Nutritional Support Reduces Circulating Cytokines in Patients with Heart Failure

Abstract

Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega-3 (n-3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01-0.01-0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02-0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01-1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF.

Keywords: cytokines; heart failure; mortality; oral supplements; outcomes.

Figure 1

Clinical associations between circulating cytokine levels and clinical characteristics of patients with HF. (A) Cytokine levels in patients with baseline overweight or obesity (n = 10) vs. patients with BMI < 25 kg/m² (n = 28). (B) Serum cytokine levels in patients with heart failure that survived and died during the study (n = 5 and n = 33 respectively. Legend: only significant associations are depicted.

Figure 2

Significant clinical correlations between circulating cytokines, body composition and biochemical parameters in patients with HF: (A) clinical correlations observed at baseline; (B) clinical correlations determined after 24 weeks of nutritional intervention; (C) six months absolute changes. Legend: only significant correlations are presented. Color boxes represent the strength of the correlation according to the color scale represented on the right side of each figure. BIVA: bioimpedance vectorial analysis, MPE: morphofunctional evaluation; RF: rectus femoris; CRP: C reactive protein.

Figure 3

Effect of a 24-week nutritional intervention (based on Mediterranean diet with or without an oral n-3 enriched nutritional supplement) on circulating cytokine serum levels in all the evaluated patients with HF. Legend: ONS: oral nutritional supplement; serum cytokines are measured in pg/mL. * p < 0.05; ** p < 0.01; *** p < 0.001; ns: non-significant.