Biochemical Markers in Cardiac

Disease
ACUTE CORONARY SYNDROME
(ACS)
 Ischemic heart diseases (acute coronary syndrome) includes:
1-Angina
2-Unstable angina
3-Myocardial infarction: most serious form of ischemia that
leads to injury or even death of myocardium.
 The most common cause of myocardial ischemia is atherosclerosis.
 Risk factors for Coronary Artery Disease:
1-Age
2-Gender
3-Family history
4-Hyperlipidemia
5-Smoking
6-Hypertension
7-Diabetes
8-Obesity
9-High plasma homocysteine levels
CRITERIA FOR DIAGNOSIS OF ACS

 Triad of criteria:
 Clinical picture
Severe & prolonged chest pain
Atypical pain (epigastric)
Silent ischemia.
 ECG changes consistent with acute MI
 Elevated serum cardiac MARKERS
 Diagnosis requires at least two of them.
CARDIAC MARKERS MUST BE:

 Located in the myocardium.

 Released in cardiac injury.
– Myocardial infarction
– Non-Q-wave infarction
– Unstable angina pectoris
– Other conditions affecting cardiac muscle
(trauma, cardiac surgery, myocarditis etc.)
 Can be measured in blood samples.
CARDIAC MUSCLE CELL

Size and subcellular distribution of myocardial proteins determines time

course of biomarker appearance in the general circulation
CLASSIFICATION OF LABORATORY
TESTS IN CARDIAC DISEASE

 Markers of cardiac tissue damage

 Markers of myocardial function

 Cardiovascular risk factor markers

 Genetic analysis for candidate genes or risk

factors
BIOCHEMICAL MARKERS IN
MYOCARDIAL ISCHAEMIA / NECROSIS

RECENT Traditional
 CK-MB (mass)  AST activity

 c.Troponins (I or T)  LDH activity

 LDH isoenzymes
 Myoglobin
 CK-Total
FUTURE:  CK-MB activity

 Ischaemia Modified Albumin  CK-Isoenzymes

 Glycogen Phosphorylase BB
 Fatty Acid binding Protein
 Highly sensitive CRP.
ASPARATATE
AMINOTRANFERASE (AST)
 An enzyme that catalysis the transfer of amino
group from amino acid to keto acid
 It is widely distributed in heart, liver, skeletal
muscle, kidney and RBCs.
 AST activity is increased after myocardial
infarction
 It is elevated in other conditions as:
 Liver disease: hepatitis, liver cirrhosis, neoplasia
 Muscle diseases: muscular dystrophy and
dermatomyositis
LACTATE DEHYDROGENASE
(LDH)
 LDH is a hydrogen transfer enzyme that catalysis the
oxidation of L-Lactate to Pyruvate.
 Level elevated 10 – 12 after acute myocardial infarction,
peak in 2 days and return to normal in 7 -10 days
 CREATINE KINASE

 CK is a dimeric enzyme that regulates high energy phosphate

production and utilization in contractile tissues.
 It is composed of two subunits:
M subunit encoded by a gene on chromosome 14.
B subunit encoded by a gene on chromosome 19.
 There are different isoenzymes:
 CK1 (CK-BB): the predominant isoenzyme found in brain.
 CK2 (CK-MB): represent 20 – 30 % of total CK in diseased cardiac
tissue
 CK3 (CK-MM): 98% in skeletal muscles and 1% in cardiac muscles.
 CK-mitochondrial (CK-Mt): located in mitochondria and encoded by a
different gene on chromosome 15.
 CREATINE KINASE
NORMAL VALUES: PATHOLOGICAL INCREASES:
Vary according to –
 Myocardial infarction or injury
 age
 sex
 Skeletal muscle injury or disease
 race  Hypothyroidism
 physical condition  IM injections
 muscle mass  Generalised convulsions
 Cerebral injury
 Malignant hyperpyrexia
 Prolonged hypothermia
MYOGLOBIN (Mb)

 Low MW protein
 Skeletal & cardiac muscle Mb identical
 Serum levels increase within 2h of muscle damage
 Peak at 6 – 9h
 Normal by 24 – 36h
 Excellent NEGATIVE predictor of myocardial injury
– 2 samples 2 – 4 hours apart with no rise in levels virtually
excludes AMI
 Rapid, quantitative serum immunoassays
 CARDIAC TROPONINS

 It consists of 3 subunits troponin C, I, and T.

