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September 9, 2026Journal of the American College of Cardiology561 citations

Circulating Levels of Cytokines and Their Endogenous Modulators in Patients With Mild to Severe Congestive Heart Failure Due to Coronary Artery Disease or Hypertension

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MTMARCO TESTAMYMichael YehPLPaul C. Lee

Key Result

In patients with congestive heart failure, the percentage of patients with elevated levels of cytokines and their soluble receptors significantly increased with NYHA functional class.

Key Points

  • To determine circulating levels of pro-inflammatory cytokines and their endogenous modulators across mild to severe congestive heart failure secondary to coronary artery disease or hypertension.
  • Cross-sectional evaluation measuring circulating concentrations of inflammatory cytokines and soluble receptors across clinical heart failure stages.
  • Patients were stratified by New York Heart Association functional class and underlying etiology (coronary artery disease versus hypertension).
  • Circulating levels of cytokines and their endogenous modulators increased progressively in parallel with increasing New York Heart Association functional class severity.
  • Significant immune activation was observed across both coronary artery disease and hypertensive etiologies, demonstrating that cytokine network activation is a general feature of heart failure progression.

Study Design

Type

Observational (n=80)

PICO

P
Population
80 patients with congestive heart failure due to coronary artery disease or hypertension, ranging from NYHA functional class I to IV.
E
Exposure / Comparator
Congestive heart failure severity
O
Primary Outcome
Circulating levels of cytokines and their respective endogenous modulators

Abstract

OBJECTIVES: This study sought to determine the circulating levels of cytokines and their respective endogenous modulators in patients with congestive heart failure of variable severity. BACKGROUND: Activation of immune elements localized in the heart or periphery, or both, may promote release of cytokines in patients with congestive heart failure. Although an increased circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor type II (sTNF-RII) is well documented, less is known about other cytokines (i.e., interleukin-1-beta IL-1-beta, interleukin-6 IL-6 and interleukin-2 IL-2 and their soluble receptor/receptor antagonists). METHODS: Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist (IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems) in 80 patients with congestive heart failure due to coronary artery disease or hypertension. The severity of their symptoms, which ranged from New York Heart Association functional class I to IV, was confirmed by measurement of peak oxygen consumption. RESULTS: The percentage of patients with elevated levels of cytokines and their corresponding soluble receptor/receptor antagonists significantly increased with functional class. For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble receptor/receptor antagonists was higher than that of patients with elevated levels of the cytokine itself. For IL-6, the percentage of patients with elevated levels of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6. All but two patients had undetectable levels of IL-2, and all but seven had levels of IL-2-sR within a normal range. CONCLUSIONS: In patients with congestive heart failure, circulating levels of cytokines increased with the severity of symptoms. In these patients, circulating levels of sTNF-RII and IL-1-Ra are more sensitive markers of immune activation than are circulating levels of TNF-alpha and IL-1-beta, respectively. Levels of IL-2 and IL-2-sR are not elevated when congestive heart failure is due to coronary artery disease or hypertension.

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Cite This Study

TESTA et al. (1996) conducted an observational in Congestive heart failure (n=80). Congestive heart failure severity was evaluated on Circulating levels of cytokines and their respective endogenous modulators. In patients with congestive heart failure, the percentage of patients with elevated levels of cytokines and their soluble receptors significantly increased with NYHA functional class.

synapsesocial.com/papers/6aa1cd349e612837183809b0https://doi.org/10.1016/s0735-1097(96)00268-9
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