Phospholipid plasmalogen, a surrogate marker of oxidative stress, is associated with increased cardiovascular mortality in patients on renal replacement therapy

Background. There is a high incidence of premature cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). Free radical-induced tissue damage. is thought to play a major role in the pathogenesis of atherosclerosis, and there are several reports indicating an increased oxidative stress in ESRD. However, it is not well established that increased oxidative stress predicts cardiovascular mortality in ESRD. Plasmalogens, a group of phospholipids with a vinyl ether bond in the sn-1 position, are considered to be sensitive markers of oxidative stress. Methods. Cardiovascular and non-cardiovascular mortality was recorded (follow-up time 1860 +/- 94 days) in 105 ESRD patients (mean age 51 +/- 2 years) in whom the fasting ratio of the erythrocyte levels of plasmalogens (DMA 16/C16:0 and DMA 18/C18:0) had been determined at the start of renal replacement therapy (RRT). The prevalence of malnutrition (subjective global assessment), diabetes mellitus (DM), smoking habits and CVD was also determined. Results. Thirty-eight patients who died of CVD (0.066 +/- 0.003) had a significantly lower DMA 16/C16:0 ratio than 15 patients who died of non-cardiovascular causes (0.078 +/- 0.005; P < 0.05) and 52 patients alive at follow-up (0.075 +/- 0.003; P < 0.05). A Cox proportional hazard model analysis showed that a low (< median) DMA 16/C16:0 ratio at the start of RRT was associated (relative risk 1.50; confidence interval 1.07-2.16; P < 0.05) with CVD mortality independently of age, gender, DM and CVD. Conclusion. These results suggest that increased oxidative stress may be a risk factor for cardiovascular mortality in ESRD.