Spleen imaging features may signal coronary artery disease risk

Researchers at Mass General Brigham have identified a new way to assess heart disease risk by looking at the spleen—an organ that most doctors never examine closely, hidden as it is within routine abdominal scans. The findings, published in Science Translational Medicine, suggest that certain visible features of the spleen on imaging may signal whether someone is at higher risk for coronary artery disease, independent of the cholesterol levels and blood pressure numbers that doctors have relied on for decades.

The study drew on data from 42,059 people in the UK Biobank, a large research database of health information and medical images. Using artificial intelligence tools to analyze abdominal imaging scans, the team identified 107 distinct features visible in the spleen. Of those, ten showed a measurable association with coronary artery disease. The researchers then performed genetic analyses to understand whether the same genes that influence these splenic features also influence heart disease risk. They found that certain genetic variants—particularly two variants at a location on chromosome 9 called 9p21—were linked both to an irregular, nonuniform texture in the spleen and to increased odds of coronary artery disease. Notably, this genetic association held up even after accounting for conventional risk factors like blood pressure, cholesterol levels, and other established markers.

The spleen's relevance to heart disease stems from its role in the body's blood-forming and immune systems. The organ stores blood, filters it, and produces immune and inflammatory cells—making it, in essence, a central hub for processes that increasingly appear connected to cardiovascular disease. Yet the spleen remains difficult to assess through standard clinical tests. Imaging offers a window into subtle changes in the organ's structure and composition that routine blood work cannot capture. Zhi Yu, one of the study's senior authors, noted that while modern medicine has made tremendous strides in lowering LDL cholesterol and managing other classical risk factors, substantial risk for heart disease persists. Understanding the spleen's role represents an attempt to address that gap.

The genetic variants identified in the study pointed to biological pathways involved in inflammation, smooth muscle cell function, hypertension, and fat cell formation—all processes relevant to heart disease. Many of these genetic associations fell within non-coding, regulatory regions of the genome, suggesting they influence how genes are turned on or off rather than changing the proteins themselves.

But the research hit an important limitation when the team tested whether their findings would hold up in real clinical practice. They examined 2,745 patients from the Mass General Brigham Biobank who had undergone imaging as part of routine medical care. Most of the associations identified in the UK Biobank cohort did not replicate in this clinical population. The difference likely reflects a fundamental distinction between the two groups: the UK Biobank participants tend to be healthier and were scanned using standardized protocols, while clinical patients often have more complex medical histories and are imaged under widely varying technical conditions. What appears as a clear biological signal in a uniform research cohort may look different when applied to the messier reality of everyday medical practice.

Meghana Kamineni, the study's lead author, framed the findings as opening a new avenue for understanding how the spleen connects to heart disease—and potentially for developing new treatments targeting that connection. The next step will be validating these patterns in more diverse patient populations and determining whether the splenic features identified in imaging scans can actually predict which individuals will develop coronary artery disease in the future. For now, the work suggests that the spleen, long overlooked in cardiovascular medicine, deserves closer attention.