動脈硬化の成因と診断をめぐって(2)

透析患者における動脈硬化の危険因子
−コレステロール逆転送系と高ホモシステイン血症に注目して−

木　村　秀　樹*1　吉　田　治　義*2
　　　　　　　　　　　　　　　　　　　　　　
Risk Factors for Atherosclerotic Vascular Disease in Patients
on Maintenance Hemodialysis−with Especial Respect to Reverse
Cholesterol Transport System and Hyperhomocysteinemia−

Hideki KIMURA, MD*1 and Haruyoshi YOSHIDA, MD*2

Hemodialysis(HD) patients have a high mortality rate due to vascular disease(VD). Therefore, we investigated the effect of uremic dyslipidemia on VD in HD patients, with special consideration of the reverse cholesterol transport(RCT) system including high-density-lipoprotein cholesterol(HDL-C), cholesteryl ester transfer protein(CETP) and its genetic(D442G) mutation. In 414 HD patients, a sub-median HDL-C level(＜48mg/dl) was an independent risk factor for VD. In the lower HDL-C status, the CETP mutation leading to CETP levels was independently associated with VD. In 210 selected patients, the CETP level was an independent protective factor against VD among those with higher HDL-C levels(＞45mg/dl).
We also measured serum homocysteine(Hcy) levels and examined its association with VD considering that hyperhomocysteinemia is a newly identified risk factor for atheroma. HD Patients(n＝545) had about 3 times the Hcy levels of the general population. A common C677T mutation in the gene of methylenetetrahydrofolate reductase(MTHFR) involved in Hcy metabolism was independently and directly related to serum Hcy levels with TT genotype patients having the highest levels. Patients with the TT genotype were younger and had a shorter duration of dialysis than those with the CT or CC genotype after adjustment for age at the initiation of dialysis, although there was no difference in VD prevalence among the genotypes and no association between Hcy levels and VD prevalence.
In conclusion, lower HDL-C and CETP status was a risk factor for VD in HD patients, suggesting the importance of RCT. Serum Hcy levels were markedly increased in HD patients and the TT genotype may be associated with higher mortality. However, a large-scale prospective study is required to clarify whether hyperhomocysteinemia or the TT genotype is a VD risk factor among HD patients.
[Rinsho Byori 50 : 793〜801, 2002]

*1Department of Clinical Laboratory Medicine and Nephrology, Faculty of Medicine, Fukui Medical Uni-versity, Yoshida-gun, Fukui-pref. 910-1194

【Key Words】hemodialysis patients(血液透析患者)，HDL-C，cholesteryl ester transfer protein(コレステリルエステル転送蛋白)，homocysteine(ホモシステイン)，MTHFR C677T mutation(メチレン 4 水素葉酸還元酵素 C677T 変異)

*1,2福井医科大学医学部臨床検査医学(腎臓内科) (〒910-1194 福井県吉田郡松岡町下合月23)

E-mail :nkimura@fmsrsa.fukui-med.ac.jp