Review of Cholesterol and

Lipoproteins
Objectives for Presentation:
• To review importance of Cholesterol and other lipids as a
risk factor for heart disease
• To review the components of cholesterol and their relative
importance
• To review cholesterol metabolism
• To understand the tests for total cholesterol and its
different lipoprotein components
 Cholesterol has important
functions in the human body
• Necessary part of cell walls
• Precursor chemical for steroid compounds:
-hydrocortisone, aldosterone, estrogens, etc.
• Formation of bile acids for digestion

The Liver is the major organ for synthesis and

metabolism of cholesterol. The body has developed
an elaborate system of cholesterol transport
 Serum Cholesterol and CHD
in 361,662 U.S. Men
18
6 Year CHD Death Rate

16
14
per 1,000 Men

12
10
8
6
4
2
0
140 160 180 200 220 240 260 280 300 mg/dL
Serum Cholesterol
Martin M. Lancet 1986;11:933-936
 Serum Cholesterol in the USA
and CHD Death
18 MRFIT NHANES II 100
16

Above Cholesterol
% U.S. Population
14 80
/1000 /6 Year
CHD Death

12

Level
10 60
8
40
6
4 20
2
0 0
140 160 180 200 220 240 260 280 300 mg/dL
Serum Cholesterol
Martin M. Lancet 1986;11:933-936
 Lipids are packaged in the
bloodstream into Lipoproteins
• Lipoproteins have different combinations of
lipids and apoproteins
• Lipoproteins carry lipids from intestine
• Lipoproteins carry lipids to and from liver
• Each lipoprotein has a different function

Lipoproteins are important in atherogenesis and

the development of heart disease
 Structure of HDL Particle
A-I
A-I
CE
TG

A-II

A-I, A-II = apolipoprotein A-I, A-II;

CE = cholesteryl ester; TG = triglycerides
 Major Lipoproteins and their function
• Chylomicrons:
– Chylomicrons transport triglycerides from intestine
• Very Low Density Lipoproteins (VLDL) and
Intermediate Density Lipoproteins (IDL) :
– VLDL produced in liver . Carry cholesterol and triglycerides
• Low Density Lipoproteins (LDL)
– LDL result from metabolism of VLDL and IDL and carry
cholesterol. LDL are important cause of heart disease
• High Density Lipoproteins(HDL)
– HDL is “good” cholesterol. It removes cholesterol and
protects against heart disease
Steps Involved in Cholesterol
Absorption

MTP
Net Cholesterol Balance in
Humans
 Exogenous Pathway Endogenous Pathway
Bile acids and ApoB -100
Dietary fat Cholesterol LDL
LDL-R

Liver Endogenous
Cholesterol LDL-R
Extra Hepatic
Intestine Dietary
Cholesterol Tissue
Remnant
Receptor

Chylomicrons Remnants VLDL IDL HDL

ApoE C-II ApoE ApoE ApoA-I
B-48 B-48 B-100 A-II
ApoE C-II
B-100

Plasma LCAT
(lecithin cholesterol
acyl transferase

Lipoprotein lipase Lipoprotein lipase

Free fatty acids Free fatty acids

Adipose tissue, muscle Adipose tissue, muscle

 LDL Levels in Populations
With and Without CHD
25 Without CHD
Frequency (%)

20 With CHD

15
10
5
0
80 100 120 140 160 180 200 220 240 260 280 300 320

LDL Cholesterol (mg/dL)

Kannel W. Am J Cardiol 1995;76:69C-77C

Effect of Blocking Bile Acid
Absorption
Inhibition of Cholesterol
Absorption
MTP
(Inhibitors)
The Liver Regulates the Concentration
of LDL-Cholesterol
 Cholesterol Biosynthetic
Pathway
HMG-CoA Squalene
reductase synthase
Dolichol

Acetyl HMG- Mevalonate Farnesyl

Squalene Cholesterol
CoA CoA pyrophosphate

Ras Farnesyl-
protein transferase

E,E,E-Geranylgeranyl
pyrophosphate
Farnesylated
proteins
Geranylgeranylated Ubiquinones
proteins
 Measurement of Cholesterol
• Total Cholesterol is the sum of cholesterol
contained in the different lipoproteins
• Fasting not required
• Measured in millimoles per Liter
(mmol/L) in Russia
– Measured in milligrams per deciliter in US
– 5.17 mmol/L = 200 mg/dL
– conversion factor 38.7
 Complete Lipid Panel
• Requires 12 hour fast
• Total Cholesterol measured directly (mmol/L)
• HDL is measured directly (mmolL)
• Triglycerides are measured directly (mg/dL)
– Conversion factor to millimoles =88.6
• LDL is usually calculated :
• LDL = Total Cholesterol - HDL- (Triglycerides/5)
• Calculation not accurate if Triglycerides > 400
mg/dL
 Values for Cholesterol
• Total Cholesterol
< 5.17 mmol/L = Good
5.17-6.19 = Borderline High
> 6.20 = High
 Values for Low Density
Lipoprotein (LDL)

< 2.58 = Good

2.58-3.33 = Near Normal
3.34- 4.12 = Borderline High
4.13-4.88 = High
> 4.88 = Very High
 Values for High Density
Lipoprotein (HDL)

< 1.03 mmol/L = LOW

(Increased Risk)

> 1.55 mmol/L = HIGH

(Lower Risk)
 Total Cholesterol/HDL Ratio
or
Coefficient of Atherogenicity
• No Longer Used in New
Guidelines
• Reliance on LDL levels
 Triglycerides
• Measured in mg/dL
– conversion to mmol/L = 88.6
• Levels:
< 150 mg/dL = normal
150-199 = borderline high
200-499 = high
> 500 = very high
 Disorders of Cholesterol and
Lipoproteins in 3 Categories
• Specific Familial/Genetic Disorders
– These comprise a small minority of patients
• Secondary to other Diseases
– Diabetes, Hypothyroid, Nephrotic syndrome, Renal
Failure, Lupus
• Dietary/Polygenic --(most common)
– This is the great majority of patients with elevated
cholesterol/LDL