The Clinical Relationship Between CTRP3 And CTRP9 And Heart Failure

Background Heart failure is a complex syndrome resulting in progressive cardiac remodeling, with significant morbidity and mortality. The discovery of new risk biomarkers for heart failure has contributed to improve screening, prevention, diagnosis and treatment of HF. Studies demonstrated that adipose tissue can secrete a series of adipokines, and part of adipokines have been found to be a marker of HF severity. Recently, an adipokine family of adiponectin paralogs were discovered, which members are widely expressed and highly conserved, designated as C1q/tumor necrosis factor-?-related proteins(CTRPs). This family plays an important role in metabolic regulation and obesity-related inflammation. Among them, CTRP3 and CTRP9 are found closely related in regulating cardiac functions. Researches confirmed that CTRP3 is an anti-apoptotic, pro-angiogenic cardioprotective adipokine, the expression of which is significantly inhibited after MI in mice. And clinic research showed that patients with acute coronary syndrome or stable angina pectoris have significantly lower circulating CTRP3 concentrations compared to normal subjects. Moreover, animal studies found myocardial ischemia-reperfusion injury resulting in lower circulating CTRP9 concentrations, and CTRP9 protein delivered at the time of reperfusionminimized the myocardial infarct size. Although the study confirmed CTRP3 and CTRP9 all have a protective effect on myocardial ischemia, but to date CTRP3 and CTRP9 have not been studied in patients with HF, so the possible role of them in relation to HF severity and mortality is unknown. Therefore, in the present study, we aim to elucidate the variation of CTRP3 and CTRP9 concentration in patients with heart failure, and the possible role of them in relation to HF severity and mortality.Aims 1. To determine the levels of CTRP3 and CTRP9 in patients with LVEF% reduced heart failure 2. To investigate whether CTRP3 and CTRP9 concentration are associated with increased morbidity and mortality in patients with LVEF% reduced heart failureMethods 1. To determine the levels of CTRP3 and CTRP9 in patients with LVEF% reduced heart failure 1.1 Establish the inclusion criteria and exclusion criteria of heart failure group and the control group. According to the inclusion criteria and exclusion criteria enroll participants for heart failure group and the control group. 1.2 Physical examination and collected medical history, plasma specimen in all participant. 1.3 Plasma CTRP3 and CTRP9 levels were evaluated by enzyme-linked immunosorbent assay(ELISA) 2 To investigate whether CTRP3 and CTRP9 concentration are associated with increased morbidity and mortality 2.1 Subjects were followed up by routine telephone calls for 3 years. The primary end-points were all-cause death or hospitalizations for heart failure 2.3 Analyze the resultsResults 1. CTRP3 and CTRP9 are decreased in patients with HF Between 2012-09 to 2012-12, 168 HFr EF patients and 176 healthy subjects were enrolled. Both CTRP3 and CTRP9 concentrations were significantly decreased in HF group compared to control group(p<0.001, respectively).Both CTRP3 and CTRP9 level were decreased with the increase of cardiac function classification. 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-pro BNP levels(CTRP3, r=-0.454, p<0.001; CTRP9, r=-0.483, p<0.001) in the HF group. In addition, CTRP3 and CTRP9 have a significant positive relationship in both control and HF groups(r=0.916, p<0.001; r=0.800,p<0.001). 2 Lower levels of CTRP3 or CTRP9 are associated with increased morbidity and mortality After a follow up for 36 months, we observed that CTRP3 or CTRP9 levels below the 25 th percentile was a predictor of total mortality and hospitalizations independent of clinical adjustment of HFr EF severity.Conclusion 1. CTRP3 and CTRP9 levels are decreased in patients with HFr EF in a manner proportionate to symptom severity(NYHA class). We also observed a significant relationship between CTRP3 and CTRP9 levels. 2. Decreased levels of CTRP3 and CTRP9 were each associated with increased mortality and hospitalization.