年龄相关的炎症和免疫系统功能障碍被认为是增加老年人长期不良手术结局风险的机制。这项研究的目的是调查基线炎症和先天性抗病毒基因表达与经导管主动脉瓣置换术(TAVR)后的结果之间的关系患有严重主动脉瓣狭窄的老年人。
我们进行了一项回顾性病例对照研究,比较了48名具有良好结局(TAVR后存活1年,生活质量[QoL]改善)的对照组与48名具有不良结局(1年死亡或1年存活,但QoL降低)的患者的术前促炎和1型干扰素(IFN)基因表达。通过(1)19个炎症相关基因和34个I型IFN反应基因的预定义复合评分评估全血中的基因表达,和(2)从基于启动子的生物信息学分析推断促炎和抗病毒转录因子活性的基因显示各组间平均表达水平差异>25%。所有分析都根据年龄进行了调整,性别,身体质量指数,糖尿病,免疫抑制,心血管疾病(CVD),和脆弱。
相对于控件,那些具有不利结果的患者在TAVR之前显示促炎基因复合物的较高表达(p<0.01),以及核因子kB(p<0.001)和激活蛋白1(p<0.001)转录因子活性升高的生物信息学指标,但I型IFN相关基因表达没有显着差异。
这些结果表明,TAVR之前的促炎状态,与CVD严重程度和虚弱状态无关,与更糟糕的长期程序结果有关。
Age-associated inflammation and immune system dysfunction have been implicated as mechanisms that increase risk for adverse long-term procedural outcomes in older adults. The purpose of this study was to investigate relationships between baseline inflammatory and innate antiviral gene expression and outcomes after transcatheter aortic valve replacement (TAVR) in older adults with severe aortic stenosis.
We performed a retrospective
case-control study comparing pre-procedural pro-inflammatory and Type 1 interferon (IFN) gene expression in 48 controls with favorable outcomes (alive 1 year after TAVR with improved quality of life [QoL]) versus 48 individuals with unfavorable outcomes (dead by 1 year or alive at 1 year but with reduced QoL). Gene expression was evaluated in whole blood via (1) pre-defined composite scores of 19 inflammation-associated genes and 34 Type I IFN response genes, and (2) pro-inflammatory and antiviral transcription factor activity inferred from promotor based bioinformatics analyses of genes showing > 25% difference in average expression levels across groups. All analyses were adjusted for age, gender, body mass index, diabetes, immunosuppression, cardiovascular disease (CVD), and frailty.
Relative to controls, those with unfavorable outcomes demonstrated higher expression of the pro-inflammatory gene composite prior to TAVR (p < 0.01) and bioinformatic indicators of elevated Nuclear Factor kB (p < 0.001) and Activator Protein 1 (p < 0.001) transcription factor activity, but no significant differences in Type I IFN-related gene expression.
These results demonstrate that a pro-inflammatory state prior to TAVR, independent of CVD severity and frailty status, is associated with worse long-term procedural outcomes.