What is Atherosclerosis?

1 Do you have to be old to have atherosclerosis?

No. The initial (or type I) lesion, consisting of lipid deposits in the intima, has been well characterized in infants and children.

2 What is a fatty streak?

Fatty streaks or type II lesions are visible as yellow-colored streaks, patches, or spots on the intimal surface of arteries. Microscopically, they are characterized by the intracellular accumulation of lipid.

3 What is a foam cell?

A foam cell is any cell that has ingested lipids, thus giving the histologic appearance of a sudsy vacuole. In general, a foam cell refers to a lipid-laden macrophage; however, other cells that uptake lipids, particularly vascular smooth muscle cells, also may be considered foam cells.

4 Describe the progression of atherosclerosis

Although the sequence of events is not always consistent, fatty streaks progress to type III or intermediate lesions. This growth is characterized by extracellular pools of lipid, which are generally clinically occult. However, when the pools coalesce to create a core of extracellular lipid (type IV lesion or atheroma), the blood vessel architecture has been altered sufficiently to become clinically overt. With smooth muscle cell (SMC) proliferation and collagen deposition, the atheroma becomes a fibroatheroma (type V). The fibroatheroma is characterized by thrombogenic surface defects that provoke intramural hemorrhage or intraluminal thrombus (type V lesion), resulting in vessel occlusion, which, in the case of a coronary artery, results in myocardial infarction (MI).

5 Of 100 medical student volunteers, how many have significant atherosclerosis?

In 1953, Enos reported autopsy findings from 300 United States male battle casualties in Korea (average age, 22 years). He noted that 77% of the hearts had some gross evidence of coronary atherosclerosis. About 39% of the men had luminal narrowing, estimated at 10%–90%, and 3% had plaques causing complete occlusion of one or more coronary vessels. However, a subsequent study evaluating 105 combat casualties in Vietnam demonstrated that only 45% exhibited atherosclerosis, and fewer than 5% were considered severe. Finally, a recent study looking at 105 trauma victims corroborated the Korean War study by demonstrating a 78% incidence of atherosclerosis, with left main or significant two- and three-vessel involvement in 20%.

6 What are the classic risk factors for atherosclerotic cardiovascular disease?

The classic risk factors include tobacco use, hyperlipidemia, hypertension, diabetes mellitus, and family history of cardiovascular disease. More recent evidence suggests the importance of obesity, emotional stress (weaker), and physical inactivity (that’s you).

7 How do such diverse risk factors produce similar disease?

That is the million-dollar question. Do parallel pathways lead to a final atherosclerotic lesion, or do the apparently dissimilar risk factors activate signals that converge to a few dominant events, promoting the development of atherosclerosis? Certainly, this question has broad therapeutic implications. It would be a lot easier to inhibit a single proximal point in this process rather than to treat multiple divergent, more distal cellular pathologic events.

8 What is the response to injury?

The premise that atherogenesis represents an exaggerated inflammatory, fibroproliferative response to injury has evolved into an attractive unifying hypothesis of vascular disease and repair. Mechanical, metabolic, and toxic insults may injure the vessel wall. The common denominator is endothelial injury. Disruption of the endothelium not only results in endothelial cell dysfunction but also allows adhesion and transmigration of circulating monocytes, platelets, and T lymphocytes. Within the developing lesion, the activated cells release potent growth-regulatory molecules that may act in both a paracrine and autocrine manner. Under the influence of cytokines and growth factors, vascular smooth muscle cells (VSMCs) adapt to a synthetic phenotype and begin proliferation and migration across the internal elastic lamina into the intimal layer. Stimulated VSMCs allow the deposition of extracellular matrix, thus converting the initial lesion to a fibrous plaque.

9 What is C-reactive protein (CRP)? Is it just another random, nonclinically relevant marker of inflammation?

CRP is one of many acute phase proteins elaborated from hepatocytes on inflammatory stimulation. Originally isolated from the serum of patients with pneumonia, it has a high binding affinity for pneumococcal C-polysaccharide. Although CRP is best known as an active peptide by neutralizing foreign antigens, controlling tissue damage, and promoting tissue repair, it is increasingly considered a sensitive marker of inflammation. Unlike other markers of inflammation, CRP levels are stable over long periods of time, have no diurnal variation, can be measured inexpensively with available high-sensitivity assays, and have shown specificity in predicting risk of cardiovascular events. Indeed, elevation of CRP levels might be more predictive of cardiac events than elevation of low-density lipoprotein (LDL) levels. These observations may influence therapy because nonhyperlipidemic patients with elevated CRP levels might benefit from aggressive statin (3-hydroxyl-3-methylglutaryl [HMG]-reductase inhibitors) therapy.

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