Arteriosclerotic Cardiovascular DZ (ASCVD) Flashcards
(82 cards)
1
Q
3 patterns of arteriosclerosis
A
- atherosclerosis (AS)
- Monckeberg’s medical calcific sclerosis
- arteriolosclerosis
2
Q
what is medial calcific sclerosis
A
- calcification of muscle wall (media) of arteries
- may ossify
- no narrowing of vessel lumen***
- patients older than 50yo
3
Q
what is arteriolosclerosis
A
- thickening and narrowing of vascular walls of small arteries and arterioles
- associated with hypertension and diabetes
4
Q
two variants of arteriolosclerosis
A
- hyaline
2. hyperplastic
5
Q
what is atherosclerosis
A
- intimal fibrofatty plaques
- narrow vascular lumen
- weaken arterial wall (media)
6
Q
major targets of atherosclerosis
A
- aorta (AAA,PVD, intestinal ischemia)
- coronary arteries (IHD, MI)
- cerebral arteries (stroke)
7
Q
epidemiology of AS
A
- 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
8
Q
reduction in death rate from IHD and stroke since 1963 d/t what?
A
- lifestyle changes (diet, smoking, control of HTN)
- improved therapy for IHD
- prevention of recurrences
9
Q
constitutional risk factors for AS
A
- 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
10
Q
acquired risk factors for AS
A
hyperlipidemia
hypertension - >160/95 5x risk than
11
Q
what is the CRP
A
- 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
12
Q
role of HDL
A
- 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
13
Q
risk factors are additive in IHD (T/F)
A
false, not additive
- two risk factors = 4x risk of MI
- 3 risk factors = 7x risk of MI
14
Q
other risk factors for AS
A
- inadequate physical activity
- type A personality
- obesity
- estrogen deficiency
- high carb diet
- hardened trans unsaturated fat intake
- chlamydia pneumoniae
- hyperhomocysteinemia
- lipoprotein Lp(a)
15
Q
hyperhomocysteinemia
A
- 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
16
Q
what is lipoprotein Lp(a)
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
17
Q
leading hypothesis for:
pathogenesis of atherosclerosis
A
- 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
18
Q
cellular events in AS
A
- endothelial injury
- lipids
- macrophages
- smooth muscle cells
- infection
19
Q
endothelial injury caused by what
A
- endotoxin
- hypoxia
- smoking
- viruses
- immune rxn
- homocysteine
- hemodynamics
- hypercholesterolemia
20
Q
how does hemodynamics affect AS formation
A
shear stress and turbulent flow
- plaques occur at branch points and posterior abdominal aorta
- lesion protected areas associated with induction of atheroprotective genes
21
Q
what evidence is available for hyperlipidemia and AS
A
- 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
22
Q
mechanism of hyperlipidemia and AS
A
- 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
23
Q
how does free radical oxidation of LDL effects in AS
A
- 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
24
Q
role of macrophages in AS
A
- 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
25
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
26
infection and AS
- organisms have been detected in plaques
- organisms may incite chronic inflammatory process contributing to AS
- antibiotic therapy reduces recurrence in IHD
27
what does an atheromatous plaque look like
melted cheese on lasagna noodle
28
how can a plaque be complicated
- calcification
- fissuring/ulceration (may embolize)
- thrombosis
- hemorrhage (may rupture)
29
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
```
30
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)
31
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)
32
pathogenesis of atherosclerotic aneurysms
- AS destroys tunica media
| - frequent mural thrombosis
33
outcome of atherosclerotic aneurysms
- rupture
- propagate
- embolize
- erode adjacent structures
34
4 syndromes of IHD
1. angina pectoris
2. myocardial infarction
3. chronic IHD
4. sudden cardiac death
35
what is IHD
aka coronary heart dz
- most common cause is atherosclerosis
- most common cause of death in developed countries
36
epidemiology of IHD
- older pts (male >60yo; female >70yo)
| - males>females until 9th decade
37
risk factors for IHD
```
HTN
DM
smoking
elevated LDL
genetic
```
38
reduce risk of IHD how?
