The Clinical Significance of Interleukin-6 in Heart Failure: Results from the BIOSTAT-CHF Study

TY - JOUR

T1 - The Clinical Significance of Interleukin-6 in Heart Failure

T2 - Results from the BIOSTAT-CHF Study

AU - Markousis-Mavrogeni, George

AU - Tromp, Jasper

AU - Ouwerkerk, Wouter

AU - Devalarja, Matt

AU - Anker, Stefan D.

AU - Cleland, John G.

AU - Dickstein, Kenneth

AU - Filippatos, Gerasimos S.

AU - van der Harst, Pim

AU - Lang, Chim

AU - Metra, Marco

AU - Ng, Leong Loke

AU - Ponikowski, Piotr

AU - Samani, Nilesh J.

AU - Zannad, Faiez

AU - Zwinderman, Aeilko H.

AU - Hillege, Hans L.

AU - van Veldhuisen, Dirk Jan

AU - Kakkar, Rahul

AU - Voors, Adriaan

AU - Meer, Peter van der

N1 - BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29]. An unrestricted research grant by Corvidia Therapeutics supported this manuscript.

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

KW - Adverse events

KW - Anaemia

KW - Heart failure

KW - Inflammation

KW - Interleukin-6

KW - Procalcitonin

UR - https://www.scopus.com/pages/publications/85065758868

U2 - 10.1002/ejhf.1482

DO - 10.1002/ejhf.1482

M3 - Article

C2 - 31087601

SN - 1388-9842

VL - 21

SP - 965

EP - 973

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 8

ER -