What Are Lipoproteins?

Lipoproteins serve to transport lipids like triglycerides and cholesterol around the body. But
first, what exactly are these lipids? Cholesterol is a type of lipid that plays important roles in
the human body. It helps form the cell membrane and also serves a precursor for steroid
hormones (like estrogen and cortisol) and bile acids (which aid in fat digestion). Its structure
consists of four fused hydrocarbon rings attached to a hydrocarbon tail at one end and a
hydroxyl group at the other end (Figure 1).

Figure 1

Credit: ©ScholarRx

Triglycerides are another type of lipid found in adipose tissue, our fat reservoir. They can be
mobilized for energy as an alternative to carbohydrates and are converted to phospholipids
that serve structural functions in cell membranes. Their structure consists of three fatty acid
molecules bound to glycerol (Figure 2).

Figure 2
Credit: ©ScholarRx

Lipoproteins: Taxis for Lipids

Because cholesterol and triglycerides are both nonpolar substances, they are insoluble in
water (hydrophobic) and need special molecules to transport them in the blood. These special
molecules are known as lipoproteins. You can think of the lipoproteins as taxis responsible
for shuttling lipids to and from various organs of the body, using the bloodstream as their
highway.

Each lipoprotein is a mixture of lipids (cholesterol and/or triglycerides) with specific

proteins. Each lipoprotein has a different composition and a different function in lipid
transport. We divide lipoproteins into different classes based on their density, which is
determined by the relative content of cholesterol, triglycerides, and proteins. There are five
classes of lipoproteins. From lowest to highest density, they are chylomicrons, very-low-
density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), low-density
lipoproteins (LDLs), and high-density lipoproteins (HDLs).

The make-up and general functions of each type of lipoprotein are shown in Table 1. Note
that the increasing relative proportion of protein within each lipoprotein corresponds to an
increase in its density (eg, high-density lipoprotein has the highest protein content).

Lipid-to-
Lipoprotein (in Order
Protein Function
of Increasing Density)
Ratio
Delivers dietary triglycerides from gut to peripheral
Chylomicron 99:1
tissues and dietary cholesterol to liver
VLDL 92:8 Delivers hepatic triglycerides to peripheral tissues
Formed from VLDL degradation; delivers
IDL 85:15
triglycerides to tissues and cholesterol to liver
LDL 80:20 Delivers hepatic cholesterol to peripheral tissues
Delivers cholesterol from peripheral tissues to liver;
HDL 50:50 donates Apo C-2 and Apo E to form mature
chylomicrons and mature VLDL
Table 1

Structure of Lipoproteins

All five lipoproteins share the same general structure (Figure 3). A phospholipid membrane
forms the exterior of the lipoprotein. The membrane has a hydrophilic exterior, which allows
it to travel through the blood, and a hydrophobic interior, which allows it to carry nonpolar
cholesterol esters and triglycerides. In addition, each lipoprotein contains different sets of
apoproteins.
Figure 3

Credit: ©ScholarRx

Apoproteins (apolipoproteins) are an important structural component of the lipoprotein. They

serve as both co-factors for various enzymes and ligands for different cell-surface receptors
during the lipoprotein’s journey through the body. If the lipoprotein is a taxi on the
bloodstream highway, apoproteins act as passes at various toll booths the taxi encounters on
its way. You should be familiar with five main classes of apoproteins (abbreviated “Apo”).
These are Apo A-1, Apo B-48, Apo B-100, Apo C-2, and Apo E. Each apoprotein has a
different function, and different combinations of apoproteins are found on different
lipoproteins.

What Are the Different Types of Lipoproteins?

Lipoproteins come in different types, with varying density, size, structure, lipid and protein
composition, and clinical significance (Figure 4). Note that each lipoprotein has a different
internal composition as well as a different set of outer apoproteins. Also note that the density
of each lipoprotein is directly proportional to its relative protein content and inversely
proportional to its relative lipid content. Let’s look at each lipoprotein in turn.

