Which of the following types of angina is most closely related with an impending mi?

Practice Essentials

Unstable angina belongs to the spectrum of clinical presentations referred to collectively as acute coronary syndromes (ACSs), which also includes ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). [1, 2] Unstable angina is considered to be an ACS in which there is myocardial ischemia without detectable myocardial necrosis (ie, cardiac biomarkers of myocardial necrosis —such as creatine kinase MB isozyme, troponin, myoglobin—are not released into the circulation). See the image below.

Signs and symptoms

With unstable angina, symptoms may (1) occur at rest; (2) become more frequent, severe, or prolonged than the usual pattern of angina; (3) change from the usual pattern of angina; or (4) not respond to rest or nitroglycerin. [3] Symptoms of unstable angina are similar to those of myocardial infarction (MI) and include the following:

• Chest pain or pressure

• Pain or pressure in the back, neck, jaw, abdomen, shoulders or arms

• Sweating

• Dyspnea

• Nausea, vomiting

• Dizziness or sudden weakness

• Fatigue

The patient’s history and diagnostic testing are generally more sensitive and specific for unstable angina than the physical examination, which may be unremarkable. Examination in a patient with unstable angina may yield the following findings:

• Diaphoresis

• Tachycardia or bradycardia

• Transient myocardial dysfunction (eg, systolic blood pressure < 100 mm Hg or overt hypotension, elevated jugular venous pressure, dyskinetic apex, reverse splitting of S2, presence of S3 or S4, new or worsening apical systolic murmur, or rales or crackles)

• Peripheral arterial occlusive disease (eg, carotid bruit, supraclavicular or femoral bruits, or diminished peripheral pulses or blood pressure)

See Presentation for more detail.

Diagnosis

The following laboratory studies are recommended in the evaluation of a patient with unstable angina:

• 12 lead electrocardiogram

• Serial cardiac biomarker assays (eg, creatine kinase MB isoenzyme [CK-MB], troponin I or T)

• Complete blood count (CBC) with hemoglobin level

• Serum chemistry panel (including magnesium and potassium)

• Lipid panel

Other tests that may be used to assess patients include the following:

• Creatinine level

• Exercise testing when patients are stable

The following imaging studies may be used to assess patients with suspected unstable angina:

• Chest radiography

• Echocardiography

• Computed tomography angiography

• Magnetic resonance angiography

• Single-photon emission computed tomography

• Magnetic resonance imaging

• Myocardial perfusion imaging

See Workup for more detail.

Management

Management is directed toward (1) reducing myocardial oxygen demands; (2) improving myocardial oxygen supply; and (3) assessing the patient's risk of progression to MI or having a complication related to treatment.

Patients with unstable angina require admission to the hospital for bed rest with continuous telemetry monitoring. One should obtain intravenous (IV) access, and provide supplemental oxygen if evidence of desaturation is noted. The course of unstable angina is highly variable and potentially life-threatening; therefore, quickly determine whether the initial treatment approach should use an invasive (surgical management) or a conservative (medical management) strategy.

The following medications are used in the management of unstable angina:

• Antiplatelet agents (eg, aspirin, clopidogrel)

• Lipid-lowering statin agents (eg, simvastatin, atorvastatin, pitavastatin, and pravastatin)

• Cardiovascular antiplatelet agents (eg, tirofiban, eptifibatide, and abciximab)

• Beta blockers (eg, atenolol, metoprolol, esmolol, nadolol, and propranolol)

• Anticoagulants (eg, heparin or low-molecular-weight heparins [LMWHs] [eg, enoxaparin, dalteparin, and tinzaparin])

• Thrombin inhibitors (eg, bivalirudin, lepirudin, desirudin, and argatroban)

• Nitrates (eg, nitroglycerin IV)

• Calcium channel blockers (diltiazem, verapamil, or nifedipine)

• Angiotensin-converting enzyme inhibitors (ACEIs) (eg, captopril, lisinopril, enalapril, and ramipril)

Surgical intervention in unstable angina may include the following:

• Cardiac catheterization

• Revascularization

See Treatment and Medication for more detail.

Background

Chest pain is a nonspecific symptom that can have cardiac or noncardiac causes (see DDx). Unstable angina belongs to the spectrum of clinical presentations referred to collectively as acute coronary syndromes (ACSs), which range from ST-segment elevation myocardial infarction (STEMI) to non-STEMI (NSTEMI). [1, 2] Unstable angina is considered to be an ACS in which there is myocardial ischemia without detectable myocardial necrosis (ie, cardiac biomarkers of myocardial necrosis—such as creatine kinase MB isozyme, troponin, myoglobin—are not released into the circulation). The term angina is typically reserved for pain syndromes arising from presumed myocardial ischemia.

The traditional term unstable angina was meant to signify the intermediate state between myocardial infarction (MI) and the more chronic state of stable angina. The old term preinfarction angina conveys the clinical intent of intervening to attenuate the risk of MI or death. Patients with this condition have also been categorized by presentation, diagnostic test results, or course over time; these categories include new-onset angina, accelerating angina, rest angina, early postinfarct angina, and early postrevascularization angina.

