Executive Summary
Acute coronary syndromes (ACS) are documented as one of the world’s leading health problems and the most expensive cluster of diseases to treat and manage. Expenditure on ACS runs into billions of dollars each year due to high direct health costs, productivity losses and informal care for the individual patient, while the community is exposed to substantial disease burden associated with mortality and morbidity of the population due to ACS. This report has taken the initiative to discuss at length the impact of ACS on the patient and community.
From the careful analysis of extant literature, it is evident that acute coronary syndromes serve as an umbrella term for a broad spectrum of life-threatening health conditions affecting the heart, and which are suggestive of acute myocardial ischemia. In ACS, the blood flow in the coronary arteries is suddenly blocked or reduced, normally as a result of rupture of atherosclerotic plaques and consequent thrombosis, leading to a constellation of heart conditions which include unstable angina (chest pain), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
In the Pathophysiological section, it has been demonstrated that two types of thrombi can develop – a platelet-rich clot (white clot) which develops in sections of elevated shear stress and only partly occludes the artery, or a fibrin-rich clot (red clot) that arises due to a stimulated coagulation cascade and diminished flow of oxygenated blood in the artery; overall, it has been demonstrated that the fibrin-rich clots are often superimposed on platelet-rich clots, and this aspect is to blame for the total occlusion of the arteries, leading to sudden death due to ACS. Consequently, although only platelet-rich clots are found in patients with either unstable angina or NSTEMI, fibrin-rich clots form in addition to the platelet-rich clots in patients with STEMI.
Background
Introduction
Acute coronary syndrome (ACS) is an umbrella term for a broad spectrum of life-threatening health conditions affecting the heart (Charles River Associates, 2011), and which are suggestive of acute myocardial ischemia (Nagesh & Roy, 2010). In ACS, the blood flow in the coronary arteries is suddenly blocked or reduced, normally as an outcome of rupture of atherosclerotic plaques and consequent thrombosis (Eriksson et al, 2006). A careful analysis of literature (Charles River Associates, 2011; Ferraro et al, 2010) demonstrates that ACS is a consequence of an abrupt blockage of blood supply to the heart arising from cholesterol upsurge and the formation of a blood clot in the heart’s arteries. According to Nagesh & Roy (2010), the ultimate clinical implication for the resulting undersupply of oxygen to the heart may vary from assuredly benign to potentially fatal, but is known to lead to a constellation of heart conditions which include unstable angina (chest pain), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) (Kumar & Cannon, 2009).
It is the mandate of this pathology report to critically evaluate existing literature on ACS, to bring into light the various dimensions of the syndromes, including the risk factors and presenting symptoms involved, diagnosis and classification of ACS, pathophysiology and management of ACS, and the impact of the syndromes on the patient and community.
Brief Statistics on ACS
The high-risk manifestations of coronary atherosclerosis associated with ACS are expected to be the principal cause of death worldwide within the next 15 years, in large part due to a rapidly increasing prevalence in developing nations and the rising frequency of obesity and diabetes in the Western world (Dominguez-Rodriguez et al, 2009). Indeed, these authors posit that “…cardiovascular disease causes 38% of all deaths in North America and is the most common cause of death in European men under 65 years of age and the second most common cause in women” (p. 367). These figures are reinforced by Housholder-Hughes (2006), who not only observes that conditions associated with ACS are the foremost cause of death in the United States, but also reveals that one-third of the 2 million patients admitted to hospitals with an ACS have STEMI, while the remaining two-thirds suffer from NSTEMI-related complications.
Risk Factors & Presenting Symptoms of ACS
Extant literature demonstrates that a number of risk factors are to blame for the increasing prevalence of ACS. According to Kanichy et al (2010), these factors “…include diabetes, dyslipidemia, hypertension, obesity, smoking, aging, gender and ethnicity” (p. 3). Researchers and practitioners are in agreement that the presenting symptoms of ACS can be varied due to the broad spectrum of conditions associated with the term. A careful meta-analytic review of the literature ( Dager,2007; Labounty, & Eagle, 2007; Kumar & Cannon, 2009) notes that symptoms of ACS may, but do not always, include: shortness of breath; chest pain or pressure; pain in other locations including the neck, jaw, back, abdomen, and upper extremities; lightheadedness; vomiting; unexplained fatigue; diaphoresis; dyspnea; syncope, and; nausea. It is important to note that the risk of ACS varies between patients and, consequently, it is always imperative for health practitioners to evaluate the risk on an individual basis so that the most suitable treatment approach is adopted for optimal patient outcomes (Marshall, 2011).
Diagnosis & Classification of ACS
In diagnosis, researchers and practitioners maintain that “…careful and focused history taking and physical examination are essential both to assessing the likelihood that the presenting illness is ACS and to determining the risk of adverse outcome” (Kumar & Cannon, 2009, p. 919). This view is reinforced by Marshall (2011), who argues that it is imperative for practitioners to rely on evidence-based knowledge of how patients should be evaluated for ACS, particularly in history-taking, physical assessment, electrocardiogram (ECG) recordings and biochemical markers, if the patients’ experiences and outcomes are to be enhanced. These assessments, according to Mahaffey (2006), are intrinsically important in not only determining whether the presenting symptoms are suggestive of ACS, but in narrowing down the focus to rightly classify the type of ACS affecting the patient. It is imperative to note that the 5 most significant history-related dynamics associated with ACS, ranked in order of significance, are the nature and scope of the anginal symptoms, a history of cardiovascular diseases, male sex, relatively old age, and a multiplicity of established risk factors such as hypertension, smoking and hypercholesterolemia (Kumar & Cannon, 2009).
As noted by Marshall (2011), patients are classified as having STEMI or NSTEMI depending on the outcomes of the electrocardiogram. A careful analysis of literature (Kumar & Cannon, 2009a; Marshall, 2011; Labounty & Eagle, 2007; Ueda et al, 2004) reveals that patients classified as suffering from STEMI most probably experience characteristic chest pain for more than 20 minutes and persistent ST-segment elevation, while those classified as having NSTEMI or unstable angina most probably experience acute chest pain without persistent ST-segment elevation. Marshall (2011) is particularly categorical that the persistent ST-elevation that eventually leads to STEMI arises when a coronary artery supplying a large section of the myocardium with oxygenated blood becomes totally occluded. This author also proposes that patients without persistent ST-segment elevation but with acute chest pain can be further categorized as having either NSTEMI or unstable angina based on the outcomes of tropin tests. On their part, Kumar & cannon (2009) posit that “…a diagnosis of NSTEMI can be made when the ischemia is sufficiently severe to cause myocardial damage that results in the release of a biomarker of myocardial necrosis into the circulation” (p. 917). In contrast, an individual is believed to have suffered from unstable angina if all of the biomarkers assessed by physicians are absent from the blood hours after the preliminary inception of the ischemic chest pain.
Pathophysiology of ACS
Available literature demonstrates that not only has our knowledge and understanding of the pathophysiology of ACS increased tremendously over the last two decades (Dominguez-Rodriguez et al, 2009), but this understanding, along with an elevated understanding of the classification, epidemiology and natural history of ACS, has inarguably assisted researchers and practitioners to understand the complexity of the condition (Marshall, 2011). This section, which is the major focal point of this report, deals entirely with the pathophysiology of ACS.
Commencement of Atherosclerosis: Role of Endothelium
According to Kumar & Cannon (2009), “…atherosclerosis is the ongoing process of plaque formation that involves primarily the intima of large- and medium-sized arteries; the condition progresses relentlessly throughout a person’s lifetime, before finally manifesting itself as an acute ischemic event” (p. 917-918). These authors further observe that several coronary risk factors, which include hypercholesterolemia, hypertension, diabetes and smoking, are known to influence the initiation of atherosclerosis by damaging the endothelium of the blood vessel. This damage, according to Marshall (2011), results in endothelial dysfunction – a key trigger of the atherosclerotic process. Indeed, Eriksson et al (2006) reinforce this fact by noting that coronary atherosclerosis with ensuing plaque development and irregular or enduring coronary artery occlusion is the foremost pathophysiological background for ACS. However, to better understand the dynamics involved, Kumar & Cannon (2009) posit that a dysfunctional endothelium is typified by abridged bioavailability of “nitric oxide and by disproportionate generation of endothelin 1” (p. 918), which not only impairs the much needed vascular homeostasis but increases the expression of adhesion molecules and also increases the thrombogenicity of blood through the secretion of numerous locally active substances.
Development of Atherosclerotic Plaque: Role of Inflammation
A careful analysis of existing literature demonstrates that inflammation plays a critical role in the pathophysiology of ACS. Kumar & Cannon (2009) are particularly categorical that “…once the endothelium has been damaged, the inflammatory cells, especially monocytes, migrate into the subendothelium by binding to endothelial adhesion molecules; once in the subendothelium, they undergo differentiation, becoming macrophages” (p. 918). The macrophages convert into foam cells by “…digesting oxidized low-density lipoprotein (oxLDL) that has also infiltrated the arterial wall, resulting in the accumulation of lipids of the LDL particles in the walls of blood vessels and subsequent formation of fatty streaks” (Eriksson et al, 2006, p. 430). While Kumar & Cannon (2009) argue that these macrophages play a decisive role in plaque vulnerability and the inclination for rapture, Eriksson et al (2006) argue that it is the evolving lesion coupled with the apoptosis of many of the lipid-laden foam cells to generate a necrotic core with cholesterol crystals, free cholesterol, cholesterol esters and cell debris, which serves as precursors for the eventual rapture. It is imperative to underline the fact that inflammation in atherosclerosis is largely a vascular response to a multiplicity of damage-causing stimuli (Dominguez-Rodriguez et al, 2009), which leads to plaque rupture and, subsequently, may result in ACS (Kumar & Cannon, 2009; Ravkilde, 2005; Philipson et al, 2010).
Stability of Atherosclerotic Plaques & Inclination for Rapture
There exist broad consensus among scholars and practitioners that the stability of atherosclerotic plaque varies. Marshall (2011) argues that “…unstable plaques that are prone to rapture have a large lipid base, a low density of smooth muscle cells, a high concentration of inflammatory cells and a thin fibrous cap covering the lipid core” (p. 48). This view is supported by Kumar & Cannon (2009), who posit that the distinctiveness of susceptible plaques includes a large lipid core, slender stringy caps, thickness of macrophages and T lymphocytes, a relative scarcity of smooth muscle cells, locally elevated expression of matrix metalloproteinases that mortify collagen, unconventional outward remodeling, and “…enlargements in plaque neovascularity and intraplaque hemorrhage” (p. 918). While some researchers have observed that the composition of human atherosclerotic plaque is outstandingly diverse even within the same individual (Kumar & Cannon, 2009), others have suggested that inflammation is a predominantly significant determinant of the susceptibility of plaques as it is associated with an increase in the activity of macrophages at the location of the plaque (Lorenzova & Penicka, 2008), the underlying consensus is that the increased activity at the site leads to an enlargement of the lipid base and a lessening of the plaque cap – aspects that render the plaque more susceptible to rapture (Kumar & Cannon, 2009; Marshall, 2011; Radovanovic et al, 2010).
Plaque Disturbance, Thrombosis, and ACS
Housholder-Hughes (2006) posits that “…rupture or erosion of the cap exposes the highly thrombogenic contents of the plaque to the circulation” (p. 9). Consequently, according to this author, the circulating platelets stick to the subendothelial collagen and are stimulated by collagen and/or other localized “…biochemical and mechanical stimuli, such as adenosine diphosphate (ADP), thromboxane A2(TXA2), thrombin, and high-shear stress of coronary circulation” (p. 9). Extant literature demonstrates that two types of thrombi can develop – a platelet-rich clot (white clot) which develops in sections of elevated shear stress and only partly occludes the artery, or a fibrin-rich clot (red clot) which arises due to an aroused coagulation cascade and diminished flow of blood in the artery (Lee et al, 2008); overall, Kumar & Cannon (2009) note that fibrin-rich clots are often superimposed on platelet-rich clots and this aspect is to blame for the total occlusion of the arteries, leading to sudden death due to ACS.
The above view is supported by Lorenzova & Penicka (2008), who argue that not only does a thrombosis occur immediately after denudation of the endothelium even in the absence of the plaque rupture, but the coagulation cascade is aroused consequent to contact with collagen fibers of subendothelium. Kumar & Cannon (2009) note that the pathogenesis of ACS involves a convoluted interaction between “…the endothelium, the inflammatory cells, and the thrombogenicity of the blood” (p. 918). These authors’ further note that aspects such as the fat and tissue factor composition of the plaque, the level of inflammation at the location of rapture, the blood flow in the section, the gravity of the plaque rupture, and the patient’s “antithrombotic and prothrombotic equilibrium” are fundamentally significant in not only controlling the magnitude of thrombus development, but also in determining whether a particular plaque rapture will eventually result in ACS (also, Radovanovic et al, 2010; Ravkilde, 2005).
