© 2005 European Society of Cardiology
The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure
a Service de Cardiologie C, Hôpital Cardiologique, Centre Hospitalier Régional et Universitaire de Lille Boul Prof J Leclercq, 59037 Lille cedex, France
b INSERM U508, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille cedex, France
c Thoraxcenter, Erasmus Medical Centre Rotterdam, The Netherlands
* Corresponding author. Tel.: +33 3 20 44 50 45; fax: +33 3 20 44 48 81. E-mail address: pdegroote{at}chru-lille.fr
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Abstract |
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Objective: Discordant results have been published regarding a possible association between beta-adrenoreceptor (βAR) gene polymorphisms and survival in patients with congestive heart failure (CHF). The aim of the study was to analyze the impact of five functional βAR gene polymorphisms in patients with stable CHF.
Methods: We prospectively studied 444 consecutive patients with CHF related to left ventricular systolic dysfunction. The β1ARSer49Gly, β1ARGly389Arg, β2AR Arg16Gly, β2AR Gln27Glu and β2AR Thr164Ile polymorphisms were determined. Patients underwent echocardiography, radionuclide angiography and a cardiopulmonary exercise test.
Results: Mean age was 56.6±11.9 years old, left ventricular ejection fraction (LVEF) was 32±12%, and peak VO2 was 15.5±4.9 ml/min/kg or 63±18% of maximal predicted VO2. Most of the patients (95%) were receiving angiotensin converting enzyme inhibitors and 91% β-blockers. There was no statistically significant differences between baseline characteristics among β1AR and β2AR genotypes. During a median follow-up period of 1232 days, there were 110 cardiac-related deaths and five urgent transplantations. Independent predictors of survival were percent (%) of maximal predicted VO2 (p<0.0001), age (p<0.0001), LVEF (p=0.004), creatinine (p=0.02) and atrial fibrillation (p=0.04). No βAR polymorphisms were associated with survival. However, patients with the combined β2ARGly16Gly/β2ARGln27Gln genotype, who express receptors highly sensitive to down-regulation, had a significantly lower survival rate than patients with other genotypes but only in univariate analysis.
Conclusions: In this prospective study, we found no association between five functional βAR polymorphisms and survival in patients with stable CHF. However, we demonstrated, only in univariate analysis, a possible association between the combined β2ARGly16Gly/β2ARGln27Gln genotype and survival.
Key Words: Heart failure • Prognosis • Genetics • Receptors adrenergic beta
Received April 7, 2004; Revised July 8, 2004; Accepted October 14, 2004
No author has any conflict of interest.
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