Coronary 18F-Fluoride Uptake and Progression of Coronary Artery Calcification

Abstract

Background Positron emission tomography (PET) using ¹⁸F-sodium fluoride (¹⁸F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between ¹⁸F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease. Methods Patients with established multivessel coronary atherosclerosis underwent ¹⁸F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume. Results In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased ¹⁸F-fluoride uptake in at least one vessel. Individuals with increased ¹⁸F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39-166] versus 35 [7-93] AU; P<0.0001). Indeed, the calcium score only increased in coronary segments with ¹⁸F-fluoride uptake (from 95 [30-209] to 148 [61-289] AU; P<0.001) and remained unchanged in segments without ¹⁸F-fluoride uptake (from 46 [16-113] to 49 [20-115] AU; P=0.329). Baseline coronary ¹⁸F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively; P<0.0001 for all). At the segmental level, baseline ¹⁸F-fluoride activity was an independent predictor of calcium score at 12 months (P<0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score (P=0.50). Conclusions Coronary ¹⁸F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02110303.

Keywords: atherosclerosis; calcium; coronary angiography; positron emission tomography; risk factors.

Figure 1.

The proportion of ¹⁸F-fluoride positive and negative participants with increasing baseline total calcium score. Increased overall disease burden is associated with an increased frequency of ¹⁸F-fluoride activity.

Figure 2.

¹⁸F -fluoride activity predicts progression of coronary arterial calcification. In an ¹⁸F-fluoride positron emission tomography (PET) positive lesion (A–E), contrast-enhanced computed tomography (CT) coronary angiography (A) and fused PET-CT (B) demonstrate ¹⁸F-fluoride uptake in the left main stem (LMS) at baseline overlying a mixed plaque shown on coronal view (A) and cross-section (C). Repeat CT coronary angiography at one year demonstrates progression of calcification in this segment with a higher calcium score (D) and dense calcium visible on cross-section (E). Calcium score 75 AU at baseline, maximum tissue-to-background ratio (TBR_max) 1.7, calcium score 110 AU at one year. In the same patient, a calcified plaque in a proximal obtuse marginal branch without evidence of increased ¹⁸F-fluoride activity is shown on coronal (F and G) and cross-section views (H). This plaque does not demonstrate progression in calcium score at one year (I and J). Calcium score 186 AU at baseline, TBR_max 1.0, calcium score 172 AU at one year.

Figure 3.

The relationship between baseline ¹⁸F -fluoride activity and coronary calcification at one year. A–C, Display the change in calcium score (A), mass (B), and volume (C) in ¹⁸F-fluoride positive vs negative lesions over 12 months. Median and interquartile range displayed.

Figure 4.

Ratio of calcification at follow-up to baseline. Ratio of follow-up total calcium mass (A) and Agatston score (B) to baseline in individual positron emission tomography (PET)-positive and PET-negative segments in participants with at least one PET-positive lesion.