What Is the Ideal Level of hs-CRP?

Large scale clinical trials have used a hs-CRP cut point of 2 mg/ml for defining
This would imply that those who have hs-CRP above 2 mg/ml are at increased
However, a desirable value is probably less than 1 mg/ml. An hs-CRP level h
•Low risk: less than 1.0 mg/L
•Average risk: 1.0 to 3.0 mg/L
•High risk: above 3.0 mg/L
•Above 10 mg/mL usually indicates acute inflammation
CORONARY HEART DISEASE
Dysfunction of heart based on imbalance between oxygen supply
and oxygen demand.
Mechanism of ischemia :
1.Atherosclerosis with / without thrombus
2.Coronary arterial spasm
3.Embolism

Occlusion can be partial or complete and can be sudden or gradual.

ENZYME IN CORONARY HEART DISEASE
(SERUM CARDIAC MARKERS)
Coronary Heart Disease, chronic illness in which the coronary arteries, that
supply oxygen-carrying blood to the heart, become narrowed.
The coronary arteries become narrowed because of atherosclerosis, a
process in which fatty deposits called plaque build up on the inside wall of an
artery .
Plaque
- Oily molecules known as cholesterol, fibrous proteins, calcium
deposits, platelets, and debris from dead cells.
- Formation often begins in adolescence and progresses very slowly
over the course of decades. Gradually, the growing plaque thickens the wall
of the artery, reducing the space for blood to flow through.
 Blood supply reduced -- the heart does not receive sufficient
oxygen- oxygen deficit leads to two main consequences:
chest pain known as angina pectoris, or heart attack
in which part of the heart dies because oxygen deprivation.

ANGINA PECTORIS
A person has coronary arteries enough to supply blood to the
heart during normal activities, but too narrow to deliver sufficient
blood and oxygen when extra work is required of the heart / the
heart do not receive enough oxygen.
Angina is typically felt as a heavy, squeezing pain in the center of
the chest, pain may also spread to the neck, jaw, back, and left arm.
HEART ATTACK / MYOCARDIAL INFARCTION
Also known as a myocardial infarction,
Usually occurs when a blood clot forms inside a
coronary artery at the site of an atherosclerotic plaque.
The blood clot cuts off blood flow to part of the
heart.
In a small percentage of cases, blood flow is cut off
when the muscles in the artery wall contract suddenly.
This constriction, called vasospasm, can occur in an
artery that is only slightly narrowed by
atherosclerosis or even in a healthy artery.
If the oxygen deprivation is so severe and prolonged
that heart muscle cells begin to die for lack of
oxygen.
Obstuction of coronary blood suply :
* Partial or Complete
* Gradual or Sudden

Hypoxia

Myocard ishemia

Myocard infarc/ Cell damage

Cellular content appear in circulation

CK – CKMB – AST--LDH - TROPONIN

INCREASE
LABORATORY for MYOCARD INJURY
- CK AND CKMB
- Troponin I and Troponin T
- SGOT/AST
- LDH
- HBDH/ Alpha Hydroxy Butyric Dehygrogenase
- Myoglobin
- BNP
LABORATORY DIAGNOSIS
ATTENTION TO LAB EXAMINATION :
1.AVOID IM INJECTION
2.NEVER USE HEMOLYTIC SERA
3.STORE SERUM IMMEDIATELY IF EXAMINATION DELAYED
 Why It Is Done
Cardiac enzyme studies are done to:
1. Determine whether the patient are having a heart attack or
a threatened heart attack (unstable angina) --clinicaly have chest
pain, shortness of breath, nausea, sweating, and abnormal electrocardiography
results.
2. Check for injury to the heart after bypass surgery.
3. Determine if a procedure, such as percutaneous coronary intervention
(PCI)
4. Medicine to dissolve the blockage (thrombolytic medicine)
has successfully restored blood flow through a blocked coronary artery.
CARDIAC ENZYME STUDIES
* Cardiac enzyme studies measure the levels of the enzyme creatine
phosphokinase (CPK, CK), the protein troponin (TnI, TnT) in
the blood.
* Several enzyme AST, LDH, HBDH are not specific enzyme no longer
use --- lack specificity (Some of these enzymes and proteins are also
found in other body tissues, their levels in the blood may rise when
those other tissues are damaged )
* Low levels normally found in blood----- if heart muscle is
injured, such as from a heart attack -----the enzymes and proteins
leak out of damaged heart muscle cells -----levels in the bloodstream
rise.
* Cardiac enzyme studies must always be compared with
symptoms, physical examination findings, and
ECG /EKG (electrocardiogram) results.
CREATINE KINASE
Creatine kinase (CK) is an enzyme that is found in striated muscle,
myocard, tissues of the brain, kidney, lung, and gastrointestinal tract.
CK has 3 iso enzyme :
CK MB : high concentration in myocard.
CK BB : high concentration in brain tissue.
CK MM : high concentration in muscle .

