Correlation between Cardiovascular Disease Risk and Bilateral Carotid Artery Molecular Calcification Assessed by [18F] Sodium Fluoride PET/CT

Introduction: Atherosclerosis, a leading cause of mortality and morbidity worldwide, is a chronic inflammatory disease that involves the progressive formation and calcification of plaques. Accumulation of plaque can increase the likelihood of ischemic events such as myocardial infarction or stroke. The early detection of the molecular changes underlying atherosclerosis is therefore critical for effective disease management. While structural imaging approaches such as computed tomography are often used to evaluate atherosclerosis clinically by providing high resolution of plaque structure, their utility is limited in early diagnosis as macroscopic plaque formation is a relatively late-stage manifestation of the disease. In the present study, we used combined positron emission tomography/computed tomography (PET/CT) with [¹⁸F] sodium fluoride (NaF) to visualize biologically-active vascular microcalcification in a study population consisting of patients at risk for cardiovascular disease (CVD) and healthy volunteers. We investigated the relationship between cardiovascular risk factors and [¹⁸F] NaF uptake in the left and right common carotid arteries (LCC / RCC) to assess the diagnostic potential of [¹⁸F] NaF PET/CT in subclinical atherosclerosis.

Methods: A total of 102 subjects (mean age 48.2 ± 14.1 years, 51% males) comprising both patients at-risk for CVD and healthy volunteers (n = 38 and n = 64, respectively) underwent blood pressure measurements, blood analyses, and 90-minute hybrid [¹⁸F] NaF PET/CT imaging. Radiotracer uptake was measured by quantifying the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice image. Average SUVmax (aSUVmax) values of [¹⁸F] NaF in the LCC and RCC were calculated over all slices for each subject and correlated with the 10-year risk for development of CVD based on the Framingham Risk Score (FRS). A linear regression model was used to determine correlations between bilateral [¹⁸F] NaF aSUVmax and known cardiovascular risk factors.

Results: Direct correlations were found between [¹⁸F] NaF uptake and cardiovascular risk factors such as age (p < 0.01 in LCC and RCC), BMI (p < 0.01 in LCC and RCC), smoking history (p < 0.01 in LCC and RCC), fibrinogen (p = 0.02 in LCC and p = 0.01 in RCC), and HDL cholesterol (p < 0.01 in RCC only). Inverse associations were observed between [¹⁸F] NaF uptake and male gender (p = 0.04 in LCC and p < 0.01 in RCC) and levels of C-reactive protein (CRP) (p = 0.03 in RCC only) (Figure 1a). At-risk subjects showed a higher [¹⁸F] NaF uptake compared to healthy volunteers (p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated risk of cardiovascular (p < 0.01 in LCC only) events as measured by the FRS (Figure 1b).

Conclusions: Bilateral carotid [¹⁸F] NaF uptake strongly correlates with known cardiovascular risk factors in a matter that is largely consistent with previous studies associating known cardiovascular risk with [¹⁸F] NaF uptake in other vascular beds, including the thoracic aorta and coronary arteries. Notably, some correlations differed between LCC and RCC. It is possible that the observed discrepancies derive from the distinct anatomy of these two vessels within the human cardiovascular system, thereby differentially predisposing each carotid to risk factors. Overall, our findings support the potential use of [¹⁸F] NaF PET/CT as a sensitive tool for the early detection of atherosclerosis and assessment of cardiovascular risk. Future research, particularly prospective and longitudinal clinical trials, is needed to validate the predictive value of [¹⁸F] NaF PET/CT and its potential impact on clinical outcomes.

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