Disease of Lipoprotein Metabolism

and Lipidemia, Obesity

By Krairat Komdee, MD.
Department of Internal Medicine, Phayao Hospital

Dietary cholesterol
~ 300-700mg/day

Biliary cholesterol
~ 1000mg/day

Adapted from Champe PC, Harvey RA. Biochemistry. 2nd ed. Philadelphia: Lippincott Raven, 1994; Glew RH. In Textbook of Biochemistry with Clinical
Correlations. 5th ed. New York: Wiley-Liss, 2002:728-777; Ginsberg HN, Goldberg IJ. In Harrisons Principles of Internal Medicine. 14th ed. New York:
McGraw-Hill, 1998:2138-2149; Shepherd J Eur Heart J Suppl 2001;3(suppl E):E2-E5; Hopfer U. In Textbook of Biochemistry with Clinical Correlations. 5th
ed. New York: Wiley-Liss, 2002:1082-1150.

Physiologic role of cholesterol

Normal biologic function
Component of cell membranes
Precursor of other steroids
Cortisol, progesterone, estrogen, testosterone, bile
acids
Excess cholesterol
CHD
Xanthomas
Adapted from Saladin KS. Anatomy and Physiology. 2nd ed. Boston: McGraw-Hill, 2001; Jones PH et al. In Hurst s The Heart. Arteries and Veins. 9th ed.
New York: McGraw-Hill, 1998:1553-1581; Ginsberg HN, Goldberg IJ. In Harrisons Principles of Internal Medicine. 14th ed. New York: McGraw-Hill,
1998:2138-2149.

Fredrickson Classification of Dyslipidemias

Phenotype

Lipoprotein
elevated

Serum
Cholesterol
Level

Serum
Triglyceride
Level

Chylomicrons

Normal to

IIa

LDL

IIb

LDL and VLDL

+++

III

IDL

+++

Atherogenicity

None seen
Normal

+++

IV

VLDL

Normal to

VLDL and
chylomicrons

Notmal to

Types of Dyslipidemia
1. Hypertriglyceridemia
2. Hypercholesterolemia
3. Hyperalphalipoproteinemia
4. Hypoalphalipoproteinemia
5. Hypobetalipoproteinemia

Common genetic dyslipidemia

Familial hypercholesterolemia
Polygenic hypercholesterolemia
Familial defective apolipoprotein B100
Familial hypertriglyceridemia
Familial combined hyperlipidemia

LDL-Cholesterol defects
Disoder

Lipid levels

Confirmatory
studies

Physical findings

Familial
hypercholesterolemia

High TC
TG usually normal

LDL receptor defect by Tendon xanthomata in

cell studies or DNA
patient or one 1st or
mapping
2nd degree relative

Familial combined
hyperlipidemia

High TC
TG usually normal

LDL-chol/apo B < 1.2

Xanthelasma ; corneal
arcus, tendon
xanthomas

Familial
TC and/or TG> 90th
LDL-chol/apo B <1.2
hyperapobetalipoprotei percentile in pt and 1st
nemia
or 2nd degree relatives
c similar profile

Xanthelasma

Polygenic
hypercholesterolemia

Exclusion : tendon
xanthomata in patient
or family members

TC > 90th percentile

TG < 90th percentile

Secondary cause of hyperlipidemia

LDL
Elevated

HDL
Reduced

Hypothyroidism
Nephrotic
syndrome
Cholestasis
Acute
intermittent
porphyria
Anorexia
nervosa
Hepatoma
Drugs: thiazides,
cyclosporine,
tegretol

Elevated

Alcohol
Severe liver
Exercise
disease
Drugs: estrogen
Malabsorption
Malnutrition
Gaucher disease
Chronic
infectious
disease

Hyperthyroidism

Drugs: niacin
toxicity

Reduced

Smoking
DM2
Obesity
Malnutrition
Gaucher disease
Drugs: anabolic
steroids,
betablocker

VLDL

Chylomicron

Elevated

Elevated

Autoimmune
Obesity
DM2
disease
Glycogenstorage Drug:
disease
Isotretinoin
Alcoholic
hepatitis
Renal failure
Cushing
syndrome
Pregnancy
Acromegaly
Lipodystrophy
Drugs: estrogen,
betablocker,
furosemide,
glucocorticoids,
PIs, retinoic acid

CHD risk based on risk factors

other than LDL level
Positive risk factors
Male more than 45 years
Female more than 55 years or postmenopausal without estrogen replacement therapy
FH of premature CHD (definite MI or sudden death before age 55 in father or other male firstdegree relative or before age 65 in mother or other female first-degree relative)
Current cigarette smoking
HT
HDL cholesterol level less than 35mg/dL
Diabetes mellitus
Negative risk factor
High HDL cholesterol level more than 60mg/dL

Screening for risk group

1. Hx of CAD, CVA, PAD
2. Whom has CHD risk
1. Age; male 45, female 55
2. FH; male 55, female 65
3. DM2
4. HT
5. Smooking
3. Positive finding on PE; corneal arcus, tendon xanthoma,
xanthelasma,palmar xanthoma,eruptive xanthoma

Lipoprotein measurement

Total cholesterol, Triglyceride, HDL-C

Calculate LDL-C by Friedewald equation :

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

TG-C must be less than 400 for calculate

Prepare before Exam

NPO 9-12hrs
Regular diet more than 3 weeks
12 wks after pregnancy, surgery, critical care,
infection
12th hrs or after 6 weeks after acute MI
48th hrs or after 12 weeks after CVA

NCEP guidellines : LDL-C Treament

Cutpoints and target for therapy
Category

LDL-C target

Diet

Drug

No CHD, <2RF

<160

160

190

No CHD, 2RF

<130

130

160

with CHD or other

aterosclerotic disease

100

>100

130

Management of dyslipidemia
Lifestyle modification
exercise and weight reduction
Medical Treatment
Bile acid sequestrant resins : Cholestyramine
HMG Co A reductase inhibitors; statin
Fibric acid and derivatives
Nicotinic acid and derivatives
Selective cholesterol absorption inhibitor; ezetimibe

Bile acid sequestrant resins

bind bile acid in intestine and promote excretion
in stool; interrupt enterohepatic bile acid
circulation
used in hypercholesterolemia
low side effects ; bloating, constipation
drugs of choice in children, pregnancy, lactation

HMG CoA reductase inhibitors

Inhibits HMG-CoA reductase
Interpatient variability in response to statin
most common side effect; myopathy,
hepatotoxicity

Nicotinic acid and derivatives

inhibits lipoprotein secretion
used in hypercholesterolemia
side effects; flushing, itching, hepatitis,
oesophageal reflux
increase HDL-C at high dose

Selective cholesterol
absorption inhibitor
improve LDL-C, TC, HDL, TG
cholesterol absorption inhibitors
target cholesterol absorption in intestine
mechanism of action complementary of statin
achieves lipid reductions greater than statin alone
may be use as mono therapy for patients intolerant to
statin