Hyperhomocysteinemia In Patients With Chronic Renal Failure And Its Role In Cardiovascular Disease Seen In The Patients

Background and Objective It is well known that patients withchronic renal failure (CRF), especially with end-stage renal disease (ESRD), have a high prevalence of cardiovascular disease. Despite the development and effectiveness of the dialysis in the prevention of the immediately fatal consequences of ESRD, the mortality still remains high among dialysis patients, and most of these deaths involve cardiac disease. Morbidity of atherosclerotic cardiovascular disease (AVD), such as cardiac infarction and stroke, in the dialysis patients is more 5~10 times higher than it is in the general population. The most common cause of death in ESRD patients with dialysis is of cardiovascular disease (about 50%), which is 10-20 times greater than it is in the general population. Traditional AVD risk factors, such as hypertension, glucose intolerance or diabetes, dyslipidemia and smoking, are widespread prevalent in CRF patients, but they do not totally explain the high AVD-specific morbidity and mortality in the CRF population. So it is very necessary that the risk factors for cardiac disease in CRF patients be identified. Homocysteine (Hey) is a sulfur-containing amino acid formed during the metabolism of methionine. Substantive investigations have confirmed that mortality for myocardial infarction and stroke in the people with elevatingplasma Hey concentration greatly exceeds in those with normal plasma Hey concentration. It has recently become clear that hyperhomocysteinemia is an independent risk factor for coronary artery heart disease, stroke and other AVD. Because people with CRF are at substantially increased mortality and morbidity compared with the general population, the relationship between hyperhomocysteinemia and AVD has arrested our attention.There are many differences in the distribution of the CRF patients' age, in the dominant protopathies and in races between China and the western countries. We do not know the plasma Hey concentration in Chinese CRF patients and its role in the pathogenesis of AVD yet. Our study aims at investigating hyperhomocysteinemia in the patients with CRF, its prevalence, etiology, potential relationship to atherosclerotic events and its role in the pathogenesis of cardiovascular disease seen in these patients.Methods 1. Patients: One hundred and ninety-seven patients withCRF (mean age 46.65 ± 12.91 years, 125 males, 72 females), 31 patients with coronary artery heart disease but no liver and kidney disorders (mean age 51.97 ± 7.71 years, 26 males, 5 females), and 53 healthy volunteers (mean age 48.87± 12.03 years, 28 males, 25 females) were involved in this study.2. Assay Procedures: Venous blood samples from all patients and control subjects were drawn into syringes in mornings after an overnight fast. Plasma or serum was isolated at 4 ℃ immediately and stored at - 70 ℃ until analysis. The concentration of plasma total homocysteine (tHcy) was determined by using fluorescence polarization immunoassay. Hyperhomocysteinemia is defined as a tHcy concentration greater than that of 95th percentile (mean+2SD) of levels in our healthy control subjects. Plasma malondialdehyde (MDA), representing lipid peroxidation level, was analyzed by thiobarbituric acid reaction. The activityof glutathione peroxidase (GSHPx) in plasma was measured by spectrophotometry. Serum C- reactive protein (CRP), interleukin? (IL ?6) and tumor necrosis factor?a (TNF?a ) were determined by enzyme linked immunosorbent assay (ELISA). Intima-medial thickness (IMT) of extracranial common carotid artery and the presence of atherosclerotic plaques was determined by using non-invasive high-resolution B-mode ultrasonography. The changes in brachial artery diameter during reactive hyperemia (Dh) and after administration of sublingual nitroglycerin (Dn), representing function of arterial vasodilation, were analyzed during ultrasonic examination.3. Cardiomyocyte Culture: For study the effect of Hey on myocardial protein and DNA synthesis, primary myocardial cells from Sprague-Dawle...