Abstract
BackgroundBiochemical 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.MethodsClinical 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.ResultsBoth 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).ConclusionsCTRP3 and CTRP9 are decreased in patients with HFrEF, proportionate to disease severity, and each is associated with increased morbidity and mortality.Trial registrationNCT01372800. Registered May 2011.
Highlights
Biochemical marker has revolutionized the approach to the diagnosis of heart failure
At total of 168 Heart failure with reduced ejection fraction (HFrEF) patients were recruited. 65% of the patients were treated with an ACE inhibitor, 36% were treated with an angiotensin II antagonist, 69% received a β-blocker, 80% were treated with digoxin and 80% were using a diuretic
We found the more advanced the HFrEF symptom status according to New York Heart Association (NYHA) class, the lower the C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) concentrations were (Fig. 1a and b)
Summary
Biochemical marker has revolutionized the approach to the diagnosis of heart failure. 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 discovery of novel risk markers for heart failure (HF) has contributed to improved screening, prevention, diagnosis and treatment of HF [1, 2]. In certain cases, such as for extremely high BNP or NT-proBNP levels, these biomarkers cannot reflect the severity of HF or morphologic changes of the heart. Fat tissue contributes to energy homeostasis and can secrete a number of adipokines that have cardioprotective properties [3]. Researches have shown adiponectin level was a predictor of mortality, independent of risk markers of CHF severity. The number of proteins in the CTRP family currently comprises 15 members in addition to adiponectin. In our previous in vivo studies, we found CTRP (C1q/TNF-Related Protein) 3 and CTRP9 were closely related to cardiovascular diseases [7,8,9]
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