Creatine Kinase has low sensitivity and specificity for cardiac

damage. (CK levels may be elevated in a number of noncardiac conditions,
including trauma, seizures, renal insufficiency, hyperthermia, and
hyperthyroidism).
.
CK
RISES WITHIN 4 - 6 HOURS AFTER MYOCARDIAL INJURY,
PEAKS BY 12 TO 24 HOURS
RETURNS TO BASELINE WITHIN THREE DAYS.

A serum CK level may be used as a screening test to

determine the need for more specific testing.
Although CK commonly was measured serially (along with CK-MB)
at the time of hospital admission and six to 12
hours after admission, this marker largely has been
replaced by cardiac troponins and CK-MB
CK MB
CK-MB is much more cardiac specific than CK alone,
and is useful for the early diagnosis of acute myocardial infarction.
CK-MB typically is detectable in the serum :
4 – 6 hours after the onset of ischemia,
peaks in 12 to 24 hours,
normalizes in 2 – 3 days.
Like the CK level, the peak CK-MB level does not predict infarct
size;
however, it can be used to detect early re infarction.
Serial CK-MB levels commonly are obtained at admission to the
emergency department and are repeated every 8 hours.
TROPONIN
There are three different troponins: troponin C, troponin T and troponin I.
Troponins T and I are only found in cardiac muscle
A troponin test measures the levels troponin T or troponin I proteins in the blood.
These proteins are released when the heart muscle has been damaged, such as occurs
with a heart attack.
The more damage there is to the heart, the greater the amount of troponin T and I there
will be in the blood.
Troponin T (1)
84% sensitivity for myocardial infarction 8 hours after onset of symptoms (1); 81%
specificity (1)
Troponin I
90% sensitivity for myocardial infarction 8 hours after onset of symptoms (1); 95%
specificity (1)
The most common reason to perform this test is to see if a heart
attack has occurred.
ORDER THIS TEST IF
- Have chest pain and other signs of a heart attack.
- Have angina that is getting worse, but no other signs of a heart
attack.
- To help detect and evaluate other causes of heart injury.
RESULT OF TROPONIN TEST
Slight increase in the troponin level will often mean there has been some damage to the
heart.
Very high levels of troponin are a sign that a heart attack has occurred.
Most patients who have had a heart attack have increased troponin levels within 6 hours.
After 12 hours, almost everyone who has had a heart attack will
have raised levels.
Troponin levels may remain high for 1 to 2 weeks after a heart
attack.
The test is usually repeated two more times over the next 6 to 24 hours.
Having normal troponin levels 12 hours after chest pain has started means a heart attack
is unlikely.
Increased troponin levels may also be due to:
- Abnormally fast heart beat
- High blood pressure in lung arteries (pulmonary hypertension)
- Blockage of a lung artery by a blood clot, fat, or tumor cells
(pulmonary embolus)
- Congestive heart failure
- Coronary artery spasm
-Inflammation of the heart muscle usually due to a virus
(myocarditis)
- Prolonged exercise (for example, due to marathons or triathlons)
- Trauma that injures the heart, such as a car accident/ trauma from surgery
- Weakening of the heart muscle (cardiomyopathy)
- Long-term kidney disease
TROPONIN
The most sensitive and specific test for myocardial damage. Because it has increased specificity
compared with CK-MB, troponin is a superior marker for myocardial injury.
After myocyte injury, troponin is released in 3 – 6 hours and persists for up to 7 - 10 days.
This allows MI to be detected if the patient presents late.

CKMB
It is relatively specific when skeletal muscle damage is not present.
Since it has a short duration, it cannot be used for late diagnosis of acute MI but can be used to
suggest infarct extension if levels rise again.
This is usually back to normal within 2–3 days.
ANOTHER ENZYME ( NOT SPECIFIC )
SGOT / AST :
RISE WITHIN 3 – 8 HOURS AFTER CARDIAC INJURY

LDH :
RISE WITHIN 12 – 24 HOURS AFTER CARDIAC INJURY, PEAK AT THIRD DAYS AND BECOME
NORMAL AT 8 - 9 DAY.

CONSENTRATION LDH1 AND LDH2 :

IF INFARK MYOCARD : LDH1 >LDH2 AND IT VERY CLEAR IN 24 HOURS.
LDH 1 > LDH2 : FLIPPED LDH
ENZ MEASUREMENT MUST BE REPEATED EVERY 8 – 12 HOURS.

