HYPERHOMOCYSTEINEMIA IS ASSOCIATED WITH ATHEROSCLEROTIC OCCLUSIVE ARTERIAL ACCIDENTS IN PREDIALYSIS CHRONIC-RENAL-FAILURE PATIENTS

Hyperhomocysteinemia has been shown to constitute an independent risk factor for premature occlusive arterial disease. Moderate hyperhomocys teinemia is present in chronic uremic patients, who often develop prem ature atherosclerosis, but no direct evidence of an association betwee n the occurrence of atherosclerotic cardiovascular accidents (CVAs) an d hyperhomocysteinemia has yet been reported in such patients. We seri ally determined total plasma homocysteine (Hey) levels in a cohort of 93 consecutive chronic renal failure, undialyzed patients (57 males, 3 6 females) with creatinine clearance (Ccr) <50 ml/min 1.73 m(2) and ag e greater than or equal to 50 years at start of follow-up, together wi th serial assessment of Ccr and blood lipid parameters. From January 1 989 to December 1995, 24 patients (group 1) experienced myocardial inf arction (18 cases, 13 males) or cerebral infarction (6 cases, 3 males) while the remaining 69 (group 2) remained free of CVAs. Patients in g roups 1 and 2 did not differ with respect to age (66 +/- 1.8 vs. 65 +/ - 1.1 years, mean +/- Se) or serum creatinine (227 +/- 24 vs. 251 +/- 36 mu mol/l) at onset of a CVA (group 1) or at the end of follow-up (g roup 2). The mean Hcy level was significantly higher in group 1 (20.7 +/- 1.6 vs. 12.8 +/- 0.5 mu mol/l, p < 0.0001), as was the proportion of patients with Hey in excess of 14 mu mol/l, the upper limit in heal thy controls (83 vs. 30%, p < 0.0001). Logistic regression analysis id entified Hey as an independent risk factor for CVA, with an odds ratio of 11.4 (95% confidence interval 3.5 - 37.7), which remained signific ant after adjustment on other variables. We conclude that an elevated Hey level is associated with a risk of occlusive arterial accidents in patients with chronic renal failure and that hyperhomocysteinemia con tributes to the accelerated atherosclerosis complicating chronic uremi a.