C1q/TNF-related protein 3 (CTRP3) and 9 (CTRP9) concentrations are decreased in patients with heart failure and are associated with increased morbidity and mortality

Chao Gao, Shasha Zhao, Kun Lian, Baibing Mi, Rui Si, Zhijun Tan, Feng Fu, Shuai Wang, Rutao Wang, Xinliang Ma, Ling Tao, Chao Gao, Shasha Zhao, Kun Lian, Baibing Mi, Rui Si, Zhijun Tan, Feng Fu, Shuai Wang, Rutao Wang, Xinliang Ma, Ling Tao

Abstract

Background: Biochemical marker has revolutionized the approach to the diagnosis of heart failure. However, it remains difficult to assess stability of the patient. As such, novel means of stratifying disease severity are needed. C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) are novel adipokines that contribute to energy homeostasis with additional anti-inflammatory and anti-ischemic properties. The aim of our study is to evaluate concentrations of CTRP3 and CTRP9 in patients with HFrEF (heart failure with reduced ejection fraction) and whether associated with mortality.

Methods: Clinical data and plasma were obtained from 176 healthy controls and 168 patients with HFrEF. CTRP3 and CTRP9 levels were evaluated by enzyme-linked immunosorbent assay.

Results: Both CTRP3 and CTRP9 concentrations were significantly decreased in the HFrEF group compared to the control group (p < 0.001). Moreover, patients with higher New York Heart Association class had significantly lower CTRP3 or CTRP9 concentrations. Correlation analysis revealed that CTRP3 and CTRP9 levels were positively related with LVEF% (CTRP3, r = 0.556, p < 0.001; CTRP9, r = 0.526, p < 0.001) and negatively related with NT-proBNP levels (CTRP3, r = - 0.454, p < 0.001; CTRP9, r = - 0.483, p < 0.001). After a follow up for 36 months, after adjusted for age, LVEF and NT-proBNP, we observed that CTRP3 or CTRP9 levels below the 25th percentile was a predictor of total mortality (CTRP3,HR:1.93,95%CI1.03~3.62,P = 0.042;CTRP9,HR:1.98,95%CI:1.02~3.85,P = 0.044) and hospitalizations (CTRP3,HR:2.34,95% CI:1.43~3.82,P = 0.001;CTRP9,HR:2.67,95%CI:1.58~4.50,P < 0.001).

Conclusions: CTRP3 and CTRP9 are decreased in patients with HFrEF, proportionate to disease severity, and each is associated with increased morbidity and mortality.

Trial registration: NCT01372800 . Registered May 2011.

Keywords: Biomarker; C1q/TNF-related Protein3 (CTRP3); C1q/TNF-related Protein9 (CTRP9); Heart failure with reduced ejection fraction.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Concentration of CTRP3 (a) and CTRP9 (b) according to the severity of HFrEF stratified by NYHA functional class. Scatterplots of the association between CTRP3/CTRP9 and LVEF% (c and d) and with log transformed values of NT-proBNP (e and f) in HFrEF patients. *p < 0.05, **p < 0.01 vs. Control group
Fig. 2
Fig. 2
Distribution of CTRP3 and CTRP9 according to sex (a and b). Correlation between CTRP3 and CTRP9 in control group (c) and HFrEF group (d)
Fig. 3
Fig. 3
Kaplan-Meier survival curves according to the above or below 25th centile of CTRP3 or CTRP9 concentrations. a Event free survival rate of CTRP3. b Free of HFrEF hospitalization rates of CTRP3. c Event free survival rate of CTRP9. d Free of HFrEF hospitalization rates of CTRP9

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