Abstract
Calcification in a coronary artery is accepted as definite evidence of coronary atherosclerosis. The extent and density of calcification, as combined in the Agatston score, is associated with the risk of a patient experiencing a major acute coronary event (MACE). The higher the Agatston score, the greater the higher likelihood of MACE. Atherosclerosis occurs because damaged endothelial cells allow low density lipoprotein cholesterol (LDLc) to leak into subintimal tissue. Proteoglycans in subendothelial collagen have a high affinity for LDLc, retaining the lipoprotein cholesterol complex. As the endothelial damage is repaired, the subintimal LDLc is trapped in subintimal glycosaminoglycans. Trapped LDLc induces an inflammatory response in the overlying endothelium, resulting in expression of chemotactic peptides. Chemotactic peptides attract circulating monocytes, which follow the concentration gradient to enter the tissue and then become tissue macrophages to phagocytize and digest the LDLc. In the process of digesting LDLc, enzymes produced by these macrophages oxidize the LDLc complex. However, oxidized LDL is toxic to macrophages; when present in sufficient quantity, it may cause macrophage death, thereby further contributing to inflammation in the atheroma. In the necrotic inflammatory lesion, the regulatory mechanisms that normally control tissue concentrations of calcium and phosphorous are lost, allowing the solubility product of calcium phosphate to be exceeded, resulting in the formation of microscopic dystrophic calcium-phosphate crystals. With ongoing inflammation, additional calcium-phosphate crystals are formed, which may aggregate. When these aggregated calcium phosphate crystals exceed ~ 0.2mm, the lesions become visible on clinical CT as coronary calcifications. Serial gated CT scans of the heart have demonstrated that once formed, CT visible calcifications do not decrease significantly in size, but they may increase. Although dystrophic vascular calcification is a ‘tombstone,’ it does not identify the lesions likely to cause MACE. Atheroma that are actively undergoing calcification are the most likely to cause major acute events, and molecular PET/CT imaging with ionic 18F fluoride identifies such lesions. Recent data suggest that 18F-fluoride imaging may be a sensitive and specific marker of lesions likely to cause MACE. A multicenter trial is needed to define whether this marker identifies patients at high risk of MACE.
- Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.