Figure 4

Credit: ©ScholarRx

Chylomicrons

Chylomicrons deliver dietary fats and cholesterols from the intestine into the bloodstream and
then to the tissues, so they are the key mediators of the exogenous lipid pathway (ie, from
outside, in the diet). Lipid metabolism begins when we ingest fats and cholesterols and our
intestinal cells absorb them. The intestinal cells then assemble chylomicrons, filling them
with triglycerides, cholesterol, and the fat-soluble vitamins A, D, E, and K. Triglycerides
actually make up about 90% of the chylomicron. An enzyme called microsomal transfer
protein (MTP) loads Apo B-48 onto the chylomicron within the intestinal cell. At this point,
the lipoprotein is still a nascent chylomicron because it is not complete and contains only one
apoprotein, Apo B-48. The nascent chylomicron is secreted into the intestinal lymphatic
system, from where it enters the blood.

Nascent chylomicrons contain only Apo B-48.

Clinical Correlation

Abetalipoproteinemia is a disorder caused by a mutation in MTP. MTP is responsible not

only for loading Apo B-48 onto chylomicrons, but also for loading Apo B-100 onto VLDL.
As you can imagine, an inability to form chylomicrons or VLDL impairs absorption of fat
from the diet. These patients have steatorrhea, which means fatty stool, because they cannot
properly absorb fat. They also have a deficiency of fat-soluble vitamins, especially vitamin E.
Once in the plasma, the nascent chylomicron encounters HDL. Think of HDL as a helper
molecule (note that common letter H). HDL carries Apo C-2 and Apo E, both of which it
transfers onto the nascent chylomicron, which completes it. This mature chylomicron is now
free to finish its journey (Figure 4, left, and Figure 5).

Figure 5

Credit: ©ScholarRx

The mature chylomicron next encounters an enzyme called lipoprotein lipase (LPL). LPL is
anchored to the capillary endothelium of most peripheral tissues except the liver. It
hydrolyzes the chylomicron’s triglycerides into glycerol and fatty acids, using Apo C-2 as a
co-factor. The glycerol can travel to the liver to be used for glycolysis, gluconeogenesis, or
new lipid synthesis (VLDL). The fatty acids can provide fuel for muscle cells, get stored in
the adipose tissue, or remain in the blood bound to albumin.

Once the chylomicron has delivered its contents to the peripheral tissues, the Apo C-2 is
returned to HDL. The remaining molecule, now called the chylomicron remnant (see Figure
5), delivers its cholesterol to the liver, which has a receptor for Apo E. Apo E mediates
endocytosis of the chylomicron remnant by the liver, where it is then degraded.

Clinical Correlation

Deficiencies of LPL or Apo C-2 cause familial hyperchylomicronemia. These individuals

cannot activate LPL and hydrolyze their chylomicron contents, which leads to an
accumulation of chylomicrons in the plasma. If you were to centrifuge their blood, you would
find a creamy layer in the supernatant due to all the excess chylomicrons. Patients can present
with pancreatitis due to excess triglycerides.

Apo C-2 activates LPL, and it comes to the chylomicron

from HDL.
Very-Low-Density and Intermediate-Density Lipoproteins

In contrast to chylomicrons, the lipoproteins VLDL, IDL, and LDL mediate the endogenous
lipid pathway, in which lipids are synthesized, not ingested. We’ll start with VLDL and IDL.

VLDLs are synthesized in the liver and mainly function to deliver triglycerides from the liver
to the peripheral tissues (Figure 6). The nascent VLDL contains mainly triglycerides with a
bit of cholesterol. Recall that in the intestinal cells, microsomal transfer protein (MTP) was
responsible for loading Apo B-48 onto a nascent chylomicron. MTP has a similar function in
the liver, except this time it loads Apo B-100 onto a nascent VLDL. The liver then secretes
nascent VLDL into the blood.

Figure 6

Credit: ©ScholarRx
In the blood, nascent VLDL encounters the helper molecule HDL. Do you remember how
HDL helped out chylomicrons earlier? That’s right; it transferred two very important
apoproteins, Apo C-2 and Apo E, onto the chylomicrons. HDL does the exact same favor for
nascent VLDL so that now, a mature VLDL molecule is formed.

VLDL continues through the bloodstream where it encounters capillary lipoprotein lipase
(LPL). Remember that Apo C-2 is the co-factor responsible for activating LPL. LPL
hydrolyzes the VLDL triglycerides to glycerol for use as energy in the tissues. The loss of
triglycerides increases the density of the VLDL. The higher-density molecule that is formed
is referred to as intermediate-density lipoprotein, or IDL. IDL initially carries Apo B-100 and
Apo E but has fewer triglycerides than VLDL does.

About 50% of this cholesterol-rich IDL is taken up by into the liver by endocytosis, mediated
by Apo E. The remainder lose their Apo E and continue to lose triglycerides in the capillaries,
becoming smaller and denser. When the cholesterol content becomes dominant, the IDLs
become low-density lipoprotein (LDL).

VLDL delivers triglycerides from the liver to peripheral

tissues.
Low-Density Lipoproteins

The LDLs’ main role is to carry cholesterol to the peripheral tissues. They have a high ratio
of cholesterol to triglycerides, and they only carry one apolipoprotein, Apo B-100.

How does LDL deliver its cholesterol to peripheral tissues? This is done by a process known
as receptor-mediated endocytosis (Figure 7).
Figure 7

Credit: ©ScholarRx

LDL receptors on peripheral tissues are found on clathrin-coated pits in the cell membrane.
Apo B-100 on LDL binds the LDL receptor, and the clathrin-coated pit engulfs LDL,
internalizing it to form an endosome. The membrane component, which contains LDL
receptor, is recycled back to the plasma membrane. The cholesterol-containing contents of
LDL are transferred to lysosomes for degradation.

LDLs are notoriously known as the bad cholesterol. But where does their lousy reputation
come from? LDLs are considered bad because they carry cholesterol from the liver to the
tissues and in the process deposit cholesterol along arterial walls. This contributes to
atherosclerotic disease.

Clinical Correlation

Absence or deficiency of LDL receptors or Apo B-100 is known as familial

hypercholesterolemia. Because of lack of LDL uptake, patients have markedly elevated blood
cholesterol levels and develop accelerated atherosclerosis due to LDL deposits along the
endothelium; they can have myocardial infarction before age 20 years! Familial
hypercholesterolemia should be suspected in young patients with findings such as tendinous
xanthomas (Figure 8).

Figure 8
Credit: © 2012 Bell et al, publisher and licensee Dove Medical Press Ltd.

LDLs are derived from VLDLs and IDLs as they lose their
triglycerides. They carry cholesterol for uptake in the
peripheral tissues.
High-Density Lipoproteins

We’ve already mentioned HDLs a number of times in their role as helper cholesterol,
delivering apolipoproteins to other lipoproteins. HDL is known as the good cholesterol
because it mediates transport of cholesterol from the peripheral tissues to the liver. This is
good because it removes the cholesterol from the peripheral circulation, where it is at risk of
forming atherosclerotic plaques. The liver then can use the absorbed cholesterol to make bile
salts, included in the bile that helps us absorb fats from the intestine.

Nascent (early) HDLs are made in the liver and small intestine. They have a discoid shape,
without much cholesterol (Figure 9). Among other apoproteins, HDL contains Apo A-1,
which is found only in HDL. Apo A-1 is important because it activates a protein called
lecithin-cholesterol acyltransferase (LCAT) in the blood vessel wall. LCAT esterifies
cholesterol to form cholesteryl esters, which are added to the nascent HDL. This makes the
HDL more spherical, and it’s then considered a mature HDL.

