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HyperlipidemiaBy.Dr.Simaie
بدن؟ در چربی ترکیبات ترین اصلی
TG Cholestrole phospholipide
چیست؟ بدن در کلسترول نقشاصلیسلول 1. غشاء ساختار در حضورمخصوصا 2. ها هورمون ساخت سوبسترای
استروئیدهاصفراوی 3. اسیدهای ساخت نیاز پیش
سلولها برای کلسترول منبعسلولها chسنتز 1. خود داخل در.2 – : غذا ها هپاتوسیت سیستمیک گردشخون در
خون وارد فرمی چه به کلسترولشود؟ می
Intracellular cholestrol synthesis HMG-COA Reductase ACAT
Checking lipids Nonfasting 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)
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.
Apolipoprotein سازد می را ها پروتئین لیپو ساختمانی شکل آنزیمی سیستم شدن فعال سلول به پیوند
ها لیپوپروتئین انواع VLDL LDL HDL chylomicrone
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.
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
Atherosclerosis
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)
Dietary sources of CholesterolType 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
Lowers LDL, Raises HDL
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
Goals for Lipids LDL
< 100 →Optimal 100-129 → Near optimal 130-159 → Borderline 160-189→ High ≥ 190 → Very High
Total Cholesterol < 200 → Desirable 200-239 → Borderline ≥240 → High
HDL < 40 → Low ≥ 60 → High
Serum Triglycerides < 150 → normal 150-199 → Borderline 200-499 → High ≥ 500 → Very High
Determining Goal LDL CHD and CHD Risk Equivalents:
Peripheral Vascular Disease Cerebral Vascular Accident Diabetes Mellitus
Risk factor Age Hypertension Diabet Smoking Stress Low HDL Family history
Presence of 2 RF:
LDL should be below 100 Presence of 1 RF:
below 160
Treatment of Hyperlipidemia Lifestyle modification
Low-cholesterol diet Exercise
Medications for HyperlipidemiaDrug 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
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%.
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.
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
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
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.
water-soluble B vitamin Sustained-release (timed-release) dosage
forms of niacin were developed to reduce the flushing side effects associated with crystalline niacin.
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.
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
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
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
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.
Gemfibrozil mild GI symptoms (nausea, dyspepsia, abdominal pain)
Fenofibrate causes a rash in 2% to 4% of patients
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.
o The presence of myositis is an indication to withdraw fibrate therapy,
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.
1) BP2) Lipids3) Diet4) Smoking5) Activity6) Weight7) Aspirin use
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.
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?
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.
Case # 2 (cont.) What is this patient’s goal LDL? Would you start medication, and if so,
what?
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 300. Her Hgba1c is 6.5%.
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?