The relationship between tumor necrosis factor-α, brain natriuretic peptide and atrial natriuretic peptide in patients with chronic heart failure

https://doi.org/10.1016/j.ijcard.2008.11.146Get rights and content

Abstract

Background

Cytokines such as tumor necrosis factor-α (TNF) contribute to cardiac dysfunction in chronic heart failure (CHF). Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are thought to reflect cardiac functional and structural damage.

Methods and results

To study the relationship between BNP, ANP, and TNF, these parameters were measured in fasting venous blood samples of 25 CHF patients (age 66 ± 2 years, pVO2 17.4 ± 2.1 mL/kg/min, NYHA class 2.8 ± 0.2, all mean ± SEM) and 8 healthy controls (age 71 ± 2 years). Patients with CHF had higher plasma levels of BNP (p < 0.05), ANP (p < 0.05), norepinephrine (p < 0.01), and echocardiographic left ventricular end-diastolic diameter (LVEDD, p < 0.05) compared to controls, whereas TNF and epinephrine were not significantly different. There were significant correlations between natriuretic peptides and markers of inflammation and myocardial dysfunction in CHF patients: BNP vs. TNF (r = 0.64, p = 0.0006), vs. LVEDD (r = 0.59, p = 0.0025); ANP vs. TNF (r = 0.60, p = 0.0016), vs. LVEDD (r = 0.65, p = 0.0006); TNF vs. LVEDD (r = 0.57, p = 0.004). After adjustment for NYHA, creatinine clearance, and age TNF correlated with BNP (all p = 0.01) and ANP (all p < 0.002). The cachectic CHF patients (n = 7, > 6% weight loss) had the highest BNP (p < 0.001 vs. controls, p < 0.05 vs. non-cachectic CHF) and ANP levels (p = 0.01 vs. controls). Concentrations of uric acid, epinephrine, and norepinephrine also correlated with ANP and BNP.

Conclusion

In CHF, TNF is closely related to BNP and ANP (independently of CHF severity and ventricular dysfunction), particularly in patients with cardiac cachexia. TNF may causally contribute to intrinsic cardiac dysfunction thereby stimulating BNP and ANP secretion.

Introduction

Atrial natriuretic peptide (ANP) has recently been identified as playing a role in regulating postprandial lipid oxidation, energy expenditure and concomitantly arterial blood pressure [1]. In chronic heart failure (CHF) increased plasma levels of ANP and brain natriuretic peptide (BNP) have been reported [2]. They are closely related to the extent of ventricular dysfunction [3], cardiac filling pressures [4], NYHA class [5], peak oxygen consumption (pVO2) [6] and left ventricular ejection fraction (LVEF) [7]. High levels of both ANP and BNP predict poor clinical outcome in CHF [8], [9], [10]. Furthermore, BNP is increasingly used as a quantitative plasma biomarker and is highly accurate in the diagnosis of CHF [11].

Under the assumption that tumor necrosis factor-α (TNF) exerts direct detrimental effects on the myocardium we hypothesised a correlation between concentrations of both ANP and BNP with TNF. Cachectic CHF patients are known to have the strongest immune activation [12]. Therefore, we further expect them to have the most abnormal ANP and BNP levels. This has not yet been studied.

Section snippets

Study population

We studied 25 patients with CHF (male: n = 22) and 8 healthy control subjects (male: n = 6) of similar age (66 ± 2 vs. 71 ± 2 years, p > 0.20, mean ± standard error). The diagnosis of CHF was based on a history of CHF with symptomatic exercise intolerance, cardiomegaly, and objective evidence of left ventricular (LV) dysfunction for a period of at least 6 months. The patients had no clinical signs of acute infection or other chronic inflammatory conditions. Patients with haemodynamically important valve

Results

The clinical details of the study population are given in Table 1. The total group of CHF patients did not significantly differ from healthy control subjects in age and body mass index (BMI), but had substantially reduced pVO2. Patients with CHF were in NYHA functional class II (44%), III (36%) and IV (20%).

