The underlying cause of ACS is a form of atherosclerosis known as CHD. In CHD, lipids, calcium, fibrin, and other cellular substances/cellular debris are deposited in the lining of the arteries, forming atherosclerotic plaques at sites with low-velocity blood flow (e.g., branch points, inner curvatures) [31]. Although the exact mechanisms are not completely understood, most researchers agree that injury to the inner (endothelial) layer of the artery initiates a series of biochemical events that result in the formation of atherosclerotic plaque. High levels of low-density lipoprotein (LDL) alone can cause atherosclerosis; however, it is most often the case that lower levels of LDL combined with other identified risk factors, including cigarette smoke, low levels of high-density lipoprotein (HDL), hypertension, diabetes, male sex, and family history, lead to atherosclerosis [31]. Individuals with very low LDL typically do not develop clinically significant atherosclerotic plaques, even in the presence of these risk factors.

Formation of a thrombus occurs when the fibrous cap of an atherosclerotic lesion erodes or ruptures, exposing the red cell-rich lipid core to circulating blood. It is thought that the same stimuli that are responsible for the initial injury to the vessel wall are also responsible for causing erosion or rupture of vulnerable plaque (i.e., inflammation). Cigarette smoking and high levels of circulating LDL head the list of injurious agents along with hypertension and diabetes [1,31,32,33,34].

When a thrombus occludes a coronary artery, oxygen supply to the area of the heart supplied by that vessel is reduced. When the supply becomes insufficient to meet the tissue's metabolic demands, the myocardial cells become ischemic; ischemia can develop within 10 seconds. After 1 minute of inadequate oxygen supply, the heart's function is affected. Irreversible tissue death and damage will occur after 20 minutes of ischemia [34].

The Framingham Heart Study identified the first risk factors, and these factors were integrated into a risk-assessment tool, the Framingham Risk Score [49]. The factors in the Framingham Risk Score include age, total cholesterol level, HDL level, systolic blood pressure, treatment for hypertension, and cigarette smoking, and the score is used to determine the 10-year risk of so-called hard CHD (defined as MI or coronary-related death) among asymptomatic adults. The Framingham risk score is one of several scores that involve several traditional risk factors for assessing risk; other scores recommended include the Systematic Coronary Risk Evaluation (SCORE), PROCAM (men) and Reynolds (separate scores for men and women) [50]. The use of one of these risk calculators is a class IB recommendation from the American College of Cardiology Foundation and American Heart Association [50]. It is important to consider the populations on which these risk scores are based. For example, the Framingham Risk Score was developed on the basis of risk factors identified in the Framingham Heart Study, which involved a primarily White, middle-aged population. When the risk score has been evaluated in other populations, it has been found to underestimate the risk of CHD among older (mean age: 73.5 years) Black and White individuals, especially women [51]. ACC/AHA guidelines published in 2013 recommend that race- and sex-specific Pooled Cohort Equations be used to predict 10-year risk of a first hard atherosclerotic cardiovascular disease event in non-Hispanic Black and non-Hispanic White individuals (class IB) [52]. These equations were developed on the basis of data on participants from several large racially and geographically diverse studies [52]. The guidelines also note that the sex-specific pooled cohort equations for non-Hispanic White individuals may be considered to estimate risk for people other than Black and non-Hispanic White individuals (class IB) [52].

Increased emphasis has been placed on better management of lifestyle habits as primary prevention of CHD. Lifestyle risk factors such as obesity, poor diet, and physical inactivity have a great influence on traditional risk factors such as blood pressure and cholesterol levels, as well as on novel risk factors, such as inflammation and endothelial function [78]. Lifestyle management is a key component of the new guidelines for the treatment of cholesterol levels and hypertension, and several other guidelines have addressed issues related to lifestyle behaviors, such as obesity, diet, and physical activity. The ACC/AHA/TOS (The Obesity Society) developed a guideline on the management of overweight and obesity, and some members of the Expert Panel authored a separate review on the evidence statements related to cardiovascular risk [79,80]. The AHA/ACC also published a guideline on lifestyle management to reduce cardiovascular risk in 2013 [81]. In its guideline of cardiac screening, the ACP notes that strategies to improvement lifestyle behaviors should be emphasized [65]. The USPSTF recommends counseling to promote a healthful diet and physical activity to prevent cardiovascular disease, and the AHA focuses on changing lifestyle behaviors in its guide for improving cardiovascular health at the community level [82,83,84]. The decision to offer or refer adults without cardiovascular risk factors to behavioral counseling should be individualized by the primary care provider [85].

