1. Hyperlipidemia
By.Dr.Simaie

2. اصلی ترین ترکیبات چربی در بدن؟TG
Cholestrole
phospholipide

3. نقش اصلی کلسترول در بدن چیست؟
حضور در ساختار غشاء سلول
سوبسترای ساخت هورمون ها مخصوصا استروئیدها
پیش نیاز ساخت اسیدهای صفراوی

4. منبع کلسترول برای سلولها
سنتز chدر داخل خود سلولها
در گردش خون سیستمیک:هپاتوسیت ها –غذا

5. کلسترول به چه فرمی وارد خون می شود؟

6. Intracellular cholestrol synthesis
HMG-COA Reductase
ACAT

8. Checking lipids Nonfasting lipid panel Fasting lipid panel
measures HDL and total cholesterol
Fasting lipid panel
Measures HDL, total cholesterol and triglycerides
LDL cholesterol is calculated:
LDL cholesterol = total cholesterol – (HDL + triglycerides/5)

9. Most laboratories can measure
LDL-C directly and should be asked to do so when the TG is>400 mgldL or the patient has not fasted.

10. Apolipoprotein شکل ساختمانی لیپو پروتئین ها را می سازد
فعال شدن سیستم آنزیمی
پیوند به سلول

12. انواع لیپوپروتئین ها
VLDL
LDL
HDL
chylomicrone

13. The story of lipids
Chylomicrons transport fats from the intestinal mucosa to the liver
In the liver, the chylomicrons release triglycerides and some cholesterol and become low-density lipoproteins (LDL).
LDL then carries fat and cholesterol to the body’s cells.
High-density lipoproteins (HDL) carry fat and cholesterol back to the liver for excretion.

14. The story of lipids (cont.)
When oxidized LDL cholesterol gets high, atheroma formation in the walls of arteries occurs, which causes atherosclerosis.
HDL cholesterol is able to go and remove cholesterol from the atheroma.
Atherogenic cholesterol → LDL, VLDL, IDL

15. Atherosclerosis

16. Causes of Hyperlipidemia
Diet
Hypothyroidism
Nephrotic syndrome
Anorexia nervosa
Obstructive liver disease
Obesity
Diabetes mellitus
Pregnancy
Obstructive liver disease
Acute heaptitis
Systemic lupus erythematousus
AIDS (protease inhibitors)

18. Dietary sources of Cholesterol
Type of Fat
Main Source
Effect on Cholesterol levels
Monounsaturated
Olives, olive oil, canola oil, peanut oil, cashews, almonds, peanuts and most other nuts; avocados
Lowers LDL, Raises HDL
Polyunsaturated
Corn, soybean, safflower and cottonseed oil; fish
Saturated
Whole milk, butter, cheese, and ice cream; red meat; chocolate; coconuts, coconut milk, coconut oil , egg yolks, chicken skin
Raises both LDL and HDL
Trans
Most margarines; vegetable shortening; partially hydrogenated vegetable oil; deep-fried chips; many fast foods; most commercial baked goods
Raises LDL

20. Goals for Lipids LDL Total Cholesterol HDL Serum Triglycerides
< 100 →Optimal
→ Near optimal
→ Borderline
→ High
≥ 190 → Very High
Total Cholesterol
< 200 → Desirable
→ Borderline
≥240 → High
HDL
< 40 → Low
≥ 60 → High
Serum Triglycerides
< 150 → normal
→ Borderline
→ High
≥ 500 → Very High

21. Determining Goal LDL CHD and CHD Risk Equivalents:
Peripheral Vascular Disease
Cerebral Vascular Accident
Diabetes Mellitus

22. Risk factor Age Hypertension Diabet Smoking Stress Low HDL
Family history

23. Presence of 2 RF:
LDL should be below 100
Presence of 1 RF:
below 160

24. Treatment of Hyperlipidemia
Lifestyle modification
Low-cholesterol diet
Exercise

26. Medications for Hyperlipidemia
Drug Class
Agents
Effects (% change)
Side Effects
HMG CoA reductase inhibitors
Lovastatin
Pravastatin
LDL (18-55), HDL (5-15)
 Triglycerides (7-30)
Myopathy, increased liver enzymes
Cholesterol absorption inhibitor
Ezetimibe
 LDL( 14-18),  HDL (1-3)
Triglyceride (2)
Headache, GI distress
Nicotinic Acid
LDL (15-30),  HDL (15-35)
 Triglyceride (20-50)
Flushing, Hyperglycemia,
Hyperuricemia, GI distress, hepatotoxicity
Fibric Acids
Gemfibrozil
Fenofibrate
LDL (5-20), HDL (10-20)
Triglyceride (20-50)
Dyspepsia, gallstones, myopathy
Bile Acid sequestrants
Cholestyramine
 LDL
 HDL
No change in triglycerides
GI distress, constipation, decreased absorption of other drugs

27. BILE ACID RESINS not absorbed from gastrointestinal (GI) tract
Reduce total and LDL cholesterol in a dose-dependent manner
initiated with one packet
administered in one or two divided doses daily.
The standard daily dose reduces
LDL-C by 15% to 18%.

28. Mechanism of Action
anion exchange agents that bind bile acids in the intestinal lumen and cause them to be eliminated in the stool. the liver is stimulated to convert hepatocellular cholesterol into bile
acids. This in turn causes a reduction in the concentration of cholesterol in the hepatocyte, prompting the up regulation of LDL receptor synthesis.

29. Adverse Effects
GI symptoms: constipation,bloating, epigastric fullness,nausea,flatulence
The older resins also can raise TG levels by 3% to 10% or more, especially in patients with high TG levels.
Reduction in the absorption
of fat-soluble vitamins and folic acid

30. EZETIMIBE cholesterol absorption inhibitors.
reduces LDL-C by 18% to 22%, but has little effect on TG or HDL-C.
Once a day as a 1O-mg tablet
added to the maximal dose of a statin, causes further LDL-C reduct

31. Ezetimibe interferes with the active absorption of cholesterol from the intestinal lumen into the enterocyte
Ezetimibe inhibits the absorption of sitosterol, a plant sterol, from the gut, resulting in about a 40% reduction in blood sitosterol levels
Ezetimibe's side effects include diarrhea, arthralgias, cough,fatigue.

32. water-soluble B vitamin
Sustained-release (timed-release) dosage forms of niacin were developed to reduce the flushing side effects associated with crystalline niacin.

33. Niacin inhibits the mobilization of free fatty acids from peripheral adipose tissue to the liver, which, either alone or together with other hepatic effects, results in reduced synthesis and secretion of VLDL particles by the liver.

34. taking 325 mg of aspirin 30 minutes before the morning dose of niacin (to inhibit prostaglandin synthesis, which is thought to mediate these side effects).
Nausea, dyspepsia activation of peptic ulcer. hyperuricemia, gout, and transient worsening of glucose tolerance in some diabetic patients
Hepatotoxicity

35. STATINS most potent cholesterol-lowering
potential is composed of the statins.
atorvastatin , simvastatin lovastatine, pravastatin
inhibit the enzyme responsible for converting HMG-CoA to mevalonate in an early, rate-limiting step in the biosynthetic pathway of cholesterol

36. Statin
Headache; myalgias (without CPK changes); and GI symptoms, including dyspepsia. flatus, constipation. and abdominal pain, occasionally are expcrienced.
Gemfibrozil with a statin cause the increase risk of miosit

39. FIBRIC ACID DERIVATIVES
Clofibrate, gemfibrozile
Reduce TG level
In hyper TG patients may lead to increase HDL
In patients who have TG levels> 1,000 mgldL and are at risk for developing pancreatitis, fibrates, along with niacin, are the drugs of choice.

40. Gemfibrozil mild GI symptoms (nausea, dyspepsia, abdominal pain)
Fenofibrate causes a rash in 2% to 4% of patients

41. Patients who receive gemfibrozil or fenofibrate therapy alone or in combination with a statin should be monitored for symptoms of muscle soreness and pain. ]f these symptoms emerge, a CPK level should be obtained. A CPK level> 10 times the upper limit of normal along with muscle symptoms, supports a diagnosis of myositis.
The presence of myositis is an indication to withdraw fibrate therapy,

42. Gemfibrozil increases biliary secretion of cholesterol, which increases the lithogenicity of bile and results in the development of cholesterol gallstones.
Presumably, the same effect occurs with all fibrates.

43. Develop a 7 point Prevention RX for ASCVD with each Patient
1) BP
2) Lipids
3) Diet
4) Smoking
5) Activity
6) Weight
7) Aspirin use

44. Case # 1
A 55-year-old woman without symptoms of CAD seeks assessment and advice for routine health maintenance. Her blood pressure is 135/85 mm Hg. She does not smoke or have diabetes and has been postmenopausal for 3 years. Her BMI is 24. Lipoprotein analysis shows a total cholesterol level of 240 mg/dL, an HDL level of 55 mg/dL, a triglyceride level of 85 mg/dL and a LDL level is 180 mg/dL. The patient has no family history of premature CAD.

45. Case # 1 (cont.) What is the goal LDL in this woman?
What would you do if exercise/diet change do not improve cholesterol after 3 months?
How would your management change if she complained of claudication with walking?

46. Case # 2
A 40- year-old man without significant past medical history comes in for a routine annual exam. He has no complaints but is worried because his father had a “heart attack” at the age of 45. He is a current smoker and has a 23-pack year history of tobacco use. A fasting lipid panel reveals a LDL 170 mg/dL and an HDL of 35 mg/dL. Serum Triglycerides were 140 mg/dL. Serum chemistries including liver panel are all normal.

47. Case # 2 (cont.) What is this patient’s goal LDL?
Would you start medication, and if so, what?

48. Case # 3
A 65 year-old woman with medical history of Type II diabetes, obesity, and hypertension comes to your office for the first time. She has been told her cholesterol was elevated in the past and states that she has been following a “low cholesterol diet” for the past 6 months after seeing a dietician. She had a normal exercise stress test last year prior to knee replacement surgery and has never had symptoms of CHD. A fasting lipid profile was performed and revealed a LDL 130, HDL 30 and a total triglyceride of Her Hgba1c is 6.5%.

49. Case # 3 (cont.) What is this patient’s goal LDL?
What medication would you consider starting in this patient?
What labs would you want to monitor in this patient?