CHD which is also known as coronary artery disease or ischemic heart disease is a complex chronic disease which involves the remodelling and narrowing of the coronary arteries providing myocardial oxygen to the heart (Sayols-Baixeras, Lluis- Ganella et al. 2014). The underlying pathophysiological mechanism of CHD is known as atherosclerosis, which starts and develops for decades prior to an acute event (Ambrose and Singh 2015). Briefly, atherosclerosis is a silent progressive process
characterized by accumulation of lipids, fibrous elements, and inflammatory molecules in the inner walls of the coronary arteries that is accelerated by well-known risk factors such as high blood pressure, high cholesterol, smoking, diabetes, and genetics (Sayols-Baixeras, Lluis-Ganella et al. 2014, Ambrose and Singh 2015).
Consequently, the inner layer of the coronary arteries is gradually thickened, which may over time lead the lumen of the artery to be narrow in various degrees.
Atherosclerotic plaque growth and changes are shown in Figure 2.1.
Figure 2-1 Formation stages of coronary atherosclerotic plaque and the consequences
The top of the diagram represents longitudinal and cross-sectional images of the coronary artery, in which stages of the atherosclerotic plaque and the effects were shown.
Labels are as following: (1) Cross section of normal artery; (2) Start of extracellular lipid accumulation in the inner layer (intima) of coronary artery; (3) The stage of fibrofatty; (4) The progression of lesions when the fibrous cap was weakened; (5) The
rupture of the fibrous cap and stimulation of thrombogenesis; (6) The response with thrombus resorption, accumulation of collagen and growth of smooth muscle cell; (7) The erosion of endothelial layer, may cause acute myocardial infarction.
The blue arrows show the chance to develop ST elevation in clinical presentation of patients.
(Reproduced from Libby, P; et al.(Libby 2001) and Davies, M.J.(Davies 2000))
At the first stage, low-density lipoprotein (LDL) cholesterol starts to efflux to the subendothelial space, and then be modified and oxidized by various agents.
Oxidized/modified LDL cholesterol particles are potent chemotactic molecules including expression of vascular cell adhesion molecule and intercellular adhesion molecule at the endothelial surface, and contribute to monocyte adhesion and the movement to the subendothelial space. Monocytes differentiate to macrophages in the intima (Ghattas, Griffiths et al. 2013, Sayols-Baixeras, Lluis-Ganella et al. 2014).
Foam cells enhance macrophages binding to oxidized LDL cholesterol via scavenger receptors (Glass and Witztum 2001), resulting in pro-inflammatory actions, including the release of cytokines. This process ends with the formation of the first typical atherosclerotic lesion, i.e., the fatty streak (Sayols-Baixeras, Lluis-Ganella et al. 2014).
In the sub-endothelial space, the accumulation of other types of leukocytes occurs, including lymphocytes and mast cells (Libby, Ridker et al. 2011). The mix between monocytes, macrophages, foam cells, and T-cells results in cellular, immune responses, and a chronic inflammatory state (Sayols-Baixeras, Lluis-Ganella et al.
2014). Migration of smooth muscle cells from the medial layer of the artery into the intima follows, resulting in the development from a fatty streak to a more complex
lesion (Glass and Witztum 2001). In the intima, smooth muscle cells produce extracellular matrix molecules and creates a fibrous cap covering the original fatty streak. The death of foam cells inside the fibrous cap releases lipids, which accumulates in the extracellular space and forms a lipid-rich pool, namely the necrotic core. This process results in the second atherosclerotic lesion, the fibrous plaque.
The thickness of the fibrous cap is very important for the integrity of the atherosclerotic plaque (Sakakura, Nakano et al. 2013), and depending on that thickness, two types of plaque can be classified, i.e., stable and unstable or vulnerable. Stable plaques are normally made with an intact, thick fibrous cap formulated by smooth muscle cells in a matrix rich in type I and III collagen (Finn, Nakano et al. 2010). This kind of plaque often causes flow-limiting stenosis, leading to tissue ischemia and potentially stable angina. In contrast, vulnerable plaques have a thin fibrous cap composed mostly of type I collagen and few or no smooth muscle cells, but abundant macrophages and pro- inflammatory and pro-thrombotic molecules (Sakakura, Nakano et al. 2013). These plaques can be subject to erosion or rupture, releasing the core of the plaque to circulating coagulation proteins, causing thrombosis, sudden occlusion of the artery lumen, and usually an acute coronary syndrome (ACS) (Tanaka, Nakamura et al. 2004, Libby, Ridker et al. 2011, Ghattas, Griffiths et al. 2013).
The position, amount and changes in size over time of the atherosclerotic plaques can lead to various degrees of coronary artery lumen obstruction. When the myocardial oxygen consumption is increased due to an increase in heart rate and myocardial contractility, depending on the time and volume of the coronary artery lumen obstruction, this may result in the imbalance between myocardial oxygen supply and
oxygen consumption. Patients may have some ischemic chest symptoms as a result of this imbalance especially when the coronary lumen diameter reduces to over 50% of the normal size (Shugman 2012).
One or more coronary arteries may narrow through the development of atherosclerotic plaques. During a period of increased demand for myocardial oxygen, such as following exercise, the symptoms of ischemia can be triggered and the spectrum of CHD may present. Clinically, the spectrum of clinical presentations of CHD has been classified into chronic or stable CHD, ACS and sudden cardiac death (Sayols- Baixeras, Lluis-Ganella et al. 2014). Chronic CHD comprises silent ischemia and stable angina while the spectrum of ACS is characterised by acute symptoms and includes unstable angina, non-ST-segment elevation myocardial infarctions (NSTEMI) and ST-segment elevation myocardial infarctions (STEMI) (Figure 2.1).
These classifications are determined by the electrocardiogram (ECG) and cardiac biomarker levels which includes creatine kinase (CK), creatine kinase MB (CKMB) and/or the more specific and sensitive cardiac biomarkers, Troponins (Troponin T [TnT] or Troponin I [TnI]) (Thygesen, Alpert et al. 2007). Among the range of ACS, STEMI is the most severe form that often results in mechanical instability, cardiac rhythm disturbance and/or sudden cardiac death.