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 mortalit y from atherosclerotic/atherothrombotic vascular disease (AVD). However, th e role of an elevated plasma total homocysteine (tHcy) level as a risk fact or is uncertain in ESRD. Methods: We enrolled 55 ESRD patients in a prospec tive follow-up study in order to evaluate the prognostic significance of th eir tHcy levels, common methylenetetrahydrofolate reductase (MTHFR) gene po lymorphism, and other atherosclerotic risk factors, in combination with the results of B mode ultrasound for carotid arteries. Results: Mean intima-me dia thickness of the common carotid artery (CCA-IMT) in ESRD patients was t hicker than that in 102 age- and sex-matched healthy controls. Carotid plaq ue was more frequently present in patients compared with controls, as was c alcified plaque more common in patients (p < 0.001). Plasma tHcy levels (me an +/- 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 determina nt of elevated tHcy levels in ESRD patients. During the followup period of 31 +/- 3 months, 14 patients had one or more AVD complications, and 10 cons equently 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), an d presence of diabetes mellitus (relative risk of 6.62, 95% Cl 1.07 +/- 40. 8) were independent predictors of future AVD events, and tHcy levels (relat ive risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% C l 1.15 - 3.83) were those of AVD mortality. We also found a significant ass ociation between carotid plaque prevalence and AVD events (chi (2) = 11.6, p = 0.001). Conclusion: Hyperhomocysteinemia, diabetes mellitus, and caroti d atherosclerosis appeared to contribute independently to increase the risk of AVD outcome in Japanese patients with ESRD.