ATHEROSCLEROSIS ATHEROSCLEROSIS : CAUSES AND COMPLICATIONS
John P. Veinot MD  Ottawa Hospital, Civic Campus


Atherosclerosis is responsible for the majority of deaths in our society. It is also responsible for a huge amount of morbidity.

If one studies insurance tables, atherosclerosis causes a large contribution to years of potential life lost.

Atherosclerosis is predominantly a disease of arteries both large and medium-sized.

It affects elastic and muscular vessels. Atherosclerosis may also involve veins when they become vein grafts and are exposed to arterial pressure.
 

The effects of atherosclerosis depend upon:
the degree of stenosis
the time of development of the stenotic lesion
the presence of collaterals vessels that also supply the area supplied by the stenotic vessel
the demand of the tissue
Risk factors for atherosclerosis include those, which are modifiable, and those, which are not.
Age - in general, atherosclerosis increases with age. The earliest lesions of atherosclerosis are present after the age of 10 years old and some believe that this is a disease present since infancy
Gender atherosclerosis is present more in males, however females catch up after menopause. Some old dated thinking regarded females as having less atherosclerosis than males. However, it is recognized now that females do develop significant atherosclerosis. Estrogen is protective as it has multiple effects including effects on lipids, nitric oxide, vascular tone and antioxidant properties.
Smoking causes multiple malignancies and accelerates and initiates atherosclerosis. Many effects on the endothelial cell including poor vascular tone with vasoconstriction, oxidation, and prothrombotic products.
Hypertension - accelerates the development of atheroma
Hyperlipidemia
Inactivity and obesity
Diabetes affects endothelium and lipids
Family history probably multifactorial based on many of the above factors
Hyperlipidemia is an important risk factor for atherosclerosis but it should be stressed, is only one of many factors.

Lipids will be further discussed separately  in the endocrine block. In general LDL cholesterol levels correlate with atherogenesis and HDL cholesterol is protective.

Of the types of cholesterol some, such as small dense and oxidized LDL, are especially atherogenic.

It should be recognized other risk factors exist including homocystine and coagulation abnormalities.
 

ATHEROSCLEROSIS THE LESION

The earliest lesion of atherosclerosis is a fatty streak a localized intimal collection of macrophages filled with fat. Aorta with fatty streaks

The next lesion is a fibrous plaque, which is an intimal aggregation of lipids, blood proteins and inflammatory cells.

These plaques may become complicated ruptured or thrombotic or have plaque hemorrhage and this leads to disease progression. Complicated aortic atherosclerosis

The natural history of atherosclerosis is the early development of fatty streaks followed by fibrous plaques and complicated plaques. When plaques complicate, the lesion may become symptomatic leading to different manifestations of disease depending on which organ is affected, ie heart heart attack, brain stroke, limbs gangrene.

Plaque complications:
Calcification
Ulceration
Thrombosis and hemorrhage
Aneurysmal dilatation
Embolization
Stenosis
ATHEROMA ATHEROSCLEROSIS - PLAQUE COMPONENTS:
The plaques have three main components:  Atherosclerosis high power view;
 Atherosclerotic plaque in coronary artery
Cells endothelial cells, smooth muscle cells, macrophages, and lymphocytes, and others
Connective tissues including collagen, elastic fibers and proteoglycans
Lipids, and calcium
Atherosclerosis forms as a reaction to injury hypothesis, which is now essentially proven.

The endothelial cells are thought to become dysfunctional or denuded allowing blood products and macrophages to adhere and penetrate the vascular wall.

The denudation or endothelial cell dysfunction also leads to platelet clumping. Platelets are a rich source of mediators, as are the monocytes, which lead to prominent release of mediators diffusing into the wall.

Smooth muscle cells from the adjacent media migrate into the plaque and this is followed by synthesis of abundant extracellular matrix.

The macrophages accumulate below the endothelial cells and phagocytize fat leading to the earliest lesions the fatty streaks. With time, there is necrosis of the inflammatory cells including the macrophages, in part due to the oxidation of lipids and apoptosis. This leads to a necrotic core. Microcalcification occurs.
 

Numerous mediators are involved including platelet derived growth factor, fibroblast and
transforming growth factor.


 ENDOTHELIUM
The healthy endothelial cell is a barrier, is antithrombotic, is a vasodilator and provides a structural lining for the vasculature. It is also metabolically active being a vasodilator producing nitric oxide and produces mitogens, chemotatic factors and is involved in the uptake of LDL.

The injured or dysfunctional endothelial cell becomes procoagulative, permeable; releases factors and the vessel walls dilate poorly.

Smooth muscle cells also change phenotype from contractile myofibril rich cells to synthetic cells (containing abundant cytoplasmic organelles including rough endoplasmic reticulum) and produce extracellular matrix

Atherosclerosis consequences proportional to
Stenosis
Occlusion
Embolism
Aneurysm

Reflect the end organ involved :
Heart myocardial infarct
Legs gangrene
Aorta atherosclerotic aneurysm
Viscera infarcts
INTERVENTIONS:

The most important intervention, it should be stressed, is primary prevention with lifestyle modification to minimize risk factors.

Symptoms may be controlled by medications and there is evidence that lipid lowering therapy stabilize and may shrink plaques.

Control of exacerbating conditions such as diabetes and hypertension are important.

Interventions include surgical procedures saphenous vein bypass grafting, internal mammary artery bypass grafting, coronary endarterectomy and non-surgical procedures thrombolytics, balloon angioplasty, stenting and atherectomy.

All of these procedures are associated with complications.