Arteriosclerosis is the scientific term used to describe what is commonly referred to as “hardening of the arteries.” The process most often responsible for this transformation is atherosclerosis, arterial hardening due to the deposition of fat, calcium, cellular debris, and other substances within the arterial wall. Because of its greater specificity, the term atherosclerosis will be used here. The importance of atherosclerosis lies in the fact that it is the process responsible for most forms of cardiovascular disease, the leading cause of death in the United States and many other Western nations. About 60% of all deaths in the United States are completely or partially attributable to underlying cardiovascular disease. Thus, the process of atherosclerosis has important implications for the individual as well as society at large.

Atherosclerosis is a progressive process that has been shown to begin in childhood. The disease is characterized by changes within the arterial wall in the space just beneath the innermost layer of the vessel. Fats migrate into this space, where they are chemically modified; this triggers an accelerating cascade of biochemical events that causes an influx of inflammatory cells, dysfunction of the cells lining the blood vessel, and remodeling of the vessel wall with the deposition of calcium and other substances. The end result is the formation of an atherosclerotic plaque.

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As the plaque grows, it impinges on the arterial lumen, thereby reducing blood flow. When the tissue downstream from the lesion becomes sufficiently starved of oxygen and other nutrients, the patient begins to experience symptoms. Initially, this manifests as pain when the oxygen and nutrient demands of the tissue are greatest, that is, during exercise. Decreased blood flow through peripheral arteries causes attacks of lameness and pain in the legs with walking, whereas reduced perfusion of the heart presents as chest pain that radiates to the left arm and shoulder (angina pectoris). By inducing aberrant behavior among the cells that form the inner lining of the artery, atherosclerotic plaques also predispose the vessel to sudden occlusion by promoting the formation of blood clots. Clots formed in an artery supplying the heart result in a heart attack, whereas clot formation in a vessel feeding the brain manifests as a stroke.

Several atherosclerosis risk factors have been identified, including high concentrations of low-density lipoprotein cholesterol (“bad cholesterol”), low concentrations of high-density lipoprotein cholesterol (“good cholesterol”), smoking, high blood pressure, ovarian dysfunction, and diabetes. Some psychosocial factors have also been shown to correlate with the development of atherosclerosis. These include depression, anxiety, personality and character traits (e.g., competitiveness, anger, and hostility), social isolation and lack of social support, and acute and chronic life stresses. In contrast, submissiveness appears to be protective. It has been proposed that these psychosocial factors affect the development of atherosclerosis through their effects on behaviors (smoking, diet, compliance with therapeutic regimens) as well as by directly modifying the biochemical cascade responsible for the disease. The ultimate development of atherosclerosis is likely the result of several risk factors working in concert through multiple mechanisms.

Treatment of atherosclerosis focuses on risk factor modification. This includes smoking cessation, control of blood sugar for patients with diabetes, blood pressure control, and modification of cholesterol levels. The latter can be accomplished by reducing dietary saturated fat and cholesterol, which decreases bad cholesterol, and by increasing exercise, which increases good cholesterol. Several drugs are also available to modulate cholesterol levels. When cardiovascular disease becomes clinically evident (e.g., heart attack or stroke), treatment focuses on the surgical restoration of blood flow through the atherosclerotic artery using techniques such as angioplasty and arterial bypass grafts. In general, these treatments are aimed at slowing the progression and limiting the consequences of atherosclerosis; much less is known about ways to reverse the process once it has begun.


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