Systemic Inflammation, Arterial Stiffness, and Vascular Endothelial Dysfunction in Patients with Chronic Lung Disease

  • Abdullah M. Arafah

    Student thesis: Doctoral ThesisDoctor of Philosophy

    Abstract

    Chronic lung disease (CLD) is considered a heterogeneous, complex, and multicomponent condition. Types of CLD include bronchiectasis, chronic obstructive pulmonary disease (COPD), and asthma. Cardiovascular events and peripheral vascular disease are highly prevalent among patients who are known to have CLD. It is increasingly acknowledged that cardiovascular comorbidities contribute to the disease’s severity. The underlying mechanisms that link CLD and cardiovascular disease (CVD) are inadequately understood. Systemic inflammation is a key component that could describe the link between CLD and CVD. Changes in vascular endothelial function accompany the increased cardiovascular events in CLD. Atherosclerosis and calcification of macrovascular and microvascular lead to further decrease vascular compliance. These structural changes in the vascular wall contribute to increased arterial stiffness observed in patients with CLD. Endothelial dysfunction and arterial stiffness are early signs of vascular disease and the development of cardiovascular events. Chronic systemic inflammation plays a vital role in linking CLD to the development of endothelial dysfunction and arterial stiffness. Therefore, this study aims to investigate the association between CLD and CVD. To successfully achieve the aims of this project, four work packages were employed, including a systematic review, a retrospective study, a Mendelian randomisation study, and a cross-section study involving the BRIDGE study. The systematic review study related to arterial stiffness in patients with CLD using various pulse wave velocity (PWV) methods, which assessed and summarised the outcomes of all relevant studies regarding the link between CLD and CVD. The retrospective study analysed anonymous data from the SUMMIT study to assess the vascular function in patients with CLD in the presence of CVD and type 2 diabetes mellitus, and shows a significantly greater PWV; p-value = 0.015 and carotid intima-media thickness (CIMT) in the CLD patients; p-value = 0.001. The Mendelian randomisation study investigated potential genetic causal links between CLD and arterial stiffness, which shows a significant association; p-value = 0.021. The cross-section study and BRIDGE study utilised biomarkers to determine if there are shared pathways that contribute to the development and progression of CLD and CVD, and shows significant differences in PWV, and microvascular function; p-value = 0.001, blood biomarkers include adiponectin, VCAM-1, GDF-15, coagulation factor III, syndecan-1, and matrix metalloproteinase (MMP-10); p-value = 0.001. In conclusion, this study revealed a significant association between CLD and CVD. Therefore, monitoring CVD risk, including assessment of endothelial dysfunction and arterial stiffness, in patients with CLD might be helpful for risk stratification and for identifying future CVD pathologies and disease progression. This emphasises the need to identify and manage comorbid CLD and CVD to target new or existing therapeutic approaches to control systemic inflammation and improve overall lung and cardiovascular health.
    Date of Award2024
    Original languageEnglish
    SponsorsMinistry of Education, Saudi Arabia
    SupervisorFaisel Khan (Supervisor) & James Chalmers (Supervisor)

    Keywords

    • Cardiovascular disease
    • Arterial stiffness
    • Endothelial dysfunction
    • Pulse wave velocity
    • PWV
    • Systemic inflammation
    • Chronic obstructive pulmonary disease,
    • COPD
    • Bronchiectasis
    • Asthma

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