Cardiac Markers
Biochemical Markers
for Diagnosis of
Myocardial Infarction
• Myocardial Infraction is one type of Ischemic
heart disease.
• acute myocardial infarction (AMI) refers to a
situation in which death of myocytes is due to
an imbalance between myocardial oxygen
supply and demand.
• 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 Infraction” (abbreviated as “MI” )
• MI is the death & necrosis of myocardial cells
as a result of coronary prolonged & irreversible
ischemia
Causes of myocardial infarction
The major cause of ACS is atherosclerosis, which
contributes to significant narrowing of the artery
lumen and thrombus formation.
• Total loss of coronary blood flow results in a clinical
syndrome associated with what is known as ST
segment elevation AMI (STE AMI).
• Partial loss of coronary perfusion can lead to necrosis
as well, which is generally less severe and is known as
NSTEMI (non–ST elevation myocardial infarction).
• Other events of still lesser severity called angina,
which can range from stable to unstable.
Diagnosis of Acute Myocardial Infarction :
• required that at least two of the following
criteria be met:
(1) a history of chest pain
(2) evolutionary changes on the ECG, and/or
(3) elevations of serial cardiac marker .
The symptoms of myocardial infarction
• Shortness of breath
• Nausea, vomiting, and/or general epigastric (upper
middle abdomen) discomfort
• Sweating
• Heartburn and/or indigestion
• Arm pain (more commonly the left arm, but may be
either arm)
• Upper back pain
• General malaise (vague feeling of illness)
Risk factors
Primary risk factors have been identified:
Hyperlipidemia, Low HDL < 40-Elevated LDL / TG
Diabetes mellitus,
Hypertension,
Male gender,
Family history of atherosclerotic arterial disease.
Smoking
Poor diet -Lack of diet rich in fruit, veggies, fiber
Lake of Exercise
Ageing
Obesity
Carbon monoxide poisoning is risk factors for myocardial infarction but
also cardiomyopathy.
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 contents ECG
(chest pain) to blood changes
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 of Biochemical Markers for Myocardial
Infarction:
[Link] Enzymes (isoenzymes):
AST
Total CK ,CK-MB activity , CK-MB mass
Lactic Acid Dehydrogenase (LDH)
2- Cardiac proteins:
Myoglobin
Troponins
[Link] Enzymes (isoenzymes):
AST :
• The first cardiac markers to be used.
• Short window of AST elevation .
• high false negative rate
• Non espesific for cardiac damage.
LDH :
• Compared with AST, LDH was found to be a more sensitive
marker of MI that remains elevated for significantly longer post-
MI, up to 2 weeks.
• Non-specific: enzyme elevated with damage to many body
tissues. (i.e. heart, liver, skeletal muscle, brain and RBC’s)
• Five different isoforms of LD (LD-1to LD-5) ,LD-1 is
most abundant in the myocardium.
• It eleveated 24 to 48 hours after the onset of symptoms of MI
and remains elevated for up to 2 weeks.
• Thus it has great utility as an early biomarker in the
management of patients presenting several days after
possible MI
Creatine kinase(CK):
• In MI patients , serum total CK levels eleveted
within 6 to 8 hours, to reach a peak by 24 hours, and
decline to the normal level after 3 to 4 days.
• plasma CK increased in aother disorders such muscle
,brain disordors , pulamonary disease and alcholism
• Non espesific for MI.
• CK exists in three cytoplasmic isoenzymes:
_ CK MM
_ CK BB
_ CK MB
• 15% to 30% of CK in the myocardium is MB,
compared with 1% to 3% in aother striated
Muscle.
• Detection of elevated CK-MB was shown to
be highly specific to myocardial damage.
• elevations in serum CK-MB at 4 to 6 hours
after the onset of MI symptoms, to reach a peak
by 24 to 48 and drop to baseline levels by 2 to 4
days post-MI(early diagnosis).
• CK-MB was long considered the most reliable
serum marker of MI and is still widely used
today.
CK MB estimation:
_ CK MB activity
_ CK MB mass :
• Measure CK-MB in terms of protein concentration
μg/L, using two-site immunoassay technology based on
anti-M subunit .
- more sensitive than CK-MB activity
[Link]
• Is an iron- and oxygen-binding protein found
exclusively in the muscle and is normally absent
from the circulation.
• It level is elevated Quickly after muscle damage(1
Hour) and retain to baseline with 24hours
• Highly sensitive ,useful for early diagnosis.
• Non especific
Cardiac proteins:
1. Cardiac Troponins
• a complex of three proteins that is located on the thin
filament of striated muscles, responsible for transmitting
the calcium signal that triggers muscle contraction.
• [Link] C
• [Link] I
• [Link] T
• This subunits exist in a number of isoforms ,it is
distribution varies between cardiac muscle and slow and
fast twitch skeletal muscle.
• cTnI & cTnT are used are biomarkers for MI
Diagnosis.
• Highly specific
• Sensitive
• Cardiac troponins, are detectable in the plasma at 3
to 12 hours after myocardial injury, peaking at 12 to 24
hours and remaining elevated for more than 1 week
( 8 to 21 days for TnT and 7 to 14 days for TnI).
• Cardiac troponin (I or T) is currently the preferred
Biomarker for myocardial necrosis.
• Immunoassay is method of choice for it estimation.
SERIAL SERUM CARDIAC MARKERS AFTER ACUTE
MYOCARDIAL INFARCTION
50 cTnT
Amplitude of increase (x normal)
cTnl
CK-MB
Total CK by ASTl
15
LDl
10 Myoglobin
05
0 1 2 3 4 5 6 7 10
Days after onset of AMI
CARDIAC PROFILE TESTS
CK-MB CTnI CTnT Myoglobin
Early appearance
High specificity
Wide Diagnostic Window
Indicator reinfarction after 2-
4 days
Characteristics of serum markers for Myocardial Damage
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 – 14 days
Total CK 6– 8 h 12 – 24 h 3 – 4 days
CK-MB 4–6h 24 h 48 – 72 h
cTnI 6h 24 h 7 – 10 days
cTnT 6h 12 – 48 h 7 – 10 days
Myoglobin 2h 6–7h 24 h
BIOCHEMICAL MARKERS IN
MYOCARDIAL ISCHAEMIA / NECROSIS
RECENT Traditional
• CK-MB (mass) • AST activity
• LDH activity
• [Link] (I or T)
• LDH isoenzymes
• CK-Total
FUTURE: • CK-MB activity
Ischaemia Modified Albumin • CK-Isoenzymes
Glycogen Phosphorylase BB
Fatty Acid binding Protein
Highly sensitive CRP.
