Is pulse pressure a predictor of new-onset diabetes in high-risk hypertensive patients?: a subanalysis of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial

Abstract

Objective: Hypertensive patients have an increased risk of developing diabetes. Accumulating evidence suggests a close relation between metabolic disturbance and increased arterial stiffness. Here, we examined the association between pulse pressure and the risk of new-onset diabetes in high-risk Japanese hypertensive patients.

Research design and methods: The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial examined the effects of candesartan and amlodipine on the incidence of cardiovascular events in 4,728 high-risk Japanese hypertensive patients. In the present study, we analyzed the relationship between pulse pressure at baseline and new-onset diabetes in 2,685 patients without diabetes at baseline (male 1,471; mean age 63.7 years; mean BMI 24.8 kg/m(2)) as a subanalysis of the CASE-J trial.

Results: During 3.3 +/- 0.8 years of follow-up, 97 patients (3.6%) developed diabetes. In multiple Cox regression analysis, pulse pressure was an independent predictor for new-onset diabetes (hazard ratio [HR] per 1 SD increase 1.44 [95% CI 1.15-1.79]) as were male sex, BMI, and additional use of diuretics, whereas age and heart rate were not. Plots of HRs for new-onset diabetes considering both systolic and diastolic blood pressure (DBP) revealed that a higher pulse pressure with a lower DBP, indicating that the increased pulse pressure was largely due to increased arterial stiffness, was strongly associated with the risk of new-onset diabetes.

Conclusions: Pulse pressure is an independent predictor of new-onset diabetes in high-risk Japanese hypertensive patients. Increased arterial stiffness may be involved in the development of diabetes.

Figure 1

Risk of new-onset diabetes by SBP and DBP at enrollment. HR of DBP of 90 mmHg in the SBP <160 mmHg category was assigned a reference value of 1.0.

Figure 2

Effect of candesartan and amlodipine on the incidence of new-onset diabetes stratified by quartile of PP_f. PP_f (linear and quadratic terms), the allocated drugs, and their interaction terms were entered in multiple Cox regression model. P value was calculated based on the Wald test.