Download Clinic Laboratory Tests in Cardiac Disease1.82 MB

Clinic Laboratory Tests in
Cardiac Disease
Prof. Dr. ARZU SEVEN
Cardiac markers should be:
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absolutely heart specific
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highyl sensitive
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able to differentiate irreversible damage from
reversible
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able to detect reocclusion and reinfarction
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able to monitor reperfusion therapy
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able to estimate size of infarct and prognosis
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stable
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able to make measurements rapidly
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easy to perform
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cost effective
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Ruling out AMI requires a test with high diagnostic
sensitivity.
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Ruling in AMI requires a test with high specificity.
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A single test that will quickly and accurately assess AMI
(acute myocardial infarction) does not exist.
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A combination of markers is used :
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An early marker that increases within 6 hr. after
onset of symptoms
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A definite marker that increases after 6-9 hrs.
and remains high for several days
Enzymes as Cardiac Markers
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Creatine kinase (CK or CPK)
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Aspartate amino transferase (AST)
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Lactate dehydrogenase (LDH or LD)
Creatine Kinase
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A cytoplasmic and mitochondriac enzyme
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Total CK is %40 sensitive and %80 specific
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CK-1(BB) : Brain
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CK-2(MB) :Myocardium
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CK-3(MM) :Skeletal muscle ,heart
CK-3 has 3 isoforms :CK-31, CK-32 and CK-33
(posttranslational products)
CK-2 has 2 isoforms
Half life :CK-31 > CK-32>CK-33, CK-21>CK-22
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CK-MB (CK-2) has the most specificity for cardiac
muscle (>%85)
CK-MB (CK-2) accounts for only 3-20 % of total
CK activity in heart
Normal skeletal muscle contains 1 % CK-2
CK-2 is increased in severe skeletal muscle injury
(trauma/surgery ),chronic muscle disease (muscular
dystrophy, polymyositis ) and extreme exercise.
Reason:Regeneration process of muscle (reexpression of
CK-MB genes )
In AMI,CK-MB increases at least 4-6 hr.after onset of
chest pain,makes a peak at 12-24 hr. and returns to
baseline level in 2-3 days (t 1/2 is 10-12 hr )
Factors that might affect the classic pattern :
1-Size of infarction
2-CK-2 composition in myocardium
3-Concomitant skelatal muscle injury and
reperfusion
Differentation of increased CK-2 due to heart
or muscle  monoclonic anti CK-2 antibody
based assays
%relative index (%RI)= CK-2 activity /total CK X %100
helpful in the detection of AMI
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CK-22: the predominant isoform in blood collected
2-6 hr. after AMI .It makes a peak ≈10-18
hr.,decreases rapidly 12-24 hr concomitantly as
CK-21 gradually increases.
Following trombolitic therapy in AMI patients,
greater than two fold increases of CK-2 occur
within 90 min. of reperfusion
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The rate of which CK-2 isoform is released from
the myocardium to circulation appears to be the
more useful index of coronary reperfusion
CK22 ∕ CK-21 ratio→best discriminant within
1 hr. after treatment
Lactate Dehydrogenase (LDH)
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A cytoplasmic enzyme found in skeletal, muscle,
liver, heart, kidney and red blood cells
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5 izoenzymes, composed of 4 subunit peptides of
2 distinct types:M (muscle ), H (heart)
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LDH isoenzyme determination increases
specificity for cardiac tissue.
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LD1 (HHHH):moves fastest towards anode
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LD5 (MMMM):moves closest towards cathode
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LD2 (HHHM )
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LD3 (HHMM )
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LD4 (HMMM )
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LD1 in heart,kidney(cortex), red blood cells
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LD5 in liver,skeletal muscle
In healthy adults:
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14-26 % LD1 (slow removal )
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29-39% LD2
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20-26% LD3
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8-16 % LD4
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6-16 % LD5 (rapid disappearance )
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Not a tissue specific enzyme
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In AMI total LD -elevation at 12-18 hr
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peak at 48-72 hr
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return to baseline level after 6-10 days
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LD 1 (heart)
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elevation at 10-12 hr
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clinical specificity 85-90 in patients
suspected of AMI
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peak at 72-144 hr
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return to normal >10 days
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Total LD patern ≈LD1 pattern (contrast with total
CK and CK-2 pattern)
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Because of its prolonged half life, LD-1 is a
clinically sensitive (%90) marker for infarction
when measured after 24 hr.
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LD1∕LD2 >1,0 →FLIPPED PATTERN
(clinical sensitivity %75 , clinical specificity 85-90 in
patients suspected of AMI)
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if CK-2 values are diagnostic for AMI, cancel LD
isoenzyme test request, because LD isoenzyme
results don’t increase the clinical specificity of
diagnostic CK-2 results for AMI
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As with CK-2 in skeletal muscle, the heart specific
LD-1 isoenzyme in skeletal muscle can increase
twofold during a 9-wk exercise training, with
paralel decreases in LD-5
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LD and isoenzymes play no role in unstable and
stable angina.
Aspartate aminotransferase (AST )
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Widely distributed in many tissues
Highest concentrations are found in cardiac tissue,
liver and skeletal muscle.
Clinical utility in hepatocellular disorders and skeletal
involvement.
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Unuseful in diagnosis of AMI
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Beginsto rise within 6-8 hr.
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Makes a peak at 24 hr.
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Generally returns to normal within 5 days.
Myoglobin
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O2 binding protein of cardiac and skeletal muscle.
Low molecular weight and cytoplasmic location-early
appearance in circulation after muscle injury
Cleared rapidly by kidney→unreliable as a long term
marker of cardiac damage
Cardiac muscle trauma, skeletal muscle trauma, Crush
injury and AMI cause an increase in myoglobin levels.
