Temporal trajectories of disease progression following hypertensive disorders of pregnancy

Thesis

Hypertension in pregnancy leaves a lasting imprint on women’s health, increasing the risk of disease across multiple organ systems long after childbirth. Yet the trajectories linking hypertensive pregnancy to long-term disease risk are not fully understood. This thesis investigates whether women with hypertensive pregnancies show early organ remodelling which predisposes them to later disease, and whether these early structural alterations set accelerated trajectories towards long-term dysfunction.

Within the current literature, there is consistent evidence of functional changes across the heart, kidneys, brain and microvasculature before, during and after hypertension during pregnancy. Despite reports of apparent recovery in renal function postpartum, the use of magnetic resonance imaging in this thesis demonstrates that women with hypertensive pregnancies show subclinical structural renal impairments at six to twelve months postpartum, which may underlie their future renal disease susceptibility.

Analyses of the retinal microvasculature at the same timepoint revealed that women with hypertensive pregnancies show increased arteriolar and venular narrowing, compared to their normotensive counterparts; with the degree of narrowing being equivalent to values typically seen in women two decades older, indicating premature microvascular ageing. Additionally, increased microvascular narrowing was consistently observed at 15-25 years postpartum, suggesting a fixed microvascular phenotype over time.

Longitudinal cardiac assessments further highlighted the prevalence of early diastolic dysfunction and concentric remodelling in women with hypertensive pregnancies. These phenotypes remained consistent across two decades postpartum, highlighting pregnancy as a critical inflection point that sets long-term cardiovascular trajectories. Furthermore, there was evidence of an accelerated increase in left ventricular mass in women with hypertensive pregnancies, underscoring the need for increased cardiovascular monitoring in this population.

Collectively, these findings suggest that hypertensive pregnancy disorders induce early, fixed phenotypes across multiple organs, providing a mechanistic substrate for the elevated lifetime risk of disease. As such, they highlight the need for early postpartum screening, targeted prevention, and pre-pregnancy risk stratification. Future research should prioritise integrating imaging biomarkers with clinical data to develop risk stratification models and to explore artificial intelligence-driven tools for automated, scalable organ phenotyping in maternal health.

Authors: Cutler, HR

• DOI: 10.5287/ora-dxpzzeyna
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: longitudinal disease progression; hypertensive disorders of pregnancy; temporal trajectories
• Subjects: Hypertension in pregnancy