Literature Review: Acute Coronary Syndrome

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Acute coronary syndrome (ACS) is caused by lack of adequate blood in the heart. In particular, the condition occurs when the coronary arteries are blocked hence limiting their ability to supply oxygenated blood to the heart muscles. Unstable angina refers to the chest discomfort that is caused by the lack of enough blood flow. Unstable angina is more severe compared to stable angina but less severe than myocardial infarction. Unstable angina which is also known as the angina pectoris is characterized by pain in the chest. When the left anterior descending artery is occluded, the walls of the left ventricle, the interventricular septum and other parts are affected. When the right coronary artery is affected the right atrium and the left ventricle become ischemic. On the other hand, when the circumflex artery is occluded the left ventricle, atrium, fasciculus, and the bundle branches become ischemic.

The etiology of this condition focuses on the formation of atherosclerotic plaques. The process starts with endothelial dysfunction. Endothelial dysfunction refers to a condition whereby the inner linings of the endothelium fail to function properly. Remember, the endothelium plays an important role in regulating blood clotting but this function is likely to be affected by several conditions including metabolic syndrome, hypertension, smoking and inactivity. According to Balasubramaniam, Viswanathan, Marshall and Zaman (2012) endothelial dysfunction is characterized by an imbalance between vasodilating and vasoconstricting substances, and an increase in leucocyte adhesion, hence leading to vascular reactivity. Ultimately, endothelial dysfunction leads to atherosclerosis.

According to the American Heart Association, more than a million people are affected by this condition every year. In 2006 alone, more than 1.4 million patients were discharged with a primary or secondary diagnosis of acute coronary syndrome. Currently, there are more than 7 million people living with this condition. Beside death, coronary heart disease can lead to premature, chronic disability to the affected patients. Following a discharge, patients suffering from acute coronary syndrome require re-hospitalization within the first six months. One in every five patients diagnosed with non-ST elevation myocardial infarction and ST-segment elevation, dies after hospitalizations. In total, acute coronary syndrome accounts for half of all mortality related to cardiovascular diseases. The cost of rehabilitating patients with acute coronary syndrome is enormous. The direct costs of treatment are estimated to be $75 billion while the indirect costs of treating patients with acute coronary syndrome are more than $142 billion.

A number of studies have been conducted to examine the threat of ACS among the American population. One such study was conducted by Doyle, Simon, and Stenzel-Poore (2008) using a Behavioral Risk Factor Surveillance. Using self-reported data, the researchers found out that the Southern Eastern states are the ones that are heavily affected by the ACS menace. The study analyzed the risk factors that are responsible for the high prevalence rates in the South Eastern states. One of the risk factor that was examined is the ethnic background and socioeconomic status. The southern eastern part is mainly occupied by minority communities including the blacks and the socioeconomic status of the occupants there is much lower compared to the rest of the nation. The high prevalence rate can also be explained by the lifestyle factors such smoking. The southeasterners also suffer from contributing diseases such as diabetes, coronary heart diseases and hypertension. Due to the high prevalence rates, death rates as a result of ACS are also significantly higher, in the southeastern regions, compared to the other parts around the nation.

ACS has affected other developed countries. In the UK, ACS is a leading cause of disability, and a leading cause of death. Currently, there are around 1 million ACS survivors while an estimated 150,000 people are diagnosed with ACS every year. The majority of those affected by ACS in the UK are the elderly and the leading risk factor is obesity. In England, Northern Ireland, Scotland and Wales, 25% of the whole population is considered obese. The levels of activity among the residents in these four countries are also very low and this explains why ACS is responsible for a significant percentage of deaths that are reported in the country. Overall, £ 8 billion is spent in ACS-related costs.

