In this study, we investigated the associations between circulating levels of NT pro-BNP, hs-CRP and big-ET and all-cause mortality in patients with DCM. Our major new finding suggests that at admission, plasma NT pro-BNP and hs-CRP, but not big-ET, were strong predictors of all-cause mortality in DCM patients, and this association was independent of traditional risk factors for adverse outcomes in HF and DCM such as age, LV diameter, NYHA functional class, and the LVEF.
Concentrations of NT pro-BNP are related to LV filling pressures and wall stress . B-type natriuretic peptide levels have been shown to be elevated in patients with symptomatic LV dysfunction and correlate to LV filling pressure, NYHA classification and prognosis [27–29]. NT pro-BNP levels increase during left ventricular dysfunction and acute myocardial infarction, and serve to counteract mechanisms of heart failure through diuresis, natriuresis and antihypertensive effects [4–8]. Various timing of the natriuretic peptide measurements among hospitalized HF patients indicated that NT pro-BNP levels were associated with outcomes including mortality and morbidity [30–33]. There is also evidence that a BNP- or NT proBNP-guided strategy could improve morbidity related to chronic HF; a BNP-guided therapeutic strategy was superior to a clinically guided approach in NYHA functional class II to III patients who were considered optimally treated by chronic HF specialists [34, 35]. There were limited data on the prognostic value of BNP or NT pro-BNP in DCM patients; the BNP or NT pro-BNP levels increased and were associated with cardiac events or mortality [36, 37]. In the present study, NT pro-BNP was increased in patients in NYHA classes III and IV with depressed LVEF and larger dilated RV and LA diameters, and NT pro-BNP was one of the independent predictors of all-cause mortality in DCM patients.
Many studies have suggested that the role of CRP in cardiac disease is as an acute phase-reactant protein. CRP is mainly produced in the liver in response to interleukin-6 and plays many pathophysiological roles in the inflammatory process. Elevated levels of CRP have been observed in patients with HF [13–15], and activation of the immune response may play a role in heart failure through modifications in the renin-angiotensin-aldosterone and sympathetic systems [38, 39]. There is evidence that chronic activation of the immune system such as monocyte-macrophage and lymphocyte activation exists in HF [38, 39]. CRP may not only be a marker of chronic systemic inflammation but also may be directly involved in CHF. CRP can cause myocardial cell apoptosis, and thus ventricular damage or dysfunction . In the present study, hs-CRP was increased in patients in NYHA classes III and IV with depressed LVEF, more dilated right ventricular and left atrial diameters. Patients with an hs-CRP >3.90 pmol/L also had higher all-cause mortality, and hs-CRP was one of the independent predictors of all-cause mortality in DCM patients.
As for big-ET, although many studies showed that big-ET levels were elevated and were prognostic markers of survival in patients with chronic heart failure [21–24], in the present study, big-ET was not one of the independent predictors of all-cause mortality in DCM patients.
The present study has several limitations; as with many studies of chronic disease, there may be variation in the length of the preclinical phase that influences the relationships between the three biomarkers of NT pro-BNP, hs-CRP, big-ET and death. The cohort in the present study included only patients with DCM who required hospitalization, and thus, the data described herein cannot be extrapolated to the entire DCM population. In addition, the medicines on admission should add some influence to the Cox multivariate analysis as without long-term medicine data. Finally, we measured the three biomarkers just at admission without the discharge values or more in the present study.