Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis independently increase atherosclerotic vascular disease outcome in Japanese patients with end-stage renal disease.
BACKGROUND
Patients with end-stage renal disease (ESRD) have high mortality from atherosclerotic/atherothrombotic vascular disease (AVD). However, the role of an elevated plasma total homocysteine (tHcy) level as a risk factor is uncertain in ESRD.


METHODS
We enrolled 55 ESRD patients in a prospective follow-up study in order to evaluate the prognostic significance of their tHcy levels, common methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and other atherosclerotic risk factors, in combination with the results of B mode ultrasound for carotid arteries.


RESULTS
Mean intima-media thickness of the common carotid artery (CCA-IMT) in ESRD patients was thicker than that in 102 age- and sex-matched healthy controls. Carotid plaque was more frequently present in patients compared with controls, as was calcified plaque more common in patients (p < 0.001). Plasma tHcy levels (mean +/- SD) in patients (39.1 +/- 27.2 nmol/ml) were higher than that (8.8 +/- 2.7 nmol/ml) in controls (p < 0.001). Folic acid was the major determinant of elevated tHcy levels in ESRD patients. During the follow-up period of 31 +/- 3 months, 14 patients had one or more AVD complications, and 10 consequently died from AVD causes. Proportional hazards modeling showed that 5-year intervals of age (relative risk of 2.95, 95% CI 1.62 - 5.37), 10 nmol/ml intervals of tHcy levels (relative risk of 2.31, 95% CI 1.31 - 4.08), and presence of diabetes mellitus (relative risk of 6.62, 95% CI 1.07 +/- 40.8) were independent predictors of future AVD events, and tHcy levels (relative risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% CI 1.15 - 3.83) were those of AVD mortality. We also found a significant association between carotid plaque prevalence and AVD events (X(2) = 11.6, p = 0.001).


CONCLUSIONS
Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis appeared to contribute independently to increase the risk of AVD outcome in Japanese patients with ESRD.
Haraki
T
T
Department of Internal Medicine, Fukui Prefectural Hospital, Japan. tatsuo.h@p2242.nsk.ne.jp
Takegoshi
T
T
Kitoh
C
C
Kajinami
K
K
Wakasugi
T
T
Hirai
J
J
Shimada
T
T
Kawashiri
M
M
Inazu
A
A
Koizumi
J
J
Mabuchi
H
H
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology* / Q000401:mortality; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000150:complications* / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D048909:Diabetes Complications; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D007564:Japan / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D014463:Ultrasonography
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)