Transcript Lecture 1 - UMF IASI 2015

Cardiovascular disease is the leading cause
of death among adults worldwide (1996)
Coronary disease
7.2 million
Cancer
6.3
Cerebrovascular disease
4.6
Acute lower respiratory tract infections
3.9
Tuberculosis
3.0
COPD (chronic obstructive pulmonary disease)
2.9
Diarrhea (including dysentery)
2.5
Malaria
2.1
AIDS
1.5
Hepatitis B
1.2
Coronary mortality:
alarming worldwide forecasts
Atherosclerosis:
a multifactorial disease
Arterial wall:
structure and function
Different stages of atherosclerotic plaque
development
Vascular endothelium modification
in atherosclerosis
Plaque formation
1 — Fatty streak
Lipid core constitution
LDL oxidation
Lipid core constitution
Activated macrophages accumulate lipids
Plaque formation
2 — Fibrous cap
Plaque formation
3 — Lipid core
From plaque to thrombosis, key event:
plaque rupture
Plaque vulnerability
Key role of macrophages
Vulnerable plaque
Key role of the macrophage in vascular wall inflammation
Vulnerable plaque
Key role of the macrophage in the degradation of the fibrous cap
Parietal vascular inflammation
The activated macrophage produces inflammatory cytokines
Parietal vascular inflammation
NFkB action in the inflammation process
Thrombus formation
The macrophages release coagulation factors
Oxidized LDL and thrombogenesis
Plaque disruption
(plaque cracking, fissuring, rupture – thrombosis start point)
Dyslipidemia and atherosclerosis
Diabetes and atherosclerosis
Tobacco and atherosclerosis
HTN, hemodynamic factor and atheroclerosis
Atherosclerosis
Inflammation links classic risk factors to altered cellular
behavior within the arterial wall and secretion of
inflammatory markers in the circulation.
Fibrinogen is an independent risk factor
for atherosclerosis
Pathophysiology of atherosclerotic plaque
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Plaque rupture
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 inflammation markers (CRP (C-reactive protein), amyloid A)
Intracoronary thrombus
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 increased coagulation factors and proteins (prothrombin fragments F1+2; II – ATIII
(thrombin – antithrombin III complex)
 increased soluble fibrin monomers
 increased P-selectin (a platelet membrane protein)
reduced blood coronary flow
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 imaging changes
 fibrinolytic system activation (spontaneous / therapeutic)
 increased P-AP2 (plamin – antiplasmin 2) complexes, fibrin degradation products (Ddimer)
Myocardial ischemia
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 early ischemic indicators: glygogen phosphorylase BB
 ECG - ST depression
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Myocardial necrosis
 biochemical markers: CKMB, cTnT, cTnI
 ECG - ST elevation
Cardiac markers
Enzymes:
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CK, isoenzyme CK-MB, isoforms CK-MB2 and CK-MM3
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CK-MB mass
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ASAT, ALAT
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LDH, isoenzyme LDH1
Non-enzymatic markers:
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Troponins cTnT, cTnI
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Myoglobin
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H-FABP
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NT-proANP, NT-proBNP
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Galectin
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Inflammatory markers:
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hsCRP
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IL6
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VCAM1
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Fibrinogen
Fig. 1
Fig. 2