Although the etiology and definition of unstable angina can be broad, interplay between disrupted atherosclerotic plaque and overlaid thrombi is present in many cases of unstable angina, with consequent hemodynamic deficit or microembolization. Thus, the condition is distinct from stable angina, in which the typical underlying cause is a fixed coronary stenosis with compromised blood flow and slow, progressive plaque growth that allows potential development of collateral vessels.

Other causes of angina, such as hypertrophic obstructive cardiomyopathy (HOCM) or microvascular disease (syndrome X), cause ischemia by means of different mechanisms and are considered separate entities.

Pathophysiology

Factors involved in the pathophysiology of unstable angina include the following:

• Supply-demand mismatch

• Plaque disruption or rupture

• Thrombosis

• Vasoconstriction

• Cyclical flow

Supply-demand mismatch

The myocardial ischemia of unstable angina, like all tissue ischemia, results from excessive demand or inadequate supply of oxygen, glucose, and free fatty acids.

Increased myocardial oxygen demand may be caused by the following:

• Fever

• Tachyarrhythmias (eg, atrial fibrillation or flutter)

• Malignant hypertension

• Thyrotoxicosis

• Pheochromocytoma

• Cocaine use

• Amphetamine use

• Aortic stenosis

• Supravalvular aortic stenosis

• Obstructive cardiomyopathy

• Aortovenous shunts

• High-output states

• Congestive heart failure (CHF)

Decreased oxygen supply may be caused by the following:

• Anemia

• Hypoxemia

• Polycythemia

• Hypotension

The above causes must be investigated because a number of them are reversible. For example, anemia from chronic gastrointestinal (GI) bleeding is not uncommon in elderly patients. This can coexist with coronary artery disease (CAD). However, patients may not benefit from or may be harmed by treatments such as anticoagulants and antiplatelet drugs. Avoidance or treatment of the underlying condition is paramount.

Excess demand from increased myocardial workload (the product of heart rate and systolic blood pressure) or wall stress is responsible for nearly all cases of stable angina and perhaps one third of all episodes of unstable angina.

Plaque disruption

Accumulation of lipid-laden macrophages and smooth muscle cells, so-called foam cells, occurs within atherosclerotic plaques. The oxidized low-density lipoprotein cholesterol (LDL-C) in foam cells is cytotoxic, procoagulant, and chemotactic. As the atherosclerotic plaque grows, production of macrophage proteases and neutrophil elastases within the plaque can cause thinning of the fibromuscular cap that covers the lipid core.

Increasing plaque instability, coupled with blood-flow shear and circumferential wall stress, leads to plaque fissuring or rupture (see the image below), especially at the junction of the cap and the vessel wall. (See Vulnerable Plaque Pathology.)

The degree and consequences of plaque disruption cover a wide spectrum. Minor fissuring is typically nonocclusive and hence clinically silent, and repeat occult episodes of plaque ulceration and healing with a gradual growth of plaque volume have been histologically documented. Moderate-to-large plaque disruptions commonly result in unstable angina or acute infarction.

As many as 50% of MIs are due to lesions that are angiographically considered functionally insignificant. [4] Angiographically mild lesions can still be dangerous because they have an unstable thin-cap fibroatheroma (TCFA). This means that focal treatments such as percutaneous coronary intervention (PCI) are incomplete and that medical therapy to protect the entire vascular tree is complementary and crucial, particularly in patients with a history of ACS.

Vasoconstriction and thrombosis

Most patients with ACS have recurrent transient reduction in coronary blood supply because of vasoconstriction and thrombus formation at the site of atherosclerotic plaque rupture. These events occur as consequences of episodic platelet aggregation and complex interactions among the vascular wall, leukocytes, platelets, and atherogenic lipoproteins.

Exposure of subendothelial components provokes platelet adhesion and activation. Platelets then aggregate in response to exposed vessel wall collagen or local aggregates (eg, thromboxane and adenosine diphosphate). Platelets also release substances that promote vasoconstriction and production of thrombin. In a reciprocating fashion, thrombin is a potent agonist for further platelet activation, and it stabilizes thrombi by converting fibrinogen to fibrin.

ACS may involve a clot in flux (ie, forming and enlarging, chipping off and embolizing). Over time, this dynamic clot formation or lysis, in conjunction with coronary vasoreactivity and resistance in the microvascular bed, causes intermittent and alternating (or cyclical) occlusion and flow.

The nonocclusive thrombus of unstable angina can become transiently or persistently occlusive. Depending on the duration of the occlusion, the presence of collateral vessels, and the area of myocardium perfused, recurrent unstable angina, non-Q-wave MI (NQMI), or Q-wave MI can result.

Genetics

Although the etiology of cardiovascular disease is strongly linked to modifiable environmental factors, it is known that genetics also play a significant part in the development of CAD and unstable angina. Much of the literature regarding the genetics of cardiovascular disease concerns MI and the development of CAD; however, there is a growing body of literature concerning unstable angina itself.

A number of genetic contributions are known to play a part in unstable angina. Genome-wide association studies (GWAS) have found linkage with unstable angina at chromosome 2q36-q37.3, chromosome 3q26-q27, and chromosome 20q11-13. [5] A polymorphism in glycoprotein Ia was associated with an increased time before platelet aggregation occurs in heterozygotes for the polymorphism in a Chinese population [6] ; it was postulated that the difference in platelet aggregation affected the pathogenesis of unstable angina.

