Preventing left ventricular hypertrophy by ACE inhibition in hypertensive patients with type 2 diabetes: a prespecified analysis of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT)

Piero Ruggenenti, Ilian Iliev, Grazia Maria Costa, Aneliya Parvanova, Annalisa Perna, Giovanni Antonio Giuliano, Nicola Motterlini, Bogdan Ene-Iordache, Giuseppe Remuzzi, Bergamo Nephrologic Diabetes Complications Trial Study Group, Piero Ruggenenti, Ilian Iliev, Grazia Maria Costa, Aneliya Parvanova, Annalisa Perna, Giovanni Antonio Giuliano, Nicola Motterlini, Bogdan Ene-Iordache, Giuseppe Remuzzi, Bergamo Nephrologic Diabetes Complications Trial Study Group

Abstract

Objective: In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evidence of LVH (ECG-LVH).

Research design and methods: This prespecified study compared the incidence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), who had no ECG-LVH at baseline and were randomly assigned to at least 3 years of blinded ACE inhibition with trandolapril (2 mg/day) or to non-ACE inhibitor therapy. Treatment was titrated to systolic/diastolic blood pressure <130/80 mmHg. ECG readings were centralized and blinded to treatment.

Results: Baseline characteristics of the two groups were similar. Over a median (interquartile range) follow-up of 36 (24-48) months, 13 of the 423 patients (3.1%) receiving trandolapril compared with 31 of the 376 patients (8.2%) receiving non-ACE inhibitor therapy developed ECG-LVH (hazard ratio [HR] 0.34 [95% CI 0.18-0.65], P = 0.0012 unadjusted, and 0.35 [0.18-0.68], P = 0.0018 adjusted for predefined baseline covariates). The HR was significant even after adjustment for follow-up blood pressure and blood pressure reduction versus baseline. Compared with baseline, both Sokolow-Lyon and Cornell voltages significantly decreased with trandolapril but did not change with non-ACE inhibitor therapy.

Conclusions: ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to its blood pressure-lowering effect. Because ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes, early ACE inhibition may be cardioprotective in this population.

Trial registration: ClinicalTrials.gov NCT00235014.

Figures

Figure 1
Figure 1
Kaplan-Meier curves for the percentages of subjects receiving ACE inhibitor therapy with trandolapril (ACEi YES) or receiving non-ACE inhibitor therapy (ACEi NO) who developed ECG-LVH. The difference in ECG-LVH adjusted for prespecified baseline covariates was significant (P = 0.0018).

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