Exploring the relationship between body composition, systemic inflammation, and outcomes in vascular surgical disease

Bradley, Nicholas Andrew (2025) Exploring the relationship between body composition, systemic inflammation, and outcomes in vascular surgical disease. PhD thesis, University of Glasgow.

Abstract

Cardiovascular disease remains the leading global cause of death, with a predicted increase in the future due to a range of demographic and social factors. Within this spectrum of illnesses, vascular surgical conditions are an important group of problems. The typical underlying pathophysiology is atherosclerosis, which has a well described risk factor profile. The disease entities which comprise the majority of vascular surgical practice are aortic aneurysm (AAA), chronic limb threatening ischaemia (CLTI), and cerebrovascular disease (CVD).

Sarcopenia, defined as a progressive loss of skeletal mass and function (EWGSOP2 definition), has recently emerged as an important factor associated with a range of chronic illnesses. It has been evaluated as a potential prognostic factor, with the largest amount of evidence coming from patients with cancer. CT-derived body composition analysis (CT-BC) is a technique used to quantify sarcopenia through measurement of cross-sectional tissue areas, allowing muscle and fat indices to be derived and quantitatively analysed.

A key aetiological factor in the development of both cardiovascular disease and sarcopenia is the systemic inflammatory response (SIR). The SIR can be quantified using inflammation-based prognostic scoring systems, such as the neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS), both of which have been independently associated with inferior survival in patients with cancer.

In vascular surgical conditions, both sarcopenia as measured by CT-BC, and the SIR, are less widely reported than in other conditions. The aim of the present thesis was to describe the existing evidence base describing these factors, and evaluate their associations and potential prognostic value, in patients with AAA, CLTI, and CVD.

In chapter 2 the literature describing the potential prognostic role of CT-BC in patients undergoing elective endovascular repair (EVAR) of AAA was reviewed, and on meta-analysis a clear association between low skeletal muscle mass and inferior survival outcomes was observed, however the existing studies had limited methodology.

In chapter 3, CT-BC parameters were evaluated in a multicentre cohort of patients undergoing EVAR for AAA. There was an independent association between low skeletal muscle index (SMI) and inferior survival outcomes in this cohort.

In chapter 4 the literature describing the association between elevated NLR and PLR and outcomes in patients undergoing intervention for AAA was reviewed. Elevated NLR and PLR were generally associated with inferior long-term survival., despite limitations in methodology observed.

In chapter 5 the NLR and mGPS were combined into the systemic inflammatory grade (SIG), which aims to provide a more comprehensive assessment of the SIR. There was an independent association between increasing SIG and inferior survival outcomes in patients undergoing intervention for AAA.

In chapter 6 Combining the factors of interest from chapters 3 and 5 in chapter 6 allowed for a description of the combined potential prognostic value of both CT-derived sarcopenia (as measured through CT-SS, a novel observation in this patient group) and the SIR (as measured through SIG). There was a marked observation of significantly inferior survival in patients with both low skeletal muscle mass/density and elevated SIG.

In chapter 7 a possible association between sarcopenia and inferior physiological fitness as assessed by cardiopulmonary exercise testing (CPEX) was explored, with sarcopenia assessed using the CT-Sarcopenia Score (CT-SS), which combines muscle mass and density. There was no significant association between sarcopenia and CPEX parameters. compared to CPEX parameters, CT-SS demonstrated greater association with survival.

In chapter 8 patients undergoing intervention for AAA were compared to patients undergoing resection for colorectal cancer (CRC). The magnitude of the SIR and low skeletal muscle density (SMD) were more prevalent in patients with CRC, and there was an association between increasing age and decline in CT-BC parameters in both patient groups.

In chapter 9 the post-operative SIR was examined in relation to survival following both elective and emergency repair of AAA. Elevated day 3 CRP was associated with inferior survival outcomes in both the elective and emergency cohorts, though at different timepoints.

In chapter 10 the literature describing survival outcomes, disease severity, and technical success of intervention in patients with CLTI, in relation to NLR and PLR, was reviewed. Methodology was heterogenous in the 34 studies, however the majority of studies report an association between elevated NLR/PLR and the outcomes of interest.

In chapter 11 the effect of frailty (as measured by the clinical frailty score, CFS), CT-BC, and the SIR on survival in a cohort of patients with CLTI was described. CT-SS, mGPS, and CFS were independently associated inferior survival outcomes.

In chapter 12 the association between CT-BC, the SIR, and survival was described in a cohort of patients undergoing carotid endarterectomy for symptomatic carotid lesions. The SMD at C3 and elevated SIG were shown to be independently associated with inferior survival.

In chapter 13 the longitudinal change in CT-BC was investigated in patients undergoing intervention for AAA. A decline in both SMI and SMD was observed following intervention for AAA. The decline in SMD was of a greater magnitude than SMI. Statin therapy was associated with a lower risk of baseline low SMI.

In chapter 14 the cross sectional liver area was recorded in patients with AAA at baseline and at follow-up CT, and the association between survival and relationship to CT-BC parameters was tested. Low liver area was associated with inferior survival. There was a decline in liver area, but a preservation of liver density. CT-BC muscle parameters had a greater associated with survival than liver parameters.

The present thesis reports a multitude of novel observations which demonstrate an association between CT-BC, the SIR, and survival, as well as their associations, in patients with vascular surgical conditions. These results support the work performed in different conditions, and highlight the possible role of these factors in clinical risk prediction and patient selection.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QP Physiology; R Medicine > R Medicine (General); R Medicine > RD Surgery
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Supervisor's Name: McMillan, Professor Donald and Guthrie, Mr. Graeme
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85439
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 08 Sep 2025 10:47
• Last Modified: 08 Sep 2025 10:49
• Thesis DOI: 10.5525/gla.thesis.85439
• URI: https://theses.gla.ac.uk/id/eprint/85439

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