Atherosclerosis - Exam 2 Flashcards
What is the innermost layer of the artery? What does it consist of?
Tunica Intima
endothelium, subendothelial layer, and elastic membrane
_____ is the inner lining of the tunica intima. What is its role? What 4 things does it modulate?
Endothelium
Thromboresistant layer between blood and subendothelial tissue
tone, growth, hemostasis and inflammation throughout circulatory system
What is the middle layer of the artery? It consists of ______ and ______
Tunica Media
smooth muscle cells and elastic membrane
What is the outer layer of the artery? What is it composed of?
Tunica Externa / Adventitia
extracellular matrix with fibroblasts, mast cells and nerve terminals
What layer of the artery? ______ creates the pathway for oxygenated blood to be carried to the site of perfusion
tunica intima
What layer of the artery? ______ is comprised of smooth muscle that dilates and constricts in response to cardiac output needs
Tunica media
What layer of the artery? _______ connects arteries to other structures in the body
Tunica externa / adventitia
What are the 6 steps in the progression of atherosclerosis?
What does the fatty streak formation occur as a result of? What type of cells specifically?
Thickening of the intima due to the accumulation of foam cells (recall from our lipid lecture!) and extracellular matrix
foam cells
When foam cells accumulate in the intima, we see fatty streak formation
During the fatty streak formation, _______ precipitates monocyte binding to endothelium. _______ cross endothelium and become activated tissue ______. ______ “eat” oxidized LDL, becoming ______. T cells release ______, which further activates macrophages and cause smooth muscle cells to proliferate. Smooth muscle cells move to subendothelial space, producing ______ and taking up LDL, adding to foam cell accumulation
Vascular injury
monocytes
macrophages
macrophages
foam cells
cytokines
collagen
What is step 2 called? What happens during the phase?
plague formation
Plaque eventually evolves from the fatty streak and develops as connective tissue and debris accumulate
During step 2, what does the connective tissue and debris accumulation consist of?
Consists of lipid-containing smooth muscle cells and an extracellular lipid pool
What is step 3? What happens during this step?
development of advanced lesions
As plaque builds, we see a necrotic lipid–rich core and calcified regions that develop over time
A larger plaque that is building in step 3 is called an _______. What happens as a response?
atheroma
Coronary arteries remodel in response to atheroma formation
What is the difference between positive and negative remodeling? What step is this commonly seen in?
positive: increased vessel size occurring early in CHD to compensate for plaque accumulation in an effort to reduce lumen loss
aka the vessel gets bigger so blood can continue to flow
negative: results in vessel shrinkage
seen in step 3, development of advanced lesions
What is step 4? What is happening? What is the goal?
Step 4: Fibrous Cap Formation
As plaque/atheromas develop, a dense collagen-based layer of connective tissue covers the well-defined lipid core of an atherosclerotic plaque
further provides stability
At what step is the plaque considered stable? What step results in critical changes as a result of continuing developing plaques?
step 4
step 5
What is the vasa vasorum? What is its role?
The vasa vasorum is a network of micro-vessels that provides oxygen and nutrients to outer layers of arterial wall
What is step 5? What is happening in this step?
Step 5: Disruption of the Vasa Vasorum
as the atherosclerotic plaques expand into the vasa vasorum it results in microvascular hemorrhaging, further inflammation, and worsening atherosclerosis/potential thrombosis
What is step 6? This occurs a result of _______. What does this lead to?
Step 6: Intraplaque Hemorrhage
A result of plaque neovascularization
Critical event that leads to accelerated plaque progression, instability, and ischemic vascular events → unstable plaque can rupture leading to thrombosis
What step is considered the critical event? Why is it considered so harmful?
