Atherosclerosis CVS lecture 2 Atherosclerosis Shaesta Naseem.
Pathology of the Vessels: Atherosclerosis · Pathology of the Vessels: Atherosclerosis PathoBasic...
Transcript of Pathology of the Vessels: Atherosclerosis · Pathology of the Vessels: Atherosclerosis PathoBasic...
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Pathologie Prof. Dr. med. Katharina Glatz
Pathology of the Vessels: Atherosclerosis
PathoBasic July 31, 2018
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• Cardiovascular risk factors
• Pathogenesis of atherosclerosis
• Myocardial ischemia
• The cholesterol lie: what is true?
Agenda
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Cardiovascular Risk Factors
• High Cholesterol – LDL high, HDL low
• High arterial blood pressure • Age, sex (m) • Genetic predisposition (family history!) • Smoking • Diabetes mellitus • Adipositas, sendetary lifestyle
• Hyperuricemia • Stress, noise, air pollution • Hormones...
influencable
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Arteriosclerosis
Atherosklerosis (a) Medial calcification (Mönckeberg’sche Mediaverkalkung) (b)
Arteriolosclerosis (c)
a b c
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?
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Pathogenese der Atherosklerose
Nature. 2011 May 19;473(7347):317-25. Progress and challenges in translating the biology of atherosclerosis. Libby P1, Ridker PM, Hansson GK.
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I Initial lesion •Normal histology •Macrophages •Scattered foamy cells
II Fatty streak Intracellular Lipid accumulation
III Preatheroma IC lipid accumulation Small extracellular lipid lakes
IV Atheroma IC lipid accumulation EC lipid core
V Fibroatheroma Lipid core Fibrosis, calcification
VI Complicated lesion Surface defect Hemorrhage Thrombosis
from 1st decade
from 3rd decade
4th decade
Growth by lipid accumulation
Increase of smooth muscle and fibres
Thrombosis and / or hematoma
Silent
Silent or sympto- matic
En
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Atherosclerosis grade
□ No significant atherosclerosis
□ Mild atherosclerosis
□ Moderate atherosclerosis
□ Severe atherosclerosis
□ Atherosclerosis with plaque disruption
□ Surface thrombus
□ Calcific atherosclerosis
Cardiovascular Pathology 2015, 24 (5): 267-278 Cardiovascular Pathology 2015, 24 (5): 267-278
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Coronary Heart Disease
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Culprit Lesion
60-75% Plaque rupture 25-40% Plaque erosion (more frequent in NSTEMI)
European Heart Journal – Cardiovascular Imaging (2016) 17:1128–1137
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Vulnerable plaque:
Large lipid core
Large amount of inflammatory cells
Thin fibrous cap
Disproportion of matryx synthesis and
degradation
Nodular calcifications
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Normal Collateral circulation
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Subendocardial ischemia Normal
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Subacute subendocardial infarction
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Not ischemic
Region supplied by occluded coronary artery (risk area)
Necrosis
Time is muscle!
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80% perioperative Myokardischämien symptomlos 10-fache Mortalität 30d postoperativ Meist Missverhältnis von Sauerstoffangebot/bedarf Behebung der Ursache (Anämie, Arrhythmie, Hypotonie...)
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Cholesterol Lie: What is true?
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• Cholesterol rich food is no CV risk factor
• High LDL in the blood is no CV risk factor
• Statins cancer and dementia
• Statins myositis, myalgia
What are the claims?
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• Cholesterol rich food is no CV risk factor
• High LDL in the blood is no CV risk factor
• Statins cancer and dementia
• Statins myositis, myalgia
What are the claims?
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What is the evidence?
"there are no studies demonstrating that plant stanol esters have an impact on population-based CHD morbidity and mortality rates".
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Correlation Causation
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• Cholesterol rich food is no CV risk factor
• High LDL in the blood is no CV risk factor
• Statins cancer and dementia
• Statins myositis, myalgia
What are the claims?
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What is the evidence?
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What is the evidence?
LDL-cholesterol MI, stroke, death
200 studies 2’000’000 patients 20’000’000 person-years of follow up 150’000 cardiovascular events (death, infarction, stroke) Intervention lowers risk >30 RCTs, >200’000 patients
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• Cholesterol rich food is no CV risk factor
• High LDL in the blood is no CV risk factor
• Statins cancer and dementia
• Statins myositis, myalgia
What are the claims?
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What is the evidence?
Lancet 2016;388:2532
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What is the evidence?
Lancet 2016;388:2532
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What is the evidence?
N Engl J Med 2017; 377:633-643
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What is the evidence?
N Engl J Med 2017; 377:633-643
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What is the evidence?
blinded ranomised phase
non-blinded ranomised phase
Statins and myositis, myalgia: Nocebo effect Myositis (CK ): 0.01% Myalgias: 1%
N=10’150 Atorvastatin 10mg vs. placebo
Lancet 2017;389:2473
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Why does it matter?
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Summary
Lowering LDL cholesterol by 2 mmol/L with an effective statin regimen for about 5 years in 10 000 patients would typically prevent major vascular events in about 1000 (10%) patients at high risk of heart attacks and strokes (eg, secondary prevention) and 500 (5%) patients at lower risk (eg, primary prevention).
Lancet 2016;388:2532
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• LDL-cholesterol causal and cumulative factor in atherosclerosis
• LDL 1mmol/l 20% MI/stroke/death
• Evidence +++
• Well tolerated drugs (statins, ezetrol, PCSK9i)
• Target level LDL <1.8 mmol
Summary