Measurement of Arterial Activity on Routine FDG PET/CT Images Improves Prediction of Risk of Future Cardiovascular Events

Study Questions:

Does increased 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) uptake in the aorta identify patients at increased risk of cardiovascular events?

Methods:

This retrospective study examined 513 individuals who underwent 18F-FDG-PET and computed tomography (CT) imaging as part of an oncologic evaluation who were without active cancer, at least 30 years of age, and with no prior history of cardiovascular disease. FDG uptake was measured in the ascending aorta and indexed to venous uptake to provide a target-to-background ratio (TBR) as a measure of aortic inflammation. The relationship between TBR and cardiovascular events was evaluated, with the latter including stroke, transient ischemic attack, acute coronary syndrome, revascularization, angina, peripheral arterial disease, heart failure, and cardiovascular death.

Results:

Median age was 55 years, and 42% were male. Over a median follow-up of 4.2 years, there were 44 cardiovascular events. Patients with events were older, and had increased prevalence of risk factors including smoking, hypertension, hyperlipidemia, and diabetes (p < 0.05 for each). In comparison to patients without events, those with events had higher median (interquartile) 10-year Framingham risk scores [9 (4-17) vs. 19 (11-27)%, p < 0.001], higher coronary artery calcium scores [0 (0-6) vs. 19 (0-82), p < 0.001], and higher TBR by FDG [2.0 (1.8-2.2) vs. 2.2 (1.9-2.3), p < 0.001]. After adjustment for cardiovascular risk factors and age, patients in the highest tertile of TBR (vs. lowest tertile) had an increased risk of cardiovascular events (hazard ratio [HR], 4.7; 95% confidence interval [CI], 2.0-11.2; p < 0.001). After further adjustment including the coronary artery calcium score, the highest tertile of TBR remained associated with an increased risk (HR, 4.1; 95% CI, 1.6-10.8; p = 0.004). The addition of the TBR to a model using the Framingham risk score increased the c-statistic from 0.62 to 0.66. Net reclassification improvements for the 10% and 6% Framingham risk groups were 27.5% and 22.3%, respectively.

Conclusions:

In patients undergoing cancer surveillance imaging, an increased FDG update in the ascending aorta is independently associated with an increased risk of cardiovascular events.

Perspective:

This retrospective study of patients undergoing cancer surveillance imaging finds that the presence of increased 18F-FDG-PET uptake in the ascending aorta is associated with a greater risk of cardiovascular events even after adjusting for traditional risk factors and coronary artery calcium score. As 18F-FDG-PET uptake increases in areas of rapid glycolysis and activated macrophages, it appears to represent a promising surrogate to identify areas of active arterial wall inflammation. This study is an important addition to prior literature, and suggests a potential future role for 18F-FDG-PET to identify high-risk patients. Prospective studies are needed to determine whether these findings extend to non-oncological patients, and whether the clinical utility of these results exceeds the associated risks and cost of the study.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Computed Tomography, Nuclear Imaging, Hypertension, Smoking

Keywords: Inflammation, Acute Coronary Syndrome, Neoplasms, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Macrophages, Hyperlipidemias, Peripheral Arterial Disease, Risk Factors, Smoking, Calcium, Positron-Emission Tomography, Prevalence, Fluorodeoxyglucose F18, Glycolysis, Tomography, Heart Failure, Confidence Intervals, Coronary Vessels, Hypertension, Diabetes Mellitus


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