Cardiac Markers

BY
DR : FADI AIDI

Definition and Efficacy

Cardiac markers are used in the diagnosis and
risk stratification of patients with chest pain
and suspected acute coronary syndrome
(ACS). The cardiac troponins, in particular,
have become the cardiac markers of choice for
patients with ACS. Indeed, cardiac troponin is
central to the definition of acute myocardial
infarction .

 For example, patients with elevated troponin

levels but negative creatine kinase-MB (CK-MB)
values who were formerly diagnosed with
unstable angina or minor myocardial injury are
now reclassified as nonST-segment elevation MI
(NSTEMI), even in the absence of diagnostic
electrocardiogram (ECG) changes.
Similarly, only 1 elevated troponin level above the
established cutoff is required to establish the
diagnosis of acute MI.

BIOMARKER
A biomarker is a substance used as an
indicator of a biologic state.
Three criteria for biomarkers
Accurate repeated measurements at
reasonable cost .
Must provide additional information .
Should aid treatment .

CARDIAC BIOMARKERS
Cardiac biomarkers are protein molecules
released into the blood stream from damaged
heart muscle
These biomarkers have a characteristic rise
and fall pattern .

CHARACTERISTICS OF AN IDEAL
CARDIAC MARKER

High cardiac specificity

Pharmacokinetics of cardiac biomarker
Easy diagnosis
Marker should play a designed role in the
treatment and management of clinical
subject.

HISTORY OF CARDIAC BIOMARKERS

1954 - SGOT (AST)

1955 - LDH
1960 - CPK
1972 - CPK isoforms by Electrophoresis
1975 - CK - MB by immunoinhibition
1975 - Myoglobin
1985 - CK - MB Mass immunoassay
1989 - Troponin T
1992 - Troponin I

CLASSIFICATION OF CARDIAC
BIOMARKERS
Biomarkers of myocardial injury :
markers of myocardial necrosis
markers of myocardial ischemia
Biomarkers of haemodynamic stress
Inflammatory and prognostic Biomarkers

BIOMARKERS OF MYOCARDIAL INJURY

Markers of myocardial necrosis
Creatine kinase MB
Myoglobin
Cardiac troponins
Markers of myocardial ischemia

Ischemia Modified Albumin (IMA)

Heart-type fatty acid binding protein (H-FABP)

Zones of Ischemia Injury and Infarction with

Transmural and Subendocardial Infarction

CREATINE KINASE
Creatine kinase (CK/CPK) is an enzyme expressed in a
number of tissues.
Function: it catalyses the conversion of creatine to
phosphocreatine degrading ATP to ADP
The CK enzyme consists of two subunits, B (brain type) or
M (muscle type), Making three different isoenzymes: CK-MM,
CK-BB and CK-MB
CK-BB occurs mainly in tissues, rarely of any significance in the
bloodstream

Skeletal muscle expresses CK-MM (98%) and low levels of CKMB (1%)
The myocardium has CK-MB .

CK-MB
High specificity for cardiac tissue
Begins to rise 4-6 hours after onset of infarction
Peaks at about 12 hours
Returns to baseline at 24-36 hours
Can be used to indicate early re-infarction if level normalizes
and then increases again .
????? Size of infarction ???

DRAWBACKS
False positive (for MI) CK-MB elevation can be seen in:
Significant skeletal muscle injury
The MB fraction is determined to be expressed during the
process of muscle regeneration
Cardiac injury for reason other than MI
Defibrillation
Blunt chest trauma
Cocaine abuse
The search for cardiac specificity continues

MYOGLOBIN
Small-size heme protein found in all tissues mainly assists in
oxygen transport .
It is released from all damaged tissues .

Increases often occur more rapidly than TI and CK .

Released from damaged tissue within 1 hour
Timing:
Earliest Rise: 1-3 hrs
Peak
6-9 hrs
Return to normal:
12 hrs

CONDITIONS FOR MYOGLOBIN

INCREASE

Acute myocardial infarction

Skeletal muscle damage, muscular dystrophy,

inflammatory myopathies

Renal failure, severe uremia

Shock and trauma

CLINICAL USEFULNESS OF
MYOGLOBIN
Rapid monitor of success of thrombolytic therapy

DRAWBACKS
Due to poor specificity, myoglobin levels do not
always predict myocardial injury .
Not utilized often for AMI/cardiac damage
assessment because of its very rapid metabolism .

CARDIAC TROPONINS
Troponin is a complex of three regulatory proteins that is
integral to non-smooth muscle contraction in skeletal as well
as cardiac muscle
Troponin is attached to the tropomyosin sitting in the groove
between actin filaments in muscle tissue
Troponin has three subunits, TnC, TnT, and TnI
Troponin-C has calcium binding ability and has no
diagnostic value
Troponin-T binds the troponin tropomyosin complex,
Troponin-I is an inhibitory protein

Cardiac Troponin Release after MI

TROPONIN LEVELS
Troponin levels begin to rise 2-3 hours after onset of
myocardial injury
Elevations in Troponin-I and Troponin-T can persist for up to
10 days after MI .
Remember, CK-MB returns to baseline by 48 hours .
Thus far, studies have failed to find a source of Troponin-I
outside the heart, but have found some Troponin-T in skeletal
muscle

Marker Responses to AMI

B
A A

A = myoglobin or CKMB isoforms

B = cardiac troponin
C = CKMB
D = cardiac troponin after
unstable angina