Step 6: Intraplaque Hemorrhage
ischemic vascular events → unstable plaque can rupture leading to thrombosis
Why does endothelial dysfunction result in worsening atherosclerosis? What does atherosclerosis impede development of? Why is this important?
because endothelial dysfunction FEEDS atherosclerosis through inflammation
impede the availability of nitric oxide (NO)
NO is needed so the vessels can dilate and constrict properly
Name 4 additional CV risk factors that decrease the availability of NO. Why are these considered especially harmful?
smoking, HTN, HLD, and diabetes
damage precipitates inflammation, leading to worsening atherosclerosis thereby contributing to the cycle
______ plays a key role in the pathogenesis of atherosclerosis. What eats oxidized LDL? What happens as an end result?
Inflammation
macrophages
This releases inflammatory substances, cytokines, and growth factors leading to further plaque proliferation
chronic inflammation results in the _____ plaques and active inflammation results in the ______ plaques
Chronic inflammation → stable plaques
Active inflammation → unstable & ruptured plaques
Atherosclerosis is usually asymptomatic until the plaque causes _____ stenosis of the vessel lumen. Then what happens?
70-80%
blood flow is impeded and s/s of angina may start showing
What are the 2 ways atherosclerotic plaques can progress? What is happening in the lumen during each?
Chronic → slow luminal narrowing
Acute → rapid luminal narrowing associated with plaque hemorrhage and/or luminal thrombosis
______ occurs as the vessel erodes and the plaque continues to grow → this compromises the ______ nature of vessel walls
Plaque erosion
antithrombotic
How will plaque rupture or erosion present? What is it characterized by? What does it lead to?
usually silent with no acute symptoms
Characterized by repeated ruptures and thrombosis followed by wound healing
Leads to increased plaque burden, progression of vessel stenosis, and negative arterial remodeling
What is the #1 cause of death in the US? What is the average age of ACS presentation?
CHD/Atherosclerotic CAD
68 years
**What are the 5 CHD risk equivalent dz?
Symptomatic carotid artery disease
Peripheral arterial disease (PAD)
Abdominal aortic aneurysm (AAA)
Diabetes mellitus
Chronic kidney disease (CKD)
**What are the 6 modifiable CHD risk factors? What is the highlighted one?
Cigarette smoking
**What are the 3 unmodifiable risk factors for CHD?
_____ is the #1 preventable cause of death and illness in the US. Also has higher risk of _____ and ______
cigarette smoking
IHD and sudden cardiac death
Give 3 reasons smoking promotes atherosclerosis. What is the major one?
increasing platelet adhesiveness
raised endothelial permeability
SNS stimulation by nicotine
Why does hypercholesterolemia have a directly proportional relationship with atherosclerosis and CHD?
-plaques contain cholesterol and cholesterol esters
- Risk increases progressively with higher levels of LDL and declines with higher levels of HDL
- Populations having hypercholesterolemia have higher mortality from CHD
What 4 groups of people would benefit from taking a statin?
What are the 4 high-intensity statins?
Rosuvastatin (Crestor) 20-40 mg
Atorvastatin (Lipitor) 40-80 mg
Why does persistently high HTN lead to plaque formation?
Endothelial injury resulting from persistent high BP leads to plaque formation as per response to injury hypothesis
What is the trend between DM and atherosclerosis?
Atherosclerosis develops at an early age in people with both Type 1 and Type 2 DM even when their BS is well controlled
At least ____ of people with diabetes die of some form of heart or blood vessel disease
65%
At what age does the risk increase for men? for women? Postmenopausal women on ____ have an increased risk of CV events.
men: risk increases at 45
women: risk increases at 55
hormone replacement therapy
When do fully-developed atheromatous plaques tend to appear?
40s and beyond
What is the genetic component with regards to CHD and risk? Give both male and female
CHD in male first degree relative <55 years
CHD in female first degree relative <65 years
What ethnicity has the highest risk for heart disease?
black
What are the USPSTF recommendations with regards to AAA?
men aged 65-75 who have even smoked- grade B
men aged 65-75 who have NEVER smoked - grade C
**What are the USPSTF recommendations for ASA use?
Grade C
aka must meet the criteria for ASA use and it is NOT recommended to give it just anyone as a preventative measure
