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Hyperlipidemia

Michele Ritter, M.D.


Argy Resident – February, 2007
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  Obstructive liver
 Hypothyroidism disease
 Nephrotic syndrome  Acute heaptitis
 Anorexia nervosa  Systemic lupus
 Obstructive liver erythematousus
disease  AIDS (protease
 Obesity inhibitors)
 Diabetes mellitus
 Pregnancy
Dietary sources of Cholesterol
Type of Fat Main Source Effect on
Cholesterol levels
Monounsaturated Olives, olive oil, canola oil, peanut oil, Lowers LDL, Raises
cashews, almonds, peanuts and most HDL
other nuts; avocados
Polyunsaturated Corn, soybean, safflower and cottonseed Lowers LDL, Raises
oil; fish HDL

Saturated Whole milk, butter, cheese, and ice cream; Raises both LDL and
red meat; chocolate; coconuts, coconut HDL
milk, coconut oil , egg yolks, chicken skin

Trans Most margarines; vegetable shortening; Raises LDL


partially hydrogenated vegetable oil; deep-
fried chips; many fast foods; most
commercial baked goods
Hereditary Causes of Hyperlipidemia
 Familial Hypercholesterolemia
 Codominant genetic disorder, coccurs in heterozygous form
 Occurs in 1 in 500 individuals
 Mutation in LDL receptor, resulting in elevated levels of LDL at birth and
throughout life
 High risk for atherosclerosis, tendon xanthomas (75% of patients), tuberous
xanthomas and xanthelasmas of eyes.
 Familial Combined Hyperlipidemia
 Autosomal dominant
 Increased secretions of VLDLs
 Dysbetalipoproteinemia
 Affects 1 in 10,000
 Results in apo E2, a binding-defective form of apoE (which usually plays
important role in catabolism of chylomicron and VLDL)
 Increased risk for atherosclerosis, peripheral vascular disease
 Tuberous xanthomas, striae palmaris
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)
When to check lipid panel
 Two different Recommendations
 Adult Treatment Panel (ATP III) of the National Cholesterol
Education Program (NCEP)
 Beginning at age 20: obtain a fasting (9 to 12 hour) serum lipid profile
consisting of total cholesterol, LDL, HDL and triglycerides
 Repeat testing every 5 years for acceptable values
 United States Preventative Services Task Force
 Women aged 45 years and older, and men ages 35 years and older
undergo screening with a total and HDL cholesterol every 5 years.
 If total cholesterol > 200 or HDL <40, then a fasting panel should be
obtained
 Cholesterol screening should begin at 20 years in patients with a
history of multiple cardiovascular risk factors, diabetes, or family
history of either elevated cholesteral levels or premature
cardiovascular disease.
Goals for Lipids
 LDL  HDL
 < 100 →Optimal  < 40 → Low
 100-129 → Near optimal  ≥ 60 → High
 130-159 → Borderline  Serum Triglycerides
 160-189→ High  < 150 → normal
 ≥ 190 → Very High  150-199 → Borderline
 Total Cholesterol  200-499 → High
 < 200 → Desirable  ≥ 500 → Very High
 200-239 → Borderline
 ≥240 → High
Determining Cholesterol Goal
(LDL!)
 Look at JNC 7 Risk Factors
 Cigarette smoking
 Hypertension (BP ≥140/90 or on anti-
hypertensives)
 Low HDL cholesterol (< 40 mg/dL)
 Family History of premature coronary heart
disease (CHD) (CHD in first-degree male relative
<55 or CHD in first-degree female relative < 65)
 Age (men ≥ 45, women ≥ 55)
Determining Goal LDL
 CHD and CHD Risk Equivalents:
 Peripheral Vascular Disease
 Cerebral Vascular Accident
 Diabetes Mellitus
LDL Goals
 0-1 Risk Factors:
 LDL goal is 160
 If LDL ≥ 160: Initiate TLC (therapeutic lifestyle changes)
 If LDL ≥ 190: Initiate pharmaceutical treatment
 2 + Risk Factors
 LDL goal is 130
 If LDL ≥ 130: Initiate TLC
 If LDL ≥ 160: Initiate pharmaceutical treatment
 CHD or CHD Risk Equivalent
 LDL goal is 100 (or 70)
 If LDL ≥ 100: Initiate TLC and pharmaceutical treatment
Treatment of Hyperlipidemia
 Lifestyle modification
 Low-cholesterol diet
 Exercise
Medications for Hyperlipidemia
Drug Class Agents Effects (% change) Side Effects
HMG CoA reductase Lovastatin LDL (18-55), HDL (5-15) Myopathy, increased liver
inhibitors Pravastatin  Triglycerides (7-30) enzymes

Cholesterol Ezetimibe  LDL( 14-18),  HDL (1-3) Headache, GI distress


absorption inhibitor Triglyceride (2)
Nicotinic Acid LDL (15-30),  HDL (15-35) Flushing, Hyperglycemia,
 Triglyceride (20-50) Hyperuricemia, GI distress,
hepatotoxicity
Fibric Acids Gemfibrozil LDL (5-20), HDL (10-20) Dyspepsia, gallstones,
Fenofibrate Triglyceride (20-50) myopathy

Bile Acid Cholestyramine  LDL GI distress, constipation,


sequestrants  HDL decreased absorption of
other drugs
No change in triglycerides
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?