Major Lesser, Uncertain, or Nonquantitated

Nonmodifiable

Increasing age Obesity

Male gender Physical inactivity

Family history Stress ("type A" personality)

Genetic abnormalities Postmenopausal estrogen deficiency

High carbohydrate intake

Potentially Controllable

Hyperlipidemia Alcohol

Hypertension Lipoprotein Lp(a)

Cigarette smoking Hardened (trans)unsaturated fat intake

Diabetes Chlamydia pneumoniae

high blood lipid levels, such as familial hypercholesterolemia, which was discussed in Chapter 5 .

Other, nongenetic risk factors, particularly diet, lifestyle, and personal habits, are to a large extent potentially reversible. The four major risk factors potentially responsive to change are

hyperlipidemia, hypertension, cigarette smoking, and diabetes.

Hyperlipidemia.

Hyperlipidemia is a major risk factor for atherosclerosis. Most of the evidence specifically implicates hypercholesterolemia. Elevated levels of serum cholesterol are sufficient to stimulate

lesion development, even if other risk

Figure 11-10Estimated 10-year risk of coronary artery disease according to various combinations of risk factor levels, expressed as the probability of an event in 10 years. HDL-C, high

density lipoprotein cholesterol (From Kannel WB, et al: An update on coronary risk factors. Med Clin North Am 79:951, 1995.)

Figure 11-11Evolution of arterial wall changes in the response to injury hypothesis. 1, Normal. 2, Endothelial injury with adhesion of monocytes and platelets (the latter to denuded

endothelium). 3, Migration of monocytes (from the lumen) and smooth muscle cells (from the media) into the intima. 4, Smooth muscle cell proliferation in the intima. 5, Well-developed

plaque (see Fig. 11-7 for details of mature plaque structure).

Figure 11-12Schematic diagram of hypothetical sequence of cellular interactions in atherosclerosis. Hyperlipidemia and other risk factors are thought to cause endothelial injury, resulting

in adhesion of platelets and monocytes and release of growth factors, including platelet-derived growth factor (PDGF), which lead to smooth muscle cell migration and proliferation. Foam

cells of atheromatous plaques are derived from both macrophages and smooth muscle cells—from macrophages via the very-low-density lipoprotein (VLDL) receptor and low-density

lipoprotein (LDL) modifications recognized by scavenger receptors (e.g., oxidized LDL), and from smooth muscle cells by less certain mechanisms. Extracellular lipid is derived from

insudation from the vessel lumen, particularly in the presence of hypercholesterolemia, and also from degenerating foam cells. Cholesterol accumulation in the plaque reflects an imbalance

between influx and efflux, and high-density lipoprotein (HDL) likely helps clear cholesterol from these accumulations. Smooth muscle cells migrate to the intima, proliferate, and produce

extracellular matrix, including collagen and proteoglycans.

TABLE 11-3-- Types and Causes of Hypertension

Essential Hypertension

Date: 2016-04-22; view: 601