atherosclerosis.pdf

8/10/2019 atherosclerosis.pdf

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The Pathogenesis of Atherosclerosis

By: M argaret Banning BSc (Hons) MSc PGDE SRN SCM

This 2.0 Contact Hour Educational Design II program is presented by the Stony Brook School of Nursing, which has been

approved as a provider of Continuing Education by the New York State Nurses Associations Council on Continuing

Education, which is accredited by the American Nurses Credentialing Centers Commission on Accreditation.

It has been assigned Code 4FEQ5U-PRV-2022.

Description:

Problems that result from the effects of Atherosclerosis may be attributed to some causes of death in

Western societies. In specifically, it may well account for over 50% of the mortalities in the UK and

the USA which at a estimate may be circa 500 individuals / day or 170,000 annually.

It is a disease that involves the circulation of low density lipoproteins within the blood stream, these

eventually accumulate in the cell wall of large and medium sized arteries to form plaques or

atherosclerotic patches which later inhibit the flow of blood. Stasis of blood promotes clot formation

which can be lethal to major organs in particular the heart and cerebrum. Prevention of lipid-

mediated changes to arterial structure can only be achieved through dietary modification or lipid

modifying drugs. The ultimate goal for nurses is to help reduce the incidence of heart disease through

appropriate health education.

Purpose: To examine the pathophysiological concepts pertinent to the development of

atherosclerosis and its consequences

L eaning object ive s: By the completion of this educational programme the student should be able to undertake the following:

By the completion of this educational programme the student should be able to undertake the following:

1. Discuss the epidemiological evidence thought to be related to the development of atherosclerosis

2. List the risk factors associated with the development of atherosclerosis

3. Describe the changes that occur in atherosclerotic arteries

4. Identify the role of lipoproteins in the development of atherosclerosisIndicative content

Content Outline:

Epidemiological evidence which supports the demographic details of the prevalence of

Atherosclerosis.


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Explore the groups of individuals who may be at risk of developing Atherosclerosis

Pathogenic changes to the arterial cell structure

Role of lipoproteins in the development of Atherosclerosis

Genetic influences to the development of Atherosclerosis

Response to injury hypothesis

Oxidation hypothesis

LDL receptor hypothesis

Myocardial infarction and its consequences

Role of the nurse as a health educator

Atherosclerosis is a major cause of death with atherosclerotic lesions isolated in large and medium

sized arteries, the brain, the heart and the legs. Staryet al

., (1984) offered the first evidence that the

development of atherosclerosis was a multifactorial process that commenced during childhood

(Mohler, 2000). The process involves the macrophage that develops into a foam cell is deposited

within the junction of the tunica intima and tunica medial layers of the artery during the first weeks of

life and later progresses into a fibrous atheroma from 30 years of age onwards (Napoli et al.,

1999). In 1984, Faggiatto & Ross, suggested that an association existed between the endothelial

cells and the macrophage. This relationship was later developed into the response to injury

hypothesis. Since this time, the pathogenic processes underpinning the development of

atherosclerosis remain conjectural.

Epidemiological evidence in support of the prevalence of atherosclerosis

Anand et al., (2000) examined the differences in risk factors for atherosclerosis and cardiovascular

disease in North Americans of European, Chinese and Southern Asian origin. Anand et al.,

assessed the prevalence of cardiovascular disease using the mean maximum intimal medial thickness

of coronary arteries as an indicator of the extent of carotid atherosclerosis. Cumulative data show

that Southern Asians had higher readings compared to equivalent data in European and Chinese

North Americans. This index may also be used as a marker for the presence of small plaques that

may progress to rupture and contribute to coronary occlusion and potential ischaemia (Chambless et

al., 1997).


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In addition, Canadians of Southern Asian descent presented with raised values for novel risk factors

such as plasma fibrinogen, plasminogen activator inhibitor 1, lipoprotein a and homocysteine. As

well as the highest serum level for glucose and plasma lipid abnormalities.

