Acute coronary syndrome Dr LM Murray Chemical Pathology Block SA13-2014
Acute myocardial infarction (MI) MI is still the leading cause of death in many countries It is characterized by severe chest pain, and takes place when there is interrupted blood supply to myocytes and necrosis follows
Coronary artery disease Clinical presentation: Angina pectoris: Chest pain: dull or stabbing pain, radiating to the arm or jaw Associated with shortness of breath, diaphoresis, nausea and vomiting Clinical classification of angina: Stable angina: pain occurs only with exertion Unstable angina: pain occurs at rest Myocardial infarction: pain persists without interruption and irreversible myocyte damage has occurred
Causes of coronary artery disease Type Atherosclerosis or ischemic heart disease (IHD) Spasm Emboli Congenital Comments Most common. Risk factors: HT, Chol, DM, smoking and family history Most prevalent in Japanese. Mediated by histamine, serotonin, catecholamine and endotheliumderived factors Rare, may occur from vegetations in patients with endocarditis 1-2% of population, mostly asymptomatic
Atherosclerosis Affects medium and large vessels Inflammatory process that begins early in life and results in the deposition of lipid, fibrin and calcium in the intimal layers of the arteries; which harden, narrow and eventually occlude the vessel Exact mechanism is unclear
Response to injury theory Endothelium is damagedby oxidized lipoprotein, infectious agents, glucose, homocysteine, smoking or HT?? LDL migrates into intima LDL oxidizes produces VCAM-1 and MCP-1 Attracts monocytes into intima Macrophages Macrophages take up oxidezed LDL Foam cells Growth factors and cytokines produced proliferation of smooth muscle cells and secrete collagen cap formation covering lipids This plaques grows and eventually blocks the lumen blood flow leads to ischemia
Risk factors for IHD Primary Genetic predisposition HT Smoking Hyperlipidaemia Life style factors Nutrition Fat Antioxidants Salt intake Environmental influence in early life Secondary Age Male sex Lack of exercise Obesity DM Stress Alcohol Ethnicity Socioeconomic factors Homocysteine CRP (C-reactive protein)
Acute coronary syndrome Definition:ACS is used when symptoms and signs are indicative of myocardial ischemia Classification: MI with typical ST segment elevation (STEMI) MI without ST segment elevation (NSTEMI) Unstable angina It is vital to be able to diagnose MI early to start thrombolytic treatment and improve patient survival
WHO criteria for MI diagnosis Include two of the three criteria: History of chest pain ECG changes Elevated troponin or CK-MB
Biochemical diagnosis of acute MI Injured myocardial cells leak enzymes and proteins and these enzymes and proteins (or cardiac biomarkers) are measured to determine if a MI is present
Characteristics of cardiac markers Cardiac marker Rise (hour) Peak (hour) Time to return to normal (day) CK 3-8 10-24 3-4 CK-MB 3-8 10-24 2-3 LD1 8-12 72-144 8-14 Myoglobin 1-3 6-9 1 Troponin I 3-8 24-48 4-10 Troponin T 3-8 24-48 4-10
Time course of cardiac enzymes after acute MI
CK-MB Cardiac marker Rise (hour) Peak (hour) Time to return to normal (day) CK 3-8 10-24 3-4 CK-MB 3-8 10-24 2-3 The pattern of CK-MB release may be influenced by: The size of the infarct Concomitant skeletal muscle injury Composition of myocardium Reperfusion (after thrombolytic therapy or spontaneous)
Injury to skeletal muscle may the absolute amount of CKMB but the relative concentration is usually <5 % Measurement of CK-MB mass is more specific for MI than CK-MB activity measurement. Sensitivity of CK-MB: On admission: 17-62 % 3 hrs: 92-100 % The sensitivity of CK-MB improves with serial measurements at 0, 3, 6, and 9 hours after presentation
Troponins Troponin consists of three proteins T, C and I where it is a regulator complex of muscle Troponin T and I are very cardiac specific
Sensitivity of troponin I and T for MI diagnosis 100% by 12 hours after onset of pain Disadvantages of Troponins Troponin T is cleared by the kidneys, thus may be in renal failure Not good at detection of MI in early hours But more sensitive troponin assays are developed which could diagnose MI within 3 hours after chest pain onset.
Cardiac marker Rise (hour) Peak (hour) Time to return to normal (day) Troponin I 3-8 24-48 4-10 TroponinT 3-8 24-48 4-10 Elevated troponin are seen in other conditions indicative of myocardial damage, where it is a poor prognostic sign Sepsis Pulmonary Embolism Hypothyroidism Cardiac failure Pericarditis Myocarditis
Increase in troponin after A: Acute Myocardial infarction B: Minor Myocardial infarction C: Myocarditis www.circ.ahajournal.org
Myoglobin Cardiac marker Rise (hour) Peak (hour) Time to return to normal (day) Myoglobin 1-3 6-9 1 Myoglobin is an oxygen-carrying haem protein present in skeletal and cardiac muscle Due to is small size it is released earlier than other proteins from damaged cells Useful biomarker to diagnose early MI A negative result will exclude MI, but a positive result needs to be confirmed
Important clinical facts CK-MB and troponins do not start to rise until 3-8 hours after infarction, thus not useful to diagnose early MI A negative myoglobin test in the early hours will exclude MI By 12 hours, troponins are 100 % sensitive thus important in late diagnosis of MI
Acute IM presenting within 12 hours are treated with thrombolytic treatment To assess if thrombolytic treatment has been successful we need to look at the increased release of cardiac markers, wash out phenomenon. Myoglobin is the best reperfusion marker Diagnosing myocardial ischemia after cardiac and non-cardiac surgery can be done with troponins as CK and CK-MB are released by injured skeletal tissue A high troponin in patients with unstable angina predicts higher mortality
Investigation of patients suspected of heart failure CXR ECG Laboratory: FBC: exclude anaemia UCE: / Potassium, Sodium, renal function Mg: Mg due to long term diuretic use LFT and thyroid function test BNP or NT-pro BNP
BNP (Brain naturetic peptide)is released in heart failure due to left ventricular function which leads to cardiac output Both BNP and NT-proBNP (fragment of probnp) are elevated in heart failure. Many laboratories measure NT-proBNP because is more stable in vitro (tube) Thus if BNP or NT-proBNP is negative heart failure can be excluded BNP and NT-proBNP is a prognostic marker in heart failure as well
References 1. Swaminathan R (ed). Handbook of Clinical Biochemistry, 2 th Ed 2011. World Scientific New Jersey: p 299-354. 2. Marshall WJ, Bangert SK (eds). Clinical Chemistry, 6 th Ed 2008. Mosby Edinburgh: p 271-293. 3. McPhee SJ, Hammer GD (eds). Pathophysiology of Disease: An Introduction to Clinical Medicine, 6 th Ed 2010. McGraw Hill Medical New York: p 275-278. 4. www.circ.ahajournal.org