The two primary goals of the initial evaluation in the emergency department are to determine the likelihood that an individual has ACS and to estimate the short-term risk of adverse outcome(s) [3]. The findings of the history, physical examination, ECG, and cardiac troponin levels have been integrated into risk assessment scores and clinical prediction algorithms to help identify patients at increased risk of adverse outcomes. Identifying patients at high risk is most important, as these patients will gain the greatest absolute benefit from appropriate therapy [2,3]. Because timely, appropriate treatment depends on results of the clinical findings and diagnostic testing, it is essential that this information is obtained as quickly as possible.

Research has shown that a history of traditional cardiac risk factors varies among some subgroups. Women with ACS are more likely than men to have a history of diabetes, hypertension, or hyperlipidemia [11,101,102,103,104,105,106]. (It has been suggested that this is due to the fact that women tend to develop ACS at an older age) [103,106]. Women are less likely to be smokers, to have a history of angina or MI, and to have had PCI or CABG, regardless of the cardiac history [104,107,108]. Data on the prevalence of risk factors across racial/ethnic subgroups with ACS was reported in 2008 (Table 6) [109].

Chest pain is the most commonly reported symptom in all patients with ACS, regardless of age, gender, race/ethnicity, or the presence of comorbid conditions [14,116,117]. So-called "classic" ACS-related chest pain has been described as diffuse pain or pressure in the substernal or epigastric area that frequently radiates to the neck, jaw, and left arm [22,101,118,119]. Chest pain related to ACS usually begins abruptly and lasts at least 15 to 20 minutes; however, the duration of pain varies among patients [101,120]. Pain that lasts for longer than 20 minutes is associated with increased short-term risk of MI (nonfatal or fatal) [121]. The intensity of "classic" ACS chest pain increases over time, reaching maximal intensity after a few minutes [101,122]. Pain is usually worse with activity and improves with rest [101].

An increasing number of studies have demonstrated that atypical chest pain occurs more often in several subgroups of patients, especially women, older individuals, and people with diabetes [14,102,117,126,131,132,133,134]. In addition, the findings of several studies and literature reviews have demonstrated that women with ACS are more likely to have pain or discomfort in the jaw, neck, throat, arm/shoulder, and back [102,127,131]. Failure to recognize atypical symptoms of ACS has been found to delay diagnosis and/or result in the use of less aggressive treatment. It has been estimated that more than 40% of patients with angina have one or more "atypical" elements in their chest pain description [135,136]. Atypical symptoms that have been found to be associated with ACS include shortness of breath, fatigue, lethargy, indigestion, anxiety, tingling in upper extremities, palpitations, loss of appetite, and flushing. Words commonly used to describe "atypical" chest pain associated with ACS include numbness, tingling, burning, stabbing, or pricking. Atypical chest pain location includes any area other than substernal or left sided, such as the back, area between shoulder blades, upper abdomen, shoulders, elbows, axillae, and ears [135,136].

The first of the three classic signs is ST-segment elevation. It may be followed by T-wave inversion and pathologic Q-wave formation. This sequence of changes is called the electrocardiographic evolution of an infarction. Because these changes happen over a period of time, a series of 12-lead ECG tracings may be required for accurate diagnosis. In the very early stages of infarct, clear patterns may not be immediately revealed on ECG. As always, ECG findings should be correlated with clinical signs and symptoms. Over a period of months to days, ST-segment elevation and T-wave changes will resolve and no longer be present on 12-lead ECG recordings. Pathologic Q waves, on the other hand, frequently remain permanently. Presence of a pathologic Q wave on 12-lead ECG with no evidence of ST-segment elevation or T-wave changes usually indicates that the person has had an infarct in the past [1,34,47]. It is important to note that ST-segment and T-wave changes are not specific for ACS and may be the result of another disease or condition. Left ventricular aneurysm, pericarditis, myocarditis, Prinzmetal angina, Takotsubo cardiomyopathy, early repolarization, and Wolff-Parkinson-White syndrome may cause ST-segment elevation [3]. T-wave inversion can be caused by central nervous system events and treatment with tricyclic antidepressants or phenothiazines.

Cardiac biomarkers are detectable intracellular macromolecules released into the circulation after cardiomyocyte injury and death. The biomarkers once used—creatinine kinase (CK)-MB and myoglobin—have been replaced by cardiac-specific troponin (troponin I or T) because of the latter's high concentration in myocardium, near-absolute specificity for myocardial tissue, their absence in the blood of healthy individuals, and their high clinical sensitivity [2,3,22]. Measurement of CK-MB or myoglobin levels was not useful or cost-effective [157].

