Atherosclerosis Flashcards
What is the innermost layer of an artery and what does it consist of?
Tunica intima
Does atherosclerosis effect veins?
Just arteries unless vein is used for bypass
What layer of the artery is thromboresistant?
Endothelium of tunica intima, which is a Continuous, thromboresistant layer between blood and potentially thrombogenic subendothelial tissue
Modulates tone, growth, hemostasis and inflammation throughout circulatory system
What is the middle layer of an artery, outer layer?
Tunica Media
Middle layer of an artery
Consists of smooth muscle cells and an elastic membrane
Tunica Externa / Adventitia
Outer layer of an artery
Composed of extracellular matrix with fibroblasts, mast cells and nerve terminals
Explain arterial physiology in the lens of the tunica intima, media, and externa/adventia?
At the most basic level, arteries carry oxygenated blood throughout the body
Tunica intima creates the pathway for oxygenated blood to be carried to the site of perfusion
Tunica media is comprised of smooth muscle that dilates and constricts in response to cardiac output needs
Tunica externa / adventitia connects arteries to other structures in the body
What is atherosclerosis?
Athero: porridge, fatty material
sclerosis: hardening d/t walling off the fatty material (Refers to connective tissue in the plaques)
Blood can no longer move, leading to ischemia and death
What are fatty streaks?
The first development of althersclerosis that can happen at childhood
What arteries can be affected with atherosclerosis?
All of them!
Brain = stroke
Abdominal aneurism
etc
What are the 6 histologic steps of artherosclerosis?
Fatty streak formation
Fibrous cap development (covers fat up)
Disruption of the vasa vasorum (outside of artery feeds it)
Proliferation of the fibrous plaque (becomes even thicker)
Development of an advanced lesion
Intraplaque hemorrhage (the fatty substances of blood can break up d/t nicks)
Can kill the patient
Explain the development of a fatty streak
The initial histologic step in development of atherosclerosis
Occurs as a result of:
Focal thickening of the intima d/t accumulation of foam cells (looks like fomy beer) and extracellular matrix
Smooth muscle cells can also deposit in the intima
Lipids accumulate, creating the fatty streak
Coronary arteries have a specific protein, biglycan, that can trap VLDL and LDL
Fatty streaks may also contain T lymphocytes²
Vascular injury precipitates monocyte binding to endothelium
Monocytes cross endothelium and become activated tissue macrophages
Macrophages “eat” oxidized LDL, becoming foam cells
T cells release cytokines, which further activates macrophages and cause smooth muscle cells to proliferate
Smooth muscle cells move to subendothelial space, producing collagen and taking up LDL, adding to foam cell accumulation
What is a fatty streak composed of?
foam cells
If a fatty cap becomes stable, what is formed?
Fibrous cap - it is more stable and there can be less pain (as opposed to an unstable fatty streak)
Explain the Disruption of the Vasa Vasorum
A network of micro-vessels originating from tunica adventitia of large arteries
Serve to provide oxygen and nutrients to outer layers of arterial wall
As atherosclerotic plaques expand, they acquire their OWN microvasculature. Plaque vasculature is thin-walled, extending through all layers of the arterial wall
Increased risk of microvascular hemorrhage, leading to progression of atherosclerosis and the fatty streak
this allows more RBCs to hit and can further the clots
Explain the proliferation of the fibrous plaque?
Evolves from the fatty streak
Develops as connective tissue accumulates
Consists of lipid-containing smooth muscle cells and an extracellular lipid pool
What is unstable angina?
Chest pain all the time, including at rest
stable angina, chest pain with exertion
Explain positive vs negative remodeling
Positive remodeling: increased vessel size occurring early in CHD to compensate for plaque accumulation in an effort to reduce lumen loss
Physiologically, alters arterial function leading to symptoms of unstable angina
Negative remodeling: results in vessel shrinkage
Results in obstructive plaques that lead to stable angina
What is the critical event of artherosclerosis?
A result of plaque neovascularization
Critical event that leads to accelerated plaque progression, instability, and ischemic vascular events
all of the blood and fatty tissue occlude the blood flow to the tissue leading to ischemia
What two main things do we need for atherosclerosis?
Lipids (hyperlipidemia)
Inflammation
STATINS!!!!!
Apart from lipids and inflammation, what factors can lead to the development of altherscleoris?
Endothelial Dysfunction
Inflammatory & Immunologic Factors
Plaque Rupture or Erosion
Risk Factors for Development of Disease
What is the initial step of artherosclerosis?
Endothelial vasodilator dysfunction (because you cannot vasodilates, leading to more cholestrol build-up)
What does endothelial vasodilator dysfunction a result of?
Endothelial-derived nitric oxide
What can cause endothelial dysfunction?
