Porth's Essentials of Pathophysiology, 4e

409

Disorders of Blood Flow and Blood Pressure

C h a p t e r 1 8

CHART 18-1   Risk Factors for Atherosclerosis Nonmodifiable

■■ Increasing age ■■ Male gender

■■ Genetic disorders of lipid metabolism

■■ Family history of premature coronary artery disease Potentially Modifiable

■■ Cigarette smoking

4

Internal carotid arteries

■■ Obesity

Vertebral, basilar, and middle cerebral arteries

5

■■ Hypertension

■■ Hyperlipidemia with elevated low-density lipoprotein and low high-density lipoprotein cholesterol

■■ Diabetes mellitus Additional Nontraditional

2

Proximal coronary arteries

■■ Inflammation marked by elevated C-reactive protein levels

■■ Hyperhomocysteinemia

1

Abdominal aorta and iliac arteries

■■ Increased lipoprotein (a) levels

3

Thoracic aorta, femoral and popliteal arteries

cardiovascular risk factors. Smoking affects atheroscle- rosis by several mechanisms other than its unfavorable effects on blood pressure, sympathetic vascular tone, and reduction in myocardial oxygen supply. 6 It has adverse hemostatic and inflammatory effects and it may enhance the oxidation of LDL cholesterol, causing damage to the endothelial lining of blood vessels. Obesity, type 2 diabe- tes, high blood pressure, high blood triglycerides and low HDL levels (all components of the metabolic syndrome; see Chapter 33) often can be controlled with a change in health care behaviors and medications. However, not all cases of atherosclerosis can be explained by the established genetic and environmental risk factors. Other so-called nontraditional risk factors have been associated with increased risk for development of atherosclerosis, including C-reactive protein (CRP), serum homocysteine, and lipoprotein (a). 6 There also has been increased interest in the possible connection between infectious agents (e.g., Chlamydia pneumoniae, herpesvirus, cytomegalovirus) and the development of vascular disease. 2 Genomic evidence of these organisms has been found in atherosclerotic lesions, but whether they are causally associated with lesions or simply enter the diseased vessel is unknown. 2 Considerable interest in the role of inflammation in the etiology of atherosclerosis has emerged over the past two decades. C-reactive protein is an acute-phase reactant syn- thesized in the liver that is a marker for systemic inflam- mation (see Chapter 3). A number of population-based studies have demonstrated that baseline CRP levels can predict future cardiovascular events among apparently healthy individuals. 1 High-sensitivity CRP (hs-CRP) may be a better predictor of cardiovascular risk than lipid mea- surement alone. 6 Because CRP is an acute inflammatory phase reactant, major infections, trauma, or acute hos- pitalization can elevate CRP levels (usually 100-fold or more). Thus, CRP levels to determine cardiovascular risk should be performed when the person is clinically stable.

determined alterations in lipoprotein and cholesterol metabolism have been identified, and it seems likely that others will be identified in the future. 2 The incidence of atherosclerosis increases with age. Other factors being equal, men are at greater risk for the development of CAD than are premenopausal women, probably because of the protective effects of natural estrogens. After menopause, the incidence of atherosclerosis-related dis- eases in women increases, and by the seventh to eighth decade of life, the frequency of myocardial infarction in the two genders tends to equalize. 1 The major risk factors that can be modified by a change in health care behaviors include cigarette smoking, obe- sity, hypertension, hyperlipidemia and elevated LDL cho- lesterol, and diabetes mellitus, all of which are traditional FIGURE 18-6. Sites of severe atherosclerosis in order of frequency. (From Gotlieb AI, Lui A. Blood vessels. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th ed. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &Wilkins; 2012:452.)