This document discusses the management of dyslipidemia. It begins by defining dyslipidemia and describing how abnormalities in plasma lipids can increase the risk of cardiovascular diseases. It then discusses the functions of cholesterol and triglycerides in the body before explaining the different lipoproteins and their roles in transporting lipids. The document outlines the pathophysiology of atherosclerosis and clinical presentation of dyslipidemia. It provides guidance on evaluating and treating patients, including therapeutic lifestyle changes, pharmacologic therapies like statins, fibrates, niacin and bile acid resins, and dietary interventions.

1. Dyslipidemia Management
By: Haftom N.
5/17/2023 1

2. Introduction
• Dyslipidemia can be defined as elevated total
cholesterol, LDL-C, or triglycerides level, low HDL-C, or
some combination of these abnormalities.
• Total cholesterol and LDL-C increase throughout life in
men and women
• Abnormalities of plasma lipids can result in a
predisposition to coronary, cerebrovascular, and
peripheral vascular arterial disease.
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3. Function of Fats in the body
• Cholesterol & triglycerides are essential substrates
for cell membrane formation
• Hormone synthesis
• They provide a source of free fatty acids
• The rate-limiting enzyme in the cholesterol
synthesis pathway is 3-hydroxy-3-methylglutaryl
coenzyme A reductase (HMG-CoA reductase)
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4. Lipoproteins
• Cholesterol, triglycerides, and phospholipids are
transported in the bloodstream as complexes of lipid and
proteins known as lipoproteins.
• HDL transports cholesterol from lipid-laden foam cells to
the liver (happy/good Cholesterol)
• LDL transports fat from liver to body (bad cholesterol)
• VLDL, the major lipoprotein associated with
triglycerides, is enriched with cholesterol esters
 VLDL is carried in the circulation as triglyceride (Tg)
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5. • Chylomicrons are large triglyceride-rich particles that
contain apolipoproteins B-48, B-100, and E.
 They are formed from dietary fat
• VLDL synthesis is regulated in part by diet and hormones
• VLDL is secreted from the liver and serially converted via LPL
to IDL and finally to LDL
• VLDL and LDL are calculated values:
 VLDL = Tg/5
 LDL = Total cholesterol – (VLDL + HDL).
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6. • Primary or genetic lipoprotein disorders
• classified in to six and elevations:
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7. Secondary Causes of Lipoprotein Abnormalities
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8. Pathophysiology
• Response-to-injury hypothesis states that risk factors
which lead to endothelial dysfunction and a series of
cellular interactions that culminate in atherosclerosis
such as
 Oxidized LDL,
 Mechanical injury to the endothelium
 Excessive homocysteine
 Immunologic attack or
 Infection-induced changes in endothelial
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9. • Atherosclerotic lesions arise from transport
and retention of plasma LDL through the
endothelial cell layer
• Clinical outcomes may include:
– Angina, MI, arrhythmias, stroke, peripheral arterial
disease, abdominal aortic aneurysm, and sudden
death
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10. Clinical Presentation
• Most pts are asymptomatic for many yrs
• Pts with the metabolic syndrome may have three
or more of the following:
Abdominal obesity,
Atherogenic dyslipidemia,
Increased BP,
Insulin resistance with or without glucose intolerance,
Prothrombotic state, or proinflammatory state
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11. Signs & Symptoms
Symptoms:
• None to severe chest pain, palpitations, sweating, anxiety,
shortness of breath, loss of consciousness or difficulty with
speech or movement, abdominal pain, sudden death.
Signs:
• None to severe abdominal pain, pancreatitis, eruptive
xanthomas, peripheral polyneuropathy, high BP, BMI >30
kg/m2 or waist size >40 inches in men (35 inches in
women)
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12. xanthoma
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13. Laboratory Tests
• Elevations in total cholesterol
 LDL
 Triglycerides
 Apolipoprotein B
 C-reactive protein
– Low HDL
• Other Diagnostic Tests
– tests for manifestations of vascular disease (ABI, exercise testing, MRI)
– Tests for DM (fasting glucose, OGTT, hemoglobin A1c).
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14. 5/17/2023 14

15. Patient Evaluation
• A fasting lipoprotein profile including should be measured in all adults 20
yrs and older at least once every 5 yrs
• If total cholesterol is >200 mg/dL or HDL-C is <40 mg/dL in nonfasted state
– a follow up fasting lipoprotein profile should be obtained
• After lipid abnormality is identified, evaluate:
 History (age, gender,and hormone replacement status)
 Physical examination (CVD disease)
 Laboratory investigations
 presence or absence of secondary causes of lipid abnormalities
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16. Treatment
Goals of Therapy
 To reduce the risk of first events or recurrent
events such as MI, angina, heart failure, ischemic
stroke, and
 peripheral arterial disease, such as carotid
stenosis and abdominal aortic aneurysm
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17. 5/17/2023 17

