4.sakina cardiac enzymes

DR SAKINA ,MBBS,M.D

SENIOR LECTURER ,MSU

BIOMARKERS -

DEFINITION

• A biomarker is a clinical laboratory test

which is useful in detecting dysfunction

of an organ.

• Cardiac biomarkers are protein molecules released into the blood stream from damaged heart muscle

These biomarkers are used to detect the heart diseases .

It has characteristic rise and fall pattern

CARDIAC MARKERS

TESTED IN

• i. Any chest pain

• ii. Unstable angina

• iii. Suspicious ECG changes

• iv. History suggestive of

myocardial infarction

• v. Following surgical

coronary revascularization

• vi. Patients with hypotension

and dyspnea

HISTORY OF 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

• Detecting myocardial damage whether due to AMI or other cardiac process ??

• CK-MB

• Troponin-I/T

• LD (LDH)

• Myoglobin

• AST

• BNP

• Others

• Serial testing of the following cardiac

Markers is usually done to guide the

prognosis

• i. Creatine kinase (CKMB)

• ii. Cardiac troponin I (CTI) and

Cardiac troponinT (CTT).

• iii . Myoglobin

• iv. Brain Natriuretic Peptide (BNP).

It is a reliable marker of ventricular

function

• v. LDH and AST were previously

used as markers of myocardial

infarction, but no more used in

clinical practice.

CARDIAC MARKERS

• Enzymatic:

i. CK

ii. LDH

• AST

• Nonenzymatic :

i. Myoglobin

ii. Cardiac troponin T and I

Commonly used biomarkers for

early detection of acute

myocardial infarction are:

• 1. Cardiac troponins, TnI and TnT

• 2. Creatine kinase, CK-MB

• 3. Myoglobin.

• Of these, troponins and CK-MB are

the sensitive and specific markers,

whereas myoglobin though

sensitive, is non-specific

Aspartate

transaminase(AST)

• AST was the first used as a

marker of myocardial infarction in

olden days,The level is

significantly elevated in

myocardial infarction

• Normal Range-8-20U/L

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 ,but it lacks

specificity

Released from damaged tissue within 1 hour

CONDITIONS FOR MYOGLOBIN INCREASE

• Acute myocardial infarction

Skeletal muscle damage, muscular dystrophy, inflammatory myopathies

Renal failure,

severe uremia

Shock and trauma

DRAWBACKS OF MYOGLOBIN

DRAWBACKS

Though sensitive ,Due to poor specificity, myoglobin levels do not always predict myocardial injury

Brain Natriuretic

Peptide (BNP)

• The natriuretic peptide family consists of

three peptides:

• Atrial natriuretic peptide (ANP),

• Brain natriuretic peptide (BNP), and

• C-type natriuretic peptide (CNP). clinical

significance of CNPis not clear.

• ANP is produced primarily in the

cardiac atria.

• BNP is present in human brain, but

more in the cardiac ventricles

BRAIN NATRIURETIC PEPTIDE (BNP)

Greatest proportion of circulating BNP is thought to come from the ventricles (left) Therefore it is a reliable

marker of ventricular function

• Patients with congestive

heart failure have high

plasma concentrations of

ANP and BNP.

LACTATE

DEHYDROGENASE

Lactate dehydrogenase catalyses the

conversion of pyruvate to lactate.

LDH -ISOFORMS

• M4 form is seen in skeletal

muscles while

• H4 form is seen in heart.

• Normally LDH-2 (H3M1)

concentration in blood is greater

than LDH-1 (H4); but this pattern

is reversed in myocardial

infarction;

LACTATE

DEHYDROGENASE

• LDH levels are also high in

Tissue breakdown

• Hemolysis

• cancer,

• meningitis,

• encephalitis, or HIV.

LACTATE

DEHYDROGENASE

• LDH has only limited diagnostic

value because of its

non specific nature.

• Normal value of LDH in serum

is 100-200 U/L

Creatine kinase(CK/CPK)

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

Creatine kinase(CK/MB)

• High specificity for cardiac tissue

Begins to rise 4-6 hours after onset of infarction

Peaks at about 12 hoursReturns to baseline at 24-48 hoursCan be used to indicate early re-

infarction if level normalizes and then increases again

Normal serum value for CK is 15-

100 U/L for males and 10-80 U/L

for females

• 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

• three subunits, TnC, TnT, and TnI

– Troponin-C (calcium ions)

– Troponin-T (tropomyosin)

– Troponin-I (actin)

Troponins

• Troponin T and I are not detected in

healthy individuals

• Troponins are seen in skeletal and

cardiac muscles, but not in smooth

muscles.

• Significant increase in Troponins

reflects myocardial necrosis

They are quantitated by ELISA or immuno

turbidimetric) reactions.

Troponin I (TnI)

Troponin I (TnI) is encoded by 3

different genes, giving rise to 3

isoforms;

• the "slow" and "fast" moving forms

are skeletal variety.

• Cardiac isoform is specific for

cardiac muscle;

• the amino acid sequence is different

in skeletal muscle isoform.

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

Cardiac 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.

• Therefore it has good utility for retrospectively

diagnosing AMI

• Remember, CK-MB returns to baseline by

•

Troponin Early

Rise(hrs)

Peak (Hrs) Duration

(Days)

Specficity Sensitivity

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

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

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

• Typical rise and gradual fall (troponin) or

more rapid rise and fall (CK-MB) of

biochemical markers of myocardial

necrosis with at least one of the

following:

• ischemic symptoms;

• development of pathologic Q waves on

the ECG;

• ECG changes indicative of ischemia (ST

segment elevation or depression);

• coronary artery intervention (e.g.,

coronary angioplasty)

Comparison

• SOS

• repeated at 2 and 72 hours later

• Assay times range from 5 to 30minutes

• TAT<60 min

• cTn T >0.1 ng/ml

• cTn I >1.0 ng/ml