The association of malnutrition with mortality and amputation outcomes in critical limb ischemia: a systematic review
Authors: Brice A E B , Scierka L S , Arham A A , Ahmed Z A , Castro-Dominguez Y C D , Grimshaw A G , Nagpal S N , Soedamah-Muthu S S M , Mena-Hurtado C M H , Smolderen K G S 
Published: October 2021

Abstract

Introduction
Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease with high mortality. Malnutrition has been recognized as a potentially modifiable risk factor that may be prognostic of mortality and amputation outcomes in CLI. Great variability exists in the measurement of malnutrition including surrogate markers such as albumin level and body mass index (BMI) but also validated tools including geriatric nutritional risk index (GNRI) and controlling nutritional status (CONUT).

Purpose
To conduct a systematic review examining the association of malnutrition with mortality and amputation outcomes in patients with CLI.

Methods
A systematic literature search of AMED, CINAHL, Cochrane Library, Medline, Embase, Pubmed, Scopus, Web of Science, and Google Scholar was conducted through September 12, 2020. The review protocol was registered in PROSPERO. Only CLI patients were included. It was limited by adult human studies and those after 1982, when CLI was first defined. Eligible studies were randomized controlled trials, cohort studies, and case-control studies while case series, case reports, editorials, conference abstracts, and non-English studies were excluded. Malnutrition measured by albumin, BMI, or a validated malnutrition assessment tool was included. Outcomes of interest were mortality, any amputation, amputation free survival (AFS), major adverse limb events (MALE), major adverse cardiovascular events (MACE), or a composite of these. Two reviewers independently performed screening, data extraction, and quality assessment with a third independent reviewer resolving disagreements.

Results
3290 initial studies were found. The final 33 eligible studies were from 7 countries published between 2002 to 2020. Of these 30 were retrospective cohort studies, three were prospective cohort studies, and none were randomized controlled trials. No studies were at serious or critical risk of bias by evaluation with ROBINS-I quality tool. The average sample size was 553 patients (range N=21–5110). The median age was 72 years and 67.1% were male. The prognostic association of malnutrition and outcomes varied by malnutrition tool used. Malnutrition as measured by the validated tools of GNRI and CONUT was associated with all mortality outcomes, except for GNRI and cardiovascular mortality. The malnutrition surrogate markers of albumin and BMI were only associated with mortality outcomes in 62.5–75% of results. The validated nutrition tools were also consistently prognostic of amputation outcomes in all results, whereas surrogate markers only in 62.5–67%. Overall malnutrition by validated tools was prognostic in 14/15 (93.3%) of results while surrogate markers in 29/42 (69%) of results. See table 1.

Conclusion
Malnutrition is prognostically associated with mortality and amputation outcomes in CLI. This association is most consistent when malnutrition is assessed by a validated tool.

Funding Acknowledgement
Type of funding sources: None.