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)

  1. Piero Ruggenenti, MD1,2,
  2. Ilian Iliev, MD1,
  3. Grazia Maria Costa, MD1,3,
  4. Aneliya Parvanova, MD1,
  5. Annalisa Perna, STAT SCI D1,
  6. Giovanni Antonio Giuliano, DIPL STAT1,
  7. Nicola Motterlini, STAT SCI D1,
  8. Bogdan Ene-Iordache, ENG D1,
  9. Giuseppe Remuzzi, MD, FRCP1,2 and
  10. the BENEDICT Study Group
  1. 1Clinical Research Center for Rare Diseases “Aldo & Cele Daccò,” Mario Negri Institute for Pharmacological Research, Bergamo, Italy
  2. 2Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti, Bergamo, Italy
  3. 3Unit of Cardiovascular Diseases, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
  1. Corresponding author: Piero Ruggenenti, manuelap{at}marionegri.it

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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 28 April 2008. Clinical trial reg. no. NCT00235014.

  • * A complete list of the members of the BENEDICT Study Group can be found in Online Appendix 1 (available at http://dx.doi.org/10.2337/dc08-0371).

  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received February 20, 2008.
    • Accepted April 23, 2008.
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  1. Published online before print April 28, 2008, doi: 10.2337/dc08-0371 Diabetes Care August 2008 vol. 31 no. 8 1629-1634
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