Atherosclerosis and CHD Flashcards
What is the innermost layer of the artery?
Tunica intima
What does the tunica intima consist of?
Endothelium, subendothelial layer, and elastic membrane
What is the endothelium?
- Inner lining of tunica intima
- Thromboresistant layer between blood and thrombogenic subendothelial layer
What is the function of the endothelium?
- Modulates tone, growth, hemostasis, and inflammation throughout circulatory system
What is the middle layer of the artery?
Tunica media
What does the tunica media consist of?
Smooth muscle and an elastic membrane
What is the outer layer of an artery?
Tunica externa/adventitia
What is the tunica externa/adventitia composed of?
Extracellular matrix with fibroblasts, mast cells, and nerve terminals
What is the basic function of arteries?
Carry oxygenated blood throughout the body
What is the function of the tunic intima?
Creates pathway for oxygenated blood to be carried to site of perfusion
What is the function of the tunica media?
Comprised of smooth muscle that dilate and constrict in response to cardiac output needs
What is the function of the tunica externa/adventitia?
Connects arteries to other structures in the body
What is atherosclerosis?
- Pathologic process that causes disease of the coronary, cerebral, and peripheral arteries
How does atherosclerosis begin?
With development of fatty streaks within arterial walls, can begin as early as childhood
What are the 6 histologic steps in the development of atherosclerosis?
- Fatty streak formation
- Fibrous cap development
- Disruption of the vasa vasorum
- Proliferation of the fibrous plaque
- Development of an advanced lesion
- Intraplaque hemorrhage
What causes the development of a fatty streak?
- Thickening of intima due to accumulation of foam cells and extracellular matrix (smooth muscle can also deposit)
- Lipids accumulate causing fatty streak
What can the fatty streak contain?
Foam cells, extracellular matrix, smooth muscle cells, T lymphocytes
* Coronary arteries have biglycan and can trap VLDL and LDL
What are the steps in fatty streak formation?
- Vascular injury precipitates monocyte binding to endothelium
- Monocytes cross endothelium to become macrophages
- Macrophages eat LDL and become foam cells
- T cells release cytokines which activate 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
If the plaque remains stable, what will form?
A fibrous cap
What is a fibrous cap?
- A dense, collagen-based layer of connective tissue that covers the lipid core of an atherosclerotic plaque
- Provides stability to plaque
What is the vasa vasorum?
- Micro-vessels originating from tunica adventitia
- Provide oxygen and nutrients to outer layer of arterial wall
What happens with disruption of the vasa vasorum?
- As atherosclerotic plaques expand, they acquire their own microvasculature
- Plaque vasculature is thin-walled, leading to increased risk of microvascular hemorrhage and progression of atherosclerosis
What happens during proliferation of the fibrous plaque?
- Connective tissue accumulates from the fatty streak
- Connective tissue consists of lipid containing smooth muscle and extracellular lipid pool
What happens in the development of advanced lesions?
- Necrotic lipid-rich core and calcified regions develop over time
- Coronary arteries remodel in response to atheroma formation
What is positive remodeling of advanced lesions?
- Increased vessel size early in CHD to compensate for plaque accumulation in an effort to reduce lumen loss
- Alters arterial function leading to symptoms of unstable angina (@rest/seated/exercise)
What is negative remodeling?
- Vessel shrinkage resulting in obstructive plaques that lead to stable angina
What happens during the intraplaque hemorrhage stage of atherosclerosis?
- Due to plaque neovascularization
- leads to accelerated plaque progression, instability, and ischemic vascular events
What factors contribute to the development of atherosclerosis and its complications?
- Endothelial dysfunction
- Inflammatory and immunologic factors
- Plaque rupture or erosion
- Risk factors for development of disease
What is the initial step in the pathogenesis of atherosclerosis?
Endothelial vasodilator dysfunction d/t loss of endothelial-derived nitric oxide
What precipitates endothelial vasodilator dysfunction?
oxidized LDL
What is associated with endothelial dysfunction?
- Hypercholesterolemia
- Diabetes
- Hypertension
- Cigarette smoking
What are ways to improve endothelial vasodilator dysfunction?
- Correct HLD
- ACEI if HTN present
- High doses of antioxidants (vitamin C, flavonoids)
How does inflammation impact atherosclerosis?
- Macrophages eat oxidized LDL
- Releases inflammatory substances, cytokines, and growth factors leading to plaque proliferation
What does chronic inflammation lead to?
Stable plaques
What does active inflammation lead to?
Unstable and ruptured plaques
Atherosclerosis is usually asymptomatic until the plaque causes what % stenosis of the vessel lumen?
70-80
Once the plaque causes 70-80% stenosis of the lumen, what occurs?
Blood flow impediment and symptoms of angina pectoris
What are the 2 processes that atherosclerotic plaques can progress via?
Chronic and acute
What happens in chronic atherosclerotic plaque progression?
Slow luminal narrowing
What happens in acute atherosclerotic plaque progression?
Rapid luminal narrowing with plaque hemorrhage and/or luminal thrombosis
Plaque erosion can occur in the absence of rupture when what happens?
endothelium is missing at plaque site
What does it mean for a plaque rupture or erosion to be silent?
- No acute symptoms
- Repeated ruptures and thrombosis followed by wound healing
- Leads to increased plaque burden, progression of vessel stenosis, and negative arterial remodeling
What are the effects of atherosclerosis?
