HYPERLIPIDAEMIAS

Dr.D.Rispa
Assistant Professor
Pharmacy Practice Department
Definition
 Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia
involves abnormally elevated levels of any or all lipids and/or
lipoproteins in the blood.
 It is the most common form of dyslipidemia (which also
includes any decreased lipid levels).
Lipoproteins
 A lipoprotein is a biochemical assembly that contains both
proteins and lipids, bound to the proteins, which allow fats to
move through the water inside and outside cells.
 The proteins serve to emulsify the lipid (otherwise called fat)
molecules. Many enzymes, transporters, structural proteins,
antigens, adhesins, and toxins are lipoproteins.
 Examples include the high-density (HDL) and low-density
(LDL) lipoproteins, which enable fats to be carried in the
blood stream.
 Types of Lipoproteins
%
Diam % % triglycer
Density
Class eter %protein Cholest Phospholoi ol &
(g/ml)
(nm) erol pd choleste
rol ester

>1.063 HDL 5-15 33 30 29 4

1.019-
LDL 18-28 25 50 21 8
1.063
1.006-
IDL 25-50 18 29 22 31
1.019
0.95-
VLDL 30-80 10 22 18 50
1.006
Chylomic 100-
<0.95 <2 8 7 84
rons 1000
 Chylomicrons carry triglycerides (fat) from the intestines to
the liver, to skeletal muscle, and to adipose tissue.
 Very-low-density lipoproteins (VLDL) carry (newly
synthesised) triglycerides from the liver to adipose tissue.
 Intermediate-density lipoproteins (IDL) are intermediate
between VLDL and LDL. They are not usually detectable in
the blood.
 Low-density lipoproteins (LDL) carry cholesterol from the
liver to cells of the body. LDLs are sometimes referred to as
the "bad cholesterol" lipoprotein.
 High-density lipoproteins (HDL) collect cholesterol from the
body's tissues, and take it back to the liver. HDLs are
sometimes referred to as the "good cholesterol" lipoprotein.
Classifcation
Relative prevalence of familial
Hyperlipoproteinemias
Hyperlipoproteinemia type I
 Type I hyperlipoproteinemia exists in several forms:
 Lipoprotein lipase deficiency (Type Ia), due to a deficiency of
lipoprotein lipase (LPL) or altered apolipoprotein C2,
resulting in elevated chylomicrons, the particles that transfer
fatty acids from the digestive tract to the liver.
 Familial apoprotein CII deficiency (Type Ib), a condition
caused by a lack of lipoprotein lipase activator.
 Chylomicronemia due to circulating inhibitor of lipoprotein
lipase (Type Ic)

 Type I hyperlipoproteinemia usually presents in childhood
with eruptive xanthomata and abdominal colic. Complications
include retinal vein occlusion, acute pancreatitis, steatosis
and organomegaly, and lipaemia retinalis.
Hyperlipoproteinemia type II
 Hyperlipoproteinemia type II, by far the most common form, is further classified into
type IIa and type IIb, depending mainly on whether there is elevation in the
triglyceride level in addition to LDL cholesterol.
 Type II (a)
 This may be sporadic (due to dietary factors), polygenic, or truly familial as a result
of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the
population) or the ApoB gene (0.2%). The familial form is characterized by tendon
xanthoma, xanthelasma and premature cardiovascular disease. The incidence of
this disease is about 1 in 500 for heterozygotes, and 1 in 1,000,000 for
homozygotes.
 Type II (b)
 The high VLDL levels are due to overproduction of substrates, including
triglycerides, acetyl CoA, and an increase in B-100 synthesis. They may also be
caused by the decreased clearance of LDL. Prevalence in the population is 10%.
 Familial combined hyperlipoproteinemia (FCH)
 Lysosomal acid lipase deficiency, often called (Cholesteryl ester storage disease)
 Secondary combined hyperlipoproteinemia (usually in the context of metabolic
syndrome, for which it is a diagnostic criterion)
Hyperlipoproteinemia type III
 This form is due to high chylomicrons and IDL (intermediate
density lipoprotein). Also known as broad beta disease or
dysbetalipoproteinemia, the most common cause for this form is
the presence of ApoE E2/E2 genotype.
 It is due to cholesterol-rich VLDL (β-VLDL). Its prevalence has
been estimated to be approximately 1 in 10,000.
Hyperlipoproteinemia type IV
 Familial hypertriglyceridemia is an autosomal recessive condition
occurring in approximately 1% of the population.
Hyperlipoproteinemia type V
 Hyperlipoproteinemia type V is very similar to type I, but with high
VLDL in addition to chylomicrons.
 It is also associated with glucose intolerance and hyperuricemia.
Acquired (secondary)
 Acquired hyperlipidemias (also called secondary dyslipoproteinemias)
often mimic primary forms of hyperlipidemia and can have similar
consequences.
 They may result in increased risk of premature atherosclerosis or,
when associated with marked hypertriglyceridemia, may lead to
pancreatitis and other complications of the chylomicronemia
syndrome.
 The most common causes of acquired hyperlipidemia are:
 diabetes mellitus
 Use of drugs such as diuretics, beta blockers, and estrogens
 Other conditions leading to acquired hyperlipidemia include:
 Hypothyroidism
 renal failure
 nephrotic syndrome
 alcohol usage
 Some rare endocrine disorders and metabolic disorders.
Epidemiology
 Lipid and lipoprotein concentrations vary among different
populations with countries consuming a western type of diet
having higher TC and LDL levels than those where regular
consumption of saturated fat is low.
 Despite a 50% reduction in the death rate from CVD over the
past 25 years, It remains the leading cause of premature
death and morbidity in the UK.
 The higher levels of TC in an individual the greater the
chance of developing CVD.
 TC levels tend to increase with age such that 80% of British
men aged 45-64 years have a level that exceeds 5mmol/lit
and the population average is 5.6 mmol/lit, in contrast in rural
China and Japan the average is 4 mmol/lit.
 Etiology
 The etiology can be classified into primary and secondary causes.

