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European Heart Journal Advance Access originally published online on November 5, 2007
European Heart Journal 2007 28(23):2879-2885; doi:10.1093/eurheartj/ehm486
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Clinical and prognostic value of advanced glycation end-products in chronic heart failure

Jasper W.L. Hartog1,*, Adriaan A. Voors1, Casper G. Schalkwijk2, Jean Scheijen3, Tom D.J. Smilde1, Kevin Damman1, Stephan J.L. Bakker4, Andries J. Smit4 and Dirk J. van Veldhuisen1

1 Department of Cardiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, The Netherlands
2 Department of Medicine, Academic Hospital Maastricht, Debeyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands
3 Department of Clinical Genetics, Academic Hospital Maastricht, Debeyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands
4 Department of Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands

Received 11 April 2007; revised 27 August 2007; accepted 26 September 2007; online publish-ahead-of-print 5 November 2007.

* Corresponding author. Tel: +31 50 361 2355; fax: +31 50 361 4391. E-mail address: j.w.l.hartog{at}thorax.umcg.nl

Aims: Advanced glycation end-products (AGEs) have been proposed as a novel factor involved in the development and progression of chronic heart failure (CHF). We aimed to determine whether plasma levels of N{varepsilon}-(carboxymethyl)lysine (CML) and N{varepsilon}-(carboxyethyl)lysine (CEL), two well-known AGEs, are related to the severity and prognosis of CHF.

Methods and results: A total of 102 CHF patients, aged 58 ± 12 years, with an average left ventricular ejection fraction of 28 ± 9% were followed for 1.7 (1.2–1.9) years. NYHA functional class and NT-pro-BNP were used as estimates of the severity of CHF. CML and CEL were determined by LC–MS/MS. CML levels were associated with NYHA functional class (P < 0.001) and NT-pro-BNP levels (P < 0.001). Survival analysis for the combined end-point of death, heart transplantation, ischaemic cardiovascular event, and hospitalization for heart failure revealed that CML levels predicted outcome, even after adjustment for age, gender, aetiology of CHF, identified risk modifiers, and several known predictors of outcome in CHF. The predictive value of CML subsided after correction for renal function. CEL was not associated with the severity or prognosis of CHF.

Conclusion: Plasma AGEs, in particular CML levels, are related to the severity and prognosis of CHF. The fact that the relation between CML and prognosis subsided after correction for renal function may suggest that AGE accumulation in renal failure explains part of the prognostic value of renal function in CHF. However, further investigation is warranted to exclude the possibility that CML is just an innocent marker of renal function.

Key Words: Chronic heart failure • Advanced glycation end-products • Prognosis • Carboxymethyllysine • Carboxyethyllysine


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