This document discusses various cardiac biomarkers used in the diagnosis and management of acute coronary syndrome (ACS) and myocardial infarction (MI). It provides information on biomarkers such as creatine kinase (CK), CK-MB isoenzyme, cardiac troponins, myoglobin, and others. It describes the timing of elevation, specificity, and clinical utility of each biomarker as well as situations where they may be falsely elevated or chronically elevated in conditions like heart failure or renal disease. Newer emerging biomarkers are also mentioned.

1. Dr.S.Sethupathy
RMMC,
Annamalai university

2. 
“A biomarker is a substance used as an indicator of a
biologic state.
It is a characteristic
It is objectively measured
It is evaluated as an indicator of normal biologic
processes, pathogenic processes, or pharmacologic
responses to a therapeutic intervention.
Biomarkers

3. 
“Cardiac markers are substances released
from heart muscle when it is damaged as a
result of myocardial infarction.”
Cardiac markers

4. 
Objectives
1) CKMB and TI false-positive and false-negative
possibilities should be entertained
2) Associations between TI, CKMB and CK in
patients with suspected acute coronary
syndrome and elevations in non-ACS
situations
3) New markers
Cardiac markers

5. 
Triad of Chest pain, ECG manifestations and
elevations of biomarkers of cardiac injury
 Chest Pain: highly variable and subjective
 ECG: Objective ST or T-wave changes
 Biomarker elevations: Objective data defining
ACS/AMI
Diagnosis of AMI

6. 

7. 

8. 

9. 

10. 
 Acute coronary syndrome (ACS)- any group of
symptoms attributed to obstruction of the
coronary arteries.
 Common - chest pain, often radiating to the left
arm or angle of the jaw, pressure-like in
character, with nausea and sweating.
 ACS due to one of three problems:
 non-ST segment elevation myocardial
infarction (NSTEMI) – 25%
 ST segment elevation myocardial infarction (STEMI)
– 30%,
 unstable angina (38%).
ACS

11. 
 Unstable angina is angina pectoris -disruption of
an atherosclerotic plaque with partial thrombosis
and embolization or vasospasm.
 Occurs at rest or minimal exertion and usually
lasts less than 20 minutes
 severe flank pain, new onset (i.e., within 1
month)
 more severe, prolonged, or increased frequency
than before
 50% of people with unstable angina -with
myocardial necrosis - elevated CK-MB and
troponin T or I
 non-ST elevation myocardial infarction.
Unstable angina

12. 

13. 

14. 

15. 

16. 

17. 

18. 
 Natriuretic peptide - Both B-type natriuretic peptide
(BNP) and N-terminal Pro BNP can be applied to
predict the risk of death and heart failure following
ACS.
 Monocyte chemo attractive protein (MCP)-1 -
identify patients with a higher risk of adverse
outcomes after ACS.
Prognostic markers

19. 
 Acute Myocardial infarction happens when blood
stops flowing properly to part of the heart and the
heart muscle is injured due to hypoxia.
 Troponin levels: Normally not found in serum; it is
released only when myocardial necrosis occurs.
 Creatine kinase (CK) levels: CK-MB levels increase
within 3-12 hours of the onset of chest pain, reach
peak values within 24 hours, and return to baseline
after 48-72 hours
AMI

20. 
 The ECG is the most important tool in the initial
evaluation and triage of patients in whom an acute
coronary syndrome (ACS), such as myocardial infarction,
is suspected.
 It is confirmatory of the diagnosis in approximately 80%
of cases.
 Cardiac imaging – in individuals with highly probable or
confirmed ACS, a coronary angiogram can be used to
definitively diagnose or rule out coronary artery disease.
Electrocardiography

21. 
 Myoglobin levels: Myoglobin is released more
rapidly from infarcted myocardium than is troponin;
urine myoglobin levels rise within 1-4 hours from
the onset of chest pain
 Complete blood count
 Chemistry profile
 Lipid profile
 C-reactive protein and other inflammation markers
Investigations

22. 
 Ischemia-Modified Albumin (IMA) - In cases of
Ischemia - Albumin undergoes a conformational
change and loses its ability to bind transitional
metals (copper or cobalt).
 IMA- Alb- N terminus –Cobalt binding –
DTT(dithiothreitol) – complexes with unbound –
500nm- > 85 U/ml – C.Ishemia
 IMA can be used to assess the proportion of
modified albumin in ischemia. Its use is limited to
ruling out ischemia rather than a diagnostic test for
the occurrence of ischemia.
Biomarkers