Turbulent BF
hypercholestremia
DM
HTN
smoking
anything that will damamge the lining!
Why does inflammation lead to the pathogenesis of acute and chronic atherosclerosis?
Release of growth factors
chronic inflammation leads to stable plaques
active inflammation unstable and ruptured plaques
When does atherosclerosis lead to symptoms?
Typically asymptomatic until 70-80% stenosis (sometimes even 50% though)
this is why we need to treat early and aggressive
chronic = slow luminal narrowing
acute = rapid luminal narrowing associated with plaque hemorrhage and/or luminal thrombosis
Does plaque rupture always lead to symptoms?
NO
What can atherosclerosis lead to?
Coronaries – MI, angina
CNS – Stroke, TIA
Periphery – Claudication, limb ischemia/poor healing, aneurysms
Renal Arteries – RAS
GI – mesenteric ischemia (abdominal arteries will need a stent)
all of the arteries can be affected
What is the #1 cause of death?
CHD/ atherosclerotic CAD
1 US person dies every 33 seconds :(
1 in 5 deaths are caused by
What is the average age of death atherosclerosis?
68 years
What is the MC presentation of CHD?
Death :(
silent heart attacks
What does a DM female often have as a presentation for heart attack?
Just stomach pain
What patients have the highest risk of death with atherosclerosis?
Men is MC
happens in all ethnicities
What is a coronary heart disease (CHD) equivalent?
Treated as if they have heart disease
We assume they have it
What are the CHD equivalence?
Clinical coronary heart disease (CHD)
Symptomatic carotid artery disease
Peripheral arterial disease (PAD)
Abdominal aortic aneurysm (AAA)
Diabetes mellitus
Chronic kidney disease (CKD)
CADCP
What are the modifiable risk factors of atherosclerosis?
Cigarette smoking
Dyslipidemias (↑LDL or ↓HDL)
HTN
DM
Obesity
Sedentary Lifestyle
High C-reactive protein (inflammation marker)
High triglycerides (esp women)
Sleep apnea (hypoxia, obestiy)
Stress
Persistent heavy alcohol use
elevated homocysteine (low levels of B6, B9, B12 - gastric bypass patients, vegans)
What are the unmodifiable risk factors of CHD?
Premature CHD in 1st degree relative (age <55 in men, <65 in women)
Age (men ≥ 45 y/o, women ≥ 55 y/o)
Male sex
How much does smoking risk heart disease?
Alone
2-4X
On average, how many years less do smokers live?
10 years less
What are the four groups that receive statins?
Individuals with clinical ASCVD (secondary prevention)
Individuals with primary elevations of LDL–C ≥190 mg/dL
Individuals 40-75 yrs with DM and LDL–C 70 to 189 mg/dL w/out clinical ASCVD
Individuals w/out clinical ASCVD or DM who are 40-75 yrs with LDL–C 70-189 mg/dL and have an estimated 10-year ASCVD risk of >7.5%
How does HTN lead to atherosclerosis?
Mechanical injury to the arterial wall causing it to be thicken and stiff leading to plaque formation
DM and atherosclerosis
Atherosclerosis develops at an early age in people with both IDDM and NIDDM
Even when glucose levels are under control…
Diabetes increases the risk of heart disease and stroke
Risks are even greater if blood sugar is not well controlled
At least 65% of people with diabetes die of some form of heart or blood vessel disease
CHD risk equivalent
What age is concerning of fx of heart attack for males and females?
CHD in male first degree relative <55 years; CHD in female first degree relative <65 years
Difference between age and gender of coronary heart disease
Higher incidence & severity in men
Present with problems earlier in life
Risk increases after age 45
Lower incidence in women, especially in premenopausal age¹
Risk increases after 55 yrs, although still lower than men’s risk despite increased risk after menopause
Postmenopausal women on HRT have an increased risk of CV events
Fully-developed atheromatous plaques usually appear in 40s and beyond
About 80% of people who die of CHD are >65
Why might AA have a higher risk than caucasians to have cardiovascular disease?
higher instance of high BP
According to USPSTF, what patient should you screen for AAA?
65-75 who have ever smoked
What is the recommendation according to the USPSTF for aspirin prophylaxis?
C for aspirin use if 40-59 with 10% greater of ASCVD
What is USPSTF screening for HTN, DM, tobacco
HTN: A for all patients >18
prediabetes T2DM: B
Statin: B
Smoking: A
CRP screening
Mr. Jones is a 69-year-old obese male (BMI 40) presenting to your clinic to establish care. He has a 25-pack-year history of smoking and drinks alcohol daily (3 beers/day). His blood pressure is 138/90 today. He is taking no medications and is unsure of his medical history. Based off our lecture discussion regarding cardiovascular risk prevention, what needs to be considered for this patient?
No smoking
<15 beers a week
