Creatine kinase (CK) is present in heart muscle, skeletal muscle, and brain tissue. Its isoenzymes, CK-MB, is found specifically in the heart muscle. Elevated levels of CK-MB reliably indicate acute MI. Generally,
CK-MB levels rise 4 to 8 hours after the onset of an acute MI, peak after 20 hours, and may remain elevated for up to 72 hours. (See Cardiac enzyme and protein patterns.) Normal CK levels are 55 to 170 units/L for men and 30 to 135 units/L for women. CK-MB levels are normally less than 5% for men and women.

Myoglobin, which is normally found in skeletal and cardiac muscle, functions as an oxygen-bonding muscle protein. It’s released into the bloodstream when ischemia, trauma, and inflammation of the muscle occur. Normal myoglobin values are 0 to 0.09 mcg/ml.

Rising myoglobin levels are one of the first markers of cardiac injury after an acute MI. Levels may rise within 2 hours, peak within 4 hours, and return to baseline by 24 hours. However, because skeletal muscle damage may also cause myoglobin levels to rise, other tests (such as CK-MB or troponin) may be required to determine myocardial injury.

Troponin is a protein found in skeletal and cardiac muscles. Two isotypes of troponin, troponin I and troponin T, are found in the myocardium. When injury occurs to the myocardial tissue, these proteins are released into the bloodstream. Troponin T can also be found in
skeletal muscle. Troponin I, however, is found only in the myocardium. In fact, it’s more specific to myocardial damage than CK, CK-MB isoenzymes, and myoglobin. Because troponin T levels can occur in certain muscle disorders or renal failure, they’re less specific for myocardial injury than troponin I levels.

Normal troponin I levels are less than 0.35 mcg/L and normal troponin T levels are less than 0.1 mcg/L. Troponin I levels greater than 2 mcg/L suggest cardiac injury.

Troponin levels rise within 3 to 6 hours after myocardial damage. Troponin I peaks in 14 to 20 hours, with a return to baseline in 5 to 7 days, and troponin T peaks in 12 to 24 hours, with a return to baseline in 10 to 15 days. Because troponin levels stay elevated for a prolonged time, they can detect an infarction that occurred several days earlier. Troponin T levels can be determined at the bedside in minutes, making them a useful tool for determining treatment in acute MI.

The ischemia modified albumin (IMA) test measures the changes in human serum albumin when it comes in contact with ischemic tissue. When ischemia occurs, IMA will rise rapidly. In over 80% of patients with acute coronary syndrome, IMA has been found to be elevated. However, IMA doesn’t rise in tissue necrosis.

Normally, there’s no IMA found in the blood. Increases in IMA are seen within 15 minutes of the onset of ischemia. This is significantly earlier than any other cardiac marker. When the ischemic event is resolved, IMA levels return to normal within several hours. The IMA test is used in conjunction with other cardiac markers, such as troponin, and an electrocardiogram (ECG). If the IMA test is negative and the troponin and ECG are negative, cardiac involvement is ruled out.

Homocysteine is an amino acid that’s produced by the body. High homocysteine levels can irritate blood vessels, leading to arteriosclerosis. High levels can also raise low-density lipoprotein levels and make blood clot more easily, increasing the risk of blood vessel blockages. In patients with type 2 diabetes, high homocysteine levels are seen when the patient has a decrease in renal function. Normal homocysteine levels are 4 to 17 μmol/L.

C-reactive protein (CRP) is a substance produced by the liver. A high CRP level indicates that inflammation exists at some location in the body. Other diagnostic tests are needed to determine the location of the inflammation and its cause. Elevated CRP levels can indicate such conditions as:

CRP appears in the blood 18 to 24 hours after the onset of tissue damage, and then declines rapidly when the inflammatory process regresses. Some studies have shown a correlation between increased CRP levels and coronary artery disease. Normally, CRP isn’t present in
the blood; however, levels less than 0.8 mg/dl may be reported as normal.

B-type natriuretic peptide (BNP) is a hormone polypeptide secreted by ventricular tissues in the heart. The substance is secreted as a response to the increased ventricular volume and pressure that occurs when a patient is in heart failure. It’s an excellent hormonal marker of ventricular systolic and diastolic dysfunction.

The normal BNP level in the blood is less than 100 pg/ml. Blood concentrations greater than 100 pg/ml are an accurate predictor of heart failure. The level of BNP in the blood is relative to the severity of heart failure. The higher the level, the worse the symptoms of heart failure. (See Linking BNP levels to heart failure symptom severity.)

Atrial natriuretic peptide (ANP) is a neurohormone similar to BNP that’s released by the atria in response to increased atrial pressure. ANP helps:

Normal levels of ANP are 20 to 77 pg/ml. A patient with overt heart failure will have highly elevated levels of ANP. A patient with cardiovascular disease and elevated cardiac filling pressure but no heart failure will also have increased ANP levels.

Triglycerides are the main storage form of lipids and constitute about 95% of fatty tissue. Monitoring triglyceride levels in the blood helps with early identification of hyperlipidemia and identification of patients at risk for coronary artery disease (CAD).

Triglyceride values are age- and gender-related, and some controversy exists over the most appropriate normal ranges. The most widely accepted normal values are 44 to 180 mg/dl for men and 10 to 190 mg/dl for women.

Triglyceride levels above or below these values suggest a clinical abnormality; for a definitive diagnosis, you’ll need additional tests. For example, measuring cholesterol levels may also be necessary, because cholesterol and triglyceride levels vary independently. If both triglyceride and cholesterol levels are high, the patient is at risk for CAD.