23. 
 Myeloperoxidase (MPO) - The levels of circulating
MPO, a leukocyte enzyme, elevate early after ACS
and can be used as an early marker for the condition.
 Glycogen Phosphorylase Isoenzyme BB-(GPBB) is an
early marker of cardiac ischemia and is one of
three isoenzyme of Glycogen Phosphorylase.
 Troponin is a late cardiac marker of ACS
Biomarkers

24. Diagnosing AMI/ACS
Detecting myocardial damage
Risk stratification of the patients
Commenting on Prognosis
 In ACS, pre and post PCI/reperfusion therapy
 CHF
 Renal Disease
What biomarkers are good
for:

25. 
CK (CPK)
CK-MB
Troponin-I/T
LD (LDH)
Myoglobin
ALT/AST
Others
Cardiac biomarkers

26. 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
phosphocreatine serves as an energy reservoir for the rapid regeneration
of ATP)
The CK enzyme consists of two subunits,
B (brain type) or
M (muscle type),
three different isoenzymes: CK-MM, CK-BB and CK-MB
Creatine Kinase

27. 
 CK-BB occurs mainly in tissues, rarely of any significance in the
bloodstream
 Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1%)
 Sensitive lab tests can pick up these low levels of CK-MB from
skeletal muscle
 The myocardium has CK-MM at 70% and CK-MB at ~30%
 CK therefore, lacks specificity for cardiac damage and needs to be
augmented with the MB fraction and Relative Index (RI) to indicate true
cardiac damage
CK

28. 
 Needs >two-fold increase with simultaneous increase in CK-MB
to be diagnostic for MI
 problematic for use in patients with little muscle mass
 Increases 4-6 hours after onset of MI
 Peak activity is at 18 to 24 hours
 Usually has returned to baseline levels by 36 hours
 False positive (for MI) CK elevation can be seen in:
 Significant skeletal muscle injury
 Significant CNS damage (Stroke/Trauma)
 Occasionally from GI, renal, urologic disease
 elevations due to non-cardiac causes- shows a flatter curve,
rising and disappearing at a slower pace than a cardiac source
CK

29.  High specificity for cardiac tissue
 Begins to rise 4-6 hours after onset of infarction
 Peaks at about 12 hours
 Returns to baseline at 24-36 hours
 Can be used to indicate early re-infarction if level
normalizes and then increases again
 Lab test for mass better
 mass assays are more sensitive.
CK-MB

30. 
 False positive (for MI) CK-MB elevation :
 Significant skeletal muscle injury
 Cardiac injury - other than MI
 Cardioversion, Defibrillation
 Blunt chest trauma (Sports injuries)
 Cardiac AND non-cardiac surgical procedures
 Cocaine abuse (vasospasm, tachycardia,
perfusion/demand mismatch)
 Severe myocarditis
CK-MB

31. Troponin - in skeletal as well as cardiac muscle
Troponin has three subunits, TnC, TnT, and TnI
Troponin-C binds to calcium ions
Troponin-T binds to tropomyosin
Troponin-I binds to actin in thin myofilaments to hold
the troponin-tropomyosin complex in place
So far no source of Troponin-I outside the heart,
but some Troponin-T in skeletal muscle.
Highly specific - Troponin-I
Troponin

32. 
 Increased level of the cardiac Protein isoform of
troponin circulating in the blood- a biomarker of
myocardial infarction.
 Raised Troponin levels indicate cardiac muscle cell
death as the enzyme is released into the blood upon
injury to the heart.
 cardiac troponin I and T are very sensitive and
specific indicators of damage to myocardium.
 To differentiate unstable angina and MI in chest
pain or acute coronary syndrome.
Troponin

33. 
 Laboratory range definition:
 Cutoff is set at 99th percentile of a normal reference
population
 Since troponin levels are undetectable in normal
subjects
 This 99th percentile corresponds to <0.06
 -heparin in sample can result in lowered values
 Elevated troponin level within 2-3 hours of emergency
department (ED) arrival, versus 6-9 hours or more
with CK-MB and other cardiac markers.
More about Troponin

34.  Troponin-I levels begin to rise 2-3 hours after
onset of MI and roughly 80% of patients with
AMI will have positive values at 3 hours
 Elevations in Troponin-I and Troponin-T can
persist for up to 10 days after MI
 It has good utility for retrospectively diagnosing
AMI
 CK-MB returns to baseline by 48 hours
 Troponin release can also be precipitated by
other conditions that cause myocardial damage
 Cardiac troponin T and I can be used to monitor drug and
toxin-induced cardiomyocyte toxicity.
Troponin Use

