Maintenance hemodialysis patients in the United States have a high prevalence (approximately 80%) of systolic hypertension and a high mortality (approximately 20% per year). Some reports indicate a paradoxical association between hypertension and mortality in hemodialysis patients (ie, a normal to low blood pressure is associated with poor outcome), whereas high pressure confers survival advantages, a phenomenon referred to as "reverse epidemiology." We hypothesized that malnutrition-inflammation complex syndrome may be a cause of this paradoxical association. We studied a 15-month cohort of 40 933 hemodialysis patients in the United States whose predialysis and postdialysis blood pressure values were recorded routinely during each hemodialysis treatment. Patients were 59.8+/-15.3 years old; 54% were women and 46% diabetics. Cox proportional hazard models were used for blood pressure categories (systolic <110, > or =190 mm Hg; diastolic <50, > or =110; and increments of 10 mm Hg in between). Unadjusted, case-mix and dialysis dose-adjusted, and additional malnutrition-inflammation-adjusted hazard ratios of all-cause and cardiovascular death showed progressively increasing all-cause and cardiovascular death risk for decreasing blood pressure values. The lowest mortality was associated with predialysis systolic pressure of 160 to 189 mm Hg, whereas normal to low predialysis pressure values were associated with significantly increased mortality. Adjustment for the malnutrition-inflammation mitigated only a small portion of paradoxical associations between the low blood pressure and mortality. Predialysis systolic hypertension remained a significant predictor of highest all-cause and cardiovascular survival rate. Although these associations may not be causal, they call into question whether treatment goals for the general population can be applied to dialysis patients or other similar populations.