7. LIPID STUDIES
Total cholesterol level
LDL cholesterol (LDL-C) level
HDL cholesterol (HDL-C) level
Triglyceride level
Specific lipid studies (if necessary) include the following:
Small, dense LDL-C level
Lipoprotein (a) level
Apoprotein profile
Direct measurement of LDL-C
8. C-terminal-provasopressin (Copeptin)
The more stable surrogate of arginine vasopressin (AVP)
Post AMI
increase peripheral vasoconstrictor activity
increase protein synthesis in myocytes
vasoconstriction of coronary arteries
Can rule out MI earlier in addition to a negative Troponin T test
a copeptin level of < 14 pg/ml and a Trop T level of < 0.01
an area under the curve (AUC) of receiver operating
characteristic curve (ROC) of 0.97 (negative predictive value
of 99.7%)
9. C-terminal-provasopressin (Copeptin) contd..
Can rule out MI earlier in addition to a negative
Troponin T test
a copeptin level of < 14 pg/ml and a Trop T level of < 0.01
an area under the curve (AUC) of receiver operating
characteristic curve (ROC) of 0.97 (negative predictive value
of 99.7%)
Effects are mediated via the V1 receptor
These receptors are now targets for pharmacological
therapy.
10. Heart-Type Fatty Acid Binding Protein (H-FABP)
A LMW protein involved in myocardial fatty-acid
metabolism
Rapidly released early in myocardial infarction and
necrosis into the cytosol
When added to Troponin for risk stratification
(Trop/H-FABP):(-)= H-FABP< 5.8 mcg/L
* -/- = zero mortality at six months
* -/+= 4.93-fold increase in risk of death
* +/+= 7.93-fold increase in risk of death
14. BNP/NTproBNP
BNP: One of the best known biomarkers of
biomechanical stress
Is released with the N-terminal portion of the pro-BNP
peptide (NTproBNP)
Predicts in-hospital and 180-day death or heart failure
.
15. Mid-Regional pro-Atrial Natriuretic Peptide
(MRproANP)
ANP has similar secretory profile post AMI as BNP.
MRproANP fragment substantially more stable peptide
compared to N-ANP and ANP
MRproANP is at least as good at predicting death and
heart failure as NTproBNP
16. Growth Differentiation Factor-15(GDF-15)
A member of the Transforming Growth Factor Beta
cytokine superfamily
Under episodes of stress like ischaemia and
reperfusion,its levels go up in cardiomyocytes.
Provides prognostic information following an MI or ACS
17. ET1/CTproET1
A potent vasoconstrictor peptide
It activates ETA and ETB receptors
Appears to be detrimental post-MI
Plasma concentration of CTproET-1 peaks at Day 2
Is increased in proportion to the severity of the
disease post AMI
Independent of age, Killip class and past medical
history
18. Mid-Regional-pro-Adrenomedullin (MRproADM)
Activity in the cardiovascular system is similar to that
of BNP
Post AMI, increased MRproADM associated with
death, heart failure or both at one year, over and
above information gained from NTproBNP alone
Combining the two markers increases the AUC of the
ROC from 0.77 and 0.79 to 0.84
19. HsCRP (High-sensitivity C-reactive Protein)
CRP mediates atherothrombosis
An elevated CRP associated with increased
cardiovascular risk
Benefits of hsCRP testing to screen for ischaemic
heart disease is very clear, its use post-ACS or -MI is
less clear
A new assay for Human Pentraxin 3 is now available
20. Myeloperoxidase (MPO)
Myeloperoxidase has been found in atheromatous
plaques
MPO in leucocytes may activate metalloproteinases
MPO may inactivate plasminogen activator inhibitor
Post-ACS, MPO levels higher than median predicted
future death and MI at one year
MPO levels do not predict heart failure
21. Pregnancy associated Plasma Protein A (PaPPA)
A proatherosclerotic metalloproteinase
Is highly expressed in unstable plaques and their
extracellular matrices
PaPPA > 2.9 mIU/L predicts a 4.6-fold increase in risk
of cardiovascular death, MI or revascularisation even
without a raised Troponin
22. NEWER TECHNOLOGIES: METABOLOMICS
Components from branched-chain & aromatic amino
acid as independent cardiovascular risk factors:
isoleucine, leucine, valine, tyrosine, and phenylalanine
Lipids metabolites associated with cardiovascular
disease, shown to promote atherosclerosis:
phosphatidylcholine-choline
trimethylamine N-oxide
betaine
23. GENETIC BIOMARKERS
When one twin dies of CHD, the RR for the remaining
one is as high as 4-fold for dizygotes and 8-fold for
monozygotes
Genome-wide association (GWA) studies for identifying
common SNPs that are associated with cardiovascular
disease
Locus in the 9p21 region separately reported by 3
different groups
31. Summary
Existing biomarkers for CAD & MI diagnosis,
prognosis and their limitations
Biomarkers undergoing clinical trials
Newer potential biochemical markers under
research
32. References
Harrison’s Principles of Internal Medicine; 17th Edition
Daniel Chan, Leong L Ng ;Biomarkers in acute myocardial infarction; BMC
Med. 2010; 8: 34.