Polymorphisms in several matrix metalloproteinase (MMP) genes have also been described. A guanine insertion in MMP1 is associated with smaller and more stable plaques, whereas the presence of more than 22 “CA” microsatellite repeats in MMP9 is associated with a worse prognosis for unstable angina. [7, 8]

Polymorphisms of interleukin (IL)-1 receptor antagonist (IL-1Ra) are suspected of having a role in the development of unstable angina. Studies conducted to date suggest that persons with allele-2 of IL-2Ra have increased inflammation, as measured by C-reactive protein (CRP) levels. There was an increased frequency of younger presentation in one study, [9] but a clear association between this polymorphism and an increased risk for unstable angina has not been found.

Apolipoprotein E (ApoE) polymorphisms also may play a pathogenetic role. In a study assessing the relation of ApoE4 to serum IL-10 levels, IL-10 levels were found to be lower in patients with at least 1 copy of ApoE4. [10] Higher IL-10 levels are believed to be cardioprotective, further suggesting that ApoE4 is associated with increased risk for unstable angina. [10] Ultimately, the genetics of unstable angina appear to be most closely linked with markers of inflammation and mediated by their effects on the risk of plaque rupture. [11]

Epidemiology

United States demographics

In the United States, the incidence of unstable angina is increasing, and each year, nearly 1 million hospitalized patients have a primary diagnosis of unstable angina. A similar number of unstable angina episodes likely occur outside the hospital and either go unrecognized or are managed in the outpatient setting. However, even with heightened public awareness, improved survival after MI, and an aging population, the incidence of unstable angina should continue to rise despite primary and secondary prevention measures.

Reasonably representative statistical estimates for unstable angina can be obtained from 2 registries, the GUARANTEE (Global Unstable Angina Registry and Treatment Evaluation) registry [12] and the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation) registry of the American College of Cardiology (ACC) and the American Heart Association (AHA). [13, 14] (See Table 1 below.)

Table 1. Patient Characteristics, GUARANTEE Versus CRUSADE Trials (Open Table in a new window)

GUARANTEE involved 3000 consecutive hospital admissions for unstable angina in 35 US hospitals in 6 geographic regions (Northeast, Mideast, Midwest, Southeast, Southwest, Northwest) from September 1995 to August 1996.

CRUSADE registered more than 180,000 US patients with NSTEMI from 2001 to 2006, targeting high-risk patients with unstable angina or NSTEMI according to the following inclusion criteria, either separately or in combination [13, 14] :

• Chest pain or anginal equivalent at rest, more than 10 minutes in duration

• Ischemic electrocardiographic (ECG) changes (ST-segment depression >0.5 mm, transient ST-segment elevation 0.5-1.0 mm lasting for < 10 minutes); or

• Elevated markers of myocardial necrosis (CK-MB or troponin I or T exceeding the upper limit of normal for the local laboratory assay used at each institution)

International demographics

The best international demographic data available are from the OASIS-2 (Organization to Assess Strategies for Ischemic Syndromes) registry (see Table 2 below). [15]

Table 2. Demographic Characteristics of Patients in International OASIS-2 Registry (Open Table in a new window)

Because unstable angina is intimately linked to the incidence of coronary events, an approximation of international trends might be found in the MONICA (Monitoring Trends and Determinants in Cardiovascular Diseases) registry sponsored by the World Health Organization (WHO). [16] This large project monitored more than 7 million people aged 35-64 years from 30 populations in 21 countries from the mid-1980s.

In the study, the highest average rates of heart disease were found in Glasgow and Belfast, United Kingdom; North Karelia and Kuopio, Finland; Newcastle, Australia; and Warsaw, Poland. [16] The lowest average MI rates, and presumably the lowest average unstable angina rates, were observed in Beijing, China; Toulouse, France; Catalonia, Spain; Vaud-Fribourg, Switzerland; and Brianza, Italy.

The GRACE (Global Registry of Acute Coronary Events) registry (http://www.outcomes-umassmed.org/grace/ ) is prospectively tracking contemporary ACS treatment and outcome across 30 countries and has accumulated more than 100,000 patients. [17]

In an international study comprising 8992 patients in two independent diagnostic trials enrolled at 11 centers to evaluate the relative incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction (NSTEMI), investigators found that the relative incidence and mortality of unstable angina is substantially lower than that of NSTEMI, but rate of future non-fatal MI is similar. [18]

Age-related demographics

The mean age of presentation with unstable angina is 62 years (range, 23-100 years). To put this in perspective, the mean age is 60 years for patients in clinical trials for MI, about 67 years for carotid artery stenosis, and 63 years for congestive heart failure. On average, women with unstable angina are 5 years older than men on presentation, with approximately half of women older than 65 years, as opposed to only about one third of men. Black individuals tend to present at a slightly younger age than people of other races do.

Sex-related demographics

Women with unstable angina are older and have a higher prevalence of hypertension, diabetes mellitus, CHF, and family history of CAD than men. Men tend to have a higher previous incidence of MI and revascularization, a higher proportion of positive cardiac enzymes on admission, and higher rates of catheterization and revascularization. However, outcome is related more to the severity of the illness than to sex.

