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.

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 <or= 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.

• Authors: B E de Galan, S Zoungas, J Chalmers, C Anderson, C Dufouil, A Pillai, M Cooper, D E Grobbee, M Hackett, P Hamet, S R Heller, L Lisheng, S MacMahon, G Mancia, B Neal, C Y Pan, A Patel, N Poulter, F Travert, M Woodward, ADVANCE Collaborative group
• Journal: Diabetologia (Diabetologia) Vol. 52 Issue 11 Pg. 2328-2336 (Nov 2009) ISSN: 1432-0428 [Electronic] Germany
• PMID: 19688336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Drug Combinations
• Hypoglycemic Agents
• indapamide, perindopril drug combination
• Indapamide
• Gliclazide
• Perindopril

Topics

• Aged
• Antihypertensive Agents (therapeutic use)
• Cognition (drug effects)
• Cognition Disorders (complications)
• Diabetes Mellitus, Type 2 (blood, complications, mortality, psychology)
• Diabetic Angiopathies (epidemiology, prevention & control)
• Drug Combinations
• Drug Therapy, Combination
• Educational Status
• Female
• Gliclazide (therapeutic use)
• Humans
• Hypoglycemia (epidemiology)
• Hypoglycemic Agents (therapeutic use)
• Indapamide (therapeutic use)
• Male
• Mental Status Schedule
• Myocardial Infarction (epidemiology)
• Perindopril (therapeutic use)
• Risk Factors
• Stroke (epidemiology)