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Diabetes Care Publish Ahead of Print published online ahead of print April 28, 2008
DOI: 10.2337/dc08-0371
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Original Research

PREVENTING LEFT VENTRICULAR HYPERTROPHY BY ACE INHIBITION IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES: A PRESPECIFIED ANALYSIS OF THE BENEDICT TRIAL

Piero Ruggenenti, MD*,,°, Ilian Iliev, MD*, Grazia Maria Costa, MD*,,^, Aneliya Parvanova, MD*, Annalisa Perna, Stat Sci D*, Giovanni Antonio Giuliano, Dipl Stat*, Nicola Motterlini, Stat Sci D*, Bogdan Ene-Iordache, Eng D*, Giuseppe Remuzzi, MD, FRCP*,,° and the BENEDICT Study Group (Study Organization, on-line Appendix 1)

*Clinical Research Center for Rare Diseases ‘Aldo & Cele Daccò’, Mario Negri Institute for Pharmacological Research
°Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti, Bergamo
^Unit of Cardiovascular Diseases, Policlinico Sant'Orsola-Malpighi, Bologna, Italy

manuelap{at}marionegri.it

pruggenenti{at}ospedaliriuniti.bergamo.it

ABSTRACT

Objective: In patients with type 2 diabetes left ventricular hypertrophy (LVH) predicts cardiovascular events and its prevention is cardioprotective.

Research Design and Methods: This pre-specified study compared the incidence of electrocardiographic (ECG) LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) randomized to at least 3-year blinded angiotensin-converting-enzyme (ACE) inhibition with trandolapril (2 mg/day) or non-ACE inhibitor therapy, who had no ECG-LVH at baseline. Treatment was titrated to systolic/diastolic blood pressure (BP) <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 to 48) months, 13 of the 423 patients (3.1%) on trandolapril compared to 31 of the 376 (8.2%) on non-ACE inhibitor therapy developed ECG-LVH. [Hazard Ratio (95% CI): 0.34 (0.18 to 0.65), P=0.0012 (unadjusted); 0.35 (0.18 to 0.68), P=0.0018 (adjusted for pre-define baseline covariates)]. The Hazard Ratio was significant even after adjustment for follow-up BP and BP reduction vs baseline. Compared to baseline, both Sokolow-Lyon and Cornell voltages significantly decreased on trandolapril, but did not change on non-ACE inhibitor therapy.

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


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