35. 
Since normal people have virtually nil levels
of troponin in serum, it is thought that
detectable levels indicate chronic disease
even if not acute myocardial damage
Degree of elevation of Troponin value can
give prognostic information
72-96 hour peak TI correlates with infarct size
Not with other biomarkers
Troponin Influence on
Prognosis

36. 
 Used along with aminotransferases to diagnose AMI.
 LD is non-specific for cardiac tissue , which contains
LD-1.
 pancreas, kidney, stomach tissue and red cells also
contain LD-1.
 In AMI, LD rises at about 10 hours,
 peaks at 24-48 hours,
 remains elevated for up to 8 days.
 AST very non specific – now not used for AMI
LDH

37. 
 Ubiquitous small-size heme protein released from all
damaged tissues.
 Increases often occur more rapidly than TI and CK.
 Not utilized often for AMI/cardiac damage
assessment because of its very rapid metabolism (short
plasma half-life) causing short burst increases that are
difficult to assess clinically.
 its lack of specificity for cardiac tissue.
Myoglobin

38. 
CK (U/L) Normal Range: 0-215
CKMB - < 25 U/L
 If CK-MB is elevated
 The ratio of CK-MB to total CK (relative index) is more
than 2.5–3
 it is AMI.
 A high CK with index below this value suggests that
skeletal muscle damage.
 BNP - <100 pg/ml NO HF
 > 400 pg/ml HF
Reference range

39. 
LESS THAN 0.07 NG/ML: NEGATIVE
0.07 - 0.5 NG/ML: CONSISTENT WITH
POSSIBLE CARDIAC DAMAGE AND
POSSIBLE INCREASED CLINICAL RISK.
>0.5 NG/ML: CONSISTENT WITH CARDIAC
DAMAGE, INCREASED CLINICAL RISK
AND MYOCARDIAL INFARCTION.
TROPONIN I

40. 
Timing Summary
TEST ONSET PEAK DURATION
CK/CK-MB 3-12 hours 18-24 hours 36-48 hours
Troponins 3-12 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

41. 
 “clinical evidence of myocardial ischemia” is
necessary in addition to elevated biochemical
markers .
 Example : hypoxia due to hypovolemia, GI
bleeding,CO,CN poisoning, sepsis, Pul.emb, Pul.H,
COPD,atrial fibrillation, myocarditis, myocardial
contusion, renal failure , PET and tachycardia
 Cardiac troponin T and I can be used to monitor
drug and toxin-induced cardiomyocyte toxicity.
Elevated cardiac biomarkers in non-
ACS situations

42.  Situations of prolonged mycyte ischemia
 prolonged/profound hypotension, chronic, pulmonary
hypertension
 CPR/Cardiac contusion
 Electrical Cardioversio
 PE, pericarditis, myocarditis
 Sepsis ( myocardial oxygen demand-supply mismatch)
 Apical Ballooning syndrome-- “Takotsubo
Cardiomyopathy”
 Chemotherapy, e.g. Adriamycin, Herceptin
 Toxins, cocaine
 Extreme exertion--Marathons, ultramarathons, Military
basic training
 LVH--leads to subendocardial ischemia by increased O2
demand from increased mass
 HF
Elevated cardiac biomarkers in non-
ACS sitouations

43. 
 CAD is highly prevalent in patients with end-stage renal disease and
patients on dialysis.
 HTN and DM
 ESRD as well as dialysis change homeostatic mechanisms for
lipids, calcium and electrolytes
 HF patients and ESRD patients have low levels of troponin
elevations chronically without evidence of myocardial damage,
although the mechanism and significance are not known.
 Possible reasons parallel those for HF:
 significant LVH, endothelial dysfunction, loss of
cardiomyocyte membrane integrity and possibly impaired
renal excretion
Biomarkers in Renal
Failure

44. 
 Chronically elevated troponin levels indicate a worse long-
term prognosis for cardiovascular outcomes
 False positives- with use of troponin-T in ESRD patients but
not as much with troponin-I
 CK: plasma concentrations are elevated in 30-70% of
dialysis patients at baseline, secondary to skeletal
myopathy, intramuscular injections and reduced clearance
 CK-MB: 30-50% of dialysis patients exhibit an elevation in
the MB fraction >5% without evidence of myocardial
ischemia
 The most specific marker for suspected AMI in ESRD
patients is Troponin-I with an appropriate sequential rise
Biomarkers in Renal
Failure