Evan though, the main assessment method used by Anand et al., may be classified as a novel index,

several criticisms of the method have been reported. Bell (2000) offers some generalisations

regarding the lack of clarity in the diagnosis with regard to Southern Asians, this mainly reflects the

fact that no correlation was made between the biochemistry data for Southern Asians and a

diagnosis of insulin resistance or metabolic syndrome. As Reaven et al.,(1996) points out there is a

consistent pattern between high glucose level and insulin resistance in this ethnic sub-group.

An association between insulin resistance and endothelial dysfunction has been reported previously

and used to anneal the relationship between insulin resistance and ischaemic heart disease (Despros

et al., 1996). Given the fact that South Asians demonstrate a higher frequency of insulin resistance,

they represent an ethnic group that have multiple independent risk factors which reflect a higher

propensity to develop ischaemic heart disease (Mather & Keen, 1985, McCarthy, 2000)

Although, the benefits of examining ethnic subgroups within a population cannot be discouraged, the

application of many studies to the general population are limited due to the small sample sizes

involved. The main areas of concern which need to be pursued are not mutually exclusive to other

ethnic populations and include the control of modifiable risk factors; hypertension,

hypercholesterolaemia, and cessation of cigarette smoking can reduce fatalities (Levy & Kannel,

2000).

Role of lipoproteins in the development of atherosclerosis

Fats are water insoluble products complexed in saturated and non-saturated forms as triglycerides

and cholesterol. Fats are a source of energy and provide on circa 38% of the bodies metabolic

requirements for energy. The average intake of fats is circa 90-190 mg per day. In the Western diet

the ratio of saturated to polyunsaturated fats is about 0.3 which is considered low, an ideal ratio

would be >1.0, this can be achieved by reducing the quantity of consumed saturated fats to less than

15%.


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The average daily intake of cholesterol is about 300-500 mg much of this provision can be found in

animal products such as eggs. As the quantity of dietary cholesterol consumed can significantly alter

serum levels, it is therefore ideal to maintain the average intake of cholesterol to


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Low density lipoprotein 1.55-4.4

Very low density lipoprotein 0.128-0.645

High density lipoprotein/ triglycerides 0.5-2.1

Total lipid 4.0-10g / L

LDL is composed of a core of 1500 molecules of cholesterol enclosed in layers of phospholipid and

unesterified cholesterol molecules. The hydrophilic portions of the molecule are arranged on the

outside which allows LDL to dissolve in blood or extracellular fluid. A large protein called

apoprotein B-100 is embedded in this hydrophilic layer. This protein is recognised and binds to the

LDL receptor which spans the full thickness of cells plasma membrane in clusters within specialised

regions forming craters or indented areas referred to as clathrin coated pits. These pits pinch

inward to allow LDL to be carried into the cell. This process is called receptor mediated

endocytosis. LDL is recycled and used as necessary with excess LDL digested by lysosome. Even

though cholesterol is a precursor of mineralocorticoids, glucorticoids and sex hormones and the

quantity of these hormones produced are independent on LDL metabolism.

Cholesterol levels are controlled by enzymes responsible for its metabolic synthesis such as HMG

CoA reductase. If this enzyme is suppressed, the cell becomes dependent on a supply of cholesterol

from LDL. Alternatively, stored cholesterol is derived from LDL mediated processes using an

alternative enzyme system; Acyl CoA transferase (ACAT) which chemically alters cholesterol in

order to allow appropriate deposition of cholesterol in the form of storage droplets. However, the

most important mechanism involves the reduction in cholesterol synthesis by the cell reducing the

quantity of LDL receptor sites. Cells therefore adjust the number of receptors in order to meet the

demands of cholesterol but not the excesses. If the demand exceeds the supply, then an

accumulation of cholesterol will occur.

