Arteriosclerotic Cardiovascular DZ (ASCVD) Flashcards
3 patterns of arteriosclerosis
- atherosclerosis (AS)
- Monckeberg’s medical calcific sclerosis
- arteriolosclerosis
what is medial calcific sclerosis
- calcification of muscle wall (media) of arteries
- may ossify
- no narrowing of vessel lumen***
- patients older than 50yo
what is arteriolosclerosis
- thickening and narrowing of vascular walls of small arteries and arterioles
- associated with hypertension and diabetes
two variants of arteriolosclerosis
- hyaline
2. hyperplastic
what is atherosclerosis
- intimal fibrofatty plaques
- narrow vascular lumen
- weaken arterial wall (media)
major targets of atherosclerosis
- aorta (AAA,PVD, intestinal ischemia)
- coronary arteries (IHD, MI)
- cerebral arteries (stroke)
epidemiology of AS
- responsible for half of all deaths in the western world
- ubiquitous in developed nations
- less common in central and south america, africa, asia, japan
- begins in early childhood
reduction in death rate from IHD and stroke since 1963 d/t what?
- lifestyle changes (diet, smoking, control of HTN)
- improved therapy for IHD
- prevention of recurrences
constitutional risk factors for AS
- age - 40 to 60 year olds have 5x incidence of MI
- sex - males have 5x death rate from IHD until menopause???
- genetics - familial clustering of other risk factors; genetic defects
acquired risk factors for AS
hyperlipidemia
hypertension - >160/95 5x risk than
what is the CRP
- systemic marker of inflammation synthesized by liver
- level correlates with risk of IHD/MI, stroke, PVD, SCD
- levels reduced by smoking cessation, weight loss, exercise, statins
role of HDL
- reverse transport of cholesterol from cells/plaque to liver for excretion in bile
- elevated HDL associated with reduced risk of IHD
- Exervise and ETOH elevated HDL
- obesity and smoking reduce HDL
risk factors are additive in IHD (T/F)
false, not additive
- two risk factors = 4x risk of MI
- 3 risk factors = 7x risk of MI
other risk factors for AS
- inadequate physical activity
- type A personality
- obesity
- estrogen deficiency
- high carb diet
- hardened trans unsaturated fat intake
- chlamydia pneumoniae
- hyperhomocysteinemia
- lipoprotein Lp(a)
hyperhomocysteinemia
- inborn error of metabolism resulting in high levels of circulating homocysteine
- can also be caused by low folate and vitB intake
- level correlates with CAD, PVD, stroke and venous thrombosis
what is lipoprotein Lp(a)
- altered form of LDL (apolipoprotein B-100 of LDL linked to apolipoprotein A)
- correlatoin bw increased lipoprotein Lp(a) and coronary and cerebral vascular dz
leading hypothesis for:
pathogenesis of atherosclerosis
- focal chronic endothelial injury
- endothelial dysfunction and monocyte adhesion/emigration
- smooth muscle cell emigration and macrophage activation
- macrophages and SMCs engulf lipid (foam cells)
- proliferation of SMCs, ECM deposition, extracellular lipid
cellular events in AS
- endothelial injury
- lipids
- macrophages
- smooth muscle cells
- infection
endothelial injury caused by what
- endotoxin
- hypoxia
- smoking
- viruses
- immune rxn
- homocysteine
- hemodynamics
- hypercholesterolemia
how does hemodynamics affect AS formation
shear stress and turbulent flow
- plaques occur at branch points and posterior abdominal aorta
- lesion protected areas associated with induction of atheroprotective genes
what evidence is available for hyperlipidemia and AS
- hyperlipoproteinemias are associated with accelerated AS
- hypercholesterolemias are associated with premature and severe AS
- atheromas contain cholesterol
- severity of AS correlates with total and LDL cholesterol levels
- lowering serum cholesterol slows progression and cuases regression of AS and reduces risk
mechanism of hyperlipidemia and AS
- direct endothelial dysfunction via free radical deactivation of NO (EDRF)
- accumulation of lipoproteins in intima at sites of increased endothelial permeability
- free radical oxidation of LDL
how does free radical oxidation of LDL effects in AS
- ingested by macrophages forming foam cells
- increases monocyte accumulation in lesions
- stimulates release of growth factors/cytokines
- cytotoxic to ECs and SMCs
- can induce endothelial dysfunction
role of macrophages in AS
- adhere to dysfunctional ECs
- migrate bw ECs to intima
- transform into macrophages and engulf lipoproteins (oxidized LDL) to become foam cells
- recruit WBCs
- oxidize LDL
- elaborate growth factors
role of smooth muscle cells in AS
