01B.06 · Athérosclérose VI — manifestations cliniques, plaques et inflammation

Atherosclerosis VI — clinical manifestations, plaques and inflammation

Atherosclerosis series · 55 pages

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Atherosclerosis VI — Plaques & Inflammation

1Atherosclerosis VI — Plaques & Inflammation 2Main Clinical Manifestations

Plaque Characteristics

3Hemodynamic Forces 4Laminar vs Disturbed Flow 5AMI Independent of Stenosis Degree 6Plaque Frequency vs Per-Plaque Risk 7Plaque Progression Overview 8Vulnerable vs Stable Plaque 9Macrophages & Lymphocytes in Atheroma 10Macrophages in Atheroma 11T Lymphocytes in Atheroma

Immunity & Atherosclerosis

12Blood Cell Differentiation 13Innate & Adaptive Immunity Overview 14B Cell Subsets in Atherogenesis

Atherosclerosis as Inflammatory Disease

15Ross: Comparison with Chronic Inflammatory Diseases 16Key References: Ross & Libby

Pathophysiology of Atherosclerosis

17LDL Retention & Immune Activation 18Mechanisms of Acute Coronary Syndromes

Inflammation & Biomarkers

19Acute-Phase Proteins 20CRP as CV Risk Marker 21CRP, Aspirin & MI Risk 22Combined LDL + CRP Risk Stratification

Statins & Inflammation

23Statins Reduce CRP In Vivo 24Pravastatin Lowers CRP & CHD Risk

25Primary Objectives 26Trial Design 27Biomarker Results 28Clinical Outcomes: 44% Event Reduction

Plaque Stability & Destabilization

29Cap Synthesis vs Breakdown 30Plaque Progression Recap

Plaque Stabilization

31Stabilization Rationale 32Stabilizing Measures

Anti-Inflammatory Treatment

33Residual Cholesterol vs Inflammatory Risk 34Inflammatory Pathway Targets 35CRP → IL-6 → IL-1 Upstream Cascade 36CANTOS: Canakinumab Biomarker Effects 37CANTOS: Clinical Outcomes by Dose 38CANTOS: Benefit Depends on CRP Response 39CANTOS: Safety & Adverse Events 40COLCOT: Colchicine Post-MI Trial 41COLCOT: Clinical Endpoint Results 42LoDoCo2: Colchicine in Chronic Coronary Disease 43LoDoCo2: Safety & Adverse Events

IL-6 as Therapeutic Target

44Genetic Evidence: GWAS & Mendelian Randomization 45IL-6 Predicts Future CV Events 46Murine IL-6 Inhibition Models 47ZEUS Trial: Ziltivekimab

48Atherosclerosis as Inflammatory Disease Recap 49Residual Cholesterol vs Inflammatory Risk 50Six Domains of Residual Risk

51Hemodynamic Forces Recap 52Lesion Quality > Stenosis Size 53Inflammation at All Stages 54Vulnerable vs Stable Plaque & Stabilizing Measures 55Anti-Inflammatory Treatment Reduces CV Events

01B.06Page 1Atherosclerosis VI — Plaques & Inflammation

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 1

01B.06Page 2Atherosclerosis VI — Plaques & InflammationMain Clinical Manifestations

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 2

01B.06Page 3Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsHemodynamic Forces

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 3

01B.06Page 4Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsLaminar vs Disturbed Flow

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 4

01B.06Page 5Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsAMI Independent of Stenosis Degree

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 5

01B.06Page 6Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsPlaque Frequency vs Per-Plaque Risk

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 6

01B.06Page 7Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsPlaque Progression Overview

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 7

01B.06Page 8Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsVulnerable vs Stable Plaque

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 8

01B.06Page 9Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsMacrophages & Lymphocytes in Atheroma

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 9

01B.06Page 10Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsMacrophages in Atheroma

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 10

01B.06Page 11Atherosclerosis VI — Plaques & InflammationPlaque CharacteristicsT Lymphocytes in Atheroma

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 11

01B.06Page 12Atherosclerosis VI — Plaques & InflammationImmunity & AtherosclerosisBlood Cell Differentiation

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 12

01B.06Page 13Atherosclerosis VI — Plaques & InflammationImmunity & AtherosclerosisInnate & Adaptive Immunity Overview

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 13

01B.06Page 14Atherosclerosis VI — Plaques & InflammationImmunity & AtherosclerosisB Cell Subsets in Atherogenesis

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 14

01B.06Page 15Atherosclerosis VI — Plaques & InflammationAtherosclerosis as Inflammatory DiseaseRoss: Comparison with Chronic Inflammatory Diseases

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 15

01B.06Page 16Atherosclerosis VI — Plaques & InflammationAtherosclerosis as Inflammatory DiseaseKey References: Ross & Libby

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 16

01B.06Page 17Atherosclerosis VI — Plaques & InflammationPathophysiology of AtherosclerosisLDL Retention & Immune Activation

