Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection
Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection
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DOI：
10.1093/infdis/jiw173
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发表时间：
2016-08-01
影响因子：
6.4
通讯作者：
Lundgren, Jens D.
中科院分区：
文献类型：
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作者：
Borges, Alvaro H.;O'Connor, Jemma L.;Lundgren, Jens D.
背景。白细胞介素 6 (IL-6)、高敏 C 反应蛋白 (hsCRP) 和 D-二聚体水平与人类免疫缺陷病毒 (HIV) 感染的不良后果相关，但它们与不同临床终点的关联强度值得研究。方法。对在两项 HIV 试验中接受标准护理并测量生物标志物水平的参与者进行跟踪，以确定全因死亡、非艾滋病相关死亡、艾滋病、心血管疾病 (CVD) 和非艾滋病定义的恶性肿瘤。使用 Cox 模型计算四分位数和 log(2) 转换的 IL-6、hsCRP 和 D-二聚体水平的每个终点的风险比 (HR) 和 95% 置信区间 (CI)。模拟多个事件的边际模型测试了生物标志物水平对不同终点的相同影响。结果。在 4304 名参与者中，有 157 例全因死亡、117 例非艾滋病相关死亡、101 例艾滋病病例、121 例心血管疾病病例和 99 例非艾滋病定义的恶性肿瘤。与 hsCRP 相比，IL-6 与大多数终点的相关性更强。对于 CVD 和非 AIDS 定义的恶性肿瘤，IL-6 似乎是比 D-二聚体更强的预测因子，但 95% CI 重叠。 IL-6 与非艾滋病相关死亡（HR，1.71；95% CI，1.43-2.04）和全因死亡（HR，1.56；95% CI，1.33-1.84）之间的独立关联更强，对于 CVD（HR，1.35；95% CI，1.12-1.62）和非艾滋病定义的恶性肿瘤也有类似的独立关联。 （HR，1.30；95% CI，1.06-1.61）。 IL-6 (P < .001) 存在异质性，但 hsCRP (P = .15) 或 D-二聚体 (P = .20) 作为不同终点的预测因子不存在异质性。结论。 IL-6 比 CVD 和非艾滋病定义的恶性肿瘤更能预测致命事件。应在 HIV 感染者中测试辅助抗炎和抗血栓治疗。
Background. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation.Methods. Participants receiving standard of care in 2 HIV trials with measured biomarker levels were followed to ascertain all-cause death, non-AIDS-related death, AIDS, cardiovascular disease (CVD), and non-AIDS-defining malignancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) of each end point for quartiles and log(2)-transformed IL-6, hsCRP, and D-dimer levels were calculated using Cox models. Marginal models modelling multiple events tested for equal effects of biomarker levels on different end points.Results. Among 4304 participants, there were 157 all-cause deaths, 117 non-AIDS-related deaths, 101 AIDS cases, 121 CVD cases, and 99 non-AIDS-defining malignancies. IL-6 was more strongly associated with most end points, compared with hsCRP. IL-6 appeared to be a stronger predictor than D-dimer for CVD and non-AIDS-defining malignancies, but 95% CIs overlapped. Independent associations of IL-6 were stronger for non-AIDS-related death (HR, 1.71; 95% CI, 1.43-2.04) and all-cause death (HR, 1.56; 95% CI, 1.33-1.84) and similar for CVD (HR, 1.35; 95% CI, 1.12-1.62) and non-AIDS-defining malignancies (HR, 1.30; 95% CI, 1.06-1.61). There was heterogeneity of IL-6 (P < .001) but not hsCRP (P = .15) or D-dimer (P = .20) as a predictor for different end points.Conclusions. IL-6 is a stronger predictor of fatal events than of CVD and non-AIDS-defining malignancies. Adjuvant antiinflammatory and antithrombotic therapies should be tested in HIV-infected individuals.