High-Risk Plaque: The Hidden Killer that Has Doctors Divided

 Written by Lisa O'Mary

March 20, 2025 -- More people are likely to be diagnosed with a condition that heightens the risk of heart attack and stroke, thanks to a controversial broadening of the definition that has cardiologists sharply divided. 

The condition is “high-risk” plaque, once narrowly defined as plaque built up in the arteries that are likely to rupture, possibly leading to an acute heart attack or sudden cardiac death. It was rarely diagnosed due to the need for complex imaging tests.

But treatments for high-risk plaque — and understanding of the condition itself — have grown rapidly in recent years. And a leading cardiology journal just published a proposed broadened definition of high-risk plaque and how to spot it, meaning more people might see the term show up in their imaging test reports.

“Patients these days have access to their test results,” said senior author Ik-Kyung Jang, MD, PhD, professor of medicine at Harvard Medical School. “When they see high-risk plaque in the report, they may become panicked and call their cardiologist or doctor and ask, ‘Am I going to have a heart attack? Am I going to drop dead?’”

What happens next depends on your doctor because there are two schools of thought. Likely, your doc will recommend medication and lifestyle changes to reduce plaque buildup. But some are also advocating for more tests and diagnoses that, ultimately, could pave the way for invasive interventions like a stent, a mesh tube that can keep an artery open.

Medication and lifestyle changes alone can dramatically lower the risk. But because the new definition opens the door to more invasive procedures like stents, some maintain that it’s steering us down an unnecessary and potentially harmful path.

How Serious Is High-Risk Plaque?

High-risk plaque causes up to 40% of acute coronary syndromes (sudden heart blood flow problems like unstable angina and heart attack).

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Among several types of high-risk plaque, the most dangerous is called thin-cap fibro-atheroma plaque (TCFA) and is at especially high risk for rupture.

“We have followed patients with TCFA for four years,” said Jang. “Only 1% of TCFA plaques led to acute myocardial infarction [a heart attack]. One percent.”

If doctors were to treat all TCFA with stents, “99 out of 100 patients” would be receiving unnecessary treatment, said Jang, who used to favor stenting for TCFA, but after two decades researching vascular biology in living patients, now encourages medication management.

The new definition of high-risk plaque includes a range of imaging options for diagnosis, including CT scans.

CT scans usually lack the detail needed for firm diagnosis, which is why many patients are referred to Jang for further testing. By then, patients are extremely worried — but just because high-risk plaque was detected “doesn’t mean that’s going to cause trouble,” Jang tells them.

High-risk plaques are often described to patients as volcanoes, said study co-author Gregg W. Stone, MD, a professor at Icahn School of Medicine at Mount Sinai in New York. The problem is, sometimes a seemingly dormant volcano can erupt.

“You can walk on them, they look all fine, but you don't know that there's all this molten lava going on inside, which, if it bursts through, it then causes a real problem,” Stone said.

That’s what high-risk plaque is like. “It's basically a stable plaque until it's not,” Stone said. “And then it causes a heart attack, or threatened heart attack, or even sudden cardiac death for the patient.”

Where Both Sides Agree

Stone is among the group of cardiologists who advocate for more diagnostic imaging and possibly someday — if research supports it — offering patients procedures such as stents to reduce risks.

In addition to TCFA plaques, there are two other types that, if found on imaging, would be labeled as high-risk plaque on a report.

One is called erosion-prone plaque, which is “a more fibrous plaque, where there aren’t necessarily a lot of lipid or cholesterol deposits. There may be, but there doesn't have to be. And the plaque doesn't rupture,” like with TCFA, Stone said. “In plaque erosion, the surface of the plaque becomes irregular and inflamed, and a blood clot can form on the surface of the plaque.”

The other type is an eruptive calcified nodule, “which is this big, chunky deposit of calcium or multiple deposits of calcium,” Stone said. “It's very irregular, and it causes blood flow turbulence, and that can cause a blood clot to form. So the final common denominator of all three of these types of plaques is a blood clot.”

Regardless of the type, both sides agree that aggressive medical therapy is the “foundational approach,” the new position statement says.  

The treatment involves strong medication and lifestyle changes like a healthy diet, exercise, and quality sleep. Doctors may prescribe a statin along with other drugs that help lower cholesterol, reduce inflammation, or protect the heart, such as PCSK9 inhibitors, bempedoic acid, colchicine, ezetimibe, icosapent ethyl, and inclisiran, said Matthew Budoff, MD, professor of medicine at UCLA and chair of preventive cardiology at the Lundquist Institute in Torrance, California. (Budoff wasn’t involved in writing the new definition.)

These therapies can erase the label “high risk” from plaque or even reduce the buildup.

“Without therapy, they would be high risk,” Budoff said. “We have done numerous studies with different therapies and documented that we can stabilize plaques and cause regression.”

Will You Need a Stent?

But Budoff and Stone differ on more invasive options, such as a stent.

“Another thing that we might consider that's an emergent therapy is to put a stent on the high-risk plaque,” said Stone, who was at the helm of two preliminary studies of the procedure. “And as the stent heals, it thickens the cap and presumably makes it less vulnerable because of that.”

Budoff called the expanded definition of high-risk plaque problematic.

“It lends itself to getting a stent placed in the high-risk plaque, and that is why the vast majority of authors of this document were interventional cardiologists,” Budoff said. It’s not yet established that the benefits of placing stents will outweigh the risks, he said. “There is no data to support stenting of these lesions, as we don’t know for sure which will rupture, so the treatment has to be medical, yet I think it will lead to more stents, which is problematic.”

Jang, who is an interventional cardiologist, agreed.

And despite being a proponent for stenting high-risk plaque, Stone agreed a lot more needs to be known before it goes mainstream.

“We need a lot more studies before that becomes widespread and an accepted therapy because that has the potential to totally change the way we diagnose and treat patients,” he said.