Time-dependent lipid profile inversely associates with mortality in hemodialysis patients - independent of inflammation/malnutrition.
albumin
cholesterol
chronic kidney disease
haemodialysis
inflammation
lipid profile
mortality
Journal
Journal of internal medicine
ISSN: 1365-2796
Titre abrégé: J Intern Med
Pays: England
ID NLM: 8904841
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
02
02
2021
received:
22
11
2020
accepted:
18
02
2021
pubmed:
18
5
2021
medline:
19
2
2022
entrez:
17
5
2021
Statut:
ppublish
Résumé
Patients with end-stage kidney disease have an extremely high cardiovascular mortality rate, but there is a paradoxical relationship between lipid profile and survival in haemodialysis patients. To investigate whether inflammation/malnutrition confounds the associations between lipids and mortality, we studied a full lipid profile comprising of five clinically well-established lipid parameters and its associations with mortality in a large, multinational European cohort with a median follow-up >3 years. The association between quartiles of total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, as well as triglyceride, levels and the end-points of all-cause, cardiovascular and non-cardiovascular mortality was assessed in a cohort of 5,382 incident, adult haemodialysis patients from >250 Fresenius Medical Care dialysis centres out of 14 participating countries using baseline and time-dependent Cox models. Analyses were fully adjusted and stratified for inflammation/malnutrition status and other patient-level variables. Time-dependent quartiles of total, HDL, non-HDL and LDL cholesterol were inversely associated with the hazard for all-cause, cardiovascular and non-cardiovascular mortality. Compared with the lowest quartile of the respective lipid parameter, hazard ratios of other quartiles were <0.86. Similar, albeit weaker, associations were found with baseline lipid profile and mortality. Neither time-dependent nor baseline associations between lipid profile and mortality were affected by inflammation/malnutrition, statin use or geography. Baseline and time-dependent lipid profile are inversely associated with mortality in a large, multicentre cohort of incident haemodialysis patients. Inflammation/malnutrition is not a confounder nor effect modificator of the associations between lipid profile and mortality in European haemodialysis patients.
Sections du résumé
BACKGROUND
Patients with end-stage kidney disease have an extremely high cardiovascular mortality rate, but there is a paradoxical relationship between lipid profile and survival in haemodialysis patients. To investigate whether inflammation/malnutrition confounds the associations between lipids and mortality, we studied a full lipid profile comprising of five clinically well-established lipid parameters and its associations with mortality in a large, multinational European cohort with a median follow-up >3 years.
METHODS
The association between quartiles of total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, as well as triglyceride, levels and the end-points of all-cause, cardiovascular and non-cardiovascular mortality was assessed in a cohort of 5,382 incident, adult haemodialysis patients from >250 Fresenius Medical Care dialysis centres out of 14 participating countries using baseline and time-dependent Cox models. Analyses were fully adjusted and stratified for inflammation/malnutrition status and other patient-level variables.
RESULTS
Time-dependent quartiles of total, HDL, non-HDL and LDL cholesterol were inversely associated with the hazard for all-cause, cardiovascular and non-cardiovascular mortality. Compared with the lowest quartile of the respective lipid parameter, hazard ratios of other quartiles were <0.86. Similar, albeit weaker, associations were found with baseline lipid profile and mortality. Neither time-dependent nor baseline associations between lipid profile and mortality were affected by inflammation/malnutrition, statin use or geography.
CONCLUSIONS
Baseline and time-dependent lipid profile are inversely associated with mortality in a large, multicentre cohort of incident haemodialysis patients. Inflammation/malnutrition is not a confounder nor effect modificator of the associations between lipid profile and mortality in European haemodialysis patients.
Substances chimiques
Cholesterol, HDL
0
Cholesterol, LDL
0
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
910-921Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
Références
Ebert T, Pawelzik SC, Witasp A, Arefin S, Hobson S, Kublickiene K. Inflammation and premature ageing in chronic kidney disease. Toxins. 2020;12: 4:227. http://dx.doi.org/10.3390/toxins12040227
Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073-81.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296-305.
Bikbov B, Purcell CA, Levey AS, Smith M, Abdoli A, Abebe M, et al. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2020;395:709-33.
Anon US. Renal data system 2018 annual data report: Epidemiology of kidney disease in the United States. Am J Kidney Dis. 2019;73:S1-772.
Anon. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. The Lancet. 2007;370:1829-39.
Liu J, Zeng F-F, Liu Z-M, Zhang C-X, Ling W, Chen Y-M. Effects of blood triglycerides on cardiovascular and all-cause mortality: a systematic review and meta-analysis of 61 prospective studies. Lipids Health Dis. 2013;12:159.
Navarese EP, Robinson JG, Kowalewski M, Kolodziejczak M, Andreotti F, Bliden K, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: A systematic review and meta-analysis. JAMA. 2018;319:1566-79.
Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int. 2002;61:1887-93.
Chmielewski M, Carrero JJ, Qureshi AR, Axelsson J, Heimbürger O, Berglund L, et al. Temporal discrepancies in the association between the apoB/apoA-I ratio and mortality in incident dialysis patients. J Intern Med. 2009;265:708-16.
Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis. The Lancet. 2000;356:930-3.
Kalantar-Zadeh K, Horwich TB, Oreopoulos A, Kovesdy CP, Younessi H, Anker SD, et al. Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care. 2007;10:433-42.
Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73:391-8.
Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink NE, et al. Association between cholesterol level and mortality in dialysis patients: Role of inflammation and malnutrition. JAMA. 2004;291:451-9.
Steil H, Amato C, Carioni C, Kirchgessner J, Marcelli D, Mitteregger A, et al. EuCliD® - A medical registry. Methods Inf Med. 2004;43:83-8.
de Francisco ALM, Kim J, Anker SD, Belozeroff V, Canaud B, Chazot C, et al. An epidemiological study of hemodialysis patients based on the European fresenius medical care hemodialysis network: Results of the ARO study. Nephron Clin Pract. 2011;118:c143-c154.
Floege J, Gillespie IA, Kronenberg F, Anker SD, Gioni I, Richards S, et al. Development and validation of a predictive mortality risk score from a European hemodialysis cohort. Kidney Int. 2015;87:996-1008.
Ducloux D, Klein A, Kazory A, Devillard N, Chalopin J-M. Impact of malnutrition-inflammation on the association between homocysteine and mortality. Kidney Int. 2006;69:331-5.
Lin-Tan D-T, Lin J-L, Wang L-H, Wang L-M, Huang L-M, Liu L, et al. Fasting glucose levels in predicting 1-year all-cause mortality in patients who do not have diabetes and are on maintenance hemodialysis. J Am Soc Nephrol. 2007;18:2385-91.
Sniderman AD, Blank D, Zakarian R, Bergeron J, Frohlich J. Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula. Clin Biochem. 2003;36:499-504.
Tremblay AJ, Morrissette H, Gagné J-M, Bergeron J, Gagné C, Couture P. Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with β-quantification in a large population. Clin Biochem. 2004;37:785-90.
White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011;30:377-99.
Eckardt K-U, Gillespie IA, Kronenberg F, Richards S, Stenvinkel P, Anker SD, et al. High cardiovascular event rates occur within the first weeks of starting hemodialysis. Kidney Int. 2015;88:1117-25.
Chang TI, Streja E, Ko GJ, Naderi N, Rhee CM, Kovesdy CP, et al. Inverse association between serum non-high-density lipoprotein cholesterol levels and mortality in patients undergoing incident hemodialysis. J Am Heart Assoc. 2018;7:e009096.
Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: Effects of case mix and the malnutrition-inflammation-cachexia syndrome. J Am Soc Nephrol. 2007;18:304-11.
Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69:239-41.
Storey BC, Staplin N, Haynes R, Reith C, Emberson J, Herrington WG, et al. Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation. Kidney Int. 2018;93:1000-7.
Baigent C, Landray MJ, Wheeler DC. Cardiovascular and survival paradoxes in dialysis patients: Misleading associations between cholesterol and vascular outcomes in dialysis patients: The need for randomized trials. Semin Dial. 2007;20:498-503.
Wanner C, Krane V, März W, Olschewski M, Mann JFE, Ruf G, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238-48.
Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395-407.
Ferro CJ, Mark PB, Kanbay M, Sarafidis P, Heine GH, Rossignol P, et al. Lipid management in patients with chronic kidney disease. Nat Rev Nephrol. 2018;14:727-49.
Feingold KR, Grunfeld C. Lipoproteins: Are they important components of host defense? Hepatology. 1997;26:1685-6.
Speer T, Zewinger S, Fliser D. Uraemic dyslipidaemia revisited: role of high-density lipoprotein. Nephrol Dial Transplant. 2013;28:2456-63.
Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. The Lancet. 2011;377:2181-92.
Contreras G, Hu B, Astor BC, Greene T, Erlinger T, Kusek JW, et al. Malnutrition-inflammation modifies the relationship of cholesterol with cardiovascular disease. J Am Soc Nephrol. 2010;21:2131-42.
Moradi H, Streja E, Kashyap ML, Vaziri ND, Fonarow GC, Kalantar-Zadeh K. Elevated high-density lipoprotein cholesterol and cardiovascular mortality in maintenance hemodialysis patients. Nephrol Dial Transplant. 2014;29:1554-62.
Kaysen GA, Ye X, Raimann JG, Wang Y, Topping A, Usvyat LA, et al. Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results. J Lipid Res. 2018;59:1519-28.
Kilpatrick RD, McAllister CJ, Kovesdy CP, Derose SF, Kopple JD, Kalantar-Zadeh K. Association between serum lipids and survival in hemodialysis patients and impact of race. J Am Soc Nephrol. 2007;18:293-303.
Wanner C, Tonelli M, Cass A. KDIGO clinical practice guideline for lipid management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. 2014;85:1303-9.
Miller WG, Myers GL, Sakurabayashi I, Bachmann LM, Caudill SP, Dziekonski A, et al. Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures. Clin Chem. 2010;56:977-86.