Journal Article

Baseline pro-inflammatory gene expression in whole blood is related to adverse long-term outcomes after transcatheter aortic valve replacement: a case control study

Reuben, David B., Lindman, Brian R., Cole, Steve, Karlamangla, Arun, Elashoff, David, Goldwater, Deena S., Wanagat, Jonathan M., Leng, Mei, Seeman, Teresa

2021

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Activator protein 1 / Activities of daily living / Age / Aged / Aged, 80 and over / Angiology / Antiviral drugs / Aortic stenosis / Aortic valve / Aortic Valve Stenosis - blood / Aortic Valve Stenosis - genetics / Aortic Valve Stenosis - mortality / Aortic Valve Stenosis - surgery / Bioinformatics / Biomarkers / Biomarkers - blood / Blood Transfusion Medicine / Body mass index / Cardiac Surgery / Cardiology / Cardiovascular disease / Cardiovascular diseases / Diabetes / Diabetes mellitus / Female / Frailty / Gait / Gender / Gene expression / Gene Expression Regulation / Geriatrics / Health aspects / Heart Failure & Congenital / Heart valve replacement / Host-Pathogen Interactions / Humans / Immune system / Immunity, Innate - genetics / Immunosuppression / Inflammation / Inflammation Mediators - blood / Interferon / Internal Medicine / Laboratories / Male / Medicine / Medicine & Public Health / Mortality / NF-κB protein / Older people / Patient outcomes / Patients / Quality of life / Questionnaires / Research Article / Retrospective Studies / Risk Assessment / Risk Factors / Severity of Illness Index / Stenosis / Structural Diseases / Time Factors / Transcatheter aortic valve replacement / Transcatheter Aortic Valve Replacement - adverse effects / Transcatheter Aortic Valve Replacement - mortality / Transcriptome / Treatment Outcome / United States / Variables / Viruses - immunology