18. Major Risk Factors: That Modify LDL Goals
– Age (Men:≥45 yrs, Women: ≥ 55 yrs or premature menopause without
estrogen-replacement therapy)
– Family history of premature CHD (MI or sudden death in first-degree
relative)
– Cigarette smoking
– Hypertension ( ≥ 140/90 mm Hg or on antihypertensive medication)
– Low HDL cholesterol (<40 mg/dL)
• N.B.
– Diabetes is regarded as CHD risk equivalent
– HDL ≥ 60 mg/dl counts as a “negative “risk factor: its presence removes
one risk factor from the total count
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19. Therapeutic Life Change (TLC)
• Implemented prior to considering drug therapy
• TLC may obviate the need for drug therapy, and allow for
lower doses.
• TLC include:
 Dietary therapy (reduced intake of saturated fats and cholesterol
and increased soluble fiber intake)
 physical activity (30 minutes/day for most days of the week)
 weight reduction,
 Stop smoking
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20. Dietary Interventions
• The objectives of dietary therapy are to decrease the intake
of total fat, saturated fat, and cholesterol
• Saturated fats (GOOD FATS)
– Almonds, avocados, salmon fish
– plant oils such as olive oil, peanut oil, mustard oil, sunflower oil
• Saturated fats (BAD FATS)
– Milk products like cheese, butter and ice-cream, cakes
– Meat, seafood, poultry (chicken), coconut oil and palm oil
• Trans fats (VERY BAD FATS)
– French fries and other fast foods cooked by hydrogenated oils
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21. Dietary Interventions
• Increased intake of soluble fiber(20–30 g/day) can result in useful
adjunctive reductions in total and LDL-C (5%-20%)
– Controls constipation associated to BAS (Cholestyramine)
– Demonstrated little or no effect on HDL-C or TG
– Binds chol. gut & reduces hepatic production & CL
• Fish oil supplementation provides an increased amount of the
omega-3 polyunsaturated fatty acids, such as eicosapentaenoic
acid and docosahexaenoic acid (antioxidant effect)
• Each 20 g/day ingestion of fish lowers CHD risk by 7%, and eating
fish at least once weekly should reduce CHD mortality
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22. • Weight control plus increased physical activity reduce
risk beyond LDL-C lowering, are the primary
management approach for the metabolic syndrome,
raise HDL, and reduce non-HDL-C
• Pts are given a 3-month trial (two visits 6 wks apart) of
dietary therapy and TLC before advancing to drug
therapy unless pts are at very high risk
– (eg.severe hypercholesterolemia, known CHD, CHD risk
equivalents, multiple risk factors, strong family hx).
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23. Fat Substitutes
• Olestra
– formed from the reaction of sucrose with long-chain fatty
acids.
– Approved by the FDA as a non-digestible, non-absorbable,
non-caloric fat substitute for snack foods.
– It is heat stable-suitable for fried and baked foods
– It is similar in composition to TG but not hydrolyzed in GIT by
pancreatic lipase and, consequently, is not taken up by the
intestinal mucosa
– S/E: bloating, flatulence, diarrhea
• Plant stanol/sterol esters
– Because lipids are needed to solubilize stanol/sterol esters
they are usually available in commercial margarines.

24. Pharmacologic Therapy
• Reduction of LDL reduces CHD event rates in
primary prevention, secondary intervention, and
angiographic trials
• For every 1% reduction in LDL, there is a 1%
reduction in CHD event rates
• A 1% elevation of HDL results in an approximately
2% reduction in CHD events
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25. Drug Therapy
• Despite availability of many efficacious lipid-
lowering drugs, none is effective for all
lipoprotein disorders
• Classes of drugs
 Statins
 Bile acid resins (BARs)
 Niacin
 Fibrates
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26. Effects of drug therapy on lipids and lipoproteins
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27. Statin Therapy
• First choice -most potent LDL-lowering agents
• They interrupt the conversion of HMG-CoA to
mevalonate, the rate-limiting step in de novo
cholesterol biosynthesis, by inhibiting HMG-CoA
reductase
 Lovastatin, pravastatin, simvastatin, fluvastatin, and
atorvastatin
 Rosuvastatin is the most potent statin currently on the
market
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28. Statins
• TC & LDL-C are reduced in a dose-related
fashion by at least 30% on average when
added to dietary therapy
 Reduced synthesis of LDL-C as well as enhanced
catabolism of LDL mediated through LDL
receptors
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29. Combinations
• BAS plus lovastatin
– Further reduce enterohepatic circulation of bile acid
• Statin plus Ezetimibe
 Ezetimibe inhibits cholesterol absorption across the
gut border and adds 12% to 20% further reduction
when combined with a statin or other drugs
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30. Side Effects
• Elevation of LFT’s (ALT) > 3X the upper limit
• Serious muscle toxicity (myopathy) occurs in
<0.6% of pts
• Lens opacities
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31. Bile Acid Resins (BARs)
• Include: cholestyramine, colesevelam, colestipol
• MOA
• They bind to bile acids in the intestinal lumen,
with concurrent interruption of enterohepatic
circulation of bile acids
– markedly increased excretion of acidic steroids in the
feces
• Decrease T-C & LDL-C concentrations
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32. BAR
• The increase in hepatic cholesterol biosynthesis may
be increased in liver consequently, BARs may aggravate
hypertriglyceridemia in pts with combined
hyperlipidemia.
• Side effects: GI complaints of constipation, bloating,
epigastric fullness, nausea, and flatulence are common
 Managed by increasing fluid intake, increase bulk in diet,
& use stool softeners
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33. • Other potential adverse effects include:
– Impaired absorption of fat-soluble vit. A, D, E, & K;
– Hypernatremia and hyperchloremia;
– Gastrointestinal obstruction; and
• DI: Reduced bioavailability of acidic drugs such as
coumarin, digitoxin, nicotinic acid, thyroxine,
acetaminophen, hydrocortisone,
hydrochlorothiazide, loperamide, and possibly
iron
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34. BAR-adherence
• At least 40% of patients discontinue therapy within 1
year
• Adherence rates can be improved with pharmacist
interventions
• Adverse effects can be managed by increasing fluid
intake, increase bulk in diet, & use stool softeners
• major limiting complaint is their gritty texture and
bulk- minimized by mixing the powder with orange
drink or juice.
• Tablet forms of BAR should help to improve compliance
with this form of therapy

