Clinical Significance On The Changes Of Concentration Of Plasma Ghrelin In Patients With Chronic Heart Failure

The chronic congestive heart failure (CHF) is a common clinical syndrome with high incidence and mortality. Going through the pathophysiologic research stages of hemodynamics and neuro-endocrine regulation, the conception of treatment is updated. Large scale, random and double-blind clinical trials have given much proof on the treatment of heart failure. But the mechanism of its occurrence and development is still in vague. In recent years, many researches have indicated that some peptides play an important role in the occurrence and development of heart failure, including Ghrelin. Ghrelin is the endogenic ligand of growth hormone secretagogue-recptor (GHS-R), and was first abstracted and purifed from rat gastric mucosa cells by Kojima in 1999. Ghrelin is a novel growth-hormone (GH)-releasing peptide, with important roles in the regulation of foodintake, energy balance and hemodynamics. But the role of Ghrelin in heart failure patients is still in vague, and there is no study about this in domestic.Objective: (1) To investigate the level of Ghrelin, GH, TNF in peripheral blood of heart failure patients, and to analyze their correlation and the role in the occurrence and development of heart failure.(2) To investigate the pathophysiological role of these indexes in the course of cardiac cachexia.Methods: (1) Study subjects: We studied 94 patients with CHF in cardiology department of Qilu Hospital (62 men and 32 women, range 35-77 years). The cause of CHF was coronaryatherosclerotic heart disease in 46, valvular heart disease in 25, hypertension in 15 and myocardiopathy in 8. 12 patients were classified as New York Heart Association (NYHA) functional class II, 64 patients as class III and 18 patients as class IV. The study included 15 control subjects from Health Examination Center of Qilu Hospital (9 men and 6 women, range 36-75 years). Taking nonedematous and nonintentional weight loss of >7.5% of the previous normal nonedematous weight over a period of at least 6 months as standard, 31 patients were classified as cardiac cachexia and 63 as non-cardiac cachexia. Patients were excluded from the study if they had acute inflammation, malfunction of liver and kidney, severe electrolyte disorder, autoimmune disease, diabetes, malignant tumor and were administered steroid, and the patients underwent acute myocardial infarction in 6 months.(2) Methods: Blood samples(6ml) were taken from peripheral vein in the morning after an overnight fast, 2 ml blood samples were immediately transferred into a glass tube containing EDTA (lmg/ml) and aprotinin (0.6TIU/ml) and centrifuged, plasma samples were frozen and stored at -70 °C. Ghrelin was assayed by EIA at one time in 6 months. 4 ml blood samples were centrifuged immediately and serum samples were frozen and stored at -20 °C. GH and TNF were assayed by RIA at one time in 6 months.Following clinical data were recorded: sexuality, age, body mass index (BMI), left ventricular ejection fraction (LVEF). Causes and drug treatment of patients with CHF were also recorded.Results: (1) Body mass index in cachectic patients was significantly lower than those in noncachectic patients (P<0.05) and in control subjects(P<0.01), on the cause of CHF, NYHA functional class, LVEF, and medication there was no significantdifference between cachectic and noncachectic patients(P>0.05).(2) Plasma Ghrelin level did not significantly differ between all CHF patients and control subjects(P>0.05). However, plasma Ghrelin level in CHF patients with cachexia was significantly higher than that in CHF patients without cachexia (P<0.05) and in controis(P<0.05). Plasma Ghreiin level tended to increase with the severity of NYHA functional class, but there was no statistical significance(P>0.05).(3) GH level was also significantly higher in cachectic patients than those in CHF patients without cachexia (P<0.05) and in controls (P<0.05), there was no significant difference on serum GH level between all noncachectic patients and controls (P>0.05). No significant difference was observed on GH level between patients with NYHA function class II and in and control subjects (P>0.05), however, GH level of NYHA class IV patients was significantly higher than those in other subgroups of CHF patients (P<0.05) and controls (P<0.05).TNF level of CHF patients were significantly higher than that in the controls (P<0.05). TNF level in CHF patients with cachexia was significantly higher than that in CHF patients without cachexia (P<0.05) and in controls(P<0.01)(4) In patients with CHF, there was a negative correlative relationship between plasma Ghrelin level and body mass index (r=-0.35, P<0.01). In CHF patients with cardiac cachexia, there was no significant correlative relationship between plasma Ghrelin and LVEF. Modest correlative relationship was observed between plasma Ghrelin and serum GH (r=0.28, P<0.05). And there are significant correlative relationship between plasma Ghrelin and serum TNF (r=0.31, P<0.05).Conclusions: 1. Plasma Ghrelin level was significantly elevated in cachectic patients with CHF, and it was associated with the increase in serum GH and TNF and the decrease in body mass index. There was no significant difference on plasma Ghrelin level between all CHF patients and control subjects, it tended to increase with the severity of NYHA functional class, but no statistical difference was observed. Considering Ghrelin induced positive energy effects, increased Ghrelin in plasma may represent a compensatory mechanism under catabolic/anabolic imbalance in cachectic patients with CHF. Ghrelin had com- pensatory effect on cardiac dysfunction and cachexia by GH dependent and independent pathway, so Ghrelin is profit for patients with congestive heart failure.2. Circulating GH levels of NYHA IV group and CHF with cachexia group rose significantly, and that of CHF without cachexia group and control group had no significant difference, this may be the cause of acquired GH resistance.3. Circulating THF-a level of CHF with cachexia group rose significantly, indicating thatTHF-a take an important part in the development of cardiac cachexia.