Elsevier

The Lancet

Volume 361, Issue 9363, 29 March 2003, Pages 1077-1083
The Lancet

Articles
Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study

https://doi.org/10.1016/S0140-6736(03)12892-9Get rights and content

Summary

Background

Weight loss in chronic heart failure is linked to impaired survival. We aimed to assess the frequency of weight loss in patients with this disease, whether the degree of weight loss predicts mortality, and whether weight loss can be prevented by angiotensin-converting-enzyme (ACE) inhibitors.

Methods

We investigated weight changes in 1929 patients from the SOLVD trial who had chronic heart failure, were free of oedema at baseline, and survived for at least 4 months after trial entry. Mean follow-up was 35 months (SD 13). We analysed the effect of weight loss at cutpoints of 5%, 7·5%, 10%, 15% (a priori), and 6% (post hoc) to identify which one best predicted outcome. To validate results, we analysed data for 619 patients in the V-HeFT II trial.

Findings

817 (42%) patients in the SOLVD trial had weight loss from baseline of 5% or more. At 8 months follow-up, all cutpoints for weight loss were significantly associated with impaired survival after adjustment for age, sex, New York Heart Association class, left ventricular ejection fraction, and treatment allocation. Weight loss of 6% or more at any time during follow-up was the strongest predictor of impaired survival (adjusted hazard ratio 2·10, 95% CI 1·77–2·49; p<0·0001). Patients on the ACE inhibitor enalapril had a lower hazard of 6% or more weight loss than did those not taking the drug (adjusted reduction 19%, p=0·0054). Results from analyses of V-HeFT II data lent support to our findings.

Interpretation

Weight loss occurs frequently in patients with chronic heart disease, its reversal is rare, and when present, it is independently linked to impaired survival. Weight loss of more than 6% should be used to define the presence of cachexia in patients with chronic heart failure. In chronic heart failure, treatment with an ACE inhibitor reduces the risk of weight loss.

Introduction

Cachexia is a serious complication of several chronic diseases, including heart failure, malignant cancer, acquired immunodeficiency syndrome, thyrotoxicosis, and rheumatoid arthritis, and is suggestive of a poor outlook for patients. In a previous single-centre prospective study of 171 patients, we reported that weight loss in chronic heart failure is linked to impaired survival independent of other well recognised risk factors.1 The definition of cardiac cachexia that we used in that study (ie, >7·5% loss of bodyweight from baseline) was arbitrary, and the study was done in a sole tertiary referral centre with patients who were potentially highly selected; thus our results left several questions unanswered.

Angiotensin-converting-enzyme (ACE) inhibitors are a well studied and widely available treatment that ammeliorates symptoms, reduces morbidity, and improves survival in patients with chronic heart failure. The benefits of ACE inhibitors cannot be explained solely by a haemodynamic mode of action; other effects of ACE inhibitors include modification of the neurohormonal axis and of endothelial function.2 ACE inhibitors are most successful in preventing deaths in patients who have raised catecholamines,3, 4 which are closely related to the presence of cardiac cachexia.5

We reanalysed data from patients who participated in the SOLVD trial6 to assess the frequency of substantial weight loss in patients with chronic heart failure, to ascertain whether the degree of weight loss predicts mortality, and whether ACE inhibitors can reverse or prevent weight loss. We did similar analyses with data from the V-HeFT II database.7

Section snippets

SOLVD

The SOLVD treatment study6 was a randomised, double-blind, placebo-controlled trial investigating the effects of enalapril treatment in 2569 clinically stable patients who had a left ventricular ejection fraction (LVEF) of 35% or less and evidence of overt congestive heart failure. To avoid the confounding effect of weight loss caused by reduction of oedema, we included patients from this study who (in the opinion of the local investigator and as documented in the case report form) had been

SOLVD

We included 1929 patients from SOLVD—75% of the original trial population. Apart from oedema status, baseline clinical characteristics of these patients did not differ from those of the total study population (table 1). 993 of the included patients were randomly allocated enalapril (2·5 to 20 mg daily) and 936 patients received placebo. Mean follow-up was 35 months (SD 13), during which time 757 (39%) participants died.

During follow-up, 817 patients (42%) had weight loss of 5% or more, 549

Discussion

Our results show that substantial weight loss is a common event in patients with chronic heart failure. Spontaneous reversal of substantial weight loss was a rare event, and was noted for fewer than 2% of cases. Weight loss was independently linked to impaired survival of patients with chronic heart failure. Treatment with an ACE inhibitor, enalapril, in addition to conventional treatment reduced the risk of weight loss of 6% or more by 19%.

The development of weight loss is not a sudden event,

References (32)

  • J Niebauer et al.

    Endotoxin and immune activation in chronic heart failure: a prospective cohort study

    Lancet

    (1999)
  • B Pitt et al.

    Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II.

    Lancet.

    (2000)
  • TB Horwich et al.

    The relationship between obesity and mortality in patients with heart failure

    J Am Coll Cardiol

    (2001)
  • CH Davos et al.

    Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity

    J Card Fail

    (2003)
  • B Hornig et al.

    Effect of ACE inhibition on endothelial dysfunction in patients with chronic heart failure

    Eur Heart J

    (1998)
  • K Swedberg et al.

    Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group

    Circulation

    (1990)
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