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DYSLIPIDEMIA
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Learning Objectives
 To define and classify dyslipidemia.
 To obtain relevant history and physical exam.
 To risk stratify patients.
 To decide to treat based on presence of coronary heart disease
(CHD) risk factors and LDL level.
 To list the different therapeutic options.
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DEFINITION
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Definition
 Hyperlipidemias are abnormalities of lipoprotein
metabolism and include elevations of total cholesterol,
LDL cholesterol, or triglycerides; or deficiencies of HDL
cholesterol.
 These disorders can be acquired or familial (such as
familial hypercholesterolemia).
 Hyperlipidemia is a major modifiable risk factor for
coronary heart disease.
 Studies found a graded relationship between the total
cholesterol concentration and coronary risk.
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CLASSIFICATION
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Classification of Hyperlipidemia
Type Laboratory findings Characteristics
Chylomicronemia Elevated TG (700-10,000), 5% of all hyperlipoproteinemias
(Type I-younger, V-older) VLDL, chylomicrons Serum lipemic, pancreatitis, eruptive xanthomas
Hypercholesterolemia Elevated total cholesterol 10% of all hyperlipoproteinemias
(Type IIa) (300-500), LDL (>250) LDL receptor defect.
Premature coronary heart disease (CHD), tendon
xanthomas, arcus senilis
Combined Hyperlipidemia Elevated total cholesterol 40% of all hyperlipoproteinemias
(Type IIb) (250-350), LDL, and VLDL Different patterns in different family members
cholesterol and/or elevated VLDL overproduction by the liver
TG. Premature CHD, xanthelasma, arcus senilis
Dysbetaliproteinemia Elevated total cholesterol < 1% of all hyperlipoproteinemias
(Type III) (300-600), TG (400-800). Abnormal apolipoprotein E
In addition to genotype, need other factors to
express (DM, obesity, hypothyroidism).When
patients lose weight, lipids may normalize
Premature CHD, palmar xanthoma, peripheral
vascular disease in nonsmokers.
Hypertriglyceridemia Elevated total cholesterol, 45% of all hyperlipoproteinemias
(Type IV) TG, and VLDL. LDL low. Delayed VLDL catabolism
Severe Polygenic Elevated LDL (>220) Multifactorial
Hypercholesterolemia
Defective Apolipoprotein Levels similar to Decreased LDL receptor affinity
B Hypercholesterolemia (IIa) Premature CHD, tendon xanthomas
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Hypertriglyceridemia
 In isolated hypertriglyceridemia, therapy depends on the
triglyceride level.
 Patients with triglycerides > 500 mg/dL are at increased risk of
developing acute pancreatitis.
 This risk increases very significantly as triglycerides increase to
> 1000 mg/dL.
 Although triglycerides may not normalize with the commonly
used treatments, the risk of pancreatitis is reduced.
 In patients with moderate hypertriglyceridemia (200-500
mg/dL) who have two or more CHD risk factors, an HMG
reductase inhibitor may be considered for first line therapy.
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Triglycerides and atherosclerosis

 Elevated triglyceride levels are independently associated with
cardiovascular risk, particularly coronary risk . However, the
causal relationship between hypertriglyceredemia and
atherosclerosis is not clear.
 Cholesterol accumulates in atherosclerotic arteries in large
quantities; however, triglyceride only accumulates to a minor
extent.
 It is uncertain whether lowering triglyceride levels reduces
cardiovascular risk.
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Secondary Causes of Dyslipidemia

 Type 2 diabetes mellitus
 Excessive alcohol consumption
 Cholestatic liver diseases
 Chronic renal failure
 Nephrotic syndrome
 Hypothyroidism
 Cigarette smoking
 Obesity
 Drugs:Thiazide diuretics, beta blockers, oral estrogens,
antipsychotics (clozapine & olanzapine)
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SCREENING
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U.S. Preventive Services Task Force Screening

Recommendations (1)
 Screening men: The U.S. Preventive Services Task Force
(USPSTF) strongly recommends screening men 35 years and
older for lipid disorders (A recommendation).
 The USPSTF recommends screening men 20 to 35 years of age
for lipid disorders if they are at increased risk of coronary heart
disease (CHD) (B recommendation).
 Screening women at increased risk: The USPSTF strongly
recommends screening women 45 years and older for lipid
disorders if they are not at increased risk of CHD (A
recommendation).
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U.S. Preventive Services Task Force Screening