Race-related demographics

Disparities in outcome and risk-factor prevalence among different ethnic groups have been widely reported. For instance, as a group, black persons exhibit a higher prevalence of atherosclerotic risk factors (eg, hypertension, diabetes mellitus, and smoking), greater left ventricular mass, and decreased peripheral vasodilatory response. Relative to white persons, MI more frequently results in death in black individuals at young ages.

Fewer myocardial events but more cerebral complications have also been observed in black patients with unstable angina in randomized clinical trials of heparin versus hirudin (the Global Utilization of Streptokinase and TPA [tissue plasminogen activator] for Occluded coronary arteries II [GUSTO II] trial) or eptifibatide versus placebo (the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy [PURSUIT] trial), possibly because of enhanced fibrinolytic activity and a higher prevalence of hypertension.

Racial differences also exist with regard to the delivery and response to medical care. White individuals have a higher rate of catheterization, angioplasty, and bypass surgery than individuals from other racial groups do.

Studies have shown equivalent short-term (30-day) mortality figures from unstable angina (including NQMI) for black individuals, but over the long term, persistent worse outcomes have been demonstrated.

Prognosis

The risk of MI, complications, and death in unstable angina varies because of the broad clinical spectrum that is covered by the term unstable angina. The aggressiveness of the therapeutic approach should be commensurate with the individualized estimated risk.

Patients who present with new ST-segment deviation (≥1 mm) have a 1-year death or MI rate of 11%, compared with a rate of only 6.8% in patients with isolated T-wave inversion. [19]

The current standard for cross-comparing studies is the 30-day event rate. The aggregate data for the more than 40,000 patients with ACSs (excluding STEMI), as derived from studies using contemporary treatments (albeit in varying degrees), indicate improving outcomes (see Table 3 below). The 30-day MI and death rates are currently around 8.5% and 3.5%, respectively, despite increased disease complexity and an aging cohort.

Table 3. Thirty-Day Clinical Outcome in Patients With Acute Coronary Syndromes in Clinical Trials (Open Table in a new window)

The RESCATE (Recursos Empleados en el Sindrome Coronario Agudo y Tiempos de Espera) investigators from Spain reported a 1.8% death rate and a 5.1% MI rate at 28 days (consecutive series, 1992-1994; early revascularization rate, ~6%) in 791 patients with unstable angina. [20] Compared with the rates in the North American studies listed earlier (see Epidemiology), these seem lower, probably because of the healthier case-mix; this illustrates the difficulties of direct outcome comparisons between institutions, countries, and trials.

A contemporary large clinical trial with centrally adjudicated outcomes showed that an ACS portends more adverse events in the year to come. [21] The following are the 12-month event rates for the ACS patients (final diagnosis of unstable angina, 16.6%; NSTEMI, 42.9%; STEMI, 37.5%), whose median age was 62 years, 25% of whom were diabetic, and fewer than 1% of whom were classified as above Killip class 2 [21] :

• Death from vascular causes - 4.3%

• Death from nonvascular causes - 0.6%

• MI - 5.9%

• Stroke - 1.2%

These findings present an opportunity for secondary prevention of such adverse events.

Prognostic indicators

Of note, studies have shown that the following are significant prognosticators for poor outcome in patients with unstable angina:

• Ongoing CHF

• Presence or history of poor left ventricular ejection fraction (LVEF)

• Hemodynamic instability

• Recurrent angina despite intensive anti-ischemic therapy

• New or worsening mitral regurgitation

• Sustained ventricular tachycardia

Although these factors were not evaluated in the Thrombolysis in Myocardial Infarction (TIMI) Risk Score model (see Physical Examination), they should be taken into consideration when the level of care is decided.

Other predictors of worse long-term outcome in unstable angina include underlying left ventricular systolic dysfunction and more widespread extent of CAD.

The level of troponin positivity correlates with intermediate-term death in a dose-dependent fashion (range, 1.0-7.5% at 6 weeks) independent of age, creatine kinase MB isoenzyme (CK-MB) levels, and ST-segment deviation.

More recent studies indicate that epicardial adipose tissue thickness (EAT) can also be used to predict major adverse cardiac events. [22] In a study of 200 patients hospitalized with stable angina pectoris, unstable angina pectoris, or acute myocardial infarction who underwent coronary angiography, patients with a baseline EAT of more than 7 mm suffered significantly more revascularizations, nonfatal myocardial infarction, and cardiovascular death. [22]

Patient Education

Before hospital discharge, patients with unstable angina and their family members should be educated about the manifestations of MI and the actions that must be taken in that eventuality. They should also receive training in cardiopulmonary resuscitation (CPR).

For patient information, see Cholesterol Center and Heart Health Center, as well as Cholesterol FAQs, Heart Disease FAQs, Angina Pectoris, Chest Pain, High Cholesterol, Cholesterol Charts (What the Numbers Mean), Lifestyle Cholesterol Management, Cholesterol-Lowering Medications, and Heart Attack.

1. Basra SS, Virani SS, Paniagua D, Kar B, Jneid H. Acute coronary syndromes: unstable angina and non-ST elevation myocardial infarction. Heart Fail Clin. 2016 Jan. 12 (1):31-48. [QxMD MEDLINE Link].

