Inflammatory biomarkers and effect of exercise on functional capacity in patients with heart failure: Insights from a randomized clinical trial

Abstract

Background: In patients with heart failure, inflammation has been associated with worse functional capacity, but it is uncertain whether it could affect their response to exercise training. We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake ( _ VO 2 ) among patients with heart failure. Design: Open, parallel group, randomized controlled trial. Methods: Patients with heart failure and ejection fraction 0.4 were randomized into exercise training or control for 12 weeks. Patients were classified according to: 1) inflammatory biomarkers blood levels, defined as 'low' if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median, and 'high' otherwise; and 2) galectin-3 blood levels, which also reflect pro-fibrotic processes. Results: Forty-four participants (50 AE 7 years old, 55% men, 25% ischemic) were allocated to exercise training (n ¼ 28) or control (n ¼ 16). Exercise significantly improved peak _ VO 2 among participants with 'low' inflammatory biomarkers (3.5 AE 0.9 vs. À0.7 AE 1.1 ml/kg per min, p ¼ 0.006), as compared with control, but not among those with 'high' inflammatory biomarkers (0.4 AE 0.6 vs. À0.2 AE 0.7 ml/kg per min, p ¼ 0.54, p for interaction ¼ 0.009). Similarly, exercise improved peak _ VO 2 among participants with below median (2.4 AE 0.8 vs. À0.3 AE 0.9 ml/kg per min, p ¼ 0.032), but not among those with above median galectin-3 blood levels (0.3 AE 0.7 vs. À0.7 AE 1.0 ml/kg per min, p ¼ 0.41, p for interaction ¼ 0.053). Conclusion: In patients with heart failure, levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity. Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers.

Unbalanced plasma TNF-α and IL-12/IL-10 profile in women with migraine is associated with psychological and physiological outcomes

“…Accordingly, the plasma concentrations of TNF-α soluble receptors I and II were inversely correlated with poor cardiorespiratory fitness (VO 2Peak < 18 mL kg min − 1 ) in patients with heart failure (Itoh et al, 2005). Still, a recent study investigating the effect of baseline cytokines and changes in cardiorespiratory fitness after aerobic exercise training in patients with heart failure, showed a blunted improvement response among individuals with above-median baseline plasma TNF-α levels compared to individuals with below-median levels (Fernandes-Silva et al, 2017).…”

Circulatory factors associated with function and prognosis in patients with severe heart failure

“…However, a large number of other circulatory factors such as natriuretic peptides and cytokines have also been shown to increase in cases of HF [14]. Many of these factors are related to physical capacity, and display biological function(s) that might impact on cardiac and/or skeletal muscle tissues [4,18,25,29,38,41,42,47,60,71]. Thus, physical activity, synergistically with increases in neuroendocrine factors, is critical to connect the reduced myocardial function of patients with HF with the alterations in peripheral tissues (e.g., kidney and skeletal muscle) associated with this disease.…”

Effect of exercise therapy on established and emerging circulating biomarkers in patients with heart failure: a systematic review and meta-analysis

“…In addition to their diagnostic and prognostic utility, biomarker profiles may prove beneficial in guiding HF therapy and improving treatment strategies,10 including the identification of patients with HF that may respond to exercise training 21–23. A 2010 meta-analysis24 suggested that exercise training had a favourable effect on both BNP and NT-proBNP.…”