evaluation (ADVANCE) trial
MANCIA, GIUSEPPE;
2009
Abstract
Aims/hypothesis: The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial. Methods: Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n=8,689), 24-27 ('mild dysfunction', n=2,231) and <24 ('severe dysfunction', n=212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis. Results: Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99; both p<0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46; both p≤0.05) and all-cause death (1.33, 95% CI 1.16-1.54 and 1.50, 95% CI 1.06-2.12; both p<0.03). Severe, but not mild, cognitive dysfunction increased the risk of severe hypoglycaemia (HR 2.10, 95% CI 1.14-3.87; p=0.018). There was no evidence of heterogeneity of treatment effects on cardiovascular outcomes in subgroups defined by cognitive function at baseline. Conclusions/interpretation: Cognitive dysfunction is an independent predictor of clinical outcomes in patients with type 2 diabetes, but does not modify the effects of BP lowering or glucose control on the risks of major cardiovascular events. Trial registration:: ClinicalTrials.gov NCT00145925 Funding:: Supported by grants from Servier and from the National Health and Medical Research Council of Australia. © 2009 Springer-Verlag.
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