Interleukin-6 Could Be a Potential Prognostic Factor in Ambulatory Elderly Patients with Stable Heart Failure: Results from a Pilot Study

Abstract

Introduction: Inflammation is a fundamental phenomenon in heart failure, but the prognostic or therapeutic role of markers such as interleukin-6 (IL-6) has not yet been clarified. The objective of this study is to describe the clinical profile of patients with elevated IL-6 and determine if they have worse clinical outcomes. Methods: A retrospective c.ohort observational study including 78 patients with heart failure followed up at the Heart Failure Outpatient Clinic of the Internal Medicine Department. IL-6 was determined in all patients, who were then assigned into two groups according to IL-6 level (normal or high). Clinical and prognostic data were collected to determine the differences in both groups. Results: The average age was 79 years, 60% female. A total of 53.8% of the patients had elevated IL-6 (group 2). Patients with elevated IL-6 presented more frequently with anemia mellitus (64.3% vs. 41.7%; p = 0.046), atrial fibrillation (83.3% vs. 61.9% p = 0.036), dyslipidemia (76.2% vs. 58.2%; p = 0.03), higher creatinine levels (1.35 mg/dL vs. 1.08 mg/dL; p = 0.024), lower glomerular filtration rate (43.6 mL/min/m2 vs. 59.9 mL/min/m2; p = 0.007), and anemia 25% vs. 52.4% p = 0.014. The factors independently associated with the increase in IL-6 were anemia 3.513 (1.163–10.607) and renal failure 0.963 (0.936–0.991), p < 0.05. Mortality was higher in the group with elevated IL-6 levels (16% vs. 2%; p = 0.044) with a log-rank p = 0.027 in the Kaplan–Meier curve. Conclusion: Patients with heart failure and elevated IL-6 most often have atrial fibrillation, diabetes mellitus, dyslipidemia, anemia, and renal failure. In addition, mortality was higher and a tendency of higher hospital admission was observed in stable HF patients with elevated IL-6.

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

“…3 However, the majority of data pertaining to IL-6 (and IL-1/1β, its upstream signaling precursor) in prevalent heart failure are from patients with heart failure with reduced ejection fraction (HFrEF) or all-comers with heart failure in whom ejection fraction is undefined. 8,[13][14][15][16][17][18][19][20] The CANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) reported that, in patients with a history of prior myocardial infarction and elevated hsCRP (high-sensitivity CRP), treatment with the IL-1β inhibitor, canakinumab, reduced heart failure hospitalization and heart failurerelated mortality, although an examination of these effects specifically upon HFpEF was not addressed. 10,11 ZEUS (Ziltivekimab Cardiovascular Outcomes Study) is a large phase 3 trial examining the effect of IL-6 inhibition upon cardiovascular outcomes in patients with chronic kidney disease and elevated hsCRP.…”

Inflammation-Related Biomarkers Are Associated with Heart Failure Severity and Poor Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy

“…IL-6 and TNF-α are proinflammatory cytokines produced mostly by activated monocytes and macrophages. The proinflammatory role of these cytokines in systemic inflammation is well established in various pathologies, including cardiovascular diseases such as atherosclerotic cardiovascular disease and chronic heart failure [48,49]. In addition, the prognostic role of IL-6 and TNF-α in chronic heart failure patients has been demonstrated in previous studies [50,51].…”

Frailty and heart failure: State‐of‐the‐art review

“…13 Specifically, IL-6 has been found to be more prevalent in elderly patients with a higher burden of cardiovascular co-morbidities and is associated with increased mortality in HF. 14 A post hoc analysis of the PARAGON-HF (Prospective Comparison of ARNI [angiotensin receptor-neprilysin inhibitor] with ARB [angiotensin receptor blocker] Global Outcomes in HF with Preserved Ejection Fraction) trial showed an increasing neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, with worsening frailty in HF patients. 15 Systemic inflammation also leads to progression of atherosclerosis and insulin resistance, and changes in metabolic hormonal activity such as insulin growth factor and growth differentiation factor 15 (GDF-15), which also contribute towards worsening frailty.…”

“…Pro‐inflammatory markers, such as C‐reactive protein, tissue necrosis factor and interleukin‐6 (IL‐6), are elevated in HF and are associated with a heightened risk of HF in the elderly 13 . Specifically, IL‐6 has been found to be more prevalent in elderly patients with a higher burden of cardiovascular co‐morbidities and is associated with increased mortality in HF 14 . A post hoc analysis of the PARAGON‐HF (Prospective Comparison of ARNI [angiotensin receptor–neprilysin inhibitor] with ARB [angiotensin receptor blocker] Global Outcomes in HF with Preserved Ejection Fraction) trial showed an increasing neutrophil‐to‐lymphocyte ratio, a marker of systemic inflammation, with worsening frailty in HF patients 15 .…”