Neopterin is Associated with Disease Severity and Outcome in Patients with Non-Ischaemic Heart Failure

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.

Anemia of Chronic Disease in Patients With Cardiovascular Disease

“…Serum neopterin concentrations ( n = 2,082) were measured with a radioimmunassay (BRAHMS Diagnostica, Hennigsdorf, Germany) with a sensitivity of 1 nmol/L neopterin and an interassay coefficient of variation ranging from 3.9 to 8.2% ( 28 ). We calculated the ratio of neopterin/eGFR since neopterin is excreted by the kidney and was shown to be higher/accumulate in patients with reduced kidney function ( 24 , 29 ). The high-sensitive C-reactive protein (hsCRP; n = 2,082) was quantified by immunonephelometry (N High Sensitive CRP, Dade Behring, Marburg, Germany).…”

“…Previous studies have already described a significant correlation between increased neopterin concentrations and anemia ( 17 – 20 ). Finally, higher neopterin concentrations have also been related with a poor prognosis in patients with cardiovascular disease ( 21 – 24 ).…”

Anaemia, iron status, and gender predict the outcome in patients with chronic heart failure

“…14,15 The aetiology of anaemia in CHF is often unclear, but inflammation might be a central underlying component because immune activation and increased circulating cytokine levels are observed in patients with advanced CHF. 12,16,17 Inflammation mediated induction of cytokines and of the master regulatory of iron homeostasis, hepcidin, block dietary iron uptake, and iron release of macrophages. 18,19 Hepcidin controls body iron homeostasis by interacting with the cellular iron exporter ferroportin-1, resulting in its internalization, thereby impairing duodenal iron absorption and iron egress from macrophages.…”

“…In both cases, iron availability for erythropoiesis is limited resulting in the development of anaemia over time 14,15 . The aetiology of anaemia in CHF is often unclear, but inflammation might be a central underlying component because immune activation and increased circulating cytokine levels are observed in patients with advanced CHF 12,16,17 . Inflammation mediated induction of cytokines and of the master regulatory of iron homeostasis, hepcidin, block dietary iron uptake, and iron release of macrophages 18,19 .…”

The Immunopathogenesis of Alzheimer’s Disease Is Related to the Composition of Gut Microbiota

“…However, not only decreased B vitamin availability might impair human metabolism, but also enhanced immune-mediated tryptophan degradation and the depletion of other important nutrients: An adequate tryptophan supply e.g., is essential for protein biosynthesis and also to down-regulate immune activation cascades [ 200 ]. In patients with cardiovascular disease elevated neopterin concentrations were associated with lower tryptophan concentrations [ 201 ], higher homocysteine concentrations and reduced B vitamin concentrations [ 202 ] and a worse survival [ 203 , 204 ]. Elevated neopterin concentrations also were demonstrated to coincide with decreased concentrations of vitamin C, E [ 205 ] and vitamin D [ 206 ] indicating that in patients with cardiovascular disease chronic immune activation/inflammation goes along with decreased vitamin concentrations, which are probably due to an increased consumption of vitamins.…”