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Does vascular endothelial dysfunction play a role in physical frailty and sarcopenia?

Does vascular endothelial dysfunction play a role in physical frailty and sarcopenia? A systematic review

Anjalee Thanuja Amarasekera 1 2, Dennis Chang 3, Peter Schwarz 4, Timothy C Tan 2 5 6


· 1 Blacktown Clinical and Research School, Western Sydney University, Sydney, Australia.

· 2 Department of Cardiology, Blacktown Hospital, Western Sydney Local Health District, Sydney, Australia.

· 3 Department of Pharmacology, NICM Health Research Institute, Western Sydney University, Sydney, Australia.

· 4 Department of Clinical Medicine, Endocrinology PE and Research Centre of Ageing and Osteoporosis, Rigshospitalet, Denmark.

· 5 Department of Cardiology, School of Medicine, Western Sydney University, Sydney, Australia.

· 6 Department of Cardiology, School of Medical Sciences, University of New South Wales, Sydney, Australia.


Background: Frailty is strongly associated with adverse cardiovascular outcomes; however, the underlying pathophysiological processes are largely unknown. Vascular endothelial dysfunction (VED) is the earliest stage of cardiovascular disease (CVD) progression and predicts long-term CVD outcomes. Both these conditions share an elevated inflammatory state as a common pathological factor.

Objective: Systematic literature review was conducted to examine the evidence supporting an association between VED and physical frailty and/or sarcopenia, in electronic databases including Scopus, Ovid Medline, CINAHL, ScienceDirect, ProQuest Health & Medicine and Embase from January 1980 to August 2019.

Results: A total of 18 studies met the inclusion criteria. VED is independently associated with increased frailty phenotypes and measures of sarcopenia. Several markers of VED, including higher levels of asymmetric dimethylarginine, abnormal ankle brachial index, pulse wave velocity, pulse pressure and lower levels of flow-mediated dilatation, peripheral blood flow and endothelial progenitor cell counts, have been associated with frailty/sarcopenia measurements. Some studies demonstrated the effect of inflammation on the association.

Conclusions: Recent studies, although limited, showed that VED could be one of the underlying mechanisms of frailty. It is entirely possible that inflammation-related pathological changes in the vascular endothelium are involved in the early causative mechanisms in physical frailty. The exact mechanism(s) underlying this association are still unclear and will need to be evaluated. The outcomes of these future research studies could potentially inform early preventative strategies for physical frailty and sarcopenia.

Keywords: Ageing; Frailty; Inflammation; Muscle Weakness; Older People; Sarcopenia; Vascular Endothelial Dysfunction.


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