Heart failure with preserved ejection fraction (HFpEF) is strongly linked to obesity and remains poorly understood, with limited treatment options. Not all obesity carries the same cardiovascular risk: visceral fat is more harmful than overall body weight, yet most research still relies on BMI alone.
This study investigates how different obesity patterns affect the left atrium and whether left atrial dysfunction drives the risk of atrial fibrillation, heart failure hospitalisation, and cardiovascular death in people with HFpEF.
Research questions: (1) Which obesity measures, including waist-based indices, body fat percentage, and MRI-derived visceral fat, are most causally linked to left atrial dysfunction and cardiovascular events? (2) How do inflammation, insulin resistance, and metabolic disturbances mediate this relationship? (3) Are there distinct metabolic subtypes of HFpEF that may respond differently to treatment?
Using UK Biobank data from approximately 500,000 participants, we will combine cardiac imaging, blood biomarkers, metabolomics, ECG, and genetic data. The study is designed as a target trial emulation – a rigorous causal inference framework that mimics a clinical trial using observational data – with inverse probability weighting to control for confounding. Mendelian randomisation will use genetic variants as natural experiments to strengthen causal conclusions. Mediation analyses will map the biological pathways from obesity to atrial damage.
Findings will inform clinical guidelines, support earlier detection of atrial dysfunction, and identify low-cost risk markers applicable in resource-limited healthcare settings.
