Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.

Apolipoproteins are associated with survival among patients on hemodialysis (HD), but these associations might be influenced by dysfunctional (oxidized) high-density lipoprotein (HDL). We assessed associations among apolipoproteins and oxidized HDL, mortality and cardiovascular disease (CVD) events...

Full description

Bibliographic Details
Main Authors: Hirokazu Honda, Tsutomu Hirano, Masashi Ueda, Shiho Kojima, Shinichi Mashiba, Yasuyuki Hayase, Tetsuo Michihata, Kanji Shishido, Keiko Takahashi, Nozomu Hosaka, Misa Ikeda, Daisuke Sanada, Takanori Shibata
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5436869?pdf=render
_version_ 1828487251523272704
author Hirokazu Honda
Tsutomu Hirano
Masashi Ueda
Shiho Kojima
Shinichi Mashiba
Yasuyuki Hayase
Tetsuo Michihata
Kanji Shishido
Keiko Takahashi
Nozomu Hosaka
Misa Ikeda
Daisuke Sanada
Takanori Shibata
author_facet Hirokazu Honda
Tsutomu Hirano
Masashi Ueda
Shiho Kojima
Shinichi Mashiba
Yasuyuki Hayase
Tetsuo Michihata
Kanji Shishido
Keiko Takahashi
Nozomu Hosaka
Misa Ikeda
Daisuke Sanada
Takanori Shibata
author_sort Hirokazu Honda
collection DOAJ
description Apolipoproteins are associated with survival among patients on hemodialysis (HD), but these associations might be influenced by dysfunctional (oxidized) high-density lipoprotein (HDL). We assessed associations among apolipoproteins and oxidized HDL, mortality and cardiovascular disease (CVD) events in patients on HD. This prospective observational study examined 412 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, apolipoproteins, oxidized LDL, oxidized HDL, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 at baseline, and HDL-C and hs-CRP were measured 12 months later. Patients were then prospectively followed-up (mean, 40 months) and all-cause mortality and composite CVD events were analyzed. Associations between variables at baseline and clinical outcome were assessed by Cox proportional hazards modeling (n = 412) and Cox hazards modeling with a time-varying covariate with HDL-C and hs-CRP (n = 369). Quartiles of apolipoproteins and oxidized HDL were not associated with all-cause mortality. However, Cox proportional hazards models with quartiles of each variable adjusted for confounders and hs-CRP or IL-6 identified apolipoprotein (apo)B-to-apoA-I ratio (apoB/apoA-I) and oxidized HDL, but not apoA-I or apoA-II, as independent risk factors for composite CVD events. These associations were confirmed by Cox proportional hazards modeling with time-varying covariates for hs-CRP. ApoB/apoA-I was independently associated with composite CVD events in 1-standard deviation (SD) increase-of-variables models adjusted for the confounders, oxidized HDL and hs-CRP. However, these associations disappeared from the model adjusted with IL-6 instead of hs-CRP, and oxidized HDL and IL-6 were independently associated with composite CVD events. Findings resembled those from Cox proportional hazards modeling using time-varying covariates with HDL-C adjusted with IL-6. In conclusion, both oxidized HDL and apoB/apoA-I might be associated with CVD events in patients on prevalent HD, while associations of apoB/apoA-I with CVD events differed between models of apoB/apoA-I quartiles and 1-SD increases, and were influenced by IL-6.
first_indexed 2024-12-11T09:47:23Z
format Article
id doaj.art-d357b0e9327c40dd82114d43fd55f505
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-11T09:47:23Z
publishDate 2017-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-d357b0e9327c40dd82114d43fd55f5052022-12-22T01:12:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017798010.1371/journal.pone.0177980Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.Hirokazu HondaTsutomu HiranoMasashi UedaShiho KojimaShinichi MashibaYasuyuki HayaseTetsuo MichihataKanji ShishidoKeiko TakahashiNozomu HosakaMisa IkedaDaisuke SanadaTakanori ShibataApolipoproteins are associated with survival among patients on hemodialysis (HD), but these associations might be influenced by dysfunctional (oxidized) high-density lipoprotein (HDL). We assessed associations among apolipoproteins and oxidized HDL, mortality and cardiovascular disease (CVD) events in patients on HD. This prospective observational study examined 412 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, apolipoproteins, oxidized LDL, oxidized HDL, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 at baseline, and HDL-C and hs-CRP were measured 12 months later. Patients were then prospectively followed-up (mean, 40 months) and all-cause mortality and composite CVD events were analyzed. Associations between variables at baseline and clinical outcome were assessed by Cox proportional hazards modeling (n = 412) and Cox hazards modeling with a time-varying covariate with HDL-C and hs-CRP (n = 369). Quartiles of apolipoproteins and oxidized HDL were not associated with all-cause mortality. However, Cox proportional hazards models with quartiles of each variable adjusted for confounders and hs-CRP or IL-6 identified apolipoprotein (apo)B-to-apoA-I ratio (apoB/apoA-I) and oxidized HDL, but not apoA-I or apoA-II, as independent risk factors for composite CVD events. These associations were confirmed by Cox proportional hazards modeling with time-varying covariates for hs-CRP. ApoB/apoA-I was independently associated with composite CVD events in 1-standard deviation (SD) increase-of-variables models adjusted for the confounders, oxidized HDL and hs-CRP. However, these associations disappeared from the model adjusted with IL-6 instead of hs-CRP, and oxidized HDL and IL-6 were independently associated with composite CVD events. Findings resembled those from Cox proportional hazards modeling using time-varying covariates with HDL-C adjusted with IL-6. In conclusion, both oxidized HDL and apoB/apoA-I might be associated with CVD events in patients on prevalent HD, while associations of apoB/apoA-I with CVD events differed between models of apoB/apoA-I quartiles and 1-SD increases, and were influenced by IL-6.http://europepmc.org/articles/PMC5436869?pdf=render
spellingShingle Hirokazu Honda
Tsutomu Hirano
Masashi Ueda
Shiho Kojima
Shinichi Mashiba
Yasuyuki Hayase
Tetsuo Michihata
Kanji Shishido
Keiko Takahashi
Nozomu Hosaka
Misa Ikeda
Daisuke Sanada
Takanori Shibata
Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
PLoS ONE
title Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
title_full Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
title_fullStr Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
title_full_unstemmed Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
title_short Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
title_sort associations among apolipoproteins oxidized high density lipoprotein and cardiovascular events in patients on hemodialysis
url http://europepmc.org/articles/PMC5436869?pdf=render
work_keys_str_mv AT hirokazuhonda associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT tsutomuhirano associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT masashiueda associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT shihokojima associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT shinichimashiba associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT yasuyukihayase associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT tetsuomichihata associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT kanjishishido associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT keikotakahashi associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT nozomuhosaka associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT misaikeda associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT daisukesanada associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis
AT takanorishibata associationsamongapolipoproteinsoxidizedhighdensitylipoproteinandcardiovasculareventsinpatientsonhemodialysis