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?