Original ArticleAssociations of lipoproteins with cardiovascular and infection-related outcomes in patients receiving hemodialysis
Introduction
Cardiovascular (CV) and infection-related events are the 2 leading causes of death among patients with end-stage renal disease (ESRD) receiving hemodialysis (HD).1, 2 By the United States Renal Data System (USRDS) estimates, CV mortality and CV events have stabilized, but the rates of infection-related hospitalization and death have increased.3 Total and low-density lipoprotein (LDL) cholesterol concentrations are associated with CV mortality among persons over age 50 years in the general population, but the associations between these lipoproteins and outcomes in individuals with ESRD are less certain,4 and mortality is actually higher among ESRD patients who have lower serum total cholesterol concentrations compared to those with higher serum cholesterol concentrations,5, 6, 7 Moreover, randomized controlled trials lowering LDL cholesterol concentrations in patients receiving HD have neither enhanced survival nor reduced the incidence of major CV events8, 9, 10 and have had no significant effect on all-cause mortality or CV mortality,10 suggesting that the paradigm linking lipoproteins and mortality operative in the general population may be altered in the setting of ESRD.
Lipoproteins and other protein constituents that compose lipoproteins are now understood to play roles in the innate immune system,11, 12, 13, 14, 15, 16 providing a potential mechanism for protection against leading causes of morbidity and mortality in a population with high risk of infection. To explore this hypothesis, we examined associations among serum lipoprotein concentrations and CV and infection-related outcomes in a prevalent HD cohort. We also examined all-cause mortality to determine whether any infection-related benefit observed among patients with higher lipoprotein concentrations was offset by adverse CV effects.
Section snippets
Materials and methods
The ACTIVE/ADIPOSE (A Cohort Study to Investigate the Value of Exercise in ESRD/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) study enrolled 771 prevalent HD patients who had been receiving HD for at least 3 months from 14 centers in the San Francisco CA and Atlanta GA metropolitan areas from June 2009 through August 2011.17 The study was approved by the institutional review boards at the University of California, San Francisco, and at Emory University. All
Patient characteristics
Median or mean values for each parameter are presented in Table 1. The mean age was 56.6 years, 41.1% were women, 15.9% were white, and 53.6% had diabetes. During follow-up, 63 (15%) participants had a CV-related event, 179 (41%) had an infection-related event, and 87 (20%) died. The median follow-up time for all-cause mortality was 2.7 years (25th–75th percentile range 2.2−3.4 years). Patients prescribed lipid-lowering medication had significantly lower LDL cholesterol (64.9 ± 28.7 vs
Discussion
The 2 leading causes of death and hospitalization in patients on maintenance HD are related to CV disease and infection,1, 2 and we hypothesized that higher lipoprotein concentrations might provide protection from infection, which might offset potential adverse CV effects. We found that higher concentrations of some lipoproteins, specifically LDL and its associated apolipoprotein, Apo B, were associated with lower risk of infection-related outcomes. In contrast to data from the general
Acknowledgments
This work was supported by funding from the National Institutes for Diabetes and Digestive and Kidney Diseases to Dr. Johansen (R01 DK107269 and K24 DK085153) and Dr. Ishida (K23DK103963) and from the Department of Veterans Affairs fellowship support to Dr. Chiang and Clinical Science Research and Development Program (Career Development Award 1IK2CX000527) to Dr. Delgado.
The data reported here have been supplied in part by the United States Renal Data System (USRDS). The interpretation and
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None of the authors have a conflict of interest.