- Coronary arteries: MI, angina
- CNS: stroke, TIA
- Periphery: claudication, limb ischemia/poor healing, aneurysms
- Renal arteries: RAS
- GI: mesenteric ischemia
Why is it important to manage atherosclerosis?
- Major cause of death
- # 1 cause of death in US and worldwide
- 1 person dies every 33 sec from CVD
What is the epidemiology of atherosclerosis?
- Prevalence increases with age
- Average ACS presentation is 68 yrs
How do 40-50% of adults in US present with their first sign of heart disease?
Sudden death
in 2020, _____ deaths in the US was due to CHD
1 in 5
805,000 individuals in the US suffer from an MI annually with 1 in 5 heart attacks being silent
From 2018-2019 it cost more than _______ billion per year to care for heart disease in the US
$239
This is projected to reach $1.1 trillion by 2035
What race of ethnic groups has the highest % of deaths due to atherosclerosis?
White
Native hawaiian or pacific islander
Black
What are CHD risk equivalents?
- Clinical coronary heart disease (CHD)
- Symptomatic carotid artery disease
- Peripheral arterial disease
- Abdominal aortic aneurysm
- Diabetes mellitus
- Chronic kidney disease
What are modifiable risk factors for atherosclerosis?
- Cigarette smoking
- Dyslipidemias
- HTN
- DM
- Obesity
- Sedentary lifestyle
What are unmodifiable risk factors for atherosclerosis?
- Premature CHD in 1st degree relative <55 men, <65 women
- Age >45 men, >55 women
- Male sex
What are additional risk factors for atherosclerosis/CHD?
- High serum levels of CRP
- High triglycerides
- Sleep apnea
- Stress
- Persistent heavy alcohol use
- Elevated homocysteine levels
How much does cigarette smoking increase risk of heart disease?
2-4x
On average, smokers die ______ than nonsmokers
10 years earlier
The #1 preventable cause of death and illness in the US. How much can stopping it reduce the risk of CHD?
Cigarette smoking
50%
How does cigarette smoking impact severity of atherosclerosis?
Higher risk, severity, and extent of atherosclerosis in smokers
Also higher risk of IHD and sudden cardiac death
How does smoking promote atherosclerosis?
- Increases platelet adhesiveness
- Raises endothelial permeability
- SNS stimulation by nicotine
Why is hypercholesterolemia and atherosclerosis/CHD directly proportional?
- Atherosclerotic plaques contain cholesterol and cholesterol esters
- Risk increases progressively with higher LDL and declines with higher HDL
- Populations with hypercholesterolemia have higher mortality from CHD
- Dietary regulation and administration of cholesterol-lowering drugs have beneficial effect on reducing the risk of CHD
What groups benefit from statins?
- Individuals with clinical ASCVD
- 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%
What are the high intensity statins?
Atorvastatin 40-80 mg
Rosuvastatin 20-40 mg
Look at the flowchart for primary prevention with statins and try to figure it out
:(
What are the moderate intensity statins?
Atorvastatin 10-20 mg
Rosuvastatin 5-10 mg
Simvastatin 20-40 mg
Pravastatin 40-80 mg
Lovastatin 40 mg ER
Fluvastatin 80 mg
Pitavastatin 2-4 mg
How is hypertension related to atherosclerosis?
- Causes mechanical injury to arterial wall
- Increases heart’s workload causing heart muscle to thicken and become stiff
- Endothelial injury from persistent high BP leads to plaque formation as per response to injury hypothesis
How is DM related to atherosclerosis?
- Ath develops at an early age in people with both IDDM and NIDDM
- Diabetes increases risk of heart disease and stroke
- At least 65% of people with diabetes die of some form of heart or blood vessel disease
- Considered CHD risk equivalent
How is risk for atherosclerosis/CHD different for men?
Higher incidence and severity
Presents earlier in life
Risk increases after age 45
How is risk for atherosclerosis/CHD different for women?
- Lower incidence in women, especially premenopausal
- Risk increases after 55 yrs although still lower than men’s despite increased risk post menopause
- Postmenopausal women on HRT have increased risk of CV events
Fully-developed atheromatous plaques usually appear when?
40s+
What genetic and familial factors are related to CHD and atherosclerosis?
- Increased risk of CHD with family history of premature CHD
- CHD in male first degree relative <55 years; CHD in female first degree relative <65 years
- Hereditary genetic derangements of lipoprotein metabolism predispose to high blood lipid level and familial hypercholesterolemia
- Familial predisposition to atherosclerosis may be related to other risk factors like diabetes, hypertension, and hyperlipidemia
- Children of parents with heart disease are more likely to develop it themselves
What racial and ethnic factors influence atherosclerosis and CHD?
- African americans have more severe high BP than caucasians
- Heart disease risk is also higher among mexican americans, american indians, native hawaiians, and some asian americans
What goes into calculating the 10 year ASCVD risk?
- Age and gender
- Diabetes
- Race
- Smoking
- Cholesterol
- Blood pressure
What grade is statin use in a patient with 1 or more CV risk factors and 10-year CVD risk of 10% or greater by USPSTF?
B
What grade is the USPSTF recommendation that adults with CVD risk are offered behavioral counseling interventions to promote a healthy diet and physical activity?
B
What grade is the USPSTF recommendation that patients are advised to quit tobacco use?
A