- exercise (increased vascularity , reduced MVO2)
| - moderate consumption of red wine (HDL)
39
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
40
acute plaque changes in IHD
- fissuring, hemorrhage, rupture with embolization
| - plaque enlargement and increased risk of thrombus
41
pathogenesis of acute plaque changes
-T cell activation of macrophages with secretion of metalloproteinases degrade collagen cap plus hemodynamic trauma
42
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
43
pathogenesis of coronary artery vasospasm
- preexisting AS
- TXA2 released by plt aggregates on disrupted plaque
- endothelial dysfunction with reduced EDRF
- increased adrenergic activity
- smoking
44
causes of IHD via reduced blood supply
- emboli from vegetations
- vasculitis
- systemic hypotension
45
causes of IHD d/t increased demand (LVH)
- systemic hypertension
| - valvulopathy
46
what is angina pectoris
intermittent chest pain d/t reversible myocardial ischemia
47
3 variants of angina pectoris
1. stable angina
2. Prinzmetal's or variant angina
3. unstable angina (crescendo/preinfarction angina)
48
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
49
how does nitro work
reduces preload and augments coronary blood flow
50
what is Prinzmetal's angina
aka variant
- chest pain occurs at rest or while sleeping
- vasospasm near plaque
- responds to vasodilators
51
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
52
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
53
pathogenesis of MI
- coronary artery thrombosis = most common
- pre existing plaque disrupted
- also caused by: vasospasm, plt aggregation, hypoperfusion (subendothelial infarcts)
54
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
55
infarction location
LAD (40-50%) - anterior/apical infarcts
RCA (30-40%) - posterior/basal infarcts
LCX (15-20%) - lateral
56
infarct size
- more proximal occlusion - larger the infarct
| - collateralization?
57
when are gross changes seen in MI
18-24 hours
58
when are microscopic changes seen in MI
0-18 hours
59
complications of MI
1. papillary muscle dysfunction
2. rupture
3. mural thrombi
4. acute pericarditis
5. ventricular aneurysm
60
what is papillary muscle dysfuntion
- local bulging of ventricular wall
- ischemia of papillary muscle
- heart failure with dilated LV
61
when does ruptured papillary muscle occur in MI?
1% of MI pts
3 days after MI
severe MR and acute LV failure
62
two types of myocardial rupture
1. external
| 2. internal (septal)
63
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
64
when does internal rupture of myocardium happen?
1-3% of MI pts
| acute left to right shunt and CHF
65
what is mural thrombi
thrombi form on endocardial surface overlying infarct (esp if ventricular aneurysm forms)
-may embolize causing stroke
66
acute pericarditis and MI
15% of MI pts
2-4 dyas after transmural infarct
-may cause significant effusion
67
morphology of acute pericarditis and MI
bread and butter or hemorrhagic
68
ventricular aneurysm
- fibrous myocardium bulges during systole
- anteroapical
- superimposed thrombosis
- outcome: arrhythmia, papillary muscle dysfunction, CHF, embolization
69
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)
70
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
71
lab features of MI
- electrocardiographic abnormalities (Q waves, ST changes, T wave inversions)
- cardiac enzymes: CK, troponin, LDH (not used as much)
72
what is the CK
creatinine kinase
- enzyme composed of dimers
- CKMM: muscle and heart
- CKBB: brain, lung
- CKMB: muscle and heart
73
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
74
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
75
what is arteriosclerosis
vascular dz manifested by thickening and inelasticity of arteries
76
what is chronic IHD (CIHD)
also called ischemic cardiomyopathy
- progressive CHF d/t long term ischemic myocardial injury
- angina and infarcts common
77
gross morphology of CIHD
- mod-severe CAD
- cardiomegaly (dilated)
- multiple foci of fibrosis
- cardiac hypertrophy of remaining mycardium
- thick opaque endocardium
- adherent thrombi
78
microscopic features of CIHD
- extensive fibrosis
- atrophic and hypertrophic fibers
- subendocardial vacuolation
79
clinical features of CIHD
- s/s
- -severe progressive heart failure
- -+/- angina, infarcts
- -arrhythmias
80
outcome of CIHD
death due to CHF, MI, arrhythmia
81
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
82
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
-
