Abstract
BACKGROUND: Chronic heart failure (HF) is a complex syndrome with significant morbidity and mortality, where inflammation is increasingly recognized as a critical factor in its progression. This study investigated the association of cytokine and chemokine profiles with mild cognitive impairment (MCI) and long-term mortality in patients with chronic HF. METHODS: Serum concentrations of 13 cytokines were measured in 145 patients from the Cognition.Matters-HF study baseline cohort using a bead-based multiplex assay. Detailed clinical and cognitive evaluations were conducted, and survival data were tracked over 10 years. Cox proportional hazards regression and logistic regression models were applied to assess independent associations with mortality and MCI. RESULTS: No cytokine was independently associated with MCI. However, high interleukin-8 (IL-8) levels (>5.3 pg/ml) were significantly and independently associated with all-cause mortality (HR: 2.30; 95% CI: 1.30-4.07; p = 0.004). After adjusting for age and sex, IL-8 remained a strong predictor (Adj. HR: 2.28; 95% CI: 1.29-4.05; p = 0.005). Further adjustments for clinical and biochemical variables showed that IL-8 (Adj. HR: 3.31; 95% CI: 1.61-6.79; p = 0.001) was the only cytokine independently associated with mortality. In the final multivariable model, IL-8 (Adj. HR: 2.57; 95% CI: 1.44-4.57; p = 0.001) remained a significant predictor along with age, body mass index, left atrial volume index, and six-minute walk distance. Other cytokines, including IL-6 and tumor necrosis factor-α, showed no independent associations with mortality. CONCLUSIONS: These findings suggest IL-8's unique role in HF pathophysiology and its potential as a biomarker and therapeutic target. Further research is needed to validate these results and explore the clinical utility of IL-8 modulation in HF management.