Coronary Atherosclerotic Plaque Activity and Risk of MI

Quick Takes

  • Total coronary atherosclerotic plaque activity (inflammatory, as assessed by coronary microcalcification) across the entire coronary arterial tree using 18F-sodium fluoride uptake by PET is associated with patient-level coronary events independent of obstructive CAD.
  • Coronary atherosclerotic plaque activity is independently associated with MI at the vessel level and increased coronary atherosclerotic plaque activity was predominantly seen in coronary arteries without residual obstructive lesions.
  • Patients who have a multivessel increase in coronary atherosclerotic plaque activity are at the greatest risk for fatal and nonfatal MI.

Study Questions:

Is vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography (PET) associated with patient vessel-level myocardial infarction (MI)?


PRE18FFIR (Prediction of Recurrent Events with 18F-Fluoride to Identify Ruptured and high-risk coronary artery plaques in patients with myocardial infarction) is a prospective longitudinal cohort study conducted at nine sites across Australia, England, Scotland, and the United States, enrolling patients aged ≥50 years with recent type 1 MI and multivessel coronary artery disease (CAD) between September 2015 and February 2020. They report herein a secondary analysis of patients who after intravenous administration of a target dose of 250 MBq 18F-sodium fluoride underwent attenuation-correction computed tomography (CT), dual cardiac and respiratory gated PET of the thorax, and electrocardiogram gated CT coronary arteriography (CTCA).

Image analysis was performed offline and was not used to inform clinical decision making. Vessel-specific coronary atherosclerotic plaque activity of each major vessel (left main + left anterior descending) was measured separately using coronary artery microcalcification activity derived from both intensity and volume of 18F-sodium fluoride uptake regardless of the presence of coronary artery stents.

The primary vessel-level outcome of interest was subsequent MI in the vessel-specific territory. The secondary patient-level outcomes of interest were the composite of cardiac death or MI as well as MI considered in isolation as both the first event and the total events. Follow-up continued for a minimum of 2 years.


Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients, respectively. On CTCA, 2,094 analyzable coronary arteries were identified, of which 832 (40%) were and 1,262 (60%) were not treated with percutaneous coronary intervention at index MI. During a median of 4 years of follow-up, 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) (p for interaction = 0.024). 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 (HR, 2.19; 95% CI, 1.18-4.06; p = 0.013) and total (HR, 2.50; 95%, 1.42-4.39; p = 0.002) MIs. Vessel-specific coronary atherosclerotic plaque activity was associated with MI within the same coronary artery territory, and increased coronary atherosclerotic plaque activity was predominantly seen in coronary arteries without residual obstructive lesions.


In patients with recent MI and multivessel CAD, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for MI.


Uptake of 18F-sodium fluoride PET is a noninvasive modality to measure coronary atherosclerotic plaque activity due to inflammation-triggered microcalcification. The latter correlates with sites of coronary atherosclerotic plaque instability on histology and is also associated with coronary atherosclerotic plaque progression over time.

This costly elegant study using coronary 18F-sodium fluoride PET identified persons with a first MI who may be in the 5-10% with a recurrent event in the following year. The findings suggest the technique may identify coronary lesions that are candidates for revascularization, and potentially selection of more intense therapies targeting the PCSK9 enzyme, lipoprotein(a), and next generation anti-inflammatory strategies. Among the important limitations, the PRE18FFIR study only enrolled patients with recent MI who had multivessel CAD. As a result, the findings might not be generalizable to patients with stable CAD, in whom coronary atherosclerotic plaque activity and levels of systemic and local inflammation may be different. The cost-benefit of the protocol versus intensive treatment for all patients with MI needs to be evaluated.

Clinical Topics: Noninvasive Imaging, Computed Tomography, Nuclear Imaging

Keywords: Myocardial Infarction, Plaque, Atherosclerotic, Positron-Emission Tomography

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