The inhibition of beta-1 adrenergic receptors by beta blockers acts to decrease cardiac work and myocardial oxygen demand. Beta blockers also slow the heart rate, which helps enhance coronary blood flow. A beta blocker should be given orally to all ACS patients (unless contraindicated) within 24 hours of presentation [3]. This use of beta blocker therapy has been associated with significantly lower in-hospital mortality [174]. Contraindications include signs of heart failure, low-output state, increased risk of cardiogenic shock, or other relative contraindications to beta blockade.

When administering ACE inhibitors, the following nursing actions should be taken [173]:

The ACC/AHA guideline recommends that aspirin be given as soon as possible after a patient arrives in the emergency department and continued indefinitely in patients who tolerate it [3]. However, adherence by emergency medical personnel to guidelines recommending prompt prehospital aspirin administration is only 45% [178]. Aspirin is contraindicated for patients who are allergic to the drug or who have active bleeding; clopidogrel is recommended for patients who cannot tolerate aspirin [3]. Aspirin should be nonenteric-coated and chewable, and the recommended dose is 162–325 mg. A maintenance dose of aspirin should be continued indefinitely, at a daily dose of 81–325 mg. Adherence to the recommended use of aspirin has been better than for other drug therapies for patients with UA/NSTEMI, with rates of 97% to 99% [10,140]. Rates of aspirin use have been reported to be lower for older individuals and women, especially women younger than 55 years of age [18,179].

The ACC/AHA guideline recommends enoxaparin as an option for all patients with NSTE-ACS [3]. The recommended dose is 1 mg/kg, given subcutaneously, every 12 hours, and the drug is continued throughout the hospitalization or until PCI is done [3]. The dose should be decreased to 1 mg/kg daily for patients with a creatinine clearance less than 30 mL/min.

The objective of an ischemia-guided strategy is to avoid unnecessary treatment (and associated costs) for patients at low risk for significant CHD. The ACC/AHA guideline notes that an ischemia-guided strategy may be considered for patients with NSTE-ACS who are initially stabilized and at elevated risk for clinical events (class IIbB) [3]. It is also reasonable to consider clinician and patient preference in decision making about an ischemia-guided strategy (class IIbC). Patients at low or intermediate risk who have had no ischemia at rest or with low-level activity for at least 12 to 24 hours should have noninvasive stress testing (class IB) [3].

The primary medical therapy for management of variant or vasospastic angina involves nitrates and calcium-channel blockers. Within minutes of administration, nitroglycerin has been found to effectively treat episodes of angina and myocardial ischemia caused by vasospasm. Long-acting nitrates can reduce the frequency of recurrent episodes of chest pain. Calcium-channel blockers, specifically nifedipine, amlodipine, verapamil, and diltiazem, are prescribed to prevent coronary vasospasm and the subsequent ischemia that can result. In this patient population, calcium-channel blockers are preferred over beta blockers [218,219].

Patients with cocaine-induced chest pain who show ECG and biomarker evidence of ischemia or infarct should be admitted for monitoring, observation, and further treatment as indicated. General medical therapies, similar to those used in management of non-cocaine related ACS, should be employed. In addition, the use of IV benzodiazepines as part of the early management of these patients may be indicated. In patients who use cocaine, benzodiazepines help to relieve chest pain and manage neuropsychiatric manifestations. Aspirin, calcium-channel blockers, and nitroglycerin are also recommended; beta blockers are not recommended with acute cocaine intoxication [3,48,220].

Reperfusion therapy is the cornerstone in the management of STEMI, and antiplatelet and anticoagulant agents are necessary as ancillary therapy. The options for reperfusion include revascularization procedures and/or pharmacologic (fibrinolytic) therapy. As with the treatment for NSTEMI, the use of PCI has become the primary approach to revascularization; approximately 80% to 90% of patients have PCI revascularization based on angiographic findings [224]. In addition, PCI is the preferred strategy for reperfusion because of its superior outcomes compared with fibrinolytic therapy [2,224]. However, gaining the optimal benefit from PCI depends on many factors, and timing is the most important variable in selecting a reperfusion therapy [2,221]. Care should also be taken to evaluate patients for contraindications to fibrinolytic therapy [5].

The 2013 ACCF/AHA guideline indicates that PCI is preferred over fibrinolytic therapy for patients with STEMI when it can be performed in a timely manner by experienced operators [2]. PCI should be done within less than 90 minutes after the patient's arrival at the emergency department (door-to-device time) [2]. If PCI cannot be done within 90 minutes, fibrinolytic therapy should be initiated as the reperfusion strategy within 120 minutes of the first medical contact.

