George A Kaysen1, Barbara Grimes2, Lorien S Dalrymple3, Glenn M Chertow4, Julie H Ishida5, Cynthia Delgado5, Mark Segal2, Janet Chiang6, Tjien Dwyer7, Kirsten L Johansen8. 1. Division of Nephrology, Department of Medicine, University of California Davis School of Medicine, Davis, CA, USA; Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA, USA. Electronic address: gakaysen@ucdavis.edu. 2. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. 3. Fresenius Medical Care North America, Waltham, MA, USA. 4. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. 5. Division of Nephrology, Department of Medicine, University of California, San Francisco, CA, USA; Nephrology Section, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. 6. Endocrinology Section, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Division of Endocrinology, Department of Medicine, University of California, San Francisco, CA, USA. 7. Division of Nephrology, Department of Medicine, University of California Davis School of Medicine, Davis, CA, USA. 8. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; Division of Nephrology, Department of Medicine, University of California, San Francisco, CA, USA; Nephrology Section, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
Abstract
BACKGROUND: In hemodialysis (HD) patients, higher lipid levels are associated with lower mortality. Lipid-lowering therapy does not reduce all-cause mortality or cardiovascular (CV) mortality. Lipoproteins play a role in the innate immune system. Our objective was to determine whether protection from infection might counterbalance adverse CV outcomes associated with lipoproteins. METHODS: We examined associations between serum apolipoprotein (Apo) A1, B, C2, C3, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol and triglyceride levels and infectious mortality or hospitalization, CV mortality or hospitalization, and all-cause mortality in 433 prevalent HD patients. Cox models with time-varying apolipoprotein concentrations collected every 6 months for up to 2 years were used for analyses. RESULTS: Median follow-up time for all-cause mortality was 2.7 years (25th-75th percentile range: 2.2-3.4 years). One hundred seventy-nine (41%) patients had an infection-related event. In multivariable models, higher Apo B and LDL were associated with lower risks of infection-related outcomes (hazard ratio Apo B 0.92 [95% confidence interval 0.86-0.99 per 10 mg/dL, P = .03]; hazard ratio LDL 0.93 [95% confidence interval 0.87-1.00 per 10 mg/dL, P = .05]). Sixty-three (15%) participants had a CV-related event. No significant associations were observed between lipoproteins and CV outcomes. Eighty-seven (20%) participants died. Higher Apo A1, Apo B, and Apo C3 were associated with lower risks of all-cause mortality. There was no interaction between the use of lipid-lowering medication and any of the outcomes. CONCLUSION: Associations of lipoproteins with lower risk of serious infection accompanied by no significant association with CV events may help to explain the paradoxical association between lipids and survival and lack of benefit of lipid-lowering therapies in HD.
BACKGROUND: In hemodialysis (HD) patients, higher lipid levels are associated with lower mortality. Lipid-lowering therapy does not reduce all-cause mortality or cardiovascular (CV) mortality. Lipoproteins play a role in the innate immune system. Our objective was to determine whether protection from infection might counterbalance adverse CV outcomes associated with lipoproteins. METHODS: We examined associations between serum apolipoprotein (Apo) A1, B, C2, C3, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol and triglyceride levels and infectious mortality or hospitalization, CV mortality or hospitalization, and all-cause mortality in 433 prevalent HDpatients. Cox models with time-varying apolipoprotein concentrations collected every 6 months for up to 2 years were used for analyses. RESULTS: Median follow-up time for all-cause mortality was 2.7 years (25th-75th percentile range: 2.2-3.4 years). One hundred seventy-nine (41%) patients had an infection-related event. In multivariable models, higher Apo B and LDL were associated with lower risks of infection-related outcomes (hazard ratio Apo B 0.92 [95% confidence interval 0.86-0.99 per 10 mg/dL, P = .03]; hazard ratio LDL 0.93 [95% confidence interval 0.87-1.00 per 10 mg/dL, P = .05]). Sixty-three (15%) participants had a CV-related event. No significant associations were observed between lipoproteins and CV outcomes. Eighty-seven (20%) participants died. Higher Apo A1, Apo B, and Apo C3 were associated with lower risks of all-cause mortality. There was no interaction between the use of lipid-lowering medication and any of the outcomes. CONCLUSION: Associations of lipoproteins with lower risk of serious infection accompanied by no significant association with CV events may help to explain the paradoxical association between lipids and survival and lack of benefit of lipid-lowering therapies in HD.
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