Download CORONARY ARTERY DISEASE Etiology and Pathophysiology

Section 7
500
Deaths in thousands
Cardiovascular System
806
Problems of Oxygenation: Perfusion
493,623
Males
433,825
Females
400
300
268,503
288,768
200
64,103
69,257
100
41,877
60,713
38,948
34,301
0
A
B
C
A Total CVD (Preliminary)
B Cancer
C Accidents
D
E
A
B
D
E
F
D Chronic Lower Respiratory Diseases
E Diabetes Mellitus
F Alzheimer’s Disease
FIG. 34-1 Leading causes of death for all men and women. CVD, Cardiovascular disease.
CORONARY ARTERY DISEASE
Coronary artery disease is a type of blood vessel disorder that is
included in the general category of atherosclerosis. The term atherosclerosis is derived from two Greek words: athere, meaning
“fatty mush,” and skleros, meaning “hard.” This combination indicates that atherosclerosis begins as soft deposits of fat that harden
with age. Atherosclerosis is often referred to as “hardening of the
arteries.” Although this condition can occur in any artery in the
body, the atheromas (fatty deposits) have a preference for the coronary arteries. Arteriosclerotic heart disease, cardiovascular heart
disease, ischemic heart disease, coronary heart disease, and CAD
are all terms used to describe this disease process.
Etiology and Pathophysiology
Atherosclerosis is the major cause of CAD. It is characterized by a
focal deposit of cholesterol and lipids, primarily within the intimal
wall of the artery. The genesis of plaque formation is the result of
complex interactions between the components of the blood and the
elements forming the vascular wall.2 Inflammation and endothelial
injury play a central role in the development of atherosclerosis.
Intact normal endothelium is more than a simple barrier between the vessel wall and the lumen of the vessel. Normally, it is
nonreactive to platelets and leukocytes, as well as coagulation, fibrinolytic, and complement factors. However, the endothelial lin-
ing can be injured as a result of tobacco use, hyperlipidemia, hypertension, diabetes, hyperhomocysteinemia, and infection (e.g.,
Chlamydia pneumoniae, herpes) causing a local inflammatory response3,4 (Fig. 34-2, A).
C-reactive protein (CRP), a nonspecific marker of inflammation, is increased in many patients with CAD. Chronic exposure to
even minor elevations of CRP can trigger the rupture of plaques
and promote the oxidation of low-density lipoprotein (LDL) cholesterol, leading to increased uptake by macrophages in the endothelial lining.5,6
Developmental Stages. CAD is a progressive disease that
takes many years to develop. When it becomes symptomatic, the
disease process is usually well advanced. The stages of development
in atherosclerosis are (1) fatty streak, (2) fibrous plaque resulting
from smooth muscle cell proliferation, and (3) complicated lesion.
Fatty Streak. Fatty streaks, the earliest lesions of atherosclerosis, are characterized by lipid-filled smooth muscle cells.2 As
streaks of fat develop within the smooth muscle cells, a yellow
tinge appears. Fatty streaks can be observed in the coronary arteries by age 15 and involve an increasing amount of surface area as
the patient ages. It is generally believed that treatment that lowers
LDL cholesterol may reverse this process4 (Fig. 34-2, B).
Fibrous Plaque. The fibrous plaque stage is the beginning of
progressive changes in the endothelium of the arterial wall. These
changes can appear in the coronary arteries by age 30 and increase
with age.
Normally the endothelium repairs itself immediately, but in the
person with CAD the endothelium is not rapidly replaced, allowing LDLs and growth factors from platelets to stimulate smooth
muscle proliferation and thickening of the arterial wall. Once endothelial injury has occurred, lipoproteins (carrier proteins within
the bloodstream) transport cholesterol and other lipids into the arterial intima. The fatty streak is eventually covered by collagen
forming a fibrous plaque that appears grayish or whitish.2,4 These
plaques can form on one portion of the artery or in a circular
fashion involving the entire lumen. The borders can be smooth or
irregular with rough, jagged edges.2 The result is a narrowing of
the vessel lumen and a reduction in blood flow to the distal tissues
(Fig. 34-2, C).
Complicated Lesion. The final stage in the development of the
atherosclerotic lesion is the most dangerous. As the fibrous plaque
grows, continued inflammation can result in plaque instability, ulceration, and rupture.4 Once the integrity of the artery’s inner wall
has become compromised, platelets accumulate in large numbers,
leading to a thrombus. The thrombus may adhere to the wall of the
GENDER DIFFERENCES
Coronary Artery Disease
Men
Women
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•
•
•
•
•
Men tend to manifest CAD 10-15 years
earlier than women.
Initial cardiac event for men is more often
MI than angina.
Men have a higher incidence of left ventricular hypertrophy than women.
•
•
•
CAD causes more deaths in women than in men.
Initial cardiac event for women is more often angina than MI.
Women with the long Q-T syndrome have an increased incidence of sudden cardiac death
compared to men with the same disorder.
Before menopause, women have higher HDL cholesterol levels and lower LDL cholesterol
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, myocardial infarction.
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