Department of Epidemiology, 3659 SPH Tower, 109 Observatory, Ann Arbor, MI 48104-2548, USA.
Am J Epidemiol. 2010 Aug 15;172(4):363-71. doi: 10.1093/aje/kwq177. Epub 2010 Jul 21.
This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60-101 years) in California followed in 1998-2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.
本研究探讨了巨细胞病毒(CMV)免疫反应与全因和心血管疾病(CVD)死亡率之间的关系,以及可能的中介机制。数据来自加利福尼亚州萨克拉门托地区拉丁裔老龄化研究,这是一项针对老年拉丁裔人群(60-101 岁)的基于人群的研究,于 1998-2008 年进行随访。从基线血样中检测 CMV 免疫球蛋白 G(IgG)、肿瘤坏死因子和白细胞介素-6。从死亡证明中提取全因和 CVD 死亡率的数据。分析包括 1789 名参与者中的 1468 名。与较低四分位的 CMV IgG 抗体滴度相比,对于四分位最高的个体,完全调整的模型显示,9 年内全因死亡率高出 1.43 倍(95%置信区间:1.14,1.79)。在完全调整的模型中,CVD 死亡率的风险也升高(风险比=1.35,95%置信区间:1.01,1.80)。肿瘤坏死因子和白细胞介素-6 的综合指标介导了 CMV 与全因(18.9%,P<0.001)和 CVD(29.0%,P=0.02)死亡率之间的关联的很大一部分。这项研究是第一个证明高 CMV IgG 抗体水平与死亡率显著相关的研究,并且这种关系主要是由白细胞介素-6 和肿瘤坏死因子介导的。需要进一步研究以探讨降低 IgG 抗体对 CMV 反应的方法。