Luthra, Shailly; (2024) Dental Treatment and Acute Vascular Events-Exploring The Association. Doctoral thesis (Ph.D), UCL (University College London).

Text Shailly L-18134039-Final Thesis Copy.pdf - Other Access restricted to UCL open access staff until 1 April 2025. Download (22MB)

Abstract

Background: Acute infection/inflammation is linked to increased risk of acute vascular events. Invasive dental treatments are a common cause of acute inflammation. The bacteraemia and trauma resulting from the procedures result in increased systemic inflammatory load and vascular dysfunction are plausible mechanisms in this association. The aim of this PhD was to explore the nature and mechanisms involved in this association. Methods: The research programme methodology included, critical appraisal, observational and experimental evidence generated from several studies: 1. Study I: A systematic review and meta-analysis appraising the available evidence on the association between invasive dental treatment and incident acute vascular events. 2. Study II: A systematic review and meta-analysis of the available evidence about the short- and long-term effects of the treatment of periodontitis on systemic inflammation assessed through randomised controlled clinical trials using non-surgical periodontal therapy as a means of invasive dental treatment. 3. Study III: A critical-narrative review exploring the acute changes involved in the association between treatment of periodontitis and vascular complications including inflammatory, bacterial, and vascular dysfunctional pathways. 4. Study IV: A case-control study with healthy adults exploring the effect of gingival inflammation on markers of atherosclerotic risk assessed via monocytes subsets, platelet numbers, formation of monocyte platelet aggregates (MPAs) and changes in endothelial progenitor cell (cEPC) numbers. 5. Study V: An ex-vivo study exploring the effect of bacterial stimulation using LPS from Escherichia coli (E. coli), LPS from Porphyromonas gingivalis (Pg) and whole Pg on monocytes subset populations, platelets and MPAs formation in healthy adults. 6. Study VI: A randomised controlled trial of intensive treatment of periodontitis using photodynamic therapy versus placebo on vascular function, biochemical and cellular markers of vascular health. Results: Study I demonstrated that patients undergoing common invasive dental procedures do not exhibit an increased risk of acute vascular events during the first 8 weeks after treatment. Study II confirmed the beneficial effects of the treatment of periodontitis in reducing serum CRP levels consistently up to six months and in magnitude the effect is equivalent to that observed after conventional lifestyle and drug interventions. Study III summarised available evidence on the various mechanisms which work in synchrony post an invasive dental treatment and could increase the risk of occurrence of an acute vascular event. Study IV raised a credible hypothesis that an increase in gingival inflammation enhance monocyte–platelet crosstalk and could contribute to platelet and monocyte activation, along with increased CD34+ cells and decrease in EPC counts, all of which add to increased risk for vascular events. In Study V cellular response to a common periodontal pathogen translated into a “pro-atherogenic” populations of monocytes, and high risk MPA subsets. Conclusion: This research programme provided credible evidence on the links between invasive dental treatment and increased risk of acute vascular events. Further studies should explore the nature and the impact of invasive dental treatment on acute risk for acute vascular events in patients with periodontitis.

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