George Markousis-Mavrogenis1, Jasper Tromp1,2, Wouter Ouwerkerk3,4, Matt Devalaraja5, Stefan D Anker6,7,8,9,10, John G Cleland11, Kenneth Dickstein12, Gerasimos S Filippatos13,14, Pim van der Harst1, Chim C Lang15, Marco Metra16, Leong L Ng17,18, Piotr Ponikowski19,20, Nilesh J Samani15, Faiez Zannad21, Aeilko H Zwinderman22, Hans L Hillege1, Dirk J van Veldhuisen1, Rahul Kakkar5, Adriaan A Voors1, Peter van der Meer1. 1. Department of Cardiology, University of Groningen, Groningen, The Netherlands. 2. National Heart Centre Singapore, Singapore. 3. Department of cardiology, national heart center Singapore. 4. Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands. 5. Corvidia Therapeutics, 35 Gatehouse Dr., Waltham, MA, USA. 6. Division of Cardiology and Metabolism - Heart Failure, Cachexia & Sarcopenia, Charité University Medicine, Berlin, Germany. 7. Department of Cardiology (CVK), Charité University Medicine, Berlin, Germany. 8. Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine, Berlin, Germany. 9. Department of Cardiology and Pneumology, University Medicine Göttingen (UMG), Göttingen, Germany. 10. DZHK (German Center for Cardiovascular Research), University Medicine Göttingen (UMG), Göttingen, Germany. 11. National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK. 12. Stavanger University Hospital, University of Bergen, Stavanger, Norway. 13. School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 14. Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece. 15. Division of Molecular & Clinical Medicine, University of Dundee, Dundee, UK. 16. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Institute of Cardiology, University of Brescia, Brescia, Italy. 17. Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester, UK. 18. NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. 19. Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland. 20. Poland and Cardiology Department, Military Hospital, Wroclaw, Poland. 21. Inserm CIC 1433, Université de Lorrain, CHU de Nancy, Nancy, France. 22. Department of Epidemiology, Biostatistics & Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
Abstract
AIMS: Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)-α were largely unsuccessful. Interleukin (IL)-6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL-6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. METHODS AND RESULTS: Interleukin-6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT-CHF cohort. The primary outcome was all-cause mortality and HF hospitalization during 2 years, with all-cause, cardiovascular (CV), and non-CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL-6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N-terminal pro-brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF-α/IL-1-related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL-6 levels. IL-6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11-1.21), P < 0.001], all-cause mortality [1.22 (1.16-1.29), P < 0.001] and CV as well as non-CV mortality [1.16 (1.09-1.24), P < 0.001; 1.31 (1.18-1.45), P < 0.001], but did not improve discrimination in previously published risk models. CONCLUSIONS: In a large, heterogeneous cohort of HF patients, elevated IL-6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL-6 as a potential therapeutic target in specific HF subpopulations.
AIMS: Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)-α were largely unsuccessful. Interleukin (IL)-6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL-6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. METHODS AND RESULTS:Interleukin-6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT-CHF cohort. The primary outcome was all-cause mortality and HF hospitalization during 2 years, with all-cause, cardiovascular (CV), and non-CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL-6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N-terminal pro-brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF-α/IL-1-related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL-6 levels. IL-6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11-1.21), P < 0.001], all-cause mortality [1.22 (1.16-1.29), P < 0.001] and CV as well as non-CV mortality [1.16 (1.09-1.24), P < 0.001; 1.31 (1.18-1.45), P < 0.001], but did not improve discrimination in previously published risk models. CONCLUSIONS: In a large, heterogeneous cohort of HF patients, elevated IL-6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL-6 as a potential therapeutic target in specific HF subpopulations.
Authors: Florian Wunderer; Lisa Traeger; Haakon H Sigurslid; Patrick Meybohm; Donald B Bloch; Rajeev Malhotra Journal: Pharmacol Res Date: 2020-01-25 Impact factor: 7.658
Authors: Amany H Abdelrahman; Iman I Salama; Somaia I Salama; Dalia M Elmosalami; Mona H Ibrahim; Eman M Hassan; Mark O Dimitry; Zahraa I Aboafya; Mohammad Gouda Mohammad; Mohamed Amin Journal: Future Sci OA Date: 2021-02-04
Authors: Daniela Tomasoni; Leonardo Italia; Marianna Adamo; Riccardo M Inciardi; Carlo M Lombardi; Scott D Solomon; Marco Metra Journal: Eur J Heart Fail Date: 2020-06-24 Impact factor: 17.349