LDL is generated by the bodies fat-transport system via two mechanisms; the exogenous and the

endogenous pathways. The exogenous pathway begins in the intestine, and commences as the

dietary fats become packaged into lipoprotein particles called chylomicrons. These are large

particles composed mainly of triglyceride, synthesised in the small intestinal mucosa and transported


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from dietary fat.. Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for

example apo B48, apo A-1, apo 11, C 11 and apo-E. The presence of the apo-C-11 surface

protein activates the capillary endothelial enzyme lipoprotein lipase that is responsible for the

conversion of chylomicrons into chylomicron remnants or esters and VLDL. Both of these products

are then activated by apo C-11 and circulate in peripheral tissues to be later absorbed by hepatic

apo B and apo E receptors.

Triglycerides or the FFA are removed by lipolysis with the apo A-1, apo A-11, apo C transferred

to HDL. The liver and intestine are the major sites of HDL catabolism, this lipoprotein contains 25-

50% of the circulating cholesterol. HDL is the substrate for lecithin cholesterol acyltransferase

(LCAT) which catalyses the conversion of free cholesterol to the cholesterol ester which also

involves fatty acids. This esterification reaction involves the major proteins; Apo 1 & Apo 11.

Excess triglycerides can be transported to storage sites such as adipose tissue or muscle to supply

energy through oxidation

In contrast, the endogenous pathway begins when the liver secretes very low density lipoproteins

(VLDL) into the bloodstream. VDLs are the products of endogenous triglyceride synthesis within

the liver. They contain the apo B-100 and apo-E proteins which are catabolised by lipoprotein

lipase within peripheral tissues. VLDL upon reaching capillaries of adipose tissue or muscle extract

the triglyceride units leaving enriched cholesterol esters with two apoprotein units. VLDL upon

reaching capillaries of adipose tissue or muscle extract the triglyceride units leaving enriched

cholesterol esters with two apoprotein units. These are referred to as intermediate density

lipoproteins or IDL and are removed from the circulation about 2-6 hours after their formation.

VLDL are broken down with small apolipoproteins and transferred to HDLs which produce smaller

fragments or IDLs, these are taken up by hepatocyte LDL receptors facilitated by binding onto the

IDL surface apo E protein. IDLs can be converted to LDL through the hydrolysis of triglcyerides via

hepatic lipase. LDL is the major cholesterol carrying lipoprotein in normal plasma. They enter liver

cells by binding to high affinity receptors found in the clathrin coated pit region that recognises the

apo B 100 protein. Following binding LDL is internalised, metabolised and then releases free

cholesterol that partially contributes to the endogenous cholesterol level.


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Liver sinosoidal endothelial cells and macrophages act as scavenger pathways which aim to

consume available LDL via acetyl-LDL receptors, by absorbing LDL modified by oxidation. This

process converts macrophages into foam cells or primary lesions found in atherosclerotic arteries.

Genetic influences in the development of atherosclerosis

Numerous genes for 10 apolipoproteins and 4 lipoproteins have been isolated for chromosomes 1,

2, 3, 6, 8, 11, 15, 16 and 19, with the gene for the LDL receptor has been located on chromosome

19. Mutants of this gene have been associated with familial hypercholesterolaemia. This genetic

condition occurs in individuals who inherit a mutant gene or are heterozygotes and possess less than

50% of the required LDL receptors. Heterozygotes possess one normal gene but inherit a mutant

gene that contains the genetic code responsible for the LDL receptor protein. These individuals

synthesise about 50% of the usual quantity of LDL receptors and can bind and degrade 50% of the

normal rate of LDL. Roughly, 1:500 people are affected by this mutation. Plasma LDL levels are

high, and a large proportion of patients will suffer from a cardiac incident by the age of 35 years. In

contrast, the homozygotes possess 2 mutant genes or possess a genetic predisposition to

hypercholestrolaemia. These inherited defective LDL receptor genes are both incapable of

synthesizing normal receptor and maintain an abnormally high LDL concentration due to an

increased production of LDL and decreased removal of LDL.

LDL and cholesterol levels can be used as biochemical predictors for the development of coronary

heart disease. The cholesterol deposits found in atheromatous lesions are derived from LDL as it

enters lesions by a rate-dependent response into the plasma concentration.

