Myeloperoxidase (MPO), which is secreted during activation of neutrophils, may serve as one mechanistic link among persistent inflammation, oxidative stress, and cardiovascular disease. This study related MPO activity to inflammatory and oxidative stress biomarkers, comorbidity, and ongoing medication in prevalent hemodialysis (HD) patients. In a cross-sectional evaluation of 115 prevalent (vintage 25 mo) HD patients (62 men; 63 +/- 1 yr), data on comorbidity (Davies score), diabetes, medication (statins and antihypertensive drugs), nutritional status (subjective global assessment), blood lipids (cholesterol, HDL cholesterol, and triglycerides), inflammatory biomarkers (serum albumin, C-reactive protein, TNF-alpha, and IL-6), oxidative stress biomarkers (pentosidine, 8-hydroxydeoxyguanosine, and MPO activity) were recorded. Patients with MPO activity greater than the median had significantly (P < 0.05) lower serum albumin levels (33.2 +/- 0.7 versus 35.0 +/- 0.5 g/L), higher 8-hydroxydeoxyguanosine levels (1.26 +/- 0.08 versus 1.05 +/- 0.06 ng/ml), and a lower prevalence of statin treatment (18 versus 36%). Therefore, the median MPO activity was significantly (P < 0.05) lower (17.7 versus 26.6 deltaOD630/min per mg protein) in the subgroup of 31 HD patients with ongoing statin treatment. In a multiple regression model, correction for the impact of age, gender, vintage, serum cholesterol, serum albumin, comorbidity, diabetes, and statin use, only diabetes (P < 0.01) and statin use (P < 0.01) were significantly associated to MPO activity. Fourteen patients who had diabetes and were receiving statin treatment had markedly (P = 0.001) lower median (19.9 versus 41.2 deltaOD630/min per mg protein) MPO activity compared with 18 who had diabetes and were not taking statins. This cross-sectional study suggests that both diabetes and statin treatment affect MPO activity in prevalent HD patients.