Researchers at the Mass General Brigham Heart and Vascular Institute examined how multiple cardiovascular risk factors together relate to the burden and type of atherosclerotic plaques in the three major coronary arteries. Instead of focusing on single risk factors or select patient groups, the team analyzed whether the total number of risk factors—both modifiable and non-modifiable—was associated with the presence and distribution of vulnerable plaques that are more likely to precipitate adverse cardiac events such as heart attacks.
The work was published in JACC: Advances and used intravascular imaging to characterize plaque features across patients who had not yet received certain types of treatment for coronary disease.
The investigators reviewed optical coherence tomography (OCT) imaging from a registry at Massachusetts General Hospital. OCT is a near-infrared light–based intravascular imaging modality that provides high-resolution, cross-sectional views of coronary arteries and plaque microstructure.
The cohort comprised 131 patients who underwent OCT of all three major coronary arteries. Across these patients the researchers identified and analyzed a total of 534 plaques. The analysis evaluated associations between plaque counts and characteristics with participants’ documented risk factors, considering modifiable and non-modifiable factors separately and combined.
Overall, the number of plaques visible on OCT rose as the number of risk factors increased. Crucially, a higher count of risk factors was linked not only to more plaques but specifically to a greater number of vulnerable plaque phenotypes. The study highlighted two vulnerable plaque types:
Quantitatively, among participants with at least four modifiable risk factors, approximately one in two plaques were thin-cap fibroatheromas and four in five were lipid-rich plaques. The authors emphasized that a larger burden of vulnerable, rupture-prone plaques increases the probability that one will trigger an adverse clinical event.
The study separated risk factors into modifiable and non-modifiable categories. The five modifiable risk factors recorded were high low-density lipoprotein (LDL) cholesterol, high blood pressure, diabetes mellitus, obesity, and cigarette smoking. Non-modifiable factors included age, sex, and family history of coronary artery disease.
Findings showed that an increased number of modifiable risk factors—but not non-modifiable factors—was associated with a broader distribution of high-risk plaques across all three major coronary arteries. In contrast, non-modifiable risk factors were more often associated with more stable plaque morphologies rather than the rupture-prone types observed with multiple modifiable risks.
Study investigators and quoted authors propose that the link between modifiable risk factors and plaque vulnerability is largely mediated by inflammation. They noted that dyslipidemia, hypertension, diabetes, obesity, and smoking are known to promote vascular inflammatory processes, which can destabilize plaques and favor the development of TCFA and lipid-rich lesions.
By contrast, non-modifiable risk factors such as age, sex, or family history may drive atherosclerotic progression through pathways that are less directly inflammation-driven, accounting for their association with more stable plaque types in this cohort.
The authors acknowledge important limitations. The dataset derived from a specific hospital registry of patients who had not yet received certain coronary treatments and who were eligible for OCT imaging. Because of that selection, the findings are most directly applicable to a similar patient population and may not generalize to all patients with coronary artery disease.
The researchers call for larger, prospective studies, including people who have received treatment for blocked arteries, to confirm whether aggressive management of modifiable risk factors can reduce plaque vulnerability and lower the incidence of adverse cardiac events. As noted in the report, the natural next step would be trials testing whether intensive control of these risk factors changes plaque composition and clinical outcomes.
Within the study population, the number of modifiable cardiovascular risk factors correlated with both the quantity and the vulnerability of coronary plaques visualized by OCT. The investigators conclude that these results underscore the potential value of early, intensive, and sustained interventions to control dyslipidemia, hypertension, diabetes, obesity, and smoking in order to reduce the burden of rupture-prone plaques and help prevent future heart attacks.
The authors stress that further research is needed before these findings are generalized broadly, but they present additional imaging-based evidence linking commonly targeted, modifiable cardiovascular risks to plaque phenotypes associated with higher clinical risk.