Coronary artery calcification: does it predict obstructive coronary artery disease?

Abstract

Calcification of the coronary arteries plays a key role in the pathophysiology of atherosclerosis. Coronary calcification is an active process culminating in extracellular matrix deposition of calcium by osteoblast-like cells that has some resemblance to bone formation [1]. Subintimal coronary calcification is almost exclusively associated with the presence of coronary atherosclerosis and is considered the hallmark of coronary atherosclerosis. Coronary calcific lesions are considered advanced lesions and calcification following plaque rupture of a high-risk plaque is thought to be part of the healing process [2]. The presence of coronary calcification is a surrogate marker of the overall plaque burden. Not all plaques are calcified and histological studies have revealed that the total calcium area was approximately 20 % of the total atherosclerotic plaque burden area [3]. There is no generally accepted relationship between plaque calcification and plaque stability. Traditionally calcific plaques are considered to be stable but plaques with spotty calcification (small amount of calcification in a spotty distribution) have been associated with plaque instability and acceleration to progression of CAD [4, 5]. However, the extent of calcification is a marker of instability somewhere in the coronary tree rather than a marker of local plaque instability [4]. Coronary calcification can be easily detected by computed tomography (CT). The epicardial vessels can be readily identified on a non-contrast enhanced CT scan (calcium scan), because the density of the coronary wall and blood is higher than the surrounding peri-coronary fat. Coronary calcium deposits have a 2 to 10 fold higher density than surrounding tissues and coronary calcium is identified as a hyper-attenuating coronary lesion above a threshold of 130 Hounsfield units (HU). The amount of calcium is quantified using the Agatston score (calcium score) which is derived from the product of the area of calcification (mm2) and a factor determined by the maximal density (HU) within that area. The factor is 1,2,3,4 with a density of 130 to 199, 200 to 299, 300 to 399 or >400 HU respectively [6]. The calcium scan does not require contrast medium and can be acquired with a low radiation dose of less than 1.0 mSv [7]. This is associated with a lifetime attributable risk of cancer that for men and women at 50 years of age at 8 and 20 per 100,000 persons per year, respectively. The calcium score is a significant predictor of risk of adverse cardiovascular events that has independent incremental value of risk prediction beyond the traditional risk prediction scores such as the Framingham risk score or the Euro risk score. Increasingly higher calcium scores are associated with increasingly higher risk of adverse cardiovascular events and all-cause mortality. The calcium score can also be used to predict the presence of obstructive coronary artery disease (CAD).