806 Section 7 Problems of Oxygenation: Perfusion

ing can be injured as a result of tobacco use, hyperlipidemia, hy-

493,623 pertension, , hyperhomocysteinemia, and infection (e.g., 500 433,825 Males Chlamydia pneumoniae, herpes) causing a local infl ammatory re- sponse3,4 (Fig. 34-2, A). 400 Females C-reactive protein (CRP), a nonspecifi c marker of infl amma- tion, is increased in many patients with CAD. Chronic exposure to 300 288,768 268,503 even minor elevations of CRP can trigger the rupture of plaques

Cardiovascular System Cardiovascular and promote the oxidation of low-density lipoprotein (LDL) cho- 200 lesterol, leading to increased uptake by in the endo- 5,6 64,103 thelial lining.

Deaths in thousands 69,257 41,877 100 60,713 Developmental Stages. CAD is a progressive disease that 34,301 38,948 takes many years to develop. When it becomes symptomatic, the 0 disease process is usually well advanced. The stages of development ABCDE ABDEF in are (1) fatty streak, (2) fi brous plaque resulting from smooth muscle cell proliferation, and (3) complicated lesion. A Total CVD (Preliminary) D Chronic Lower Respiratory Diseases B Cancer E Diabetes Mellitus Fatty Streak. Fatty streaks, the earliest lesions of atherosclero- 2 C Accidents F Alzheimer’s Disease sis, are characterized by lipid-fi lled smooth muscle cells. As streaks of fat develop within the smooth muscle cells, a yellow FIG. 34-1 Leading causes of death for all men and women. CVD, Cardiovas- cular disease. tinge appears. Fatty streaks can be observed in the coronary arter- ies by age 15 and involve an increasing amount of surface area as the patient ages. It is generally believed that treatment that lowers CORONARY DISEASE LDL may reverse this process4 (Fig. 34-2, B). Coronary artery disease is a type of blood vessel disorder that is Fibrous Plaque. The fi brous plaque stage is the beginning of included in the general category of atherosclerosis. The term ath- progressive changes in the endothelium of the arterial wall. These erosclerosis is derived from two Greek words: athere, meaning changes can appear in the coronary by age 30 and increase “fatty mush,” and skleros, meaning “hard.” This combination indi- with age. cates that atherosclerosis begins as soft deposits of fat that harden Normally the endothelium repairs itself immediately, but in the with age. Atherosclerosis is often referred to as “hardening of the person with CAD the endothelium is not rapidly replaced, allow- arteries.” Although this condition can occur in any artery in the ing LDLs and growth factors from platelets to stimulate smooth body, the atheromas (fatty deposits) have a preference for the coro- muscle proliferation and thickening of the arterial wall. Once en- nary arteries. Arteriosclerotic heart disease, cardiovascular heart dothelial injury has occurred, lipoproteins (carrier proteins within disease, ischemic heart disease, coronary heart disease, and CAD the bloodstream) transport cholesterol and other lipids into the ar- are all terms used to describe this disease process. terial intima. The fatty streak is eventually covered by collagen forming a fi brous plaque that appears grayish or whitish.2,4 These Etiology and Pathophysiology plaques can form on one portion of the artery or in a circular Atherosclerosis is the major cause of CAD. It is characterized by a fashion involving the entire lumen. The borders can be smooth or focal deposit of cholesterol and lipids, primarily within the intimal irregular with rough, jagged edges.2 The result is a narrowing of wall of the artery. The genesis of plaque formation is the result of the vessel lumen and a reduction in blood fl ow to the distal tissues complex interactions between the components of the blood and the (Fig. 34-2, C). elements forming the vascular wall.2 Infl ammation and endothelial Complicated Lesion. The fi nal stage in the development of the injury play a central role in the development of atherosclerosis. atherosclerotic lesion is the most dangerous. As the fi brous plaque Intact normal endothelium is more than a simple barrier be- grows, continued infl ammation can result in plaque instability, ul- tween the vessel wall and the lumen of the vessel. Normally, it is ceration, and rupture.4 Once the integrity of the artery’s inner wall nonreactive to platelets and leukocytes, as well as coagulation, fi - has become compromised, platelets accumulate in large numbers, brinolytic, and complement factors. However, the endothelial lin- leading to a thrombus. The thrombus may adhere to the wall of the

GENDER DIFFERENCES Coronary Artery Disease Men Women • Men tend to manifest CAD 10-15 years • CAD causes more deaths in women than in men. earlier than women. • Initial cardiac event for women is more often angina than MI. • Initial cardiac event for men is more often • Women with the long Q-T syndrome have an increased incidence of sudden cardiac death MI than angina. compared to men with the same disorder. • Men have a higher incidence of left ven- • Before menopause, women have higher HDL cholesterol levels and lower LDL cholesterol tricular hypertrophy than women. levels than men. • After menopause, LDL levels increase. • Women complain of palpitations more frequently than men.

CAD, Coronary artery disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MI, .

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