Abstract
BackgroundGhrelin, a gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients. However, it is unclear whether the interaction between ghrelin and BMI is associated with a risk of all-cause and CV death in this population.MethodsA prospective observational study was performed on 261 MHD outpatients (39% women, mean age 68.6 ± 13.6 years) recruited from October 2010 through April 2012, and were followed until November 2014 (median follow-up-28 months, interquartile range-19–34 months). We measured acyl-ghrelin (AG) levels, appetite, nutritional and inflammatory markers, prospective all-cause and cardiovascular (CV) mortality.ResultsDuring follow-up, 109 patients died, 51 due to CV causes. A significant interaction effect of high BMI and high AG (defined as levels higher than median) on all-cause mortality was found. Crude Cox HR for the product termed BMI x AG was 0.52, with a 95% confidence interval (CI): 0.29 to 0.95 (P = 0.03). Evaluating the interaction on an additive scale revealed that the combined predictive value of BMI and AG is larger than the sum of their individual predictive values (synergy index was 1.1). Across the four BMI-AG categories, the group with high BMI and high AG exhibited better all-cause and cardiovascular mortality irrespective of appetite and nutritional status (multivariable adjusted hazard ratios were 0.31, 95% CI 0.16 to 0.62, P = 0.001, and 0.35, 95% CI 0.13 to 0.91, P = 0.03, respectively). Data analyses made by dividing patients according to fat mass-AG, but not to lean body mass-AG categories, provided similar results.ConclusionsHigher AG levels enhance the favourable association between high BMI and survival in MHD patients irrespective of appetite, nutritional status and inflammation.
Highlights
Ghrelin, a gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients
Low plasma AG has demonstrated a significant association with cardiovascular morbidity [10] and low total ghrelin has been associated with all-cause and cardiovascular mortality risks, especially when considered in conjunction with nutritional status, inflammation and other weight-regulating hormones, such as leptin [11]
Patients with high BMI had lower Kt/v and malnutrition-inflammation score (MIS), higher prevalence of Diabetes mellitus (DM), higher levels of albumin, creatinine, uric acid, body composition indicators and geriatric nutritional risk index (GNRI), and fewer men and smokers were in this group than in the low BMI group
Summary
A gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients. An inverse association between body mass index (BMI) and mortality, named the obesity paradox, has been established in different populations including maintenance hemodialysis (MHD) patients [1, 2] Suggested reasons for this effect have been published and discussed elsewhere [2]. Two to threefold higher plasma ghrelin levels in end-stage kidney disease (ESKD) patients have been reported in some studies, mainly on account of DAG [7, 8], conflicting results have been presented by others [9] In this population, low plasma AG has demonstrated a significant association with cardiovascular morbidity [10] and low total ghrelin has been associated with all-cause and cardiovascular mortality risks, especially when considered in conjunction with nutritional status, inflammation and other weight-regulating hormones, such as leptin [11]. It is not at all clear if MHD patients with high BMI and high ghrelin levels will benefit more in terms of clinical outcome than MHD patients with high BMI and low ghrelin levels
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