What is arteriosclerosis? |

Causes and Symptoms

The human body’s arterial system is designed to carry oxygen, hormones, various types of blood cells (such as red and white blood cells), and other nutrients in the blood from the heart to the periphery and all organ structures of the body. The
arteries are composed of three separate layers: adventia (the outer layer), media (the middle layer), and intima (the inner layer). Atherosclerosis or arteriosclerosis, derived from the Greek words that mean “hardening of the arteries,” refers to the different diseases that compromise one or more of the layers of the large or medium-sized arteries or smaller arterioles. Most commonly, fat, cholesterol, and calcium deposits are laid down along the intima and inner portion of the media. These components build up, forming plaques, which then may produce stenosis (narrowing) or occlusion (closure) of the arterial lumen. Accumulation of platelets and other blood cells can form a thrombus along with plaque buildup, which also obstructs the arteries. Pieces of plaque or thrombotic material can break off, causing emboli to lodge in the vessels acutely. Atherosclerosis begins with some form of damage to the delicate lining of the intima (the endothelium), by infections, inflammation, hypertension, or even natural toxins. That damage induces platelet adherence and other repair mechanisms, creating an opportunity for the accumulation of fat and calcium deposits in plaques.

Depending on the arterial segment in the body that is affected, various diseases and symptoms may occur. As the blood vessels become diseased with plaque buildup, the body will try to compensate by the development of collaterals, small vessels that bypass the diseased artery. Collateral vessels are smaller than the native arteries and cannot accommodate the same amount of blood. Normally, during exercise, there is an increased demand for additional blood flow to the muscles; flow will increase and the arteries will dilate. With atherosclerosis, since the arteries are blocked and collaterals cannot accommodate the additional blood volume, waste products in the muscles build up, causing pain. In the heart, this process affects the flow in the coronary arteries, and angina (chest pain) may occur. In lower extremity arteriosclerosis, stenosis or occlusions of the aorta, iliac, femoral, popliteal, or tibial arteries may occur, producing intermittent claudication.

As the disease progresses, more blood vessels become stenosed or occluded and collateral formation will maximize, but the circulation is severely limited and
ischemia may result. In atherosclerotic heart disease, significant ischemia may then result in a myocardial infarct, or heart attack. In the lower extremities, patients may develop rest pain. The most severe symptoms of lower extremity arteriosclerosis are the development of nonhealing ulcers and gangrene (tissue death) in the lower portion of the foot, similar to a heart attack. When the disease process has become this severe, there are multisegmental areas of arterial occlusions and no further compensatory mechanisms. Monckeberg’s sclerosis, not usually thought of as a true form of atherosclerosis, refers to the disease in which calcification of the tibial arteries is noted, often in diabetic patients.

Acute arterial
ischemia is a sudden onset of ischemia as opposed to the more common chronic processes described above. The usual cause of acute arterial ischemia is an embolus (portion of a clot) that lodges in thearteries. The most common source of embolization is the heart; embolization from the heart occurs in patients who have recently had a heart attack, who have mitral valvular disease, or who have
atrial fibrillation (irregular heartbeats). Another cause of acute arterial ischemia is thrombosis of, or embolization from, an aneurysm. An aneurysm, another disease process, produces a weakening of the adventia and a “ballooning” of the arteries with a thrombus (clot). Rupture or thrombosis (clotting off)
may be a consequence of aneurysmal disease. In such cases, because no significant collaterals have developed in the area of the acute blockage, immediate revascularization is mandatory to prevent significant tissue death.

In cerebrovascular disease, atherosclerosis affects the arteries supplying the circulation to the brain (the carotid and vertebral-basilar system). The most common symptoms noted are
Transient ischemic attacks (TIAs), also referred to as ministrokes. TIAs usually last less than twenty-four hours. Most TIAs are produced by embolization, in which pieces of plaque in the major arteries break off and temporarily block the blood flow to certain areas of the brain. Once the symptoms last more than twenty-four hours, a cerebrovascular accident (CVA), cerebral infarct, or stroke has occurred. Atherosclerosis in the cerebrovascular system will behave in a manner similar to that previously described, with increasing stenosis and eventual occlusion. Collateral development seems to be especially prominent in the cerebrovascular system, since the
brain is a greedy organ needing blood at all times. The majority of CVAs are caused by occlusion or thrombosis of a major vessel, producing significant ischemia in a portion of the brain.

Cerebral aneurysms due to atherosclerosis can rupture (sometimes as the result of uncontrolled hypertension) and bleed, causing tissue destruction from both the presence of blood and the compensatory vasospasm and ischemia. The result is a CVA or even death.