Specific strategies that have improved the door-to-device time interval focus on three key components: door-to-ECG time, ECG-to-catheterization laboratory time, and laboratory arrival-to-device time. The ACCF/AHA provides the following steps as a general protocol in improving door-to-device times [2]:

Bleeding may occur from the arterial puncture site. Initial indications include frank bleeding from the puncture site and/or development of a hematoma in the area surrounding the site. A retroperitoneal bleed may also occur; an early sign is a complaint of severe flank pain. To reduce the likelihood of bleeding, the patient should be maintained on bed rest as specified by physician orders. The length of time bed rest is indicated depends on the method used to close the arterial puncture site. The arterial puncture site, often the femoral artery, should be monitored frequently for signs of bleeding or hematoma formation [34,233].

A significant drop in platelet count may be caused by an allergy or intolerance to infusing glycoprotein IIb/IIIa inhibitors. With a drop in platelet count, the patient's risk of bleeding increases. Patients receiving glycoprotein IIb/IIIa inhibitors should have a complete blood count checked at designated intervals to make sure that platelet counts are not dropping. Parameters should include orders to notify the physician if the platelet count drops below a specified level. If a patient develops a significant drop in platelet count, the infusion of the glycoprotein IIb/IIIa inhibitor is discontinued and the patient is placed on bleeding precautions and observed carefully for any signs of bleeding [34,233].

Although the focus of treatment for patients presenting with STEMI is often given to PCI, fibrinolytic therapy is the treatment of choice for some patients. If a patient arrives at or is transported by EMS to a non-PCI-capable facility, the decision whether to immediately transfer to a PCI-capable facility or administer fibrinolytic therapy must be made. Factors that affect this decision include the time from onset of symptoms, the risk of complications related to STEMI, the risk of bleeding with fibrinolysis, the presence of shock or severe heart failure, and the time required for transfer to a PCI-capable hospital. The ACCF/AHA guideline recommends that, in the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of first medical contact [2].

Immediately following reperfusion with fibrinolytics, the patient is at risk to develop serious bleeding episodes or to reocclude the infarct-related vessel [34,227]. Nursing assessment during this period is crucial and should include [34]:

The drug of choice to manage the pain associated with STEMI is intravenous morphine sulfate [2]. Morphine is indicated to relieve ongoing ischemic discomfort, control hypertension, ameliorate anxiety, or manage pulmonary edema. The initial dose should be 4–8 mg, with lower doses in the elderly. Additional doses of 2–8 mg may be given at intervals of 5 to 15 minutes [2].

The use of an oral ACE inhibitor is a strong recommendation for all patients recovering from STEMI, including those with anterior infarction, pulmonary congestion, or LVEF of less than 0.40, as well as those with normal LVEF in whom cardiovascular risk factors are well controlled [2]. Adherence to this recommendation has increased since the late 1990s but remains low [190,261,262,263]. In addition, the doses used in clinical practice have been lower than the target doses used in clinical trials [263].

Early treatment with dihydropyridine calcium antagonists (nifedipine and nicardipine) has not been found to improve rates of mortality or reinfarction [2]. Nifedipine is contraindicated in the treatment of STEMI. Although verapamil and diltiazem may be useful to relieve ongoing or recurrent ischemia, lower blood pressure, or control the ventricular response rate to atrial fibrillation when beta blockers are contraindicated (and the patient has well-preserved left ventricular function and no clinical evidence of congestive heart failure or pulmonary congestion), no specific recommendation for their use exists in the 2013 STEMI guideline [2,3]. Both drugs have been associated with significantly reduced mortality and major cardiovascular events [267,268]. Verapamil should not be used for patients with heart failure or bradyarrhythmias, and diltiazem should not be used for patients with left ventricular dysfunction [2].

Quitting smoking has been described as "probably the most important thing a smoker with acute MI can do to improve future health" [272]. Mortality after an ACS event for a patient who smokes cigarettes is twice that for a patient who does not, but cessation of smoking reduces reinfarction and death rates at one year [2]. Clinicians should use the in-hospital period after MI and each office visit as an opportunity to ask patients who were smokers if they have quit or are ready to quit and should offer counseling, pharmacologic support, and information on formal quit programs. The in-hospital period is unique because many patients are motivated to quit and are typically unable to smoke for three to nine days. Randomized controlled trials have shown that repeated contacts during the hospital stay and at and beyond three months (typically by telephone) are more likely to result in smoking cessation [2]. A Cochrane review showed that only intensive counseling programs work and that nicotine replacement further increases the rates of successful cessation among patients in intensive programs [273]. Another Cochrane review found high-quality evidence for a benefit of combined pharmacotherapy (with any type of nicotine-replacement therapy, bupropion, nortriptyline, or varenicline) and behavioral treatment compared with usual care, brief advice, or less intensive behavioral support [274]. However, many clinicians are reluctant to add another drug to the multitude of medications prescribed after MI.

