Exercise-induced changes in left ventricular strain are affected by interleukin-6 activity: An exploratory analysis of a randomised-controlled trial in humans with abdominal obesity

Abstract

Whilst the exercise-induced myokine interleukin-6 (IL-6) plays a beneficial role in cardiac structural adaptations, its influence on exercise-induced functional cardiac outcomes remains unknown. We hypothesised that IL-6 activity is required for exercise-induced improvements in left ventricular global longitudinal strain (LV GLS). In an exploratory study 52 individuals with abdominal obesity were randomised to 12 weeks' high-intensity exercise or no exercise in combination with IL-6 receptor inhibition (IL-6i) or placebo. LV strain and volume measurements were assessed by cardiac magnetic resonance. Exercise improved LV GLS by -5.4% [95% CI: -9.1% to -1.6%] (P = 0.007). Comparing the change from baseline in LV GLS in the exercise + placebo group (-4.8% [95% CI: -7.4% to -2.2%]; P < 0.0004) to the exercise + IL-6i group (-1.1% [95% CI: -3.8% to 1.6%]; P = 0.42), the exercise + placebo group changed -3.7% [95% CI: -7.4% to -0.02%] (P = 0.049) more than the exercise + IL6i group. However, the interaction effect between exercise and IL-6i was insignificant (4.5% [95% CI: -0.8% to 9.9%]; P = 0.09). Similarly, the exercise + placebo group improved LV global circumferential strain by -3.1% [95% CI: -6.0% to -0.1%] (P = 0.04) more compared to the exercise + IL-6i group, yet we found an insignificant interaction between exercise and IL-6i (4.2% [95% CI: -1.8% to 10.3%]; P = 0.16). There was no effect of IL-6i on exercise-induced changes to volume rates. This study underscores the importance of IL-6 in improving LV GLS in individuals with abdominal obesity suggesting a role for IL-6 in cardiac functional exercise adaptations.

Keywords: cardiac adaptations; exercise; interleukin‐6.

FIGURE 1

Flowchart of study. This figure is modified, with permission, from a previous publication (Wedell‐Neergaard et al., 2019). Importantly, the resistance training group is not part of this study but was published separately (Christensen, Wedell‐Neergaard, et al., 2019). CMR, cardiac magnetic resonance imaging; FU, follow‐up; IL‐6i, interleukin‐6 receptor inhibition.

FIGURE 2

Effects of exercise on left ventricular function in combination with placebo or IL‐6i (n = 52). (a) LV GLS relative (%) change from baseline; (b) LV GCS relative (%) change from baseline; (c) NPER relative (%) change from baseline; (d) NPFR relative (%) change from baseline. Significant differences are denoted: *within‐group difference from baseline; #between‐group difference in change from baseline (P < 0.05). Ex, exercise; IL‐6i; interleukin‐6 receptor inhibition; LV, left ventricle; LV GCS, LV global circumferential strain; LV GLS, LV global longitudinal strain; NPER, normalised peak ejection rate; NPFR, normalised peak filling rate; Pl, placebo.