Response to injury hypothesis

Stated that the endothelium helped to regulate homeostasis of the cardiovascular system. This

proposal was supported by the fact that an intact endothelium is capable of releasing antithrombic

and fibrinolytic factors in addition to the potent vasodilator nitric oxide. In normal blood vessels,

nitric oxide and acetylcholine induce vasodilation, but with endothelium damage, disruption of cell

state negates normal function and the actions of potent vasodilators. The damaged endothelium

causes abnormal responses from acetylcholine by increasing the production of vasoconstricting


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agents such as thromboxane A2 and prostaglandins. In addition to eliciting the development of

abnormal intracellular signalling mechanisms which augment an increase in intracellular Ca2+ and

endothelin-derived vasoconstricting factors.

Endothelial damage also triggers platelets to adhere and aggregate at the site of the damage, this enhances

monocytes to enter the tunica intima, and proliferation within the tunica-media junction of the artery. This

effect causes the arterial wall to herniate at this site. With increased monocyte invasion into arteries, and

continual herniation the lumen of the artery can become processively reduced. This combination of

biochemica l and anatomical alte rat ions contributes to oxidat ive stress and increased vascular damage; the

so-called precursors for atherogenic changes within arteries.

An increase in plasma cholesterol and its main transporter, LDl is an important risk factor in

atherosclerosis. One variant of LDL has an apoprotein which reduces fibrinolytic activity and can

induce thrombosis.

Oxidation hypothesis

The prerequisite for macrophage uptake and cellular accumulation of cholesterol is oxidative

modification of LDL (Witzum & Steinberg, 1991). The initiation of the oxidation process is induced

by the intracellular generation of lipoperoxides which are transferred to LDL through the

development of O2derived free radicals. These species later initiate a series of chemical reactions

that are generally referred to as lipid peroxidation. These chemical reactions are maintained by the

conversion of lecithin to lysolecithin catalysed by the plasma membrane bound enzyme

phospholipase A2. Lipid peroxidation contributes to the destruction of the lipid components of the

plasma membrane and enhances the release of fatty acids through fatty acid fragmentation and the

formation of the reactive intermediate species referred to as lipoperoxides. These overwhelm LDL

and are generated continuously by Cu2+ ions in conjuction with peroxy radicals. Lipoperoxides are

toxic to plasma membranes as they re-arrange the chemical structure of the double bonds found infatty acids, they also combines with apo B and phospholipids to prevent LDL from binding to the

LDL receptor.

LDL can undergo acetylation to an oxidised form which is then unable to bind onto native receptors.

Oxidised LDL contains lysophosphatidylcholine this is a potent chemoattractant for macrophages


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(Kume et al., 1992). Lysophosphatidylcholine upregulates the expression of vascular cell adhesion

molecule such as ICAM-1 which is present within the endothelium and increases monocyte

adhesion. Available LDL uses the macrophage as a scavenge molecule, it binds onto and internalises

the LDL. Internalised oxidised LDL then inhibits monocyte motility. Macrophages that have

phagocytosed LDL are referred to as foam cells due to their lipid- like appearance on microscopy

(Quinn et al., 1987).

The LDL Receptor Hypothesis

In 1984, Brown & Goldstein suggested that high levels of LDL contributed to atherosclerosis as a

result of are due to down regulation of LDL receptors via apo B100 and failure of receptor

mediated endocytosis. Implying that LDL accumulated within the blood and could not be degraded

within the cell. This situation arises in patients with Familial Hypercholestrolaemia and in individuals

who consume a diet which is high in high in saturated animal fat. The continual exposure to a high

serum level of LDL has an inverse effect on the quantities of LDL receptors.

