7- Cardiac markers

Cardiac anatomy

• Enclosed by pericardium

• Walls made up of three muscle layers- epicardium, myocardium and endocardium

• 4 chambers- atria and ventricles

• Atrioventricular and semilunar valves

• Blood vessels- aorta, vena cava, pulmonary artery, pulmonary vein

Cardiac cycle

• Venous return of blood during diastole

• AV valves open and atria contract

• Ventricles contract, AV valves close and SL valves open

Ways heart diseases progress

• Ischaemia- inadequate blood/oxygen supply caused by blockage of blood vessel, reversible

• Infraction- cell death after prolonged ischaemia

Coronary artery disease

• Largely caused by atherosclerosis, plaque formation

• Made up of lipids, cell debris, foam cells (macrophages that engulf cholesterol), calcium

• Covered by fibrous cap made up of collagen and smooth muscle cells

• Lumen narrows and blood flow is reduced, plaque can break off into a clot

Syndromes stemming from coronary artery disease

• Stable angina

• Acute coronary syndromes- unstable angina, non-ST elevated MI, ST-elevated MI

Angina

• Heart pain with no damage to cardiac muscle

• Advanced atherosclerosis, pain on exertion due to ischaemia as blood supply cannot be increased across restricted vessels

• Stable- reversible, same risk factors as CHD

• Unstable- rupture of fibrous cap, blockage in vessel, pain at rest

Acute myocardial infraction

• Gross necrosis of the myocardium as a result to prolonged ischaemia to the area

• Blood supply to coronary muscle reduced below critical point due to plaque rupture and supsequent coronary thrombosis

• Coronary thrombosis- crushing chest pain, electrocardiogram changes (PQRST), release of cardiac muscle enzymes / markers

ECG changes during AMI

• ST elevation- complete blockage of coronary artery, severe

• ST depression- partial blockage

Diagnosis of AMI

• History, clinical presentation

• Changes in ECG, may take up to 24h

• Cardiac markers- troponin, myoglobin, creatine kinase, lactose dehydrogenase, aspartate transaminase

• Activity of enzymes measured, not amount

Usefulness of markers

Troponin complex structure and location

• Composed of 3 subunits

• Troponin C- binds calcium

• Troponin I- inhinitory component

• Troponin T- tropomyosin binding

• Found in myofibrils, released into circulation upon injury

• Isoforms vary between cardiac and skeletal muscle

Troponins used as cardiac markers

• Two isomers of troponin C, heart and skeletal are identical, not useful

• Cardiac specific- cTnT, cTnI

• cTnT- 11 unique amino acids provide specificity, small amount found in skeletal muscles but can be increased in patients with muscular dystrophy

• cTnI- unique to cardiac muscle, one isomer identified

Myoglobin

• Oxygen binding protein found in skeletal and cardiac muscle

• Is found in the cytoplasm and has a low molecular weight, increases rapidly after injury but is not specific

Creatine kinase

• Catalyses formation of phosphocreatine from creatine and ATP

• Cytosolic form is a dimer composed of M and B subunits

• Three isoenzymes- CK1 (BB), CK2 (MB), CK3 (MM)

• Mitochondrial form has two isoenzymes- CKMB (more heart specific), CKMM (heart and skeletal)

Lactate dehydrogenase

• Catalyses reduction of pyruvate to (L)-lactate using NADH as electrol donor

• High activity in skeletal muscle, liver, heart, kidney, RBC

• Not tissue specific, increases in many conditions

• Composed of four subunits of two peptides

• LD1 (H4- heart, kidney, RBC), LD2 (H3M), LD3 (H2M2), LD4 (HM3), LD5 (M4- liver, skeletal muscle)

Troponin measurement

• Troponin I- serum or used, monoclonal antibody immunoassay, 7-30 minute run time

• Troponin T- quantitative, serum or plasma used, immunoassay specific from cTnT, lateral flow assay can also be used

Measurement of myoglobin and creatine kinase

• Myoglobin- serum or plasma used in monoclonal immunoassay, allows for early AMI detection, also used as predictor for myocardial injury

• CK- enzymatic, immunoassay detection (100% specific), electrophoresis

Criteria for AMI diagnosis and properties of ideal cardiac marker

• Evidence of myocaridal ischaemia, rise and fall in troponin, at least one troponin result > or equal to 99th percentile

• Ideal marker should provide early AMI diagnosis

• Assist in risk stratification, monitor treatment, detect relapse, results within 60 minutes

Which markers are used in the clinical setting

• Troponins cTnT and cTnI (more specific)- stay elevated and have caridiac specificity, most useful 12h after MI, useful for late presentation, not useful for relapse as they stay elevated for days

• Myoglobin- not used for diagnosis, only confirmatory, released and cleared quickly, poor specificity (<80%)

Tests used to estimate risk of CHD

• Lipid screen- LDL, HDL, cholesterol, triglycerides

• CRP- indicates inflammation but increased levels are associated with future risk of cardiovascular events (high-sensitivity CRP used to detect low levels)

• Homocysteine- increased levels indicate developing CAD, used to screen those with family history

Natriuretic peptides

• Ring shaped molecules that promote sodium and water excretion

• Four subtypes- ANP, B type ANP (BNP), C type, D type

• B type produced by atria and ventricles, released when heart is stretched due to volume overload

• Hypervolaemia is commonly caused by heart failure which often occurs as a result of damage to the heart my MI