Modifiable risk factors tied to high-risk coronary plaque

Clinical takeaway: Modifiable factors were tied to rupture-prone plaque that can lead to cardiac events. That makes it even more worthwhile to encourage patients to establish and/or maintain control of their blood pressure, cholesterol, diabetes, weight, and smoking.

The case for controlling modifiable risk factors has rested on outcomes: fewer cardiac events over time. This study adds a more tangible mechanism that clinicians can see. Using high-resolution imaging of all three coronary arteries, researchers found that treatable risk factors were the ones tied to vulnerable, rupture-prone plaque, while immutable factors such as age and family history mostly added stable, calcified plaque instead.

Most imaging work on plaque vulnerability has looked at one lesion or one vessel, or focused on patients already experiencing an MI. That gives a partial picture, since a single vulnerable plaque is only one part of a patient's overall coronary risk. This study instead assessed every plaque across all three major arteries in a broader group, allowing researchers to examine whether risk-factor burden tracks with vulnerability across the entire coronary tree, not just at the culprit site.

The type of plaque a patient carried depended on the type of risk factor. Each additional modifiable risk factor was independently tied to a 36% higher number of vulnerable, rupture-prone features across all three coronary arteries.

The same held for the most dangerous features on their own. Thin-cap fibroatheromas are lipid-rich plaques most prone to rupture. They rose about 48% per added modifiable factor. Cholesterol crystals, a sign that a plaque's lipid core is destabilizing, rose about 50%.

Non-modifiable factors showed no such association with vulnerability. What age, sex, and family history added instead was more plaque, but not more dangerous features. More non-modifiable factors tracked with more plaque overall, but the excess was stable, calcified plaque, which roughly doubled with each added factor.

Because modifiable and non-modifiable factors tend to cluster in the same patients, risk burden rarely comes one factor at a time. Patients carrying at least five risk factors of any kind had more than twice as many rupture-prone plaques as those with two or fewer, a reminder that the modifiable share of that burden is where the vulnerability, and the opportunity to intervene, concentrates.

Researchers scored 534 plaques from 131 patients in a Massachusetts General Hospital OCT registry, all imaged across the three major coronary arteries, none with prior stenting. They related each patient's risk-factor count to plaque number, type, and vulnerable features.

The modifiable factors, in order of how common they were in this cohort, were high cholesterol and high blood pressure (each in about six of 10 patients), then smoking and diabetes (about three in 10), and obesity (6%); non-modifiable factors were age, sex, and family history. The retrospective analysis best fits patients who have not had coronary stenting and whose anatomy suits three-vessel imaging.

The risk factors already at the center of prevention were the ones tied to the plaque morphology that ruptures, while the factors patients cannot change mostly added stable disease. That separation suggests the vulnerability behind acute events may be the part of a patient's risk that is most open to treatment.

"The higher the number of vulnerable, or rupture-prone plaques, the greater the chance that one of them will trigger an adverse event. Our findings highlight the importance of early, intensive and sustained interventions to control the modifiable risk factors and prevent future events," said senior author Ik-Kyung Jang, MD, PhD, of the Mass General Brigham Heart and Vascular Institute.

Source: Chmiel J, et al. JACC Adv. 2026 Jul 23. Association Between Cardiovascular Risk Factors and Pan-Coronary Plaque Burden, Phenotype, and Vulnerability: 3-Vessel Imaging Study