Cardiovascular morbidity and endothelial dysfunction in chronic haemodialysis patients: is homocyst(e)ine the missing link?

Background. Haemodialysis patients exhibit an excessive burden of atherothr ombotic disease, which is not explained adequately by traditional risk fact ors. Hyperhomocyst(e) inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e) i naemia is associated with cardiovascular complications in dialysed patients . Methods, In a cohort of 63 stable chronic haemodialysis patients, we examin ed the causal relationship between hyperhomocyst (e)inaemia and vascular en dothelial and haemostatic function. All their markers were determined befor e and after an X-week course of a 10 mg per day oral folate supplementation , a manoeuvre known to decrease hyperhomocyst(e) inaemia in uraemic patient s. Results. History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence o f vascular calcifications in 70%; Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P < 0.001), despite the lack of clinical and biological evidence of malnutrition. Fibri nogen, von Willebrand factor and plasminogen activator inhibitor type 1, bu t not endothelin I, were significantly higher in haemodialysis patients tha n in controls. After adjustment for all variables, past history of cardiova scular events was independently associated with higher levels of homocyst(e )inaemia only (odds ratio (OR) 1.06; 95% confidence interval(CT) 1.01-1.12; P < 0.026). The presence of aortic calcifications was independently and si gnificantly associated with age(OR 1.37; 95% CI 1.07-1.75; P < 0.025), homo cyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P < 0.05) and fibrinogen concent ration only (OR 9.74; 95% CI 1.25-75.2; P < 0.05). None of the endothelial- haemostatic factors was, however, related to homocyst(e)ine levels. Mid-ter m folate supplementation decreased plasma homocyst(e)ine levels significant ly without achieving normal values. No significant change of endothelial-ha emostatic markers was observed, however, despite the drop in plasma homocys t(e)ine. Conclusions. Hyperhomocyst(e)inaemia is associated with increased cardiovas cular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst (e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be deter mined in prospective trials.