Plasma Ghrelin Levels Are Associated with Coronary Microvascular and Endothelial Dysfunction in Peritoneal Dialysis Patients

Abstract

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED)is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 ± 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of < 2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR < 2 and ≥ 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 ± 82.1 pg/mL) in patients with CFR ≥ 2 were significantly higher than those in patients with CFR< 2 (63.3 ± 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 ± 37.81 ng/mL vs. 63.95 ± 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.

Cardiac Biomarkers and Noninvasive Predictors of Atherosclerosis in Chronic Peritoneal Dialysis Patients

“…Impairment of the CFR (CFR <2) has been suggested to be a preclinical sign of CV events and is characterized by a decreased capacity of the coronary dilatation following an increase in myocardial metabolic demands [7,8,9,10]. In this study, decreased CFR values were noted in 29 of 37 (78%) patients.…”

“…The CFR measurement which reflects coronary microvascular function and endothelial functions of epicardial coronary arteries by TTDE, as a cheaper and easy screening test, may be used as a detection method in the assessment of major epicardial coronary arteries [7,8,9,10]. Impairment of the CFR (CFR <2) has been suggested to be a preclinical sign of CV events and is characterized by a decreased capacity of the coronary dilatation following an increase in myocardial metabolic demands [7,8,9,10].…”

“…The intra-observer variability of CFR measurement was 3.6% in the current study. CFR <2.0 was considered abnormal [8,9,10]. …”

“…Decreased CFR values (CFR <2) reflect coronary ED and may be evidence of severe coronary artery disease [6,7,8,9]. In our previous study, we have also demonstrated that impaired CFR was significant in PD patients [10]. However, its measurement requires specialized medical staff and dedicated echocardiographic equipment, which is not readily available in every hospital.…”

Plasma ghrelin levels are closely associated with severity and morphology of angiographically-detected coronary atherosclerosis in Chineses patients with diabetes mellitus

“…As previously demonstrated by us and others, ghrelin inhibits pro-atherogenic changes in in vitro and in vivo experimental models. Ghrelin exhibits protective effects against the development of atherosclerosis by increasing coronary blood flow [3] , improving endothelial function [4] , inhibiting endothelial injury [5] , inducing vasodilation, enhancing cholesterol efflux in macrophages [6] , inhibiting smooth muscle cell (SMC) proliferation and apoptosis [7,8] and exerting anti-inflammatory effects [9][10][11] on the cardiovascular system. Low plasma ghrelin levels were found in diabetic patients compared to weightmatched non-diabetic subjects [12] .…”