Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program
1 Division of Cardiology, University of Colorado Denver, Aurora, CO, USA
2 Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
3 London School of Hygiene and Tropical Medicine, London, UK
4 University of Glasgow, Glasgow, UK
5 Brigham and Women's Hospital, Boston, MA, USA
6 Department of Medicine, Sahlgrenska University Hospital/Östra, Göteburg, Sweden
7 McMaster University, Hamilton, Ontario, Canada
8 AstraZeneca LP, Wilmington, DE, USA
* Corresponding author. Tel: +1 919 668 8919, Fax: +1 919 668 7063, Email: michael.felker{at}duke.edu
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Abstract |
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Aims: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated.
Methods and results: We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P < 0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P < 0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square).
Conclusion: Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.
Key Words: Heart failure • Bilirubin • Liver function tests • Hepatic congestion • Prognosis • Death • Laboratory tests
Received March 27, 2008; Revised September 26, 2008; Accepted November 17, 2008