High serum level of pentosidine, an advanced glycation end product (AGE), is a risk factor of patients with heart failure.
BACKGROUND
Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling, causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure.


RESULTS
Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with end points of cardiac death or rehospitalization. Serum concentration of pentosidine was significantly higher in New York Heart Association (NYHA) Class III/IV patients than in NYHA class I/II patients (P < .0001). Serum pentosidine was also higher in patients with cardiac events than in event-free patients (P < .001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume, and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold).


CONCLUSIONS
Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure. Patients were divided into 4 groups based on the serum pentosidine levels.
Koyama
Yo
Y
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
Takeishi
Yasuchika
Y
Arimoto
Takanori
T
Niizeki
Takeshi
T
Shishido
Tetsuro
T
Takahashi
Hiroki
H
Nozaki
Naoki
N
Hirono
Osamu
O
Tsunoda
Yuichi
Y
Nitobe
Joji
J
Watanabe
Tetsu
T
Kubota
Isao
I
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015897:Comorbidity; D048909:Diabetes Complications / Q000453:epidemiology; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000453:epidemiology; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis
D015415:Biomarkers; D002316:Cardiotonic Agents; D004232:Diuretics; D004077:Digoxin; D001120:Arginine; C062187:pentosidine; D008239:Lysine