Developing countries have not also been spared either. In India the prevalence of ACS has been on the rise and this occurrence has been attributed to an increase in the aged population. In Cuba, the crude mortality from ACS is 84 per 100,000 population while in the neighboring countries it is the second leading cause of death (Bonita & Beaglehole, 2871). Just like in India, a significant percentage of the total population in Cuba is made up of elderly people. Incidences of ACS in the developing countries are attributed to several factors. Firstly, low and medium income earning countries account for almost 80% of all chronic noncommunicable diseases that are reported in the world. At the same time, the local population in the developing countries continues to engage in lifestyle choices such as eating high-fat diets, smoking and living a sedentary lifestyle. As the residents continue to adopt the western lifestyle it is expected that the prevalence of ACS will continue to rise. These statistics illustrate to us that ACS is a serious condition which takes huge resources to rehabilitate patients. In addition, the disease has an adverse effect due to the loss in productivity. It is on this basis that it becomes important to evaluate the events surrounding the disease and how it can be prevented and managed.

Literature review

Acute cardiovascular syndrome is a form of cardiovascular disease and is a leading cause of death in the America. Death results when the atherosclerotic plaque breaks up hence stimulating platelet aggregation and thrombus formation. The thrombus formed then prevents myocardial perfusion. Remember, the myocardial cells require oxygen to function properly but the formation of the thrombus restricts the supply of the oxygen hence increasing the myocardial demand for the oxygen. As a result, the ischemic tissues become necrotic leading to decreased renal perfusion. Ultimately, decreased renal perfusion stimulates the release of renin, angiotensin, aldeosterone, antidiuretic hormone hence increasing workload of myocardium.

Balasubramaniam, Viswanathan, Marshall and Zaman (2012) evaluated the role of the endothelial cells in the atherosclerosis process. In the article Balasubramaniam, Viswanathan, Marshall and Zaman Balasubramaniam (2012) argues that endothelial dysfunction plays a pivotal role in the expression of atherosclerosis. When the endothelium becomes impaired it fails to maintain vascular homeostasis. As a result, a number of abnormalities are experienced and they include loss of nitric oxide, over-production of vasoconstrictors, and reduction of the ability to control inflammation, thrombosis and cell growth. The endothelium also plays the role of producing vasodilators such as nitric oxide, and prostacyclin while regulating the effect of vasoconstrictors such as endothelin-1 and angiotensin. The loss of vasodilators and over-production of vasoconstrictors affects the integrity of the arteries. One such vasoconstrictor is angiotensin. Angiotensin not only plays an important role in the loss of normal arterial compliance and patency, but it also mediates the plaque weakening process in a number of ways. Firstly, it leads to the up-regulation of the IL6 gene which is produced by the plaque microphages. Secondly, it leads to the up-regulation of the MMP genes which then lead to the degradation of the plaque fibrous cap. Thirdly, it leads to the activation of the nitrogen-activated protein kinase cascades and tyrosine kinases. Finally, it mediates the stimulation of neo-vascularisation.

In the article, Balasubramaniam, Viswanathan, Marshall and Zaman (2012) further look at the impact of the risk factors such as diabetes in the progression of atherosclerosis. In their view, diabetes mellitus is a strong predictor, and the studies that have been conducted indicate that patients suffering from diabetes have very a little opportunity of recovering from ACS. Mortality rates for diabetes mellitus patients with acute myocardial infarction are also high. In this article, they also look at the role of endothelial NO synthase in the inflammation process. As a vasodilator, eNOS plays an important plays an important role in preventing leukocyte (Balasubramaniam, Viswanathan, Marshall & Zaman, 2012) adhesion while maintaining the antiflammatory state of the endothelium. However, the ACS leads to the low production of eNOS and the endothelial cells are activated to produce vascular cell adhesion molecules such as the VCAM-1 and ICAM-1. These vascular cell-adhesion cells promote the adhesion of the leukocytes to the endothelial surface.

In this article, Balasubramaniam, Viswanathan, Marshall and Zaman (2012) further argue that diabetes increases the platelet aggregation and adhesion process in several ways. Firstly, the condition leads to reduced platelet membrane fluidity. Secondly, the condition leads to increased production of thromboxane, hence increasing platelet sensitivity. Thirdly, it increases the expression of platelet adhesion molecules and the number of platelets. These two actors play an important role in the pro-coagulant activity. Fourthly, diabetes increases the expression of platelet surface receptors and generation thrombin. Fifthly, diabetes mellitus reduces the sensitivity of the platelets to the effects of the vasodilators. Sixthly, platelets of patients with diabetes mellitus are rich in cytokines and chemokines which contribute to inflammation of the endothelium. These findings are supported by Al Thani et. al. (2012) who concluded that diabetes is an independent predictor for presence of polyvascular diseases and ACS.