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serum myoglobin methods are unable to
distinguish the tissue of origin
reference intervals vary according to age, rate
and sex
1. age   myoglobulin 
2. male > female
3. black > white
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very sensitive early diagnostic marker for AMI
(%90-100) ,poor clinical specificity (%60-95)
rises as early as 1 hr. after AMI, peaks in 4-12 hr 
reflects the early course of myocardial necrosis,
lasts for 24 hr.
the role of myoglobin in the detection of AMI is
within 0-4hr. (CK-2 is within its reference level).
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To improve clinical specificity,carbonic anhydrase III
(CAIII) should be measured.
After AMI, CK-2 and myoglobin increase,but CA III
remains unchanged.In severe skeletal muscle trauma
(exercise, shock and i.m injection ), CK-2, myoglobin and
CAIII increase.
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If myoglobin remains unchanged and within reference
levels on multiple,early samplings within 3-6 hr. after
onset of chest pain,there is 100 %certainty that muscle
(either skeletal or cardiac ) injury has NOT occurred
recently—Negative predictor
Myoglobin/total CK >5 reperfusion indicator (clinical
sensitivity 75 %,clinical specificity 96 % )
Cardiac Troponins
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Contractile proteins found in muscle that play role in
actin-myosin interaction
Complex of 3 protein subunits :
1. troponin C: calcium binding component
2. troponin I: inhibitory component
3. troponin T:tropomyozin_binding component
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Subunits exist in many isoforms like CK
Distribution of these isoforms varies between cardiac
muscle and slow/fast twitch skeletal muscle
Only 2 major isoforms of troponin C are found in
human heart and skeletal muscle
Troponin is located in ;
1. myofibril (%94-97)
2. cytoplasm (%3-6)
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Cardiac troponin I and T have different amino acid
sequences
Human cTn I has an additional 3I AA residue
compared to skeletal muscle Tn I (cardiac specificity)
11 AA residue gives troponin T unique cardiac
specificity
Early release kinetics of both cTnI and cTnT are
similiar to CK-2 after AMI
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Elevation at 4-8 hr.
Remains elevated at 4-10 days (replaces LD
isoenzyme assay in the detection of patients
presenting late after AMI)
Cardiac specificity of troponin I and T eliminate the
false clinical impression of AMI in patients with high
CK-2 after skeletal muscle injury
Troponin T (cTnT)
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Clinical sensitivity is similiar to that of CK-2 in the 48
hr. after the onset of pain (%50-65)
Rises within a few hrs. after chest pain,peaks by day
2 →Like CK-2, cTnT is insufficient for effective early
diagnosis
However cTnT remains high for a longer time (up to
7-10 days) giving high clinical sensitivity (>%90) up to
5-7 days after AMI .
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When AMI patients are grouped separately from
other cardiovascular pathologies 
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Clinical specificity for cTnT  %40-60
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“
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“ CK-2  %75-80
When AMI patients are grouped with unstable
angina and minor myocardial injury  specificity for
cTnT improves to >%80
Troponin I (cTnI)
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Comparable to CK-2 for diagnostic sensitivity of AMI
in the first 48-72 hr.
After 72-96 hr cTnI sensitivity increases
Has serial rise and fall kinetics similiar to CK-2 after
AMI during 48-72 hr, remains elevated 3-7 days
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In patients with high CK-2 concentrations due to
acute skeletal muscle injury following marathon
racing, Duchenne’s muscular dystrophy, chronic renal
failure requiring dialysis, cTn I is NOT elevated
cTn I should be measured in patients with falsely
increased CK-2 values for the detection of cardiac
injury
cTn I has (+) predictive value (%95) and (-) predictive
value (%100)
cTnI is successful:
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in ruling out AMI patients with cocaine induced chest
pain
in accurately detecting cardiac injury in patients with
blunt chest trauma
in accurately determining high incidence of cardiac
injury in critically ill patients
in risk stratification analysis
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neither cTn I nor cTn T offered advantages over
myoglobin in the early (< 2 hr) screening for AMI,
both troponins could identify AMI > 6 hr after
presentation.
elevation of troponin T or I within 6 hr of symptoms
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increased risk of complication
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need for intervention
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increased cTnI in unstable angina predicts a poorer
clinical outcome
to determine the effects of reperfusion, cTnT
should be measured at the time of trombolytic
therapy initiation and 90 min. after therapy
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BNP and NT – pro BNP
(Brain natriuretic peptide)
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To diagnose congestive heart failure
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To grade the severity of heart failure
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To differentiate between heart failure and lung disease
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To monitor the effects of therapy for heart failure
NT pro BNP is a marker in the blood for BNP, a hormone that
rises during cardiac stress
Homocysteine
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An amino acid
Too much homocysteine in the blood is related
to a higher risk of coronary heart diseases,
stroke and peripheral vascular diseases.
Has an effect on atherosclerosis.
High levels of homocysteine are the result of
lack of certain B Vitms. ,inheritance or dietary
excess and have been implicated in vascular wall
injury.
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Testing for plasma homocysteine levels can
improve the assessment of risk, particularly in
patients with a personal family history of
cardiovascular disease.
CRP
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Sensitive marker of acute and chronic
inflammation and infection and in such cases is
increased several hundred- fold.
Useful in predicting the risk for a thrombotic
event ( a blood clot causing MI )
Heart patients who have persistant CRP levels
between 4-10 mg/dl with clinical evidence of
low grade inflammation should be considered to
be at increased risk for thrombosis.
CRP protein results may be affected by the use of
-oral contraceptives
-NSAID’s
-steroids
-salicylates
-IUD
Homocysteine levels may be affected by
-smoking
-DM
-coffee
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