Prognostic Performance Of Multiple Biomarkers In Patients With Chronic Heart Failure And Depression

Part Ⅰ The influence of depressive symptoms on plasma levels of soluble ST2, NT-pro BNP and ghrelin in patients with systolic heart failureObjective:To identify the influence of depressive symptoms on plasma levels of soluble ST2(sST2) and neurohormones [N-terminal pro-brain natriuretic peptide (NT-pro BNP) and ghrelin] in patients with systolic heart failure (HF).Methods:A cohort of146HF patients with left ventricular ejection fraction≤40%was followed up for1year. The primary endpoint was all-cause mortality and HF-related hospitalization. Psychological status was evaluated by Hospital Anxiety and Depression Scale and Hamilton Depression Scale. Plasma levels of sST2, NT-pro BNP and ghrelin were measured at baseline.Results:HF patients with depressive symptoms (n=52,35.6%) had higher levels of sST2(55.3ng/ml vs.41.1ng/ml, p<0.001) and NT-pro BNP (5886pg/ml vs.2682pg/ml, p<0.001), but lower levels of ghrelin (7.0ng/ml vs.7.9ng/ml,p=0.041), compared with those without depressive symptoms. Levels of sST2and NT-pro BNP were independently associated with depressive symptoms. After1-year follow-up,33patients (22.6%) died and53(36.3%) patients achieved the primary endpoint. The hazard ratio (HR) of all-cause death and HF-related hospitalization was2.2[95%confidence interval (CI)1.34-3.52,p=0.002] in patients with depressive symptoms when adjusted for clinical covariates. Depressive symptoms combined with upper risk threshold levels of sST2(>36.0ng/ml, HR3.65,95%CI1.66-8.02, p=0.001) or NT-pro BNP (>1000pg/ml, HR2.99,95%CI1.24-7.21, p=0.014) were independently associated with increased risks of death and HF-related hospitalization.Conclusions:Depressive symptoms were independent risk factors of HF and provided additional prognostic information to that of sST2and NT-pro BNP. Objective:To assess the predictive effect of soluble ST2(sST2) and depressive symptoms in patients with heart failure (HF) and to determine whether prognosis of HF patients with preserved ejection fraction (HFpEF) differs from those with reduced ejection fraction (HFrEF).Methods:A cohort of258HF patients was followed up for1year. Depressive symptoms were evaluated by Hamilton depression rating scale (HAMD) and Hospital Anxiety and Depression Scale (HADS-D). The primary endpoint was all-cause mortality and HF-related hospitalization. For the analysis of survival, the left ventricular ejection fraction (LVEF) cut-offs for defining HFpEF were set at50%,45%and40%respectively.Results:With increasing LVEF, levels of sST2were gradually decreased (45.2ng/ml,35.8ng/ml and32.1ng/ml in patients with LVEF≤40%,41%to49%and≥50%, respectively,p for trend<0.001), as well as the prevalence of depressive symptoms (34.6%,33.3%and20.4%, respectively,p for trend=0.024). After1-year follow-up,148patients (57.4%) achieved the primary endpoint and57patients (22.1%) died. Depressive symptoms were independent risk factors of all-cause mortality and HF-related hospitalization. The combined presence of elevated sST2(>36.0ng/ml) and depressive symptoms was associated with a3.3-fold increased risk of the primary endpoint. Regardless of LVEF cut-offs, the associated risk of adverse outcomes in HFpEF was as high as in HFrEF after adjustment for significant risk factors including sST2and N-terminal pro-brain natriuretic peptide.Conclusions:Depressive symptoms provided additional prognostic information to that of sST2in HF patients. The prognosis of HFpEF patients was similar to that of HFrEF patients. Background:Depression is prevalent in patients with heart failure (HF) and associated with high mortality and morbidity rates, the mechanisms are not yet well understood. Dysregulation of microRNAs has been shown to play a crucial role in HF and neurological disorders. This study aimed to explore concentrations of microRNA-16and mircroRNA-18a in HF patients with or without depressive symptoms, and to assess the prognostic value of microRNA-16and microRNA-18a in these subjects.Methods:Plasma concentrations of microRNA-16, microRNA-18a, NT-pro BNP and soluble ST2(sST2) were determined in100HF patients and30healthy controls. Depressive symptoms were evaluated by Hamilton depression Scale (HAMD) and Hospital Anxiety and Depression Scale (HADS-D). All patients were followed for1year. The primary endpoint comprised cardiovascular death and HF-related hospitalization.Results:Levels of microRNA-16and microRNA-18a were both higher in HF patients than controls (both p<0.001), those with depressive symptoms (n=37) had even higher microRNA-16(p=0.010). MicroRNA-16levels were positively associated with NT-pro BNP (r=0.37, p<0.001) and sST2levels (r=0.24, p=0.006). After1-year follow-up,14patients died and56patients achieved the primary endpoint. Univariate Cox regression analysis showed that increased microRNA-16was associated with an increased risk of cardiovascular death and HF-related hospitalization in HF patients (HR1.10,95%CI1.06-1.20, p=0.001), however, statistical significance was lost on multivariate analysis. Conclusions:Concentrations of circulating microRNA-16were increased in patients with HF, especially in those with depressive symptoms. Elevation of microRNA-16was associated with an increased risk of1-year cardiovascular death and HF-related hospitalization but did not add independent prognostic information to traditional risk factors in HF patients.