Lipids

Cholesterol & Triglycerides

Functions of Lipids

Cholesterol is essential for cell wall formation.

Cholesterol is necessary for the formation

of steroid hormone and bile acids.

Triglycerides are an important energy store.

 Lipoproteins

• Lipoproteins transfer lipids from one

place to another.

• They are spherical particle made up of

hundreds of lipids and protein molecules

• Surface proteins gives structural stability

Apolipoproteins

• Provides structural stability to lipoproteins.

• Determine the metabolic fate of the particles

upon which they reside.

• Major Apolipoproteins are

Apo A-I, Apo A-II, Apo A-IV, Apo B-48, Apo B-100,
Apo C-I, Apo C-II, Apo C-III, Apo-E
Lipoproteins
Classification of Lipoproteins

• Chylomicrons

• Very low density lipoprotein (VLDL)

• Intermediate density lipoprotein (IDL)

• Low density lipoprotein (LDL)

• High density lipoprotein (HDL)

Chylomicrons

• They carry dietary triglycerides from

the intestine to Liver
VLDL

• They carry endogenous triglycerides

from the Liver to other parts of the
body.

• Unloads to form IDL

IDL

• They carry endogenous Cholesterol

esters from the VLDL to other parts of
the body.

• They get convert themselves to LDL

LDL

• They carry endogenous Cholesterol

esters from the IDL to other parts of
the body.

• Bad cholesterol
HDL

• They carry endogenous LDL-C from

peripheral parts of the body back to the
liver.

• Good cholesterol
Pathways for Lipoprotein transport

• Exogenous pathway

Transport of Lipids from outside (diet) to

inside(liver)

• Endogenous pathway

Transport of lipids from Liver to other tissues

and back to liver inside the body
Exogenous Pathway Endogenous Pathway

Dietary fat Bile acids +

Cholesterol

LDL
Extrahepatic
B-100
LDL Receptors tissues
Remnant receptors

Chylomicrons Remnants VLDL IDL HDL

B-48 B-48 B-100 B-100 A-1 A-2

Plasma
LCAT
Lipoprotein lipase Lipoprotein lipase

FFA FFA

Adipose tissues & muscles Adipose tissues & muscles

Apolipoproteins of Lipoproteins

Chylomicrons : B-48

VLDL - C : B-100

IDL - C : B-100

LDL - C : B-100

HDL - C : A-I, A-II

Hyperlipidaemia

• Increase in the lipids above normal

levels.

• It is also referred as following

1. Hypercholesterolemia
2. Hypertriglyceridaemia
3. Mixed hyperlipidemia
Dyslipidaemia

• Dysbalance of the lipids

• following changes may takes place

1. Low HDL-C
2. High Triglycerides
3. No change in TC
WHO Classification of Hyperlipidemia

Type Lipoprotein Cholesterol Triglyceride

elevated

I Chylomicrons Elevated or Elevated

normal

IIa LDL Elevated Normal

IIb LDL and VLDL Elevated Elevated

WHO Classification of Hyperlipidemia

Type Lipoprotein Level of Triglyceride

elevated cholesterol

III VLDL with high Elevated Elevated

cholesterol

IV VLDL Normal or Elevated

elevated

V Chylomicrons Elevated Elevated

and VLDL
Normal levels of Lipids

TC : < 200 mg/dL

LDL- C : < 100 mg/dL

HDL : > 40 mg/dL

TG : < 200 mg/dL

Plasma lipid fractions

• Total cholesterol is combination of all cholesterol

TC = LDL + IDL + HDL + VLDL

• Friedwald’s equation for LDL.

LDL = ( TC - HDL ) - ( TG/ 5 )

• VLDL = TG/0.5 ( if TG < 400 )

Lipids and IHD

• Hyperlipidemia is associated with an increased

risk of atherosclerosis and Ischaemic Heart Disease.

• High levels of LDL - C found to be associated with IHD

• Low levels of HDL - C found to be associated with IHD.

• High levels of TG is also associated with some of the

abnormalities in diabetic & CVD patients.
Management of Hyperlipidemia

• The main aim of treatment in patients with

hypercholesterolemia is to limit the process of
atherosclerosis and thus reduce risk of CAD/IHD.

• Lifestyle modification (Diet & Exercise)is very

critical before medical treatment with drugs.

• Management has got two arms Primary

prevention Secondary prevention.
NCEP Guidelines - ATP III

Universal guidelines laid by National Heart, Lung &

Blood Institute for the management of hyperlipidemia.

Identifies LDL-C as major risk for CAD and hence

LDL-C is known as “Bad Cholesterol”

Risk classification of LDL Cholesterol (mg/dL)

<100 Optimal
100–129 Near optimal/above optimal
130–159 Borderline high
160–189 High
190 Very high
NCEP Guidelines - ATP III

Low levels of HDL cholesterol is an independent

risk factor for CAD.

Risk classification of HDL Cholesterol (mg/dL)

<40 Low (Positive risk for CAD)

<60 High (Negative risk for CAD)

High levels of HDL cholesterol prevents CAD and hence

HDL - C is known as “Good Cholesterol”.
NCEP Guidelines - ATP III

High levels of Total cholesterol increases the risk of CAD.

Risk classification of Total Cholesterol (mg/dL)

<200 Desirable
200-239 Borderline high
>240 High
NCEP Guidelines - ATP III

Risk categories for modification of LDL-C

Risk Category LDL Goal (mg/dL)

CHD and CHD risk <100

equivalents

Multiple (2+) risk factors <130

Zero to one risk factor <160

Lipid lowering (Modifying) agents

• Bile acid binding resins

• Fibric acid derivatives

• HMG-Co-A reductase inhibitors (Statins)

• Nicotinic acid derivatives

• Antioxidants & other agents

Bile acid binding resins

• They are basic ion exchange resins.

• They decreases absorption of cholesterol by

forming insoluble complex with dietary lipids.

• They decrease intrahepatic cholesterol

production. They increases activity of LDL
receptor and thus increases uptake by liver.
e.g. Cholestyramine & Cholestipol
Bile acid binding resins

• They mainly decrease LDL-C

• They are used in type II a Hyperlipidemia.

• They are unpalatable and causes nausea,

flatulence, heart burn, constipation. They bind
and reduce the absorption of many drugs.

• Not used in clinical practice regularly.

Fibric acid derivatives

• They lower significantly VLDL and hence TG

with a modest (10%) reduction in LDL-C and an
approximately 10 % increase in HDL-C

• Increases Lipoprotein lipase activity.

Decreases release of free fatty acids from
peripheral adipose tissues. Reduces VLDL
secretion from liver and increase production of HDL
apolipoprotein e.g. Clofibrate,
Gemfibrozil, Bezafibrate, Fenofibrate
HMG-Co-A reductase inhibitor

• Highly effective and widely used lipid lowering agents

commonly known as “ Statins ”

• Produce significant reduction in LDL-C and marginal

increase in HDL-C.

• Indicated for reduction of total and LDL-C in patients of

hypercholesterolemia (II a & II b)

• Validated by many clinical trials e.g.

Lovastatin, Simvastatin, Atorvastatin
 Statins : Mode of Action
Acetoacetyl-Co-A

HMG-Co-A

Statins acts here HMG-Co-A Reductase

Mevalonate

Farnesyl diphoasphate

Cholesterol
Lovastatin
• It is prototype of this class

• It is indicated in hypercholesterolemia (II a & II b)

• The recommended dose is 20 mg once a day and can be

titrated upto a max. dose of 80 mg / day in single or divided
dose.

• Lovastatin decreases LDL by 25-30 %.

• Lovastatin has been found to be very effective validated in

primary prevention by a landmark trial
(AFCAPS/TexCAPS)
Atorvastatin

• Most effective agent of this class.

• It produces marked reduction in LDL even at low dose.

• The recommended dose is 10 mg once a day and

can be titrated upto a max. dose of 80 mg / day in
single or divided dose.

• It lowers TG significantly hence can be given given

in patients with high LDL and TG
Nicotinic acid

• It is a B - group vitamin which modifies lipids when

given in high doses.

• It lowers LDL-C (10-20%), VLDL and hence TG (30 %)

• Most effective agent for raising HDL-C ( 25-35 %).

• It’s hypolipidemic action is unrelated to it’s vitamin action

• It also decreases Lp(a)

Lipoprotein (a)

• It is a powerful independent risk factor for

CAD.

• It is genetically determined and especially high

levels found in Indian population.

• It is structurally similar to LDL.

• It is highly atherogenic and thrombogenic.

Lipoprotein (a)

• Lp(a) is 10 times more atherogenic and

thrombogenic than LDL-C.

• Lp(a) levels can not be altered with lifestyle

modification like diet & exercise.

• No lipid lowering agents reduces Lp(a) significantly.

• Niacin is highly effective in reducing Lp(a)

Nicotinic acid - Mode of Action

• Decreases free fatty acids in blood.

• Increases the activity of Lipoprotein lipase

• Decrease hepatic secretion of VLDL and

decreases rate of synthesis of LDL

• Nicotinic acid increases the levels of

Apo A-1 (apolipoprotein of HDL- C)
Niacin - Clinical Effects

TC : - 30 %

LDL- C : - 20 %

HDL : +30 %

VLDL : - 40 %

TG : - 30 %