Coronary arterial inflammation linked to high cardiac event risk even without CAD

In a recent study published in The Lancet, researchers investigate whether coronary arterial inflammation contributes to major adverse cardiac events (MACE) or cardiovascular deaths among individuals with or without coronary artery disease (CAD).

Study: Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study. Image Credit: Axel_Kock / Shutterstock.com

How is CAD diagnosed?

Coronary computed tomography angiography (CCTA) is often the first imaging test used for patients who present with stable chest pain to determine the need for coronary revascularization due to obstructive CAD. Despite its widespread use, many symptomatic patients who undergo CCTA do not have any detectable build-up of plaque within their coronary arteries, are not diagnosed with CAD, and are subsequently discharged.

Even in the absence of CAD, vascular inflammation can lead to acute coronary syndromes. Thus, there remains an urgent need to identify and treat patients with inflamed coronary arteries.

To this end, the researchers of the current study previously developed a technology that allows for the assessment of coronary inflammation by measuring changes in perivascular adipose tissue from CCTA images. The fat attenuation index (FAI) and FAI Score are then used to quantify these changes to estimate the extent of inflammation present within the patient’s coronary arteries.

AI-Risk, an artificial intelligence (AI)-assisted algorithm, was then developed using FAI Scores of each coronary artery, in addition to data on atherosclerotic plaque burden and the presence of known CAD risk factors, to better estimate the patient’s risk of future cardiovascular events.

What patients typically undergo CCTA?

The first aim of the current study was to better understand the risk profile of patients undergoing CCTA. To this end, data from the United Kingdom National Health Service (NHS) was obtained from 40,091 adult patients across eight hospitals, with a mean follow-up period of 2.7 years.

About 19% of the study cohort were diagnosed with obstructive CAD and had a significantly increased risk of myocardial infarction, new heart failure, ischemic stroke, and all-cause mortality. Comparatively, 81.1% of the study cohort were not diagnosed with CAD; however, these patients accounted for 66.3% and 63.7% of all MACE and total cardiac deaths in this cohort, respectively. These findings demonstrate the urgent need to improve risk management approaches in patients without obstructive CAD.  

How does coronary arterial inflammation without CAD affect patient outcomes?

The researchers were then interested in determining how coronary arterial inflammation, measured using FAI Scores from any coronary artery, might contribute to cardiac mortality or MACE in patients with and without CAD.

This cohort included 3,393 patients, with a median follow-up period of 7.7 years between 2010 and 2015. Data on incident MACE, such as myocardial infarction, new heart failure, and cardiac mortality, were obtained from nationwide databases.

FAI Score was found to effectively predict both cardiac mortality and MACE among patients with and without a history of myocardial infarction or revascularization. Furthermore, FAI Scores consistently identified residual inflammatory risk among these patients even after adjusting for any risk factors and the presence of non-obstructive atheroma.

An increased number of vessels with FAI Scores above the 75^th percentile were associated with an increased risk of both cardiac mortality and MACE as compared to patients with three arteries below the 25^th percentile, regardless of whether obstructive CAD was present.

Assessing the performance of AI-Risk

The third and final aim of the current study was to evaluate the performance of AI-Risk in the same cohort of 3,393 patients used to assess coronary arterial inflammation outcomes. To this end, AI-Risk was found to align well with both predicted and observed events in patients with and without obstructive CAD. However, this classification system overestimated the risk of patients with obstructive CAD by suggesting invasive coronary angiography and interventions to reduce the risk of cardiovascular events in the near future.

Nevertheless, the AI-Risk algorithm was a significant and independent predictor of both cardiac mortality and MACE over a 10-year period. Moreover, patients classified by AI-Risk as being at a very high risk of cardiovascular events were at a significantly greater risk of both cardiac mortality and MACE, regardless of the presence of obstructive CAD diagnosis.

The researchers were also interested in evaluating the impact of AI-Risk on clinical decision-making processes through the use of surveys provided to clinical care teams. Accordingly, AI-Risk led to changes in management decisions for 45% of patients, 24% and 13% of whom were initiated on statins or had their statin dosages increased, respectively. AI-Risk also led clinicians to prescribe additional treatments beyond statins in 8% of patients, such as aspirin, colchicine, or icosapent ethyl, for 2.4%, 8.3%, and 0.4%, respectively.

The AI-Risk algorithm, which incorporates FAI Score, the extent of coronary atheroma, as well as the patient’s traditional risk factors, was able to powerfully predict cardiac mortality and MACE over 10 years, both in the presence and absence of coronary atherosclerosis.”

Conclusions

The measurement of coronary artery inflammation by FAI scores identified that over 25% of patients who were not diagnosed with obstructive CAD were at a significantly greater risk of both cardiac mortality and MACE over a ten-year period. As the number of inflamed coronary arteries increased, which correlated with an increased FAI Score, the risk of cardiac mortality and MACE also rose.

CCTA is widely used throughout the world to manage stable chest pain. The study findings demonstrate that patients who undergo CCTA should be monitored more carefully, even if they are not diagnosed with CAD through this diagnostic technique, as they are at a similarly high risk of cardiovascular events.