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
