DR.

KRINA VIROLIYA
DR. MOHANA PREESHA
 BIOMARKER DEFINATION

• Biomarker is a biologic feature that can be used to

measure the presence or progress of disease or the
effect of treatment. i.e. RA factor, CEA, PSA.

• Cardiac biomarkers are protein molecules released

into the blood when the heart is damaged or
stressed.
 DETECTION

• Unstable angina
• Diagnosis of acute myocardial infarction/acute
coronary syndrome
• Suspicious EKG changes
• Following surgical coronary revascularization
• To monitor the patients with congestive heart failure
or renal failure
 WHICH ARE THEY?

i. Creatine kinase (CKMB)

ii. Cardiac troponin I (CTI) and Cardiac
troponinT (CTT).
iii . Myoglobin
iv. Brain Natriuretic Peptide (BNP).
v. LDH and AST
 NATRIURETIC PEPTIDES
• The natriuretic peptide family consists of three
peptides:
• Atrial natriuretic peptide (ANP) - primarily in the
cardiac atria.
• Brain natriuretic peptide (BNP) - present in human
brain, but more in the cardiac ventricles.
• C-type natriuretic peptide (CNP) - clinical
significance of CNP is not clear.
 Brain natriuretic peptide

• BNP is secreted by right and left ventricular myocytes

and released in response to stretch, volume
overload, and elevated filling pressures.
• Serum levels of BNP are elevated in patients with
asymptomatic LV dysfunction as well as symptomatic
HF.
• A serum BNP of <100 pg/ml has a good negative
predictive value and typically excludes HF as primary
diagnosis in dyspneic patients. BNP levels correlate
with the severity of HF.
Neither the clinical
presentation nor the EKG
alone has adequate clinical
sensitivity and specificity for
detecting MI without the use
of biomarkers.
• Enzymatic:
i. CK
ii. LDH
iii. AST

• Nonenzymatic :
i. Myoglobin
ii. Cardiac troponin T and I
 Aspartate transaminase(AST)

• AST was the first cardiac biomarker to

be used in 1954.
• It is found in the liver, heart, skeletal
muscles, brain, kidneys.
• Normal Range: 8-20U/L
• Lack of specificity
 LACTATE DEHYDROGENASE

• LDH catalyzes the reversible conversion of muscle

lactic acid into pyruvic acid, an essential step in the
metabolic process that ultimately produces cellular
energy.
• There are 5 isoenzymes of LDH:
• LDH1 and LDH2 appear primarily in the heart, RBCs
and kidneys.
• LDH3 concentrated primarily in the lungs.
• LDH4 and LDH5 are located in the liver, skin, and the
skeletal muscles.
• Normally LDH-2 concentration in blood is
greater than LDH-1; but this pattern is
reversed in myocardial infarction called “flipped
LDH”.

 Normal value of LDH in serum is 100-200 U/L.

LDH elevates in 24-48 hours
peaks in 48-72 hours after the episode

• Because LDH is present in almost all body

tissues, any type of cellular damage i.e.
hemolysis, cancer, infectious process
increases total serum LDH, limiting the
diagnostic usefulness of this test.
 MYOGLOBIN
• Myoglobin is an oxygen storing protein found in
skeletal and cardiac muscle.
• It is released into circulation as early as one hour
after myocardial injury.
• Myoglobin typically rises 2 - 4 hours after onset of
myocardial injury, peaks at 8 - 12 hours and returns
to normal within 24 hours.
• Acute myocardial infarction
• Skeletal muscle damage
• Muscular dystrophy
• Inflammatory myopathies
• Renal failure
• Severe trauma
• Shock
DRAWBACKS OF MYOGLOBIN

DRAWBACKS
• Myoglobin levels do not always
predict myocardial injury. Thus
it has sensitivity but lacks
specificity.
• Used less frequently; sometimes
performed with troponin to
provide early diagnosis.
 CREATINE KINASE
• Creatine kinase (CK/CPK) is an enzyme
expressed in a number of tissues.
• Function: it catalyzes the conversion of
creatine to phosphocreatine degrading
ATP to ADP.
• The CK enzyme consists of two subunits:
B (brain type),
M (muscle type);
Making three different isoenzymes: CK-MM,
CK-BB and CK-MB
 Creatine kinase
(CK-MB)
 Normal serum value
15- 100 U/L for males
10-80 U/L for females

High specificity for cardiac tissue,

Begins to rise 4-6 hours after onset of infarction,
Peaks at about 12-14 hours,
Returns to baseline at 48-72 hours.

 Can be used to indicate early re-infarction if level

normalizes and then increases again.
 Troponins
• Troponins are seen in skeletal and cardiac
muscles, but not in smooth muscles.

• Significant increase in Troponins

reflects myocardial necrosis and the
extend of the damage.

They are quantitated by ELISA or immuno

turbidimetric) reactions.
 Troponin I (cTnI)

• Troponin I is released into the blood

within 4 hours after the onset of
symptoms of myocardial ischemia;
peaks at 14-24 hours and remains
elevated for 3-5 days post-infarction
 Troponin T (cTnT)
• Serum level of Troponin T (TnT)
increases within 6 hrs of myocardial
infarction, peaks at 72 hours and
then remains elevated up to 7-14
days.
The diferrence between cardiac troponin T and cardiac
troponin I is that cardiac troponin I has never been
expressed in normal, regenerating or diseased human or
animal skeletal muscle.

However, small amounts of cTnT are made by skeletal

muscle during human fetal development, in regenerating
muscle, and in diseased muscle.
Thus cTnT has been found in skeletal muscle specimens
obtained from individuals with muscular dystrophy,
polymyositis and chronic renal disease.
 Timing Summary

TEST ONSET PEAK DURATION

CK/CK-MB 3-12 hours 18-24 hours 36-48 hours
Troponins 4-10 hours 18-24 hours Up to 10 days
Myoglobin 1-4 hours 6-7 hours 24 hours
LDH 6-12 hours 24-48 hours 6-8 days
 Troponin Early Peak (Hrs) Duration Specficity Sensitivity
Rise(hrs) (Days)

Tn T 4-6 10-24 10-24 80% >98%

Tn I 3-6 1-24 4-7 95% >98%

• Therefore it has good utility for retrospectively

diagnosing AMI
• Remember, CK-MB returns to baseline by
•
Referrences :

1. A Look at Emerging Cardiac Biomarkers ; Genna Rollins , Jan 2012 ;

American Board of Clinical Chemistry
https://www.aacc.org/publications/cln/articles/2012/januar y/cardio-
biomarkers
2. Cardiac Biomarkers for Rapid Evaluation of Chest Pain ; Christian W.
Hamm ; Mar 2018 ; American Heart Association
https://www.ahajournals.org/doi/full/10.1161/circ.104.13.1454
3.Implimentation of new Troponin Test Aids In Diagnosis of MI ; June 5;
James Louis Januzzi ; Massachusets General Hospital
https://advances.massgeneral.org/cardiovascular/article.aspx?id=1040
4. Changes in brain natriuretic peptide and norepinephrine over time and
mortality and morbidity in the Valsartan Heart Failure Trial ( Val- HeFT) ;
circulation 2013 ; 107; 1278-83