Date of Award
2024
Document Type
Thesis - ECU Access Only
Publisher
Edith Cowan University
Degree Name
Doctor of Philosophy
School
School of Medical and Health Sciences
First Supervisor
Professor Wei Wang
Second Supervisor
Dr Lois Balmer
Abstract
Despite advanced therapies, cardiometabolic diseases (CMDs), including cardiovascular disease (CVD) and diabetes, are major causes of morbidity and mortality worldwide. Unraveling new biomarkers to facilitate risk identification and early targeted intervention is an unmet need for precision medicine.
Disruption of hematopoietic system homeostasis, especially monocytosis and its related inflammatory cascade, play a major role in the pathogenesis of CMDs. Converging evidence has linked a variety of unfavorable lifestyle patterns and cardiometabolic abnormalities to increased monocytosis, highlighting the need for investigating the role of circulating monocyte changes in the development of CMDs. For example, nutrient overload, physical inactivity, insufficient sleep, excess weight and metabolic disorders, including hypertension, hyperglycemia and cholesterol defects, can potentially induce monocytosis. In contrast, increasing high-density lipoprotein (HDL) levels has been shown to eliminate the proinflammatory and pro-oxidative effects of monocytosis. While emerging evidence has shed light on the monocyte-related mechanisms underlying the development of CMD, limited population-based epidemiological studies have investigated the utility of monocyte-related inflammatory biomarkers for incident CMD.
In this context, several sub analyses based on data from a community-based, real-life, prospective cohort in China (the Kailuan study) were conducted to provide data-driven epidemiological insights into the role of monocytic inflammation in developing CMDs and all-cause mortality, especially examining the potential confounding effects of diverse cardiometabolic abnormalities and lifestyles.
This thesis is composed of 8 chapters: an overview of the thesis (Chapter 1), a comprehensive literature review (Chapter 2), 5 results chapters (Chapters 3–7), and a final chapter with a general discussion of the main findings and future directions (Chapter 8). The first chapter of the thesis includes an introduction and overview of the thesis. This is followed by a comprehensive literature review on the epidemiology and pathophysiology of CMDs, monocyte-related inflammation and feasible biomarkers IV (Chapter 2). Firstly, the association between the cumulative monocyte-to-HDL ratio (MHR) and incident diabetes incidence and considered its interaction with high[1]sensitivity C-reactive protein (hsCRP) was investigated (Chapter 3). Thereafter, I examined the risk prediction value of chronic inflammation assessed by hsCRP and the MHR for incident diabetes (Chapter 4). Additionally, I investigated the role of the MHR in incident myocardial infarction and specially assessed MHR-related residual cardiovascular risk within ideal LDL-C levels (Chapter 5). In Chapter 6, I investigated the effect of elevated monocyte counts on all-cause death and its ability to predict all-cause mortality risk. Furthermore, I examined the age-specific association between elevated monocyte counts and all-cause death and the joint effect of increasing age and monocytosis on mortality (Chapter 7). Chapter 8 contains a general discussion of the studies covered in this thesis. It underscores that monocyte-related biomarkers, both the MHR and the monocyte count, significantly improved the risk prediction and stratification of incident diabetes, myocardial infarction and all-cause death. Additionally, an imbalance in monocyte and HDL-C levels may be a potential target for further addressing residual cardiovascular risks. Finally, elevated monocyte levels synergistically enhanced the all-cause death risk among individuals with cardiometabolic abnormalities (e.g., diabetes, hypertension, or advanced age) in a supra-additive pattern, which informs health-promoting strategies for extending longevity among at-risk subgroups.
DOI
10.25958/17wv-c426
Access Note
Access to this thesis is embargoed until 12 September 2029
Recommended Citation
Wu, D. (2024). Monocytic inflammation and cardiometabolic diseases and mortality. Edith Cowan University. https://doi.org/10.25958/17wv-c426