Precision cardiovascular phenotyping in transgender populations: a multicentre study to define normative reference ranges and inform personalised care

Open to UK applicants only

Supervisors:

• Dr Ranjit Arnold jra14@le.ac.uk
• Dr Emer Brady
• Dr Jennifer Creese

Project Description:

Background

Transgender individuals represent a growing yet historically underserved population within healthcare systems, with recent estimates suggesting that approximately 1 in 200 people in England and Wales identify as transgender. As these individuals age, the burden of cardiovascular disease in this population is expected to increase. However, there are currently no validated cardiac reference ranges for transgender individuals, limiting accurate diagnosis and contributing to potential health inequalities.

Quantitative evaluation of cardiac volumes and function is critical for identifying pathological cardiovascular states and enabling accurate differentiation between physiological adaptation and disease. Accordingly, age and sex-specific reference values have been established using cardiovascular magnetic resonance (CMR), the gold standard non-invasive imaging modality for characterising cardiac morphology and function. Recent studies have investigated the effects of sex, ethnicity and factors such as diabetes on cardiac volumes and function, highlighting the diagnostic importance of population-specific reference standards.

In the England and Wales 2021 census, 262,000 people (0.5%) identified as transgender and 2.9 million (6.0%) left the gender identity question unanswered. Despite this, there are currently no studies evaluating cardiac structure and function in individuals receiving gender-affirming hormone therapy (GAHT). GAHT induces significant physiological changes in body composition, haemodynamics and metabolic profile, all of which may influence cardiac structure and function. Existing CMR reference ranges are derived exclusively from cisgender populations and are not directly applicable to transgender individuals receiving GAHT. Therefore, establishing population-specific reference ranges is essential to ensure accurate diagnosis, avoid misclassification of normal physiology as disease, and support equitable cardiovascular care in transgender populations.

This PhD builds on pilot work from our group which demonstrated the feasibility of recruiting from this population locally. The studentship will deliver a multicentre, cross-sectional study to establish robust, generalisable reference ranges for transgender people. Recognising that transgender individuals are historically underrepresented in clinical research, this study will also address barriers to participation by evaluating inclusive and scalable recruitment strategies across multiple sites. 

Aims:
1. Establish clinically relevant reference ranges for cardiac structure and function in transgender individuals receiving GAHT
2. Identify determinants of cardiac phenotype (hormone exposure, demographics, cardiometabolic factors)
3. Develop inclusive recruitment strategies for underrepresented populations 

Study population:
• Participants aged ≥18 years will be recruited 
• Participants who have been on GAHT for ≥2years (n=150, 75 transfeminine and 75 transmasculine)

Assessments:
• A single imaging assessment per participant will take place across 4-5 CMR centres including Glenfield Hospital Leicester, and other UK centres with whom the supervisors have existing collaborative links.
• CMR scans will comprise functional assessment (long- and short-axis Cine assessment) for quantification of left and right ventricular end-diastolic/end-systolic volumes, ejection fraction and myocardial mass. Scar assessment (involving gadolinium injection) is optional
• The study will also evaluate determinants of cardiac phenotype, including hormone therapy type and duration, biological sex, age, and cardiometabolic risk factors. 
• The multicentre design will enhance diversity, improve generalisability, and strengthen the clinical applicability of findings across healthcare settings.
• A qualitative assessment (remote interview) will explore barriers and facilitators to research participation, informing best-practice approaches for inclusive study design.
• This will help develop and optimise inclusive recruitment and engagement strategies, supporting improved engagement and participation of transgender people in clinical research.

Expected outcome
This project will provide the first clinically relevant reference ranges for cardiac imaging in transgender populations, directly informing diagnostic accuracy and personalised cardiovascular care. The findings will underpin future longitudinal and interventional studies, including investigations into cardiovascular risk, disease progression and the long-term effects of GAHT. By addressing a major evidence gap in an underserved population, this work aligns strongly with NIHR priorities in cardiovascular disease, multimorbidity, and equality, diversity and inclusion (EDI), and has clear potential to inform clinical guidelines and future funding applications.

This studentship will provide a well-rounded interdisciplinary training experience involving cardiac imaging and experience in multicentre study design and delivery. The mixed-methods design will provide both quantitative and qualitative analytical skills, and additional skills in participant engagement, interviewing, and thematic analysis. 

Please refer to the application advice below before submitting your online application.

References
1. Petersen SE, Matthews PM, Francis JM, et al. Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (UK Biobank population). JAMA Cardiology. 2017;2(4):417–425. 
2. Parke KS, Brady EM, Alfuhied A et al. Ethnic differences in cardiac structure and function assessed by MRI in healthy South Asian and White European people: A UK Biobank Study. J Cardiovasc Magn Reson. 2024. doi: 10.1016/j.jocmr.2023.100001. 
3. Nota NM, Wiepjes CM, de Blok CJM, et al. Occurrence of acute cardiovascular events in transgender individuals receiving hormone therapy. Circulation. 2019;139(11):1461–1462. 
4. Reisner SL, Poteat T, Keatley J, et al. Global health burden and needs of transgender populations: a review. The Lancet. 2016;388(10042):412–436. 
5. Safer JD, Tangpricha V. Care of transgender persons: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2017;102(11):3869–3903. 
6. Office for National Statistics. Gender identity, England and Wales: Census 2021. London: ONS; 2023. 
7. National Institute for Health and Care Research (NIHR). Improving inclusion of under-served groups in clinical research: NIHR INCLUDE project. London: NIHR; 2020.