Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis.
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DOI：
10.1371/journal.pone.0177980
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Shibata T
中科院分区：
文献类型：
--
作者：
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
载脂蛋白与血液透析(HD)患者的生存相关，但这些相关性可能受到功能失调(氧化)高密度脂蛋白(HDL)的影响。我们评估了HD患者的载脂蛋白和氧化高密度脂蛋白、死亡率和心血管疾病(CVD)事件之间的关系。这项前瞻性观察研究调查了412名流行的HD患者。透析前采血检测血脂、载脂蛋白、氧化型低密度脂蛋白、氧化型高密度脂蛋白、超敏C反应蛋白、白介素6，12个月后检测高密度脂蛋白胆固醇、超敏C反应蛋白。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心血管事件。基线变量与临床结果之间的关系通过COX比例风险模型(n=412)和随时间变化的协变量与高密度脂蛋白胆固醇和hs-CRP的COX风险模型(n=369)进行评估。载脂蛋白和氧化高密度脂蛋白的四分位数与全因死亡率无关。然而，COX比例风险模型将每个变量的四分位数调整为混杂因素，hs-CRP或IL-6确定载脂蛋白(Apo)B/apoA-I比率(apoB/apoA-I)和氧化型高密度脂蛋白(apoA-I)为复合CVD事件的独立危险因素，而不是apoA-I或apoA-II。这些关联通过具有随时间变化的hs-CRP协变量的COX比例风险模型得到证实。在调整混杂因素、氧化高密度脂蛋白和超敏C反应蛋白的1-标准差(SD)变量增加模型中，apoB/apoA-I与复合心血管事件独立相关。然而，这些关联从用IL-6而不是hs-CRP调整的模型中消失，氧化的高密度脂蛋白和IL-6独立地与复合CVD事件相关。研究结果类似于COX比例风险模型的结果，该模型使用随时间变化的协变量，并用IL-6调整高密度脂蛋白胆固醇。结论：氧化型高密度脂蛋白和apoB/apoA-I均可能与HD患者的心血管事件有关，而apoB/apoA-I与心血管事件的相关性在apoB/apoA-I四分位模型和1-SD升高模型中不同，并受IL-6的影响。
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.