Contributing or significant risk factors in the development of atherosclerosis include hypertension (high blood pressure),
hyperlipidemia (high amounts of fats or lipids in the blood), smoking,
diabetes mellitus, and family history. Inflammation, especially from infections, is a significant risk factor as well. Also, depending on the significance and the location of atherosclerosis, a variety of symptoms and conditions can result. In atherosclerotic heart disease, the first symptom is angina. As in intermittent claudication, chest, shoulder, or upper back pain may occur during exercise or stress as a result of the decreased blood supply to the tissues of the end organ, the myocardium (heart muscle). As the disease progresses, the angina will become more unstable and patients will become progressively limited in
minor activities. Symptoms of a heart attack may include severe, crushing chest pain, shortness of breath, pain in the left arm, and tingling of the fingers. Cessation of breathing and cardiac arrest indicate a significant heart attack. Immediate medical attention during the severe symptomatic phase or with cardiac arrest will aid in reducing further damage to the heart muscle and may prevent death. Many heart attacks are “silent” in that, although portions of the cardiac muscle are “dead,” symptoms will have been negligible or minor, because of sufficient collateralization.

In lower extremity atherosclerosis, patients with intermittent claudication will complain of pain or cramping in their calves, thighs, or buttocks while walking or exercising; symptoms will be relieved by rest. Claudication is usually described by distances, such as “one block” claudication or “half a mile” claudication. Rest pain occurs mostly at night at the most distal portion of the extremity, usually the toes and forefoot. Often patients will sleep in chairs or with their legs hanging off the bed to relieve the pain. On physical examination, the foot is usually cool to the touch, with a slightly bluish discoloration. There is hardening of the nails, dryness of the skin, and loss of hair in the lower portion of the leg. Pulses are absent or diminished. Often, when the leg is in a dependent position, dependent rubor, a purplish discoloration of the leg, is seen, produced by dilation of the small blood vessels in the skin to provide the maximum amount of blood. Elevating the leg will produce a cadaverous white
pallor. Because of the limited blood supply, ulcers will not heal and gangrene can develop. Patients with symptoms of severe claudication, rest pain, or neuropathic diabetes should be evaluated prior to undergoing any podiatry procedures because their compromised circulation will result in poor healing. Patients with acute arterial ischemia of the lower extremity will complain of the “five P’s”: pain, pallor, pulselessness, paresthesia (decrease of feeling), and paralysis. As previously described, emergent revascularization of the acutely ischemic limb is necessary to prevent limb loss or amputation.

Although aneurysmal disease is a separate entity, it may be associated with atherosclerotic disease in certain cases. Most aneurysms produce no symptoms. Detection of aneurysms is usually incidental; during a physical examination, for example, a physician may note a pulsatile mass in the abdomen (aorta, iliac), in the groin (femoral), or behind the knee (popliteal). Incidental diagnosis of aneurysms may also occur during routine chest X rays; the X ray may reveal a calcium rim around the body of the aneurysm. As aneurysms increase in size, the probability of rupture increases; therefore, elective surgery is usually recommended once certain sizes are achieved: more than six centimeters for an abdominal aneurysm and more than two centimeters for femoral and popliteal aneurysms. Symptoms of a rupturing abdominal aneurysm include severe lower back pain and a decrease in blood pressure, whereas thrombosis of a popliteal or femoral aneurysm will cause an acutely ischemic leg. Symptomatic aneurysms
are considered medical emergencies, since ruptures may result in death and thrombosis in limb loss.

Symptoms of TIAs due to thrombosis in the carotid arteries, which supply the front of the brain, include hemiparesis (weakness) or paresthesia, aphasia (speech disorder) when the left carotid is affected, and amaurosis fugax (loss of vision likened to seeing a window shade being pulled down) resulting from blockage of the ophthalmic artery (which branches off the carotid) on the side of the blindness. Other symptoms include dizziness, vertigo, imbalance, and other visual disturbances. These more generalized symptoms are referable to the vertebral-basilar circulation, which supplies the back portions of the brain, or are a result of multisegmental cerebrovascular disease in which a low-flow state can affect multiple areas of the brain and produce diverse symptoms. A stroke is an event whose symptoms will last more than twenty-four hours. Often these are permanent deficits, affecting the patient for the rest of his or her life.

