Association of Cardiovascular Fibrosis, Remodeling, and Dysfunction With Frailty, Prefrailty, and Functional Performance: The Multi-Ethnic Study of Atherosclerosis

Abstract

Abstract Background Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remains unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods As part of the MESA study, 3 045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010 and 2012. Of these, 1 743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up exam: 2016–2018) which were used to generate a binary combined frail/prefrail versus robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction). Results Participants were 66 ± 8 years, 52% female at the time of imaging, and 29.4% were classified as frail or prefrail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (odds ratio [OR] 1.89, p = .008; Coef. −52.9, p < .001), increased ECV (OR 1.10, p = .002; Coef. −4.0, p = .001), and worsening left atrial strain rate at early diastole (OR 1.56, p ≤ .001; Coef. −22.75, p = .027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m). All associations with 6MWT performance were attenuated with adjustments for risk factors whereas ECV and LA strain rate remained independently associated with frailty. Conclusions These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis, and physical frailty.