Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients.
ESKD
PCSK9
cardiovascular
clinical outcomes
dialysis
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
11 May 2024
11 May 2024
Historique:
revised:
05
04
2024
received:
11
01
2024
accepted:
11
04
2024
medline:
11
5
2024
pubmed:
11
5
2024
entrez:
11
5
2024
Statut:
aheadofprint
Résumé
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies. The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis. During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HR PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.
Sections du résumé
BACKGROUND
BACKGROUND
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies.
METHODS
METHODS
The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis.
RESULTS
RESULTS
During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HR
CONCLUSIONS
CONCLUSIONS
PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14235Informations de copyright
© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.
Références
Zoccali C, Mallamaci F, Adamczak M, et al. Cardiovascular complications in chronic kidney disease: a review from the European renal and cardiovascular medicine working Group of the European Renal Association. Cardiovasc Res. 2023;00:1‐16. doi:10.1093/cvr/cvad083
Ference BA, Ginsberg HN, Graham I, et al. Low‐density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel. Eur Heart J. 2017;38(32):2459‐2472. doi:10.1093/EURHEARTJ/EHX144
De Nicola L, Provenzano M, Chiodini P, et al. Prognostic role of LDL cholesterol in non‐dialysis chronic kidney disease: multicenter prospective study in Italy. Nutr Metab Cardiovasc Dis. 2015;25(8):756‐762. doi:10.1016/j.numecd.2015.04.001
Liu Y, Coresh J, Eustace JA, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA. 2004;291(4):451. doi:10.1001/jama.291.4.451
Webster A, Palmer S, Ruospo M, Strippoli GFM. Statins for end‐stage kidney disease treated with dialysis. Nephrol Ther. 2015;20(4):302‐303. doi:10.1111/nep.12435
Wanner C, Tonelli M. KDIGO clinical practice guideline for lipid management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. 2014;85(6):1303‐1309. doi:10.1038/KI.2014.31
Gu HM, Zhang DW. Hypercholesterolemia, low density lipoprotein receptor and proprotein convertase subtilisin/kexin‐type 9. J Biomed Res. 2015;29(5):356‐361. doi:10.7555/JBR.29.20150067
Lagace TA. PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells. Curr Opin Lipidol. 2014;25(5):387‐393. doi:10.1097/MOL.0000000000000114
Alonso R, Mata P, Muñiz O, et al. PCSK9 and lipoprotein (a) levels are two predictors of coronary artery calcification in asymptomatic patients with familial hypercholesterolemia. Atherosclerosis. 2016;254:249‐253. doi:10.1016/J.ATHEROSCLEROSIS.2016.08.038
Leander K, Mälarstig A, Van'T Hooft FM, et al. Circulating proprotein convertase subtilisin/Kexin type 9 (PCSK9) predicts future risk of cardiovascular events independently of established risk factors. Circulation. 2016;133(13):1230‐1239. doi:10.1161/CIRCULATIONAHA.115.018531
Konarzewski M, Szolkiewicz M, Sucajtys‐Szulc E, et al. Elevated circulating PCSK‐9 concentration in renal failure patients is corrected by renal replacement therapy. Am J Nephrol. 2014;40(2):157‐163. doi:10.1159/000365935
Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross‐sectional study. Am J Kidney Dis. 2014;63(4):584‐589. doi:10.1053/J.AJKD.2013.10.042
Hwang HS, Kim JS, Kim YG, et al. Circulating PCSK9 level and risk of cardiovascular events and death in hemodialysis patients. J Clin Med. 2020;9(1):244. doi:10.3390/jcm9010244
Kajingulu FPM, Lepira FB, Nkodila AN, et al. Circulating proprotein convertase subtilisin/Kexin type 9 level independently predicts incident cardiovascular events and all‐cause mortality in hemodialysis black Africans patients. BMC Nephrol. 2022;23(1):123. doi:10.1186/s12882-022-02748-0
Enkhmaa B, Kim K, Zhang W, et al. PCSK9 in African Americans and Caucasians in relation to Lp(a) level, apo(a) size and heritability. J Endocr Soc. 2020;4(7):bvaa073. doi:10.1210/JENDSO/BVAA073
Jia F, Fei SF, Tong DB, Xue C, Li JJ. Sex difference in circulating PCSK9 and its clinical implications. Front Pharmacol. 2022;13:13. doi:10.3389/fphar.2022.953845
