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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein
  • Heart Failure* / complications
  • Heart Failure* / diagnosis
  • Heart Failure* / therapy
  • Humans
  • Interleukin-6
  • Male
  • Natriuretic Peptide, Brain
  • Prognosis
  • Stroke Volume / physiology

Substances

  • Interleukin-6
  • C-Reactive Protein
  • Natriuretic Peptide, Brain