Figure 9

Credit: ©ScholarRx
Mature HDL transports cholesteryl esters from the peripheral tissues to the liver, where they
are converted to bile, and to the adrenal cortex and gonads, where they are used to make
steroid hormones. It also transfers cholesterol to other lipoproteins (VLDL, IDL, LDL) in
exchange for triglycerides, using cholesterylester transfer protein (CETP).

It activates LCAT, which esterifies cholesterol and creates

mature HDL.
Table 2 summarizes the functions and roles of the different apoproteins and helps you
remember how they interact with the above lipoproteins.

Protein Function Found in Mnemonic

Required for HDL formation; Acquires cholesterol from
Apo A-1 HDL
activates LCAT periphery
Apo B- Mediates synthesis and secretion
Chylomicrons Builds (chylomicron)
48 of chylomicrons
Mediates VLDL synthesis and Builds (VLDL) and binds
Apo B-
secretion; binds LDL receptor IDL, LDL, VLDL LDL receptor (larger Apo-B
100
and mediates LDL endocytosis has more work)
Chylomicrons,
Apo C-2 Binds and activates LPL Co-factor (activates LPL)
VLDL, HDL
Chylomicrons,
Apo E Mediates endocytosis of remnants Endocytosis of remnants
HDL, IDL, VLDL
Table 2

Case Connection

Back to Introduction arrow_upward

Thinking back to your patient, how do you explain IDL and VLDL?

“I don’t think it will give us more useful information than we already have,” you say. “VLDL
is mainly composed of triglycerides. As some of these triglycerides are metabolized, VLDL
becomes IDL. IDL continues to more lose triglycerides, and at some point, it will contain
mostly cholesterol. Now it’s known as LDL. So if we look at your lipid profile from last
month, we know what your triglycerides and LDL are, and they are excellent. I’d say keep up
the good work. Exercise regularly, keep eating a diet low in cholesterol and saturated fat, and
maintain your healthy weight. I wouldn’t recommend that you get the extra bloodwork.”

Summary

 Lipoproteins are special molecules that transport cholesterol and triglycerides in the
blood. Each type of lipoprotein has a different structure and composition and is
associated with different sets of apoproteins.
 Chylomicrons transport dietary triglycerides and cholesterol from the intestines to the
peripheral tissues.
 Apo B-48 is a structural apoprotein that is unique to chylomicrons.
  VLDLs transport triglycerides synthesized in the liver from the liver to peripheral
tissues. They contain Apo B-100.
 Apo C-2 and Apo E are both transferred from HDL to chylomicrons and VLDLs.
 Apo C-2 helps activate lipoprotein lipase (LPL), and Apo E mediates endocytosis of
chylomicron and VLDL remnants into the liver.
 LDL is considered bad cholesterol because it transports cholesterol to peripheral
tissues, where it can contribute to atherosclerosis.
 Apo B-100 on LDL binds tissue LDL receptors to facilitate receptor-mediated uptake
of cholesterol.
 HDL is sometimes called good cholesterol since it transports cholesterol from
peripheral tissues to the liver.
 Apo A-1 on HDL activates LCAT, which esterifies cholesterol and adds it to the
HDL.

What Are Primary Lipid Disorders?

Lipid disorders or dyslipidemias are a class of disorders that involve abnormalities in lipids
(fats) or lipoproteins in the blood. They play an important role in the development of many
disease processes, most notably in cardiovascular disease. Lipid disorders are very common,
with statins (lipid-lowering drugs) being the second most commonly prescribed drug in the
United States.

Lipid disorders are classified into primary and secondary. Primary lipid disorders, the focus
of this discussion, are inherited disorders that directly cause defects in lipid metabolism. We
will discuss a few of these where specific genetic causes have been identified. Secondary
dyslipidemias are much more common; these elevations of cholesterol and triglycerides are
related to disorders like diabetes mellitus, chronic kidney disease, liver disease,
hypothyroidism, obesity, smoking, medications (ie, hydrochlorothiazide), and excessive
alcohol consumption. All patients with elevated blood lipids should have these secondary
conditions ruled out first. Let’s start by looking at the less common but very interesting
primary genetic lipid disorders.

Secondary dyslipidemias are more common than primary

dyslipidemias.
How Do Primary Lipid Disorders Arise?

You would think that genetic diseases that lead to hypercholesterolemia or

hypertriglyceridemia would mostly be due to abnormally increased synthesis of these
substances. Well, it turns out that this is not true. Instead, they are largely abnormalities of
lipoprotein structure or of the lipoprotein receptors, rather than of cholesterol or triglycerides
themselves.

Remember, lipoproteins are the molecules by which cholesterol and triglycerides are
transported in the bloodstream between gut, liver, and tissues. They are needed because both
triglycerides and cholesterol are nonpolar and hydrophobic, so they do not dissolve in the
blood. Lipoproteins are made up of varying amounts of cholesterol, triglycerides, and specific
proteins called apoproteins (apolipoproteins). The specific mix of these is critical to the
function of the lipoprotein:
  Chylomicrons deliver triglycerides and cholesterol from the intestines into the
bloodstream and then deliver triglycerides to peripheral tissues.

 VLDLs (very-low-density lipoproteins) deliver triglycerides from the liver to the

tissues.

 IDLs (intermediate-density lipoproteins) deliver triglycerides to the tissues and

cholesterol to the liver.

 LDLs (low-density lipoproteins) deliver cholesterol from the liver to the tissues. This
is known by some as “bad cholesterol,” associated with atherosclerotic disease.

 HDLs (high-density lipoproteins) deliver cholesterol from the tissues to the liver. It
also serves as “helper” cholesterol (remember the H), donating important
apolipoproteins to different lipoproteins so they can be recognized and taken up by
appropriate tissues. This is “good cholesterol,” with blood levels inversely related to
cardiac disease.

As we will next see, the primary lipid disorders lead to abnormal structure and function of
one or more of these lipoproteins, and this gives rise to the hyperlipidemia characteristic of
the disorders.

The Fredrickson Classification of Primary Lipid Disorders

One system of classification of the primary (genetic) disorders uses the Fredrickson
phenotype (Table 1). Each numbered type represents a pattern of lipoprotein elevation, and
we will discuss five diseases that fall in these patterns. Of these patterns, types IIa, IIb, and
IV are the most common, accounting for >95% of patients with these primary lipid disorders.

Disease Name and Elevated Lipoprotein Cholesterol Triglyceride

Fredrickson Phenotype Lipoproteins Abnormality Levels Levels
Familial
↓ LPL or Apo C-
hyperchylomicronemia Chylomicrons Normal to ↑ ↑↑↑↑
2
(type I)
Familial
hypercholesterolemia LDL ↓ LDL receptors ↑↑ Normal
(type IIa)
Familial combined
LDL and VLDL ↑ Apo B-100 ↑↑ ↑↑
hyperlipidemia (type IIb)
Familial
IDL and
dysbetalipoproteinemia APOE mutation ↑↑ ↑↑↑
chylomicrons
(type III)
Familial hypertriglyceridemia Abnormality
VLDL Normal to ↑ ↑↑
(type IV) unknown
Table 1
As you can see, this system sorts these disorders based on which type of lipoproteins are
elevated (Table 1, column 2). For each of these lipoprotein elevations, there is a characteristic
apolipoprotein or receptor abnormality (shown in column 2) that gives rise to the problem.

What Are the Most Common Primary Lipid Disorders?

Now that we have an idea of what primary lipid metabolism disorders look like, we’ll dive
deeper into the specific disorders. We’ll cover them starting with the three most common
disorders (although none is seen in more than 1%-2% of the population).

Familial Hypercholesterolemia (Fredrickson Type IIa)

Familial hypercholesterolemia is present in 0.2%-0.5% of the population and is inherited in

an autosomal dominant fashion. The lipid profile in familial hypercholesterolemia typically
shows very high LDL cholesterol levels, even at birth. Triglyceride levels are near normal.
It’s caused by specific mutations that lead to an absence or lack of LDL receptors. The
resultant elevated LDL causes severe atherosclerosis. Atherosclerotic heart disease in young
adulthood is common, especially in men.

In familial hypercholesterolemia, patients have an absence

or dearth of LDL receptors, which leads to elevated LDL
cholesterol in the blood.
Familial Combined Hyperlipidemia (Fredrickson Type IIb)

Familial combined hyperlipidemia is another autosomal dominant lipid metabolism disorder,

present in about 0.5% of the population. Patients have moderately high levels of both
cholesterol and triglycerides. They also demonstrate insulin resistance and obesity, looking a
bit like patients with metabolic syndrome or type 2 diabetes (but without the hyperglycemia).

Why do we call this disorder “combined” hyperlipidemia? Because basically all the bad
lipids are elevated: labs will likely show increased levels of LDL, VLDL, and triglycerides. It
accounts for as many as 20% of cases of premature coronary artery disease. Most commonly,
the liver overproduces apolipoprotein B-100 (often called apo B-100), the lipoprotein
associated with small VLDL particles as well as small, dense LDL particles. We think these
small LDLs are especially atherogenic.

There are probably multiple genetic defects that contribute to familial combined
hyperlipidemia, so think of this disorder more along the lines of complex polygenic illnesses
like diabetes rather than single-gene deficiencies like familial hypercholesterolemia.

LDL and VLDL cholesterol and triglycerides.

Familial Hypertriglyceridemia (Fredrickson Type IV)

Familial hypertriglyceridemia is present in 1% of the general population. Labs will show

elevated VLDL and triglycerides; recall that the two are related so they’ll increase together.
The total cholesterol is relatively normal, and the HDL is often low in these patients.
These patients can look a lot like those with familial combined hyperlipidemia because they
can also demonstrate insulin resistance and obesity. But because the LDL levels aren’t
affected, there hasn’t been a strong association between familial hypertriglyceridemia and
atherosclerotic heart disease. However, these patients are at increased risk for acute
pancreatitis because of their high triglyceride levels (usually occurring when the triglycerides
are >1000 mg/dL), likely due to pancreatic capillary obstruction.

Familial hypertriglyceridemia likely comes from multiple genetic defects, which have not yet
been identified.

High levels of which type of lipid can lead to acute

pancreatitis?
Less Common Primary Lipid Disorders

The following autosomal recessive disorders are rare diseases but have some unique
presentations.

Familial hyperchylomicronemia (Fredrickson type I) is an autosomal recessive disorder that

results from a lipoprotein lipase deficiency (most common) or sometimes an apolipoprotein
C-2 deficiency. Patients have very high levels of triglycerides, with near-normal cholesterol
levels. The supernatant of spun blood is creamy due to the triglycerides. Patients are
primarily at risk for pancreatitis, presumably because high levels of chylomicrons in the
blood can obstruct capillaries in the pancreas and cause ischemia. The risk for ischemic heart
disease is not increased.

Familial dysbetalipoproteinemia (Fredrickson type III) is another rare autosomal recessive

disorder, caused by a mutation in the gene APOE. This leads to poor lipoprotein clearance by
the liver, causing chylomicrons and IDL to remain in circulation. Patients with this disorder
have moderate elevations in total cholesterol and triglycerides, and they are at increased risk
for heart disease.

These patients may have unique types of xanthomas, notably palmar xanthomas (yellow or
pale patches in the palmar creases) and tuberoeruptive xanthomas (larger growths usually
seen on the knees, elbows, and buttocks). Palmar xanthomas are only seen in this lipid
disorder.

