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Role of Inflammation and Malnutrition

Yongmei Liu, MD; Josef Coresh, MD, PhD; Joseph A. Eustace, MD, MHS; J. Craig Longenecker, MD, PhD; Bernard Jaar, MD, MPH; Nancy E. Fink, MPH; Russell P. Tracy, PhD; Neil R. Powe, MD, MPH, MBA; Michael J. Klag, MD, MPH

JAMA. 2004;291:451-459.

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 10 mg/L, or interleukin 6 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.

Author Affiliations: Johns Hopkins University, Baltimore, Md (Drs Liu, Coresh, Eustace, Longenecker, Jaar, Powe, and Klag and Ms Fink); Kuwait University, Kuwait (Dr Longenecker); and University of Vermont, Burlington (Dr Tracy).

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