Atherosclerosis Flashcards
What is atherosclerosis?
-a progressive, chronic inflammatory disease of large arteries that starts in childhood and rapidly progresses in the third decade or later
Where does atherosclerosis invade?
-med and large arteries - in the artial intima forming plaques
Major modifiable risk factors for atherosclerosis;
- *Smoking**
- HTN - esp when get older
- hyperlipidemia
- diabetes
- C-reactive protein
RISK FACTORS ARE ADDITIVE
Non modifiable risk factors for atherosclerosis
age
male
-family history
What blood component is pro-atherogenic:
- LDL - bad lipoprotein
- Liporotein Lp(a)
I Familial lipoprotein lipase deficiency
-increase in what?
-inc chylomicrons - no premature atherosclerosis (AS)
IIa Familial hypercholesterolemia
-inc in what?
-Inc LDL - premature AS
IIb Familial combined hypercholesterolemia
-inc in what?
- inc LDL
- inc VLDL
- premature AS
III familial type III lipoproteinemia
-inc in what?
-inc in IDL - premature AS
IV Familial hypertriglycidemia
-inc in what?
-inc in VLDL - premature AS
V Only familial AI/CII deficiency
-what problem?
-no HDL - severe AS
Unusual associations with AS?
- elevated plasma homocysteine (use folate and Vit B)
- Chlamydia pneumonia in plaques (organisms that induce inflammation)
content of atherosclerotic lesions
1) similar to chronic inflammation
- infiltration by macrophages and lymphs
- mesenchymal cell prolif
- fibrosis
- cell necrosis
- neovascularization
2) additional (not in chornic inflam)
- lipid accumulation - esp cholesterol
Hypothesis for atherogenesis:
- starts with endothelial cell injury due to hypercholesterolemia, disturbed flow, smoking…etc
- vascular response to injury
- macrophages release agents locally which sustain a chronic inflammatory reaction
- endothelial cells over-express vascular adhesion molecule-1 (VCAM-1)=inc cellular adhesion and inflammatory cells+cytokines (MCP-1- most potent)
- most macrophages accumulate modified lipids = foam cells and fatty streaks
role of macrophages:
- plasma LDL gets into the intima = modification or oxidation by free radicals (becomes toxic) –> macrophage takes up = macrophage foam cell
- macrophages, SMCs, and endothelial cells release monocyte chemo-attractant protein 1 (MCP-1) = more monocytes and proliferation of smooth muscle
-smooth muscle can also take up fat but not seen as much as macrophages-macrophages are primary
significance of foam cells:
these foam cells start secreting
- growth factors
- hydrolytic enzymes
- active oxygen metabolites (radicals)… etc
key features of AS:
- smooth muscle cell proliferation (change from contractile to secretory type)
- accumulation of connective tissue elements –> collagen, elastin, proteoglycans
- lipid deposition –> intra- and extracellular
the necrotic core of an AS plaque has:
-what is risk?
a bunch of shit - collagen, fat, foam cells…
one thing being cholesterol cleft (artifact due to slide prep - cholesterol polymerized)
-if this plaque ruptures = instant thrombus
Over decades what happens to AS plaques?
they calcify = plasticity of vessel altered
role of hemodynamics in atherogenesis
- pressure (HTN)
- regions of low shear and/or disturbed flow
- flow recirculation zones (eddies) - associated with arterial branches and bifurcations
Lesion complications:
- calcification
- rupture or ulceration
- hemorrhage
- thrombosis
What is a vulnerable plaques?
-one that has a very thin fibrotic cap and is soft = easily rupture especially6 in shoulder region
==> thrombus
Late clinical issues of AS?
- aneurysms + rupture
- occlusion by thrombus
- critical stenosis
Primary therapies for clinical AS:
- statins
- control BP & DM
- Clotting control
- diet and lifestyle
Secondary therapies of clinical AS:
- tissue plasminogen activator
- angioplasty with stent placement (coronary of carotid)
- carotid endarterectomy
- CABG (by-pass)
most complex AS lesions where?
superficial femoral artery
Ankle brachial pressure index of what is considered abnormal? What does this suggest?
-the lower the number then the more severe the arterial disease
- if >1.3 = calcification of walls of arteries and incompressible vessels ==> severe peripheral vascular disease
- important predictor of mortality
Clinical manifestations of AS?
ischemic injury to organs and tissues:
- MI
- ischemic stroke
- peripheral arterial disease (PAD)–> gangrene
- visceral infarction
- atherosclerotic aneurysms
Glagov’s coronary remodeling hypothesis:
- basically as you get more AS in the intima the lumen size remains constant.
- the lumen doesnt start to get occluded until late stage disease
Diagnostic modality for AS?
- intravascular ultrasound (IVUS)
- cannot predict RUPTURE DURP
lumen reduction to what percent of normal yields perfusion issues?
if occluded 70-80% of normal area
women vs men risk
men more at risk
-risk becomes approx equal after women pass menopause
