1. Baseline pro-inflammatory gene expression in whole blood is related to adverse long-term outcomes after transcatheter aortic valve replacement: a case control study.
- Author
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Goldwater DS, Leng M, Karlamangla A, Seeman T, Elashoff D, Wanagat JM, Reuben DB, Lindman BR, and Cole S
- Subjects
- Aged, Aged, 80 and over, Aortic Valve Stenosis blood, Aortic Valve Stenosis genetics, Aortic Valve Stenosis mortality, Biomarkers blood, Female, Gene Expression Regulation, Host-Pathogen Interactions, Humans, Immunity, Innate genetics, Male, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Time Factors, Transcatheter Aortic Valve Replacement mortality, Transcriptome, Treatment Outcome, United States, Aortic Valve Stenosis surgery, Inflammation Mediators blood, Transcatheter Aortic Valve Replacement adverse effects, Viruses immunology
- Abstract
Background: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2021. The Author(s).)
- Published
- 2021
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