Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations

Maria Cybularz; Sandy Wydra; Katharina Berndt; David M Poitz; Peggy Barthel; Ahmad Alkouri; Felix M Heidrich; Karim Ibrahim; Stefanie Jellinghaus; Uwe Speiser; Axel Linke; Marian Christoph; Christian Pfluecke

doi:10.1016/j.exger.2021.111317

Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations

Exp Gerontol. 2021 Jul 1:149:111317. doi: 10.1016/j.exger.2021.111317. Epub 2021 Mar 17.

Affiliations

¹ Internal medicine, cardiology and intensive care medicine, Heart Center Dresden, Technical University Dresden, Dresden, Germany.
² Department of Cardiology, Universitätsklinikum Leipzig, Leipzig, Germany.
³ Institute for Clinical Chemistry and Laboratory Medicine, Technical University Dresden, Dresden, Germany.
⁴ Department of Cardiology, Technische Universität Dresden, Klinikum Chemnitz, Germany.
⁵ Internal medicine, cardiology and intensive care medicine, Heart Center Dresden, Technical University Dresden, Dresden, Germany. Electronic address: christian.pfluecke@mailbox.tu-dresden.de.

PMID: 33744391
DOI: 10.1016/j.exger.2021.111317

Abstract

Aim of the study: Frail patients with high grade aortic valve stenosis (AS) undergoing Transcatheter Aortic Valve Implantation (TAVI) have an increased mortality. A connection between frailty and inflammation has been suggested. Monocyte subpopulations are associated with both cardiovascular diseases and chronic inflammatory diseases. This study investigates the association of frailty with monocyte subpopulations and systemic inflammatory parameters in elderly patients undergoing TAVI.

Methods: A total of 120 patients with symptomatic AS was examined. Before TAVI implantation, frailty was assessed by a bedside evaluation (eyeball test). In all patients a flow cytometry analysis has been performed. Monocyte subpopulations were defined as follows: classical (CD14⁺⁺CD16^-), intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14⁺CD16⁺⁺). Expression of CD11b was measured as a marker for monocyte activation. Pro-inflammatory cytokines such as interleukin IL-8, as well as CRP were measured with Cytometric Bead Array or standard laboratory methods.

Results: 28 out of 120 patients were frail. These patients showed both, signs of elevated chronic systemic inflammation reflected by elevated CRP (3.7 (1.4-5.4) vs. 5.9 (3.7-29.1), p = 0.001) and an elevated level of intermediate monocytes (37 (24-54) vs. 53 (47-63), p = 0.001). At 6 months after TAVI, 19 of 120 patients died, primarily without relevant dysfunction of the implanted aortic valve. Mortality was significantly higher in the frail as compared with non-frail patients (9 of 28 frail patients vs. 10 of 92 non frail patients, p < 0.001). A binary logistic regression analysis validated frailty and intermediate monocytes as independent predictors for early mortality after TAVI.

Conclusion: Chronic systemic inflammation and increased levels of intermediate monocytes are associated with frailty in old patients with severe aortic valve stenosis. Both the syndrome of frailty and elevated intermediate monocytes showed an association with early mortality after TAVI.

Keywords: Chronic inflammation; Frailty; Tavi.

MeSH terms

Aged
Aortic Valve Stenosis* / surgery
Frail Elderly
Frailty*
Humans
Inflammation
Monocytes
Risk Factors
Transcatheter Aortic Valve Replacement*
Treatment Outcome