Examination of lower limb endothelial function and response to (poly)phenols in healthy people and people with diabetes mellitus
Creators: name: Bapir, Mariam
Publisher: name: University of Surrey
Year: 2023

description: Chapter 1: Lower extremity peripheral artery disease (PAD) is a major growing healthcare burden worldwide and responsible for the majority of leg amputations, particularly in people with diabetes (T2DM). Early biomarkers of lower extremity artery health that could serve as therapeutic target for PAD prevention and treatment do not exist. Endothelial dysfunction is an early key event in the development of arterial disease. The measurement of endothelial function by flow-mediated dilation (FMD) in the brachial artery (BA) has been established as a surrogate marker for global cardiovascular risk related to coronary and cerebrovascular atherosclerosis. Only few studies have evaluated FMD in atherosclerosis prone lower extremity arteries. This could serve as a marker of lower extremity artery health in the future. The overall aim of the PhD work was to further the development of leg endothelial function assessment towards a lower extremity artery health biomarker. It is the specific hypothesis that endothelial function of lower limb arteries is impaired in people with diabetes, that are at increased risk for PAD, and that cocoa flavanols (CF), that are associated with lower PAD risk, can improve this. This PhD by publication comprises of 5 publications with the first 4 describing work leading to the fifth paper which answers the hypothesis. <br>
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description: Chapter 2: This paper includes an analysis of BA FMD values from 1,579 apparently healthy individuals (aged 18–76, data from 44 studies, 6 institutions, 22 operators) and meta-analysis of 82 published trial. It provides an age-adapted frame of BA FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health (Cardiovasc Res. 2022). <br>
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description: Chapter 3: Investigation of the reproducibility and tolerability of BA and femoral artery (FA) FMD in 20 healthy participants. The results show that reproducibility of FA FMD is similar to BA FMD and endothelial function declines similarly with age in the FA and the BA in healthy adults. The age-dependent FA enlargement results in a critical decrease in WSS that may explain part of the age-dependent predisposition for PAD. (Under review in Life). <br>
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description: Chapter 4: Description of a software to analyse optical coherence tomography angiography (OCTA) images for non-invasive visualization and characterization of the cutaneous microvasculature. OCTAVA is a user-friendly, opensource toolbox to automate the pre-processing, segmentation, and quantitative analysis of en face OCTA maximum intensity projection images in a standardized workflow and can accurately and reproducibly determine metrics for microvascular metrics. (PlosONE 2021). <br>
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description: Chapter 5: This study evaluated the individual variability of BA FMD, blood pressure and arterial stiffness responses to commercially available CF supplement in everyday life using a series of n-of-1 trials in healthy individuals carrying personal devices. The data confirm that this cocoa supplement can improve FMD under laboratory conditions and can decrease blood pressure and arterial stiffness in everyday life when elevated within the normal range. (Front Nutr. 2022). <br>
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description: Chapter 6: This study assesses if FA endothelial function and dermal microcirculation are impaired in individuals with T2DM and evaluates the acute effect of CF consumption on FA endothelial and microvascular function. The results show that individuals with T2DM exhibit decreased endothelial function that is more pronounced in the FA than in the BA. CF increase endothelial function not only in the BA and the FA both in healthy individuals and in those with T2DM who are at increased risk of developing lower extremity PAD and foot ulcers (Food Funct 2022). Chapter 7: The results are compatible with the concept that measurement of endothelial function in leg arteries can serve as biomarker of lower limb vascular health. The work warrants further research to develop leg artery FMD as a personalised therapeutic target to prevent PAD in the future.<br>