 The complex regulates the contraction of
striated muscle.
1. TnC binds to calcium ions.
2. TnI binds to actin and inhibits actin-myosin
interaction.
3. TnT binds to tropomyosin, attaching to thin
filament.
THE TROPONIN REGULATORY
COMPLEX
ISCHAEMIA-MODIFIED ALBUMIN
(IMA)
 Serum albumin is altered by free radicals released from ischaemic
tissue
 Angioplasty studies show that albumin is modified within minutes of
the onset of ischaemia.
 IMA levels rise rapidly, remain elevated for 2-4 h + return to baseline
within 6h
 Clinically may detect reversible myocardial ischaemic damage
 Not specific (elevated in stroke, some neoplasms, hepatic cirrhosis,
end-stage renal disease)
 Thus potential value is as a negative predictor
Glycogen phosphorylase BB (GPBB):

 Glycogen phosphorylase (GP) is a glycolytic enzyme which

plays an essential role in the regulation of carbohydrate
metabolism.
 It functions to provide energy supply for muscle contraction
 Three GP isoenzymes are found in human tissues:
o GP-LL in liver
o GP-MM in muscle
o GP-BB in brain.
 GP-BB is the predominant isoenzyme in myocardium. With the
onset of tissue hypoxia when glycogen is broke down, GP-BB is
converted from structurally bound to cytoplasmic form.
 In AMI GP-BB: Increases 1 – 4 after onset of chest pain
 Peaks before CK-MB and cTnT
 Return to reference interval 1 – 2 days after
AMI.
 However it is not cardiac specific.
BIOCHEMICAL MARKERS IN ACS:
RELEASE, PEAK AND DURATION OF ELEVATION

Marker start Peak Duration of

elevation
LD-1 24 – 47 h 48 – 72 h 7 – 10 days
Total CK 3–8h 12 – 30 h 3 – 4 days
CK-MB 4–6h 24 h 48 – 72 h
CK-MB 2–3h 18 h < 24 h
isoforms
cTnI 6h 24 h 7 – 10 days
cTnT 6h 12 – 48 h 7 – 10 days
Myoglobin 2h 6–7h 24 h
IMA Few minutes 2–4h 6h
BIOCHEMICAL MARKERS IN ACS:
RELEASE, PEAK AND DURATION OF ELEVATION
“ACS REDEFINED”

 If Troponins are not available, best alternative is CK-

MBmass
 Degree of elevation of the marker is related to clinical risk
 CK(total), AST & LDH (Cardiac Enzymes) should NOT be
used!
 Combine early (myoglobin) & late (Troponins) markers
 Serial testing: admission, 6 – 9 h, 12 – 24 h
 An elevated Troponin level in the absence of clinical
evidence of ischaemia should prompt searching for other
causes of cardiac damage
ACS REDEFINED
Revised Criteria: Acute/Evolving/ Recent MI
 Typical myocardial necrosis-associated rise & fall of
Troponin or CK-MBmass
PLUS
 One of:
– Cardiac Ischaemia symptoms
– Q waves on ECG
– ST segment changes indicative of ischaemia
– Coronary artery imaging (stenosis/obstruction)

 OR Pathologic findings of an acute MI

 BIOCHEMICAL MARKERS IN AMI
ASSESSMENT OF REPERFUSION

Successful  “Washout” phenomenon –

reperfusion enzymes & proteins have
direct vascular access when
occluded coronary circulation
Marker Level

becomes patent
Unsuccessful  Peak concentrations earlier &
reperfusion
at higher levels if reperfusion
successful

Time

Due to short plasma half life (t½ = 10 min) Myoglobin is considered the
best re-perfusion marker
BIOCHEMICAL MARKERS IN ACS
CURRENT RECOMMENDATIONS

 AMI – Routine diagnosis Troponins (CK-MBmass)

 Retrospective diagnosis Troponins
 Skeletal muscle pathology Troponins
 Reinfarction Mb, CK-MBmass
 Reperfusion Mb, Tn, CK-Mbmass

 Infarct size Troponins

 Risk stratification in UA Troponins
BIOCHEMICAL MARKERS OF
MYOCARDIAL FUNCTION

CARDIAC NATRIURETIC PEPTIDES:

(ANP, BNP & pro-peptide forms)

 Family of peptides secreted by cardiac atria (+ ventricles)

with potent diuretic, natriuretic & vascular smooth muscle
relaxing activity
 Levels of these neuro-hormonal factors can be measured
in blood
 Clinical usefulness (especially BNP/N-terminal pro-BNP)
– Detection of LV dysfunction
– Screening for heart disease
– Differential diagnosis of dyspnea