Coronary atherosclerotic plaque activity is independently associated with myocardial infarction (MI) at the vessel level and further contributes to estimates of patient-level risk, a new analysis concludes. The research team found that among untreated coronary arteries, those with increased coronary atherosclerotic plaque activity had a fourfold increase in risk of MI compared to those without increased coronary atherosclerotic plaque activity. “Coronary revascularization had modified some of the coronary atherosclerotic plaques, thereby partially negating the influence of increased coronary atherosclerotic plaque activity,” said the paper’s authors, in explaining this observation. “…More likely…increased coronary atherosclerotic plaque activity in the treated coronary arteries characterizes disruption of the culprit coronary atherosclerotic plaque causing index MI, thereby triggering coronary revascularization.” In this secondary analysis of the Prediction of Recurrent Events With 18F-Fluoride to Identify Ruptured and High-Risk Coronary Artery Plaques in Patients With Myocardial Infarction (PRE18FFIR) study, coronary 18F-sodium fluoride positron emission tomography (PET) was used to identify vessel-level MI. Main results Led by Kang-Ling Wang, MD, from the Centre for Cardiovascular Science, University of Edinburgh, Scotland, the analysis, which was published Monday online, found increased 18F-sodium fluoride uptake in 679 of 2,094 coronary arteries and 414 of 691 patients. MI occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.16-3.72; P=0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Further findings revealed that increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or MI (HR: 2.43; 95% CI: 1.37-4.30; P=0.002) as well as first MI (HR: 2.19; 95% CI: 1.18-4.06; P=0.013) and total MIs (HR: 2.50; 95% CI: 1.42-4.39; P=0.002). “Taken together, these findings underline the central importance of coronary atherosclerotic plaque activity in driving the cause of MI irrespective of stenosis severity,” said the authors of the paper, which was published in the June 4 issue of the Journal of the American College of Cardiology, and noninvasive assessment of coronary atherosclerotic plaque activity is going to be essential if we are to improve our approaches to risk stratification and the focused application of preventative treatment.” The role of markers Zahi A. Fayad, PhD, and Philip M. Robson, PhD, from the Icahn School of Medicine at Mount Sinai, New York, and Valentin Fuster, MD, PhD, from the Icahn School of Medicine and the Centro Nacional de Investigaciones Cardiovasculares in Madrid, commented on the role of markers in further increasing risk stratification for future coronary events. These include novel markers such as perivascular fat inflammation on computed tomography (CT), invasive optical coherence tomography, intravascular ultrasound, and near infrared imaging. Also mentioned was the potential of advanced magnetic resonance imaging of intraplaque hemorrhage, vessel wall permeability, or use of novel elastin-specific contrast agents. General markers of disease burden and patient-level risk that could be considered, included coronary CT angiography and CT calcium scores, as well as dyslipidemia, diabetes and smoking. “Moreover, combined markers such as this will also benefit from the quantitative nature of PET; the predictive value of quantitative evaluation of plaque vulnerability is yet to be fully explored,” the experts said in their accompanying editorial comment. Limitations of the study Commenting on the investigation’s limitations, the experts highlighted that MI diagnoses were made by the treating physicians and recorded by site investigators instead of being independently reviewed, which could lead to potential diagnostic inaccuracies. However, they added that there was no significant evidence suggesting discrepancies in diagnosis between site investigators and independent adjudication committees, and invasive coronary angiography confirmed most identified culprit vessels. Other limitations include the need for continued examination of how these plaques influence outcomes on coronary CT angiography, considering the analysis explored the relationship between coronary atherosclerotic plaque activity and MI. Looking ahead, the experts anticipated that novel, more advanced, composite, patient-level risk metrics would emerge that incorporated assessments of both specific vulnerability and patient-level risk. “It is exciting to consider the impact of advanced image analysis involving radiomics, leveraging recent advances using genetics and multiomics to predict lifestyle-intervention-induced changes in health measures, and the enhanced predictive modeling of artificial intelligence and machine learning,” they concluded. Study methods The design and results of PRE18FFIR have been published previously. The study population comprised 691 patients, of whom 414 (60%) had increased total coronary atherosclerotic plaque activity at the patient level. These patients were categorized according to the number of coronary arteries with increased coronary atherosclerotic plaque activity: multiple (n=207; median age 66 years [interquartile range (IQR): 58-72]), single (n=207; median age 64 years [IQR: 58-71]); none (n=277; median 61 years [IQR: 56-67]). Among 1,258 coronary arteries analyzed in these 414 patients, 679 (54%) had increased coronary atherosclerotic plaque activity. After intravenous administration of a target dose of 250 MBq 18F-sodium fluoride, all patients underwent attenuation-correction CT, dual cardiac and respiratory gated PET of the thorax, and electrocardiogram gated CTCA according to the study protocol. Annual clinical follow-up continued for a minimum of 2 years, with the primary vessel-level outcome of interest being MI in the vessel-specific territory. Sources: Wang K-L, Balmforth C, Meah MN, et al. Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction. J Am Coll Cardiol. 2023;83: 2135–2144. Fayad ZA, Robson PM, Fuster V. Rethinking Heart Attack Prevention: The Myth of the “Vulnerable Plaque” and Reality of Patient Risk. J Am Coll Cardiol. 2023;83: 2145–2147. Image Credit: wuttichai1983 – stock.adobe.com