Association Between Cholesterol Level and Mortality in Dialysis Patients: Role of Inflammation and Malnutrition

Abstract

CONTEXT: Total cholesterol level is inversely associated with mortality in dialysis patients, a group at high risk of cardiovascular disease (CVD). This paradox may be explained by systemic inflammation and/or malnutrition, which are associated with lower cholesterol levels and higher mortality. OBJECTIVE: To determine the relationship between cholesterol level and outcome in patients undergoing dialysis, accounting for inflammation and malnutrition. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 823 patients enrolled from October 1995 to June 1998 who recently initiated dialysis, from 79 clinics, classified by absence or presence of inflammation and/or malnutrition (defined as serum albumin levels <3.6 mg/dL, C-reactive protein > or =10 mg/L, or interleukin 6 > or =3.09 pg/mL). MAIN OUTCOME MEASURES: All-cause and cardiovascular disease mortality. RESULTS: During a median follow-up of 2.4 years, 324 deaths (159 CVD deaths), 153 renal transplantations, and 10 losses to follow-up occurred. Average serum cholesterol level was lower in the presence of inflammation/malnutrition than in its absence. In a Cox model adjusted for age, race, and sex, a 40-mg/dL (1.0-mmol/L) increment in baseline total serum cholesterol level was associated with a decreased risk of all-cause mortality overall (relative hazard [RH], 0.92; 95% confidence interval [CI], 0.87-0.98) and in the presence of inflammation/malnutrition (RH, 0.89; CI, 0.84-0.95). In contrast, serum cholesterol level was associated with an increased risk in the absence of inflammation/malnutrition (RH, 1.32; 95% CI, 1.07-1.63). For CVD mortality, an inverse trend was not statistically significant in the presence of inflammation/malnutrition, and a positive association was evident in the absence of inflammation/malnutrition (RH, 1.41; 95% CI, 1.04-1.89). Further adjustment for traditional CVD risk factors, dialysis modality, comorbidity, and inflammatory markers attenuated the inverse association but strengthened the positive association. CONCLUSIONS: The inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations. These findings support treatment of hypercholesterolemia in this population.