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BIOCHEMICAL MAKERS OF CARDIAC DISEASE
Learning Objectives
What are Cardiac Markers Enumerate different cardiac markers Importance/Role of different biochemical
markers in the diagnosis of Acute MI
Cardiac Marker
A cardiac marker is a clinical labaratory test useful in detection of AMI or a minor myocardial injury.
ACUTE MYOCARDIAL INFARCTION
Ischaemic necrosis of myocardium Major cause: Atherosclerotic CAD with
super- imposed thrombosis
ACUTE MYOCARDIAL INFARCTION
AMI- PRECIPITATING FACTORS
• No precipitating factors identified in majority of cases
• Modest or usual exertion : 18% • Heavy physical exertion : 13% • Surgical procedure : 06% • Rest : 51% • Sleep : 08%
Diagnosis Of Acute Myocardial Infarction
Clinical history Evolutionary changes in ECG
Initial ECG : Positive in 50% of AMI cases Serial tracings : Sensitivity is above 75%
Abnormal cardiac enzymes/ proteins WHO Criteria : Two out of three
positive for diagnosis of AMI
CLINICAL HISTORY
Chest Pain Its character? tight", "heavy",
"constricting" Its location? typically retrosternal, Its duration? "prolonged", i.e. at least
20 minutes, and usually much longer.
BIOMARKERS OF CARDIAC INJURY
Cardiac Enzymes
Creatine Kinase (CK)
Lactate dehydrogenase(LD)
Aspartate aminotransferase(AST)
Cardiac Proteins
Troponin-I, Troponin-T
Myoglobin
Serum Creatine Kinase (CK) (Reference Range: 25 - 192 U/L)
Non specific for diagnosis of AMI present in :
Skeletal muscle Heart muscle Brain and other tissues
Isoenzyme: Different molecular forms of proteins with the same catalytic activity
CK has Two polypeptide subunits M & B and has three isoenzymes:
CK‑MM (or CK‑1) in skeletal muscle CK‑MB (or CK‑2) in cardiac muscle
CK‑BB (or CK‑3) in brain tissue
Distribution of CK activity
Total CK
Plasma CK activity 97% by CK-MM<3% by CK-MB
Starts to rise 3-8 hrs post chest pain Peak 12-24 hrs return to normal 3-4 days not specific
CK-MB (CK-2)
• Current ‘gold standard’Diagnosis of Acute MIReperfusion injuryReinfarction
• Starts to rise 3-6 hrs post chest pain
• Peak 10-24 hrs
• Return to normal 2-3 days
• Minor myocardial injury not detected
CK-MB (CK-2)
• Concentration in myocardium is 20 times more than in skeletal muscle
• Plasma activityNormal <6% of total CKIn MI >6 % of total CK
• Methods of detectionElectrophoresisImmunoinhibitionTwo site immunoassay i.e CK-MB mass
CK-MB (CK-2)
• SamplingSensitivity <50% if one sample is takenSensitivity >98% if serial sampling at 0, 6h,12h, 24 hSpecificity 100%
• Other causes of raised plasma activity of CK-MBCardiac proceduresCrush syndromeMajor surgeryRhabdomyolysisSevere exercise
AST(Aspartate Aminotransferase)
• Starts to rise 7-9 hrs post chest pain
• Peak 24-48 hrs
• Return to normal in 4-6 days
• Not specific
Serum LD (lactate dehydrogenase)
• Cytoplasmic enzyme - all tissues, highest in muscle, liver, kidneys, RBCs.