Another study that was conducted by Zhong, Tang, Zeng, Wang, Yi, Meng, Mao, and Mao (2012) investigated the role of cholesterol content in atherosclerotic plaque progression. Zhong et al. (2012) used a sample of 136 participants. The researchers assessed the cholesterol content of erythrocyte membranes. It is well acknowledged that cholesterol plays an important role in plaque formation. The key feature of the plaque formation is the erythrocyte membrane. Erythrocyte membrane is a key source of cholesterol in plaques. Their findings are supported by () who found out that CEM in ACS patients is significantly higher that in patients with stable angina pectoris. In the study, Zhong, Tang, Zeng, Wang, Yi, Meng, Mao, and Mao (2012 also (2012) investigated some of the factors that determine the size of the plaque in the artery. Obviously, the amount of the cholesterol determines the size of the lipid core. The researchers concluded that erythrocytes played a major role in plaque expansion by increasing the lipid content. In addition, they argued that cholesterol encouraged apoptosis of macrophages and formation of foam cells.

The role of the low-density lipoproteins as a cause of ACS was investigated by Meisinger, Baumert, Khuseyinova, Loewel, and Koenig (2005). Very Low-density lipoproteins are secreted from the liver, and are then converted to low-density lipoproteins (LDLs). LDLs may accumulate in the artery wall if their rate of removal is low (Meisinger, Baumert, Khuseyinova, Loewel, & Koenig, 2005). The LDLs stimulate the endothelial cells to express the monocyte chemotactic protein-1 (Meisinger, Baumert, Khuseyinova, Loewel, & Koenig, 2005). MCP-1 then attracts monocytes from the blood. In addition, LDLs encourages differentiation of monocytes into macrophages. Macrophages promote the formation lipid-cell foam cells, which are the hallmark of the atherosclerosis process. Following this narration it is rather apparent that low-density proteins mark the start of atherosclerosis process, and its subsequent progression.

Plaque rupture

According to Kumar and Cannon (2009) the molecules in the endothelium mediate the adhesion of leukocytes on the endothelial surface. The monocytes penetrate the endothelial wall, where they interact with oxidized LDL, transforming into foam cells. The foam cells produce cytokines and other substances that maintain atherosclerosis progression. The plaque usually has a thin fibrous cap which is destabilized by the inflammation cells such as the monocytes, macrophages and T-cells. In the article titled, Coronary events, Armin, Masataka, Renu and Valentin (2012) revisit how the plaque forms and how it later erupts. An atherosclerotic plaque normally has a large necrotic core but a small layer of the fibrous cap. The expansion of the atherosclerotic plaque is facilitated by the accumulation of free cholesterol, and macrophage infiltration. The fibrous cap only has a few smooth muscle tissues and is often inhabited by macrophages and T lymphocytes. Once the fibrous cap erupts, it exposes the thrombogenic materials to the blood stream. Following the rupture of the plaque, thrombi are formed. It is the rupture of the fibrous cap that leads to the development of unstable angina and myocardial infarction.

A lot of research has focused on how the plaque ruptures. One likely cause is the accumulation of T-lamphocytes and microphages-derived foam cells which secrete cytokines and proteolytic enzymes leading to the depletion of smooth muscle cells. The apoptosis of smooth muscle cells is promoted by the mast cells which are abundant in the plaque. The reduction of the smooth muscle cells impairs the repair process. Remember, smooth muscle cells produce the cap-stabilizing collagen and so a significant reduction of the cells is likely to have deleterious effects. Plaque rupture is also facilitated by the blood flow-induced shear stress. It is assumed that as the plaque grows, the tensile stress on the plaque shoulders increases hence leading to fissuring and subsequent rupturing. Armin, Masataka, Renu and Valentin (2012) found out that areas of low shear stress had advanced plaques than areas with high stress. Armin, Masataka, Renu and Valentin (2012) further notes that not all plaque ruptures lead to coronary events.

