D3.308 - Frailty in elderly with C1 Inhibitor Hereditary Angioedema: first evidence from a monocentric ITACA cohort

Hereditary Angioedema (HAE MIM #106100) is a rare autosomal dominant disease characterized by recurrent cutaneous and submucosal swelling episodes due to mutations in SERPING1 coding for C1-esterase inhibitor (C1-INH). Patients with C1INH-HAE could experience a relevant burden of both lifelong disease and medical treatments. The coexistence of additional comorbidities concurs to the reduction of the quality of life (QoL) often resulting in social-psychological isolation and potential multidimensional vulnerability. Frailty is characterized by a functional decline across multiple physiological systems. No study has tried to analyze frailty in C1INH-HAE. We aimed at assessing for the first time frailty in elderly with C1INH-HAE by using a comprehensive geriatric assessment. 

Observational prospective cohort study included patients over 65 years of age consecutively admitted for C1INH-HAE to the ITACA Reference Centre in Rome (Policlinico Tor Vergata), Italy. Patients had a defined diagnosis of C1INH-HAE (type 1-2) and were compared to a control group of elderly referring to the Geriatric Unit at the same Hospital. In patients, the C1IN-HAE burden was assessed by HAE-QoL. All subjects in the study underwent comprehensive geriatric assessment including: Mini Mental State Examination (MMSE) as cognitive screening, the standardized Geriatric Depression Scale (GDS, a score ≥5 indicated depressive states), Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs) as indicators of functional status, and the Tinetti test for assessing the risk of falling (a score ≥24 indicated a lower risk of falling). Furthermore, the comorbidity burden was measured by Charlson Comorbidity Index (CCI) and frailty status was assessed using the Clinical Frailty Scale (CFS). 

Thirty C1INH-HAE patients were included: they were age/sex matched with the control group comprising 50 subjects (see Table). In accordance with the HAE-QoL, 10% of C1INH-HAE patients (n=3) had severe disease. MMSE had a similar mean value between patients and controls with a proportion of subjects with normal MMSE slightly higher in patients (93.4%) than controls (80%). A GDS score ≥5 resulted in a similar proportion between patients and controls. Subjects with ≥ 1 ADL loss were fewer in patients than controls (P=0.01) while no difference occurred in IADL loss between the groups. The risk of falling resulted similarly distributed in patients and controls. No differences resulted between patients and controls in mean values of CCI and CFS.  No correlations between HAE-QoL and scores for multidimensional assessments results.

In elderly with C1INH-HAE age-related frailty appears to be similar to that from general geriatric population.

However, frailty related to disease remains unexplored and different frailty-associated indicators might be identified in C1INH-HAE. As the proportion of C1INH-HAE patients achieving the geriatric age threshold is growing, frailty should be identified to improve outcomes in elderly.