Factors Associated with Atherosclerosis

Cigarette Smoking

The metabolites of cigarette smoke are allylamine and the end product acrolein and reactive oxygen

species. It is thought that oxidative stress reduces the level of antioxidants available causing reduced

ability to inhibit lipid peroxidation, endothelial dysfunction in particular subendothelial oedema and

mitochrondial swelling (Zimmerman & McGeachie, 1987). The development of fatty streaks may

occur before endothelial cell denudation by a process involving severe cytotoxic changes to oxidised

LDL. Normally, oxidised LDL will aid the formation of a benign streak which then develops into a

complicated lesion. This adaptive change is enhanced by the altered function of the endothelial cell

which permits circulating monocytes to penetration into the intimal layers and act as a scavenger

receptor for oxidised LDL. The mature monocytes or macrophage after consuming oxidised LDL

forms a foam cell or a so called cholesterol clefts which acceleratee the formation of the fatty

streak. Smoking also increases platelet aggregation and the plasma concentrations of fibrinogen

which both contribute to the occlusion of arteries (Badimonet al., 1999).


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Diabetes

Hyperglycaemia contributes to interactions between endothelial functions producing abnormal

responses to acetylcholine, increased production of thromboxane and prostaglandins, raised

intracellular Ca2+all of which contribute to the release of endothelial vasoconstricting agents such as

acetylcholine and endothelin 1. The shunt in glucose to sorbitol via aldose reductase produces

fructose. Sorbitol enhances cell damage by augmenting cell swelling. Endothelium derived aldose

reductase contributes to highly abnormal cellular functioning and oxidative stress. Hyperglycaemia

also accelerates the generation of free radical mediated LDL oxidation (Kawamura et al., 1994).

Furthermore, available glucose can bind covalently to proteins by a process called glycation. This

process increases the production of free radicals causing glycoxidation, and glycative stress within

the cell, raises the quantity of glycated LDL and the athrogenic potential of LDL.

More recently, Schmidt et al., (1999) examined the role of pro-inflammatory mediators and their

contribution to the development of atherosclerosis in patients with an increased propensity to

develop Type 2 diabetes mellitus. The main findings showed that an increased risk was associated

with raised levels of acute phase proteins; orosomucoid,-1, antitrypsin and haptoglobin, indicating

that autoimmunity may be a systemic factor in the development of both conditions.

Hypertension

Hyertension induces similar endothelial dysfunction by reducing Nitric Oxide (NO) mediated

vasodilation and increased vascular resistance (Panza et al., 1993). This may relate to increased

Ca2+ by either reduced NO synthetase or excess production of oxygen derived free radicals which

inhibit NO production.

Fibrinogen

Fibrinogen is the precursor of fibrin which influences blood viscosity, flow and coagulation. Raised

levels promote platelet aggregation, fibrin and thrombi formation which stimulates cell proliferation

and plaque formation. These processes may also involve elevated levels of Factor VII and

plasminogen activator which can act as predictors of atherosclerosis (Cortellaro et al., 1993).


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Hypercholestrolaemia.

Small, dense LDL is more atherogenic than larger, buoyant forms. When accompanied by raised

triglycerides, reduced HDL, decreased LDL binding to apo-A1 occurs. Insulin resistance increases

the susceptibility to oxidation with HDL synthesised de novo within the intestine, liver, circulation or

peripheral tissues. Excessive levels of phospholipid or cholesterol attenuate the protective function of

HDL. As lipoprotein lipase positively correlate with HDL, low concentrations increase apo A1 &

II, catabolism reduces levels of available lipoprotein lipase and increases hepatic lipase leading to

hypertriglyceridaemia (Brinton et al., 1991).

Reduced levels of HDL-cholesterol

The predictive role of HDL may be to mediate hepatic excretion of cholesterol by reverse transport

to the periphery. Genetic factors known to contribute to low HDL-cholesterol concentrations

involve the following alterations:

a. genes for apolipoprotein A1-C11

b. Lipoprotein lipase

c. Cholesteryl ester transfer protein

d. Hepatic lipase

e. Lecithin-cholesteryl acyltransferase.

