Hyperlipidemia , dyslipidemia , and drug therapy also Fat transport and metabolisim and pathophysiology of lipoprotein clincal importance of 1. Hypertriglycredemia 2. Hypercholesterolemia 3.Combined hyperlipidemia 4. Some other lipoprotein disorders Including disorder of HDL_C

2. abnormally elevated levels of any or all lipids
and/or lipoproteins in the blood but Plasma
cholesterol and triglyceride are clinically
important because they are major modifiable
risk factors for cardiovascular disease, whilst
severe hypertriglyceridaemia also predisposes
to acute pancreatitis.

3. Intestinal phase of fat metabolism

4. Fat transport and metabolisim
The term 'lipid' refers to substances (including free cholesterol ,
cholesterol ester , phospholipid , triglyceride ) with poor
water solubility therefore to be transport and metabolize
should combined with apolipoproteins to form spherical or
disk-shaped lipoprotein which consist of a hydrophobic core
and a hydrophilic coat The structure of apolipoproteins enables
them to act as cell receptor ligands (by which lipoprotein can
attach to the cells ) . Thus, variation apolipoproteins
composition results in the formation of distinct classes of
lipoproteins with different metabolic functions.

6. Therefore according to different type of apolipoproteins and lipids
those they contain . lipoproteins can subdivided to
HDL LDL IDL VLDL Chylomicron R.
Apo A-1 ApoB100 ApoB100 ApoB100 ApoB48

7. Lipids transport and metabolism

8. role of ( HDL )

9. ●Chylomicron transport fats from the intestinal mucosa to the liver stay
up to 6_10 hours so in fasting state of 12 hour will not detected and
therefore fasting measurement more reliable if fasting 12 hours .
● In the liver the chylomicron release triglyceride and some cholesterol.
●VLDL carries TG and cholesterol (but contain more TG ) therefore will
elevated markedly especially in hypertriglyceridaemia
● LDL carries TG and cholesterol (but contain more cholesterol) to the
body's cells therefore markedly elevated in hypercholesterolemia .
● When LDL become high , atheroma will form in the vessel and
atherosclerosis will occur .
● HDL carry cholesterol to the liver for excretion
● HDL is able to go and remove cholesterol from the atheroma
● Atherogenic cholesterol (bad cholesterol) are
●good cholesterol is

10. Disorder of hyperlipidemia
Some other
Including disorder of

12. Sites of pathology in
3

13. 1. Primary cause (rare )
2. Secondary cause (more common)

14. Secondary
1.↑CHO (>60% of caloric intake)
2.Alcohol
3.Obesity and Insulin R.
5.Chroinc kidney diseas
6.Cushing syndrome
7.Acute hepatitis due to
Infection,drugs or alcohol But in
severe hepatitis& liver
failure are associated with dramatic
reductionsTG & C due to reduced
lipoprotein biosynthetic capacity
8.Drugs (b blocker, corticosteroid)
Obesity and Insulin R.

15. Primary
1.Familial hypertriglycerimia
Mild to moderate ↑ TG
2.Hyperchylomicronimia
a.Familial a poC- 11 deficiency
c.Lipoprotein lipase deficiency

16. S&S of hypertriglyceridemia
>4000 mg/dl
milky appearance of the veins
and arteries of the retina
accumulations of
chylomicrons within
macrophages > 1000
mg/dL
>5000 mg/dl
Acute pancreatitis

18. Sites of hypercholesterolemia
pcsk protein

19. 1.Primary cause ( rare but common than primary
hypertriglyceridemia )
2. Secondary cause ( common)

20. Secondary
Cholestatic liver disease
1.↑ trans and saturated FA
2.Hypothyroidism
3.Pregnancy (not well known)
Others
Hyperparathyroidism
Nephrotic syndrome
Anorexia nervosa

21. Primary
1.Familial hypercholesterlimia 1:250
2.Familial defective apo B 100
3.PCSK 9 mutation
Pcsk , its an enzyme responsible for
LDL R degredation .

22. S & S of hypercholesterolemia
A major risk of CVD,
including myocardial
infarction and stroke , as
well as total mortality
xanthelasma
Corneal arcus
Not significant if in
elderly

24. Combined hyperlipidemia
1.Familial comined Hyperlipidemia
(polygenic) Not fully understood
↑VLDL or both ↑VLDL + LDL or just ↑LDL
↑apo B
2. Dysbetalipoproteinemia
VLDL + - LDL c
3. Hepatic lipase deficiency

25. (Fchl)
FCHL is generally characterized by moderate
elevations in plasma levels of triglycerides (VLDL)
and cholesterol (LDL) and reduced plasma levels
of HDL-C. Approximately 20% of patients who
develop CHD under age 60 (premature coronary
heart disease) have FCHL
The presence of a mixed dyslipidemia (TG 200 _ 800
mg/dL and total C 200 _400 mg/dL, usually with
HDL-C levels <40 mg/dL in men and <50 mg/dL in
women) and a family history of hyperlipidemia
and/or premature CHD strongly suggests the
diagnosis of FCHL.

26. HDL C disorders
↑ HDL
CETP deficiency
↓ HDL
.Hypoalphalipoproteinemia
HDL ↓ variable C & TG
.LCAT deficiency
HDL ↓ 10 mg
Variable ↑TG

27. Screening and measurement
Plasma lipid and lipoprotein levels should be
measured in all adults , preferably after a 12-h
overnight fast

28. Evaluation
cholesterol should be measured
1- Children with parents having hyperlipedemia
or CAD that Developed before 55 years
2-any adult with 1st degree relative having lipid
disorder or vascular Disorder.
3.Investigation for every patient with clinical
feature of hyperlipidemia
4.Screening for primary and secondary
prevention of cardiovascular disease .