- maturation and growth of AS lesions by action of growth factors (PDGF, FGF, TGF-alpha)
- implicated in monoclonal hypothesis of atherogenesis
infection and AS
- organisms have been detected in plaques
- organisms may incite chronic inflammatory process contributing to AS
- antibiotic therapy reduces recurrence in IHD
what does an atheromatous plaque look like
melted cheese on lasagna noodle
how can a plaque be complicated
- calcification
- fissuring/ulceration (may embolize)
- thrombosis
- hemorrhage (may rupture)
AHA classification of AS lesions
type I: fatty dot typeII: fatty streak type III: intermediate lesion type IV: atheroma type V: fibroatheroma type VI: complicated plaque
what is an aneurysm
abnormal dilatation of arteries/veins d/t weakening of vessel wall
ex. congenital defect (berry aneurysm), local infection (mycotic aneurysm), trauma, systemic dz (AS, CMN, syphilis)
atherosclerotic aneurysms
- most common cause of aortic aneurysm
- male predominance (5:1 after 5th decade)
- most located in infrarenal aorta
- possible underlying genetic defect in connective tissue
- variable shape (saccular, cylindroid, fusiform)
- size (15cmx25cm)
pathogenesis of atherosclerotic aneurysms
- AS destroys tunica media
- frequent mural thrombosis
outcome of atherosclerotic aneurysms
- rupture
- propagate
- embolize
- erode adjacent structures
4 syndromes of IHD
- angina pectoris
- myocardial infarction
- chronic IHD
- sudden cardiac death
what is IHD
aka coronary heart dz
- most common cause is atherosclerosis
- most common cause of death in developed countries
epidemiology of IHD
- older pts (male >60yo; female >70yo)
- males>females until 9th decade
risk factors for IHD
HTN DM smoking elevated LDL genetic
reduce risk of IHD how?
- exercise (increased vascularity , reduced MVO2)
- moderate consumption of red wine (HDL)
pathogenesis of IHD
- coronary artery atherosclerosis
- critical stenosis >75% narrowing
- dynamic changes in plaque morphology:
1. acute plaque changes
2. coronary artery thrombosis
3. coronary artery vasospasm
acute plaque changes in IHD
- fissuring, hemorrhage, rupture with embolization
- plaque enlargement and increased risk of thrombus
pathogenesis of acute plaque changes
-T cell activation of macrophages with secretion of metalloproteinases degrade collagen cap plus hemodynamic trauma
what is a coronary artery thrombosis
plaque rupture exposes thrombogenic lipids and subendothelial collagen
- complete occlusion results in AMI
- incomplete occlusion results in UA or sudden death or microinfarcts downstream
pathogenesis of coronary artery vasospasm
- preexisting AS
- TXA2 released by plt aggregates on disrupted plaque
- endothelial dysfunction with reduced EDRF
- increased adrenergic activity
- smoking
causes of IHD via reduced blood supply
- emboli from vegetations
- vasculitis
- systemic hypotension
causes of IHD d/t increased demand (LVH)
- systemic hypertension
- valvulopathy
what is angina pectoris
intermittent chest pain d/t reversible myocardial ischemia
3 variants of angina pectoris
- stable angina
- Prinzmetal’s or variant angina
- unstable angina (crescendo/preinfarction angina)
what is stable angina
- episodic chest pain associated with exertion or stress (predictable)
- chest pain is crushing, squeezing, may radiate to left arm
- fixed lesions >75% vessel lumen narrowed
- relieved by rest, NTG
how does nitro work
reduces preload and augments coronary blood flow
what is Prinzmetal’s angina
aka variant
- chest pain occurs at rest or while sleeping
- vasospasm near plaque
- responds to vasodilators
what is unstable angina
- aka crescendo and pre infarction angina
- increasing frequency of chest pain
- more intense and longer duration
- d/t acute plaque change - thrombus, embolization, vasospasm
what is MI
myocardial infarction
- local ischemia leading to corresponding myocardial necrosis
- single most common cause of death in industrialized nations
- same risk factors as CAD
pathogenesis of MI
- coronary artery thrombosis = most common
- pre existing plaque disrupted
- also caused by: vasospasm, plt aggregation, hypoperfusion (subendothelial infarcts)
evolution of MI
- necrosis after 20 to 30 minutes and max size after 3 to 6 hours
- –window for thrombolytic therapy
- initally subendocardial
- –last perfused
- –high pressure
- location and size depends on site of occlusion, collaterals
infarction location
LAD (40-50%) - anterior/apical infarcts
RCA (30-40%) - posterior/basal infarcts
LCX (15-20%) - lateral
infarct size
- more proximal occlusion - larger the infarct
- collateralization?