What type of xanthoma is pathognomonic for familial

dysbetalipoproteinemia?
1 LP, 2 LD, 3 with E, 4 gets more:
Type 1 (familial hyperchylomicronemia) is a lipoprotein
lipase (LPL) deficiency.
Type 2 (familial hypercholesterolemia) is an LDL receptor
deficiency.
Type 3 (familial dysbetalipoproteinemia) is due to an
APOE variant.
Type 4 (familial hypertriglyceridemia) gets more VLDL
production (also VLDL has 4 letters).

How Do Lipid Disorders Present Clinically?

Of the above syndromes, those with high LDL levels (ie, types IIa, IIb, and III) can all
present with early or severe atherosclerotic disease, eg, ischemic heart disease, stroke, or
peripheral artery disease (leg claudication). On the other hand, types I and IV, presenting
with elevated triglycerides and near-normal serum cholesterol levels, do not lead to severe
heart disease. Instead, patients are at risk for pancreatitis, especially if their triglycerides are
above 1000 mg/dL.

Another clinical finding that may be seen in these diseases is a corneal arcus; lipid deposits
in the cornea appear as a white ring around the edge of the iris (Figure 1).

Figure 1

Credit: Courtesy of Dr. Richard Usatine.

Xanthomas are a build-up of lipids in the skin that lead to yellow-white papules and plaques,
histologically composed of lipid-laden macrophages:

 Xanthelasma: eyelid plaques (Figure 2A)

 Extensor surfaces (Figure 2B)

 Achilles tendon (Figure 2C and D)

 Palmar: seen only in type III

Figure 2

Credit: © 2012 Bell et al, publisher and licensee Dove Medical Press Ltd.

Eruptive xanthomas (Figure 3)—associated with hypertriglyceridemia and familial

chylomicronemia—are reddish bumps that appear suddenly over elbows, forearms, trunk,
legs, or buttocks.
Figure 3

Credit: Courtesy of Dr. Richard Usatine

Lipemia retinalis occurs in patients with triglyceride levels over 2000 mg/dL. On
fundoscopic exam, the retinal arteries appear yellow or white rather than red because of an
excessive accumulation of lipids.

How Do We Treat Primary Dyslipidemias?

Because of the deleterious effects that elevated lipids can have, it is important that they be
treated. Both lifestyle modifications and pharmacologic therapy are used for primary
dyslipidemias.

Lifestyle Modification

For patients with primary dyslipidemias, lifestyle modification is a cornerstone of treatment.

Weight loss for obese patients, aerobic exercise, smoking cessation, avoidance of
concentrated sugars and alcohol, and strict glucose control for patients with diabetes remain
first-line steps. Patients should be encouraged to adopt a dietary approach of portion control
and to limit carbohydrates. They should consume fish that have high levels of omega-3 fatty
acids: a diet rich in omega-3 fatty acids has been shown to reduce the rate of fatty acid
incorporation into triglycerides, thus decreasing triglyceride levels.
Clinical Correlation

Fish that are rich in omega-3 oils include canned anchovies, Atlantic salmon, Atlantic
herring, bluefin tuna, and Atlantic mackerel.

Pharmacologic Therapy

When goals are not met with lifestyle modifications, pharmacological therapy is indicated to
lower lipid levels. The goal is reducing the risk of cardiovascular disease and preventing
pancreatitis. Most patients with hypercholesterolemia benefit from a high-intensity statin.
These drugs inhibit the enzyme HMG-CoA reductase, which is the key regulatory step in
cholesterol biosynthesis. Those with marked elevations in blood triglycerides generally start
with a fibrate.

All patients with signs of ischemic heart disease (eg, chest pain) will need appropriate
treatment, including aspirin, β-blockers, and nitrates. Blood pressure should be maintained
below 130/80 mm Hg for all patients with cardiovascular disease, per recent guidelines, using
one or more agents.