Cardiovascular Block

Cardiac Enzymes
for Diagnosis of
Myocardial Infarction
Dr. Suhaemi, SpPD.
 What is Myocardial Infarction?
• Myocardial ischemia results from the reduction of coronary
blood flow to an extent that leads to insufficiency of oxygen
supply to myocardial tissue

• When this ischemia is prolonged & irreversible, myocardial

cell death & necrosis occurs ---this is defined as:
myocardial infarction

is the death & necrosis of myocardial cells

as a result of coronary prolonged & irreversible
ischemia
 Biochemical Changes in Acute Myocardial Infarction
(mechanism of release of myocardial markers)
ischemia to myocardial muscles (with low O2 supply)

anaerobic glycolysis

increased accumulation of Lactate

decrease in pH

activate lysosomal enzymes

disintegration of myocardial proteins

cell death & necrosis

clinical manifestations release of intracellular ECG

(chest pain) contents to blood changes
BIOCHEMICAL
MARKERS
Diagnosis of Myocardial Infarction

SHOULD depend on THREE items

(as recommended by WHO)

1- Clinical Manifestations
2- ECG
3- Biochemical Markers
 criteria for ideal markers
for myocardial infarction
1- Specific: to myocardial muscle cells (no false positive)

2- Sensitive: - rapid release on onset of attack (diagnose early cases)

- so, can detect minor damage
- no miss of positive cases (no false negative)

3- Prognostic: relation between plasma level & extent of damage

4- Persists longer: so, can diagnose delayed admission

6- Reliable: procedure depends on evidenced principle

5- Simple, inexpensive: - can be performed anywhere by low costs

- no need for highly qualified personnel

7- Quick: low turnaround time

Types ofBiochemical Markers for
Myocardial Infarction
1- Cardiac Enzymes (isoenzymes):
Total CK
CK-MB activity
CK-MB mass

2- Cardiac proteins:
Myoglobin
Troponins
 CARDIAC MUSCLE CELL

Size and subcellular distribution of myocardial proteins determines time

course of biomarker appearance in the general circulation
Markers of Cardiac Necrosis
 Cardiac Enzymes
• Total CK (sum of CK-MM, CK-MB & CK-BB)
non specific to cardiac tissue (available in skeletal ms.)

• CK-MB (CK-2) activity

more specific than total CK
BUT: less specific than troponin I (available in sk. Ms)

appears in blood: within 4-6 hours of onset of attack

peak: 12 - 24 hours
returns to normal: within 2 - 3 days (no long stay in blood)

Advantages: - useful for early diagnosis of MI

- useful for diagnosis reinfarction

Disadvantages: not used for delayed admission (more than 2 days)

not 100% specific (elevated in sk.ms damage)
• CK-MB mass
- appears one hour earlier than CK-MB activity (more sensitive)

- So, useful for diagnosis of early cases & reinfarction

- BUT: not for diagnosis of delayed admission cases

& less specific than troponin I

• Relative index = CK-MB mass / Total CK X 100

more than 5 % is indicative for MI
 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 •
 CREATINE KINASE: CK-MB

In normal population CK-MB < 6% Total CK

Sensitive marker with rapid rise & fall:
Serum CK-MB levels rise within 2~8 hours after AMI.
CK-MB values return to normal 2~3 days after the
event.
More specific than total CK but has limitations:
False elevations in:
-perioperative patients without cardiac injury
-Skeletal muscle injury
-Marathon runners
-Chronic renal failure
-Hypothyroidism
MB Index = (CKMB /total CK) x 100
Combined use with MB Index helps to rule-out patients with
skeletal muscle injury
 Cardiac Proteins
• Myoglobin
cytosolic protein

- not specific for cardiac tissue (also in sk.ms. & renal tissue)

- appears in blood EARLIER than other markers (within 1-4 hours)

So, with high sensitivity

- BUT: Returns to normal in 24 hours

So, not for delayed admission cases (after one day of onset
of attack)
• Cardiac Troponins
Protein complex located on the thin filament of striated muscles
consists of 3 subunits: cTn T, cTnI & cTn C
with different structures & functions

cTnI & cTnT are used are biomarkers for MI diagnosis

Cardiac troponins (cTn) are different from skeletal muscle tropnins

So, more specific for MI diagnosis

cTnI:

• 100 % cardiac specific

• With greater sensitivity for diagnosing minor damage of MI
• Appears in blood within 6 hours after onset of infarction
• peak: around 24 hours
• Disappears from blood after about one week (stays longer)
So, useful for diagnosis of delayed admission cases
• Prognostic marker (relation between level in blood & extent of cardiac
damage)
 Recommendations for use of biochemical
markers for diagnosis of myocardial infarction
1- Recommended for all patients complaining of chest pain (with clinical examination & ECG)