The plasma concentrations of TNF in healthy control subjects were similar to those in patients with CHF (Table 2). There was a strong trend for TNF to be higher in cachectic compared to

Dicussion

We have demonstrated a strong positive correlation between plasma concentrations of TNF and ANP as well as BNP levels, independently of the LVEDD, NYHA functional class, CrCl, or age. The subgroup of cachectic CHF patients showed the highest plasma levels of ANP and BNP compared to non-cachectic CHF patients and healthy volunteers. These findings indicate that higher levels of circulating natriuretic peptides may be characteristic particularly in CHF patients with immune activation and cardiac

Acknowledgements

AVP was supported by a postgraduate fellowship from the Competence Network Heart Failure, funded by the German Ministry of Education and Research (FKZ 01GI0205). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [28].

References (28)

  • J.C. Burnett et al.

    Atrial natriuretic peptide elevation in congestive heart failure in the human

    Science

    (1986)
  • R.J. Cody et al.

    Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion

    J Clin Invest

    (1986)
  • A.E. Raine et al.

    Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure

    N Engl J Med

    (1986)
  • H. Nakaoka et al.

    Plasma levels of atrial natriuretic factor in patients with congestive heart failure

    N Engl J Med

    (1985)

    • Cited by (48)

    • Protective effects of AS-IV on diabetic cardiomyopathy by improving myocardial lipid metabolism in rat models of T2DM

      2020, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      Inflammatory response is able to promote the deposition of type I collagen in the myocardial interstitial and perivascular in diabetic rats, eventually promoting the development of myocardial fibrosis [37,38]. TNF-α is one of the specific markers of inflammatory response and has become an independent predictor of prognosis in patients with heart failure [39]. The heart is both a place to produce TNF-α and a target organ for its action [40].

    • Animal models of cardiac cachexia

      2016, International Journal of Cardiology
      Citation Excerpt :

      Moreover, in the context of subacute and chronic disease, the persistent inflammation determines also the onset of hypothalamic inflammation (responsible for the regulation of appetite, body mass and energy homeostasis) and the transition from sickness to cachexia [21]. Finally, it has been found that CC patients show high plasma levels of noradrenaline and brain and atrial natriuretic peptides (BNP and ANP) and that TNF-α is strongly associated with BNP and ANP secretion [22,23]. As stated above, along with skeletal muscle mass wasting, there is also a decrease in fat mass in CC.

    • Biomarkers for cardiac cachexia: Reality or utopia

      2014, Clinica Chimica Acta
      Citation Excerpt :

      SNS and RAAS-induced volume expansion and pressure overload stimulate the secretion of NP by the heart [34,35], whose functions are antagonists of the aforementioned systems and include vasodilatation [35–39], natriuresis and diuresis promotion [35–39] and RAAS inhibition [36–39]. Pérez et al. [40] found higher plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) on cachectic CHF patients when compared with non-cachectic patients and healthy volunteers. The role of the heart in metabolism is highlighted by the lipolytic activity of ANP and BNP, as well as by its actions on slowing gastric emptying and absorption, and inhibiting renin and angiotensin release.

    • Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: Results from a pilot study in elderly chronic heart failure patients

      2013, International Journal of Cardiology
      Citation Excerpt :

      Despite the strength of inflammatory parameters as prognostic biomarkers in cardiovascular diseases and in CHF patients [2,27,31], our results suggest that BNP addition to SHFM may have incorporated some of the prognostic power of TNF-α, hs-CRP, and IL-6 ceasing their independent predictive ability. Recent evidences in CHF patients have shown a high positive correlation between natriuretic peptides and TNF-α [32], suggesting that BNP-added SHFM could have already included the prognostic gain in mortality prediction of TNF-α. Prealbumin additive power to BNP-SHFM observed in our pilot study supports the mounting clinical evidence [33] about the use of this inexpensive but informative parameter.

    • Safety of using anti-TNF-α blockers in cardiac failure associated with systemic inflammatory disease and the risk of Kounis syndrome

      2013, International Journal of Cardiology

    • The importance of biological sex in cardiac cachexia

      2022, American Journal of Physiology - Heart and Circulatory Physiology
    View all citing articles on Scopus
    View full text
    Crown copyright © 2008 Published by Elsevier Ireland Ltd. All rights reserved.