45. 
 Small elevations in TI are chronically found in patients with heart
failure, without current symptoms of ischemia
 The presence of TI remained an independent predictor of death
 A positive TI in a hospitalized patient with HF is associated with a
higher in-hospital mortality.
 The presumed mechanism of cardiac troponin release in HF is from
 myocardial strain-volume and pressure overload of both ventricles
causing excessive wall tension leading to decreased
subendocardial myocyte perfusion.
 There is a correlation of elevated BNP and TI release
 myocyte death- (sympathetic stimulation, inflammatory cytokines)
-progressive myocyte apoptosis and cardiac dysfunction
Biomarkers in Heart
Failure

46. 1. Heart-type fatty acid binding protein
2. Kinetically similar to myoglobin but
more specific to cardiac tissue which
contains a greater percentage of this
protein than skeletal muscle
3. May also have role in prediction-
prognosis in patients with NSTEMI
Newer markers - H-FABP

47. 
H-FABP Protein 15 kd
myoglobin 17 kd
Released 3 hours early marker
Plasma level returns within 24
hours
H-FABP

48. 

49. 

50. 

51. 
62 yo male with PMH of HTN x20 years, DM
II x 10 years presents with 2 hours of mid-
sternal chest pain radiating to left arm and
jaw, with associated SOB and diaphoresis. He
was given O2, ASA 325mg and SL NTG en-
route by EMS. Upon arrival to ED his CP is
5/10, somewhat relieved by the nitro, His
ECG shows TWI in v2-v6. BP 150/100, P115,
R18, 96% 2L NC
Case 1

52. 
 What is your pre-test probability for ACS before you
get cardiac biomarkers in this patient?
 Which biomarkers to you think will be positive at
this time? In 12 hours?
 Will you wait for the biomarker results to start
treatment for ACS?
Case 1 Discussion

53. 
55 yo female with no significant PMH but
positive FHx for early MI in her brother at 48
years, and her father at 56 years, presents with
mid-epigastric pain episodes lasting 1hr each, off
and on for the last 24 hours after her labor Day
BBQ (1st episode 24hrs ago), and she thinks her
right arm is “tingly.” The last episode was 2
hours ago, but the pain is gone now. The ED
gave her 1” nitropaste, 81mg asa x4 and Lovenox
1mg/kg, as well as Zofran and Morphine. Her
ECG shows TWI in lead II. Pulse is 100. Other VS
WNL.
Case 2

54. 
 What is your pre-test probability of ACS in this
patient and how are you going to utilize your blood
tests?
 Obviously the ED physician felt this was likely to be
ACS, do you agree?
 If her troponin comes back as 0.07 with a normal CK
and CK-MB what will you do?
Case 2 Discussion

55. 73 yo AAM presents to clinic for routine HF
check. By office scale he has gained 10# since
last visit 2 months ago. He admits to sleeping
upright and has1block DOE. He denies
angina/chest pain. In-office ECG is notable
for strain pattern. He is diagnosed with HF
exacerbation and direct admitted. AMI panel
is drawn and CK is 250, MB is 8, TI is 1. BNP
is 3500. 2nd TI is 1.2 and 3rd is 1.1. He is
hypertensive but stable.
Case 3

56. 
 What is the likely explanation for this patient’s
elevated cardiac biomarkers?
 How do you plan to manage this patient from here?
Does he need to be in the CICU? Does he need
further enzyme studies?
Case 3 Discussion

57. 
 44 yo AAF with ESRD secondary to HTN on dialysis
(HD x 7 years) presents with chest pain at dialysis.
Her end-HD BP was 190/100 and she reports a
headache. ECG shows Q-waves in the inferior leads
but no acute changes. She got her flu shot at dialysis
today. You draw AMI panel and CK is 300, MB 15,
RI 4% and TI is 1.13
Case 4

58. 
If her serial enzymes stay at the same levels what
is her general Cardiovascular prognosis?
Given the story, what other findings do you
expect on her ECG?
What is the likely physiological mechanism for
her elevated CK? Her TI?
She refuses cath. What is the best, simplest way
to attenuate her cardiovascular mortality?
Case 4 Discussion

59. 
Thank you