Recommendations (2)
 The USPSTF recommends screening women 20 to 45 years of
age for lipid disorders if they are at increased risk of CHD (B
recommendation).
 Screening young men and all women not at increased risk: The
USPSTF makes no recommendation for or against routine
screening for lipid disorders in men 20 to 35 years of age, or in
women 20 to 45 years who are not at increased risk of CHD (C
recommendation).
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EVALUATION
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History
 Dyslipidemia is typically asymptomatic.
 It is a laboratory diagnosis.
 History elements:
o Dietary habits
o Smoking history
o Exercise habits
o Personal history of thyroid or coronary heart disease
o Familial history of coronary heart disease
o Previous levels of increased cholesterol
o Current medications.
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Physical Exam
 A general physical exam with focus on:
o Weight
o Height
o Blood pressure
o Waist circumference
o Xanthomas
o Xanthelasma
o Presence of corneal arcus.
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Diagnostic Tests
 The usual screening tests for dyslipidemia are total cholesterol,
HDL cholesterol levels, LDL cholesterol levels and triglycerides.

 Abnormal screening test results should be confirmed by a

repeated sample on a separate occasion.

 Other tests are needed if diabetes, renal, liver or thyroid

diseases are suspected..
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LDL and Non-HDL Calculation

 LDL can be calculated using the Friedenwald equation:
Total cholesterol – ( HDL + Triglycerides/5)

 If triglyceride level is > 400 mg/dl, the blood sample has to be

subjected to a non routine special ultra centrifugation
technique.

 Non-HDL cholesterol: total cholesterol - HDL cholesterol

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Additional Tests
 Any person with elevated LDL cholesterol or any other form of
hyperlipidemia should undergo clinical or laboratory
assessment to rule out secondary dyslipidemia before initiation
of lipid-lowering therapy.

 Causes of secondary dyslipidemia include diabetes mellitus,

hypothyroidism, obstructive liver disease, chronic renal failure,
and some medications.

Risk Stratification- Framingham Risk Score
STEP 1:: Determine major
cardiovascular risk factors
- Smoking
- Hypertension
- Low HDL <40
- Family history of
premature CHD ( Men 1st
degree relative <55 year;
Women 1st degree relative
<65)
- Age (Men ≥45; Women
≥55)
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STEP 2:Determine CHD risk STEP 3: Calculate
equivalent conditions Framingham risk
- Diabetes Mellitus If two or more major
- Peripheral vascular cardiovascular risks, but no
disease CHD risk equivalent
- Carotid artery disease conditions, calculate
- Abdominal aortic Framingham risk:
aneurysm Risk>20%; high risk
Risk 10-20%; moderately
high risk
Risk <10%; moderate risk.
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MANAGEMENT
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Management
 Decision to treat is based on presence of coronary heart
disease (CHD) risk factors and LDL level.
 Treatment options include dietary and pharmacologic therapy
with advice regarding other cardiovascular risk factors.

Dyslipidemia Medication General Diet

LDL: 100-129 mg/dL None None
LDL: 130-159 mg/dL If CHD present All
LDL: 160-189 mg/dL If CHD or 2 risk factors for CHD are
present
LDL: 190-220 mg/dL All men above 35 y or
postmenopausal women
LDL: >=220 mg/dL All
Triglycerides 200-500 mg/dL Evaluate other risks
Triglycerides > 500mg/dL All
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Non-Pharmacologic Treatment
 Stop smoking
 Diet
o General diet advice: reduce saturated fat and substitute with
monosaturated and polyunsaturated fats; reduce total
calories to maintain ideal body weight.
o Step I (10% of calories saturated fat): cholesterol
<300mg/day, total fat <30% of calories.
o Step II (7% of calories saturated fat): cholesterol
<200mg/day, total fat <30% of calories.
 Exercise: 30 minutes of aerobic activity at least 5 days a week.
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Pharmacologic Treatment (1)

