Hyperhomocysteinemia Confers an Independent Increased Risk of Atherosclerosis in End-Stage Renal Disease and Is Closely Linked to Plasma Folate and Pyridoxine Concentrations

Abstract

Background A high level of total plasma homocysteine is a risk factor for atherosclerosis, which is an important cause of death in renal failure. We evaluated the role of this as a risk factor for vascular complications of end-stage renal disease. Methods and Results Total fasting plasma homocysteine and other risk factors were documented in 176 dialysis patients (97 men, 79 women; mean age, 56.3±14.8 years). Folate, vitamin B ₁₂ , and pyridoxal phosphate concentrations were also determined. The prevalence of high total homocysteine values was determined by comparison with a normal reference population, and the risk of associated vascular complications was estimated by multiple logistic regression. Total homocysteine concentration was higher in patients than in the normal population (26.6±1.5 versus 10.1±1.7 μmol/L; P <.01). Abnormally high concentrations (>95th percentile for control subjects, 16.3 μmol/L) were seen in 149 patients (85%) with end-stage renal disease ( P <.001). Patients with a homocysteine concentration in the upper two quintiles (>27.8 μmol/L) had an independent odds ratio of 2.9 (CI, 1.4 to 5.8; P =.007) of vascular complications. B vitamin levels were lower in patients with vascular complications than in those without. Vitamin B ₆ deficiency was more frequent in patients than in the normal reference population (18% versus 2%; P <.01). Conclusions A high total plasma homocysteine concentration is an independent risk factor for atherosclerotic complications of end-stage renal disease. Such patients may benefit from higher doses of B vitamins than those currently recommended.