Atherosclerosis with thrombosis superimposed, atherothrombosis, is the main cause of coronary heart disease (CHD), peripheral artery disease, and large-artery stroke.1,2,3 The development of thrombosis-prone atherosclerotic plaques, also known as high-risk or vulnerable plaques,4 in the coronaries and other arteries is the leading cause of death and severe disability, not only in affluent countries, but also worldwide.5,6
Causal and modifiable risk factors for atherosclerotic cardiovascular disease are well known (eg, smoking, dyslipidemia, high blood pressure, diabetes) and account for most heart attacks in both sexes.7 However, for unknown reasons, the individual susceptibility to these risk factors varies greatly, and consequently, their predictive value is limited.8,9 Most first heart attacks occur among people with average or only slightly elevated risk factor levels.10,11,12 Recurrent events still occur despite lowering of these levels,13,14 indicating that we need both better detection and better treatment of those who are destined for a heart attack. Better detection of at-risk individuals may be achieved by visualizing the diseased arterial wall rather than just assessing risk factors for getting the disease.15,16,17 The prospect for atherosclerosis-based risk assessment will be discussed in the concluding section of this chapter.
ATHEROGENESIS AND PLAQUE DEVELOPMENT
Atherosclerosis is a chronic, lipid-driven inflammatory disease of the arterial wall leading to multifocal plaque development,18,19,20 predominantly at sites characterized by low and oscillatory endothelial shear stress (bifurcations, inner wall of curvatures) and preexisting intimal thickenings.21,22 The speed of disease progression varies greatly, but it usually takes decades to develop the advanced atherosclerotic lesions responsible for clinical disease. Plaques are very heterogeneous in size and composition, even plaques located next to each other and exposed to the same systemic risk factors (Fig. 32–1). Most plaques remain asymptomatic (subclinical disease), some become obstructive (stable angina), and a few, if any, become vulnerable and lead to atherothrombotic events such as a fatal heart attack or a disabling stroke.
Heterogeneity of atherosclerotic plaques. Cross-section of a coronary artery cut just distal to a bifurcation. The plaque to the left (circumflex branch) is fibrotic with a dense calcification, whereas the plaque to the right (marginal branch) contains a large lipid-rich necrotic core covered by a thin fibrous cap that is disrupted with mural thrombosis. The lumen contains contrast medium injected postmortem. Trichrome, staining collagen blue and thrombus red.
The endothelium, located at the interface between the blood and the arterial wall, plays a key role in the development of atherosclerosis.22 In lesion-prone areas, apoprotein B–containing lipoproteins extravasate into intima, where they are retained and modified (eg, oxidized) into cytotoxic, proinflammatory, ...