Clinical Investigation
High Serum Level of Pentosidine, an Advanced Glycation End Product (AGE), is a Risk Factor of Patients with Heart Failure

https://doi.org/10.1016/j.cardfail.2006.11.009Get rights and content

Abstract

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.

Methods and 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.

Section snippets

Study Subjects

We measured serum concentration of pentosidine in 141 patients (88 male and 53 female, mean age 66 ± 13 years) who admitted to the Yamagata University Hospital for diagnosis or treatment of heart failure and 18 age-matched control subjects (8 male and 10 female, mean age 64 ± 13 years). The diagnosis of heart failure was based on a history of dyspnea and symptomatic exercise intolerance with signs of pulmonary congestion or peripheral edema or documentation of left ventricular enlargement or

Results

Baseline clinical characteristics of patients with heart failure and control subjects are shown in Table 1. B-type natriuretic peptide (BNP), uric acid, LVEDD, LVESD, IVS, PW, EDV, ESV, and LV mass were significantly higher in patients with heart failure than in control subjects. EF was significantly lower in patients with heart failure than in control subjects. As shown in Fig. 1, pentosidine concentration was significantly increased in patients with NYHA Class III/IV than in control subjects

Discussion

In the present study, we showed that serum pentosidine level was higher in patients with severe heart failure with NYHA functional Class III/IV than in those with mild heart failure with NYHA Class I/II. Pentosidine level was also higher in patients with cardiac events than in those without events. Multivariate Cox proportional hazard analysis demonstrated that pentosidine was the most powerful factor to predict adverse clinical outcomes in patients with heart failure. The highest quartile of

Conclusions

Serum pentosidine concentration is related to the severity of heart failure and is an independently risk factor to predict adverse clinical outcomes in patients with heart failure. Pentosidine may be a novel marker for risk stratification of patients with heart failure.

References (35)

Cited by (116)

  • Enhanced carbonyl stress and disrupted white matter integrity in schizophrenia

    2020, Schizophrenia Research
    Citation Excerpt :

    Carbonyl stress is a state caused by increased rich reactive carbonyl compounds (RCOs) (Miyata et al., 1999), which facilitate the formation of advanced glycation end products (AGEs), including pentosidine. AGEs have been associated with various age-related illnesses, such as cardiovascular events (Nin et al., 2011), heart failure (Koyama et al., 2007), and Alzheimer's-type dementia (Srikanth et al., 2011). Recent accumulating evidence has suggested that AGEs are associated with schizophrenia (Arai et al., 2010).

View all citing articles on Scopus

This study was supported in part by a grant-in-aid for Scientific Research (No. 17590702) from the Ministry of Education, Science, Sports and Culture, Japan, a grant-in-aid from the 21st Century Center of Excellence (COE) program of the Japan Society for the Promotion of Science, and grants from Takeda Science Foundation and Fukuda Foundation for Medical Technology.

View full text