At a glance
A clinical trial of more than 3,600 patients evaluated for chest pain showed that fatty liver disease was linked to nearly double the rate of heart attacks and related events.
Heart CT scans showed that people with fatty liver had substantially more “soft,” rupture-prone plaque in their coronary arteries, revealing a pathway that helps explain their higher risk.
The findings reinforce the concept of a “liver-heart” connection, where excess fat and inflammation in the liver drive coronary artery changes that can lead to heart attacks.
A large, multicenter clinical trial has found that people with hepatic steatosis, commonly called fatty liver disease, have significantly more rupture-prone plaque in their coronary arteries and nearly twice the rate of heart attacks and related events than those without steatosis.
Fatty liver disease is already known to raise the risk of heart disease, but until now, researchers hadn’t understood how. The new findings, published May 20 in Clinical Gastroenterology and Hepatology, reveal a specific biological mechanism behind the link. The researchers suspect there will be others.
The work suggests that cardiac CT scans already being used to evaluate chest pain could also be used to check for hepatic steatosis and help identify patients who need more aggressive prevention strategies.
The findings bolster the understanding that fatty liver disease “is not only a liver condition but also an important marker of heart disease risk,” said first author Jan Brendel, Harvard Medical School research fellow in radiology at Massachusetts General Hospital. “Fatty liver disease can be detected on routine cardiac CT scans and could help guide earlier, more targeted preventive treatment.”
Fatty liver disease is marked by an accumulation of excess fat in liver cells and affects an estimated 30 to 40 percent of American adults. The new findings reinforce the idea of a “liver-heart” connection, where excess fat and inflammation in the liver help drive artery changes that can lead to heart attacks.
HMS researchers at Mass General and their collaborators at Duke University, Oregon Health & Science University, Tufts University, and European institutions drew on data from 3,637 participants in the PROMISE trial, a multicenter study of stable outpatients with chest pain.
The researchers analyzed cardiac CT scans from participants evaluated for chest pain across 193 clinical sites in North America. The scans captured both the coronary arteries and, incidentally, portions of the liver, allowing the team to simultaneously assess coronary plaque and detect fatty liver disease. Just over 25 percent of participants had the condition.
Patients with fatty liver had 24 percent more soft, cholesterol-rich plaque in their coronary arteries than those without the condition, even after adjusting for obesity and standard cardiovascular risk factors. This type of plaque, known as noncalcified plaque, is more prone to rupturing and triggering a blood clot than the hardened, calcified type and is considered the more dangerous of the two.
Over roughly two years of follow-up, 4.1 percent of participants with fatty liver disease experienced a major cardiovascular event — including death, heart attack, or hospitalization for chest pain caused by reduced blood flow to the heart — compared with 2.5 percent of those without it.
After accounting for cardiovascular risk factors, obesity, and the extent of blocked arteries, fatty liver disease was associated with a 69 percent higher risk of a serious heart-related event.
The buildup of this dangerous soft plaque explained about 11 percent of that excess risk — suggesting it is one mechanism by which fatty liver disease raises cardiovascular danger. The remaining risk appears to operate through other pathways not yet identified, the authors said.
Because fatty liver disease can be spotted incidentally on the same CT scans used to evaluate coronary artery disease, the findings support using that information when it is present to help incorporate liver assessment into routine cardiac imaging. The authors note, however, that they are not recommending CT scans be ordered solely to look for fatty liver.
The researchers say future studies should examine whether treatments such as cholesterol-lowering statins or newer weight-loss and diabetes medications known as GLP-1 receptor agonists (such as those marketed as Zepbound and Wegovy) can slow or reverse dangerous plaque buildup in patients with fatty liver disease.
Randomized trials will be needed to determine whether targeting liver fat or high-risk plaque actually lowers the risk of heart attacks and related events.
Authorship, funding, disclosures
Borek Foldyna, HMS assistant professor of radiology at Mass General, is senior author of the study. Additional authors include Thomas Mayrhofer, Nóra M. Kerkovits, Márton Kolossváry, Sara Ersözlü, Brooke Alhanti, Kathleen E. Corey, Neha Pagidipati, Svati H. Shah, Nandini M. Meyersohn, Maros Ferencik, Michael T. Lu, Stefania Lamon-Fava, Udo Hoffmann, and Pamela S. Douglas.
This study was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (grants R01HL098236, R01HL098237, R01HL098305, 1R01HL170877, and R01HL146145).
A full list of disclosures can be found in the paper.
