Association of Homocysteine and Asymmetric Dimethylarginine With Atherosclerosis and Cardiovascular Events in Maintenance Hemodialysis Patients

• DOI: 10.1053/j.ajkd.2006.08.003
• Publication Date: 2007-02-06T16:05:03Z
• Authors: Hiromichi Kumagai; Miyuki Sakurai; Takako Takita; Yukitaka Maruyama; Shuichi Uno; Naoki Ikegaya; Akihiko Kato; Akira Hishida
• Keywords: Male; Comorbidity; Middle Aged; Arginine; Atherosclerosis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cardiovascular Diseases; Renal Dialysis; Risk Factors; Humans; Kidney Failure, Chronic; Regression Analysis; Female; Nitric Oxide Synthase; Homocysteine; Proportional Hazards Models

Homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) recently were recognized as potential risk factors for atherosclerosis in the general population, and the metabolism of each of these substances seems to be closely related. This study investigates the association between these substances and whether elevated serum Hcy and ADMA levels are related to high risk for atherosclerosis and cardiovascular events in maintenance hemodialysis (HD) patients.A study was made of 197 HD patients (132 men, 65 women; mean age, 56.9 +/- 8.6 years) for the correlation between plasma total Hcy (tHcy) and ADMA concentrations and the association of these substances with atherosclerotic indices of cervical intima-media thickness, plaque diameter, aortic calcification index, and aortic elongation. Cardiovascular events were followed up for 5 years in these patients.Mean plasma tHcy (37.3 +/- 25.8 micromol/L) and ADMA (0.77 +/- 0.16 micromol/L) levels were significantly greater in HD patients than in healthy subjects. Plasma tHcy level did not correlate with plasma ADMA level (r = -0.1; P = not significant). Although ADMA level was associated significantly with atherosclerotic indices from a simple regression analysis, this association was less from multiple regression analysis. When patients were classified into 3 groups according to ADMA level, cardiovascular events during 5 years were significantly greater in the group with the highest ADMA levels than in the other groups, confirmed by using a Cox proportional hazard model. However, no association was found between tHcy levels and atherosclerotic indices or cardiovascular events.ADMA level emerged as a potential risk factor for cardiovascular events that might be mediated in part by atherosclerosis in HD patients. Conversely, neither high nor low plasma tHcy levels were associated with atherosclerotic indices and cardiovascular events. This result for our HD patients does not fulfill the terms of traditional epidemiology and paradoxical reverse epidemiology of Hcy.