2- Sample
Type: plasma
Timing: i. on admission
ii. serial ( at least every one hour in a period 6-9 hours)
should be referenced to admission & onset of pain

3- Test should be with low turnaround time

less than one hour (accepted)
less than half an hour is preferred

4- Types of Markers used: two types

early markers: as Myoglobin: appears in blood early (within less 4 fours)
BUT not specific & not persists for long period (less than 2 days)

definitive markers: Troponin: appears in blood later than myoglobin (within 6 hours)
BUT 100% specific, prognostic & stays longer (one week)

5- Troponin is currently the marker of choice

should be available in all cardiac & emergency centers
(if not, CK-MB mass is the second choice)
 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 •
 ASPARATATE
AMINOTRANFERASE (AST)
An enzyme that catalysis the transfer of amino •
group from amino acid to keto acid which is
important for providing α keto acid for tricarboxylic
acid cycle (energy production) and providing
amino acid for urea cycle.
It is widely distributed in hear, 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.
It is composed of 4 subunits of 2 types •
M type encoded by a gene on ch 11
H type encoded by a gene on ch 12.
There are 5 isoenzymes: •
LD-1 (4 H subunits)
LD-2 (3 H and 1 M sumunits)
LD-3 (2 H and 2 M sumunits)
LD-4 (1 H and 3 M sumunits)
LD-5 (4 M subunits)
 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 •
Spectrophotometric assay for IMA adapted for automated clinical •
chemistry analysers
FDA approved as a rule-out marker in low risk ACS patients (2003) •
 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: •
GP-LL in liver o
GP-MM in muscle o
GP-BB in brain. o
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 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 –
Natriuretic Peptides
 Natriuretic Peptides
Present in two forms, atrial (ANP) and •
brain (BNP)
Both ANP and BNP have diuretic, •
natriuretic and hypotensive effects
Both inhibit the renin-angiotensin system •
and renal sympathetic activity
BNP is released from the cardiac •
ventricles in response to volume
expansion and wall stress
 BNP
BNP has also shown utility as a •
prognostic marker in acute coronary
syndrome
It is associated with increased risk of •
death at 10 months as concentration at 40
hours post-infarct increased
Also associated with increased risk for •
new or recurrent MI
 C-Reactive Protein
Multiple roles in cardiovascular disease •
have been examined
Screening for cardiovascular risk in otherwise –
“healthy” men and women
Predictive value of CRP levels for disease –
severity in pre-existing CAD
Prognostic value in ACS –
 C-Reactive Protein
Pentameric structure consisting of five 23- •
kDa identical subunits
Produced primarily in hepatocytes •
Plasma levels can increase rapidly to •
1000x baseline levels in response to
acute inflammation
“Positive acute phase reactant” •
 C-Reactive Protein:
Risk Factor or Risk Marker?
CRP previously known to be a marker of •
high risk in cardiovascular disease
More recent data may implicate CRP as •
an actual mediator of atherogenesis
Multiple hypotheses for the mechanism of •
CRP-mediated atherogenesis:
Endothelial dysfunction via ↑ NO synthesis –
↑LDL deposition in plaque by CRP-stimulated –
macrophages
CRP and CV Risk
Elevated levels predictive of: •
Long-term risk of first MI –
Ischemic stroke –
All-cause mortality –
Circulation. 2003;107:391-397.
N Engl J Med. 2002;347:1157-1165
 Homocysteine
Intermediary amino acid formed by the •
conversion of methionine to cysteine
Moderate hyperhomocysteinemia occurs •
in 5-7% of the population
Recognized as an independent risk factor •
for the development of atherosclerotic
vascular disease and venous thrombosis
Can result from genetic defects, drugs, •
vitamin deficiencies, or smoking
 Homocysteine
Elevated levels appear to be an •
independent risk factor, though less
important than the classic CV risk factors
Screening recommended in patients with •
premature CV disease (or unexplained
DVT) and absence of other risk factors
Treatment includes supplementation with •
folate, B6 and B12
 Homocysteine
Elevated levels appear to be an •
independent risk factor, though less
important than the classic CV risk factors
Screening recommended in patients with •
premature CV disease (or unexplained
DVT) and absence of other risk factors
Treatment includes supplementation with •
folate, B6 and B12
PATHOPHYSIOLOGY OF ACS

Proinflammatory Cytokines •
IL-6 •
Plaque Destabilization •
MPO •
Plaque Rupture •
sCD40L •
Acute Phase Reactants •
hs-CRP •
Ischemia •
IMA •
Necrosis •
cTnT •
cTnI •
Myocardial Dysfunction •
BNP •
NT-proBNP •
 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. 
BIOCHEMICAL MARKERS IN ACS
CURRENT RECOMMENDATIONS

Troponins (CK-MBmass) AMI – Routine diagnosis •

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

Troponins Infarct size •

Troponins Risk stratification in UA •
THANK YOU