Many patients will be asymptomatic (have no symptoms) and not develop TIAs but will have a stroke, which may result from eventual occlusion or thrombosis of the cerebral vessels and infarcts in a particular section of the brain. Asymptomatic cerebrovascular disease is often detected by the presence of a bruit (French for “noise”). Stenosis in arteries resembles rapids in a river: Flow will go very fast through the blockage and then be turbulent. The turbulence will produce a bruit which can be detected with a stethoscope. Turbulence from stenoses ranging from 20 to 80 percent can cause a bruit. The absence of a bruit does not mean that the arteries are disease-free. Once the stenosis reaches critical proportions, the flow is diminished and turbulence may be negligible. An occluded artery will also have no bruit, since there is no flow. Once the narrowing has reached 60 to 80 percent, many doctors will recommend elective surgery to reestablish flow and prevent eventual occlusion and possible stroke. About 75 percent of strokes are ischemic, resulting from this process. Bruits may be appreciable in other parts of the body and
can also indicate the presence of atherosclerosis in those areas.

Atherosclerosis of the renal arteries, which supply the kidneys, may cause a condition known as renovascular hypertension. This type of high blood pressure is often difficult to control with medication, and continued high blood pressure will contribute to progression of the atherosclerotic process elsewhere in the body.

Another condition that results from atherosclerosis is chronic mesenteric ischemia. Here the blood vessels supplying the intestines, the stomach, and many of the organs associated with the digestive process are affected. Patients may experience pain with eating and significant weight loss. This condition is often missed until an extensive workup for cancer or other chronic diseases yields negative results. In acute mesenteric ischemia, by contrast, thrombosis of the superior mesenteric artery occurs. As with other acute arterial conditions, emergent revascularization is necessary to prevent gangrene of the intestines.

Treatment and Therapy

A complete history and physical examination are usually the first methods of diagnosing atherosclerosis. Eliciting symptoms, noting significant risk factors and physical findings, will aid the physician in determining areas at risk.

In lower extremity atherosclerosis, a common noninvasive method utilizes Doppler ultrasound. A series of blood pressure cuffs are attached to the extremity, and segmental blood pressure and plethysmographic waveforms are measured. A drop of more than twenty millimeters of mercury (mm Hg) of pressure between segments or extremities is indicative of a significant stenosis at that level, or a ratio of less than 0.5 when the ankle pressure is compared to the brachial pressure (a normal ratio is 1.0). Exercise testing will demonstrate whether there are significant drops in pressure, confirming the diagnosis and severity of claudication.

Duplex ultrasound machines utilize B-mode (brightness-mode) ultrasound to visualize the vessels and type of plaque, while Doppler ultrasound can audibly evaluate the blood flow in the vessels. Using real-time spectrum analyzers, the Doppler signals are then analyzed in terms of velocities and waveform characteristics. The greater the velocities, the greater the amount of stenosis. Absence of blood flow will denote occlusions. The use of color duplex ultrasound, in which the Doppler signals are color-coded in terms of flow direction and speed to denote the various flow patterns in normal and diseased vessels, has enhanced the diagnostic accuracies in the examinations. The use of color Doppler in many of the ultrasound machines is aiding in more rapid detection of arterial lesions in cardiac, cerebrovascular, and lower extremity arterial circulation.

Arteriography or
angiography is an invasive procedure. The delineation of the blockages and collateral pathways detected through this method—in which the patient is hospitalized and a catheter is used to inject dye containing iodine into the arteries—is then used to plan a revascularization procedure.

Ultrasound is the primary diagnostic tool for detecting and measuring the size of aneurysms. Computed tomography (CT) scanning is an alternative radiological modality to visualize aneurysms.

The majority of patients with mild to moderate intermittent claudication can be treated conservatively. Cessation of smoking, alterations to diet, and a carefully controlled exercise plan will alleviate or decrease the progression of symptoms. Less than 5 percent of patients with intermittent claudication will develop gangrene sufficient to warrant a major amputation within a five-year period.

Some medications available work by decreasing the stickiness of the platelets in the blood; these are often prescribed for patients with claudication. Aspirin is often prescribed to alleviate symptoms of TIAs and to protect patients from strokes or heart attacks. Although it is a powerful drug in decreasing the incidence of embolization, a national study has demonstrated that patients with TIAs and severe stenosis of the carotid arteries should undergo surgical revascularization to protect against major strokes. It has become clear that aspirin may also be helpful because of its anti-inflammatory properties, particularly now that the role of damage to the endothelium from inflammation and infections is understood.