Armin, Masataka, Renu and Valentin (2012) examined the atherosclerotic process and the effect it has on the size of the artery. During the initial stage, the size of the artery is usually normal. In the second stage, as the plaque formation progresses, the artery remodels itself to avoid lumen encroachment. In the third stage, the plaque ruptures and hemorrhages leading to formation of intramural thrombi. Armin, Masataka, Renu and Valentin (2012 notes that mostly the plaque heals and continues to grow. Alternatively, the thrombogenic materials may be embolized distally leading to coronary arterial insufficiency or asymptomatic micro-infarctions. In the fourth stage, if the right conditions exist, the rupture of the plaque leads to the occlusion of the affected arteries.

In the article, Armin and his colleagues also looked at the interplay of factors that contribute to acute coronary event risk (2012). One factor is plaque burden which is determined by the blood viscosity, platelet function, stress and smoking (Armin, Masataka, Renu & Valentin, 2012). The other coronary plaque characteristic is lumen encroachment which depends on shear stress, circadian variation, obesity, catecholamine surge and pollution (Armin, Masataka, Renu & Valentin, 2012). Other coronary plaque characteristics include lesion locations, plaque composition, plaque biology, plaque configuration, endothelial dysfunction and plaque remodeling ((Armin, Masataka, Renu & Valentin, 2012).

On their part, David and Valentin (1999) looked at the activities surrounding the atheromatous plaques. The formation of plaques according to can be traced to the early lesions. Early lesions then grow bigger as the extracellular lipid and cholesterol content increase and fibrous cap grow thin. This development according to David and Valentin (1999) occurs in 5 phases. During phase 1 the development of lesion types I-III occurs while in the phase 2, lesion types IV and Va develops (David & Valentin, 1999). Plaque disruption starts from phase 3, eventually leading to the growth of more complicated plaques. The acute coronary syndrome occurs in phase IV, when plaques are more complicated (David &Valentin, 1999). However, plaques may fail to rupture and occlude the affected arteries. Such plaques characterize the last stage of the plaque development.

Clinical sequellae and symptoms

The eruption of the fibrous cap exposes the content of the plaque to the blood elements. In addition, an alteration of the blood flow is experienced around the ruptured plaque and the blood flow supporting myocardial distal is reduced (David &Valentin, 1999). Vasoconstriction at the site of the ruptured plaque makes coronary events to become much more severe. (David &Valentin, 1999) If the ruptured plaque does not significantly disrupt the flow of the blood, only an asymptomatic progression of the lesion is experienced (David &Valentin, 1999). On the other hand, if the rupture leads to complete vessel occlusion, acute myocardial infarction results (David &Valentin, 1999). The common symptoms of ACS include chest pain, arrhythmia, shortness of breath, fatigue, weakness, heart palpitations, nausea, numbness, confusion, slurred speech, vertigo and headache.

Diagnosis

Detection of atherosclerosis is one of the main objectives of the diagnostic tools. One such advancement is the use of plasma markers. One of the markers that have been used widely is the C-reactive protein and the lipoprotein associated phospholipase A2. Such markers are used to predict coronary events. Using peripheral blood has become popular due to the low cost that is associated with this process. An alternative method that is used in diagnosing coronary patients is the non-invasive imaging. Some of the imaging tools that can be used for identifying vulnerable carotid plaques include: ultrasound, MRI, nuclear imaging and X-Ray multi-detector. A CT angiogram and a nuclear scan could also be used to check the site of rupture and identify whether the arteries are constricted or blocked. Other diagnostic tests include an electrocardiogram, blood tests, chest X-ray, and coronary angiogram.