• Timing• Starts to rise 8-12 hrs post chest pain• Peak 72-144 hrs• return to normal 8-14 days
• Not specific for Ac. MI
Isoenzymes of lactate dehydrogenase
LD Isoenzyme 1 2 3 4 5
Subunit structure H4 H3M H2M2 HM3 M4
Normal serum + ++ + trace trace
Heart muscle ++ + trace - -
Liver - - - + ++
Skeletal muscle - - - + ++
MI : Flipping (LD1 to LD2 >1)
Cardiac Proteins
• Serum Myoglobin
• Cardiac Troponin T (cTnT)
• Cardiac Troponin I (cTnI)
Serum Myoglobin
• Haem containing protein of cardiac and skeletal muscles
• Earliest detectable marker
• Analytical methods: Unable to distinguish tissue of origin
• Rise Pattern• Released from myocardium: within 1-2 hrs
• Peak levels: 4-8 hours
• Revert to normal: 1 day
• Role in diagnosis of AMI• During early 4 hrs, when CK-2 still within the range
• Sensitivity (90-100%), Specificity (60-90%)
Serum Troponins
Structural proteins inside myocyte Troponin-C: binds calcium and initiates
contraction Troponin-T: binds troponin complex to
the tropomysin strand Troponin-I: inhibits contraction in the
resting state. > 90% in myofibrils & 3-6% in cytoplasm
Serum Troponins
Troponin-T: • increased 3-8 hr post chest pain• peak 1- 4 days• increased for up to 14 days Troponin-I:• increased 3-8 hr post chest pain• peak 1-2 days• returns to normal 5days• More specific & sensitive as compared to cTnT Both specific for myocardium
Brain Natriuretic Peptide (BNP) • Synthesized in myocardium • Associated with poor prognosis• Have potential to complement standard
cardiac markers• Requires versatile and applicable
analytical assays
Emerging Cardiac Risk Factors
• C-Reactive Protein
• Lipoprotein (a)
• Fibrinogen
• Homocysteine
The Four Big Ones
Possible future Markers
• BB isoenzyme of glycogen phosphorylase
• Acute phase proteins
• Selectin P
• Fibrin/FDP
Cardiac Makers : summary
Cardiac Enzymes & Protein contribute in:
• Diagnosis of acute MI
• Estimate of quantity of infarcted tissue
• Assessment of re-infarction
• Monitoring treatment
• Prognosis
MONITORING TREATMENT
Successful coronary reperfusion following
intravenous thrombolytic treatment results
More rapid rise in plasma Proteins
Earlier peaks in enzyme activities
HEART FAILURE
Complex clinical syndrome structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject bloodCharacterized by specific symptoms &signs
• Dyspnea • Fatigue• Fluid retention.
ANP & BNP
Secreted from Atria and ventricles In response to
Volume expansion Possibly increased wall stress.
Plasma concentrations are increased Heart failure (HF) Asymptomatic left ventricular dysfunction Symptomatic left ventricular dysfunction
Biochemical Tests Heart failure (HF)
Serum electrolytes and creatinine Baseline to follow when initiating-diuretics and/or ACEI Liver function tests Hepatic congestion Fasting blood glucose Diabetes mellitus Thyroid function tests Over the age of 65 Atrial fibrillation Hypothyroidism Thyrotoxicosis
Biochemical Tests
Iron studies (ferritin and TIBC) Hereditary hemochromatosis (HH)
Evaluation for pheochromocytoma Thiamine, carnitine, and selenium levels Plasma Atrial Natriuretic
Peptide(ANP) Plasma Brain Natriuretic Peptide
(BNP)
CARDIAC MARKERS
Which of the following Cardiac markers have the high specificity for cardiac injury
a) Globulin b) CK-MB mass assay c) Total CK d) AST e) LDH
CARDIAC MARKERS
A serum Troponin T concentration is of most value to the patient with a myocardial infarction when:
Sample being drawn within 3 to 6 hours of the onset of symptoms
The CK-MB has already peaked and returned to normal concentrations
The myoglibin concentrations is extremely elevated
The Troponin I concentration has returned to normal concentration
CARDIAC MARKERS
A normal myoglobin concentration 8 hours after onset of symptoms of a suspected myocardial infraction will:
Essentially rule out acute myocardial infraction Provide a definitive diagnosis of acute myocardial
infarction Must be interpreted with careful consideration of
the Troponin T concentration Give the same information as the total CK-MB
CARDIAC MARKERS
After myocardial infarction CPK rises within 30 minutes Four Hours Twelve hours 24 hours
CARDIAC MARKERS
Which of the following Cardiac markers have the high specificity for cardiac injury
a. CK-MB assay b. Troponin I c. Total CK d. AST e. LDH
CARDIAC MARKERS
In acute coronary syndrome trop T better reflects myocardial damage and peaks at 1-2 hours 6-12 hours 12-24 hours 24-48 hours 36-72 hours
CARDIAC MARKERS
Four hours after abdominal surgery a 65 years old male was found to have some equivocal ECG changes and markedly raised serum CK (> 1500 U/L). Which of the following cardiac markers would be the most specific investigations to rule out myocardial infarction in this patient: CK-MB activity measurement CK-MB mass measurement CK-MM activity measurement Myoglobin estimation in the blood Estimation of Cardiac Troponin T.
CARDIAC MARKERS
A 64 year old man was admitted to coronary care unit with history of central chest pain for last 8 hours. ECG on admission indicated changes of MI including Q wave. Which of the following enzymes do you expect to raise maximum in this patient?
a) AST b) CKMM c) LDH d) CKMB e) CKBB
A 40 years old farmer was admitted to the hospital with chest pain which had developed during the afternoon. He gave history of spending 4 hours digging in his fields. There were no specific signs of myocardial infarction on the ECG. He was kept in acute coronay unit for 48 hours. How you interpret his lab results.
Answer
Although Creatinine kinase (CK-NAC) activity is increased but normal CK-MB shows no cardiac injury. Total cholesterol levels and LDL-cholesterol can be measured in non-fasting individuals and recent food intake affects total cholesterol concentration less than 1.5%. However, serum triglyceride can increase markedly after eating.