Vecchié A, Bonaventura A, Meessen J, et al. PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study. J Intern Med. 2021;289(2):179‐192. doi:10.1111/joim.13150
Jager KJ, Zoccali C, MacLeod A, Dekker FW. Confounding: what it is and how to deal with it. Kidney Int. 2008;73(3):256‐260. doi:10.1038/SJ.KI.5002650
Ferri N, Ruscica M, Coggi D, et al. Sex‐specific predictors of PCSK9 levels in a European population: the IMPROVE study. Atherosclerosis. 2020;309:39‐46. doi:10.1016/j.atherosclerosis.2020.07.014
Shi J, Zhang W, Niu Y, et al. Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population‐based cohort study. Cardiovasc Diabetol. 2020;19(1):209. doi:10.1186/s12933-020-01185-3
Zhang Z, Wei TF, Zhao B, et al. Sex differences associated with circulating PCSK9 in patients presenting with acute myocardial infarction. Sci Rep. 2019;9(1):3113. doi:10.1038/s41598-018-35773-x
Ghosh M, Gälman C, Rudling M, Angelin B. Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol. J Lipid Res. 2015;56(2):463‐469. doi:10.1194/jlr.M055780
Ma L, Zhao S. Risk factors for mortality in patients undergoing hemodialysis: a systematic review and meta‐analysis. Int J Cardiol. 2017;1(238):151‐158. doi:10.1016/j.ijcard.2017.02.095
Wu J, Yang R, Wang X, et al. Total cholesterol and mortality in peritoneal dialysis: a retrospective cohort study. BMC Nephrol. 2023;24(1):142. doi:10.1186/s12882-023-03187-1
Nakano T, Hiyamuta H, Yotsueda R, et al. Higher cholesterol level predicts cardiovascular event and inversely associates with mortality in hemodialysis patients: 10‐year outcomes of the Q‐cohort study. Ther Apher Dial. 2020;24(4):431‐438. doi:10.1111/1744-9987.13455
Lamprea‐Montealegre JA, Katz R, Scharnagl H, et al. Triglyceride‐rich lipoproteins, apolipoproteins, and atherosclerotic cardiovascular events among patients with diabetes mellitus and end‐stage renal disease on hemodialysis. Am J Cardiol. 2021;1(152):63‐68. doi:10.1016/j.amjcard.2021.04.023
Luo D, Luo Y, Zou Y, et al. Non‐high‐density lipoprotein cholesterol may predict the cardio‐cerebrovascular risk in patients on maintenance hemodialysis. Lipids Health Dis. 2021;20(1):159. doi:10.1186/s12944-021-01546-1
Gonzáles‐Rubianes DZ, Figueroa‐Osorio LK, Benites‐Zapata VA, Pacheco‐Mendoza J, Herrera‐Añazco P. Utility of TG/HDL‐c ratio as a predictor of mortality and cardiovascular disease in patients with chronic kidney disease undergoing hemodialysis: a systematic review. Hemodial Int. 2022;26(2):137‐146. doi:10.1111/hdi.12981
Shoji T, Akiyama Y, Fujii H, et al. Association of Kidney Function with serum levels of cholesterol absorption and synthesis markers: the CACHE study CKD analysis. J Atheroscler Thromb. 2022;29(12):1835‐1848. doi:10.5551/jat.63311
Luquero A, Badimon L, Borrell‐Pages M. PCSK9 functions in atherosclerosis are not limited to plasmatic LDL‐cholesterol regulation. Front Cardiovasc Med. 2021;23(8):639727. doi:10.3389/fcvm.2021.639727
Nozue T. Lipid lowering therapy and circulating PCSK9 concentration. J Atheroscler Thromb. 2017;24(9):895‐907. doi:10.5551/jat.RV17012
Rubinstein A, Weintraub M. Escape phenomenon of low‐density lipoprotein cholesterol during lovastatin treatment. Am J Cardiol. 1995;76(3):184‐186. doi:10.1016/S0002-9149(99)80057-5
Sotler T, Šebeštjen M. PCSK9 as an atherothrombotic risk factor. Int J Mol Sci. 2023;24(3):1966. doi:10.3390/ijms24031966
Chen CH, Wang Z, Giovanna Lupo M, et al. Independent association of PCSKK with platelet reactivity in subjects without statin or antiplatelet agents. Front Cardiovasc Med. 2022;9:934914.
Pęczek P, Leśniewski M, Mazurek T, Szarpak L, Filipiak KJ, Gąsecka A. Antiplatelet effects of pcsk9 inhibitors in primary hypercholesterolemia. Lifestyles. 2021;11(6):466. doi:10.3390/life11060466
Puteri MU, Azmi NU, Ridwan S, et al. Recent update on PCSK9 and platelet activation experimental research methods: in vitro and in vivo studies. J Cardiovasc Dev Dis. 2022;9(8):258. doi:10.3390/jcdd9080258
Schulz R, Schlüter KD, Laufs U. Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9). Basic Res Cardiol. 2015;110(2):4. doi:10.1007/s00395-015-0463-z
Morena M, Le May C, Chenine L, et al. Plasma PCSK9 concentrations during the course of nondiabetic chronic kidney disease: relationship with glomerular filtration rate and lipid metabolism. J Clin Lipidol. 2017;11:87‐93. doi:10.1016/j.jacl.2016.10.005