Date of Award
2026
Keywords
hypertensive disorders of pregnancy, gestational diabetes, heterogeneity, risk stratification, insulin resistance, oxidative stress, postpartum cardiometabolic risk
Document Type
Thesis - ECU Access Only
Publisher
Edith Cowan University
Degree Name
Doctor of Philosophy
School
School of Medical and Health Sciences
First Supervisor
Wei Wang
Abstract
Despite advances in perinatal surveillance and care, hypertensive disorders of pregnancy (HDP) remain a major cause of maternal morbidity and mortality worldwide. Increasing evidence positions HDP as a critical window for lifelong cardiometabolic risk. Defining the heterogeneous long-term trajectories linking HDP to cardiometabolic diseases (CMDs), including cardiovascular disease (CVD) and diabetes, and identifying the factors shaping these associations remain important unresolved challenges.
Metabolic dysregulation, particularly insulin resistance and its interactions with inflammatory and oxidative stress pathways, is associated with the development of postpartum CMDs. Accumulating evidence indicates that HDP are linked to long-term risk through multiple interconnected processes, potentially involving genetic susceptibility, endothelial dysfunction, oxidative stress, chronic inflammation, and persistent metabolic abnormalities, and are reflected in heterogeneous postpartum risk trajectories. Clinical features, such as maternal age and comorbidities including gestational diabetes (GDM), may identify subgroups with distinct risk patterns, while genetic and biomarker studies provide complementary insights into this heterogeneity. However, population-based evidence remains limited, and postpartum care largely relies on relatively uniform approaches, with insufficient differentiation of individual risk. This thesis focuses on heterogeneity in cardiometabolic risk following HDP, integrating phenotypic patterns, biomarker evidence, and limitations in current clinical practice to inform more refined approaches to long-term risk assessment. In this context, I integrate evidence from meta-analyses, hospital-based longitudinal cohorts in China, UK Biobank data, and large-scale genome-wide association study (GWAS) summary statistics to characterize clinical heterogeneity and examine the associations of insulin resistance, oxidative stress, and inflammatory mediators with postpartum CMDs, extending the analysis to GDM and antenatal depression. This thesis is composed of six chapters: an overview of the thesis and a theoretical framework (Chapter 1), a comprehensive literature review (Chapter 2), and three results chapters (Chapters 3–5), followed by a general discussion of the main findings and future directions (Chapter 6).Chapter 1 introduces HDP and reviews the epidemiology, pathophysiology, and postpartum sequelae, while outlining an integrative conceptual framework that considers HDP in relation to women’s long term cardiometabolic health. This is followed by a comprehensive literature review on the epidemiological and mechanistic links between HDP, antenatal depression, and offspring neurodevelopment (Chapter 2). In Chapter 3, I investigated heterogeneity in postpartum cardiovascular risk among women with HDP by integrating latent class analysis with systematic review and meta-analysis. Distinct clinical phenotypes were identified, which showed differential associations with the risk of incident postpartum hypertension. Thereafter, I examined the role of insulin resistance in postpartum cardiovascular disease among women with a history of HDP using observational analyses and Mendelian randomization approaches (Chapter 4). The findings supported a potential role of insulin resistance in the development of postpartum CVD. In Chapter 5, I extended this framework to investigate pathways linking GDM to postpartum type 2 diabetes using causal mediation analysis. Oxidative stress and inflammatory pathways were examined as potential mediators of this association. Chapter 6 is a comprehensive discussion of all studies in this thesis. This thesis integrates multi-source data to systematically characterize the heterogeneity of postpartum cardiometabolic risk associated with HDP, shifting from a unified model to a risk-stratified analytical perspective. Based on distinct prognostic trajectories, potential metabolic pathways, and comorbidity-related mechanisms, this study provides key evidence for establishing a risk-stratified clinical decision-making framework. Overall, this study examines the association between HDP and postpartum cardiometabolic health from a life-course perspective and provides a scientific basis for developing more targeted postpartum precision prevention strategies.
Access Note
Access to this thesis is embargoed until 12th August 2031
Recommended Citation
Lin, D. (2026). Hypertensive disorders of pregnancy and postpartum cardiometabolic risk: Heterogeneity and risk stratification. Edith Cowan University. https://doi.org/10.25958/25tj-z188