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Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from
Ståle H Nymo1, Johannes Hulthe, Thor Ueland
1Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Insights
Interleukin-8 (IL-8) predicts outcomes in chronic heart failure (HF) patients. While IL-8 shows promise, its clinical utility as a biomarker in unselected HF populations requires further investigation.
Area of Science:
- Cardiology
- Biomarkers
- Inflammation
Background:
- Chronic systolic heart failure (HF) is a significant clinical challenge.
- Identifying reliable biomarkers for predicting HF outcomes is crucial for patient management.
- Prototypical inflammatory cytokines are implicated in HF pathophysiology.
Purpose of the Study:
- To investigate the predictive ability of inflammatory cytokines for clinical outcomes in a large cohort of chronic systolic heart failure patients.
- To assess the independent predictive value of specific cytokines after adjusting for established risk factors.
Main Methods:
- Analysis of serum levels of tumor necrosis factor-α (TNF-α), soluble TNF receptors (sTNF-RI, sTNF-RII), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) in 1464 patients from the CORONA study.
- Patients were aged ≥ 60 years, with chronic ischemic systolic HF (NYHA class II-IV).
- Outcomes included primary endpoint, coronary events, all-cause mortality, cardiovascular mortality, and a composite of worsening HF hospitalization or CV mortality.
Main Results:
- TNF-α, sTNF-RI, sTNF-RII, and IL-8 were independent predictors of most outcomes, excluding coronary events, in multivariable models.
- After adjustment for clinical variables, estimated glomerular filtration rate, ApoB/ApoA-1 ratio, NT-proBNP, and high-sensitivity C-reactive protein, IL-8 remained a significant predictor for all endpoints (except coronary).
- Soluble TNF receptor type I (sTNF-RI) remained independently associated with cardiovascular mortality.
- Adding IL-8 to the model significantly improved reclassification for all-cause mortality and CV hospitalization.
Conclusions:
- Interleukin-8 (IL-8) is associated with adverse outcomes in patients with chronic heart failure.
- While IL-8 demonstrates predictive capacity, its clinical usefulness as a biomarker in unselected heart failure populations remains uncertain.
- Further research is needed to clarify the role of IL-8 in guiding clinical decisions for heart failure management.
Aim:
We investigated the ability of prototypical inflammatory cytokines to predict clinical outcomes in a large population of patients with chronic systolic heart failure (HF).
Methods And Results:
Serum levels of tumour necrosis factor-α (TNF-α), soluble TNF receptors type I and II (sTNF-RI and sTNF-RII), and the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) were analysed in 1464 patients with chronic ischaemic systolic HF in the CORONA study, aged ≥ 60 years, in NYHA class II-IV, and related to the primary endpoint (n = 320), as well as any coronary event (n = 255), all-cause mortality (n = 329), cardiovascular (CV) mortality (n = 268), and the composite endpoint hospitalization from worsening heart failure (WHF) or CV mortality (n = 547). TNF-α, sTNF-RI, sTNF-RII, and IL-8, but not MCP-1, were independent predictors of all endpoints except the coronary endpoint in multivariable models including conventional clinical variables. After further adjustment for estimated glomerular filtration rate, the ApoB/ApoA-1 ratio, NT-proBNP, and high-sensitivity C-reactive protein, only IL-8 remained a significant predictor of all endpoints (except the coronary endpoint), while sTNF- RI remained independently associated with CV mortality. Adding IL-8 to the full model led to a significant improvement in net reclassification for all-cause mortality and CV hospitalization, but only a borderline significant improvement for the primary endpoint, CV mortality, and the composite endpoint WHF hospitalization or CV mortality.
Conclusion:
Our study supports a relationship between IL-8 and outcomes in patients with chronic HF. However, the clinical usefulness of IL-8 as a biomarker in an unselected HF population is at present unclear.
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