2. Hedayati T, Yadav N, Khanagavi J. Non-ST-segment acute coronary syndromes. Cardiol Clin. 2018 Feb. 36 (1):37-52. [QxMD MEDLINE Link].

3. What are the symptoms of heart attack and unstable angina?. eMedicineHealth. May 8, 2013. Available at http://www.emedicinehealth.com/heart_attack_and_unstable_angina-health/page5_em.htm#Symptoms.. Accessed: May 9, 2013.

4. Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011 Jan 20. 364(3):226-35. [QxMD MEDLINE Link].

5. Harrap SB, Zammit KS, Wong ZY, et al. Genome-wide linkage analysis of the acute coronary syndrome suggests a locus on chromosome 2. Arterioscler Thromb Vasc Biol. 2002 May 1. 22(5):874-8. [QxMD MEDLINE Link].

6. Zhao YH, Xu Y, Gu YY, Li Y, Zhang JY, Su X. Functional effect of platelet membrane glycoprotein ia gene polymorphism in the pathogenesis of unstable angina pectoris. J Int Med Res. 2011. 39(2):541-8. [QxMD MEDLINE Link].

7. Fiotti N, Moretti ME, Bussani R, et al. Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms. Atherosclerosis. 2011 Mar. 215(1):153-9. [QxMD MEDLINE Link].

8. White AJ, Duffy SJ, Walton AS, et al. Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease. Cardiovasc Res. 2007 Sep 1. 75(4):813-20. [QxMD MEDLINE Link].

9. Manzoli A, Andreotti F, Varlotta C, et al. Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. Cardiologia. 1999 Sep. 44(9):825-30. [QxMD MEDLINE Link].

10. Tziakas DN, Chalikias GK, Antonoglou CO, et al. Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease. J Am Coll Cardiol. 2006 Dec 19. 48(12):2471-81. [QxMD MEDLINE Link].

11. Willerson JT. Systemic and local inflammation in patients with unstable atherosclerotic plaques. Prog Cardiovasc Dis. 2002 May-Jun. 44(6):469-78. [QxMD MEDLINE Link].

12. Scirica BM, Moliterno DJ, Every NR, et al. Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators. Am J Cardiol. 1999 Nov 15. 84(10):1145-50. [QxMD MEDLINE Link].

13. Skolnick AH, Alexander KP, Chen AY, et al. Characteristics, management, and outcomes of 5,557 patients age > or =90 years with acute coronary syndromes: results from the CRUSADE Initiative. J Am Coll Cardiol. 2007 May 1. 49(17):1790-7. [QxMD MEDLINE Link].

14. Hoekstra JW, Pollack CV Jr, Roe MT, et al. Improving the care of patients with non-ST-elevation acute coronary syndromes in the emergency department: the CRUSADE initiative. Acad Emerg Med. 2002 Nov. 9(11):1146-55. [QxMD MEDLINE Link].

15. Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Lancet. 1999 Feb 6. 353(9151):429-38. [QxMD MEDLINE Link].

16. Luepker RV. WHO MONICA project: what have we learned and where to go from here?. Public Health Rev. 2012. Accessed: May 8, 2013. 33(2):373-96. [Full Text].

17. GRACE, Global Registry of Acute Coronary Events. Available at http://www.outcomes-umassmed.org/grace/. Accessed: September 16, 2010.

18. Puelacher C, Gugala M, Adamson PD, et al. Incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction. Heart. 2019 Apr 24. [QxMD MEDLINE Link].

19. Cannon CP, McCabe CH, Stone PH, et al. The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia. J Am Coll Cardiol. 1997 Jul. 30(1):133-40. [QxMD MEDLINE Link].

20. Lupon J, Valle V, Marrugat J, et al. Six-month outcome in unstable angina patients without previous myocardial infarction according to the use of tertiary cardiologic resources. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempos de Espera. J Am Coll Cardiol. 1999 Dec. 34(7):1947-53. [QxMD MEDLINE Link].

21. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10. 361(11):1045-57. [QxMD MEDLINE Link].

22. Tanindi A, Erkan AF, Ekici B. Epicardial adipose tissue thickness can be used to predict major adverse cardiac events. Coron Artery Dis. 2015 Dec. 26 (8):686-91. [QxMD MEDLINE Link].

23. Karcz A, Holbrook J, Burke MC, et al. Massachusetts emergency medicine closed malpractice claims: 1988-1990. Ann Emerg Med. 1993 Mar. 22(3):553-9. [QxMD MEDLINE Link].

24. Li Z, Liu X, Wang J, et al. Analysis of urinary metabolomic profiling for unstable angina pectoris disease based on nuclear magnetic resonance spectroscopy. Mol Biosyst. 2015 Dec 10. 11 (12):3387-96. [QxMD MEDLINE Link].

25. Gurses KM, Kocyigit D, Yalcin MU, et al. Enhanced platelet toll-like receptor 2 and 4 expression in acute coronary syndrome and stable angina pectoris. Am J Cardiol. 2015 Dec 1. 116 (11):1666-71. [QxMD MEDLINE Link].

