Rosuvastatin effect on atherosclerotic plaque metabolism: A subclinical atherosclerosis imaging study with 18F-NaF PET-CT

Background and aims: Atherosclerotic plaque fluorine-18 sodium fluoride (F-18-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma F-18-NaF uptake. Methods: Subjects with high CV risk but without CV events underwent F-18-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant F-18-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by F-18-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma F-18-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. Results: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 +/- 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 +/- 33.8 to 58.8 +/- 20.7 mg dL(-1) (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque F-18-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003). Conclusion: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque F-18-NaF uptake was significantly reduced after six months of high-intensity statin.