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. 2023 Apr;16(4):e010051.
doi: 10.1161/CIRCHEARTFAILURE.122.010051. Epub 2023 Mar 10.

Adverse Outcomes Associated With Interleukin-6 in Patients Recently Hospitalized for Heart Failure With Preserved Ejection Fraction

Leanne Mooney  1 , Colette E Jackson  1 , Carly Adamson  1 , Alex McConnachie  2 , Paul Welsh  1 , Rachel C Myles  1 , John J V McMurray  1 , Pardeep S Jhund  1 , Mark C Petrie  1 , Ninian N Lang  1
Affiliations

Adverse Outcomes Associated With Interleukin-6 in Patients Recently Hospitalized for Heart Failure With Preserved Ejection Fraction

Leanne Mooney et al. Circ Heart Fail. 2023 Apr.

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.

Keywords: heart failure; inflammation; interleukin; natriuretic peptide, brain; tumor necrosis factor.

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Conflict of interest statement

Dr Welsh reports receiving grants from Roche Diagnostics, AstraZeneca, Boehringer Ingelheim, Merck, Vifor, and AstraZeneca outside the submitted work. Dr Jhund received personal fees from Novartis and Cytokinetics and grants from Boehringer Ingelheim outside the submitted work. M.C. Petrie reports receiving grants and personal fees from Novartis, Novo Nordisk, AstraZeneca, Eli Lilly, Napp Pharmaceuticals, Takeda Pharmaceutical, Alnylam, Bayer, Resverlogix, Cardiorentis, and Boehringer Ingelheim outside the submitted work. Dr McMurray reports payments to his employer, Glasgow University, for work on clinical trials, consulting, lecturing, and other activities: Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and personal lecture fees from Abbott, Hikma, Sun Pharmaceuticals, and Servier. Dr Lang received speaker’s fees from Roche, Pfizer, and Novartis and research grant support from Roche Diagnostics outside the submitted work. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Clinical outcomes for patients with heart failure with preserved ejection fraction according to IL (interleukin)-6 tertile. A, Cumulative probability for all-cause death. B, Cumulative probability for cardiovascular death. C, Cumulative probability for subsequent heart failure hospitalization.
Figure 2.
Figure 2.
Association between IL (interleukin)-6 levels and the risk of all-cause death, cardiovascular death, and subsequent heart failure hospitalization (restricted cubic spline analysis). A, All-cause death. B, Cardiovascular death. C, Subsequent heart failure hospitalization. Model adjusted for age, female sex, systolic blood pressure, creatinine, body mass index, New York Heart Association (NYHA) class, diabetes, myocardial infarction, stroke, prior heart failure hospitalization, and log(B-type natriuretic peptide [BNP]).
See this image and copyright information in PMC

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