Atheroma definition and description
Ath-er-o-ma is adeposit or degenerative accumulation of lipid-containing plaques on the innermost layer of the wall of an artery.
Atheroma is the most common cause of ischemic heart diseases, stroke and peripheral vascular diseases.
Family history of myocardial infarction confers an increased risk of ischemic heart diseases. Geneic factor is also important in the development of atheroma.
Pathophysiology
Atheromatous plaques are focal lesios of large and medium sized arteries. Atheroma start as fatty streaks in the intima and prgress to proliferative fibro-fatty growth that can protrude into the vascular lumen and limit blood flow.
These plaques are rich in both extracellular and intracellular cholesterol. During they development, they do not initially give rise to symptoms, but they may cause angina pectoris, intermittent claudication (clinical diagnosis gives for muscle pain ) or other symptoms depending on their anatomical location. They may rupture or ulcerate, in which the subintima acts as focus for thromboss , platelet-fibrin thrombi propagate and can occlude the artery, causin myocardial infarction or stroke.
Epidermiological observation have shown that there is a strong positive relationship between the concentration of circulation cholesterol, specifically of low-density lipoprotien (LDL) fraction, and the risk of atheroma.
This relationship is non-linear and depends stongly on the presence or absence of other risk factors, including male sex, arterial hypertension, cigarette smoking, diabtes mellitus and left ventricular hypertrophy.
Cholesterol is mobilized from tissues in form of HDL particles. These are not atherogenic - indeed, epidemiological studies have identified HDL as being stromgly negatively correlated with coronary heart diseases.
There is a closed relationship between apolipoprotein A (Apo-a) and plasminogen linking atherogenesis to thrombosis.
Apo-a is present in a lipoprotein A (LP-A). The plasma concentration of LP-A varies over
a 100-fold range and is strongly genetically determind.
Most drugs have little efect ( nicotinic acid is an exception)
APO-A contains multiple repeats of one of the kringles of plasminogen ( kringle is a doughnut-shaped loop of amino acid held together by three internal disulphide bonds )
This leads to interference by LP-A with the function of plasminogen, which is the precursor of the endogenous fibrinolytic plasmin, and hence to a predisposition to thrombosis on atheromatous plaques.
Atheroma is classified to 8 types
- Type I : Isolated macrophage from cell
- Type II : Multiple from cell layers.
- Type III : Preatheroma, intermediate lesion.
- Type IV : Atheroma.
- Type V : Fibroatheroma.
- Type VI : Fissured, ulcerated, hemorrhagic, thrombotic lesion.
- Type VII :Calcific lesion
- Type VIII: Fibrotic lesion
Prevention and tratment of atheroma
Modifiable risk factors are potentially susceptible to therapeutic intervention.
These include smoking, obesity, sedentary habits, dyslipidaemia, glucose intolerance and hypertension.
Disappointingly hope, that hormone replacement treatment of post-menopausal woman would prevent atheromatous diseases were disproved by randomized controlled trials
* SOMKING *
Cigarette smoking is strong risk factor for vascular diseases. It causes vasoconstriction via activation of the sympathetic nervous system and platelet activation / aggregation with a consequent increase in thromboxan A2 biosynthesis, although the mechanism whereby smoking promotes atheroma is unknown.
* DIET AND EXERCISE *
Obesity is incresingly common and is an important risk factor, partly via its association with hypertension. Treatment is notoriously difficult.
Sedentry habit is a risk factor and regulare exercise reduce cardiovascular risk by reducing systemic blood pressure and increasing HDL.
* DYSLIPIDEMIA *
Most patient with dyslipidemia have a combination of genetic and dietary factors. Reducing the total plasma cholesterol concentration reduces the risk of coronary heart diseases and can cause regression of atheroma.
Dietary advice focuses on reducing saturated fat and correcting obsity rather than reducing cholesterol intake.
