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
2008
Gupta, Ajay K. | Dahlöf, Björn | Dobson, Joanna | Sever, Peter S. | Wedel, Hans | Poulter, N.R.
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. RESEARCH DESIGN AND 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.
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