Severe disabling claudication, rest pain, ulceration or gangrene of the lower extremity, and unstable angina and heart attacks require some sort of surgical intervention. Usually
bypass surgery is planned to revascularize the ischemic portion of the extremity or myocardial tissue to prevent limb loss or further cardiac events. The arteriogram will illustrate the areas of blockage, and, depending on the results of this test, various types of bypasses can be performed. Inflow procedures refer to bypasses performed above the groin. Aorto-iliac or aorto-femoral are the most common types performed, usually utilizing a prosthetic (plastic) material. Outflow procedures are those performed below the groin; these include femoral-popliteal or femoral-tibial bypasses. Prosthetics are sometimes used, but the best bypass material in terms of durability is the patient’s own vein, either removed and reversed, or in situ (in place). Depending on the type of bypass procedure performed, the five-year patency rates (number of bypasses open at five years) exceed 85 percent for aorto-iliac/aorto-femoral bypasses and 75 percent for lower extremity reconstructions. Coronary artery bypass grafts (CABGs)
typically employ the saphenous veins of the legs or the mammary artery of the chest wall to bypass the diseased segments in the heart vessels.

Endarterectomy
, a surgical technique in which the intima and part of the media are excised, effectively “scrapes out” atherosclerotic plaques. Although used in other arterial segments, endarterectomy is the most common surgical procedure used to revascularize the carotid arteries.

Other interventional modalities have been developed. Percutaneous balloon angioplasty involves placing a balloon catheter in the diseased segment during an angiogram and opening up the area of stenosis or small segmental occlusion. This method has been employed in the coronary arteries as well as in the vessels of the aorta, iliacs, and lower extremities.

New lytic drugs, which “dissolve” clots, are sometimes employed alone, or in combination with balloon angioplasties or surgery, especially in the more acute cases of lower extremity arterial ischemia and myocardial infarctions.

Perspective and Prospects

Atherosclerosis of the coronary and cerebrovascular system is a major cause of death. Heart attacks are the primary cause of death in the United States, with approximately 650,000 people dying annually. Half of those deaths are sudden, with no prior significant symptoms. Stroke is the third leading cause of death in the United States, with approximately 155,000 deaths annually. There are 400,000 strokes annually, and about one-fourth of all nursing home patients are permanently impaired from strokes. These statistics have a great impact on the amounts of health care moneys spent annually to care for victims of heart disease and strokes.

Since the 1960s, the rates of death from both heart attacks and strokes in the United States have decreased significantly. Control of blood pressure and diet, the development of new drugs and diagnostic techniques, and the advent of cardiovascular surgery in the early 1950s have aided in this decrement. Unfortunately, atherosclerotic diseases are still prevalent. Autopsies of Korean War and Vietnam War American soldiers demonstrated that atherosclerotic plaque was evident even at an early age. This was attributed to the high-fat diet of most Americans. It is recognized that this disease is more prevalent in young males and that females are more protected until the onset of menopause; then the death rates tend to equalize. High-salt diets, which may increase the incidence of hypertension, also contribute to the development and progression of atherosclerosis. Since the 1960s, extensive education of the American public regarding dietary control has had a favorable impact. More recently, the benefits of exercise have helped to stem the atherosclerotic process.

The 1950s saw the development of cardiovascular surgery. The first bypass (arterial autograft) probably occurred during the Korean War. Coronary artery
bypass surgery and carotid endarterectomies are among the most common surgical procedures performed today. Recognition of and prompt treatment of cardiac and cerebrovascular symptoms remain the key to better survival rates. With development of newer bypass materials for lower extremity bypass surgery in the 1970s, as well as better surgical techniques for utilization of the saphenous veins, the amputation rate has significantly decreased. Research into graft materials that better mimic the native arteries and veins continues.

Since the 1950s, a number of noninvasive and invasive procedures have been developed to diagnose atherosclerotic disease. The development of ultrasound devices in the 1950s initiated the research into using these noninvasive devices to diagnose atherosclerotic disease. The duplex devices, introduced commercially in the late 1970s and early 1980s, opened a new diagnostic field for detection of atherosclerotic disease. These devices allow for visualization of plaque morphology (composition of the plaque such as thrombus, calcium, and hemorrhage) and the blood-flow characteristics for a better understanding of the atherosclerotic process. Future developments in the field of ultrasound include holographic imaging for three-dimensional visualization of plaques. These noninvasive technologies will also allow physicians to monitor the effects of new drugs and techniques in the treatment of atherosclerosis. Advances in digital subtraction and computer enhancement of angiographic techniques, along with new contrast media, are making arteriograms safer and more accurate.

Current diagnostic technologies include
magnetic resonance imaging (MRI), a nonradiological modality for visualizing structures in the brain and other portions of the body. MRI is used with the aid of computerization to do MR angiography. Magnetic resonance is also utilized to measure, noninvasively, actual flow in individual arterial segments of the body in terms of cubic centimeters per minute. Positron emission tomography (PET) scanning, a non-X-ray method, gives brilliant, color-enhanced visualization of blood flow to tissues.

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