 Primary causes are due to single or multiple gene mutations resulting

in a disturbance of LDL and triglyceride production or clearance.
 They vary in location of genetic defect, inheritance pattern,
prevalence, clinical features, and treatment.
 At least 18 separate entities have been described. The suspicion for a
primary lipid disorder should be especially high in patients with
premature atherosclerotic disease, a family history of early
atherosclerotic disease, a significantly elevated serum cholesterol
level (>240 mg/dL), and physical signs of hyperlipidemia.
 Primary dyslipidemias are most commonly seen in children and young
adults and cause only a small percentage of cases in adults.
 Most adult cases of dyslipidemia are secondary in nature.
 In Western civilizations, sedentary lifestyle and excessive
consumption of saturated fats, trans-fatty acids, and cholesterol are
the most important secondary causes.
 Certain medical conditions are commonly associated with
dyslipidemia, including chronic renal insufficiency, renal failure,
diabetes mellitus, hypothyroidism, cholestatic liver disease, and
alcohol dependency.
 Certain drugs, including high-dose thiazide diuretics, oral
estrogens, glucocorticoids, anabolic steroids, and atypical
antipsychotics such as olanzapine and clozapine have also been
implicated in causing mild-to-moderate degrees of dyslipidemia.
 Use of atypical antipsychotics, such as olanzapine and clozapine,
and of beta-blockers without intrinsic sympathomimetic or alpha-
blocking activities are associated with reduced HDL-cholesterol
levels.
Pathophysiology
 Hypercholesterolemia develops as a consequence of
abnormal lipoprotein metabolism, mainly reduction of LDL
receptor expression or activity, and consequently diminishing
hepatic LDL clearance from the plasma.
 It is a major predisposing risk factor for the development of
atherosclerosis.
 This mechanism is classically seen in familial
hypercholesterolemia and when excess saturated fat or
cholesterol is ingested.
 In addition, excessive production of VLDL by the liver, as
seen in familial combined hyperlipidemia and insulin
resistance states such as abdominal obesity and type 2
diabetes, can also induce hypercholesterolemia or mixed
dyslipidemia.
Pathways
 A current theory for the initiating event in atherogenesis is that
apoprotein B-100-containing lipoproteins are retained in the
subendothelial space, by means of a charge-mediated
interaction with extracellular matrix and proteoglycans.
 This allows reactive oxygen species to modify the surface
phospholipids and unesterified cholesterol of the small LDL
particles.
 Circulating LDL can also be taken up into macrophages through
unregulated scavenger receptors.
 As a result of LDL oxidation, isoprostanes are formed.
Isoprostanes are chemically stable, free radical-catalyzed
products of arachidonic acid, and are structural isomers of
conventional prostaglandins.
 Isoprostane levels are increased in atherosclerotic lesions, but
they may also be found as F2 isoprostanes in the urine of
asymptomatic patients with hypercholesterolemia.
 A strong association exists between elevated plasma concentrations of
oxidized LDL and CHD.
 The mechanisms through which oxidized LDL promotes atherosclerosis
are multiple and include damage to the endothelium, induction of growth
factors, and recruitment of macrophages and monocytes.

 Vasoconstriction in the setting of high levels of oxidized LDL seem to be

related to a reduced release of the vasodilator nitric oxide from the
damaged endothelial wall as well as increased platelet aggregation and
thromboxane release.

 Smooth muscle proliferation has been linked to the release of cytokines

from activated platelets.

 The state of hypercholesterolemia leads invariably to an excess

accumulation of oxidized LDL within the macrophages, thereby
transforming them into "foam" cells. The rupture of these cells can lead
to further damage of the vessel wall due to the release of oxygen free
radicals, oxidized LDL, and intracellular enzymes.
 Symptoms
 Hyperlipidemia usually does not cause symptoms.
 Very high levels of lipids or triglycerides can cause:
Fat deposits in the skin or tendons ( Xanthelasma and Xanthoma )
 Pain, enlargement, or swelling of organs such as the liver, spleen, or
pancreas ( Pancreatitis )
Obstruction of blood vessels in heart and brain

 If not treated, high lipids can cause:

Heart Attack
Stroke
Atherosclerosis (hardening of the arteries)
 Diagnosis
 This condition is diagnosed with blood tests.
These tests measure the levels of lipids in the blood.
The National Cholesterol Education Program advises that you have your
lipids checked at least once every five years, starting at age 20.
Also, the American Academy of Pediatrics recommends lipid screening
for children at risk (eg, a family history of hyperlipidemia).
 Testing may consist of a fasting blood test for:
Total cholesterol
LDL (bad cholesterol)
HDL (good cholesterol)
Triglycerides
 Your doctor may recommend more frequent or earlier testing if you
have:
Family history of hyperlipidemia.
Risk factor or disease that may cause hyperlipidemia.
Complication that may result from hyperlipidemia.
Treatment
Non Pharmacologic:
 Diet, lifestyle changes, and medication can help treat
hyperlipidemia.
 Diet Changes
Eat a diet low in total fat, saturated fat, and cholesterol.
Reduce or eliminate the amount of alcohol you drink.
Eat more high-fiber foods.
 Lifestyle Changes
If you are overweight, lose weight.
If you smoke, quit.
Exercise regularly.
Talk to you doctor before starting an exercise program.
You may already have hardening of the arteries or heart disease.
These conditions increase your risk of having a heart attack while
exercising.
Pharmacological:
 Classfication:
HMG CoA Reductase Inhibitors (statins):
 Lovastatin, Simvastatin, Atorvastatin
Bile acid sequesterants:
 Cholestyramine, Colestipol
Activated lipo protein lipase (fibric acid derivatives):
 Gemfibrozil, Clofibrate, Fenofibrate
 Inhibit lipolysis and TG synthesis:
 Nicotinic acid
 Others:
 Ezetimibe, Gugulipid
Statins(Atorvastatin, Lovastatin)
Dose-Atorvastatin
Inital: 10 or 20 mg once daily, may increase slowly if needed. Max: 80 mg/day.
Lovastatin
Initial: 10-20 mg/day at bedtime, may increase 4-wkly if needed. Max: 80
mg/day (immediate-release)
Adverse Effects:
 Gastrointestinal: Diarrhea (up to 14.1% )
 Musculoskeletal: Arthralgia (up to 11.7% ), Myalgia (up to 8.4% )
 Renal: Urinary tract infectious disease (up to 8% )
 Respiratory: Nasopharyngitis (8.3% )
 Other: Pain, In extremity (up to 9.3% )
 Dermatologic: Dermatomyositis
 Hepatic: Increased liver enzymes (0.2% to 2.3% ), Liver failure
 Immunologic: Autoimmune disease, Systemic lupus erythematosus
 Musculoskeletal: Disorder of muscle, Rhabdomyolysis, Rupture of
tendon.
Gemfibrozil
 Dose: 1.2 g/day in 2 divided doses. Maintenance: 0.9-1.5
g/day
 Gastrointestinal: Abdominal pain (9.8% ), Acute
appendicitis (1.2% ), Indigestion (19.6% .)
 Hepatic: Increased liver function
 Musculoskeletal: Rhabdomyolysis
Clofibrate
Dose: 2 g/day in divided doses.

Cardiovascular Effects
Cardiac dysrhythmia
Cardiomyopathy
Cardiovascular finding
Thrombophlebitis

Dermatologic Effects
Dermatological finding
Stevens-Johnson syndrome

Endocrine/Metabolic Effects
Endocrine finding
Increased body temperature
Metabolic finding
Weight gain
Bile acid sequesterants(Cholestyramine,
Colestipol)
 Dose: 5 g 1-2 times/day, up to 30 g/day if needed

 Gastrointestinal: Abdominal discomfort, Constipation,

Flatulence, Nausea and vomiting
Niacin
 Dermatologic: Flushing (88% )
 Gastrointestinal: Nausea (4% to 9% ), Vomiting (2% to 9% )
 Hepatic: Hepatic necrosis, Hepatotoxicity
 Musculoskeletal: Rhabdomyolysis
Gugulipid
 diarrhea
 nausea
 hiccup
 abdominal discomfort
 headache
 restlessness
 hypersensitivity rash
THANK
YOU