Predictive value of Serum CCL21 and CCL19 levels in heart failure patients: A prospective study

BackgroundChemokine C-C motif ligand (CCL)21 and CCL19 are well-recognized to associate with adverse events of cardiovascular disease, especially long-term prognosis. However, few studies have reported its correlation with heart failure. PurposeTo investigate and compare the predictive value of CCL21 and CCL19 serum levels in patients with heart failure. MethodsIn this prospective, observational, single-center study, 221 patients with heart failure and 55 healthy controls were included. ROC curves were generated to analyze and compare the serum levels of CCL21 and CCL19 in predicting all-cause mortality and composite events. Cox regression and Kaplan-Meier survival analyses were performed to identify independent risk factors for prognosis. Pearson correlation was used to measure the correlation between creatinine and CCL21 / CCL19 levels. ResultsThe study observed 108 events (30 deaths and 78 occurred composite endpoints) over a median follow-up of 494.5(231.5,950.0) days. CCL21 showed strong predictive value for both all-cause mortality (AUC were 0.694, P=0.001) and composite endpoints (AUC 0.661, P=0.006 and <0.001). while the combination of CCL21 and NT-proBNP further improved the predictive power, with AUC being 0.796 and 0.662 on all-cause mortality and composite endpoints, respectively (both P<0.001). K-M survival analysis revealed that patients with increased CCL21 and CCL19 exhibited higher all-cause mortality (both P<0.05). Meanwhile, higher incidence of composite endpoint events was also observed in patients with elevated CCL21 (P<0.05). Importantly, multivariate COX regression analysis demonstrated that smoking, higher level of CCL21 and ischemic heart disease were independent risk factors for all-cause mortality (P<0.001). Furthermore, diabetes and elevation of CCL21 were associated with an increased risk of composite endpoints (P<0.001). On the other hand, changes in CCL19 levels showed a graded association with worse renal function, resulting in a slight increasing trend in G3 and G4/5, (HR = 2.64, 95% CI= 2.26-2.66, vs. HR 2.67, 95% CI 2.57-2.91, overall interaction P<0.05), with higher concentrations in G3 and G4/5(HR = 3.67, 95% CI= 3.27-3.85, vs. HR 4.11, 95% CI 3.67-4.38; overall interaction P<0.05). ConclusionsSerum concentrations of CCL21 and CCL19 were significantly elevated in heart failure patients. High level of CCL21 is an independent risk factor for the adverse events in heart failure and may complement the prediction of those events which are less affected by renal function.