Carlsson Axel C, Juhlin C Christofer, Larsson Tobias E, Larsson Anders, Ingelsson Erik, Sundström Johan, Lind Lars, Arnlöv Johan
Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Atherosclerosis. 2014 Nov;237(1):236-42. doi: 10.1016/j.atherosclerosis.2014.09.005. Epub 2014 Sep 16.
Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.
The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).
In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatings TNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.
An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
实验证据支持肿瘤坏死因子α可溶性受体是导致心血管疾病和癌症潜在病理过程的重要介质。然而，关于循环可溶性肿瘤坏死因子受体-1（sTNFR1）与人类死亡率之间关系的前瞻性数据尚缺。我们旨在探究并验证sTNFR1与死亡率之间的关联，并探究其他已确定的死亡风险因素（包括其他炎症标志物）的影响。
在两个基于社区的老年队列中研究血清sTNFR1与死亡风险之间的关联：乌普萨拉老年人血管前瞻性研究（PIVUS；女性占50%，n = 1005，平均年龄70岁，中位随访7.9年）和乌普萨拉成年男性纵向研究（ULSAM，n = 775，平均年龄77岁，中位随访8.1年）。
在随访期间，PIVUS队列中有101名参与者死亡，ULSAM队列中有274名参与者死亡。在针对炎症、生活方式和已确定的心血管风险因素进行调整的多变量Cox回归模型中，sTNFR1每升高一个标准差（SD），PIVUS队列中死亡风险比（HR）为1.37，95%置信区间（CI）为1.17 - 1.60；ULSAM队列中HR为1.22，95%CI为1.10 - 1.37。此外，在ULSAM队列中，循环sTNFR1与心血管死亡率（sTNFR1每SD的HR为1.24，95%CI为1.07 - 1.44）和癌症死亡率（sTNFR1每SD的HR为1.32，95%CI为1.11 - 1.57）相关。高水平的sTNFR1在全身炎症水平高和低的人群中均识别出死亡风险增加的个体。
在两个独立的基于社区的队列中发现并验证了循环sTNFR1与死亡风险增加之间的关联。sTNFR1在识别不良结局和死亡的高危患者方面未来的临床作用尚未确定。
