Effect of Ghrelin on Mortality and Cardiovascular Outcomes in Experimental Rat and Mice Models of Heart Failure: A Systematic Review and Meta-Analysis

Abstract

BackgroundHeart failure (HF) continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF.MethodsData sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014) which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration) on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE’s risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3.ResultsA total of 325 animals (rats and mice) were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47) i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more) as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66) while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48) and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02) were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29) and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6.82, P=0.59).ConclusionsThe existing data provides evidence to suggest that Ghrelin may lower the risk of mortality and improve cardiovascular outcomes. However; the quality of evidence as assessed by GRADEpro is low to very low. Clinical judgments to administer Ghrelin to patients with HF must be made on better designed animal studies.

Body composition, appetite-related hormones, adipocytokines, and heart failure in adult patients with congenital heart disease: A preliminary study

“…As observed in the current study, lower ghrelin levels might have a negative impact on severe HF. Non‐CHD adults with HF reportedly have much lower ghrelin levels than those without HF . Moreover, plasma ghrelin levels are significantly high in children with CHD .…”

“…Ghrelin is an orexigenic hormone of gastric origin 22 and is a natural endogenous ligand of the growth hormone (GH) secretagogue receptor that was identified as a stimulant for GH release. 22 Ghrelin and its receptors are ubiquitously expressed in heart and vessels [23][24][25][26][27][28] and are considered to regulate appetite, energy, body weight, and metabolism of glucose and fat as well as to modulate gastrointestinal, cardiovascular, pulmonary, immune functions, and cell proliferation/apoptosis by its direct effects and via its role in GH release. [22][23][24][25][26][27][28] In some animal studies, exogenous administration of ghrelin led to the dilatation of peripheral blood vessels, regulation of atherosclerosis, improved endothelial function, and inhibition of myocardial cell apoptos.…”

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

“…In a meta‐analysis on the effect of ghrelin on mortality and cardiovascular outcomes in experimental rat and mouse models of HF, Khatib et al 25. consider the existing data to provide suggestive evidence that ghrelin may lower the risk of mortality and improve cardiovascular outcomes.…”

Cholecystokinin Expression in the Development of Postinfarction Heart Failure

“…Hormonal imbalances may be important contributors to worse prognoses in patients with heart failure [1, 2]. Researchers have become increasingly interested in using appetite-regulated hormones, such as orexigenic peptides (ghrelin) [3-5] and anorexigenic peptides (leptin) [6], as biomarkers of cardiac and systemic abnormalities and as potential drugs in the treatment of heart failure, especially in cardiac cachexia [4, 7]. …”