26. Meune C, Balmelli C, Twerenbold R, et al. Patients with acute coronary syndrome and normal high-sensitivity troponin. Am J Med. 2011 Dec. 124(12):1151-7. [QxMD MEDLINE Link].

27. Susilovic Grabovac Z, Bakovic D, Lozo M, Pintaric I, Dujic Z. Early changes in platelet size and number in patients with acute coronary syndrome. Int J Angiol. 2017 Dec. 26 (4):249-52. [QxMD MEDLINE Link].

28. Misra D, Leibowitz K, Gowda RM, Shapiro M, Khan IA. Role of N-acetylcysteine in prevention of contrast-induced nephropathy after cardiovascular procedures: a meta-analysis. Clin Cardiol. 2004 Nov. 27(11):607-10. [QxMD MEDLINE Link].

29. Calmarza P, Lapresta C, Martínez M, Lahoz R, Povar J. Utility of myeloperoxidase in the differential diagnosis of acute coronary syndrome. Arch Cardiol Mex. 2017 Dec 7. [QxMD MEDLINE Link].

30. Than M, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011 Mar 26. 377(9771):1077-84. [QxMD MEDLINE Link].

31. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct. 33(20):2551-67. [QxMD MEDLINE Link]. [Full Text].

32. Januzzi JL, Cannon CP, DiBattiste PM, Murphy S, Weintraub W, Braunwald E. Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (The TACTICS-TIMI 18 Trial). Am J Cardiol. 2002 Dec 1. 90(11):1246-9. [QxMD MEDLINE Link].

33. Acara AC, Bolatkale M. Endothelial nitric oxide level as a predictor of coronary complexity in patients with unstable angina pectoris. Am J Med Sci. 2019 Feb 13. [QxMD MEDLINE Link].

34. [Guideline] Acute coronary syndrome and myocardial infarction. EBM Guidelines. Evidence-Based Medicine [internet]. Helsinki, Finland: Wiley Interscience. John Wiley & Sons; 2011. [Full Text].

35. de Zwaan C, Bar FW, Wellens HJ. Characteristic electrocardiographic pattern indicating a critical stenosis high in left anterior descending coronary artery in patients admitted because of impending myocardial infarction. Am Heart J. Apr 1982. ;103(4 Pt 2):730-6. [QxMD MEDLINE Link].

36. Nisbet BC, Zlupko G. Repeat Wellens' syndrome: case report of critical proximal left anterior descending artery restenosis. J Emerg Med. 2010 Sep. 39(3):305-8. [QxMD MEDLINE Link].

37. Kwong RY, Chan AK, Brown KA, et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation. 2006 Jun 13. 113(23):2733-43. [QxMD MEDLINE Link].

38. Kwong RY, Sattar H, Wu H, et al. Incidence and prognostic implication of unrecognized myocardial scar characterized by cardiac magnetic resonance in diabetic patients without clinical evidence of myocardial infarction. Circulation. 2008 Sep 2. 118(10):1011-20. [QxMD MEDLINE Link]. [Full Text].

39. Stratmann HG, Younis LT, Wittry MD, Amato M, Miller DD. Exercise technetium-99m myocardial tomography for the risk stratification of men with medically treated unstable angina pectoris. Am J Cardiol. 1995 Aug 1. 76(4):236-40. [QxMD MEDLINE Link].

40. Udelson JE, Spiegler EJ. Emergency department perfusion imaging for suspected coronary artery disease: the ERASE Chest Pain Trial. Md Med. 2001 Spring. Suppl:90-4. [QxMD MEDLINE Link].

41. Tegn N, Abdelnoor M, Aaberge L, et al, for the After Eighty study investigators. Health-related quality of life in older patients with acute coronary syndrome randomised to an invasive or conservative strategy. The After Eighty randomised controlled trial. Age Ageing. 2018 Jan 1. 47 (1):42-7. [QxMD MEDLINE Link].

42. [Guideline] Amsterdam EA, Wenger NK, Brindis RG, et all, for the ACC/AHA Task Force Members. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 23. 130(25):e344-426. [QxMD MEDLINE Link]. [Full Text].

43. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16. 345(7):494-502. [QxMD MEDLINE Link].

44. Beavers CJ, Naqvi IA. Clopidogrel. 2017 Jun. [QxMD MEDLINE Link]. [Full Text].

45. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003 Oct 7. 108(14):1682-7. [QxMD MEDLINE Link].

46. Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 Nov 20. 288(19):2411-20. [QxMD MEDLINE Link].

47. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22. 360(4):354-62. [QxMD MEDLINE Link].

48. Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010 Oct 28. 363(18):1704-14. [QxMD MEDLINE Link].

49. Park KW, Kim HS. Options to overcome clopidogrel response variability. Circ J. 2012. 76(2):287-92. [QxMD MEDLINE Link].

50. O'Connor FF, Shields DC, Fitzgerald A, Cannon CP, Braunwald E, Fitzgerald DJ. Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood. 2001 Dec 1. 98(12):3256-60. [QxMD MEDLINE Link].

51. De Servi S, Goedicke J, Schirmer A, Widimsky P. Clinical outcomes for prasugrel versus clopidogrel in patients with unstable angina or non-ST-elevation myocardial infarction: an analysis from the TRITON-TIMI 38 trial. Eur Heart J Acute Cardiovasc Care. 2014 Dec. 3(4):363-72. [QxMD MEDLINE Link].