CRP :
RISE ITS MARKS OF INFLAMATIONS (NON SPECIFICS FOR IMA)

HBDH / Alpha Hydroxy Butyric Dehydrogenase:

LDH now replace HBDH in cardiac enzyme.
MYOGLOBIN
Myoglobin present in both cardiac and skeletal muscle.
It can be detected in the serum as early as two hours after
myocardial necrosis begins.
Myoglobin has low cardiac specificity but high sensitivity,
which makes it most useful for ruling out myocardial infarction if
the level is normal in the first four to eight hours after the onset of
symptoms. 9

Myoglobin should be used in conjunction with other serum

markers, because its level peaks and falls rapidly in patients
with ischemia.
 Enzyme Hours Days

Starts to rise Peaks Return to normal

Total CPK 4–6 12 – 24 Around 3
CK – MB 4-6 12 – 24 2-3
AST 3-8 72 4
LDH 12 - 24 12 – 24 8–9
Troponin T 3- 6 12 – 24 7 - 14
Troponin I 3-6 12 - 24 7 – 14
BNP (Brain Natriuretic Peptide )
Also known as B type natriuretic peptide
- Amino acid polypeptide secreted by the ventricles of the heart in
response to excessive of heart muscle cells ( cardio myocytes)
- BNP named as such because it was originally identified in
extracts of porcine brand although in humans it is produced
mainly in the cardiac ventricles.
-
BNP test measures the amount of the BNP in blood.
BNP is made by heart and shows how well heart is working.
Normally, only a low amount of BNP is found in blood.
But if heart has to work harder than usual over a long period of
time, such as from heart failure ----- the heart releases more
BNP,---- increasing the blood level of BNP.
The BNP level may drop when treatment for heart failure is working.
CLINICAL SIGNIFICANCE
- Both BNP and NT ( proBNP ) levels in the blood normal level
rules out acute heart failure in the emergency setting.
- BNP or NT-proBNP can also be used for screening and
prognosis of heart failure

- BNP and NT-proBNP are also typically increased in patients

with left ventricular dysfunction, with or without symptoms
but the tests rather low specificity .
BNP also elevated in renal failure ( BNP is excreted renally ) and
decreased in obesity.
Normal values : < 50 pg /mL
100 – 500 pg/mL not conclusive
> 500 pg/mL consider positive
1.Indications Myocardial Infarction Evaluation
2.Best protocol for identifying AMI when EKG normal
1.Protocol
1.Obtain Troponin at 0 hours, 8 hours and 16 hours
1.Primary cardiac marker: Specific for cardiac event
2.Not useful for monitoring event extension
(Levels stay elevated for 14 days)
2.Obtain CK-MB at 0 hours, 8 hours, and 16 hours
1.Primary purpose: Follow cardiac event extension
2.Decreases more rapidly than Troponin after event
2.Test Sensitivity of combined protocol
1.Test Sensitivity: >98% at 8 hours
2.Test Specificity: 80 to 95% at 8 hours
3.References
1.Jernberg (2000) Am J Cardiol 86:1367
Troponin
Rises: 3-6 hours
Peaks: 20 hours
Duration: 7 - 14 days
Subunits
Troponin T
Troponin I (>1.0 suggests Acute MI)

Creatine Phosphokinase (CPK)

Rises: 4-6 hours
Peaks: 12-24 hours
Duration: 3 - 4 days
Subunits (Fractionate to CK-MB only if CPK increased)
CK-MB Fraction (duration for 2-3 days)
CK-MB over 5% of total CPK suggests Myocardial Injury
Myoglobin
Advantage: First cardiac marker to increase
Disadvantage: Poor Specificity (only helps if negative)
Rises: 1-2 hours
Peaks: 4-6 hours
Duration: 1-2 days

Glutamic oxaloacetic transaminase (AST, SGOT)

Peaks: 24-36 hours
Duration: 5 days
Lactic Dehydrogenase (LDH)
Peaks: 24-48 hours
Duration: 14 days .

