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The severity of a patient’s symptoms of coronary artery disease are not always a reliable indicator of the extent of atherosclerosis, according to a new study in JACC: Cardiovascular Imaging.

“There’s been a reliance on stenosis severity as a predictor of the likelihood of having symptoms, but that relationship is known to be inconsistent,” said Jonathon Leipsic, MD, a cardiologist at St. Paul’s Hospital in Vancouver, British Columbia, who led the study. “I think far too often clinicians have assumed in the absence of a focal lesion, the symptoms must be related to the microcirculation.”

Leipsic and his colleagues used new artificial intelligence-enabled tools to quantify the amount of plaque in a patient’s arteries and functional indices such as fractional flow reserve-CT (FFR-CT) and compare them to their reported symptoms. The study used the ADVANCE registry, a study on the impact of FFR-CT on clinical decision-making.

They analyzed 4382 patients in the registry — 1079 with no symptoms, 438 with dyspnea, 277 with noncardiac chest pain, 1621 with atypical chest pain, and 967 with typical angina. The amount of plaque was quantified using total percentage atheroma volume (TPAV) and the significance of stenosis was measured using FFR-CT. The analysis showed that the presence or absence of symptoms was not independently associated with either TPAV or FFR-CT.

When the various symptoms were examined individually, some associations emerged. For patients with typical angina — constricting discomfort in the chest, neck, jaw, shoulder, or arm brought on by physical exertion and relieved by rest or nitrates — the relationship between symptoms and plaque was clear: They tended to have higher TPAV and a lower, and therefore abnormal, FFR-CT.

But atypical chest pain, noncardiac chest pain, and dyspnea were not associated, or even inversely associated, with TPAV and FFR-CT.

“While you would think there is a relationship between symptoms and plaque, the symptom status was not terribly predictive of the amount of disease,” Leipsic said.

Even having no symptoms was not a reliable indicator of cardiovascular health in these patients. “Just because a patient doesn’t report any symptoms doesn’t mean there is no atherosclerosis,” he said.

Matthew Budoff, MD, a cardiologist at the University of California, Los Angeles, said cardiologists rely heavily on symptoms to determine how severe cardiovascular disease is, but the new research is beginning to dispel that idea.

“We can’t totally rely on symptoms to determine what the next step for that patient would be,” he said.

Budoff said the new findings support the idea CT angiography should be a bigger part of the diagnostic process, so clinicians can look not only at whether a patient has stenosis but also go beyond to see if they have any atherosclerosis or plaque that might be a target for medical therapy.

The 2021 clinical guidelines on chest pain from the American Heart Association and the American College of Cardiology are already moving toward using CT as a first approach to untangle the differences between symptoms, plaque, and stenosis, he added. “Trying to unravel the plaque severity in somebody who comes in without typical symptoms may be very helpful for our diagnostic algorithms,” he said.

Budoff reported no relevant financial conflicts of interest. Leipsic reported receiving support from and consulting to HeartFlow and CircleCVI; and stock options in HeartFlow and Circle CVI.

Brian Owens is a freelance journalist based in New Brunswick, Canada.