Therapeutic Management and Approaches for ACS
According to Kumar & Cannon (2009), “…the severity of findings on coronary angiography and angioscopy parallels the clinical severity of ACS” (p. 918). These authors further argue that although only platelet-rich clots are found in patients with either unstable angina or NSTEMI, fibrin-rich clots form in addition to the platelet-rich clots in patients with STEMI. Consequently, the dissimilarities in the underlying pathophysiology for unstable angina/NSTEMI and STEMI call for divergent therapeutic management and approaches. In unstable angina/NSTEMI, the objective of antithrombotic therapy should be focused on preventing further thrombosis and permitting endogenous fibrinolysis to soften the thrombus and reduce the level of coronary stenosis. Consequently, revascularization is often employed to enhance blood flow and avert re-occlusion or recurrent ischemia (Marshall, 2011; Kumar & Cannon, 2009; Uenda et al, 2004). In STEMI, Kumar & Cannon (2009) note that “…the infarct-related artery is usually totally occluded, and immediate pharmacological or catheter-based reperfusion is the initial approach, with the goal of obtaining coronary blood flow” (P. 919). Consequently, the aim of therapeutic management should be focused on attaining swift reperfusion by primary angioplasty or fibrinolytic therapy (Marshall, 2011).
Impact of ACS on the Patient & Community
Acute coronary syndromes (ACS) are not only a burden to society due to their high rate of prevalence and the high costs involved in treatment (Ioannides-Demos et al, 2010), but the mortality rates associated with these conditions are substantial as half of all deaths occurring due to cardiovascular disease are attributed to ACS (Zhenxiang & Winget, 2011). With the large number of patients impacted by ACS, along with the huge societal burden and high economic costs occasioned by these diseases, it becomes increasingly important to conduct a critical analysis of the impact of ACS on the patient and community.
Impact of ACS on the Patient
For the patient, the substantial economic costs associated with ACS include, but are not limited to, treatment-related costs (drugs and hospitalization), as well as costs arising from loss of productivity (Kanichy et al, 2010). In medical costs, Dager (2007) observes that the “…direct US costs in 2007 for CHD – most of which consist of ACS, physician, and other professional costs – [were] estimated at $83.6 billion” (p. 237). In the loss of productivity, Zhenxiang & Winget (2011) note that in 2009 alone, the American Heart Association estimated that loss of productivity for coronary heart disease accounted for about $81.1 billion. Kanichy et al (2010) observe that many health institutions advise patients diagnosed with acute myocardial infarction to return to full normal responsibilities, including work, 6-8 weeks after being diagnosed with the syndrome, leading to the loss of productivity for the patients involved.
Even though depression has been established as a risk factor for ACS due to the fact that depressed people are more likely to engage in injurious lifestyle behavior such as smoking and physical inactivity, there exist compelling “…evidence that depression is significant in the recovery process following an acute cardiac event” (Page et al, 2010, p. 737). Consequently, the impact of depression on patients with ACS may be so enormous to a point of either jeopardizing treatment and management options for the various variants of ACS, or condemning the patient to a life of misery, stress and unproductiveness (Dager, 2007). In addition to these impacts, it is a well-known fact that ACS is associated with disability, implying that a sizeable number of patients and their families have to suffer through a decline in their quality of life (Charles River Associates, 2011). Indeed, according to the Charles River Associates report, “over 327,000 disability-adjusted life years are lost due to ACS in a year” (p. 1)
Impact of ACS on the Community
According to the report by Charles River Associates (2011), these syndromes have a cost to the economy, in large part due to death of qualified employees, a premature departure from work, and sick leave owing to poor health. The report is clear that these syndromes “…are responsible for an estimated 1.5 million days of sick leave per year in the UK” (p. 3). Available literature demonstrates that the economic impact of ACS has been projected to exceed $150 billion annually by the end of 2011 (Zhenxiang & Winget, 2011). But according to Kanichy et al (2010) these economic costs bear direct consequences on the community as the dead automatically belong to a community, and the patients who prematurely retire from gainful employment (morbidity) due to ACS end up increasing the disease burden shouldered by the community. It is known that there is a substantial burden associated with patients experiencing loss in both length and quality of their life due to morbidity caused by ACS (Charles River Associates, 2011; Kanichy et al, 2010), and it is the community that pays to reduce this burden. According to Ioannides-Demos et al (2010), CVD – of which ACS is central – contributes substantially to the mortality and morbidity of the Australian population, accounting for an estimated 18 percent of the entire burden of disease in 2003. These, according to Dager (2007), are the social costs of ACS that the community has to shoulder.
List of References
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