C h a p t e r 1 8
Disorders of Blood Flow and Blood Pressure
407
Several factors, including nutrition, genetics, comor-
bid conditions, medications, and metabolic diseases,
can raise blood lipid levels. Most cases of elevated
levels of cholesterol are probably multifactorial.
Hypercholesterolemia can be divided into two types:
primary or secondary. In primary hypercholesteremia
elevated cholesterol levels develop independent of other
causes. Secondary hypercholesterolemia is associated
with other health problems and behaviors.
Many types of primary hypercholesterolemia have
a genetic basis. There may be a defective synthesis of
the apolipoproteins, a lack of lipoprotein receptors,
defective receptors, or defects in the handling of cho-
lesterol in the cell that are genetically determined.
1,2,9
For example, the LDL receptor is deficient or defec-
tive in the genetic disorder known as
familial hyper-
cholesterolemia (type 2A).
This autosomal dominant
type of hyperlipidemia results from a mutation in the
gene specifying the receptor for LDL. It is one of the
most common of all Mendelian disorders, with hetero-
zygotes having one defective gene representing about 1
in 500 persons in the general population.
1,2,9
Because
most of the circulating cholesterol is removed by recep-
tor-dependent mechanisms, blood cholesterol levels are
markedly elevated in persons with this disorder. Plasma
LDL levels in heterozygotes range between 250 and
500 mg/dL, whereas in homozygotes LDL cholesterol
levels may rise to 1000 mg/dL. Although heterozygotes
commonly have an elevated cholesterol level from
birth, the disorder does not typically manifest until
adult life, when
xanthomas
(i.e., cholesterol deposits)
develop along the tendons, and atherosclerosis appears
(Fig. 18-5). Myocardial infarction before 40 years of
age is common. Homozygotes are much more severely
affected; they have cutaneous xanthomas in childhood
and may experience myocardial infarction by as early
as 1 to 2 years of age.
Secondary causes of hypercholesterolemia include
obesity with high-calorie intake, sedentary lifestyle, and
diabetes mellitus.
9,11
High-calorie diets increase the pro-
duction of VLDL, with triglyceride elevation and high
conversion of VLDL to LDL. Excess ingestion of cho-
lesterol may reduce the formation of LDL receptors and
thereby decrease LDL removal from the blood. Diets
that are high in saturated fats increase cholesterol syn-
thesis and suppress LDL receptor activity. A sedentary
lifestyle influences interactions among lipids and lipo-
proteins. Diabetes mellitus and the metabolic syndrome
are associated with elevated triglycerides, low HDL, and
minimal or modest elevation of LDL. Other systemic
disorders that can elevate lipids include hypothyroidism,
the nephrotic syndrome, and obstructive liver disease.
Medications such as beta-blockers, estrogens, and prote-
ase inhibitors (used in the treatment of human immuno-
deficiency virus [HIV] infection) can also increase lipid
levels.
Diagnosis of Hyperlipidemia.
Diagnosis of hyperlip-
idemia depends on a person’s complete lipid profile (total
cholesterol, LDL, HDL, and triglyceride levels) after an
overnight fast.
9,11
Most clinical laboratories measure
the total serum cholesterol, total triglycerides, and the
amount of cholesterol carried in the HDL fraction. The
LDL is then estimated by subtracting the HDL from
the total serum cholesterol and the triglycerides divided
by5
*
(i.e.,LDL[mg/dL]=totalcholesterol[mg/dL]−HDL
[mg/dL] − triglycerides [mg/dL]/5). The relationship
between the different lipid fractions can then be used
as a means for determining an individual’s risk for
developing coronary heart disease and other athero-
sclerosis-related diseases. Cholesterol is carried in the
blood as VLDL, LDL, and HDL, with the total serum
cholesterol being equal to the sum of these three com-
ponents.
11,12
Thus, total serum cholesterol levels may
A
B
C
D
FIGURE 18-5.
Xanthomas in the skin and
tendons
(A, C, D)
. Arcus lipoides represents the
deposition of lipids in the peripheral cornea
(B).
(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; 2012:459.)
*When using SI units (expressed in mmol/L), the triglycerides are
divided by 2.2.
