Hertzel C Gerstein1, Michael E Miller2, Faramarz Ismail-Beigi3, Joe Largay4, Charlotte McDonald5, Heather A Lochnan6, Gillian L Booth7. 1. Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. Electronic address: gerstein@mcmaster.ca. 2. Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA. 3. Case Western Reserve University and Cleveland VA Medical Center, Cleveland, OH, USA. 4. Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. 5. St Joseph's Health Care London, Schulich School of Medicine, Western University, London, ON, Canada. 6. Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. 7. Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada.
Abstract
BACKGROUND:Hyperglycaemia could substantially increase the risk of ischaemic heart disease in patients with type 2 diabetes. We investigated whether intensive lowering of glucose concentrations affects risk. METHODS: We assessed 10,251 adults aged 40-79 years with established type 2 diabetes, meanglycated haemoglobinA1c (HbA1c) concentration of 67 mmol/mol (8·3%), and risk factors for ischaemic heart disease enrolled in the ACCORD trial. Participants were assigned to intensive or standard therapy (target HbA1c less than 42 or 53-63 mmol/mol [less than 6·0% or 7·0-7·9%], respectively). We assessed fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina, and new angina during active treatment (mean 3·7 years) plus a further mean 1·2 years. This trial is registered with ClinicalTrials.gov, number NCT00000620. FINDINGS:Myocardial infarction was less frequent in the intensive than in the standard therapy group during active treatment (hazard ratio [HR] 0·80, 95% CI 0·67-0·96; p=0·015) and overall (0·84, 0·72-0·97; p=0·02). Findings were similar for combined myocardial infarction, coronary revascularisation, and unstable angina (active treatment HR 0·89, 95% CI 0·79-0·99, overall 0·87 0·79-0·96) and for coronary revascularisation alone (0·84, 0·75-0·94) and unstable angina alone (0·81, 0·67-0·97) during full follow-up. With lowest achieved HbA1C concentrations included as a time-dependent covariate, all hazards became non-significant. INTERPRETATION: Raised glucose concentration is a modifiable risk factor for ischaemic heart disease in middle-aged people with type 2 diabetes and other cardiovascular risk factors. FUNDING: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Eye Intitute, and Centers for Disease Control and Prevention.
RCT Entities:
BACKGROUND: Hyperglycaemia could substantially increase the risk of ischaemic heart disease in patients with type 2 diabetes. We investigated whether intensive lowering of glucose concentrations affects risk. METHODS: We assessed 10,251 adults aged 40-79 years with established type 2 diabetes, mean glycated haemoglobin A1c (HbA1c) concentration of 67 mmol/mol (8·3%), and risk factors for ischaemic heart disease enrolled in the ACCORD trial. Participants were assigned to intensive or standard therapy (target HbA1c less than 42 or 53-63 mmol/mol [less than 6·0% or 7·0-7·9%], respectively). We assessed fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina, and new angina during active treatment (mean 3·7 years) plus a further mean 1·2 years. This trial is registered with ClinicalTrials.gov, number NCT00000620. FINDINGS:Myocardial infarction was less frequent in the intensive than in the standard therapy group during active treatment (hazard ratio [HR] 0·80, 95% CI 0·67-0·96; p=0·015) and overall (0·84, 0·72-0·97; p=0·02). Findings were similar for combined myocardial infarction, coronary revascularisation, and unstable angina (active treatment HR 0·89, 95% CI 0·79-0·99, overall 0·87 0·79-0·96) and for coronary revascularisation alone (0·84, 0·75-0·94) and unstable angina alone (0·81, 0·67-0·97) during full follow-up. With lowest achieved HbA1C concentrations included as a time-dependent covariate, all hazards became non-significant. INTERPRETATION: Raised glucose concentration is a modifiable risk factor for ischaemic heart disease in middle-aged people with type 2 diabetes and other cardiovascular risk factors. FUNDING: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Eye Intitute, and Centers for Disease Control and Prevention.
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