Spleen Imaging Signatures May Reveal Hidden Coronary Artery Disease Risk

Coronary artery disease (CAD) remains a leading cause of death despite major gains in managing traditional risk factors. Clinicians still struggle to quantify residual risk and the upstream biology that drives events. The spleen, a hub for hematopoiesis and immune activity, is difficult to evaluate with routine testing. To help address this challenge, investigators have developed AI analysis of abdominal imaging to uncover splenic features linked to CAD and its genetic architecture.

Researchers at Mass General Brigham applied machine learning to abdominal scans and paired the imaging outputs with clinical outcomes and genomic data. The approach extracted quantitative features from the spleen and assessed whether they tracked with CAD risk. The study was published on September 9, 2026, in Science Translational Medicine.

The team analyzed data from 42,059 UK Biobank participants. From 107 spleen-derived imaging features, 10 showed associations with CAD. They then performed genome-wide association analyses to test whether known CAD genes also correlated with spleen features captured on imaging.

Genes linked to both spleen features and CAD were related to inflammation, smooth muscle cell function, hypertension, and fat cell formation. Many associated variants localized to noncoding regulatory regions. Two variants at the 9p21 locus on chromosome 9 were tied to a nonuniform, irregular splenic texture and to higher odds of CAD independent of blood pressure, cholesterol, and other conventional risk factors.

The investigators next asked whether these population findings would generalize to routine care. In 2,745 patients imaged within the Mass General Brigham Biobank, most associations did not persist. The authors note that research cohorts such as the UK Biobank are typically healthier and scanned under uniform protocols, whereas clinical patients have more complex histories and varied imaging, potentially reflecting different biological states.

Taken together, the work highlights splenic imaging signatures that co-map with CAD genetics and points to an underexplored hematologic-immune axis. The features suggest potential targets for prevention and treatment that merit further study. The findings also outline practical challenges for translating population imaging-genetics into heterogeneous clinical workflows.

"Evidence increasingly ties the blood-forming system to heart disease, and the spleen is a central hub of that system, storing and filtering blood and producing immune and inflammatory cells. But the spleen is hard to assess through routine tests, so imaging is a powerful way to see nuanced changes in the organ and ask whether they reflect, or even forecast, disease," said Zhi Yu, MB, Ph.D., an investigator in the Clinical and Translational Epidemiology Unit and Center for Genomic Medicine at Mass General Brigham.

"These findings shed light on novel mechanisms linking the spleen to CAD, providing potential targets for therapeutic intervention to address this unexplored axis," said Meghana Kamineni, MD, an internal medicine resident at Mass General Brigham.

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