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![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](https://image.slidesharecdn.com/biomarkersofcadmi-presentation-140505233237-phpapp01/75/Biomarkers-of-cad-mi-presentation-45-2048.jpg)
Uploaded byNilesh Chandra
Biomarkers of cad & mi presentation
This document discusses various biomarkers for coronary artery disease and myocardial infarction. It begins by outlining existing diagnostic and prognostic biomarkers, and then describes several new biomarkers under investigation. These include biomarkers of biomechanical stress like BNP, biomarkers of neurohormonal activation like copeptin, and biomarkers of plaque instability like CRP. The document also discusses newer technologies like metabolomics and genetic biomarkers. Throughout, it provides details on each biomarker and their clinical significance.
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Biomarkers of cad & mi presentation
- 1. BIOMARKERS OF CAD& MI: RECENT ADVANCES -Dr. Nilesh Chandra
- 2. OBJECTIVES: Brief Reviewof Existing biomarkers New Diagnostic Biomarkers New prognostic Biomarkers Biomarkers under research
- 3. DIAGNOSTIC MARKERS SerumMarkers Fractional Flow Reserve Echocardiography Nuclear Imaging Studies Computed Tomography Scanning Electron Beam Computed Tomography Scanning
- 4. DIAGNOSTIC MARKERS (CONTD.) Optical Coherence Tomography Imaging Magnetic Resonance Imaging Positron Emission Tomography Coronary Angiography Doppler Velocity Probes Ultrasonography Histology
- 5. SERUM MARKERS Troponins(I or T) Creatine kinase with MB isozymes Lactate dehydrogenase and lactate dehydrogenase isozymes Serum aspartate aminotransferase
- 6. PROGNOSTIC MARKERS Biomarkers: Lipid Studies Copeptin H-FABP Urinary albumin-to-creatinine ratio Homocysteine Renin B-type natriuretic peptide CRP
- 7. LIPID STUDIES Totalcholesterol 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) Themore 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 AcidBinding 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
- 11. PROGNOSTIC BIOMARKERS 1)Biomarkers of biomechanical stress: BNP/NTproBNP Mid-Regional pro-Atrial Natriuretic Peptide (MRproANP Growth Differentiation Factor-15(GDF-15) ST2 ET1/CTproET1
- 12. PROGNOSTIC BIOMARKERS (CONTD..) 2) Biomarkers of neurohormonal pathway activation Mid-Regional-pro-Adrenomedullin (MRproADM) Copeptin 3) Biomarkers of plaque instability and inflammation HsCRP (High-sensitivity C-reactive Protein) Myeloperoxidase (MPO) Pregnancy associated Plasma Protein A (PaPPA)
- 13. PROGNOSTIC BIOMARKERS (CONTD..) 4) Other Novel biomarkers MMP9 MMP2 TIMP1
- 14. BNP/NTproBNP BNP: Oneof 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 NatriureticPeptide (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 potentvasoconstrictor 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) Activityin 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-reactiveProtein) 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) Myeloperoxidasehas 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 PlasmaProtein 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 Whenone 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
- 24. Chr SNP Riskallele frequency (%) Odds ratio (95% CI) per risk allele Gene(s) of interest within or near associated interval 6q26– 6q27 rs3798220 2 1.47 (1.35–1.60) LPA rs10455872 7 1.68 (1.43–1.98) LPA 9p21 rs4977574 56 1.29 (1.25–1.34) CDKN2A-CDKN2B-ANRIL 21q22 rs9982601 13 1.20 (1.14–1.27) SLC5A3-MRPS6-KCNE2 1p13 rs646776 81 1.19 (1.13–1.26) CELSR2-PSRC1-SORT1 1p32 rs17114036 91 1.17 (1.13–1.22) PPAP2B 10q11 rs1746048 84 1.17 (1.11–1.24) CXCL12 2q33 rs6725887 14 1.17 (1.11–1.23) WDR12 3q22 rs9818870 15 1.15 (1.11–1.19) MRAS 1p32 rs11206510 81 1.15 (1.10–1.21) PCSK9 19p13 rs1122608 75 1.15 (1.10–1.20) LDLR 1q41 rs17465637 72 1.14 (1.10–1.19) MIA3 11q23 rs964184 13 1.13 (1.10–1.16) ZNF259, APOA5-A4-C3-A1 12q24 rs3184504 40 1.13 (1.08–1.18) SH2B3 6p24 rs12526453 65 1.12 (1.08–1.17) PHACTR1
- 25. Endogenous Bioactive Peptides Adiponectin, an adipocytokine Heregulin-β1 (neuregulin-1 type I), a neuron growth factor Glucagon-like peptide-1 (GLP-1), an incretin hormone Salusin-α
- 26. Effects of newnovel peptides on the cardiovascular system. Adiponectin Heregulin-β1 GLP-1 Salusin-α VSMC proliferation ↓ ↓ ↓ ↑ eNOS ↑ ↑ ↑ → Cardiomyocyte protection + + + + Anti-inflammation + + + NE Anti-oxidation + + + NE
- 27. Effects of newnovel peptides on macrophage foam cell formation. Adiponectin Heregulin-β1 GLP-1 Salusin-α Foam cell formation ↓ ↓ ↓ ↓ ACAT1 ↓ ↓ ↓ ↓ SR-A ↓ ↓ → → ABCA1 ↑ ↑ → →
- 28. Comparisons of circulatingheregulin-β1 and salusin-α levels between CAD and non-CAD subjects
- 29.
- 30. Markers and stageof appearance
- 31. Summary Existing biomarkersfor CAD & MI diagnosis, prognosis and their limitations Biomarkers undergoing clinical trials Newer potential biochemical markers under research
- 32. References Harrison’s Principlesof 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
- 33.
- 34. Killip Classification: Killipclass 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 echocardiographyhelps 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.
- 38. COMPUTED TOMOGRAPHY SCANNING Allow excellent visualization of the coronary arteries: Multidetector computed tomography (MDCT) scanning Low-dose CT attenuation correction (CTAC) hybrid positron emission tomography (PET)/CT single-photon emission computed tomography (SPECT) CT myocardial perfusion imaging (MPI)
- 39. ELECTRON BEAM COMPUTEDTOMOGRAPHY 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 TOMOGRAPHYIMAGING 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 Invivo 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 FLOWRESERVE 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 inevaluating brachial artery reactivity and carotid artery intima media thickness: Brachial Artery Reactivity Carotid artery intima-media thickness Intravascular Ultrasonography
- 47. HISTOLOGY A systemdevised 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-likeprotein 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 mortalityor 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