Obesity is another well-documented risk factor for CHD, and weight management programs and information on healthy eating/caloric intake should be promoted as appropriate [271]. The patient's body mass index and waist circumference should be measured at each visit. The goal is to attain a body mass index of 18.5–24.9 and a waist circumference of no greater than 35 inches (women) or 40 inches (men) [271]. When weight reduction is needed, the initial goal is weight loss of 5% to 10% from baseline [271].

The recommended antiplatelet therapy after discharge is a combination of aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) [2,146,271]. The findings of studies have suggested that lower doses of aspirin (≤100 mg daily) are as effective as higher doses but have a better safety profile [180,245,248,276]. The recommended daily dose of aspirin is 75–100 mg for all patients, and the ACC/AHA guidelines for the management of STEMI and NSTE-ACS and duration of dual antiplatelet therapy state that it is reasonable to use an 81-mg dose [2,3,146,245,248]. However, despite the better safety profile of low-dose aspirin, data have indicated that 325 mg is the most common dose, prescribed for 55.7% of patients with UA/NSTEMI [277].

Questions about clopidogrel maintenance therapy remain, as the optimal dose and duration of therapy have not been identified [146,183,278,279]. Another concern is the effect of stopping clopidogrel. In a 2008 study of 3,137 patients with ACS (treated either medically or with PCI) who took clopidogrel for a mean of 9 to 10 months, there was a significantly high risk of adverse events in the initial 90 days after stopping treatment with clopidogrel [280]. The reason for this phenomenon is unclear, and the authors suggested that strategies to reduce the incidence of such early events should be identified [280]. Additionally, the response to clopidogrel varies among patients, and diminished responsiveness has been observed [146]. A 2010 retrospective study of 2,017 patients with ACS, conducted to confirm the findings of the 2008 study, found that the 0- to 90-day interval after stopping clopidogrel was associated with higher risk of death/MI compared with the 91- to 360-day interval. There was a similar trend of increased adverse events 0 to 90 days after stopping clopidogrel for various subgroups (i.e., women versus men, medical therapy versus PCI, stent type, and ≥6 months or <6 months of clopidogrel treatment) [281]. Warfarin is recommended as an antithrombotic for patients with UA/NSTEMI or STEMI who are allergic to aspirin [146,271].

The goal of statin therapy is to achieve an LDL level less than 100 mg/dL for patients with average risk, and an LDL level of less than 70 mg/dL is reasonable for high-risk patients [2]. If the triglyceride level is 200 mg/dL or higher, the non-HDL cholesterol should be less than 130 mg/dL in patients with average risk, whereas a non-HDL cholesterol level of less than 100 mg/dL is reasonable for very-high-risk patients. Statin therapy should be supplemented with dietary modification, weight management, and exercise. Patients should be encouraged to follow a diet with an increase of fresh fruits and vegetables, with less than 7% of total calories as saturated fat, less than 1% of total calories as trans fatty acids, and less than 200 mg per day of cholesterol [2,271].

In addition, blood pressure should be controlled according to the 2017 Guideline for High Blood Pressure in Adults, which recommends treatment when blood pressure is elevated, defined as 120–129/<80 mm Hg [67]. The guideline recommends initial treatment with nonpharmacologic interventions and lifestyle changes. Initiation of pharmacologic treatment is recommended for secondary prevention in patients with clinical cardiovascular disease and an average systolic blood pressure of 130 mm Hg or greater or an average diastolic blood pressure of 80 mm Hg or greater and for primary prevention in adults with an estimated 10-year atherosclerotic cardiovascular disease risk of 10% or higher and an average systolic blood pressure of 130 mm Hg or greater or an average diastolic blood pressure of 80 mm Hg or greater [67]. The AHA/ACCF recommends initial treatment with a beta blocker and/or an ACE inhibitor as secondary prevention for patients with CHD [271].

Lack of patient compliance with medications is also a serious problem and has been referred to as an unrecognized risk factor for CHD, because of its association with significant increases in adverse events and health costs [306,307]. Among individuals with CHD (many of whom had experienced a recent ACS event), compliance with guideline-recommended medications has ranged from 18% to 55%. Approximately 54% of individuals have been compliant with all of their initial medications, and compliance decreases over time [307,308,309]. One study showed that compliance was 60.3% at one year, 53.7% at two years, and 48.8% at five years [310]. Individuals who discontinue medications are more likely to be older, female, unmarried, and less educated [309]. Several other factors have been found to be associated with noncompliance with medications [307,308,309]: