: Plasma Lipoproteins
protective against atherosclerosis. Because hepatic lipase
deficiency causes an increase in triglyceride-enriched
HDL (and IDL), it is associated with premature atheroscle-
rosis. Examples of low plasma HDL cholesterol which
are not associated with coronary artery disease are also
known. In both Tangier disease and fisheye disease (dis-
cussed earlier), despite low plasma or HDL cholesterol
levels, coronary artery disease is an inconsistent finding.
In individuals with apo A-lMiiano* despite low HDL choles-
terol levels, longevity has been observed in the affected
Elevated Lp(a) is a major independent risk factor
for atherosclerosis in patients with familial hypercholes-
terolemia. This risk is independent of levels of LDL, HDL,
age, sex, and smoking habits, and is primarily dependent
on genetic factors. The exact mechanism of Lp(a) accel-
eration of atherosclerosis is not understood but may be
attributable to its potential inhibition of blood clot disso-
lution caused by its structural similarity with plasminogen
(see above and Chapter 36).
In evaluating the plasma cholesterol level with respect
to CHD, the measurement of LDL and HDL cholesterol
is therefore useful. These two levels can be determined
by measurement of plasma triacylglycerol and cholesterol
after a 12- to 14-hour fast. In the absence of chylomi-
crons and remnant lipoproteins, VLDL cholesterol is equal
to triacylglycerol divided by 5. HDL cholesterol is esti-
mated in the supernatant obtained from precipitation of
non-HDL lipoproteins by heparin-Mn2+, dextran sulfate
500, or phosphotungstate-Mg2+. LDL cholesterol is calcu-
lated from the following formula (all values are expressed
as mg/dL):
LDL cholesterol = total cholesterol—
(VLDL cholesterol + HDL cholesterol)
LDL cholesterol = total cholesterol—
Direct measurements of serum LDL cholesterol and HDL
cholesterol are currently used. Lor example, a direct LDL
cholesterol measurement is obtained by immunosepara-
tion. In this procedure, addition of antibodies against apo
A-I and apo E removes the HDL and VLDL fractions,
respectively, allowing LDL cholesterol to be measured di-
rectly in the filtrate. Measurement of apo A-I, apo B, and
apo E may prove to be equally useful, if not better, for the
assessment of CHD. For example, the predictive values
for CHD of LDL cholesterol and apo B-100 values are
similar, as are those of HDL cholesterol and apo A-I.
Lipid-Lowering Methods
Since hypercholesterolemia (in particular, LDL choles-
terol) increases the risk of CHD, it seems reasonable
to lower cholesterol levels in patients whose levels put
them at risk. Before treatment, other risk factors such
as hypertension, cigarette smoking, obesity, and glucose
intolerance need to be evaluated and corrected. Disor-
ders that exacerbate hyperlipoproteinemia (e.g., chronic
ethanol abuse, hypothyroidism, diabetes mellitus) need to
be treated before lipid-lowering measures are taken (dis-
cussed earlier, Table 20-7).
In uncomplicated hyperlipoproteinemia, the first step is
to reduce dietary intake of cholesterol and saturated fats
and to establish an ideal body weight. Daily dietary choles-
terol consumption should be limited to 300 mg or less and
fat intake to 30% of total energy intake, with a polyunsat-
urated fat to saturated fat ratio of 1:1. Polyunsaturated fats
include the
family (found mostly in fish oils) and the
family of essential fatty acids (found mostly in veg-
etable oils). The lipid-lowering effects of &>-3 fatty acids
(particularly of decreases in fatty acid and VLDL syn-
thesis in liver) are much greater than those of
acids. The former also decrease platelet aggregation. The
lipid-lowering effect and decreased platelet aggregation
are beneficial in lowering the risk of CHD. The low death
rate from CHD among Greenland Eskimos is probably
due to daily consumption of 5-10 g of
essential fatty
acids that enter their diet by way of marine phytoplankton
eaten by fish, which in turn are eaten by seals, walruses,
and whales.
Hypocholesterolemia can also be brought about by
diets rich in water-soluble fibers. Sources include pectins,
gums, certain hemicellulosees, and storage carbohydrates
(Chapter 9). Water-soluble fibers are found in fruits, oats,
barley, and legumes; oat bran and dried beans are par-
ticularly rich sources. The cholesterol-lowering effect is
not shared by water-insoluble fibers (e.g., cellulose, found
in wheat bran). The specific cholesterol-reducing mecha-
nisms of water-soluble fiber may be related to its ability
to bind bile acids in the intestine. This decreases bile acid
reabsorption and results in less cholesterol being avail-
able for lipoprotein synthesis in the liver. In addition to
their lipid-lowering effect, water-soluble fiber increases
intestinal transit time, delays gastric emptying, and slows
glucose absorption. The last effect may be beneficial in
the treatment of diabetes mellitus.
If dietary therapy is unsuccessful, drug therapy should
be employed. Five classes of drugs are available for treat-
ment of hyperlipoproteinemias; their effects are due to
decreased production or enhanced removal of lipoprotein
from plasma.
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