Acute Coronary Syndrome - Ischemic Heart Disease

Acute coronary syndrome (ACS, formerly called ischemic heart disease) refers to a large spectrum of clinical conditions including unstable angina, myocardial injury, and myocardial infarction (MI). ACS is caused by a sudden onset of cardiac tissue ischemia secondary to impaired blood flow. The precipitating event is blockage in the coronary arteries or a mismatch between the demand and supply of blood to cardiac tissue. The resulting tissue ischemia can cause symptoms such as substernal chest pressure; radiation of pain to the left arm, shoulder, or jaw; and changes on an electrocardiogram (ECG). Patients who present with symptoms of ACS, including chest pain, should be immediately evaluated. The recommended evaluation includes a clinical assessment, electrocardiography, and laboratory testing. Laboratory testing for ACS includes diagnostic testing for markers of damage to heart tissue such as cardiac troponins (cTns) I and T (cTnI and cTnT), as well as prognostic testing (eg, B-type natriuretic peptide).

Quick Answers for Clinicians

Which laboratory tests should be performed when a patient presents with chest pain?

Patients presenting with chest pain should be tested for cardiac troponins (cTns) I and T (cTnI and cTnT). These markers are the mainstays of acute coronary syndrome (ACS) diagnosis and also have prognostic value. If possible, high-sensitivity troponin testing should be performed. Serum creatinine, B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide, and midregional pro-A-type natriuretic peptide tests may also provide prognostic value.

What is the difference between traditional C-reactive protein and high-sensitivity C-reactive protein?

C-reactive protein (CRP) is a marker for acute phase inflammation (eg, in relation to autoimmune disease or infection) and is not useful in the evaluation for acute coronary syndrome (ACS). High-sensitivity CRP (hsCRP) is sensitive enough to detect much lower levels of CRP, such as those present in patients with atherosclerosis. Thus, hsCRP can be used to stratify atherosclerotic cardiovascular disease risk in standard-risk individuals with borderline test results or individuals at intermediate or higher risk who have low-density lipoprotein (LDL) levels <130 mg/dL. See the Atherosclerotic Cardiovascular Disease Risk Markers topic for more information on ACS risk assessment.

What are the differences between the various types of troponin tests (I, T, conventional, and high sensitivity)?

Serial measurements of either cardiac troponin (cTn) I or T (cTnI or cTnT) can be used to evaluate patients for acute coronary syndrome (ACS). However, recent evidence suggests that while cTnI is specific to myocardial injury, the cTnT assay may also detect proteins released in response to skeletal muscle injury. Conventional cTn assays can detect myocardial injury 2-4 hours after symptom onset; therefore, measurements at presentation and at 3-6 hours after symptom onset are recommended. High-sensitivity cTn (hs-cTn) testing can detect elevated levels sooner after symptom onset, and measurements can be made more frequently to detect a rising/falling pattern. It is important to use the same test when performing serial measurements and to ensure the use of the appropriate upper reference limit for the particular test being used.

Which biomarkers are not currently recommended for use in acute coronary syndrome?

Midregional proadrenomedullin, growth differentiation factor 15, and copeptin are all being investigated for their prognostic value in acute coronary syndrome (ACS). However, they are not currently recommended for clinical use. Additionally, although creatine kinase-muscle and brain isoenzyme (CK-MB) and myoglobin were both previously recommended for ACS, they are no longer preferred tests unless troponin testing is unavailable.

Indications for Testing

Laboratory testing for ACS is used to:

Screen and assess risk for future ACS in adults
Diagnose ACS in patients who present with prolonged chest pain (which may radiate to the left arm, shoulder, or jaw) and other symptoms such as diaphoresis, dyspnea, nausea, abdominal pain, syncope, and suggestive ECG changes
Determine prognosis in patients diagnosed with or being evaluated for ACS

Laboratory Testing

Screening and Risk Assessment

Multiple organizations recommend laboratory testing, such as high-sensitivity C-reactive protein (hsCRP) screening, to guide risk assessment for and implementation of preventive measures against future ACS. See the Atherosclerotic Cardiovascular Disease Risk Markers topic for information on ACS screening and risk assessment.

Diagnosis

cTnI and cTnT are the preferred biomarkers for the evaluation of myocardial injury and MI; high-sensitivity cTn (hs-cTn) assays are recommended if available. cTn levels are generally elevated within 2-4 hours of symptom onset but may not become abnormal for up to 12 hours. cTn elevations may persist for >14 days. Although cTns are generally only released in response to cardiac injury, recent evidence suggests that cTnT may be detected in response to skeletal muscle injury.

In addition to ACS, elevations in cTn may arise from a number of conditions (including tachyarrhythmias, heart failure, hypertensive emergencies, critical illness, myocarditis, Tako-Tsubo cardiomyopathy, structural heart disease, aortic dissection, pulmonary embolism/pulmonary hypertension, and renal dysfunction with associated cardiac disease). Therefore, serial measurements that demonstrate a rise or fall in cTn levels are required to identify acute injury and thus ACS. Current guidelines recommend a first cTn test on presentation with chest pain, and a second test 3-6 hours later (or sooner if using hs-cTn). Patients who present very early or very late after symptom onset may require additional testing to detect an increase or decrease in cTn values.

Diagnostic Criteria for ACS
	Unstable Angina	Myocardial Injury	MI
cTns	Not elevated	Elevated cTn with at least 1 value above the 99th percentile upper reference limit: Acute if rise/fall in serial troponin values Chronic if values are consistently elevated	Acute myocardial injury plus clinical evidence of ischemia plus rise and/or fall of cTn values with at least 1 cTn value above the 99th percentile upper reference limit
Other findings	Chest pain without ST segment elevation on ECG	n/a	One of the following: Symptoms consistent with myocardial ischemia New ECG changes consistent with myocardial ischemia Pathologic Q waves Evidence of new loss of myocardium or new regional wall motion abnormality consistent with myocardial ischemia Coronary thrombus identified by angiography or autopsy
ACC, American College of Cardiology; AHA, American Heart Association; ESC, European Society of Cardiology; n/a, not applicable; WHF, World Heart Federation Sources: ESC/ACC/AHA/WHF, 2018; ESC, 2015

Prognosis

The presence and magnitude of cTn elevations at presentation are useful for prognosis of short- and long-term mortality in ACS. In addition to measurements at presentation, it may be reasonable to remeasure troponin on day 3 or 4 in patients with MI to assess infarct size and the dynamics of necrosis. Several additional biomarkers, including natriuretic peptides, have also been associated with mortality and comorbidities that confer added risk of mortality (such as heart failure) in ACS.