Calcification of the coronary arteries; reproducibility, risk factors and risk

Cardiovascular disease is a major contributor of disability and death. 1 Development of atherosclerosis is the main underlying mechanism leading to the occurrence of vascular diseases. 2;3 Atherosclerosis tends to develop slowly and gradually over the years and remains subclinical, i.e., a-symptomatic for a long time. 4 Only when lesions or plaques rupture, acute symptoms occur, leading to disability or death. Indeed for a large proportion of the population sudden death is the only symptom from atherosclerosis development. 5 Traditionally, cardiovascular epidemiology focused on the relation between etiologic factors, i.e., vascular risk factors, and the occurrence of vascular events. In the past decades a shift has been made from events towards atherosclerosis, since the ability to obtain information on the atherosclerotic process using minimal or non-invasive approaches has dramatically increased. 6-9 This has lead to a large number of studies into the role of etiologic factors on subclinical atherosclerosis development, and studies on the presence and extent of subclinical atherosclerosis as a predictor of future events. In addition, studies have been launched to investigate the additional value of subclinical atherosclerosis measurements in the risk profiling of subjects. 10-12 Moreover, measurements of change in subclinical atherosclerosis are currently used in randomized controlled trials on the efficacy of drug treatment. 13;14 At present there are several possibilities to assess atherosclerosis in a minimal or non-invasive approach as have been detailed in several reviews. 9;15-19 This includes for example ultrasound with measurement of (carotid) intima-media thickness (CIMT) 15, and plaques 16, magnetic resonance imaging 17 with measurement of plaques and plaque tissue characteristics and computed tomography 18;19 with measurement of arterial calcifications. Electron-beam computed tomography (EBCT) has been shown to be able to measure calcium deposits in the coronary arteries. These deposits have been validated with pathological anatomical specimens and shown to indeed reflect atherosclerosis in the coronary arteries. Although data on coronary calcium has mainly come from studies using EBCT, nowadays multi detector CT (MDCT) is much more widely available and also allows for measurement of coronary calcium. The present thesis focuses on various aspects of the coronary calcium measurements on which information is not widely present. This includes studies into the reproducibility of the coronary calcium measurements by MDCT (chapter 2). Furthermore, several studies on the relation of presence and/or change in risk factors over time to coronary calcium and also the relation of risk factors to segment specific coronary calcium (chapter 3). In chapter 4 we examined the relation between coronary calcium and other marker of myocardial damage. Finally, the findings presented in this thesis are being put into perspective (chapter 5)