Oxidative stress, inflammation and cardiovascular mortality in haemodialysis--role of seniority and intravenous ferrotherapy: analysis at 4 years of follow-up.

BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality in haemodialysis patients. The classic risk factors do not account for all cases of elevated cardiovascular disease in this patient population and it is becoming increasingly clear that other cardiovascular risk factors are implicated. The objective of this study was to analyse whether or not C-reactive protein (CRP) and plasma copper oxidized anti-lipoprotein (oxLDL) antibody titre are risk factors for cardiovascular mortality during 4 years of follow-up. METHODS: A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 48 months (July 1999-July 2003) (gender: 50 males and 44 females; mean age: 67+/-14 years). Eighty-four per cent of these patients were receiving intravenous erythropoietin and 63% were receiving intravenous ferrotherapy (iron gluconate). Basal markers of inflammation and oxidative stress were determined at the beginning of the study. CRP levels were determined by chemiluminescent enzyme-labelled immunometric assay. The oxLDL antibody titre was measured by enzyme-linked immunosorbent assay using native LDL and oxLDL as antigens. RESULTS: Fifty deaths occurred during the study, 66% (n = 33) of which were due to cardiovascular disease. Patients presented with basal CRP and oxLDL levels indicative of chronic inflammation and elevated oxidative stress CRP median: 5.16 mg/l (25-75% percentile: 0.35-88.7 mg/l); oxLDL antibodies median: 153 (optical density at 495 nm x 1000) (25-75% percentile: 112-214)]. A positive correlation was found between CRP and age (r = 0.33, P = 0.003). Study of the risk factors demonstrated that age (P = 0.007), oxLDL antibody titre (P = 0.04) and albumin (P = 0.02) were the only predictors of cardiovascular mortality at 4 years of follow-up in this patient population. The Cox proportional hazards model for cardiovascular mortality showed that of the markers studied, oxLDL antibody titre was an independent risk factor for cardiovascular mortality. CONCLUSIONS: Oxidative stress (oxLDL antibody titre) is one of the principal risk factors for cardiovascular mortality in this population of haemodialysis patients. Intravenous ferrotherapy, due to its pro-oxidant properties, probably favours oxidative stress. Serum concentration of CRP was not a good predictive factor of cardiovascular mortality during 4 years of follow-up, possibly because of the slight positive correlation that exists between CRP and age.