Frailty is an ageing-related health state of increased vulnerability to poor recovery to a stressor.[1] Frailty has a complex interrelationship with both comorbidity and disability,[2] and frailty may be related to severity of disease in chronic limb-threatening ischaemia (CLTI).[3] Successful revascularisation may therefore lead to an improvement in frailty status among individuals with CLTI living with frailty. The aim of this prospective cohort study was to assess change in change in frailty and cognitive assessments at 3-months following intervention for individuals with CLTI.

Single-centre, prospective cohort study.[4] Individuals aged ≥65 years (minimum age lowered to ≥50 years during the study) presenting with CLTI and planned surgical or endovascular intervention were eligible for inclusion. Baseline assessments included Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS), Montreal Cognitive Assessment (MoCA), Vascular Quality of Life (VascuQoL) questionnaire, Barthel Index, Hospital Anxiety and Depression Score (HADS), grip strength, and short physical performance battery (SPPB). Delirium screening was undertaken for all patients at 24- and 72-hours post-procedure using the 4 A's Test and Single Question in Delirium. All study participants who underwent a procedure were invited for follow-up at 3-months where baseline assessments were repeated. The study was open to recruitment from 10/05/2019 until 14/10/2021. Recruitment was paused between 13/03/2020 and 12/10/2020, and between 06/01/2021 and 15/02/2021 due to the COVID-19 pandemic. 3-month follow-up was by telephone-only between 13/03/2020 and 01/06/2021 due to COVID-19 related restrictions and mitigations. Ethical approval was provided by the UK Health Research Authority (reference: 19/LO/0132). Patients with an EFS score ≥8 were considered as living with frailty. Associations of baseline variables with frailty were investigated using χ2 test for categorical data, t-test for normally distributed continuous data, and Kruskal-Wallis test for both skewed continuous data and ordinal data. Logistic regression models were constructed to investigate associations with post-operative delirium (POD), non-home discharge and 30-day readmission with results reported as odds ratios (OR) with 95% confidence intervals (CI). A negative binomial regression model was constructed to investigate associations with length of stay (LoS) with results reported as incidence rate ratios (IRR) with 95% CI. Change in frailty and cognitive impairment assessments at 3-months were investigated with analysis of covariance. A p-value <.050 was considered statistically significant.

Ninety-nine patients underwent baseline assessments (Figure 1). Forty-five patients (45%) had an EFS ≥8 and classified as frail. Frailty was associated with greater multi-morbidity (higher CCI score), anaemia (lower haemoglobin) and polypharmacy (greater number of medications) (Table 1). Frailty was associated with worse cognition (lower MoCA scores) (p<.001), disability (lower Barthel Index scores) (p<.001), worse physical function (lower SPPB scores) (p<.001), lower grip strength (p<.001), worse mood (lower HADS scores) (p<.001), and worse quality of life (QoL) (lower VascuQoL scores) (p=.011) at baseline (Table 2). Individuals with frailty had lower VascuQoL scores across all domains at baseline (Figure 2). Eighty-seven patients underwent an initial procedure (Figure 1). Cognitive impairment (OR 8.52 [95% CI 1.12, 64.67]; p=.038) and greater CCI score (OR 1.88 [95% CI 1.03, 3.45]; p=.041) were both independently associated with POD. Older age (IRR 1.02 [95% CI 1.00, 1.04]; p=.039) and general anaesthesia (IRR 2.10 [1.44, 3.05]; p<.001) were independently associated with LoS. There was a trend to independent associations of frailty with both non-home discharge (OR 4.45 [95% CI 0.40, 50.15]; p=.227) and 30-day readmission (OR 2.08 [95% CI 0.64, 6.76]; p=.224), but these were not statistically significant. Seventy-one patients (88% of those eligible) completed 3-month follow-up (Figure 1). Frailty was associated with worse improvement in QoL (lower VascuQoL scores) and mood (lower HADS scores) at 3-months (Table 2). At 3-months, using the CFS to define frailty, 4 (12%) of those with frailty at baseline transitioned to non-frailty at 3-months compared to 10 (27%) of those without frailty at baseline transitioned to frailty.

Frailty is highly prevalent among individuals presenting with CLTI. Individuals with frailty have worse cognitive and physical function, with a greater degree of disability and worse quality of life at baseline. Individuals with frailty have a more limited QoL benefit at 3-months following intervention for CLTI. In a small number of individuals, successful revascularisation may improve frailty status however a larger proportion of non-frail individuals with CLTI will transition to frailty at 3-months.

1. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752-62 doi:10.1016/s0140-6736(12)62167-9. 2. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59:255-63 doi:10.1093/gerona/59.3.m255. 3. Houghton JS, Nickinson AT, Helm JR, Dimitrova J, Dubkova S, Rayt HS, et al. Associations of clinical frailty with severity of limb threat and outcomes in chronic limb-threatening ischaemia. Ann Vasc Surg. 2021 doi:10.1016/j.avsg.2021.04.017. 4. Houghton JSM, Nduwayo S, Nickinson ATO, Payne TJ, Sterland S, Nath M, et al. Leg ischaemia management collaboration (LIMb): study protocol for a prospective cohort study at a single UK centre. BMJ Open. 2019;9:e031257 doi:10.1136/bmjopen-2019-031257.