Harper & Jacobson, (1999) found that 11% of males in the US presented with low HDL-

cholesterol, a rationale for this level was unclear and still remains an enigma. In patients with a

history of familial HDL deficiency, the rationale for the disease may be a consequence of an

autosomal recessive disorder linked to key mutations found in the ATP-binding cassette (ABC1)

transporter gene, which encodes for cholesterol-efflux regulatory protein (CERP). Mutations in this

gene underpin the reduction in the quantity of protein and its functional activity and therefore

cholesterol transportation. This defect is common in the pathogenesis of Tangier Disease; a rare

disease diagnosed in about 40 patients world wide in which cholesteryl-ester disposition occurs in

several tissues and has also been isolated in 40% of cases of familial HDL deficiency (Macil, et al.,

1999).


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Trafficking of HDL in patients who have a deficiency of HDL usually present with cholesterol

depleted HDL particles that are rapidly catabolised and reduced cellular cholesterol efflux. This

disorder is an inborn error of metabolism and is referred to as familial HDL deficiency. Patients with

HDL deficiency are not usually diabetic and do not exhibit hypertriglyceridaemia but are likely to

present with an HDL-cholesterol concentration of 0.4-0.9mmol / L. The effects of deficient

production of HDL requires more research to evaluate fully the relationship to coronary heart

disease.

Pathogenic changes to the arterial cell structure

Affects large & medium-sized arteries. Lesions comprise fatty streaks, fibrolipid plaques and

complicated lesions (Table III).

Table II. Components of plaques

Tissue related components Biochemical components

Smooth muscle Calcium

Macrophages Triglycerides

Fibroblasts & fibrin Cholesterol

Elastin Phospholipids

Collagen & glycosaminoglycans Cholesterol esters

Myocardial infarction and its consequences

The fragility of atheromatous plaques has been related to their irregular formation and propensity to

rupture. Unstable atherogenic plaques have an increased tendency to rupture which can then

progress to an acute occlusion of arteries and develop significant conditions such as major organ

ischaemia as found in Myocardial Infarction or stroke. This form of pathological change is normally

associated with fissuring of the coronary artery plaques leading to spontaneous coronary dissection

and coronary embolism. Alternatively, rupture may result from iatrogenic causes such as coronaryartery bypass, catheter-based vascularization or local factors such as coronary artery artheroma or

superimposed thrombus or plaque haemorrhage (John et al, 1999). Atherosclerosis has multiple

consequences (Table III).


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Infarction is the ischaemic death or necrosis of tissue. Necrosis is the organised cell death of a tissue

and mainly involves inflammatory infiltration, leukocytosis and fibrous repair mechanisms following

the release of enzymes form the ischaemic tissue. Fuster et al., (1992) has shown that Myocardial

Infarction, myocardial ischaemic events and cardiac necrosis can result from the irregularity of

atheromatous plaques. Plaque instability have been associated with systemic factors such as

infection, involvement of a genetic predisposition, autoimmunity.

Table III. Potential complications of Atherosclerosis

Myocardial infarction Myocardial rupture

Cardiac arrhythmias Emboli formation

Cardiac failure Cardiac aneurysm

Mitral valve incompetence Ischaemic heart disease &

fibrosis

Numerous systemic variables have been investigated with the aim of developing some association

between plaque instability / rupture and the cardiac pathologies. The most commonly reviewed

factors examined involve; plaque anatomy, the relevance of sheer stress; the influence of

inflammation and haemorrhage (Touboul, 1994); pre-existing infection and the inflammatory

response (Danesh et al.,1997, Bosch, 1999).

