Coronary artery calcification: Pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association

Atherosclerotic calcification is an organized, regulated process similar to bone formation that occurs only when other aspects of atherosclerosis are also present. Nonhepatic Gla-containing proteins like osteocalcin, which are actively involved in the transport of calcium out of vessel walls, are suspected to have key roles in the pathogenesis of coronary calcification. Osteopontin and its mRNA, known to be involved in bone mineralization, have been identified in calcified atherosclerotic lesions. Calcified human atherosclerotic plaque also contains mRNA for bone morphogenetic protein-2a, a potent factor for osteoblastic differentiation, and cells that are capable of osteoblastic differentiation. These cells may be the ones from which vascular calcifying cells are derived. These and other recent findings indicate that calcification is an active process and not simply a passive precipitation of calcium phosphate crystals, as once thought. Although calcification is found more frequently in advanced lesions, it may also occur in small amounts in earlier lesions that appear in the second and third decades of life. Histopathological investigation has shown that plaques with microscopic evidence of mineralization are larger and associated with larger coronary arteries than are plaques or arteries without calcification. The relation of arterial calcification to the probability of plaque rupture is unknown. Although the amount of coronary calcium correlates with the amount of atherosclerosis in different individuals and to a lesser extent in segments of coronary tree in the same individuals, it is not known if the quantity of calcification tracks the quantity of atherosclerosis over time in the same individuals. Further research is needed to better elucidate the relation of calcification to the pathogenesis of both atherosclerosis and plaque rupture. In vivo epidemiological evidence and postmortem studies show that the prevalence of coronary calcium deposits in a given decade of life is 10 to 100 times higher than the expected 10-year incidence of coronary heart disease events for individuals of the same age. This disparity is less evident in the elderly and symptomatic than in the young and asymptomatic. Realization of this fact has generated the need to determine clinically useful threshold levels of coronary calcium content (such as calcium score determined by electron beam computed tomography[EBCT]) in order to make appropriate management decisions. The limited evidence linking radiographically detectable coronary calcium to future coronary heart disease events of death and infarction suggests that this link is strongest in symptomatic and very high-risk subjects. The results of ongoing epidemiological studies will be needed to further elucidate this connection. Fluoroscopy, electron beam, and helical computed tomography can identify calcific deposits; EBCT and, to a lesser extent, double-helical CT have the enhanced capability to localize coronary calcification and detect smaller and less dense calcific deposits. Only EBCT can quantitate the amount or volume of calcium. The absence of calcific deposits on an EBCT scan implies the absence of significantly angiographic coronary narrowing; however, it does not imply the absence of atherosclerosis, including unstable plaque. Similarly, calcification may frequently be seen in the absence of significant angiographic narrowing and before there has been sufficient plaque build-up to narrow the vessel to the extent that ischemia would be apparent on stress electrocardiograms or stress-thallium determinations. According to the available evidence, a negative EBCT coronary calcium study, when no calcium is detected, does not absolutely rule out the presence of atherosclerotic plaque, but does imply a very low likelihood of significant luminal obstruction. The majority of patients who have had angiographically normal coronary arteries have negative EBCT scans and low risk of a cardiovascular event within the next 2 to 5 years. Women tend to have low scores or negative scans before menopause. On the other hand, a positive scan, that is, one in which some calcium is detected in at least one vessel, confirms the presence of atherosclerotic plaque. The greater the amount of calcification, the greater the likelihood of obstructive disease, but there is not a one-to-one relation, and the findings are not site specific. A high calcium score may be consistent with a moderate to high risk of a cardiovascular event within the next 2 to 5 years.