Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial--Blood Pressure Lowering Arm and the relative influence of antihypertensive medication.
OBJECTIVE
The purpose of this study was to determine the baseline predictors of new-onset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD.


METHODS
Among 19,257 hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol +/- thiazide or amlodipine +/- perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores.


RESULTS
NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine +/- perindopril in comparison with atenolol +/- thiazide treatment (hazard ratio 0.66 [95% CI 0.59-0.74]), high HDL cholesterol, alcohol use, and age >55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise >5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.


CONCLUSIONS
Baseline FPG >5 mmol/l, BMI, and use of an atenolol +/- diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects.
Gupta
Ajay K
AK
International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College, London, UK.
Dahlof
Bjorn
B
Dobson
Joanna
J
Sever
Peter S
PS
Wedel
Hans
H
Poulter
N R
NR
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D004739:England; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D020913:Perindopril / Q000627:therapeutic use; D013548:Sweden
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017311:Amlodipine; D001262:Atenolol; D020913:Perindopril