European Heart Journal Advance Access originally published online on September 26, 2008
European Heart Journal 2008 29(21):2641-2650; doi:10.1093/eurheartj/ehn420
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Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme
1 Medical Statistics Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
2 University of Glasgow, Glasgow, UK
3 Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada
4 Duke University Medical Center, Durham, NC, USA
5 Astra Zeneca LP, Wilmington, Del, USA
6 Karolinska Hospital, Stockholm, Sweden
7 Department of Medicine, Brigham and Women’s Hospital, Boston, USA
8 Department of Cardiology, Charité, Berlin, Germany
9 Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Göteborg, Sweden
Received 4 July 2008; revised 30 July 2008; accepted 28 August 2008; online publish-ahead-of-print 26 September 2008.
* Corresponding author. Tel: +44 207 927 2413, Fax: +44 207 637 2853, Email: stuart.pocock{at}lshtm.ac.uk
Aims: The curiosity that leanness is associated with poor survival in patients with chronic heart failure (CHF) needs further insight by investigating the impact of weight loss on prognosis in a large sample of patients across a broad spectrum of both reduced and preserved left ventricular (LV) systolic function.
Methods and results: We investigated the change in weight over 6 months in 6933 patients in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) programme, and its association with subsequent mortality (1435 deaths) over a median 32.9 months follow-up using Cox proportional hazard models to account for the impact of body mass index and other risk predictors. We then used time-updated Cox models to relate each patient’s ongoing data on annual weight change to their mortality hazard. The percentage weight loss over 6 months had a highly significant monotonically increasing association with excess mortality, both for cardiovascular and for other causes of death. Patients with 5% or greater weight loss in 6 months had over a 50% increase in hazard compared with those with stable weight. Weight loss carried a particularly high risk in patients who were already lean at study entry. Findings were similar in the presence of dependent oedema, preserved or reduced LV ejection fraction, and treatment with candesartan, although weight loss was significantly less common on candesartan. The time-updated analyses revealed an even stronger link between weight loss and short-term risk of dying, i.e. risk increased more than four-fold for patients whose last recorded annual weight loss exceeded 10%. Weight gain had a more modestly increased short-term mortality risk. Weight loss accelerates in the year prior to death.
Conclusions: Weight loss and leanness are important predictors of poor prognosis in CHF. Being lean and losing weight is particularly bad. The detection of weight change, and particularly weight loss, should be considered as an adverse sign prompting further evaluation.
Key Words: Chronic heart failure • Clinical trial database • Weight loss • Mortality
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