when are gross changes seen in MI
18-24 hours
when are microscopic changes seen in MI
0-18 hours
complications of MI
- papillary muscle dysfunction
- rupture
- mural thrombi
- acute pericarditis
- ventricular aneurysm
what is papillary muscle dysfuntion
- local bulging of ventricular wall
- ischemia of papillary muscle
- heart failure with dilated LV
when does ruptured papillary muscle occur in MI?
1% of MI pts
3 days after MI
severe MR and acute LV failure
two types of myocardial rupture
- external
2. internal (septal)
when does external rupture of myocardium happen
10% of mI pts
first 2 weeks due to poorly developed granulation tissue/fibrosis
hemopericardium and cardiac tamponade
when does internal rupture of myocardium happen?
1-3% of MI pts
acute left to right shunt and CHF
what is mural thrombi
thrombi form on endocardial surface overlying infarct (esp if ventricular aneurysm forms)
-may embolize causing stroke
acute pericarditis and MI
15% of MI pts
2-4 dyas after transmural infarct
-may cause significant effusion
morphology of acute pericarditis and MI
bread and butter or hemorrhagic
ventricular aneurysm
- fibrous myocardium bulges during systole
- anteroapical
- superimposed thrombosis
- outcome: arrhythmia, papillary muscle dysfunction, CHF, embolization
clinical features of MI
- severe crushing sub sternal chest pain +/- radiate to neck, jaw, epigastrium, shoulder, left arm for hours to days unrelieved by NTG
- rapid weak pulse, diaphoretic, dyspnea (pulm edema) shock (if >40% of LV infarcted)
- 50% preceded by angina
- 20-30% are silent (DM, HTN, elderly)
outcome after MI
- 25% sudden cardiac death
- 75% reach hospital
- -10-20% no complications
- -75-95% arrhythmias
- -60% LVF with pulm edema
- -10% cardiogenic shock
- -4-8% rupture
- -15-49% thromboembolism
lab features of MI
- electrocardiographic abnormalities (Q waves, ST changes, T wave inversions)
- cardiac enzymes: CK, troponin, LDH (not used as much)
what is the CK
creatinine kinase
- enzyme composed of dimers
- CKMM: muscle and heart
- CKBB: brain, lung
- CKMB: muscle and heart
CK cardiac index
total CK: rise 2-4 hrs peak 24 hrs decline 72 hrs
CKMB: rise 2-4 hrs, peak 18 hrs, decline 48 hrs
-if no change after 2 days, MI ruled out
what are troponins
- contractile proteins in human muscle and heart
- troponin T & I in heart
- troponin I more cardiospecific than CKMB
- rise 2-4 hours persisits 4-7 days after CK MB normalizes
- elevated also in unstable angina progressing to AMI
what is arteriosclerosis
vascular dz manifested by thickening and inelasticity of arteries
what is chronic IHD (CIHD)
also called ischemic cardiomyopathy
- progressive CHF d/t long term ischemic myocardial injury
- angina and infarcts common
gross morphology of CIHD
- mod-severe CAD
- cardiomegaly (dilated)
- multiple foci of fibrosis
- cardiac hypertrophy of remaining mycardium
- thick opaque endocardium
- adherent thrombi
microscopic features of CIHD
- extensive fibrosis
- atrophic and hypertrophic fibers
- subendocardial vacuolation
clinical features of CIHD
- s/s
- -severe progressive heart failure
- -+/- angina, infarcts
- -arrhythmias
outcome of CIHD
death due to CHF, MI, arrhythmia
what is sudden cardiac death
sudden immediate death ~ w/i 24 hrs of onset
- 300-400k/year in US (50% of all cardiac deaths)
- MC mechanism is lethal ventricular arrhythmia (Vfib) d/t IHD
- 50% of IHD pts will die of SCD
morphology of SCD
severe CAD - >75% narrowed in 2+ vessels
-arrhythmia d/t thrombosis and/or vasospasm superimposed on ruptured plaque (occlusive thrombi absent in 80%)
-recent or remote infarcts
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