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P A R T 8
Drugs acting on the cardiovascular system
T
he drugs discussed in this chapter lower serum levels
of cholesterol and various lipids. These drugs are some-
times called
antihyperlipidaemic agents
used to treat
hyperlipidaemia
—an increase in the level of lipids in
the blood. There is mounting evidence that the inci-
dence of coronary artery disease (CAD), the leading
killer of adults in the Western world, is higher among
people with high serum lipid levels. The cause of CAD
is poorly understood, but some evidence indicates that
cholesterol and fat may play a major role in disease
development. Lipid and triglyceride levels play a role in
metabolic syndrome
, a collection of factors, including
insulin resistance, abdominal obesity, low high-density
lipoprotein and high triglyceride levels, hypertension
and proinflammatory and prothrombotic states, that
has been shown to increase the incidence of CAD. See
Table 47.1.
it becomes less distensible and less reactive to many
neurological and chemical stimuli that would ordinarily
dilate or constrict it. As a result, the coronary vessels
are no longer able to balance the myocardial demand
for oxygen with increased blood supply. More recent
evidence indicates that the makeup of the core of the
atheroma may be a primary determinant of which ath-
eromas might rupture and cause acute blockage of a
vessel. The softer, more lipid-filled atheromas appear to
be more likely to rupture than the stable, harder cores.
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TABLE 47.1 Clinical aspects of the metabolic
syndrome
Parameter
Significant values
Insulin
resistance
Fasting blood glucose >7.0 mmol/L
Abdominal
obesity
Waist measurement >94 cm in
men; >80 cm in women; >90 cm
in men from Middle Eastern,
South Asian, Chinese, Asian-
Indian, South and Central
American backgrounds
Lipid
abnormalities
High density lipoproteins (HDLs)
>1.0 mmol/L; any triglycerides
(TG) >2.0 mmol/L
Hypertension
Blood pressure >130/85 mmHg
Proinflammatory
state
Increased macrophages, increased
levels of interleukin-6 and tumour
necrosis factor (TNF)
Prothrombotic
state
Increased plasminogen activator
levels
CORONARY ARTERY DISEASE
As explained in Chapter 46, CAD is characterised by
the progressive growth of atheromatous plaques, or
atheromas, in the coronary arteries. These plaques,
which begin as fatty streaks in the endothelium, event
ually injure the endothelial lining of the artery, causing
an inflammatory reaction. This inflammatory process
triggers the development of characteristic foam cells
containing fats and white blood cells that further injure
the endothelial lining. Over time, platelets, fibrin, other
fats and remnants collect on the injured vessel lining
and cause the atheroma to grow, further narrowing the
interior of the blood vessel and limiting blood flow.
The injury to the vessel also causes scarring and
a thickening of the vessel wall. As the vessel thickens,
Unmodifiable risk factors
•
Genetic predispositions
: CAD is more likely to occur
in people who have a family history of the disease,
particularly if the disease occurs in relatives younger
than the age of 55 years.
•
Age
: The incidence of CAD increases with age.
•
Gender
: Men are more likely than premenopausal
women to have CAD; however, the incidence is almost
equal in men and postmenopausal women, possibly
because of a protective effect of oestrogens (see
Box 47.3).
Modifiable risk factors
•
Gout
: Increased uric acid levels seem to injure vessel
walls.
•
Cigarette smoking
: Nicotine causes vasoconstriction
and may have an effect on the endothelium of blood
vessels; over time, smoking can lower oxygen levels in
the blood.
•
Sedentary lifestyle
: Exercise increases the levels of
chemicals that seem to protect the coronary arteries.
•
High stress levels
: Constant sympathetic reactions
increase the myocardial oxygen demand while causing
vasoconstriction and may contribute to a remodelling
of the blood vessel endothelium, leading to an
increased susceptibility to atheroma development.
•
Hypertension
: High pressure in the arteries causes
endothelial injury and increases afterload and
myocardial oxygen demand.
•
Obesity
: This may reflect altered fat metabolism and
will increase the heart’s workload.
•
Diabetes
: Diabetics have a capillary membrane
thickening, which accelerates the effects of
atherosclerosis and abnormal fat metabolism, which
increases lipid levels.
•
Other
factors
that, if untreated, may contribute
to CAD include bacterial infections (
Chlamydia
infections have been correlated with onset of
CAD, and treatment with tetracycline and
fluororoentgenography has been associated with
decreased incidence of CAD, indicating a possible
bacterial link) and autoimmune processes (some
plaques contain antibodies and other products of
immune reactions, making autoimmune reactions a
possibility).
■■
BOX 47.1
Risk factors for coronary artery disease
