Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition

JAMA. 2004 Jan 28;291(4):451-9. doi: 10.1001/jama.291.4.451.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / mortality
  • Cause of Death
  • Cholesterol / blood*
  • Female
  • Humans
  • Hypercholesterolemia
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Male
  • Malnutrition / blood*
  • Middle Aged
  • Nutritional Status
  • Proportional Hazards Models
  • Prospective Studies
  • Renal Dialysis / mortality*
  • Risk Factors
  • Serum Albumin / metabolism


  • Inflammation Mediators
  • Interleukin-6
  • Serum Albumin
  • C-Reactive Protein
  • Cholesterol