White Blood Cell Count

Predicts adverse events in Unstable Angina
Morbidity and mortality increase with increased
WBCs
WBC Count >10,000: High risk of adverse event
WBC Count >15,000: Very high risk of adverse event

References
Cannon (2001) Am J Cardiol 87:636
Copeptin in blood circulation
The concentration of copeptin in the blood circulation ranges from
1 to 12 pmol/L in healthy individuals.
The levels of copeptine are slightly higher in men than in
women and are not influenced by age.
In response to serum osmolality fluctuations, the kinetics of
copeptine are comparable to those of vasopressin.
For example, patients with an electrolyte disorders such
as diabetes insipidus with very low levels of vasopressin also
show very low levels of copeptin in blood plasma.
On the other hand, patients suffering from syndrome of
inappropriate antidiuretic hormone secretion show both high
levels of vasopressin and copeptin.[9]
Copeptin and acute myocardial infarction
Several studies have shown that copeptin is released very early
during the onset of an acute myocardial infarction(AMI), raising
the question of its potential value in the diagnosis of AMI and
particularly in ruling-out AMI.
Indeed, copeptin is released much earlier than Troponin making
the interpretation of their complementary kinetics a useful tool
to rule-out AMI.
It has been shown that the combination of
a negative
result of troponin together with a negative result
of copeptin can rule-out AMI at emergency
department presentation with a negative
predictive value ranging from 95% to 100%.[11]
Copeptin and cardiogenic shock
High concentrations of vasopressin during a cardiogenic
shock have been widely described.
It has been shown that the kinetics of copeptin are similar to
vasopressin in that context.

Copeptin in heart failure.

The prognostic value of vasopressin for prediction of outcome in
patients suffering from heart failure has been known since the
nineties. Patients presenting with high levels of vasopressin have
a worsened outcome.
Recently, a similar interest has been demonstrated for copeptin
in heart failure
HIGH-SENSITIVE CARDIAC TROPONIN T (hs-cTnT)
The recent development of a high-sensitive cardiac
troponin T (hs-cTnT) assay permits detection of very low
levels of cTnT.
Using the hs-cTnT assay improves the overall diagnostic
accuracy in patients with suspected AMI, while a
negative result also has a high negative
predictive value.
The gain in sensitivity may be particularly important in
patients with a short duration from symptom onset to
admission.
Measurement of cardiac troponin T with the hs-cTnT assay may
provide strong prognostic information in patients with acute
coronary syndromes, stable coronary artery disease, heart failure
and even in the general population; however, increased sensitivity
comes at a cost of decreased specificity.
Serial testing, as well as clinical context and co-existing diseases,
are likely to become increasingly important for the interpretation
of hs-cTnT assay results.
KEPUSTAKAAN:
1.Interpertation of Diagnostic tests. 8th ed. Jacques Wallach MD 2007
2.Laboratory Tests and Diagnostic Procedures. 5th ed .Cynthia C Chernecky,
Barbara J Berger 2008
3.Laboratory Test Handbook 2nd ed . David s Jacobs cs 1988
4.Bhatia V, Nayyar P Dhindsa (2003). Brain natriuretic peptide in diagnosis and
treatment of heart failure. J Postgrad Med 49 (2) 182- 5 PMID 12867703
5.Jerenberg (2000) Am J Cardiol 86 – 1367.
6. Cannon (2001) Am J Cardiol 87:636.
7. Journal of Geriatric Cardiology 2013 Mar, 10(1) : 102 – 109
8. World J Cardiology 2015 May 26; 7(5): 243–276.
TROPONIN ELEVATION IN HEART FAILURE
Based on the type of assay used, a range of elevated cTn values, indicative of myocardial
injury with necrosis, may be seen in patients with a heart failure (HF) syndrome[23]. In
stable heart failure patients, the median concentration of hs-cTnT is 12 ng/L, which is
very close to the 99th percentile URL of 14 ng/L for this assay[24]. Hence, using hs-cTn
assays, cTn concentrations may be measured in nearly all patients with HF. Many HF
patients exceed the 99th percentile URL, especially those patients with severe
decompensated HF syndrome[25]. While type 1 MI is an important cause of acutely
decompensated heart failure, other mechanism(s) leading to troponin elevation in HF
syndromes such as supply-demand inequity (type 2 MI) should be considered. Non-
coronary triggers, such as anemia, cellular necrosis, apoptosis, or autophagy in the
context of wall stress may cause troponin release in HF, as can the toxic effects of
circulating neurohormones, toxins, inflammation, and infiltrative processes. Nonetheless,
in patients with HF, troponin elevation independent of its mechanism, is strongly
predictive of an adverse outcome and should not be ignored[25].
Go to:
HIGH SENSITIVITY TROPONIN ASSAYS
Highly sensitive assays for cTnT and cTnI are available and are widely used in
many parts of the world, although they are not generally used at the present
time in the United States[26]. Two criteria should be met for high sensitivity
troponin assays (hs-Tn). First, the coefficient of variation at the 99th percentile
value should be ≤ 10%. Second, the assay should be able to measure cTn
concentrations below the 99thpercentile in ≥ 95% of normal individuals[27].
Compared with standard cTn assays, the hs-cTn assays have improved sensitivity
and discrimination for MI, particularly in the first 3 to 6 h after symptom
onset[28]. These advantages are somewhat offset by a decrease in specificity for
MI[28-30] and concerns regarding the broad application of these tests,
especially in populations with a low MI prevalence.
There is controversy regarding the metrics that should be used with hs-cTn
assays for the diagnosis of AMI. In this regard, attempts have been made to
define in these assays the optimal value for relative change or deltas in hs-cTn
concentrations. Higher deltas increase specificity while lower ones improve
sensitivity. The potential for analytical interferences with hs-cTn assays is greater
than with conventional assays. Examples include reductions in hs-cTnT
concentrations due to hemolysis and autoantibodies or increases due to
heterophilic antibodies[31]. Studies suggest that an absolute increase of hs-cTnT
values, i.e., > 7 ng/L over 2 h, is superior to relative percentage changes from
the baseline in the diagnosis of MI[32-34].
According to the recent guideline for the management of patients with acute
coronary syndromes, blood samples for high-sensitivity cardiac troponin
measurements should be obtained at presentation and 3 h after admission[35].
Measurements of hs-cTn should be repeated 6 h after admission in patients in
whom the 3 h values are unchanged but in whom the clinical suspicion of MI is
still high[36].
Distinguishing between type 1 and type 2 MI is challenging with high sensitivity
troponin measurements. As troponin assay sensitivity increases, the frequency
of possible type 2 MI increases and the distinction from type 1 MI becomes
more complicated. Moreover, the diagnostic accuracy of a baseline
measurement of hs-cTn for presence of AMI in patients with renal insufficiency
is poor[37]. Nevertheless, elevated hs-cTns have important prognostic
implications and patients require additional evaluations because a high cTnT
level is associated with all-cause and cardiovascular mortality and with incident
heart failure in 3 population based studies[30].
The METABOLIC SYNDROME is defined as a constellation of
three or more of the following :
*ABDOMINAL OBESITY
*TRIGLYSERIDES > 150 mg / dL
*HDL CHOL < 40 mg/dL (Male) , < 50 mg/dL (Female)
*FASTING GLUCOSE > 110 mg/dL
*HYPERTENSI

