Abstract
Inflammation and immune activation play an important role in the pathogenesis of cardiac remodelling in patients with heart failure. The aim of this study was to assess whether biomarkers of inflammation and immune activation are linked to disease severity and the prognosis of heart failure patients. In 149 patients (65.8% men, median age 49.7 years) with heart failure from nonischaemic cardiomyopathy, the biomarkers neopterin and C-reactive protein were tested at the time of diagnosis. Patients were followed-up for a median of 58 months. During follow-up, nineteen patients died, five had a heart transplantation, two needed a ventricular assistance device, and twenty-one patients had to be hospitalised because of heart failure decompensation. Neopterin concentrations correlated with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations (rs = 0.399, p < 0.001) and rose with higher New York Heart Association (NYHA) class (I: 5.60 nmol/L, II: 6.90 nmol/L, III/IV: 7.80 nmol/L, p = 0.033). Higher neopterin levels were predictive for an adverse outcome (death or hospitalisation due to HF decompensation), independently of age and sex and of established predictors in heart failure such as NYHA class, NT-proBNP, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LV-EF) (HR 2.770; 95% CI 1.419–5.407; p = 0.003). Patients with a neopterin/eGFR ratio ≥ 0.133 (as a combined marker for immune activation and kidney function) had a more than eightfold increased risk of reaching an endpoint compared to patients with a neopterin/eGFR ratio ≤0.065 (HR 8.380; 95% CI 2.889–24.308; p < 0.001). Neopterin is associated with disease severity and is an independent predictor of prognosis in patients with heart failure.
Highlights
Activation and down-regulation of the immune response are important mechanisms to control tissue damage, initiate the healing process, and to remove dead cells and debris after a harmful stimulus [1]
Prolonged immune activation promotes local and systemic inflammatory processes, thereby contributing to tissue damage and organ failure over time. This has been shown in patients with chronic heart failure (CHF) [2], where increased concentrations of circulating cytokines and biomarkers of inflammation were associated with a poor outcome [3,4,5]
We show that calculation of the neopterin/estimated glomerular filtration rate (eGFR) ratio is very useful to predict a worse outcome of patients and might be well suited as a “combined” marker for immune activation and decreased kidney function
Summary
Activation and down-regulation of the immune response are important mechanisms to control tissue damage, initiate the healing process, and to remove dead cells and debris after a harmful stimulus [1]. Prolonged immune activation promotes local and systemic inflammatory processes, thereby contributing to tissue damage and organ failure over time. This has been shown in patients with chronic heart failure (CHF) [2], where increased concentrations of circulating cytokines and biomarkers of inflammation were associated with a poor outcome [3,4,5]. The balance of physiological and pathological immune activation contributes to heart failure (HF) progression and determines the outcomes of these patients [2]. Circulating endotoxins, which translocate from the intestinal tract into the systemic circulation [8], as well as the hypoxia of body tissues [9,10,11] and central inhibition of the parasympathetic nervous system appear to be involved [6]
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