pathology of the vessels: atherosclerosis · pathology of the vessels: atherosclerosis pathobasic...

Pathologie Prof. Dr. med. Katharina Glatz

Pathology of the Vessels: Atherosclerosis

PathoBasic July 31, 2018

• Cardiovascular risk factors

• Pathogenesis of atherosclerosis

• Myocardial ischemia

• The cholesterol lie: what is true?

Agenda

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

Arteriosclerosis

Atherosklerosis (a) Medial calcification (Mönckeberg’sche Mediaverkalkung) (b)

Arteriolosclerosis (c)

a b c

?

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.

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

do

thelial

dysfu

ncti

on

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

Coronary Heart Disease

Culprit Lesion

60-75% Plaque rupture 25-40% Plaque erosion (more frequent in NSTEMI)

European Heart Journal – Cardiovascular Imaging (2016) 17:1128–1137

Vulnerable plaque:

Large lipid core

Large amount of inflammatory cells

Thin fibrous cap

Disproportion of matryx synthesis and

degradation

Nodular calcifications

Normal Collateral circulation

Subendocardial ischemia Normal

Subacute subendocardial infarction

Not ischemic

Region supplied by occluded coronary artery (risk area)

Necrosis

Time is muscle!

80% perioperative Myokardischämien symptomlos 10-fache Mortalität 30d postoperativ Meist Missverhältnis von Sauerstoffangebot/bedarf Behebung der Ursache (Anämie, Arrhythmie, Hypotonie...)

Cholesterol Lie: What is true?

• 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?

• 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?

What is the evidence?

"there are no studies demonstrating that plant stanol esters have an impact on population-based CHD morbidity and mortality rates".

Correlation Causation

• 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?

What is the evidence?

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

• 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?

What is the evidence?

Lancet 2016;388:2532

What is the evidence?

Lancet 2016;388:2532

What is the evidence?

N Engl J Med 2017; 377:633-643

What is the evidence?

N Engl J Med 2017; 377:633-643

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

Why does it matter?

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

• 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