Ramachandran S. Vasan;Biomarkers of Cardiovascular Disease: Molecular
Basis and Practical Considerations; Circulation. 2006; 113: 2335-2362
Yin Ge,Thomas J. Wang;Circulating, imaging, and genetic biomarkers in
cardiovascular risk prediction;Trends Cardiovasc Med. 2011 May; 21(4):
105–112
Takuya Watanabe, Kengo Sato, Fumiko Itoh, Kohei Wakabayashi, Masayoshi
Shichiri, Tsutomu Hirano; Endogenous Bioactive Peptides as Potential
Biomarkers for Atherosclerotic Coronary Heart Disease;Sensors (Basel).
2012; 12(4): 4974–4985
34. Killip Classification:
Killip class I includes individuals with no clinical signs of heart failure.
Killip class II includes individuals with rales or crackles in the lungs, an
S3, and elevated jugular venous pressure.
Killip class III describes individuals with frank acute pulmonary edema.
Killip class IV describes individuals in cardiogenic shock or hypotension
(measured as systolic blood pressure lower than 90 mmHg), and
evidence of peripheral vasoconstriction (oliguria, cyanosis or sweating).
Within a 95% confidence interval the patient outcome was as follows:
Killip class I: 81/250 patients;32% (27–38%).Mortality rate 6%.
Killip class II: 96/250 patients;38% (32–44%).Mortality rate 17%.
Killip class III: 26/250 patients;10% (6.6–14%).Mortality rate 38%.
Killip class IV: 47/250 patients;19% (14–24%).Mortality rate 67%.
35. FRACTIONAL FLOW RESERVE
An index of functional severity of coronary
artery stenosis.
Based on the observation that myocardial
perfusion is entirely pressure dependent during
maximal hyperemia.
Represents the fraction of the normal maximal
coronary flow that can be achieved in an artery
in which flow is restricted by a coronary
stenosis.
36. ECHOCARDIOGRAPHY
Transthoracic echocardiography helps to assess LVF, wall-
motion abnormalities.
Transesophageal echocardiography used for assessing
possible aortic dissection.
Stress echocardiography used to evaluate
hemodynamically significant stenoses.
Treadmill echocardiography stress testing and dobutamine
echocardiography stress testing provide equivalent
predictive values.
37. NUCLEAR IMAGING STUDIES
Useful in assessing patients for
hemodynamically significant coronary artery
stenoses:
Treadmill nuclear stress test
Dipyridamole (Persantine)
Adenosine nuclear stress test
Dobutamine nuclear stress test.
39. ELECTRON BEAM COMPUTED TOMOGRAPHY
SCANNING
Method of evaluating calcium content in the coronary
arteries.
Used as a screening test in asymptomatic patients
Used as a diagnostic test for obstructive CAD in
symptomatic patients
40. OPTICAL COHERENCE TOMOGRAPHY IMAGING
Catheter-based, high-resolution intravascular imaging
Remarkable resolutionin the range of 10-20 µm.
Acquisition rates are near video speed
OCT imaging uses light
41. MAGNETIC RESONANCE IMAGING
Used to gain information noninvasively about blood
vessel wall structure and to characterize plaque
composition
42. POSITRON EMISSION TOMOGRAPHY
Radiation exposure 4- to 5-fold lower with PET.
PET offers better spatial and temporal resolution and
shorter imaging time.
43. CORONARY ANGIOGRAPHY
In vivo assessment
The criterion standard for detecting significant flow-
limiting stenoses that may be revascularized through
percutaneous or surgical intervention of the coronary
arteries
Limitation: only the vessel space occupied by blood is
visualized.
44. DOPPLER VELOCITY PROBES
Based on the principle of the Doppler effect
Use miniaturized crystals fixed to the tip of catheters
Allows measurement of selective coronary artery flow
velocity
45. RELATIVE CORONARY FLOW RESERVE
Calculated as follows: ([rCFR] = CFR target/CFR
reference).
Correlates with stress myocardial perfusion imaging
results
Provides additional information regarding the status of
the microcirculation in patients with CAD
46. ULTRASONOGRAPHY
Aids in evaluating brachial artery reactivity and
carotid artery intima media thickness:
Brachial Artery Reactivity
Carotid artery intima-media thickness
Intravascular Ultrasonography
47. HISTOLOGY
A system devised by Stary et al.
classifies atherosclerotic lesions according to
their histologic composition and structure.
Type I to type VIII lesions
48. ST2
an IL1-receptor-like protein
elevated when heart is under mechanical
stress
seems to have a cardioprotective role
ST2 predicts cardiovascular death following
ACS
correlates somewhat with NTproBNP
49. Copeptin
Predicts mortality or heart failure at 60 days
post AMI
Relationship of copeptin to LV dysfunction
persists for a prolonged period after the acute
event
Provides complementary prognostic
information to NTproBNP
