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|
|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|
|Inactivity and obesity|
|Diabetes – affects endothelium and lipids|
|Family history – probably multifactorial based on many of the above 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.
|Thrombosis and hemorrhage|
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|
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.
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
|Heart – myocardial infarct|
|Legs – gangrene|
|Aorta – atherosclerotic aneurysm|
|Viscera – infarcts|
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