Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex‐DHF pilot study

Abstract

BackgroundOver 50% of patients with symptomatic heart failure (HF) experience HF with preserved ejection fraction (HFpEF). Exercise training (ET) is effective in improving cardiorespiratory fitness and dimensions of quality of life in patients with HFpEF. A systemic pro‐inflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations has been proposed in HFpEF. ET modifies myocardial structure and has been related to inflammatory state. We investigated Ghrelin, related adipokines, markers of inflammation, and neuro‐hormonal activation in patients undergoing a structured ET vs. usual care are with HFpEF. Methods and resultsEx‐DHF‐P was a prospective, controlled, randomized multi‐centre trial on structured and supervised ET in patients with HFpEF. We performed a post hoc analysis in 62 patients from Ex‐DHF‐P. Ghrelin, adiponectin, leptin, IL‐1ß, IL‐6, IL‐10, tumour necrosis factor‐alpha, MR‐proANP, MR‐proADM, CT‐proET1, and CT‐proAVP were assessed to seize the impact of ET on these markers in patients with HFpEF. Thirty‐six (58%) patients were female, mean age was 64 years, and median ghrelin was 928 pg/mL (interquartile range 755–1156). When stratified for high versus low ghrelin, groups significantly differed at baseline in presence obesity, waist circumference, and adiponectin levels (P < 0.05, respectively). Overall, ghrelin levels rose significantly to 1013 pg/mL (interquartile range 813–1182) (P < 0.001). Analysis of covariance modelling for change in ghrelin identified ET (P = 0.013) and higher baseline adiponectin levels (P = 0.035) as influencing factors.ConclusionsExercise training tended to increase ghrelin levels in Ex‐DHF‐P. This increase was especially pronounced in patients with higher baseline adiponectin levels. Future trials are needed to investigate the effect of ET on endogenous ghrelin levels in regard to interactions with cardiac structure and clinically meaningful surrogate parameters.

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

“…Billebeau et al 22 observed a statistically significant (p<0.001) median decrease of 16% post-training (n=105), with no changes in control participants. In contrast, the post hoc analysis of the Ex-DHF pilot trial by Trippel et al 31 noted no significant treatment effect in patients with HFpEF.…”

“…One study by Trippel et al 31 reported on CT-proAVP levels and failed to find any statistically significant change post-training or compared with the control group in patients with HFpEF.…”

“…A general description of included studies is provided in table 1. Of the 43 included studies, two30 31 studies were from the same trial but provided different biomarker information, and two32 33 studies contained an overlap of some participants, and data were combined into one dataset for meta-analysis to eliminate data overlap. Four22 34–36 of the studies were controlled but not randomised, one37 study randomised…”

“…participants between exercise intervention groups, but the control group was not randomised, one38 study was a retrospective analysis and all remaining studies were RCTs. Seven studies,30 31 39–43 representing six trials, included participants with a mean left ventricular ejection fraction (LVEF) >50%, one43 of which also included participants with LVEF <50%. Thirty-six trials included participants with mean LVEF <50%, and the mean LVEF of at least three44–46 studies indicates the inclusion of participants with a range of ejection fractions, reduced, mid-range and/or preserved ejection fraction.…”

Exercise training in Diastolic Heart Failure (Ex‐DHF): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial

“…However, the definite impact of ET on diastolic function remains unclear and whether E/e′ is a key measure of diastolic function has to be discussed in the future. Substudies of the Ex‐DHF trial will therefore assess the effects of ET on inflammatory markers, metabolic parameters, collagen turnover, as well as on vascular function and ventriculo–arterial coupling, and novel non‐standard echocardiographic parameters of systolic and diastolic function.…”