LABORATORY DIAGNOSIS

OF ACUTE CORONARY
SYNDROME
Dennis Macapagal, MD

Objectives
By the end of this session you will be able to
1.Discuss the biochemical markers that are used
to detect acute myocardial infarction.
2.Discuss the sensitivity and specificity of CK-MB
and the Troponins for the detection of AMI
3.Discuss other tests that are indirectly helpful in
diagnosing an acute coronary syndrome.

Overview:
3 hours of ischemia=80% risk of cell
death
6 hours=100% cell death
For this reason, early recognition of
persistent ischemia and intervention
to restore blood flow are needed to
minimize cell death.

Overview:
Heart disease is an affliction
intimately tied to high technology.
Technology has had a causal role,
in part by allowing people to live
longer, and in part by enabling a
sedentary and overly consumptive
lifestyle.

Overview:
During the 20Th century, heart
disease rose from obscurity to
become the leading cause of
morbidity and mortality in developed
nations.

Overview:
Diagnosis and treatment of heart
disease also depend heavily on
advanced technology, including
electrophysiologic, imaging,
catheterization, surgical and clinical
laboratory testings.

Overview:
Heart disease statistics in the US:
1. est 80M (about 1 in 3) has some
form of CVD inc HPN.
2. 17M have a history of CHD
3. 8M have had an MI
4. 10M have had an angina pectoris
5. 6M have HF
6. 7M have experienced stroke

Overview:
Heart disease statistics in the US:
7. CVD is the underlying cause in
35% of all deaths (860K/year)
versus cancer, chronic LRTD,
accidents and DM combined.
8. annual cost is about
USD500Billion

Overview:
Heart disease statistics in the US:
8. There is an alarming increase in
obesity and type 2 DM which will
fuel the epidemic for many years
to come.

Non-laboratory risk factors for CHD:

1. Smoking (any smoking in the
past month)
2. HPN (>140/90mmHg)
3. Age (men over 45 years;F>55)
4. Obesity
5. DM
6. Sedentary lifestyle

Key points:
1. Measurement of proteins present in
cardiac myocytes indicates recent
damage to cardiac muscle.
2. Measurement of substances that are
damaging to the coronary arteries, or at
least have been proven association
with coronary heart disease, is used to
assess risk and select appropriate
preventive measures. The most
important lab risk factors are LIPIDS.

Serial sampling for cardiac markers

>>time window from death of muscle to
release markers in blood
>>ESC & ACC>>
1. on admission
2. 6-9 hours
3. 12-24 hours (if earlier specimens
were negative) and the clinical
suspicion for MI is high
>>POC testing must be available ALL

Serial sampling for cardiac markers

>>Historically: LDH & CK
>>20+ years ago>>Troponin antibodies
>>currently, the markers assay include:
-Myoglobin
-Troponins
-CK isoenzyme (MB)

CARDIAC ENZYME MARKERS:

Historical development:
1950s-La Due et al investigating
transaminases (AST)
Very simple principle:
when heart muscle diesrelease
proteins in blood (as markers)

Historical development:
Transaminases have not endured
as cardiac markers because they
are not specific to the heart. And
soon afterLDH and CK.

CREATINE PHOSPHOKINASE

Newer tests:
Troponinshighly specific
A complex of three proteins that
resides at regular intervals in the
thin filament of striated muscle.
TnT, TnI, TnC
TnC=identical forms in Type 2 and
cardiac muscle
TnI & TnT=cardiospecific

Troponins
In contrast with other markers, their
levels are almost undetectable or
zero in normal serum. (detection
limits of 0.01ng/ml)
The 99th percentile of the healthy
population is around 0.04ng/ml
depending on the assay.

Troponins
Levels above this threshold are
almost certainly indicative of
myocyte damage but possibly
reveal a much lesser amount of
damage than was detectable with
earlier cardiac markers such as CKMB.

Troponins
Note that elevation maybe found in
pericarditis, myocarditis, PE, renal
failure, sepsis, and other critical
illness.
Prolonged intense exercise, such
as marathon can cause small
elevations.

Troponins
NB:
in healthy newborns, levels as
high as 3.0ng/ml have been found!

Other markers for coronary risk:

C-REACTIVE PROTEIN

First isolated in 1930 in patients with

pneumococcal pneumonia
so named because it binds to the Cpolysaccharide of the pneumococcus
Later it was found that it appeared in
plasma during infectious or
inflammatory conditions.

It is the original acute phase

reactant protein.
Normal level=1mg/ml
in acute illness, levels may reach as
high as 300mg/ml
Baseline average was 1.5mg/ml for
those who developed MI.

It is pro inflammatory.
Still, CRP has an unclear role in the
pathogenesis of vascular disease.
But the AHA suggested:
asymptomatic men >50 years and
women >60 years be screened
even if LDL cholesterol is not
elevated.

HOMOCYSTEINE

Hcy is a sulfur containing amino

acid and a metabolic intermediate.
Homocystinuria:
-homozygous defect in the enzyme
cystathionine-Beta-synthase
-lens dislocation, osteoporosis, MR,
pyschiatric disturbance,
thromboembolic disease (e.g CHD)

High levels of Hcy:

1. endothelial injury
2. platelet activation
to name a few damaging effects
as a CHD marker, it parallels that of
a high cholesterol level

Folate supplements can bring down

elevated levels of Hcy.

Summary:
1. The most important disease
affecting heart is coronary heart
disease, which is atherosclerosis
affecting the coronary arteries.
CHD can lead to thrombotic
occlusion of coronary blood flow,
causing an acute coronary
syndrome or ACS. ACS with frank
necrosis of any amount is MI.

2. The primary tests for diagnosing

ACS are ECG, lab measurements
of cardiac markers which are
proteins released in circulation from
damaged heart muscle. The most
important cardiac marker today is
cardiac troponin (cTn).

3. Troponin is a complex of three

proteins, two of which are suitable
as specific cardiac marker tests:
cTnI and ctnT

4. There is a delay of a few hours

following MI before cTn is detected
in the circulation. It peaks about 24
hours and then declines over
several days

5. We can also measure risk factors

associated with the development
and progression of CHD: Lipids,
homocysteine, CRP

Assignment:
Read on
1. Brain natriuretic peptide
(BNP)
2. D-dimer