C h a p t e r 1 8
Disorders of Blood Flow and Blood Pressure
409
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
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.
Vertebral, basilar,
and middle cerebral
arteries
5
Internal
carotid
arteries
4
Proximal
coronary
arteries
2
Abdominal
aorta and
iliac arteries
1
Thoracic aorta,
femoral and
popliteal
arteries
3
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.)
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
■■
Obesity
■■
Hypertension
■■
Hyperlipidemia with elevated low-density lipoprotein
and low high-density lipoprotein cholesterol
■■
Diabetes mellitus
Additional Nontraditional
■■
Inflammation marked by elevated C-reactive protein
levels
■■
Hyperhomocysteinemia
■■
Increased lipoprotein (a) levels
