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ATHEROSCLEROSIS AND CORONARY ARTERY DISEASE


Atherosclerosis

Atherosclerosis is a disease caused by the accumulation of lipids, inflammatory cells and fibrous tissue that thickens and hardens the intima layer of medium and large arteries.

Atherosclerotic lesions and plaques are frequently located in areas of arteries under the greatest stress (e.g., side branches, bifurcations, and tortuous vessels). Atherosclerosis can develop in any artery in the body.

Endothelial injury (repetitive, low grade) with subsequent sub-endothelial inflammation and lipid deposition and degradation contribute to the development of immature atherosclerotic lesions or plaque. Immature plaque is unstable and is prone to tearing with vascular stress. This may lead to:

Chronic sub-endothelial inflammation is accompanied with sub-endothelial fibrosis, myocyte proliferation and calcification, resulting in the formation of mature plaque. Mature plaques are sometimes referred to as stable plaques. Mature plaques lead to hardening of the arterial walls and narrowing of the arterial lumen. This in turn may result in:

Mature plaques are often associated with collateral circulation. Several factors may contribute to endothelial injury (e.g., hypertension, diabetes, smoking).

In terms of stages of development, Atherosclerosis development follows a distinct evolutionary progression over many years. This progression can be divided into three phases:

All the cells involved in atherosclerosis are able to interact during the development process. In addition, in the later stages of atherosclerosis, thrombus formation from the rupture or erosion of atherosclerotic lesions may occur.

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Clinical Consequences of Atherosclerosis

Atherosclerotic plaque in the linings of the arteries causes the arteries to harden, and may lead to the narrowing of the artery lumen and restriction of blood flow.

Many of the consequences of atherosclerosis are life-threatening as atherosclerosis may affect any artery, including arteries in the brain as well as the heart.

Plaque build-up in peripheral vessels can cause peripheral vascular disease (PVD).

Cerebrovascular consequences of atherosclerosis include stroke and transient ischemic attacks (TIAs). Stroke occurs when blood circulation to an area of the brain is blocked and brain tissue becomes ischemic. TIAs are brief interruptions of the blood supply to the brain.

Atherosclerotic plaque in the coronary arteries may lead to arterial stenosis or coronary artery disease (CAD).

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Arterial Stenosis

Over time, atherosclerotic plaque thickens and hardens the artery walls. Up to a point, the artery can dilate to maintain the lumen. When the artery can no longer compensate by dilation, the lumen of the artery is narrowed, a condition referred to as arterial stenosis.

Arterial stenosis is characterized by de novo (lesions not previously treated) atherosclerotic lesions, and results in reduced blood flow to the tissues (ischemia).

The ischemia resulting from arterial stenosis can have serious clinical consequences, including angina or myocardial infarction.

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Coronary Artery Disease

Coronary artery disease (CAD) is a progressive condition involving formation of atherosclerotic plaques in the coronary arteries. The plaques may gradually impede blood flow through the coronary arteries or they may rupture.

CAD may be asymptomatic for many years, but if left untreated, CAD eventually may lead to angina (chest pain), myocardial infarction (MI), or death.

Atherosclerosis is the leading contributor to CAD. CAD is the leading cause of death in Canada. The risk factors for atherosclerosis and CAD are the same. The major risk factors are:

Of patients with atherosclerosis, one-half have elevated cholesterol levels. Some of the risks are reversible via life style changes or use of medication.

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Clinical Presentation of CAD

CAD is insidious in the beginning. The patient is unaware of its initiation, early progress, and the serious clinical conditions that may be developing. Yet as atherosclerotic processes progress, arterial stenosis and ischemia can result.

Patients are generally asymptomatic until arterial stenosis approaches 60% to 70%, at which time the patient may experience symptoms characteristic of angina (i.e., chest pain and/or pressure). Pain and pressure in the chest are also among the primary symptoms of MI. Interestingly in 25% of cases, the first sign of CAD is infarction with sudden death.1

The amount of stenosis is not always predictive of clinical complications because rapid progression, atherosclerotic plaque rupture, and thrombus formation can result in unstable or acute coronary conditions (i.e., unstable angina and acute myocardial infarction).

Episodes of sudden plaque rupture and thrombus formation are estimated to be responsible for 50% of unstable angina and acute myocardial infarction cases. High blood pressure, diabetes, and smoking have been associated with atherosclerotic plaque rupture.

Atherosclerosis may begin as early as childhood. It can occur anywhere in the body, but it usually affects large and medium-sized arteries. Sometimes plaque in an artery can rupture. The body's repair system in turn creates a blood clot or a thrombosis to heal the wound. The clot, however, can block the artery, leading to either a heart attack or stroke.

The goal of the PreVu® Non-Invasive Shin Cholesterol Point of Care (POC) Test, through the measurement of cholesterol that has already been diffused and deposited into skin tissue, is to provide patients and their healthcare providers with an early distance warning courtesy of this new risk marker, given skin cholesterol's strong clinical association with serious anatomical disease.

The PreVu POC Test can serve as a major tipping point for Canadians to enter for the first time, or reengage in the cholesterol conversation and to be directed follow-up with their healthcare providers for an evaluation of all their other potential risk factors for CAD towards the intervention in, and prevention of that crucial first event.

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ATHEROSCLEROSIS VIDEO presentation

This video presentation shows a vivid animation sequence focusing on how cholesterol contributes to atherosclerosis.*

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References

  1. Greenland P, Smith SC, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: Role of traditional risk factors and non-invasive cardiovascular tests. Circulation 2001;104:1863-67.

* Video produced by Pfizer. All Rights Reserved.
No endorsement of Pfizer products is implied in the provision of this educational video.