Page 12 - Rob Holtackers

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Coronary artery disease (CAD) is the most common of the cardiovascular diseases and
involves the gradual build-up of fatty streaks or ‘plaques’ in the coronary arteries, also
known as atherosclerosis. In a period that may extend over tens of years, the coronary
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arteries slowly narrow and stiffen over time (Figure 1.1). The narrowing of the arteries
prevents oxygenated blood from reaching the cardiomyocytes, which may cause chest
pain and discomfort known as ‘angina’. While angina is generally experienced with
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physical activity first, emotional stress may also trigger pain during rest. As
atherosclerotic plaques increase in size over time, a lipid-rich necrotic core can form
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that is separated from the vessel lumen by a fibrous cap. This cap averts contact of the
thrombogenic core substituents with the blood flow. Specific plaque features, such as
intra-plaque hemorrhage, may develop that are known to destabilize plaques that make
them more vulnerable to rupture. With sudden rupture of the fibrous cap, the
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thrombogenic plaque material is released into the blood stream triggering a cascade of
events. Immediate blood clotting results, which may occlude the coronary artery and
thereby cutting off the blood supply to the tributary tissue. The resulting ischemia leads
to rapid degeneration and subsequent necrosis of the cardiomyocytes, called
myocardial infarction (MI).

Among cardiovascular diseases, CAD ranks as the most prevalent with approximately
8.9 million (16%) annual deaths worldwide, leaving it the leading cause of death in

Figure 1.1: Schematic overview of the progression of atherosclerosis. Through a complex series
of cellular events within the arterial wall, a fatty streak or ‘plaque’ is formed between the inner
lining (endothelium) and middle layer (tunica media) of the blood vessel. Over time, this plaque
undergoes extensive remodeling and increases in size, thereby potentially narrowing the vessel
lumen. Specific processes, such as intra-plaque hemorrhage and thinning of the fibrous cap, may
destabilize the plaque making it vulnerable to rupture. Ultimately, in case the plaque ruptures,
the thrombogenic plaque contents are exposed to the blood stream, leading to immediate blood
clotting and obstructing or completely blocking blood flow downstream. Image adapted from the
‘Arteries atherothrombosis’ dataset by Servier Medical Art.