Biochemical Makers of Cardiac Disease

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 MI
Reperfusion injury
Reinfarction
• 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 activity
Normal <6% of total CK
In MI >6 % of total CK
• Methods of detection
Electrophoresis
Immunoinhibition
Two site immunoassay i.e CK-MB mass
CK-MB (CK-2)
• Sampling
Sensitivity <50% if one sample is taken
Sensitivity >98% if serial sampling at 0, 6h,12h, 24 h
Specificity 100%
• Other causes of raised plasma activity of CK-MB
Cardiac procedures
Crush syndrome
Major surgery
Rhabdomyolysis
Severe exercise
AST(Aspartate Aminotransferase)

• 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
• 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
The Four Big Ones

• C-Reactive Protein
• Lipoprotein (a)
• Fibrinogen
• Homocysteine
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 blood
Characterized 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.

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BIOCHEMICAL MAKERS OF

 Ischaemic necrosis of myocardium

• No precipitating factors identified in majority of

 Non specific for diagnosis of AMI

 CK‑MB (or CK‑2) in cardiac muscle

 CK‑BB (or CK‑3) in brain tissue

• Current ‘gold standard’

• Concentration in myocardium is 20 times more than

• Starts to rise 7-9 hrs post chest pain

• Cytoplasmic enzyme - all tissues, highest in muscle,

Subunit structure H4 H3M H2M2 HM3 M4

Normal serum + ++ + trace trace

Heart muscle ++ + trace - -

• Haem containing protein of cardiac and skeletal muscles

Structural proteins inside myocyte

 Troponin-T: binds troponin complex to the

 > 90% in myofibrils & 3-6% in cytoplasm

The Four Big Ones

• BB isoenzyme of glycogen phosphorylase

Cardiac Enzymes & Protein contribute in:

 Successful coronary reperfusion following

intravenous thrombolytic treatment results

 More rapid rise in plasma Proteins

 Earlier peaks in enzyme activities

Complex clinical syndrome structural or

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