1b// Coronary heart disease/athersclerosis Flashcards
modifiable risk factors of coronary heart disease
smoking lipids blood pressure diabetes obesity sendentary lifestyle
non modifiable risk factors of coronary heart disease
age
sex
genetic background
what combination of risk factors has the greatest impact on coronary heart disease
hypertension
smoking
high cholesterol
where is athersclerosis most likely to develop
at branches of vessels
e.g carotid, coronary and iliac arteries
why is atherosclerosis more likely to develop at artery branches
turbulent flow causing inflammation
where does athersclerosis happen within a blood vessel
between endothelium and internal elastic layer (intima)
what do coronary arteries do at lesion prone locations
adaptive thickening of the smooth muscle - intima widens and is larger
what is a type II lesion
macrophage foam cells infiltrate intima
what is a type III lesion/preatheroma
small pools of extracellular lipid form around the macrophage foam cells
what is a type IV lesion/atheroma
a core of extracellular lipid forms (small pools have joined up) around macrophage foam cells
what is a type V lesion/fibroatheroma
fibrous thickening around core of extracellular lipid and macrophage foam cells, hardening of vessel constriction
what is a type VI or complicated lesion?
a rupture/surface defect caused by a haematoma and fissure within intima causes a thrombus to form on outer layer of intima/lumen
when is the best time to intervene with atherosclerosis
intermediate or advanced lesions
for primary prevention of rupture/stenosis - lifestyle changes and risk factor management
what interventions are needed for complicated lesions?
stenosis/plaque rupture treatment
catheter based interventions
revascularisation surgery
treatment of heart failure
what cells are involved in athersclerosis
vascular endothelium macrophages vascular smooth muscle cells T lymphocytes platelets
how are vascular endothelial cells involved in athersclerosis
barrier function against athersclerosis
leukocyte recruitment
how are macrophages involved in athersclerosis
foam cell formation
major source of free radicals and metalloproteinases
cytokine and growth factor release
how are vascular smooth muscle cells involved in athersclerosis
migration and proliferation
collagen synthesis
remodelling, fibrous cap formation
how are t lymphocytes involved in athersclerosis
macrophage activation
how are platelets involved in athersclerosis
thrombus generation
cytokine/growth factor release
what are the two main classes of macrophages
inflammatory macrophages - kill germs
resident macrophages - homeostasis e.g osteoclasts, alveolar macrophages, spleen macrophages
what is low density lipoprotein
bad cholesterol synthesised in liver
carries cholesterol from liver to body tissues
what is high density lipoprotein
good cholesterol
reverse cholesterol transport
what are oxidised/modified LDLs
impact of free radicals on LDL
highly inflammatory and toxic forms of LDL in vessel walls
structure of low density lipoprotein
docking molecules for fat delivery lipid monolayer (micelle) cargo fat
how do LDLs cause athersclerosis
lwak through endothelial barrier
binds to proteoglycans in sub-endothelial layer
oxidated by free radicals, phagocytosed by macrophages CREATES FOAM CELLS and stimulates chronic inflammation
what is familial hypercholesterolaemia
autosomal genetic disease
elevated cholesterol
failure to clear LDL from blood
early athersclerosis - MI before 20
what are statins
HMG-CoA reductase inhibitors
how do macrophages impact atherosclerosis inflammation
generate free radicals to oxidise lipoproteins
phagocytose lipoproteins and become foam cells
express cytokines that recruit monocytes
express chemoattractants and growth factors for VSMC
generate proteinases to degrade tissue
what free radicals do macrophages produce
NADPH oxidase
myeloperoxidase
what cytokines do macrophages express to recruit monocytes
IL-1 upregulates VCAM-1
vicious cycle of self-perpetuating inflammation
what chemoattractants do macrophages express
protein growth factors for vascular smooth muscle cells, stimulate them to proliferate and deposit ECM
platelet derived growth factor (PDGF) - VSMC chemotaxis, survival and cell division
transforming growth factor beta (TGFb) - increased collagen synthesis and matrix deposition
what are metalloproteinases
degrade collagen by zinc based mechanism
what is the fate of macrophages involved in athersclerosis
protective systems overwhelmed
die by apoptosis
release toxic lipids and tissue factors into lipid necrotic core
builds up until plaque ruptures and these are spilled out into the blood encouraging a clot
what is nuclear factor kappa B
transcription factor
activated by scavenger receptors, cytokines etc
switch on inflammatory genes for metalloproteinases, nitric oxide synthase, IL-1
what macrophage scavenger receptors bind to oxidised LDL
scavenger receptor A and B (CD204, CD36)
first line management of a STEMI
antiplatelet and anti-ischaemic/coagulant treatment
then PCI/CABG
long term management of STEMI
antiplatelet therapy statin beta blocker ACEi cardiac rehabilitation + lifestyle changes
pathophysiology of STEMI
nearly always coronary plaque rupture resulting in thrombosis formation, occluding a coronary artery
pathophysiology of NSTEMI
incomplete thrombus formation, doesnt stop blood and oxygen completely but restrictio is great enough that oxygen is used up quickly. in distal arteries and arterioles, tissue death occurs due to oxygen starvation
affected area is small to not cause ST elevation but causes depression and Troponin elevation
pathophysiology of unstable angina
plaque becomes unstable, fibrous cap disrupts and forms thrombus but enough for lumen to meet demand during rest
clinical difference between unstable angina and NSTEMI
NSTEMI shows raised Troponin levels
typical angina components
precipitated by physical exertion
retrosternal pain in chest
relieved by rest or glyceryl trinitrate (GTN)
what do blood troponin levels indicate
elevated in heart damage, remain elevated for 2wk
normal levels = less likelihood of muscle damage, more likely angina
rise/fall in series of troponin results indicates heart attack
treatment of unstable angina and NSTEMI first steps
risk assessment for future coronary events
low risk NSTEMI and unstable angina patient management
conservative treatment aspirin, clopidogrel, heparin, nitrates, b blockers
stress test
low risk patients NSTEMI and unstable angina stress test results mean
negative - discharge
positive - coronary angiography (PCI, CABG etc)
high risk NSTEMI and unstable angina patients management
invasive management
coronary angiography - PCI, CABG
assessment of patient who is at high risk of future coronary events
positive troponin, ST changes, patient generally unstable
