Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: A prospective study

Renal transplant recipients have disproportionately high rates of arteriosclerotic outcomes, and recent studies provided controlled evidence that clinically stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, Few studies suggest that hyperhomocysteinemia may be a cardiovascular risk factor in renal transplant recipients. In the study presented here, the association between atherosclerotic events and homocysteine concentrations was examined in 207 stable renal transplant recipients. The role of hyperhomocysteinemia was analyzed with respect to other known cardiovascular risk factors. The mean follow-up was 21.2 +/- 1.9 mo (range, 14 to 26). Mean total homocysteine (tHcy) was 21.1 +/- 9.5 mu mol/L and median concentration was 19 mu mol/L. Seventy percent of patients (n = 153) were hyperhomocysteinemic (values >15 mu mol/L). tHcy correlated negatively with folate concentration (r = -0.3; P < 0.01). tHcy was closely related to creatinine concentration (r = 0.54; P < 0.001). Cardiovascular disease events (CVE) including death were observed in 30 patients (14.5%; 7.34 events per 1000 person-months of follow-up). Fasting tHcy values were higher in patients who experienced CVE (31.5 +/- 10.3 versus 17.8 +/- 7.5; P < 0.001). Cox regression analysis showed that tHcy was a risk factor for cardiovascular complications (relative risk [RR] 1.06; 95% confidence interval (95% CI), 1.04 to 1.09; P < 0.0001). This corresponds to an increase in RR for CVE of 6% per mu mol/L increase in tHcy concentration. Age (RR 1.55; 95% CI, 1.09 to 2.19; P < 0.01) and creatinine concentration (RR 1.34; 95% CI, 1.08 to 1.66; P < 0.01) were also independent predictors for CVE. This study demonstrates that elevated fasting tHcy is an independent risk factor for the development of CVE in chronic stable renal transplant recipients. Randomized, placebo-controlled homocysteine studies of the effect of tHcy lowering on CVE rates are urgently required in this patient population.