Elsevier

Journal of Cardiac Failure

Volume 16, Issue 11, November 2010, Pages 873-879
Journal of Cardiac Failure

Clinical Investigation
Serum YKL-40 Predicts Adverse Clinical Outcomes in Patients With Chronic Heart Failure

https://doi.org/10.1016/j.cardfail.2010.05.029Get rights and content

Abstract

Background

Human cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression.

Methods and Results

We examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048).

Conclusions

Serum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF.

Section snippets

Study Subjects

We examined 121 consecutive patients who admitted to the Yamagata University Hospital for evaluation or treatment of CHF between 2004 and 2007. The clinical diagnosis of heart failure was based on the medical history, physical examination, documentation of left ventricular enlargement or dysfunction by chest x-ray, echocardiography, or left ventriculography. Exclusion criteria were acute coronary syndrome within 3 months preceding admission, inflammatory diseases, renal failure (defined as a

Serum YKL-40 Levels in Patients with CHF

Baseline characteristics of all study subjects are listed in Table 1. Serum YKL-40 levels were significantly higher in patients with CHF than in control subjects (P = .0216). Moreover, as shown in Fig. 1, the concentration of serum YKL-40 level increased with advancing NYHA functional class and was significantly higher in severe CHF patients with NYHA Class III/IV than in control subjects (P < .0001) and mild CHF patients with NYHA Class I/II (P < .0001).

In CHF patients, serum YKL-40 levels

Discussion

In this study, we demonstrated that serum YKL-40 levels were elevated in severe CHF patients with NYHA functional Class III/IV. The patients with adverse events had significantly higher serum YKL-40 levels than event-free ones, and higher levels of YKL-40 were associated with a higher incidence of cardiac events. Moreover, YKL-40 was an independent prognostic factor for cardiac events by the multivariate Cox proportional hazard analysis.

CHF is considered as a condition characterized not only by

Conclusions

Concentration of serum YKL-40 levels was increased in patients with heart failure and was related to the severity of disease. The present study for the first time reported the prognostic role of YKL-40 as an independent risk factor to predict adverse clinical outcomes in patients with CHF.

Disclosures

None.

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    This study was supported in part by Grant-in-aid for Scientific Research (No. 21590935) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Grants from the Takeda Science Foundation, the Uehara Memorial Foundation, and Fukuda Foundation for Medical Technology.

    See page 878 for disclosure information.

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