CLINICAL STUDY: HEART FAILURE
Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype
Mariantonietta Cicoira, MD*,
Luisa Zanolla, MD*,
Andrea Rossi, MD*,
Giorgio Golia, MD*,
Lorenzo Franceschini, MD*,
Giulio Cabrini, MD ,
Alberto Bonizzato, BSc,
Maristella Graziani, PhD ,
Stefan D. Anker, MD, PhD ||,
Andrew J. S. Coats, DM, FACC and
Piero Zardini, MD*
* Divisione di Cardiologia, Università degli Studi di Verona, Verona, Italy
Laboratorio di Patologia Molecolare, Centro Regionale Fibrosi Cistica, Ospedale Civile Maggiore, Verona, Italy
Laboratory of Clinical Chemistry, Ospedale Civile Maggiore, Verona, Italy
Department of Cardiac Medicine, National Heart & Lung Institute, London, United Kingdom
|| Franz Volhard Klinik (Charite, Campus Berlin-Buch) at Max Delbrück Centrum for Molecular Medicine, Berlin, Germany
Manuscript received October 13, 2000;
revised manuscript received January 24, 2001,
accepted February 12, 2001.
Reprint requests and correspondence: Dr. Luisa Zanolla, Divisione Clinicizzata di Cardiologia, Ospedale Civile Maggiore, P.le A. Stefani, 1 37126 Verona, Italy
znllsu{at}borgoroma.univr.it
OBJECTIVES
The objective of this study was to assess whether the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism influences the adequacy of the neurohormonal response to ACE inhibitors in patients with chronic heart failure (CHF).
BACKGROUND
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of CHF, and aldosterone levels closely relate to outcome in patients with CHF. Angiotensin-converting enzyme inhibitors suppress the RAAS, but a significant proportion of patients exhibit elevated serum levels of aldosterone despite long-term administration of apparently adequate doses of these agents.
METHODS
We prospectively studied 132 patients with CHF (ejection fraction <45%) receiving long-term therapy with ACE inhibitors for over six months. Patients taking aldosterone antagonists were excluded from the study. "Aldosterone escape" was defined as being present when plasma aldosterone levels were above the normal range in our laboratory (>42 nmol/L). Patients were then divided into two subgroups according to the presence (group 1) or absence (group 2) of aldosterone escape. Genotype analysis for the ACE I/D polymorphism was performed by polymerase chain reaction.
RESULTS
The prevalence of aldosterone escape in our patients was 10% (13/132). The two groups of patients did not differ regarding the dose of ACE inhibitor, diuretics and their renal function. There was a statistically significant different distribution of genotypes between the two groups, with a higher proportion of DD genotype in group 1 compared with group 2 (62% vs. 24%, p = 0.005).
CONCLUSIONS
Patients with CHF with aldosterone escape have a higher prevalence of DD genotype compared with patients with aldosterone within the normal limits. Angiotensin-converting enzyme gene polymorphism contributes to the modulation and adequacy of the neurohormonal response to long-term ACE-inhibitor administration in CHF.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | CHF | = chronic heart failure | | D | = deletion | | I | = insertion | | LVEF | = left ventricular ejection fraction | | PCR | = polymerase chain reaction | | RAAS | = renin-angiotensin-aldosterone system |
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