many of these factors in the pathophysiology of atherosclerosis have been defined (Fuster et al., 1996). They can be classified on the basis of whether they are modifiable (Pasternak et al., 1996; Pearson et al., 1993) (Figure 1-2). Nonmodifiable risk factors include age, male gender, and a positive family history of CVD with onset at an early age. Modifiable risk factors can be behavioral (sedentary life-style, a diet high in fat and cholesterol, cigarette smoking) or physiological (elevated low-density lipoprotein [LDL] cholesterol, decreased high-density lipoprotein [HDL] cholesterol, diabetes, hypertension, obesity, postmenopausal status [in women]). The effectiveness of modifying risk factors to prevent disease has been dramatic for some risk factors. For others, the association with atherosclerotic disease is less well understood (see Appendix B).

BOX 1-2 A Transition from Hemorrhagic to Artherombotic Stroke

As life expectancy increases, acute neurological deficits or strokes may become a significant health problem before there is an increase in coronary heart disease (Reed, 1990). Early in the transition from infectious to noncommunicable diseases, many of the strokes are so-called hemorrhagic strokes, caused by bleeding from an intracerebral artery into the brain. They have a case fatality rate of 80 percent or more (Wolf, 1994). The major risk factor for all forms of stroke is high blood pressure. For hemorrhagic stroke, low blood cholesterol is also a risk factor (Iso et al., 1989; Reed, 1990). As countries develop, their populations may have increased blood pressure before they experience increased blood cholesterol. This would lead to an increase in deaths from hemorrhagic stroke. Later in the transition, stroke mortality may change from the hemorrhagic type to the atherothrombotic type. Atherothrombotic stroke is caused by atherosclerotic plaques in the arteries that supply the brain. These can undergo ulceration or thrombosis, and the pieces of plaque or thrombus that break off may occlude one or more of the arteries to the brain and cause a malfunction. If the blood flow is restored, the malfunction is a transient ischemic attack. If the blood flow is not restored, brain tissue dies as a result of the stroke. This form of stroke has a case fatality rate of approximately 20 percent, but many of the survivors are left with disabilities such as paralysis, inability to speak, or blindness. The risk factors for atherothrombotic strokes are hypertension, elevated blood cholesterol, diabetes, and obesity. Studies of mortality from stroke in rapidly developing country populations have shown consistently high mortality rates and a transition in relative importance from intracerebral hemorrhagic stroke to atherothrombotic stroke with economic development.

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