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Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
PLoS One. 2017; 12(5):e0177980.Plos

Abstract

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.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, Showa University Koto Toyosu Hospital, Tokyo, Japan. Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.Ikagaku, Research Development, Kyoto, Japan.Ikagaku, Research Development, Kyoto, Japan.Ikagaku, Research Development, Kyoto, Japan.Ikagaku, Research Development, Kyoto, Japan.Department of Dialysis, Ebara Clinic, Tokyo, Japan.Department of Dialysis, Kawasaki Clinic, Kawasaki, Japan.Division of Dialysis, Kitami Higashiyama Clinic, Tokyo, Japan.Division of Nephrology, Department of Medicine, Showa University Koto Toyosu Hospital, Tokyo, Japan. Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28542510

Citation

Honda, Hirokazu, et al. "Associations Among Apolipoproteins, Oxidized High-density Lipoprotein and Cardiovascular Events in Patients On Hemodialysis." PloS One, vol. 12, no. 5, 2017, pp. e0177980.
Honda H, Hirano T, Ueda M, et al. Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis. PLoS One. 2017;12(5):e0177980.
Honda, H., Hirano, T., Ueda, M., Kojima, S., Mashiba, S., Hayase, Y., Michihata, T., Shishido, K., Takahashi, K., Hosaka, N., Ikeda, M., Sanada, D., & Shibata, T. (2017). Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis. PloS One, 12(5), e0177980. https://doi.org/10.1371/journal.pone.0177980
Honda H, et al. Associations Among Apolipoproteins, Oxidized High-density Lipoprotein and Cardiovascular Events in Patients On Hemodialysis. PLoS One. 2017;12(5):e0177980. PubMed PMID: 28542510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis. AU - Honda,Hirokazu, AU - Hirano,Tsutomu, AU - Ueda,Masashi, AU - Kojima,Shiho, AU - Mashiba,Shinichi, AU - Hayase,Yasuyuki, AU - Michihata,Tetsuo, AU - Shishido,Kanji, AU - Takahashi,Keiko, AU - Hosaka,Nozomu, AU - Ikeda,Misa, AU - Sanada,Daisuke, AU - Shibata,Takanori, Y1 - 2017/05/18/ PY - 2016/12/03/received PY - 2017/05/05/accepted PY - 2017/5/26/entrez PY - 2017/5/26/pubmed PY - 2017/9/16/medline SP - e0177980 EP - e0177980 JF - PloS one JO - PLoS One VL - 12 IS - 5 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28542510/Associations_among_apolipoproteins_oxidized_high_density_lipoprotein_and_cardiovascular_events_in_patients_on_hemodialysis_ L2 - https://dx.plos.org/10.1371/journal.pone.0177980 DB - PRIME DP - Unbound Medicine ER -