Division of Cardiology, Department of Medicine, University of California, Los Angeles, CA, USA.
Division of Geriatrics, Department of Medicine, University of California, Los Angeles, CA, USA.
BMC Cardiovasc Disord. 2021 Aug 2;21(1):368. doi: 10.1186/s12872-021-02186-0.
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.
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接受经导管主动脉瓣置换术（TAVR）后出现不良长期手术结局风险的机制。本研究旨在探讨严重主动脉瓣狭窄老年患者 TAVR 前炎症和先天抗病毒基因表达与结局之间的关系。
我们进行了一项回顾性病例对照研究，比较了 48 例预后良好（TAVR 后 1 年存活且生活质量改善）与 48 例预后不良（1 年内死亡或 1 年内存活但生活质量降低）患者的炎症前和 I 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，以及（2）基于启动子的生物信息学分析推断出促炎和抗病毒转录因子活性，评估全血中的基因表达。基因表达水平在各组之间存在差异>25%。所有分析均调整了年龄、性别、体重指数、糖尿病、免疫抑制、心血管疾病（CVD）和虚弱。
与对照组相比，预后不良组 TAVR 前促炎基因复合表达更高（p<0.01），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也更高，但 I 型 IFN 相关基因表达无显著差异。
这些结果表明，TAVR 前促炎状态，独立于 CVD 严重程度和虚弱状态，与长期手术结局不良相关。
