selected proteins used in detecting cardiac disorders

1. UNIVERSITY OF ABUJA
COLLEGE OF HEALTH SCIENCES
SET 6 400 LEVEL MEDICAL STUDENTS PRESENTATION ON
BIOMARKERS OF CARDIAC DISEASES.
FACULTY OF BASIC CLINICAL SCIENCES-
DEPARTMENT OF CHEMICAL PATHOLOGY

2. OUTLINE
 INTRODUCTION
 DEFINITIONS
 CLINICAL SIGNIFICANCE
 CRITERIA FOR IDEAL CARDIAC
MARKERS
 CLASSIFICATION
 CONCLUSION
CARDIAC DISEASES
BIOMARKERS
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3. INTRODUCTION
 The heart muscle cells contain intracellular proteins which may functions as;
• Enzymes for metabolism e.g Creatinine Kinase, Lactate dehydrogenase.
• Contractile for cardiac contractility e.g Troponins I, T and C.
• Peptides e.g Natriuretic peptide
 The levels of these proteins increase in the blood when the heart cells are
injured; hence the name Biomarkers.
 Some are specific (found only in the heart) while some are non
specific(found in other tissues).

4. DEFINITION
 Biomarkers or biological markers refers to a broad range of measure
which captures the functioning capacity of a cell. They are used to
measure the presence or progress of a disease.
 Cardiac markers are biomarkers measured in the plasma to evaluate heart
function.
 They are often used to describe the proteins associated with myocardial
infarction(Troponin, Creatinine kinase and Lactate dehydrogenase)
 However, the term is acceptable in defining the presence of other cardiac
diseases such as myocardial ischemia , myocardial stress, inflammation.

5. CLINICAL SIGNIFICANCE
Cardiac markers are used clinically
for the following;
Diagnosis and risk stratification of patients with suspected
acute coronary syndrome and to evaluate their severity.
With early diagnosis, prompt medical intervention can be
made which is crucial to minimize further heart damage,
future complications and prevent death.
Management and prognosis in patients with acute heart
failure, pulmonary embolism and other diseases state.

6. CRITERIA FOR IDEAL CARDIAC
MARKER
 High concentration in the myocardium.
 High sensitivity and specificity.
 Rapid release in blood following myocardial injury.
 Remains in blood for several days to allow detection.
 Blood levels correlate with extent of myocardial injury.
 Easy, cheap and rapidly measured.

7. CLASSIFICATION
Cardiac markers are best classified based on associated diseases;
Biomarkers of cardiac injury;
Myocardial infarction; Creatine kinase, Myoglobin and Cardiac troponins(Most
specific)
Myocardial ischemia; Ischemia modified albumin
Biomarkers of hemodynamic stress;
Natriuretic peptide
Biomarkers of inflammation and prognosis;
C-reactive protein(CRP)
Soluble CD40 ligand (sCD40L)
Homocysteine

8. TROPONIN
Muscle regulatory proteins
present in skeletal and cardiac
muscles. It is localized
primarily in the myofibrils(94-
97%) with a similar
cytoplasmic fraction (3-6%)
Three troponins have been
reported namely troponin
C(TnC) which is calcium
binding, troponin T(TnT) which
binds tropomyosin and
troponin I(TnI) as an inhibitory
component.
There are no differences
between the cardiac and
skeletal muscle’s TnC.
However TnT and TnI are
different in both cells.
TnI and TnT appear in plasma
4-8 hours after symptoms of
chest pain and are best
measured 12 hours after the
onset of chestpain. This initial
increase is due to the
cytoplasmic fraction.
This rise may be helpful for
early diagnosis. It stays
elevated for about 7-10 days in
plasma which makes them
useful for late presentation.
The prolonged duration is due
to the myofibril fraction
release.
An increased TnI and TnT
concentration is a marker of
occult myocardial damage
even in non-ischemic
conditions .

9. CREATINE KINASE
The plasma enzyme estimation of
greatest value is that of Creatine
Kinase(CK). CK catalyzes the
reversible transfer of high-energy
phosphate from ATP to creatine,
facilitating storage of energy in
the form of phosphocreatine
When ATP decreases in the
muscle, phosphocreatine
donates phosphate to ADP to
form ATP and thus provides
temporal energy required for
muscular contraction.
CK has three isomers; CK-1(BB)
found in brain and thyroid
tissue, CK-2(MB) most specific
to myocardium and CK-3(MM) in
skeletal muscle and
myocardium.
Plasma level rises 4-6 hours
after the onset of chest pain due
to myocardial infarction. This
may help in early diagnosis
however it’s measurement alone
is not diagnostic of an
infarction.
However it is not useful for late
detection as it clears from
plasma after 2-4 days
A second rise of plasma enzyme
activities after their return to
normal may indicate extension
of the damage. A prolonged rise
in plasma CK may suggest a
cardiac ventricular aneurysm.