The total serum cholesterol test measures the circulating levels of the two forms in which cholesterol appears in the body—free cholesterol and cholesterol esters.

For adults, desirable cholesterol levels are less than 200 mg/dl. Levels are considered borderline high up to 240 mg/dl, and high if
they’re greater than 240 mg/dl. High serum cholesterol levels may be associated with an increased risk for CAD.

Lipoprotein fractionation tests are used to isolate and measure the two types of cholesterol in blood: high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs).

The HDL level is inversely related to the risk of CAD—that is, the higher the HDL level, the lower the incidence of CAD. For men, HDL values range from 37 to 70 mg/dl; in women, from 40 to 85 mg/dl.

Conversely, the higher the LDL level, the higher the incidence of CAD. In individuals who don’t have CAD, desirable LDL levels are less than 130 mg/dl, borderline high levels are in the range of 130 to 159 mg/dl, and high levels are more than 160 mg/dl.

The American College of Cardiology recommends:

Increased HDL levels can occur as a result of long-term aerobic and vigorous exercise. Rarely, a sharp rise (to as high as 100 mg/dl) in a second type of HDL (alpha₂-HDL) may signal CAD. (See Predicting CAD with the PLAC test, page 94.)

The partial thromboplastin time (PTT) test evaluates all of the clotting factors of the intrinsic pathway except platelets. The test measures the
time it takes a clot to form after adding calcium and phospholipid emulsion to a plasma sample. Normally a clot forms 21 to 35 seconds after the reagents are added.

The PTT test also helps monitor a patient’s response to heparin therapy. For a patient on anticoagulant therapy, check with the practitioner to find out what PTT results to expect.

Prothrombin, or factor II, is a plasma protein produced by the liver. The prothrombin time (PT) test (also known as pro time) measures the time required for a clot to form in a citrated plasma sample after the addition of calcium ions and tissue thromboplastin (factor III).

The PT test is an excellent screening procedure for overall evaluation of extrinsic coagulation factors V, VII, and X and of prothrombin and fibrinogen. It’s also the test of choice for monitoring oral anticoagulant therapy.

Normally PT ranges from 10 to 14 seconds. In a patient receiving warfarin therapy, the goal of treatment is to attain a PT level 1 to 2.5 times the normal control value.

The international normalized ratio (INR) system is viewed as the best means of standardizing measurement of prothrombin time to monitor
oral anticoagulant therapy. It isn’t used as a screening test for coagulopathies.

A normal INR in patients receiving warfarin therapy is 2.0 to 3.0. For patients with mechanical prosthetic heart valves, an INR of 2.5 to 3.5 is suggested. Increased INR values may indicate disseminated intravascular coagulation, cirrhosis, hepatitis, vitamin K deficiency, salicylate intoxication, uncontrolled oral anticoagulation, or massive blood transfusion.

Activated clotting time, or automated coagulation time, measures the time it takes whole blood to clot.

This test is commonly performed during procedures that require extracorporeal circulation, such as:

In a nonanticoagulated patient, the normal activated clotting time is 107 seconds. During cardiopulmonary bypass, heparin is titrated to maintain an activated clotting time between 400 and 600 seconds. During ECMO, heparin is titrated to maintain the activated clotting time between 220 and 260 seconds.

The 12-lead electrocardiogram (ECG) measures the heart’s electrical activity and records it as waveforms. It’s one of the most valuable and commonly used diagnostic tools.

The standard 12-lead ECG uses a series of electrodes placed on the patient’s extremities and chest wall to assess the heart from 12 different views (leads). The 12 leads include:

The limb leads and augmented leads show the heart from the frontal plane. The precordial leads show the heart from the horizontal plane. (See Understanding ECG leads, page 98.)

ECG can be used to identify myocardial ischemia and infarction, rhythm and conduction disturbances, chamber enlargement, electrolyte imbalances, and drug toxicity.

Because it allows continuous observation of the heart’s electrical activity, cardiac monitoring is used in patients at risk for life-threatening arrhythmias.
Like other forms of electrocardiography, cardiac monitoring uses electrodes placed on the patient’s chest to transmit electrical signals that are converted into a cardiac rhythm tracing on an oscilloscope. (See Positioning monitor leads, pages 102 and 103.)

Two types of monitoring may be performed: hardwire or telemetry. In hardwire monitoring, the patient is connected to a monitor at the bedside. The rhythm display appears at the bedside, or it may be transmitted to a console at a remote location. Telemetry uses a small transmitter connected to the ambulatory patient to send electrical signals to another location, where they’re displayed on a monitor screen. Regardless of the type, cardiac monitors can display the patient’s heart rate and rhythm, produce a printed record of cardiac rhythm, and sound an alarm if the heart rate exceeds or falls below specified limits. Monitors also recognize and count abnormal heartbeats as well as changes. (See Identifying cardiac monitor problems, page 104.)

Exercise electrocardiography is a noninvasive test that helps the practitioner assess cardiovascular response to an increased workload. Commonly known as a stress test, it provides diagnostic information that can’t be obtained from a resting electrocardiogram (ECG). This test may also assess response to treatment.

An ECG and blood pressure readings are taken while the patient walks on a treadmill or pedals a stationary bicycle, and his response to a constant or increasing workload is observed. Unless complications develop, the test continues until the patient reaches the target heart rate (determined by an established protocol) or experiences chest pain or fatigue.

Stop the test if the patient experiences chest pain, fatigue, or other signs and symptoms that reflect exercise intolerance. These may include: