High serum angiotensin-converting enzyme 2 activity as a biomarker of frailty in nursing home residents

Abstract

Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) are two of the main components of the renin-angiotensin system (RAS). Imbalanced RAS showing lower ACE2 has been associated with increased cardiovascular risk, muscular pathologies, sarcopenia, frailty, other age-related pathologies and a poorer health status. However, its role in aging remains unclear. Thus, the aim of this work was to analyze the serum enzymatic activity of ACE and ACE2, the ACE/ACE2 ratio and its association with anthropometric parameters, blood pressure, physical function, dependence and frailty in older people living in nursing homes. This study is a secondary analysis of baseline data from two randomized clinical trials in a population of 228 older individuals living in nursing homes (Spain). Serum ACE and ACE2 enzymatic activities were measured by fluorimetry. Variables linked to cardiovascular risk, physical function, dependence and frailty were measured using validated tests, indexes and scales. Association between ACE, ACE2 serum activities, the ACE/ACE2 ratio and the rest of the quantitative variables were assessed by Pearson's correlations and by partial correlations controlled by age and sex. The association between serum ACE and ACE2 activities, the ACE/ACE2 ratio and frailty scores was analyzed by generalized linear models with and without controlling for sex and age. Differences in enzymatic activities between sexes and between frail and non-frail individuals were analyzed using Student's t-test and general linear models to control analysis by age and sex. We found that higher serum ACE2 activity was associated with a higher body mass index, worse physical function, greater dependence and increased frailty. This association is consistent with the elevation of circulating ACE2 in certain pathological conditions and in line with RAS deregulation in muscular dystrophies. Serum ACE2 activity, in combination with other molecules, could be proposed as a biomarker of poor physical function, higher dependence and frailty.

Keywords: Angiotensin-converting enzyme 2; Biomarker; Frailty; Nursing home; Physical function.