Fibromuscular intimal hyperplasia is a non-atherosclerotic process that occurs in muscular arteries larger than arterioles. This is predominantly an SMCand ECM-rich lesion driven by inflammation (as in a healed arteritis or transplant-associated arteriopathy; see Chapter 11), or by mechanical injury (e.g., associated with stents or balloon angioplasty, see later). Such a healing response can cause substantial stenosis of the vessel; indeed such intimal hyperplasia underlies in-stent restenosis and is the major long-term limitation of solid organ transplants.
• Atherosclerosis, from Greek root words for “gruel” and “hardening,” is the most frequent and clinically important pattern and is the subject of the next section.
Atherosclerosis is characterized by intimal lesions called atheromas (or atheromatous or atherosclerotic plaques) that impinge on the vascular lumen and can rupture to cause sudden occlusion. It underlies the pathogenesis of coronary, cerebral, and peripheral vascular disease, and causes more morbidity and mortality (roughly half of all deaths) in the Western world than any other disorder. Atheromatous plaques are raised lesions composed of soft friable (grumous) lipid cores (mainly cholesterol and cholesterol esters, with necrotic debris) covered by fibrous caps (
Fig. 10.7 ). As they enlarged, atherosclerotic plaques may mechanically obstruct vascular lumina, leading to stenosis. Of greater concern, however, atherosclerotic plaques also are prone to rupture, an event that may result in thrombosis and sudden occlusion of the vessel. The thickness of the intimal lesions also may be sufficient to impede the perfusion of the underlying media, which may be weakened by ischemia and by changes in the ECM caused by subsequent inflammation. Together, these two factors weaken the media, setting the stage for the formation of aneurysms.
With better treatment of infectious disorders and increased access to Western dietary behaviors, atherosclerosis is also becoming increasingly prevalent in developing countries. Because coronary artery disease is an important manifestation of atherosclerosis, epidemiologic data related http://ebooksmedicine.net
Fig. 10.7 Thebasicstructureofanatheromatousplaque.
FIBROUS CAP (smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization)
NECROTIC CENTER (cell debris, cholesterol crystals, foam cells, calcium) to atherosclerosis-related mortality typically reflect deaths caused by ischemic heart disease (IHD) (Chapter 11); indeed, myocardial infarction is responsible for roughly one quarter of all deaths in the United States.
Atherosclerosis is virtually ubiquitous among most developed nations, with prevalence increasing at an alarming pace in developing countries. The mortality rate for IHD in the United States is among the highest in the world, approximately five times higher than that in Japan. However, IHD is increasing in Japan, where it is now the second leading cause of death. Furthermore, Japanese emigrants who come to the United States and adopt American lifestyles and dietary customs acquire the same atherosclerosis risk as U.S.-born individuals, emphasizing the important etiologic role of environmental factors.
The prevalence and severity of atherosclerosis and IHD have been correlated with a number of risk factors in several prospective analyses including the landmark Framingham Heart Study; some of these risk factors are constitutional (and therefore less controllable), but others are acquired or related to modifiable behaviors ( 10.3 ). These risk factors have roughly multiplicative effects. Thus, two factors increase the risk for myocardial infarction approximately 4-fold, and three (i.e., hyperlipidemia, hypertension, and smoking) increase the rate by a factor of 7 (