Interventions

Reperfusion therapy

In the article titled, Acute coronary syndromes: diagnosis and management, Cannon and Kumar (2009) looks at the interventions for the acute coronary syndrome. Reperfusion therapy has been found to improve patient outcomes. The efficacy of reperfusion therapy in acute coronary syndrome was tested in a study that was conducted by Desai (2008). The 80 participants in this study were all ACS patients. The two researchers also compared the efficacy of the percutaneous balloon angioplasty and systematic thrombolysis. The two interventions were found to increase systolic and left ventricle functions.

Antithrombotic therapy

According to Kumar and Cannon (2009) the aim of this intervention is to maintain the patency of the infarct-related artery. Antithrombotic therapies are augmented by anti-platelet strategies such as aspirin and glycoprotein IIb/IIIa antagonists. Antianginal therapy could also be used and use of nitrates to reverse the vasospasm, reduce the coronary blood flow at the site of rupture and the myocardial oxygen demand.

Coronary surgery and angioplasty

It is apparent that administration of anti-platelet and anti-thrombotic drugs improves the chances of survival to the patients. These drugs are often used before percutaneous coronary or surgery revascularization is performed. The coronary surgery is performed to bypass the affected portion of the coronary artery. The grafted artery goes around the area with the plaque, a process that creates a new path for oxygen-rich blood. The efficacy of coronary artery bypass surgery is supported by a study that was conducted Kumar and Cannon (2009). All the participants in this study had ST-segment elevation myocardial infarction. The result of the study indicates that high-risk patients who undergo surgery intervention have very high chances of survival. An alternative to the bypass surgery is the percutaneous coronary surgery otherwise known as coronary angioplasty or balloon angioplasty. The process entails using a catheter with a balloon at the tip. Once in place, the balloon inflated to compress the plaque against the artery wall. This process targets unstable plaques which have thin fibrous caps, lipid full macrophages, and deficient smooth muscle cells. During balloon angioplasty, a stent is used to maintain the patency of the occluded arteries.

References

Al Thani, H., El-Menyar, A., Alhabib, K., Al-Motarreb, A., Hersi, A., Alfaleh, H., Asaad, N., Saif, S.A., Almahmeed, W., Sulaiman, K., Amin, H., Alsheikh-A., Alnemer, K. & Suwaidi, J. (2012). Polyvascular disease in patients presenting with acute coronary syndrome: its predictors and outcomes. Scientific World Journal, 2012, 284851

Armin, A., Masataka, N., Renu, V., & Valentin, F. (2012). Acute coronary events. Circulation, 10(1), 1147-1156

Balasubramaniam K, Viswanathan G, Marshall S, & Zaman A. (2012). Increased Atherothrombotic Burden in Patients with Diabetes Mellitus and Acute Coronary Syndrome: A Review of Antiplatelet Therapy. Cardiology Research and Practice, 2012, 1-18

Bonita, R., & Beaglehole, R. (2007). ACS prevention in poor countries: Time for action. Stroke, 38(11), 2871–2

David, E. G. & Valentin, F. (1999). Pathophysiology and clinical significance of atherosclerotic plaque rupture Cardiovascular Research, 41(2), 323-333

Desai, N.D. (2008). Pitfalls assessing the role of drug-eluting stents in multivessel coronary disease. Annals of Thoracic Surgery, 85 (1), 25–7.

Doyle, K. P., Simon, R. P., & Stenzel-Poore, M. P. (2008). Mechanisms of ischemic brain damage. Neuropharmacology, 55, 310.

Kumar, M.D. & Cannon, C. (2009). Acute coronary syndromes: Diagnosis and Management. Mayo Clinic Proceedings, 84(10), 917-938

Meisinger, C., Baumert, J., Khuseyinova, N., Loewel, H. & Koenig, H. (2005). Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation, 2; 112(5):651-7.

Zhong, Y., Tang, H., Zeng, Q., Wang, X., Yi, G., Meng, K., Mao, Y., & Mao, X. (2012). Total cholesterol content of erythrocyte membrane is associated with the severity of coronary artery disease and the therapeutic effect of rosuvastatin. Upsala Journal of Medical Sciences, 117(4): 390–398