10. CREATINE KINASE

11. MYOGLOBIN
A low molecular weight haem-
containing protein found in
both skeletal and cardiac
muscles.
Because of it’s low molecular
weight it is rapidly released
from the myocardium upon
damage.
A typical rise occurs within 2-4
hours after onset of acute
myocardial infarction. Thus it
is the most sensitive early
marker
This is useful for the early
diagnosis of AMI, as the rise is
generally earlier than that of
the other currently used
markers.
However it is not useful for
late detection as it clears from
plasma after 2-4 days

12. LACTATE DEHYDROGENASE
LDH catalyzes conversion of
pyruvate to lactate in anaerobic
metabolism. It is locatedin the
cytoplasm of tissues and found
mostly in liver, heart, skeletal
muscle, kidney and red blood
cells.
5 isoenzymes are identified LD 1,
2, 3, 4 and 5. LDH-1 is found in
highest concentration in heart
muscle.
Plasma level becomes elevated
12-18 hours after onset of
symptoms. This makes it less
useful for early diagnosis.
However, It returns to normal after
7-12 days and thus a useful and
sensitive marker for late
diagnosis

13. LACTATE DEHYDROGENASE

14. ASPARTATE TRANSAMINASE(AST)
AST is not cardiac specific as
it is mostly used as a liver
biomarker. The sequence of
changes in plasma AST
activity after myocardial
infarction are similar to those
of CK.
AST catalyzes the
transamination of aspartate to
oxaloacetate and glutamate.
The two products are used up
in citric acid cycle to generate
more ATP.
A small myocardial infarct
does cause some hepatic
congestion due to right-sided
heart dysfunction, and this
may also contribute to the rise
of plasma AST activity.
Plasma level rises 6-8 hours
after the onset of chest pain
due to myocardial infarction.
Thus less useful for early
diagnosis.
It level clears after 4-6 days

15. ASPARTATE TRANSAMINASE

16. MAJOR CARDIAC MARKERS;
Cardiac marker Starts to
rise(hours)
Time after
infarction for
peak rise(hours)
Duration of rise
(days)
CK 4-6 24-48 2-4
AST 6-8 24-48 4-6
LDH 12-24 48-72 7-12
MYOGLOBIN 2-4 12-24 2-4
TROPONIN 4-6 12-24 7-10

17. MAJOR CARDIAC MARKERS
0
1
2
3
4
5
6
7
Day 1 Day 2 Day 3 Day 4 Day5-12
Myoglobin Troponin CK AST LDH

18. C-REACTIVE PROTEIN
C-reactive protein (CRP) is a
positive acute phase
reactant/protein produced
primarily by the liver.
A non specific marker of acute
inflammation. It is thought to
assist in complement binding to
foreign and damaged cells,
enhancing phagocytosis by
macrophages.
Considered to be directly
involved in coronary
atherogenesis. It is therefore
more related to coronary artery
inflammation related to
atherosclerosis rather than
injured myocardium.
It is a useful prognostic indicator
in patients with AMI; thus aiding
prediction of adverse cardiac
events at primary and secondary
prevention levels.

19. HOMOCYSTEINE
A sulfur containing compound, it is
an independent risk factor of
cardiovascular disease. High level in
blood can be due to Folate, Vit B6
&and Vit B12 deficiency.
It’s high level in blood also aids
prediction of the cardiac event at
primary and secondary prevention
levels. It contributes to coronary
artery atherogenesis.
Some of the presumed atherogenic
mechanisms are; increase in
proliferation of vascular smooth
muscle cells, induction of
thrombosis, oxidative damage, an
increase in synthesis of collagen and
deterioration of arterial wall elastic
material.

20. HOMOCYSTEINE

21. SOLUBLE CD40 LIGAND
Soluble CD40 ligand is found on the activated
platelets. It is proinflammatory for endothelial
cells and promotes coagulation by inducing
expression of tissue factor on monocytes and
endothelial cells.
It also aids in prediction of cardiac events
associated with coronary artery inflammation
secondary to atherosclerosis.

22. OTHER BIOMARKERS;
Atrial Natriuretic peptide and Brain
natriuretic peptide are released from the atria
and ventricles of the heart respectively due
to increased tension. Their increased level in
the blood indicates Chronic Heart Failure.
IschemiaModified Albumin (IMA), though still
under research, can serve as an indicator to
myocardial ischemia.
NATRIURETIC PEPTIDE IMA

23. CONCLUSION
 Cardiac markers are biomarkers measured in the plasma to
evaluate heart function.
 They are often used to describe the proteins associated with
myocardial infarction (Troponin, Creatinine kinase and Lactate
dehydrogenase)
 The troponins are more specific cardiac markers than CK.
 Myoglobin is the most specific early cardiac marker.

24. REFERENCES;
 Professor Martin Andrew Crook,Clinical Biochemistry and
Metabolism Medicine Eighth Edition by Hodder Arnold
publishers, 2012. Cardiovascular Disorders Chapter 22, Page
325.
 Deborah French, Alan H.B. Wu, in The Immunoassay Handbook
(Fourth Edition), 2013
 P.E. Puddu, ... R. Bugiardini, in Encyclopedia of Cardiovascular
Research and Medicine, 2018

25. THANK YOU FOR
YOUR ATTENTION