Honda Hirokazu, Hirano Tsutomu, Ueda Masashi, Kojima Shiho, Mashiba Shinichi, Hayase Yasuyuki, Michihata Tetsuo, Shishido Kanji, Takahashi Keiko, Hosaka Nozomu, Ikeda Misa, Sanada Daisuke, Shibata Takanori
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.
PLoS One. 2017 May 18;12(5):e0177980. doi: 10.1371/journal.pone.0177980. eCollection 2017.
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.
载脂蛋白与血液透析（HD）患者的生存情况相关，但这些关联可能会受到功能失调（氧化）的高密度脂蛋白（HDL）的影响。我们评估了HD患者中载脂蛋白与氧化HDL、死亡率和心血管疾病（CVD）事件之间的关联。这项前瞻性观察性研究对412例接受HD治疗的患者进行了检查。在基线透析前采集血样，以测量基线时的血脂、载脂蛋白、氧化低密度脂蛋白、氧化HDL、高敏C反应蛋白（hs-CRP）和白细胞介素（IL）-6，并在12个月后测量HDL-C和hs-CRP。然后对患者进行前瞻性随访（平均40个月），并分析全因死亡率和复合CVD事件。通过Cox比例风险模型（n = 412）以及使用HDL-C和hs-CRP作为时变协变量的Cox风险模型（n = 369）评估基线变量与临床结局之间的关联。载脂蛋白和氧化HDL的四分位数与全因死亡率无关。然而，在对混杂因素以及hs-CRP或IL-6进行调整的每个变量四分位数的Cox比例风险模型中，载脂蛋白（apo）B与apoA-I的比值（apoB/apoA-I）和氧化HDL被确定为复合CVD事件的独立危险因素，而apoA-I或apoA-II则不是。通过使用hs-CRP的时变协变量的Cox比例风险模型证实了这些关联。在针对混杂因素、氧化HDL和hs-CRP进行调整的1标准差（SD）变量增加模型中，apoB/apoA-I与复合CVD事件独立相关。然而，在用IL-6而非hs-CRP进行调整的模型中，这些关联消失了，并且氧化HDL和IL-6与复合CVD事件独立相关。研究结果与使用经IL-6调整的HDL-C作为时变协变量的Cox比例风险模型的结果相似。总之，氧化HDL和apoB/apoA-I可能都与接受HD治疗的患者的CVD事件相关，而apoB/apoA-I与CVD事件的关联在apoB/apoA-I四分位数模型和1-SD增加模型之间有所不同，并且受到IL-6的影响。
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