FRailty and Arterial stiffness – the role of oXidative stress and Inflammation (FRAXI study)

Abstract

Objective: There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute to vascular ageing. There are no human studies exploring links between arterial stiffness, oxidative stress, inflammaging and frailty. Our objective is to investigate arterial stiffness and inflammaging as predictors of frailty states. Methods: An observational longitudinal cohort study will be used to examine the association between arterial stiffness, oxidative stress and inflammation in 50 older adults (⩾70 years) with clinical frailty scores (CFS) ⩽6 over 6 months. All study measurements will be taken at baseline. Frailty assessment will include hand-grip strength, timed-up and go test, mini-mental state examination, geriatric depression scale and sarcopenia using body composition measurements with Tanita®. Arterial stiffness measurements will include carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) using Complior (Alam Medical, France). CAVI device will measure Cardio-ankle vascular index and ankle brachial index (ABI). Oxidative stress blood markers nitrotyrosine (NT) and 8-hydroxy-2’-deoxyguanosin (8-oxo-dG) and inflammation markers high-sensitive C-reactive protein (hs-CRP) and interlukin-6(IL-6) will be measured at baseline and 6 month along with lipid profile and glycated haemoglobin. Results (data analysis plan): Descriptive statistics for continuous data using means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be used. Participants will be categorised into CFS 1-3, and CFS 4-6. Categorical data will use frequencies and comparison between groups. Change in frailty between the groups over 6 months will be compared using paired t-test. Simple linear regression will be done between frailty measures, arterial stiffness, inflammation and oxidative stress biomarkers. Significance will be at P < .05. Conclusion: This study data will inform a larger, multi-centre study exploring further the interplay between frailty, biomarkers and arterial stiffness parameters.

Physical frailty is related to oxidative stress through thiol/disulfide homeostasis parameters

“…Several studies showed that plasma lipid peroxidation and protein oxidation, which are indicators of oxidative stress, are associated with frailty regardless of age [36]. In the FRAXI study, Mensah et al showed that nitrotyrosine and 8-hydroxy-2'deoxyguanosine, as markers of oxidative stress, were signi cantly higher in older adults living with frailty de ned by the CFS, leading to arterial stiffness [37]. Wu et al also found that the same biomarkers are associated with frailty de ned by the FFI in the older Chinese population [38].…”

The role of frailty in advanced HF and cardiac transplantation

“…This is strongly correlated with frailty, heart disease and multi-morbidity ( 42 , 43 ). For example, in the FRAXI study ( 44 ), frailty and inflammation were correlated with arterial stiffness. The correlation is explained by a dysfunctional immune state being a common mechanism for each of these conditions ( 44 , 45 ).…”