Rothewell et al., (2000) examined plaque surface morphology of carotid arteries in patients with

history of myocardial infarction. Findings indicated that an association may exist between systemic

factors and the irregularities of surface morphology of carotid arteries, with local factors having only

a limited role in the development of acute coronary events. There findings also indicate that role of

traditional risk factors requires further analysis particularly in patients who present with smooth

plaques as these are considered stable and therefore less likely to rupture. Rothwell highlights the

value of systemic factors in their potential involvement in plaque irregularity, however, the lack of

clarity with regard to inferences with regard to the marginalization of traditional risk factors has led to

severe criticism. Meschia et al., (2000) reiterates that the contribution of genetic factors to the

fragility of atherosclerostic plaques does represent a true predisposition and is substantiated by

sufficient evidence (Cortellaro et al., 1992;1993). Moreover, Violi & Loffredo, (2000) cited in


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Meschia et al., (2000) present evidence to support the contribution of hyperlipidaemia to the

instability of atherosclerotic plaques. In doing so, they indicate that the potential for rising HDL-

cholesterol and lowering triglycerides offers protection against the progression of atherosclerotic

plaques. This value of this individual risk factor cannot be overlooked especially as associations have

been made with smoking and increased thrombogenicity (Badimon et al., 1999).

Cortellaro et al., (2000) cited in Meschia et al., (2000) criticises Rothwells findings on the basis of

the techniques used. He believes that current angiographic procedures are limited by their failure to

differentiate unstable from stable plaques, as both mural and endothelialised thrombi appear with a

smooth surface and cannot be distinguished otherwise (Arbustini et al.,(1995, Bonn, 1999). It is

difficult to accept that Rothwell can do so without using alternative techniques and cannot support

the inferences made.

This is normally associated with fissuring of the coronary artery plaques leading to spontaneous

coronary dissection, coronary embolism. Iatrogenic cause (coronary artery bypass, catheter -based

revascularization) local factors Necrosis of heart muscle, usually left ventricle. Commonly due to

coronary artery atheroma & superimposed thrombus or plaque haemorrhage. Necrosis is the

inflammatory infiltration and fibrous repair. Enzymes released from necrotic muscle into blood,

leukocytosis.

Role of the nurse as a health educator

Nurses play an important role in the provision of education on how to improve the lifestyle of

patients through dietary modification and exercise. Dietary advice on how to lower cholesterol is

only one important aspect in the prevention of heart disease, particularly as this disorder is

multifactorial and is underpinned by multiple risk- and independent factors.

Dietary intake of cholesterol includes the contribution of animal fats found in red meat, cheese,

cream and whole cream milk and from cooking oils. Those oils that possess a high concentration of

saturated fats such as palmitic, stearic, myristic and lauric are known to be more athrogenic


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compared to the lower saturated fat based oils such as those containing oleic and lioleic acids. As

educators, nurses should be discouraging the use of cooking oils that possess higher levels of

saturated fats as these assist oxidation of LDL and foam cell formation (Table IV).

In an attempt to reduce the incidence of heart disease in the UK, manufacturers of margarine have

produced a range of products that aim to reduce serum cholesterol through modification of the

endogenous biochemical pathways (Mayor, 1999). One particular product in this range received

some criticism in that it does not reduce serum cholesterol in individuals who already maintain a

healthy diet (Heyningan, 1999). However, Thomson, (1999) suggests that these products are useful

for individuals at risk who do not adhere to a healthy diet, but fails to appreciate the financial

implications of purchasing expensive products for families who survive on low incomes. It is much

easier to reduce the risk of heart disease by dietary modification that does not involve the purchase

of expensive items.

In this regard, the consumption of fruit, vegetables and fish can be much more beneficial. By

encouraging patients to change the composition of their diet to include more oily fish such as

mackerel, trout and sardines. As these fish possess omega 3, 6 and omega 9 fatty acids which have

anti-atherogenic properties and therefore are of more benefit in the long term (Brown ,1999).

