cardiovascular Flashcards
define atherosclerosis
an arteriosclerosis characterized by atheromatous deposits in and fibrosis of the inner layer of the arteries
Plaques – go into bv = occlusion
Rupture = sudden occlusion
formation of an atheroma
Arise on lesion in bv where smooth endothelium is damaged
Fatty streak – precurser lesion
plts stick to damaged tissue
proliferation of endothelium
fibrous cap forms on top of endothelium
deposition of cholesterol in core - fatty core
necrotic debris
block lumen = stenosis
Rupture = thrombosis and occlusuion
RF for atherosclerosis
Age
Sex
Genetics
Hyperlipidaemia
Hypertension
Smoking
Diabetes Mellitus
have multiplicative effect
age as a RF for MI
Clinically silent until reach threshold in middle age
Risk increases 5x form 40-60 yr
And risk increases with each decade
sex as a RF for CVD
Premenopausal women protected (HRT no protection)
Postmenopausal risk increases (older ages greater than men)
After 65 oestrogen can increase risk of CVS
genetics as a RF fro cvd
FH most sig independent RF
Some mendelian disorders (eg Familial Hypercholesterolaemia)
Most multifactorial (genetic polymorphisms -> clustered risk factors HT, DM)
hyperlipidaemia as a RF for cvd
LDL – cholesterol to peripheral tissue
HDL – take from plaque to liver and excrete in bile
Exercise can increase HDL
diet rich in LDL = bad
statins - inhibit HMG-CoA reductase rate limiting enzyme in liver cholesterol synth
HTN as a rf for cvd
increases risk of IHD by 60%
HTN – risk of LV hypertrophy = myocardial ischemia
smoking as a rf for cvd
double death rate by IHD
stopping reduces the risk sig
dm as a rf for cvd
Induces hypercholestrolaemia
Increases risk of atherosclerosis
doubles IHD risk
other rf for cvd
Inflammation - associated with atherosclerosis, CRP
Metabolic syndrome - central obesity, insulin resistance, htn, dyslipidaemia – proinflammatory state, triggered by cytokines from adipocytes.
Lipoprotein (a) - correlate risk with coronary and cerebrovascuilar disease independent other RF
Haemostasis (procoagulation)
Lack of exercise
Stress
Obesity
endothelial dysfunction - more likely to get plaques
pathogenesis of atherosclerosis
response to injury hypothesis:
Endothelial disruption – interrupt flow – LDL deposit
-> inflammatory response
?
chronic inflammation and healing response -> endothelial injury
interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with endothelial cells and smooth muscle cells -> lesion progression
monocytes adhere to endothelium #
-> migrate into intima
-> macrophages and foam cells
plt adhesion
Factor release from activated platelets, macrophages, -> smooth muscle cell recruitment.
Smooth muscle cell proliferation, extracellular matric production, and recruitment of T cells.
Lipid accumulation -> extra & intracellular, macrophages & smooth muscle cells
-> thickening of wall
White – cholesterol clefts
what are fatty streaks
Earliest lesion in bv – doesn’t cause dysfunction - No flow disturbance
Lipid filled foamy macrophages
In virtually all children >10yrs
Relationship to plaques uncertain
Same sites as plaques
what is an atherosclerotic plaque
Patchy – local flow disturbances
Only involve portion of wall
Rarely circumferential
Appear eccentric
Composed of – cells, lipid, matrix
* Cells – sm, macrophages, T cells
* Matrix – collagen, elastic, proteoglycans
* Lipids – intra and extracellular lipids
what are the consequences of atheroma
stenosis
acute plaque change
summarise stenosis
critical stenosis is where demand is more thanm supply
sx at ~70% occlusion (or diameter <1mm)
Causes “stable” angina
Can lead to Chronic Ischaemic Heart Disease
Acute plaque rupture can occur
summarise acute plaque change
rupture - exposes prothrombogenic plaque contents
Erosion - exposes prothrombogenic subendothelial basement membrane
Haemorrhage into plaque – increase size
most that have acute change have asx stenosis prior
how does emotional stress -> sudden cardiac death
Fibrous cap weak – increase risk of rupturing
Adrenalin increases blood pressure & causes vasoconstriction
Increases mechanical force -> physical stress on plaque
Hence emotional stress increases risk of sudden death
Circadian periodicity to sudden death (6am-noon)
causes of vasoconstriction:
* Adrenergic agonists
* Platelet contents
* Reduced endothelial relaxing factors
* Mediators from perivascular cells
diff between a stable and a vulnerable plaque
Get inflammatory response
Stable plaque – lipid core thin and cap is thick
Vulnerable – large lipid core, and thin cap – likely to thrombosis
what is IHD
leading cause of death worldwide
Group of conditions resulting from myocardial ischaemia (most caused by atherosclerosis)
Due to inadequate coronary perfusion related to demand
Fixed atherosclerotic occlusion of coronary artery, new thrombosis/vasospasm
Imbalance of supply to demand for oxygenated blood
Also less nutrients & less waste removal -> less well tolerated than pure hypoxia
presentation of IHD
Angina pectoris – ischemia = pain, but no myocyte death.
prinzmetal agina - relates to vessel spasm
Myocardial infarction – mycotye death and necrosis
Chronic IHD with heart failure – cardiac decompensation
Sudden cardiac death – tissue damage from MI/from lethal arrhythmia
IHD epi
common
common deaths - reducing with prevention and treatment - but aging population
IHD pathogenesis
insufficient perfusion vs demand because of progressive atherosclerotic narrowing of epicardial coronary arteries and variable degrees of superimposed plaque change, thrombosis and vasospasm
vasodilation cannot compensate above stenosis
75% = pain on exercise
90% = pain at rest
narrowing can happen in LAD, LCX, RCA
Clinically significant plaques tend to occur in the first several cm of the LCA and LCX take off from the aorta, and along entire length of RCA.