52. Rudolph TK, Fuchs A, Klinke A, et al. Prasugrel as opposed to clopidogrel improves endothelial nitric oxide bioavailability and reduces platelet-leukocyte interaction in patients with unstable angina pectoris: A randomized controlled trial. Int J Cardiol. 2017 Dec 1. 248:7-13. [QxMD MEDLINE Link].

53. Effron MB, Nair KV, Molife C, et al. One-year clinical effectiveness comparison of prasugrel with ticagrelor: results from a retrospective observational study using an integrated claims database. Am J Cardiovasc Drugs. 2017 Dec 8. [QxMD MEDLINE Link].

54. US FDA approves expanded indication for BRILINTA to include long-term use in patients with a history of heart attack [press release]. AstraZeneca. September 3, 2015. Available at http://www.astrazeneca.com/Media/Press-releases/Article/20150903. Accessed: September 9, 2015.

55. Bonaca MP, Bhatt DL, Cohen M, et al, for the PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7. 372 (19):1791-800. [QxMD MEDLINE Link].

56. Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet. 2001 Jun 16. 357(9272):1915-24. [QxMD MEDLINE Link].

57. Ibbotson T, McGavin JK, Goa KL. Abciximab: an updated review of its therapeutic use in patients with ischaemic heart disease undergoing percutaneous coronary revascularisation. Drugs. 2003. 63(11):1121-63. [QxMD MEDLINE Link].

58. Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001 Dec 4. 104(23):2767-71. [QxMD MEDLINE Link].

59. Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Magee K. Heparin versus placebo for non-ST elevation acute coronary syndromes. Cochrane Database Syst Rev. 2014 Jun 27. 6:CD003462. [QxMD MEDLINE Link].

60. Cohen M, Demers C, Gurfinkel EP, et al. Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and safety of subcutaneous enoxaparin versus intravenous unfractionated heparin, in non-Q-wave coronary events. Am J Cardiol. 1998 Sep 10. 82(5B):19L-24L. [QxMD MEDLINE Link].

61. Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA. 2004 Jul 7. 292(1):45-54. [QxMD MEDLINE Link].

62. Mehta SR, Granger CB, Eikelboom JW, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol. 2007 Oct 30. 50(18):1742-51. [QxMD MEDLINE Link].

63. Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992 Jul 16. 327(3):141-5. [QxMD MEDLINE Link].

64. Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients' data. Lancet. 2002 Jan 26. 359(9303):294-302. [QxMD MEDLINE Link].

65. Metz BK, White HD, Granger CB, et al. Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators. J Am Coll Cardiol. 1998 Jun. 31(7):1493-8. [QxMD MEDLINE Link].

66. Maroo A, Lincoff AM. Bivalirudin in PCI: an overview of the REPLACE-2 trial. Semin Thromb Hemost. 2004 Jun. 30(3):329-36. [QxMD MEDLINE Link].

67. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006 Nov 23. 355(21):2203-16. [QxMD MEDLINE Link].

68. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4. 285(13):1711-8. [QxMD MEDLINE Link].

69. Murphy SA, Cannon CP, Wiviott SD, McCabe CH, Braunwald E. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009 Dec 15. 54(25):2358-62. [QxMD MEDLINE Link].

70. US FDA. Safety: statin drugs - drug safety communication: class labeling change. US Food and Drug Administration. February 28, 2012. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm293670.htm. Accessed: June 5, 2013.

71. US FDA. Safety: Zocor (simvastatin): label change - new restrictions, contraindications, and dose limitations. US Food and Drug Administration. June 8, 2011. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258384.htm. Accessed: June 5, 2013.

72. US FDA. Safety: Meridia (sibutramine): market withdrawal due to risk of serious cardiovascular events. US Food and Drug Administration. October 8, 2010. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm. Accessed: June 5, 2013.

73. Soukoulis V, Boden WE, Smith SC Jr, O'Gara PT. Nonantithrombotic medical options in acute coronary syndromes: old agents and new lines on the horizon. Circ Res. 2014 Jun 6. 114(12):1944-58. [QxMD MEDLINE Link]. [Full Text].

74. Anderson HV, Cannon CP, Stone PH, et al. One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol. 1995 Dec. 26(7):1643-50. [QxMD MEDLINE Link].

75. Boden WE, O'Rourke RA, Crawford MH, et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. N Engl J Med. 1998 Jun 18. 338(25):1785-92. [QxMD MEDLINE Link].

76. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet. 1999 Aug 28. 354(9180):708-15. [QxMD MEDLINE Link].

77. Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet. 2002 Sep 7. 360(9335):743-51. [QxMD MEDLINE Link].

78. Damman P, Hirsch A, Windhausen F, Tijssen JG, de Winter RJ. 5-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial a randomized comparison of an early invasive versus selective invasive management in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol. 2010 Mar 2. 55(9):858-64. [QxMD MEDLINE Link].

79. Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA. 2003 Sep 24. 290(12):1593-9. [QxMD MEDLINE Link].

80. Wallentin L, Lagerqvist B, Husted S, Kontny F, Stale E, Swahn E. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease. Lancet. 2000 Jul 1. 356(9223):9-16. [QxMD MEDLINE Link].

