Your liver may be predicting a deadly heart attack risk, scientists warn

Although fatty liver disease has long been associated with an increased risk of heart disease, the biological mechanism behind this link has remained unclear. The new study, published on May 20 in Clinical Gastroenterology and Hepatology, identifies a specific pathway that helps explain the connection, while suggesting that additional mechanisms may also exist.

Researchers say the findings reinforce the growing understanding that fatty liver disease is not merely a liver disorder, but also an important marker of cardiovascular risk. “Fatty liver disease can be detected on routine cardiac CT scans and could help guide earlier, more targeted preventive treatment,” said lead author Jan Brendel, a Harvard Medical School research fellow in radiology at Massachusetts General Hospital.

Fatty liver disease, characterized by excess fat accumulation in liver cells, affects an estimated 30% to 40% of adults in the United States. The study strengthens the concept of a “liver–heart axis,” in which liver fat and inflammation contribute to changes in blood vessels that increase the risk of heart attacks.

The research team, including investigators from Massachusetts General Hospital, Duke University, Oregon Health & Science University, Tufts University, and several European institutions, analyzed data from 3,637 participants enrolled in the PROMISE trial, a multicenter study involving stable outpatients presenting with chest pain.

Cardiac CT scans performed across 193 clinical sites in North America were used to evaluate coronary artery disease. Because the imaging also captured portions of the liver, researchers were able to simultaneously assess coronary plaque characteristics and identify fatty liver disease. More than 25% of participants were found to have the condition.

Patients with fatty liver disease were found to have 24% more non-calcified, or “soft,” cholesterol-rich plaque in their coronary arteries compared to those without the disease—even after adjusting for obesity and other standard cardiovascular risk factors. This type of plaque is considered more dangerous because it is more likely to rupture and trigger blood clots than calcified, more stable plaque.

Over an average follow-up period of two years, 4.1% of participants with fatty liver disease experienced a major cardiovascular event—including heart attack, death, or hospitalization for chest pain due to reduced blood flow—compared to 2.5% of those without the condition.

After adjusting for cardiovascular risk factors, obesity, and the extent of coronary artery disease, fatty liver disease was associated with a 69% higher risk of major cardiovascular events.

Researchers noted that the accumulation of high-risk soft plaque accounted for about 11% of this increased risk, suggesting it is one of several mechanisms linking fatty liver disease to cardiovascular complications. The remaining risk likely involves other biological pathways that are yet to be fully understood.

Because fatty liver disease can be incidentally detected on cardiac CT scans used to evaluate chest pain, the findings raise the possibility of integrating liver assessment into routine cardiac imaging when available. However, the authors emphasized that they do not recommend performing CT scans solely to screen for fatty liver disease.

Future research will explore whether treatments such as cholesterol-lowering statins or newer GLP-1 receptor agonist medications—used for weight loss and diabetes management, including drugs like semaglutide and tirzepatide—can reduce or reverse high-risk plaque in patients with fatty liver disease.

The researchers also highlight the need for randomized clinical trials to determine whether targeting liver fat or vulnerable plaque can ultimately reduce the risk of heart attacks and related cardiovascular events.