Adverse outcomes associated with interleukin-6 in patients recently hospitalized for heart failure with preserved ejection fraction

Mooney, L., Jackson, C. E., Adamson, C., McConnachie, A. , Welsh, P. , Myles, R. C. , McMurray, J. J.V. , Jhund, P. S. , Petrie, M. C. and Lang, N. N. (2023) Adverse outcomes associated with interleukin-6 in patients recently hospitalized for heart failure with preserved ejection fraction. Circulation: Heart Failure, 16(4), e010051. (doi: 10.1161/CIRCHEARTFAILURE.122.010051) (PMID:36896709) (PMCID:PMC10101136)

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Abstract

Background: Inflammation may play a role in the pathophysiology of heart failure with preserved ejection fraction. We examined whether circulating levels of interleukin-6 identify patients at greater risk of adverse outcomes following hospitalization with heart failure with preserved ejection fraction. Methods: We assessed relationships between interleukin-6 (IL-6) tertiles (T1-3) and all-cause death, cardiovascular death, and subsequent heart failure hospitalization (sHFH) in 286 patients recently hospitalized with heart failure with preserved ejection fraction. Associations between IL (interleukin)-6 and outcomes were examined in a Cox-regression model adjusted for risk factors including BNP (B-type natriuretic peptide). Biomarkers including hsCRP (high-sensitivity C-reactive protein) were assessed. Results: The range of IL-6 (pg/mL) in each tertile was T1 (0.71–4.16), T2 (4.20–7.84), and T3 (7.9–236.32). Compared with T1, patients in the highest IL-6 tertile were more commonly male (56% versus 35%) and had higher creatinine (117±45 versus 101±36 μmol/L), hsCRP (11.6 [4.9–26.6]mg/L versus 2.3[1.1–4.2] mg/L). In univariable analysis, rates of all-cause death, cardiovascular death, and sHFH were higher in T3 versus T1. All-cause and cardiovascular death rates remained higher in T3 versus T1 after adjustment (P<0.001). One log unit increase in IL-6 was associated with higher risk of all-cause death (hazard ratio, 1.46 [1.17–1.81]), cardiovascular death (hazard ratio, 1.40 [1.10–1.77]), and sHFH (hazard ratio, 1.24 [1.01–1.51]) after adjustment. One log unit increase in hsCRP was associated with a higher risk of cardiovascular death and all-cause death before and after adjustment for other factors but was not associated with risk of sHFH before or after adjustment. Conclusions: In patients recently hospitalized with heart failure with preserved ejection fraction, IL-6 is an independent predictor of all-cause mortality, cardiovascular death, and sHFH after adjustment for risk factors including BNP. These findings are of particular relevance in the context of current anti–IL-6 drug development.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Myles, Dr Rachel and Jhund, Professor Pardeep and Welsh, Professor Paul and Petrie, Professor Mark and Mooney, Dr Leanne and Lang, Professor Ninian and Adamson, Dr Carly and Jackson, Dr Colette and McMurray, Professor John
Authors: Mooney, L., Jackson, C. E., Adamson, C., McConnachie, A., Welsh, P., Myles, R. C., McMurray, J. J.V., Jhund, P. S., Petrie, M. C., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Circulation: Heart Failure
Publisher:American Heart Association
ISSN:1941-3289
ISSN (Online):1941-3297
Published Online:10 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Circulation: Heart Failure 16(4):e010051
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
143363Microvolt T-wave alternans in chronic heart failure: a study of prevalence and incremental prognostic value.Stuart CobbeOffice of the Chief Scientific Adviser (CSO)CZH/4/439Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science