In people without clinical evidence of atheromatous disease, the decision as to whether to initiate drug tratment at any given level of serum lipids should be informed by the risk of coronary events.
* THREE MAIN CLASSES OF DRUGS TO TRAT DYSLIPIDAEMIA *
*Statins*
Simvastatin, pravastatin, atorvastatin and rosuvastatin are available all over the world.
Randomized controlled trials have shown tha simvastatin, atorvastatin and pravastatin reduce cardiac events and prolong life, and safe.
Pravastatin is distributed selectively to the liver and is tolerated even by some individuals who develop myalgia on other statin, but is less potent.
Rosuvastatin lacks clinical end-point data, but is more potent.
Cerivastatin is highly potent statin. It was withdrawn because of rhabdomyolysis ( a rapid destruction of skeletal muscle resulting in leakage into the urine of muscle protien myoglobin)
and drug interaction.
*DRUGS USED TO REDUCE CHOLESTEROL ABSORBTION *
* DIET AND EXERCISE *
Obesity is incresingly common and is an important risk factor, partly via its association with hypertension. Treatment is notoriously difficult.
Sedentry habit is a risk factor and regulare exercise reduce cardiovascular risk by reducing systemic blood pressure and increasing HDL.
* DYSLIPIDEMIA *
Most patient with dyslipidemia have a combination of genetic and dietary factors. Reducing the total plasma cholesterol concentration reduces the risk of coronary heart diseases and can cause regression of atheroma.
Dietary advice focuses on reducing saturated fat and correcting obsity rather than reducing cholesterol intake.
In people without clinical evidence of atheromatous disease, the decision as to whether to initiate drug tratment at any given level of serum lipids should be informed by the risk of coronary events.
* THREE MAIN CLASSES OF DRUGS TO TRAT DYSLIPIDAEMIA *
*Statins*
Simvastatin, pravastatin, atorvastatin and rosuvastatin are available all over the world.
Randomized controlled trials have shown tha simvastatin, atorvastatin and pravastatin reduce cardiac events and prolong life, and safe.
Pravastatin is distributed selectively to the liver and is tolerated even by some individuals who develop myalgia on other statin, but is less potent.
Rosuvastatin lacks clinical end-point data, but is more potent.
Cerivastatin is highly potent statin. It was withdrawn because of rhabdomyolysis ( a rapid destruction of skeletal muscle resulting in leakage into the urine of muscle protien myoglobin)
and drug interaction.
*DRUGS USED TO REDUCE CHOLESTEROL ABSORBTION *
* EZETIMBE *
It is most often used in compination with diet and statins for sever hypercholesterolaemia; also in occasional patient who cannot tolerate statins or where statins are contraindicated, and in rare cases of homozygous sitosterolaemia (a rare autosomal recessively inherited lipid metabolism disorder )
Diarrhoea, abdominal pain or headache are problems. It is contraindicated in breast-feeding.
* ANION-EXCHANGE RESINS *
Colestyramine or colestipol were used for hypercholesterolaemia, but have almost completely superseded by statins.
Resins retained an important nich as addd-in treatment in sever disease which was inadequately responsive to statin monotherapy.
This role has now been taken by ezetimbe which is effective and well tolerated.
They cause malabsorption of fat soluble vitamins and interfere with the absorption of many drugs.
* FIBRATES *
Benzafibrate, gemfibrate and febofibrate are used mainly for patient with mixed dyslipidaemia with severely raised triglycerides especially if they are poorly responsive to statins.
Colfibrate, wich was used in a World Health Organization (WHO) trial, is less often used because it increases biliary cholesterol secretion and predisposes to gall-stone.
Furthermore, while it reduced the number myocardial infarction in the WHO trial, this was offset by an increased number of cancers of various kinds.
The studies have shown that fibrates have a marked effect in lowering plasma triglycerides with a modest reduction in LDL and increase in HDL.
Fenofibrate has an additional uricosuric effect.
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