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Cardiovascular disease
Using specific examples to illustrate your answer, critically evaluate how the development of atherosclerotic lesions may
lead to a variety of symptoms
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Outline how the incidence of cardiovascular disease in the United Kingdom has changed over the last forty years, go on to
relate the major cause of most cases of cardiovascular disease and critically evaluate the role of risk factor
modification in bringing about the observed changes in incidence of the disease
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33% of all deaths are a result of cvd
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Women are 3% (10% chance) more likely to die of stroke than men
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Deaths caused by CVD under the age of 75 are less frequent in women as oestrogen helps to prevent
it
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This often leads to ischemia and infarction (this is defined as regional necrosis)
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This is pain and cramping in the lower leg muscles due to restricted flow in
the vessels during exertion or exercise
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It mostly occurs in the tunica intima:
the innermost layer of the arteries
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80% of heart attacks are a result of atherosclerosis
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CVD progresses in three main stages: fatty streak to fibro-fatty plaque to complicated lesion
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It can lead to the formation of thrombus (blood clot), dilation and aneurism of blood vessels, an
embolism (the blood clot breaks away and blocks the vessel), ischaemia and infarction
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Some areas are more blocked than others
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Atheroma lesions: soft, yellow, grumous (lumpy/clotted) core of lipid (mostly cholesterol), covered
by firm white fibrous cap
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If the lining endothelial cells
are damaged and platelets adhere to the site the platelets release a “platelet derived growth factor
PDGF) from their alpha granules
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Endothelial injury: toxins, cigarette smoke, hemodynamic disturbances and hypercholesterolemia
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Areas with non turbulent flow
lead to induction of gene products that protect against atherosclerosis (such as antioxidant
superoxide dismutase)
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Vascular cell adhesion molecule (VCAM 1) binds monocytes and T cells
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Macrophages remove potentially harmful lipids but in extreme cases can accumulate adding to the
plaque
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Cytokine production (by T cell or lipid activation) occurs and even more
leukocytes migrate the area
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As a result SMC proliferation
and ECM is generated
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Lipid containing macrophages lead to fatty streaks and eventually fibrofatty atheroma
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Lipid and necrotic debris
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CXCL16 has been proposed to act as a pathogenic mediator in atherosclerosis: CXCL16: scavenger
receptor to internalize the oxidized low-density lipoprotein (ox-LDL), present in lipid-laden
macrophages and atherosclerotic lesions
CXCL16 also existed in a soluble form caused by the metalloproteinase ADAM10 cleavage, interacts
with chemokines > migration of activated T lymphocytes into the inflamed tissue
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This study has revealed that increased
levels of serum-soluble CXCL16 were independently associated with the presence of atherosclerotic
ischemic stroke
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The large lipid core is the critical component of a vulnerable plaque as lipid-rich and soft plaques are
more dangerous than collagen-rich and hard plaques, and are highly thrombogenic after disruption
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ABCA1 and ABCG1 are two known common regulators of intracellular cholesterol outflow that play
an important role in regulating foam cell formation
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Bone morphogenetic proteins (BMPs), are multi-functional growth factors that play key roles in
embryogenesis, skeletal formation, hematopoiesis, and neurogenesis
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Research
shows that inhibition of BMP signalling increases lipid efflux, thereby reducing foam cell formation,
intracellular lipid accumulation, and atherosclerosis
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Therefore, BMP4 may become a potential agent against atherosclerosis and its
complications
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2 risk factors = risk x4 and 3 factors = risk x7 of
myocardial infarction
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Risk factors are important to prevent disease
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Genetics: Family history of a factor such as hyperlipidaemia or diabetes
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Most important risk factors are:
Hyperlipidaemia, hypertension, cigarette smoking and diabetes mellitus
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There are 2 main types of
lipoproteins associated with cholesterol levels
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LDLs deliver cholesterol to the
tissues whilst HDLs remove it from atherosclerotic plaques to the liver where it can be excreted into
the bile
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LDLs are found in egg yolk, butter, animal fat
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LDLs increase with smoking and
obesity
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Statins are a drug which inhibits the enzyme responsible for limiting how much cholesterol
biosynthesis can occur in the liver
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It inhibits hydroxymethylglutaryl coenzyme A reductase
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It is important that both systolic and diastolic pressures are within the normal rage
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The normal
range is 120 or below
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Diastolic pressure is the pressure your heart is under in its resting state between beats
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Anything over 90 is considered to be hypertension
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50% of patients with hypertension will die from IHD and 30% will die of stroke
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Cigarette smoking:
Prolonged smoking of one pack or more cigarettes a day increased the chance of IHD by 200%
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The risk of strokes is also higher
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Although these are all risk factors 20% of cardiovascular events occur in the absence of any of them
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The CRP (C reactive protein) is generated in the liver and is downstream of a lot of inflammatory
triggers
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In an atheroma it can regulate thrombotic states (blood clots)
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There is no direct link proven between reduced CRP and reduced risk however, reducing smoking,
reducing obesity and exercise all reduce CRP levels
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Genotyping of patients at risk for CAD may improve the risk stratification and lead to a better prevention
regime for both, atherosclerosis and restenosis
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Collateral: if there are alternative circulatory pathway that can compensate for the blockage
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Venous thrombosis: can happen to anyone
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Homeostasis: depends upon epithelial cells, platelets and proteins
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Damage> platelet adherence > soluble factors > primary haemostatic plug > fibrin > secondary
hemostasis
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Fibrous cap: SMCs, collagen, elastin, proteoglycans
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Diabetes: risk of heart attack doubles
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Macrophage colony stimulating factor encourages macrophage division and activation
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Macrophage death by t cells or drop in CSF > releases lipid core > necrosis
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Statin inhibit HMG coA
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Changes in CVD since 1961
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1961: 330K CVD deaths
2009: halved
But CHD still biggest killer
Survival rates have improved since 60’s
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No of incidence has increased: living longer, increased survival rates
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Heavy drinking is about the same but obesity is increasing
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Now cancer is biggest killer
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Over the past four decades, dietary and smoking habits, treatment of hypertension and
dyslipidemia, outpatient therapy for CVD, and inpatient treatment of acute CVD events have
improved substantially
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but in developing countries it is increasing
as habits change and consummation of lipids and cigarettes increases
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3 trillion
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A result of increase pop size
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Framingham risk calculator (contenstion, over estimates men by 5%) or more
accurate QRISK
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Carotid intima-media thickness (cIMT) is a surrogate marker of atherosclerosis[4,5], and ultrasound
screening a valuable tool for cardiovascular risk prediction

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Modification of risk factors
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Reducing CVD risk factors (CVRFs) decreases mortality and moribitidy
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A review in America shows only small percentages of patients are actually meeting goals
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Only 2% of smokers quit
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Multiple factors: inc
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Denial of disease without symptoms, side effects, non
compliance
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Need to target behaviours
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All risks think to
carotid atheroschelrosis
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For example, Kroger et al10 reported an unexpectedly high plaque burden in the carotid and
peripheral arteries of 100 male marathoners
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Recent
reports that marathon running may intensify atherosclerotic disease progression in central and
peripheral arteries
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ncbi
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nih

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