81. Sabatine MS, Giugliano RP, Keech AC, et al, for the FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4. 376 (18):1713-22. [QxMD MEDLINE Link]. [Full Text].

82. Szarek M, White HD, Schwartz GG, et al, for the ODYSSEY OUTCOMES Committees and Investigators. Alirocumab reduces total nonfatal cardiovascular and fatal events: The ODYSSEY OUTCOMES Trial. J Am Coll Cardiol. 2019 Feb 5. 73 (4):387-96. [QxMD MEDLINE Link]. [Full Text].

83. [Guideline] American Diabetes Association. Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. Clin Diabetes. 2016 Jan. 34 (1):3-21. [QxMD MEDLINE Link]. [Full Text].

84. [Guideline] Collet JP, Thiele H, Barbato E, et al, for the ESC Scientific Document Group . 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020 Aug 29. ehaa575. [QxMD MEDLINE Link]. [Full Text].

85. Zoler ML. ESC’s revised NSTE-ACS guidelines embrace hsT, personalized anti-ischemia treatments. Medscape Medical News. September 1, 2020. Available at https://www.medscape.com/viewarticle/936676. Accessed: September 28, 2020.

86. [Guideline] Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14. 37 (3):267-315. [QxMD MEDLINE Link]. [Full Text].

87. [Guideline] Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Isc... Circulation. 2016 Mar 29. [QxMD MEDLINE Link]. [Full Text].

88. Amgen Inc. FDA approves Amgen's Repatha (evolocumab) to prevent heart attack and stroke. Available at https://www.amgen.com/media/news-releases/2017/12/fda-approves-amgens-repatha-evolocumab-to-prevent-heart-attack-and-stroke/. December 1, 2017; Accessed: December 5, 2017.

89. Sanofi-Aventis. FDA approves Praluent (alirocumab) to prevent heart attack, stroke and unstable angina requiring hospitalization [press release]. Available at http://www.news.sanofi.us/2019-04-26-FDA-approves-Praluent-R-alirocumab-to-prevent-heart-attack-stroke-and-unstable-angina-requiring-hospitalization. April 26, 2019; Accessed: April 30, 2019.

90. Busko M. New non-ST-elevation ACS guidelines: new title, new approach. Medscape Medical News from WebMD. September 29, 2014. Available at http://www.medscape.com/viewarticle/832513. Accessed: October 4, 2014.

91. Eggers KM, Jernberg T, Lindahl B. Unstable angina in the era of cardiac troponin assays with improved sensitivity-a clinical dilemma. Am J Med. 2017 Dec. 130 (12):1423-30.e5. [QxMD MEDLINE Link].

92. Nowak R, Mueller C, Giannitsis E, et al. High sensitivity cardiac troponin T in patients not having an acute coronary syndrome: results from the TRAPID-AMI study. Biomarkers. 2017 Dec. 22 (8):709-14. [QxMD MEDLINE Link].

93. Rottger E, de Vries-Spithoven S, Reitsma JB, et al. Safety of a 1-hour rule-out high-sensitive troponin T protocol in patients with chest pain at the emergency department. Crit Pathw Cardiol. 2017 Dec. 16 (4):129-34. [QxMD MEDLINE Link].

94. Driscoll A, Barnes EH, Blankenberg S, et al. Predictors of incident heart failure in patients after an acute coronary syndrome: The LIPID heart failure risk-prediction model. Int J Cardiol. 2017 Dec 1. 248:361-8. [QxMD MEDLINE Link].

Author

Walter Tan, MD, MS Associate Professor of Medicine, Wake Forest University School of Medicine; Director of Cardiac Cath Labs, Wake Forest Baptist Medical Center

Walter Tan, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American College of Cardiology, American Heart Association, American Stroke Association, National Stroke Association, Society for Vascular Medicine, Society of Interventional Radiology

Disclosure: Nothing to disclose.

Coauthor(s)

David J Moliterno, MD Professor of Medicine, Jefferson Morris Gill Professor of Cardiology, Chief, Division of Cardiovascular Medicine, University of Kentucky; Vice Chairman of Internal Medicine, Chandler Medical Center; Medical Director, Gill Heart Institute

David J Moliterno, MD is a member of the following medical societies: American College of Cardiology, European Society of Cardiology, Association of Professors of Cardiology, American College of Physicians, American Heart Association, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Richard A Lange, MD, MBA President, Texas Tech University Health Sciences Center, Dean, Paul L Foster School of Medicine

Richard A Lange, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, Association of Subspecialty Professors

Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD Associate Professor of Medicine, Director of Cardiac Catherization Laboratory and Interventional Cardiology, Mayo Clinic ArizonA

Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Acknowledgements

Steven James Filby, MD Fellow in Interventional Cardiology, The Cleveland Clinic Foundation

Disclosure: Nothing to disclose.

Justin D Pearlman, MD, ME, PhD, FACC, MA Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Director of Cardiology Quality Program KMC, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School

Justin D Pearlman, MD, ME, PhD, FACC, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Which type of angina is most closely associated with an impending myocardial infarction MI )?

Which of the following is the most common symptom of myocardial infarction MI?

Is unstable angina the same as MI?

How are angina and MI related?