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 17

01B.06Page 18Atherosclerosis VI — Plaques & InflammationPathophysiology of AtherosclerosisMechanisms of Acute Coronary Syndromes

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 18

01B.06Page 19Atherosclerosis VI — Plaques & InflammationInflammation & BiomarkersAcute-Phase Proteins

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 19

01B.06Page 20Atherosclerosis VI — Plaques & InflammationInflammation & BiomarkersCRP as CV Risk Marker

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 20

01B.06Page 21Atherosclerosis VI — Plaques & InflammationInflammation & BiomarkersCRP, Aspirin & MI Risk

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 21

01B.06Page 22Atherosclerosis VI — Plaques & InflammationInflammation & BiomarkersCombined LDL + CRP Risk Stratification

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 22

01B.06Page 23Atherosclerosis VI — Plaques & InflammationStatins & InflammationStatins Reduce CRP In Vivo

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 23

01B.06Page 24Atherosclerosis VI — Plaques & InflammationStatins & InflammationPravastatin Lowers CRP & CHD Risk

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 24

01B.06Page 25Atherosclerosis VI — Plaques & InflammationJUPITER TrialPrimary Objectives

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 25

01B.06Page 26Atherosclerosis VI — Plaques & InflammationJUPITER TrialTrial Design

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 26

01B.06Page 27Atherosclerosis VI — Plaques & InflammationJUPITER TrialBiomarker Results

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 27

01B.06Page 28Atherosclerosis VI — Plaques & InflammationJUPITER TrialClinical Outcomes: 44% Event Reduction

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 28

01B.06Page 29Atherosclerosis VI — Plaques & InflammationPlaque Stability & DestabilizationCap Synthesis vs Breakdown

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 29

01B.06Page 30Atherosclerosis VI — Plaques & InflammationPlaque Stability & DestabilizationPlaque Progression Recap

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 30

01B.06Page 31Atherosclerosis VI — Plaques & InflammationPlaque StabilizationStabilization Rationale

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 31

01B.06Page 32Atherosclerosis VI — Plaques & InflammationPlaque StabilizationStabilizing Measures

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 32

01B.06Page 33Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentResidual Cholesterol vs Inflammatory Risk

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 33

01B.06Page 34Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentInflammatory Pathway Targets

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 34

01B.06Page 35Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCRP → IL-6 → IL-1 Upstream Cascade

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 35

01B.06Page 36Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCANTOS: Canakinumab Biomarker Effects

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 36

01B.06Page 37Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCANTOS: Clinical Outcomes by Dose

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 37

01B.06Page 38Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCANTOS: Benefit Depends on CRP Response

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 38

01B.06Page 39Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCANTOS: Safety & Adverse Events

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 39

01B.06Page 40Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCOLCOT: Colchicine Post-MI Trial

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 40

01B.06Page 41Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentCOLCOT: Clinical Endpoint Results

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 41

01B.06Page 42Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentLoDoCo2: Colchicine in Chronic Coronary Disease

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 42

01B.06Page 43Atherosclerosis VI — Plaques & InflammationAnti-Inflammatory TreatmentLoDoCo2: Safety & Adverse Events

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 43

01B.06Page 44Atherosclerosis VI — Plaques & InflammationIL-6 as Therapeutic TargetGenetic Evidence: GWAS & Mendelian Randomization

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 44

01B.06Page 45Atherosclerosis VI — Plaques & InflammationIL-6 as Therapeutic TargetIL-6 Predicts Future CV Events

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 45

01B.06Page 46Atherosclerosis VI — Plaques & InflammationIL-6 as Therapeutic TargetMurine IL-6 Inhibition Models

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 46

01B.06Page 47Atherosclerosis VI — Plaques & InflammationIL-6 as Therapeutic TargetZEUS Trial: Ziltivekimab

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 47

01B.06Page 48Atherosclerosis VI — Plaques & InflammationSummaryAtherosclerosis as Inflammatory Disease Recap

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 48

01B.06Page 49Atherosclerosis VI — Plaques & InflammationSummaryResidual Cholesterol vs Inflammatory Risk

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 49

01B.06Page 50Atherosclerosis VI — Plaques & InflammationSummarySix Domains of Residual Risk

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 50

01B.06Page 51Atherosclerosis VI — Plaques & InflammationConclusionsHemodynamic Forces Recap

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 51

01B.06Page 52Atherosclerosis VI — Plaques & InflammationConclusionsLesion Quality > Stenosis Size

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 52

01B.06Page 53Atherosclerosis VI — Plaques & InflammationConclusionsInflammation at All Stages

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 53

01B.06Page 54Atherosclerosis VI — Plaques & InflammationConclusionsVulnerable vs Stable Plaque & Stabilizing Measures

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 54

01B.06Page 55Atherosclerosis VI — Plaques & InflammationConclusionsAnti-Inflammatory Treatment Reduces CV Events

Athérosclérose VI — manifestations cliniques, plaques et inflammation page 55