HYPERLIPIDEMIA

INTRODUCTION
 It is a medical condition characterized by an elevation of any or all lipid
profile and/or lipoproteins in the blood. This medical condition or problem
divided into two subtypes which are: primary hyperlipidemia and secondary
hyperlipidemia.

 Primary hyperlipidemia which is usually taken place as a result of genetic

problems i.e., mutation within receptor protein, while secondary
hyperlipidemia will arises as a result of other underlining diseases like
diabetes.

 Alteration and/ or abnormality in the metabolism of lipid and lipoproteins is

a very common condition that taken place within general population, and it
consider as one of the main risk factor in the incidence of cardiovascular
disease due to their influence on atherosclerosis.

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 Cholesterol, triglycerides, and phospholipids are the major lipids in the body.
They are transported as complexes of lipid and proteins known as lipoproteins.

 The three major classes of lipoproteins in serum are Low-Density Lipoproteins

(LDLs), High-Density Lipoproteins (HDLs), and Very-Low-Density
Lipoproteins (VLDLs).

 VLDL is carried in the circulation as triglyceride and can be estimated by

dividing the triglyceride concentration by five. Intermediate-density lipoprotein
(IDL) resides between VLDL and LDL

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  Abnormalities of plasma lipoproteins can result in a predisposition to
coronary, cerebrovascular, and peripheral vascular arterial disease and
constitutes one of the major risk factors for coronary heart disease (CHD).

 As the major plasma lipids, cholesterol and triglycerides are essential

substrates for cell membrane formation and hormone synthesis and they
provide a source of free fatty acids.

 Dyslipidemia can be defined as elevated total cholesterol, LDL-C, or

triglycerides level, low HDL-C concentration, or some combination of
these abnormalities.

 Lipids, which are water immiscible, are not present in free form in the
plasma but rather circulate as lipoproteins.

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 TOTAL Cholesterol

 According to guidelines of National Cholesterol Education Program

(NCEP), TC concentrations below 200 mg/dL have been regarded as
desirable, whereas, concentrations greater than 240 mg/dL are referred to
as hyperlipidemic.

 However, epidemiological evidence suggests that the risk of cardiac events

decreases as TC levels fall approximately to 150 mg/dL. Moreover, TC
should be less than 180 mg/dL for children.

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 TRIGLYCERIDES

 Triglycerides are another type of fat that is carried in the blood by VLDL.
Moreover, it has been shown that excess calories, alcohol or sugar in the
body get converted into triglycerides and stored in fat cells throughout the
body.

 The triglyceride concentration less than 150 mg/dL is regarded as normal,

whereas, concentrations of 200-499 mg/dL are considered as high.

 Moreover, concentrations of 500 mg/dL or higher are considered dangerous

for the development and progression of various CVDs.

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 LDL Cholesterol

 LDL is commonly known as the bad cholesterol, which is produced by the

liver and carry cholesterol and other lipids from the liver to different areas of
the body like muscles, tissues, organs and heart.

 The high levels of LDL indicate much more cholesterol in the blood stream
than necessary and hence, increase the risk of heart disease.

 According to NCEP guidelines, LDL cholesterol concentrations below

100mg/dL are considered optimal, whereas concentrations in the range of
160-189 mg/dL are considered to the higher side.

 However, increasing evidence supports that normal human LDL cholesterol

concentration can be as low as 50 to 70 mg/dL.

 Moreover, it has been comprehensively seen that the risk of CVDs decreases
as LDL cholesterol concentration decreases.
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 HDL Cholesterol
 HDL is commonly referred to as the good cholesterol, which is produced by the
liver to carry cholesterol and other lipids from tissues back to the liver for
degradation.

 High levels of HDL cholesterol have been considered as a good indicator of a

healthy heart.

 The concentrations of 60 mg/dL or higher have been considered as optimal,

whereas, HDL concentrations below 40 mg/dL are considered as major risk
factor for CVDs.

 However, HDL is often interpreted in the context of TC and LDL

concentrations, and hence may be regarded as less significant when LDL is low.

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 VLDL Cholesterol

 VLDL is similar to LDL cholesterol in the sense that it contains mostly fat
and not much protein.

 VLDL cholesterol is the lipoproteins that carry cholesterol from the liver to
organs and tissues in the body.

 They are formed by a combination of cholesterol and triglycerides.

Moreover, VLDLs are heavier than LDL, and are also associated with
atherosclerosis and heart disease.

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 CHYLOMICRONS

 Chylomicrons transport fatty acids and cholesterol derived from the diet or
synthesized in the intestines from the gut to the liver (exogenous system)

 Chylomicrons are large triglyceride-rich particles that contain apolipoproteins

B-48, B-100, and E. They are formed from dietary fat solubilized by bile salts in
intestinal mucosal cells.

 Chylomicrons normally are not present in the plasma after a fast of 12 to 14

hours.

