# Assessment of Blood-Count-Derived Biomarkers, Homocysteine Levels, MTHFR Mutation, and Clinical Manifestations in Severe Peripheral Artery Disease

## TL;DR

The study explores how blood markers, homocysteine levels, and MTHFR gene mutations relate to severe peripheral artery disease outcomes, especially in diabetic patients.

## Contribution

The study identifies associations between MTHFR mutations, hyperhomocysteinemia, and adverse outcomes in severe peripheral artery disease patients.

## Key findings

- Homozygous MTHFR mutation (C677T) was linked to significantly higher homocysteine levels in severe PAD cases.
- Pathological blood-count-derived biomarkers correlated with longer hospital stays in PAD patients.
- S. aureus and C. albicans were frequently identified in infected PAD patients.

## Abstract

Background: Infection and consequent limb amputations are complications of severe peripheral artery disease, especially in diabetic patients. Risk factors and prognostic markers are of particular importance in defining patient care. Methods: This study included 99 peripheral artery disease (PAD) patients admitted for surgical intervention in the 2020–2021 time interval. The included subjects were stratified by type 2 diabetes mellitus (T2DM) diagnosis (present/absent). Protein, albumin concentrations, blood-count-derived inflammatory markers, and cultures from gangrenous wounds were assessed. In the group of severe cases, needing lower limb amputation (n = 31), homocysteine level, and related methylene tetrahydrofolate reductase (MTHFR) gene mutations were also investigated. Results: The mean age of patients was 68.36 ± 11.79 (SD) years and T2DM patients were significantly older (p = 0.0303). The measured inflammatory markers were at normal values in 20% of the subjects. In the cohort of infected patients, S. aureus, P. mirabilis, P. vulgaris, and S. agalactiae were the most commonly identified bacteria, with C. albicans prevailing as the most common fungal pathogen. The patient length of stay (LoS) was significantly longer in patients with pathological blood-count-derived biomarkers (p = 0.0283). A total of 58% of the severe cases presented hyperhomocysteinemia (mean 17.7 ± 10.6 (SD) μmol/L), and 19% of them presented homozygous mutation of the MTHFR gene (C677T), while 39% carried a heterozygous mutation. Compared to those with normal alleles, homocysteine levels were significantly higher in subjects with homozygous mutation (p = 0.0334). Discussion: Homozygous MTHFR mutation was associated with hyperhomocysteinemia. Blood-count-derived inflammatory markers may indicate an unfavorable outcome for PAD patients, guiding clinicians in identifying patients that are prone to complications.