Hyperlipidemia

1. Hyperlipidemia
Hyperlipidemia
By Dr Muhammad Tufail
PGR Cardiology MMC

2. Hyperlipidemia
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
.

5. 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
5
1

6. Lipids transport and metabolism

7. Reverse cholesterol transfer
role of ( HDL )

8. CONCLUSION AND CLINICAL IMPORTANCE
●
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 LDL
●
good cholesterol is HDL

9. Disorder of hyperlipidemia
1
.
Hypertriglycredemia
2
.
Hypercholesterolemia
3
.
Combined hyperlipidemia
4
.
Some other lipoprotein disorders
Including disorder of HDL_C

10. 1
.
Hypertriglycredemia

11. Sites of pathology in
Hypertriglycredemia
3

12. Hypertriglycredemia
1
.
Primary cause (rare )
2
.
Secondary cause (more common)

13. Secondary Hypertriglycredemia
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
.

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

15. 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

16. 2
.
Hypercholesterolemia

17. Sites of hypercholesterolemia
pcsk protein

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

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

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

21. 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

22. 3
.
Combined hyperlipidemia

23. 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

24. Familial Combined Hyperlipidemia(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
.

25. HDL C disorders
1
.
↑
HDL
CETP deficiency
2
.
↓
HDL
A.Hypoalphalipoproteinemia
HDL ↓ variable C & TG
B.LCAT deficiency
HDL ↓ 10 mg
Variable ↑TG

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

27. 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
.

28. 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

29. normal ranges
Total cholesterol less than 200 mg
Mild increase 200 _ 250 mg /dl
Moderate increase 250 _ 300 mg /dl
Severe increase more than 300 mg /dl
LDL C less than 100 mg
HDL C less than 40 mg
Total C/ HDL ratio up to 5 normal
Triglyceride ( fasting ) 35_150 mg/dl

30. MANAGEMENT OF CHOLESTEROL TO PREVENT
CARDIOVASCU LAR DISEASE
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

31. 1st
Lifestyle
:
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
.

32. 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
.

33. PHARMACOLOGICAL INDICATION FOR
HYPERCHOLESTEROLEMIA
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)

34. 2nd
line : Pharmacologic Therapy to ↓ cholesterol
1
.
HMG-CoA reductase inhibitors (statins)
:
Action
:
①
inhibit HMG-CoA reductase , a key enzyme in cholesterol biosynthesis, lead to ↓
cholesterol s
.
②
statins 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

35. 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

36. 2
.
Cholesterole absorption inhibitor : 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%
.
3
.
Bile acid sequestrant (resin) : 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
.

37. LDL c APHERESIS
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
.