Clinical and prognostic value of advanced glycation end-products in chronic heart failure.
OBJECTIVE
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(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL), two well-known AGEs, are related to the severity and prognosis of CHF.


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.


CONCLUSIONS
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.
Hartog
Jasper W L
JW
Department of Cardiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, The Netherlands. j.w.l.hartog@thorax.umcg.nl
Voors
Adriaan A
AA
Schalkwijk
Casper G
CG
Scheijen
Jean
J
Smilde
Tom D J
TD
Damman
Kevin
K
Bakker
Stephan J L
SJ
Smit
Andries J
AJ
van Veldhuisen
Dirk J
DJ
D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis
D015415:Biomarkers; D017127:Glycation End Products, Advanced; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; D008239:Lysine