Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease

Background-Retrospective and case-control studies show that hyperhomocysteinemia is an independent risk factor for atherosclerosis in patients with end-stage renal disease. We studied prospectively the association between total homocysteine and cardiovascular outcomes. Methods and Results-In all, 167 patients (93 men, 74 women; mean age, 56.3+/-14.7 years) were followed for a mean duration of 17.4+/-6.4 months. Cardiovascular events and causes of mortality were related to total homocysteine values and other cardiovascular risk factors. Cox regression analysis was used to identity the independent predictors for cardiovascular events and mortality. Fifty-five patients (33%) developed cardiovascular events and 31 (19%) died, 12 (8%) of cardiovascular causes. Total plasma homocysteine values ranged between 7.9 and 315.0 mu mol/L. Levels were higher in patients who had cardiovascular events or died of cardiovascular causes (43.0+/-48.6 versus 26.9+/-14.9 mu mol/L, P=.02). The relative risk (KR) for cardiovascular events, including death, increased 1% per mu mol/L increase in total homocysteine concentration (RR, 1.01; CI, 1.00 to 1.01: P=.01). Conclusions-These prospective observations confirm that hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease, with an increased RR of 1% per mu mol/L increase in total homocysteine concentration. Interventional studies are needed to evaluate the possible effects of modifying this risk factor in these patients.