The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis.
OBJECTIVE
Emerging data suggest that different indices of glycaemia are risk factors for clinical events. The aim of this analysis was to investigate the relationship between fasting plasma glucose or glycated haemoglobin (GHb) levels and incident cardiovascular (CV) outcomes, death, heart failure and overt nephropathy in diabetic and non-diabetic individuals enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study.


METHODS
The adjusted 4.5-year risk of CV events (myocardial infarction or stroke or CV death), heart failure, death and overt nephropathy was analysed in relation to baseline and updated GHb levels (in 3,529 diabetic HOPE study participants) and baseline fasting plasma glucose levels (in 1,937 non-diabetic and 1,013 diabetic participants).


RESULTS
In diabetic participants, a 1% absolute rise in the updated GHb predicted future CV events (relative risk [RR]=1.07, 95% CI 1.01-1.13; p=0.014), death (RR=1.12, 95% CI 1.05-1.19; p=0.0004), heart failure (RR=1.20, 95% CI 1.08-1.33; p=0.0008) and overt nephropathy (RR=1.26, 95% CI 1.17-1.36; p<0.0001) after adjusting for age, sex, diabetes duration, blood pressure, WHR, hyperlipidaemia and ramipril. Similarly, a 1 mmol/l rise in fasting plasma glucose was related to an increased risk of CV outcomes (RR=1.09, 95% CI 1.05-1.13; p<0.0001), death (RR=1.06, 95% CI 1.01-1.12; p=0.017), heart failure (RR=1.16, 95% CI 1.06-1.13; p=0.0007) and overt nephropathy (RR=1.34, 95% CI 1.23-1.45; p<0.0001) in the group composed of diabetic and non-diabetic individuals. The significant relationship between fasting plasma glucose and CV outcomes persisted after adjustment for diabetes status (RR=1.06, 95% CI 1.00-1.12; p=0.043).


CONCLUSIONS
There is an independent progressive relationship between indices of glycaemia and incident CV events, renal disease and death. Clinical trials of glucose lowering to prevent these outcomes in diabetic and non-diabetic individuals are indicated.
Gerstein
H C
HC
McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada. gerstein@mcmaster.ca
Pogue
J
J
Mann
J F E
JF
Lonn
E
E
Dagenais
G R
GR
McQueen
M
M
Yusuf
S
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology*; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology*; D008297:Male; D010919:Placebos; D017257:Ramipril / Q000627:therapeutic use; D012016:Reference Values; D012307:Risk Factors; D014810:Vitamin E / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D010919:Placebos; D017257:Ramipril; D014810:Vitamin E