 Chylomicrons also function to deliver dietary triglyceride to skeletal muscle and

adipose tissue.

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 APOLIPOPROTEINS
 Each lipoprotein particle contains proteins on its outer surface called
apolipoproteins.

These proteins have three functions:

 (a) provide structure to the lipoprotein
 (b) activate enzyme systems
 (c) bind with cell receptors.

 Abnormal metabolism of apolipoproteins, even in the face of seemingly

normal blood cholesterol levels, can result in faulty enzyme activity or
cholesterol transport and an increased risk of atherosclerosis.

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 CLASSIFICATION OF LIPID LEVELS (AGE < 20 years)

DESIRABLE BORDERLINE UNDESIRABLE

(mg/dL) (mg/dL) (mg/dL)

Total cholesterol < 170 170-199 >= 200

LDL cholesterol < 110 110-129 >= 130

HDL cholesterol > 45 25-45 < 35

Triglycerides < 125 NA >= 125

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 DIETARY SOURCES OF CHOLESTEROL
TYPE OF FAT MAIN SOURCE EFFECT ON
CHOLESTEROL LEVELS
Monounsaturated Olives, olive oil, canola oil, peanut Lowers LDL, Raises
oil, cashews, almonds, peanuts and HDL
most other nuts

Polyunsaturated Corn, soybean, safflower and Lowers LDL, Raises

cottonseed oil; fish HDL
Saturated Whole milk, butter, cheese, and Raises both LDL and
ice cream; red meat; chocolate; HDL
coconuts, coconut milk, coconut
oil , egg yolks, chicken skin
Trans Most margarines; vegetable Raises LDL
shortening; partially hydrogenated
vegetable oil; deep-fried chips;
many fast foods; most commercial
baked goods
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 COMPONENT* RECOMMENDED INTAKE
Total fat 25%–35% of total calories
Saturated fat Less than 7% of total calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories

Carbohydrates** 50%–60% of total calories

Cholesterol <200 mg/day
Dietary fiber 20–30 g/day
Plant sterols 2 g /day
Protein Approximately 15% of total calories
Total calories To achieve and maintain desirable body weight

*Calories from alcohol not included.

**Carbohydrates should derive from foods rich in complex carbohydrates, such as whole
grains,
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fruits and vegetables.
 CLINICAL PRESENTATIONs
GENERAL
 Most patients are asymptomatic for many years before disease is clinically
evident.

 Patients with the metabolic syndrome may have : abdominal obesity,

atherogenic dyslipidemia, increased B.P., insulin resistance with or without
glucose intolerance, prothrombotic state, or proinflammatory state.

SYMPTOMS
 None to severe chest pain, palpitations, sweating, anxiety, SOB, loss of
consciousness or difficulty with speech or movement, abdominal pain, sudden
death.
SIGNS
 None to severe abdominal pain, pancreatitis, eruptive xanthomas, peripheral
polyneuropathy, high blood pressure, body mass index >30 kg/m2 or waist size
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>40 inches in men (35 inches in women)
 CAUSES OF HYPERLIPIDEMIA
 Unhealthy Diets intake
 Hypothyroidism
 Renal failure
 Nephritic syndrome
 Obstructive liver disease
 Obesity
 Diabetes mellitus
 Pregnancy
 Acute hepatitis
 Systemic lupus
erythematousus
 Smoking
 Alcoholism
 AIDS (protease inhibitors)
 Family history
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 DIAGNOSIS OF HYPERLIPIDEMIA

 The patients have to fast for at least 12 hours before taking the blood
sample, the main reason for this is that chylomicron clearance required at
least 10 hours.

 The laboratory test for this case mainly focuses on the lipid profile i.e.,
measure lipid profile which include total plasma cholesterol, HDL, LDL,
VLDL and triglycerides levels.

 The mathematical way to calculate the VLDL is by dividing triglyceride

value by 5, while for LDL it can be calculated by subtracting HDL
cholesterol and VLDL cholesterol from total plasma cholesterol value.

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 PATHOPHYSIOLOGY

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 MAJOR RISK FACTORS
 Age

Men: ≥ 45 years
Women: ≥ 55 years or premature menopause without estrogen replacement
therapy

 Family history of premature CHD (definite myocardial infarction or sudden

death before age 55 years in father or other male first-degree relative, or before
age 65 years in mother or other female first-degree relative)

 Cigarette smoking

 Hypertension (≥ 140/90 mm Hg or taking antihypertensive medication)

 Low HDL cholesterol (< 40 mg/dL)

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 MANAGEMENT USED FOR HYPERLIPIDEMIA
The major treatment used for hyperlipidemia divided into three parts which are:

Dietary control:
 This point focus on reducing intake of foods that contain high amount of
saturated fat and cholesterol i.e., foods of animal origin.
 On the other hand this point will encourage intake of food or supplements that
include fish oil or olive oil which include a very low concentration of saturated
fat.
 Or focusing on intake of vegetarian foods which are free of cholesterol. These
types of food will significant play role in reducing elevated triglyceride levels.

