www.epc-checkup.de EUROPEAN PREVENTION CENTER Asymptomatische Gefäßsklerose: Bedeutung und therpeutische Konsequenz Chiemgauer Kardiologietage 2018 Gut Ising 22. – 23. September 2018 Prof. Dr. med. Uwe Nixdorff, F.E.S.C. Internist, Kardiologe, Sportmediziner EPC GmbH - European Prevention Center, Düsseldorf / Berlin / München / Hamburg www.epccheckup.de Hanako GmbH, München www.hanako-health.com Universitätsklinikum Erlangen-Nürnberg
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Asymptomatische Gefäßsklerose: Bedeutung und therpeutische ...€¦ · Lp-PLA2 Studies Collaboration The Lp-PLA2 Studies Collaboration, Lancet 2010; 375: 1536–44 Figure 4: Adjusted
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www.epc-checkup.de EUROPEAN PREVENTION CENTER
Asymptomatische Gefäßsklerose:
Bedeutung und therpeutische
Konsequenz
Chiemgauer Kardiologietage 2018
Gut Ising
22. – 23. September 2018
Prof. Dr. med. Uwe Nixdorff, F.E.S.C.Internist, Kardiologe, Sportmediziner
Kardiale Mehrschicht-ComputertomographieEPC Check-Up eines 56-jährigen asymptomatischen Individuums
www.epccheckup.de EUROPEAN PREVENTION CENTER
Kardiale Mehrschicht-ComputertomographieEPC Check-Up eines 56-jährigen asymptomatischen Individuums
www.epccheckup.de EUROPEAN PREVENTION CENTER
Kardiale Mehrschicht-ComputertomographieEPC Check-Up eines 56-jährigen asymptomatischen Individuums
www.epccheckup.de EUROPEAN PREVENTION CENTER
Kardiale Mehrschicht-ComputertomographieEPC Check-Up eines 56-jährigen asymptomatischen Individuums
www.epccheckup.de EUROPEAN PREVENTION CENTER
Kardiale Mehrschicht-ComputertomographieEPC Check-Up eines 56-jährigen asymptomatischen Individuums
www.epccheckup.de EUROPEAN PREVENTION CENTER
Kardiale Mehrschicht-ComputertomographieEPC Check-Up eines 56-jährigen asymptomatischen Individuums
www.epccheckup.de EUROPEAN PREVENTION CENTER
www.epccheckup.de EUROPEAN PREVENTION CENTER
www.epccheckup.de EUROPEAN PREVENTION CENTER
European Guidelines on CV Disease Preventionin Clinical Practice Eur Heart J 2012; 33:1635-1701
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European Guidelines on CV Disease Prevention in Clinical Practice
Eur Heart J 2016; 37:2315-81
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Vulnerable Plaque?
Early Plaque with Lipid Pool
Thick Cap with Small Necrotic Lipid Core
“Stable Plaque”
Thin Cap “Rupture-Prone”
Plaque
Ruptured Plaque with Thrombus
in LumenAdapted from Kolodgie F, et al. Arterioscler Thromb Vasc Biol 2006.
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Lipid core
Lumen
Fibrous cap
▪ Low Lp-PLA2 content▪ May have significant stenosis▪ Thick fibrous cap / high collagen content▪ Small lipid pool▪ Few inflammatory cells
▪ High Lp-PLA2 content ▪ May have minimal stenosis▪ Thin fibrous cap / low collagen content▪ Large lipid pool▪ Many inflammatory cells
Lumen
Stable Plaque Ruptured Plaque
Stabile vs. Rupturierte PlaqueHistopathologische Charakteristika
Adapted from Corson MA et al. Am J Cardiol 2008; 101[suppl]:41F-50F.
Thrombus
Lipid Pool
Lp-LA2
Oxidized LDL
AdhesionMolecules
Foam Cell
Macrophage
Cytokines
Fibrous Cap
Formation der vulnerablen Plaque
Lerman A et al. Am J Cardiol 2008; 101[suppl]:11F-22F.
Der Unterschied zwischen Paris (France) und Paris (Texas)
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Visceral Fat and ConsequencesVan Kruijsdijk RC, et al. Cancer Epidemiol
Biomarkers Prev 2009; 18:2569–78
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Cardiometabolisches Syndrom:Atherosklerose und Inflammation
White MG, et al. Diabetes Care 2016; 371:2237-92
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JUPITER TrialAm J Cardiol 2010, 106:204-9
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2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults
Circulation 2010; 122:e584-e636
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EDUCATE: Lp-PLA2 & Carotid Ultrasound Are Complementary Predictors of CAD & CV Events
McHugh VL et al. AHA Epi Meeting Abstract 2006
32 month follow-up: 253 men < 55 & women < 65 after coronary angiography+ Carotid ultrasound defined a > 1mm IMT in bulb or focal plaque in the main body or bulb
Hazard Ratio for
> 50% Coronary Stenosis
2,3
4,1
0
2
4
6
8
10
Hazard Ratio for
Death, MI & Stroke
3,1
9,1
0
2
4
6
8
10
+ Carotid UltrasoundP = 0.055
+ Carotid Ultrasound &Lp-PLA2 Top QuartileP = 0.001
+ Carotid UltrasoundP = 0.159
+ Carotid Ultrasound &Lp-PLA2 Top QuartileP = 0.053
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Copyright 2011 diaDexus, Inc. All rights reserved.
Figure 4: Adjusted risk ratios for coronary heart disease per 1 SD higher baseline Lp-PLA2 activity, mass, and several conventional risk factors in a common set of participants – a fraction of the full study.
79,036 Participants in 32 Prospective Studies
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CANTOS TrialRidker PM, et al.
N Engl J Med 2017; August 27
• Canakinumab = monoklonalerAntikörper gegen Interleukin 1β
• n = 10.061 MI-Patienten• High sensitive CRP ≥ 2 mg/dL• 3 Dosen: 50; 150 und 300 mg gegen
Placebo, appliziert s.c. alle 3 Monate
• Endpunkt: nonfataler MI, nonfatalerStroke oder kardiovaskulärer Tod
CANTOS TrialRidker PM, et al. N Engl J Med 2017; August 27
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NEJM 2018; Sept. 16
ASPREE: Effect of Aspirin on Disability-free Survival in the Healthy Elderly
McNeil JJ; et al., NEJM 2018; Sept. 16
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ASPREE: Effect of Aspirin on Disability-free Survival in the Healthy Elderly
McNeil JJ; et al., NEJM 2018; Sept. 16
ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)
Gaziano JM, et al. Lancet 2018; Aug 24 [Epub ahead of print]
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ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)
Gaziano JM, et al. Lancet 2018; Aug 24 [Epub ahead of print]
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ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)
Gaziano JM, et al. Lancet 2018; Aug 24 [Epub ahead of print]
www.epccheckup.de EUROPEAN PREVENTION CENTER
ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)
Gaziano JM, et al. Lancet 2018; Aug 24 [Epub ahead of print]
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www.epccheckup.de EUROPEAN PREVENTION CENTER
European Guidelines on CV Disease Prevention in Clinical Practice
Eur Heart J 2016; 37:2315-81
Erreichtes LDL-Cholesterin und Atherom-Regression (IVUS-Studien)
Puri R, et al. Am Heart J. doi: 10.1016/j.ahj.2016.01.019.
2
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Me
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Average On-Treatment LDL-C (mg/dL)40 60 80 100 120