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European Journal of Heart Failure Advance Access originally published online on January 24, 2009
European Journal of Heart Failure 2009 11(3):281-291; doi:10.1093/eurjhf/hfn046
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Predictors of fatal and non-fatal outcomes in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): incremental value of apolipoprotein A-1, high-sensitivity C-reactive peptide and N-terminal pro B-type natriuretic peptide

Hans Wedel1,*, John J.V. McMurray2, Magnus Lindberg3, John Wikstrand4, John G.F. Cleland5, Jan H. Cornel6, Peter Dunselman7, Åke Hjalmarson4, John Kjekshus8, Michel Komajda9, Timo Kuusi10, Johan Vanhaecke11, Finn Waagstein4,{dagger} on behalf of the CORONA Study Group

1 Nordic School of Public Health, Göteborg, Sweden
2 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK
3 AstraZeneca, Mölndal, Sweden
4 Sahlgrenska University, Hospital, Göteborg, Sweden
5 Department of Cardiology, University of Hull, Kingston upon Hull, Yorkshire, UK
6 Department of Cardiology, Medisch Centrum Alkmaar and member of the WCN, The Netherlands
7 Amphia Hospital, Breda, The Netherlands
8 Department of Cardiology, Rikshospitalet University Hospital, Oslo, Norway
9 Department of Cardiology, Pitie Salpetriere Hospital, University Pierre et Marie Curie, Paris, France
10 Division of Cardiology, Department of Medicine, Helsinki University Hospital, Helsinki, Finland
11 Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium

* Corresponding author. Tel: +46 708 297288, Fax: +46 31 691777, Email: hans.wedel{at}biostat.se


  Abstract

Aims: Few prognostic models in heart failure have been developed in typically elderly patients treated with modern pharmacological therapy and even fewer included simple biochemical tests (such as creatinine), new biomarkers (such as natriuretic peptides), or, especially, both. In addition, most models have been developed for the single outcome of all-cause mortality.

Methods and results: We built a series of models for nine different fatal and non-fatal outcomes. For each outcome, a model was first built using demographic and clinical variables (Step 1), then with the addition of biochemical measures (serum creatinine, alanine aminotransferase, creatine kinase, thyrotrophin, apolipoproteins A-1 and B, and triglycerides) (Step 2) and finally with the incorporation of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Ranked according to the Wald {chi}2 value, age (56), ejection fraction (44), and body mass index (42) were most predictive of all-cause mortality in Step 1 (total model {chi}2 343). Creatinine was the most powerful predictor at Step 2 (48) and ApoA-1 ranked fifth (25), with the overall {chi}2 increasing to 440. Log NT-proBNP (167) was the most powerful of the 14 independently predictive variables identified at Step 3 and the overall {chi}2 increased to 600. NT-proBNP was the most powerful predictor of each other outcome. hsCRP was not a predictor of all-cause mortality but did predict the composite atherothrombotic outcome.

Conclusion: Of the two new biomarkers studied in prognostic models in heart failure, NT-proBNP, but not hsCRP, added substantial and independent predictive information, for a range of clinical outcomes, to that provided by simple demographic, clinical, and biochemical measures. ApoA-1 was more predictive than LDL or HDL.

Key Words: Chronic heart failure

Received August 19, 2008; Revised November 14, 2008; Accepted November 21, 2008

{dagger} Members of the CORONA Study Group are listed in the Appendix section.


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