THIS SYNDROME , RECODNIZED AS A MAYOR CONTRIBUTOR TO

CORONARY HEART DISEASE RISK.
RISK FACTORS FOR ISCHEMIC HEART DISEASE
1. FAMILY HYSTORY
2. MALE
3.DYSLIPIDEMIA { LOW HDL (INCL apo A), HIGHT LDL (INCL apoB)}
4.DIABETES MELLITUS
5.HYPERTENSI
6.PHYSICAL IN ACTIVITY
7.OBESITY
8. SMOKERS
What is hs-CRP?
C-reactive protein (CRP) is a protein that the liver makes when there is inflammation in the body. It's also called
a marker of inflammation, and can be measured with an hs-CRP (high-sensitivity C-reactive protein) test,
sometimes also called a CRP test. Inflammation is a way for the body to protect itself from injuries or infections,
and inflammation can be caused by smoking, high blood pressure, and high blood sugar. Excessive inflammation
has been linked to heart disease.
Why is hs-CRP tested?
hs-CRP testing is used to predict the risk of developing heart disease and its complications, such as heart
attacks, strokes, peripheral arterial disease, and sudden cardiac death. Higher hs-CRP levels are linked to a higher
risk of these problems.
About 50% of all heart attacks and strokes affect people who seem healthy and have normal cholesterol levels. hs-
CRP testing offers a way to identify some of these people so that they can reduce their heart disease risk before
they have a heart attack or stroke. That's why it's important to have both hs-CRP and cholesterol tests if your
doctor recommends it. Ask your doctor if you should have your cholesterol and/or hs-CRP levels tested.
How is hs-CRP tested?
CRP is measured with a simple blood test, called a high-sensitivity CRP (hs-CRP), that can be done in the lab using a
blood test. To save time, hs-CRP testing can be done at the same time as cholesterol testing. However, it can also
be done separately. hs-CRP testing can be done at any time of day because it does not require fasting.
What do the results mean?
In general, the higher the hs-CRP, the higher your risk of developing heart disease and its complications such
as heart attacks, strokes, peripheral vascular disease, and sudden cardiac death. The lower your hs-CRP levels, the
better. Some people with high hs-CRP levels may need to take cholesterol medications to reduce their risk of heart
disease, even if their cholesterol levels are not high.
Keep in mind that hs-CRP levels are just part of the picture. Your doctor will also consider other factors when
calculating your risk of heart disease and recommending a treatment plan.