Cardiac Biomarkers and Acute Coronary Syndrome

Cardiac Biomarkers

• Cardiac markers, which are proteins from cardiac tissue, are detected in the blood.
• These proteins are released when the heart is damaged, such as during ischemia.
• Risk factors for heart disease include obesity, insulin resistance or diabetes, high cholesterol and blood pressure, family history of heart disease, physical inactivity, smoking, unhealthy diet, and clinical depression.
• Acute Coronary Syndrome (ACS) is a serious cause of chest pain. Non-cardiac causes such as pulmonary embolism, gallbladder disease, and indigestion can also cause chest pain.
• D-dimer is an early diagnostic marker for coronary ischemia in patients with chest pain. It's a protein fragment formed when a blood clot dissolves.
• ACS involves conditions such as myocardial infarction (heart attack), unstable angina pectoris, and silent ischemia.
• Atherosclerosis and rupture of unstable atherosclerotic plaque in a coronary artery are the most common cause of acute heart diseases.
• Subsequent thrombus formation can lead to partial or complete occlusion of coronary arteries, causing unstable angina or acute myocardial infarction.
• Identifying patients with acute myocardial infarction, even if no myocyte necrosis is visible, is the objective of diagnostic cardiac markers.
• Cardiac markers used include: Medical history, physical examination, electrocardiogram (ECG), and blood tests.
• The ideal biomarker is present in high concentration in the myocardium, appears soon after ischemia onset, and is absent in non-myocardial tissue and blood.
• Almost all cardiology associations recommend that an emergency department evaluation includes physical examination and ECG within 10 minutes, and cardiac markers determination within 30 minutes.
• Patients with suspected acute coronary syndrome should be treated within an hour of admission.
• Cardiac testing should be performed continuously with a 1-hour or less turnaround time for proper diagnosis.
• Serial sampling is recommended, including an early marker (myoglobin) and a late marker (troponin) at various time points (T0, T2-T4 hours, T8 hours, T12-T24 hours).

Cardiac Markers and Chest Pain Diagnosis

• The initial evaluation of patients with chest pain involves four steps: medical history, physical examination, ECG, and blood tests (including cardiac markers).

Cardiac Markers

• Some cardiac enzymes or proteins, originating from cardiac tissue, are detectable in the blood.
• These markers are released into the bloodstream when damage occurs to the heart due to ischemia. This can occur in myocardial infarction.
• Cardiac Troponin I (cTnI) and Cardiac Troponin T (cTnT) are specifically cardiac isoforms of troponins.
• cTnI and cTnT are the preferred cardiac biomarkers for myocardial damage and in diagnosing acute coronary syndrome, particularly when ECG changes are not clear.

Troponins

• Troponins are proteins within the myofibril's contractile protein complex.
• Troponins regulate the interaction of calcium, myosin, and actin, thus supporting skeletal muscle contraction.
• Troponins allow for the detection of minor myocardial damage.
• Troponin-levels appear relatively early (on average, 4–6 hours) after cardiac muscle damage.
• Cardiac isoforms are highly specific for cardiac injury. They are not present in healthy individuals' serum.
• cTnI is never reported in skeletal muscle, confirming its specificity for cardiac damage.
• The troponins (Tnl and TnT) are measured by immunoassay techniques.

Troponin Kinetics after Myocardial Infarction

• Troponin levels increase 3–12 hours after injury, peaking 24–48 hours later.
• Elevated cTnI levels stay elevated for 5–10 days, whereas cTnT levels persist for 5–14 days.
• The long persistence of troponin elevations post-acute MI aids in late diagnosis.

Creatine Kinase (CK)

• Creatine kinase (CK) is a cytosolic protein that shifts phosphate between creatine phosphate and ADP. This process occurs in damaged cells.
• CK exists as three major isoenzymes in different tissues: CK-MM (skeletal muscle), CK-BB (brain), and CK-MB (heart).
• CK-MB is elevated in over 90% of myocardial infarctions.
• CK-MB sensitivity is approximately 95% but with less specificity compared to troponins.

CK-MB Kinetics after Myocardial Infarction

• CK-MB levels rise within 3–12 hours of injury.
• The peak concentration is typically reached after 24 hours.
• CK-MB returns to normal in 2–3 days.
• Because of this, new elevations suggest re-infarction.
• Males have a cut-off point of 7.7 ng/mL, and females 4.3 ng/mL.

Myoglobin

• Myoglobin is a low-molecular-weight heme protein located in cardiac and skeletal muscle.
• An early marker, appearing at 1-3 hours after myocardial ischemia, indicating potential MI.
• Myoglobin is not cardiac-specific and shows high sensitivity but low specificity, making it helpful for acute suspected MI but not for definitive diagnosis. It can be influenced by skeletal muscle damage and renal failure.
• Myoglobin levels rise rapidly after myocardial infarction (within 2 hours).
• The levels peak at 6–8 hours and return to normal within 20–36 hours.

Lactic Dehydrogenase (LDH)

• Typically, LDH-2 is the predominant form in the serum.
• An abnormally high LDH-1 level compared to LDH-2 suggests myocardial infarction as damaged heart tissue releases LDH.
• LDH levels peak in 3–4 days and return to normal in 10 days.
• LDH is no longer used for cardiac diagnosis, preferring troponins nowadays.

Differential Diagnosis

• Cardiac muscle damage is not just due to myocardial infarction; other conditions can increase troponin levels.
• Cardiac conditions like cardiac surgery, defibrillation, cardiomyopathy, heart failure, myocarditis, and supraventricular tachycardia can increase troponin levels.
• Non-cardiac conditions such as critical illness (e.g., sepsis), high-dose chemotherapy, pulmonary hypertension, pulmonary embolism, renal failure, and severe exercise can also elevate troponins.