35. BAR
• Colestipol may have better palatability
because it is odorless and tasteless
• Colesevelam is the newest BAR, and total and
LDL-C reduction are dose related.
• Adverse effects are common at higher doses-
• BARs are used in combination with other
drugs since low doses are better tolerated well

36. Niacin
• Reduces hepatic synthesis of VLDL, thus reduced
synthesis of LDL
• Tx. of primary hypercholesterolemia alone or in
combination with BARs
• Niacin also increases HDL
• Used primarily for tx of mixed hyperlipidemia
• First-line agent or alternative for tx. of
hypertriglyceridemia and diabetic dyslipidemia
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37. Niacin Side Effects
• GI- intolerance and flushing are common problems
• Acanthosis nigricans, a darkening of the skin in skinfold
areas and an external marker of insulin resistance, may
be seen with high doses of niacin
• Sustained-release products may minimize these
complaints in some patients
• Elevated liver function tests, hyperuricemia, and
hyperglycemia
• Preexisting gout and diabetes may be exacerbated
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38. NIACIN S/E
• Cutaneous flushing and itching appear to be
prostaglandin mediated
– Reduced by aspirin 325 mg given shortly before
niacin ingestion
– Take dose with meals and slowly titrate the dose
upward may minimize these effects
– Laropiprant is a selective antagonist of the
prostaglandin D2 receptor -vasodilation
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39. • Niacin is contraindicated in patients with active
liver disease.
• Niaspan is reported to have fewer dermatologic
reactions and a low risk for hepatoxicity.
• Concomitant alcohol and hot drinks may
magnify flushing and pruritus with niacin and
should be avoided at the time of ingestion.
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40. Fibrates
• Fibric acid (clofibrate , gemfibrozil, fenofibrate)
• monotherapy is effective in reducing VLDL, but a reciprocal
rise in LDL may occur,
– and total cholesterol values may remain relatively unchanged
• Gemfibrozil and fenofibrate are used much more commonly
than clofibrate
• Gemfibrozil reduces synthesis of VLDL and, to a lesser
extent, apolipoprotein B, with a concurrent increase in the
rate of removal of triglyceride-rich lipoproteins from plasma
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41. Fibrates
• Plasma HDL concentrations may rise 10% to 15% or
more with fibrates
• All reduce LDL-C by 20% to 25% in patients with
heterozygous familial hypercholesterolemia
• Side effects
– Gastrointestinal complaints, rash, dizziness and transient
elevations in transaminase levels and alkaline phosphatase
– Gemfibrozil and fenofibrate may enhance the formation of
gallstones but the rate is low (0.5%–7%)
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42. Fibrates
• Fibrates potentiate the effects of oral
anticoagulants
– PT and INR should be monitored very closely
• A myositis syndrome of myalgia, weakness,
stiffness, malaise, and elevations in creatinine
phosphokinase and AST more common in pts
with renal insufficiency
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43. Ezetimibe
• Ezetimibe interferes with the absorption of
cholesterol from the brush border of the intestine
– a novel mechanism that makes it a good choice for
adjunctive therapy.
• It is approved as both monotherapy and for use
with a statin.
• The dose is 10 mg once daily, given with or
without food.
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44. Fish oil supplementation (Lovaza)
• Lovaza (omega-3-acid ethyl esters) is a
prescription form of concentrated fish oil EPA 465
mg and docosahexaenoic acid 375 mg.
• The daily dose is 4 g/day ( qd or bid)
• This product lowers triglycerides by 14% to 30%
and raises HDL by about 10%.
• Side effect: thrombocytopenia and bleeding
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45. Evaluation of Outcomes
• Monitor T-C, LDL-C, HDL-C, and TG for pts being
treated
• Follow up interval is dependent on the severity of
illness, and pts with known CAD or multiple risk
factors should be monitored more closely
• Less commonly used laboratory measurements
include C-reactive protein, homocysteine,
apolipoprotein B, and lipoproteinT-C
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