Glomerular Filtration and determinants of glomerular filtration .pptx
Pandemic of cvd atlanta
1. Vulnerable Plaques andVulnerable Plaques and
Vulnerable PatientsVulnerable Patients
The 1The 1stst
Guideline ofGuideline of Association for EradicationAssociation for Eradication
of Heart Attack AEHAof Heart Attack AEHA for Definition offor Definition of
Vulnerable Plaque and Vulnerable PatientVulnerable Plaque and Vulnerable Patient
(VP.org)(VP.org)
Morteza Naghavi, Erling Falk, Mohammad Madjid,
Silvio Litovsky, James E. Muller, Ward Casscells,
Renu Virmani, Valentin Fuster, James T. Willerson
6. Atherosclerotic Diseases Are Not
Diseases of Affluence!
Only 2.7 millions of 6.3 million of whoOnly 2.7 millions of 6.3 million of who
died by IHD were in the developeddied by IHD were in the developed
country.country.
Cerebrovascular disease (stroke) killed
4.4 million people, of whom only 1.4
million were in the developed world.
7.
8.
9. Vulnerable plaques, vulnerable myocardium, andVulnerable plaques, vulnerable myocardium, and
hypercoagulable state of the blood lead tohypercoagulable state of the blood lead to
sudden cardiac death and acute myocardial infarction.sudden cardiac death and acute myocardial infarction.
Vulnerable
Blood
Vulnerable
Myocardium
Vulnerable
Plaque
Vulnerable
Patient
10. Potential Underlying Cause of All (fatal and non-fatal) Heart Attacks
(Sudden Cardiac Death + Acute Coronary Syndrome)
With Occlusive Thrombi
With Rupture
>70% Stenosis
With Significant Atherosclerosis or
Ischemic Heart
<70% Stenosis
Without Significant Atherosclerosis or
Atherosclerosis-Derived Myocardial Damage
Without Occlusive Thrombi
Without Rupture With
Old Myocardial Damage
Without
Old Myocardial Damage
Only Myocardial-Derived Factors
(conductive disorders, …)
Erosion Calcified Nodule Others
With Critical Stenosis Without Critical Stenosis
With Expansive
Remodeling
Without Expansive
Remodeling
13. InterchangeableInterchangeable
TerminologiesTerminologies
YESYES NONO
Vulnerable Plaque =Vulnerable Plaque = Vulnerable Plaque=Vulnerable Plaque=
High-Risk PlaqueHigh-Risk Plaque Soft-PlaqueSoft-Plaque
Dangerous PlaqueDangerous Plaque Non-Calcified PlaqueNon-Calcified Plaque
AHA Type IV PlaqueAHA Type IV Plaque
Non-Stenotic PlaqueNon-Stenotic Plaque
14. Proposed Histopathological and ClinicalProposed Histopathological and Clinical
Criteria for Definition of VulnerableCriteria for Definition of Vulnerable
PlaquePlaque
•• MajorMajor Criteria:Criteria:
1.1. Active Inflammation (monocyte/Active Inflammation (monocyte/
macrophage infiltration)macrophage infiltration)
2.2. Thin Cap with Large Lipid CoreThin Cap with Large Lipid Core
3.3. Endothelial Denudation with SuperficialEndothelial Denudation with Superficial
Platelet AggregationPlatelet Aggregation
4.4. Fissured / Wounded PlaqueFissured / Wounded Plaque
15. Proposed Histopathological and ClinicalProposed Histopathological and Clinical
Criteria for Definition of VulnerableCriteria for Definition of Vulnerable
PlaquePlaque
•• MinorMinor Criteria:Criteria:
1.1. Superficial Calcified noduleSuperficial Calcified nodule
2.2. Glistening YellowGlistening Yellow
3.3. Intraplaque HemorrhageIntraplaque Hemorrhage
4.4. Critical StenosisCritical Stenosis
5.5. Positive Remodeling?Positive Remodeling?
17. Diagnosis and Screening- PlaqueDiagnosis and Screening- Plaque
LevelLevel
Plaque inflammation (macrophage density or rate of monocyte infiltration)Plaque inflammation (macrophage density or rate of monocyte infiltration)
Matrix digesting enzyme activity in the cap (MMP 2, 3,9, etc)Matrix digesting enzyme activity in the cap (MMP 2, 3,9, etc)
Endothelial denudation or dysfunction (local NO production, anti/pro-Endothelial denudation or dysfunction (local NO production, anti/pro-
coagulation properties of the endothelium)coagulation properties of the endothelium)
Superficial platelet aggregation and fibrin deposition (residual muralSuperficial platelet aggregation and fibrin deposition (residual mural
thrombus)thrombus)
Plaque cap thickness with a resolution of <100 micronPlaque cap thickness with a resolution of <100 micron
Collagen content, lipid core size, mechanical stability (stiffness andCollagen content, lipid core size, mechanical stability (stiffness and
elasticity) elasticity)
18. Diagnosis and Screening- PlaqueDiagnosis and Screening- Plaque
LevelLevel
Calcification burden and pattern (nodule, scattered, intimal,Calcification burden and pattern (nodule, scattered, intimal,
deep)deep)
Angiogenesis, leaking vasa vaserum, and intraplaqueAngiogenesis, leaking vasa vaserum, and intraplaque
hemorrhagehemorrhage
Presence of certain microbial antigensPresence of certain microbial antigens
Rate of apoptosis (apoptosis protein markers, coronaryRate of apoptosis (apoptosis protein markers, coronary
microsatellite, etc)microsatellite, etc)
Shear stress imaging (flow pattern throughout coronary arteryShear stress imaging (flow pattern throughout coronary artery
19. Diagnosis and Screening-Diagnosis and Screening-
Systemic LevelSystemic Level
CRP, CD40L, ICAM-1, VCAM, and otherCRP, CD40L, ICAM-1, VCAM, and other
serological markers of inflammationserological markers of inflammation
MMPs and acidic digesting proteinases and theirMMPs and acidic digesting proteinases and their
inhibitors such as TIMMPs and cystatininhibitors such as TIMMPs and cystatin
Circulating apoptosis marker(s)Circulating apoptosis marker(s)
Markers of blood hypercoagulabilityMarkers of blood hypercoagulability
20. Diagnosis and Screening-Diagnosis and Screening-
Systemic LevelSystemic Level
Markers of blood fibrinolysisMarkers of blood fibrinolysis
Markers of lipid-peroxidationMarkers of lipid-peroxidation
PAPP-A, pregnancy associated plasma protein –PAPP-A, pregnancy associated plasma protein –
AA
Plaque specific markers of immune activationPlaque specific markers of immune activation
(anti-LDL Ab)(anti-LDL Ab)
21. A composite risk score
Plaque vulnerability index
Patient vulnerability index
(e.g. VP Score)
Screening
22. Diagnosis- Active InflammationDiagnosis- Active Inflammation
Intravascular:Intravascular:
Thermography,Thermography,
CE-MRICE-MRI
FDG-PETFDG-PET
ImmunoscintigraphyImmunoscintigraphy
Non-invasive:Non-invasive:
CE-MRI (SPIO)CE-MRI (SPIO)
Targeted CE-MRI, (macrophage specific Gd-labeledTargeted CE-MRI, (macrophage specific Gd-labeled
Ab)Ab)
23. Dx- Thin cap and large lipid coreDx- Thin cap and large lipid core
Intravascular:Intravascular:
OCTOCT
IVUSIVUS
High-resolution IVUSHigh-resolution IVUS
AngioscopyAngioscopy
NIR SpectroscopyNIR Spectroscopy
ElastographyElastography
MRIMRI
IVUS-RF analysisIVUS-RF analysis
Non-invasiveNon-invasive
MRIMRI
24. DX-Endothelial denudation withDX-Endothelial denudation with
superficial platelet aggregationsuperficial platelet aggregation
Intravascular:Intravascular:
OCTOCT
Angioscopy with dyeAngioscopy with dye
Matrix-targeted / fibrin-targeted immune-scintigraphyMatrix-targeted / fibrin-targeted immune-scintigraphy
Non-invasive:Non-invasive:
Fibrin/Matrix-targeted CE MRIFibrin/Matrix-targeted CE MRI
Platelet/fibrin-targeted SPECTPlatelet/fibrin-targeted SPECT
30. Blood FactorBlood Factor
Antithrombin III deficiencyAntithrombin III deficiency
Protein C or S deficiencyProtein C or S deficiency
Resistance to activated protein C (factor VResistance to activated protein C (factor V
Leiden)Leiden)
Antiphospholipid syndromeAntiphospholipid syndrome
Nephrotic syndromeNephrotic syndrome
Platelet polymorphismsPlatelet polymorphisms
31. MyocardialMyocardial FactorFactor
Different cardiomyopathiesDifferent cardiomyopathies
Valvular diseaseValvular disease
Primary electric disturbancesPrimary electric disturbances
Chest traumaChest trauma
Anomalous origin of coronary arteriesAnomalous origin of coronary arteries
MyocarditisMyocarditis
Myocardial bridgingMyocardial bridging
32. Different Types of Vulnerable Plaque
As underlying Cause of Acute Coronary Events
Normal
Rupture-prone
Fissured Eroded
Critical Stenosis Hemorrhage