Table IV. The variety of cooking oils

Cooking Oil Type Common Examples

Oleic based oils Olive, safflower & sunflower oils

Linoleic based oils Seed oils; grape seed oil & walnut oil

Palmitic based oils Palm & cottonseed oils

Stearic based oils Lards & dairy fats

Myristic & Lauric based oils Coconut and palm kernel oils & dairy fats

It is well established that a high dietary intake of animal fat correlates with an increased incidence of

coronary atherosclerosis. In Japan and former Yugoslavia, dietary intake of animal fat appears to be

fairly minimal, therefore the incidence of atherosclerosis is not so widespread, whereas in Finland,

Northern Ireland and Scotland, the level of intake is high along with the incidence of coronary heart

disease. Animal fats are rich in saturated fatty acids that promote the accumulation of cholesterol.


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Q5. Chylomicrons contain which of the following apolipoproteins ?

a. apo B48, apo E and apo C-11

b. apo C48

c. apo D

d. None of the above

Q6. Lipoprotein lipase is the enzyme responsible for extraction of triglyceride from which of the

following lipoproteins ?

a. Chylomicrons and VLDL

b. IDL

c. HDL

d. LDL

Q 7. The gene for the LDL receptor has been located on which chromosome ?.

a. 1

b. 11

c. 6

d. 19

e. 16

Q8. The condensate from cigarettes that have been smoked induces which of the following

pathological changes :

a. swelling of mitochrondria

b. subendothelial oedema

c. denudation of the epithelial lining of arteries

d. oxidative stress within the cell environment

e. All of the above

Q9. Rupture of atherogenic placques can contribute to which of the following:

a. thrombosis

b. occlusion of arteries


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c. cardiac arrhythmias

d. myocardial infarction

e. A, B, and D

Q 10. Nurses may encourage patients to improve their lifestyle through health education programs

that address the following:

a. Encouraging low protein, high glucose diets

b. Smoking cessation programs

c. Encourage patients to exercise using a variety of methods

d. Provide dietary advice on fat intake

e. B,C and D

References:

Anand, S., Yusuf, S., Vuksan, V., Devenesen, S., Teo, K.T., Montague, P.A., Kelemen, L., Yi, C., Lonn, E., Gerstein, H.,

Hegele, R.A., McQueen, M. (2000). Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic

groups in Canada: the study of Health Assessment and Risk in Ethnic groups (SHARE).The Lancet, 356, 279-284.

Arbustini, E., DeServi, S., Bramucci, E. 1995.Comparison of coronary lesions obtained by directional coronary atherectomy

in unstable angina, stable angina, and restenosis after either atherectomy or angioplasty.Am.J.Cardiol.,75, 675-682.

Bell, D.S.H. Cardiovascular disease in South Asians.The Lancet, 356, 1108-1116.

Chambless, L., Heiss, G., Folsom, A. (1997). Association of coronary heart disease incidence and carotid arterial wall

thickness and major risk factors: The atherosclerosis risk in communities (ARIC) study 1987-1993. Am.J.Epidemiol., 146,

483-494.

Badimon, J.J.,Zaman, A., Helft, G., Fayad, Z., Fuser, V. (1999). Acute coronary syndromes: pathophysiology and

preventative priorities.Thromb Haemostas.,82;997-1004.

Bonn, D. (1999). Plaque detection: the key to tackling atherosclerosis ?. The Lancet,354, 656.

Bosch, X. (1999). Mechanism for putative link between atherosclerosis and viruses found. The Lancet, 354, 1976-1978.

Brinton, E., Eisenberg, S. & Breslowm, J.L. (1991). Increased apo A-1 and apo II fractional catabolic rate in patients with

low density lipoprotein cholesterol levels with or without hypertriglyceridaemia. J.Clin.Invest., 87, 536-544 .

Brown, M. (1999). Do vitamin E and fish oil protect against ischaemic heart disease. The Lancet, 354, 441-443.

Brown , M.S. & Goldstein, J.L. (1984). How LDL receptors influence cholesterol and atherosclerosis. Sci.American, 251, 52-

60.

Cortellaro, M., Boschetti, C., Cofrancesco, E. and the PLAT Study group (1992). The PLAT Study: haemostatic fucntion in

relation to atherothrombotic ischemic events in vascular disease patients.Arterioscler.Thromb., 12;1063-1070.


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