29. In most clinical laboratories, the cholesterol and
TGs in the plasma are measured enzymatically ，
and then the cholesterol in the supernatant is
measured after precipitation of apoB-containing
lipoproteins to determine the HDL-C. The
LDL-C is then estimated using the following
equation:
VLDL C = TG / 5 ( in VLDL TG : C 5 :1 )
LDL-C = total cholesterol - (TG/5) - HDL-C

30. normal ranges
less than 200 mg
Mild increase 200 _ 250 mg /dl
Moderate increase 250 _ 300 mg /dl
Severe increase more than 300 mg /dl
less than 100 mg
less than 40 mg
up to 5 normal
35_150 mg/dl

31. It is important to consider and rule out secondary
causes of the hypertriglyceridemia
Patients with plasma triglyceride levels >500 mg/dL
after a trial of diet and exercise should be
considered for drug therapy to avoid the
development of chylomicronemia and It remains
controversial severe hypertriglyceridemia are at
increased risk for CVD .

32. 1. alcohol preferably eliminate their intake.
2.Diet modification
A .Dietary fat restriction to reduce the formation of
chylomicrons in the intestine.
B . simple carbohydrates discouraged because insulin
drives TG production in the liver
3. exercise has positive effect in reducing TG more effect
than lowering LDL C levels and should be strongly
encouraged in hypertriglyceridemia , Repeated 45
minutes for 5 days each week
4. patients who are overweight, weight loss can help to
reduce TG levels,.

33. 1.Fibrate : clofibrate , gemfibrozil Fibrates stimulate LPL and apoClll (↓VLDL
,↓ TG 50% ).
SE: myopathy , especially when combined with (statins,niacin)and ↑ creatinine,
potentiate warfarine and OHA , gallstone.
2. Omega 3 FA (fish oil)
Potent inhibitor of VLDL TG formation ,tablets in doses of 3-4 g/d are effective at
lowering fasting TG levels
If 15 g / d will ↓ TG 50%
SE: dyspepsia
3 . Niacin : suppresses lipolysis by its effect on the niacin receptor in the
adipocyte and effects on hepatic lipid metabolism therefore Niacin (↓TG ,
LDL-C levels and ↑ HDL-C).
SE : flushing , dyspepsia , Mild elevations in transaminases, raise plasma levels of uric
acid and precipitate gouty attacks in susceptible patients, acanthosis nigrigcans .
Because of its SE It is at best to be a third-line agent for the management of sever
hypertriglyceridemia

34. reduce LDL-C substantially reduces the risk of
CVD , including myocardial infarction and
stroke , as well as total mortality.
It is also worth noting that patients at high risk
for CVD who even have plasma LDL-C levels in
the "normal" or average range also benefit
from intervention to reduce LDL-C levels

35. :
1.↓ body weight
2.↓saturated fats, trans fats, and cholesterol in
the diet.
3.Regular exercise has relatively little impact on
reducing plasma LDL-C levels， although it
has cardiovascular benefits independent of
LDL lowering.

36. Food and additives
4.Certain foods and dietary additives are
associated with modest reductions in plasma
cholesterol levels. Plant stanol and sterol
esters interfere with cholesterol absorption
and reduce plasma LDL-C levels by 10% when
taken three times per day.

37. Indication
1.patients with CHD or risk factors even they have
"average" LDL-C levels.
2.To reduce LDL-C to <100 mg/dL in patients with
established CHD
3.all patients with markedly elevated plasma levels
of LDL-C levels (>190 mg/dL)
4.plasma LDL-C levels between 130 and 190 mg/dL
with The presence of other risk factors such as a
low plasma level of HDL-C (<40 mg/dL)

38. (statins):
Action :
①inhibit HMG-CoA reductase , a key enzyme in cholesterol biosynthesis, lead to ↓
cholesterol s.
②statins also increase hepatic LDL receptor activity and accelerated clearance of
circulating LDL
Statin ↓LDL c 60% ↓ TG 40% ↑ HDL 10%
Indication :
Usually one tablet at night (because there is ↑ action
of Hepatic enzyme at night )
Simvastatin20-40mg/d maximam 80 mg/d
Most useful and dependent way to
indicate statins uses
depend on guidelines of
British coronary prediction risk chart
If more than 20% risk over next 10 years

39. Statin SE: dyspepsia,headaches,fatigue,and muscle
or joint pains. Severe myopathy and even
rhabdomyolysis occur .The risk of myopathy is
increased in
□older age,
□renal Insufficiency,
□co_administration of drugs such as erythromycin, antifungal
agents , immunosuppressive drugs.
*Interrupt treatment if
1.CK is more than 5–10 times the upper limit of normal
(NR : m 55_170 u/l , f 30 _ 135 u/l) ,
2.elevated with muscle symptoms
3.ALT is more than 2–3 times the upper limit

40. : Ezetimibe ,
blocks the intestinal absorption of cholesterol by
inhibits NPC1Ll indicated as a combination with
statin or when statin is intolerated . 10 mg lower
LDL C 20% .
: prevent bile acid
absorption thereby reduce liver content of
cholesterol that lead to ↑ LDL receptor and LDL
clearance such cholestyramine,colestipol and
colesevelam
SE : bloating and constipation .
Because bile acidsequestrants are not systemically
absorbed , the cholesterol-lowering drug of choice
in children and in women of childbearing age , who
are lactating or pregnant.

41. Patients who remain severely
hypercholesterolemic especially of genetic
cause despite optimally tolerated and
maximam drug therapy are candidates for LDL
apheresis. In this process , the patient plasma
is passed over a column that selectively
removes the LDL and the LDL-depleted plasma
is returned to the patient.

42. Resources
1.Harrison .
2.Davidson
3.Medscape .