Lifestyle changes:
 This will include focusing on daily exercises, since regular exercises will lead
to an improvement within lipid concentrations i.e., daily walking will reduce
triglyceride level by an average of 10 mg/dL and elevation within HDL level
by 5 mg/dL.
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 Medical treatment:

 These treatments will be indicated for those patients who suffer from

hyperlipidemia since early childhood i.e., familial hyperlipidemia.

These medications include:

 HMG CoA reductase inhibitors (first line treatment for elevated LDL levels)

 Fibrates (first line treatment for triglyceride elevation)

 Bile acid sequestrants (second line treatment for elevated LDL levels)

 Nicotinic acid (niacin) (second line treatment for all lipid disorders)

 Ezetimibe and colesevelam (second line treatments to reduce absorption of

cholesterol through GIT).

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 CLASSIFICATION OF DRUGS

1) HMG Co-A REDUCTASE INHIBITORS (statins):

Lovastatin, simvastatin, pravastatin, atorvastatin, Rosuvastatin

2) BILE ACID SEQUESTRANTS (Resins):

cholestyramine, colestipol

3) LIPOPROTEIN LIPASE ACTIVATORS (Fibric Acid Derivatves):

clofibrate, gemfibrozil, bezafibrate, fenofibrate

4) INHIBITOR OF TRIGLYCERIDE SYNTHESIS AND LYPOLYSIS :

nicotinic acid

5) OTHERS :
gugulipid, ezetimibe
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 HYPOLIPIDEMIC DRUGS

DRUGS DOSE
Lovastatin 10-40mg/day
Simvastatin 5-20mg/day (max 40mg)
Pravastatin 10-40mg/day
Atorvastatin 10-40mg/day (max 80mg)
Rosuvastatin 5-20mg/day (max 40mg/day)
Cholestyramine 4g TID oral
Gemfibrozil 600mg BD
Bezafibrate 200mg TID with meals
Fenofibrate 200mg OD with meals
Nicotinic acid Start with 100mg TID, gradually increase to 2 – 6g/day in
divided doses. After food.
Gugulipid 25mg TID
Ezetimibe 10mg OD
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 EFFECTS OF DRUG THERAPY ON LIPIDS AND LIPOPROTEINS
DRUG MOA EFFECTS EFFECTS ON
ON LIPIDS LIPOPROTEI
NS
Cholestyramine, LDL catabolism cholesterol LDL
colestipol Cholesterol absorption VLDL
Niacin LDL and VLDL synthesis Triglyceride VLDL
Cholesterol LDL
HDL
Gemfibrozil, VLDL clearance Triglyceride VLDL
fenofibrate, clofibrate VLDL synthesis Cholesterol LDL
HDL
Lovastatin, pravastatin, LDL catabolism, inhibit Cholesterol LDL
simvastatin, fluvastatin, LDL synthesis
atorvastatin,
rosuvastatin,
Blocks cholesterol absorption Cholesterol LDL
Ezetimibe across the intestinal border

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 CONCLUSION

 Hyperlipidemia is a critical condition of elevated lipid levels in the body that

ultimately lead to the development and progression of various CVDs.

 The link between hyperlipidemia and occurance of CVDs has already been
established. Various studies have reported the treatment of hyperlipidemic
patients with statins, fibrates and nicotinic acid derivatives.

 Moreover, the focus on dietary management should be done in order to

prevent and treat the patients presented with hyperlipidemia.

 However, ample studies have provided the evidence for the efficacy of
already reported treatments, but further studies are mandatory in order to
provide more information about the safety and efficacy of novel
antihyperlipidemic agents.

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SOME TIPS ON HOW TO MANAGE YOUR RISK OF HIGH CHOLESTEROL
 Read food labels and choose foods with low cholesterol and saturated trans fat. 

 Limit your intake of red meat and dairy products made with whole milk
to reduce your saturated and trans fat.  Choose skim milk, low fat or fat-free
dairy products. Limit fried food, and use healthy oils in cooking, such as
vegetable oil.

 Increase the amount of fiber you eat.  A diet high in fiber can help lower
cholesterol levels by as much as 10 percent.

 Check your family history of high cholesterol.  Are you more prone to high
cholesterol based on genetics. If so, take steps to minimize your risk through
diet and exercise.

 Lose extra weight. A weight loss of 10 percent can go a long way to lowering
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your risk of or reversing hyperlipidemia
  List the types of primary hyperlipidaemia

 Write the dosage regimen of any two statins with their adverse effects

 Write the complications of Hyperlipidaemias

 Enlist different etiological conditions of Hyperlipidaemias

 Suggest in brief the life style modification of hyperlipidaemia

 Explain the role of statins in hyperlipidaemia

 Define diabetic dyslipidaemia

 Mention any four ADRs of statins

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