HMG CoA reductase inhibitors (statins)
 Most potent agents.
 Lower cholesterol, LDL and Triglyceride with minimal increase
in HDL.
 Considered as first line of treatment.
 Indicated in type IIa, type IIb, high LDL and primary
hypercholesterolemia.
 Evening doses more effective due to higher cholesterol
synthesis.
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Pharmacologic Treatment (2)

Nicotinic acid (Niacin)
 Lower LDL and Triglyceride; moderate increase in HDL.
 Indicated in elevated cholesterol with high LDL and low HDL.
 Advise patients to take it with food and avoid hot beverages
and alcohol at time of tablet intake.
 Aspirin 325 mg can be taken before the dose to decrease the
hot flashes.
 Check uric acid levels if symptoms of gout occurs.
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Pharmacologic Treatment (3)

Bile Acid Sequestrants (Cholestyramine)
 Decreases LDL; increase HDL; no effect on Triglyceride.
 Good for combination therapy.
 Monitor with fasting lipid at 6-12 weeks then periodically every
6 months.
 Powder must be mixed with liquid prior to ingestion; mix and
leave in fridge overnight.
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Pharmacologic Treatment (4)

Fibric acids
 Decreases Triglyceride and increase HDL; variable effect on LDL.
 Indicated in type IIb with triad of high Triglyceride, low HDL and
high LDL.
 Dose reductions in patients with renal insufficiency.
Omega 3 fatty acids
 Decrease Triglyceride.
 Side effects such as fishy taste and belching are uncommon;
caution in patients with fish allergy.
Ezetimibe
 Reduces LDL-C and increases HDL.
 Indicated in combination therapy.
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Pharmacologic Treatment (5)

Alirocumab and Evolocumab
 They are monoclonal antibodies targeting PCSK9.
 They are used in:
o Treatment of familial hypercholesterolemia
o Patients with atherosclerotic heart disease who require
additional lowering of LDL-cholesterol.
Summary of the Effect of Lipid Lowering Classes
Class Effect on Effect on Effect on
LDL-C HDL-C Triglyceride

Statins   
Bile acid sequestrants
  

Nicotinic acid   

Fibric acids  Or   
Omega-3 fatty acids
  

Ezetimibe   
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Management Tips
 Statins are generally considered first line therapy for high LDL.
 Combinations of agents (statins + bile acid sequestrants) may
be needed to achieve goal, especially if cholesterol>300 mg/dL.
 Combinations may also allow the use of lower doses of each
agent with reduced side effects.
 HDL >35mg/dL should be an additional goal in patients at risk
or post-myocardial infarction.
 Low HDL can best be increased with Niacin or Gemfibrozil.
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Drug Monitoring
 Fasting lipid panel, serum transaminases, CPK at base line.
 Fasting lipid panel, at 6–12 weeks after start or elevation in
dose, then periodically approximately every 6 months.
 If the transaminases are increased they should be followed
until the abnormality resolves. If transaminases increase more
than 3 times normal and persist, then stop medication.
 Check CPK if muscle symptoms develop.
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Follow up and Goals of Treatment

Risk factor Cholesterol level Recheck LDL goal (mg/dl)

No CHD & No risk Less than 240 1 year < 160

factors
More than 240 3-6 months < 160

No CHD & Less than 2 Less than 240 1 year < 160
CHD risk factors (optimal<130)
More than 240 3-6 months < 130
(optimal<100)
No CHD &2 or more Any level 3 months < 100 (optimal
CHD risk factors OR <70)
Diabetes
CHD present Any level 3 months < 100 (optimal
<70)
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INDICATIONS FOR
REFERRAL
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Indications for Referral

 Dietitian for Step-Two Diet or another 3 month trial of Step-
One Diet - if goal not reached after 3 months on Step-One Diet.

 Endocrinologist if
o Unsure about diagnosis or treatment protocol or patient does not
respond to initial drug therapy
o Cases of familial hyperlipidemias.
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References
1. Rosenson R. Approach to the patient with hypertriglyceridemia.
Uptodatecom. 2015. Available at:
http://www.uptodate.com/contents/approach-to-the-patient-
with-hypertriglyceridemia
2. Pignone M. Treatment of lipids (including hypercholesterolemia)
in primary prevention. Uptodatecom. 2015. Available at:
http://www.uptodate.com/contents/treatment-of-lipids-
including-hypercholesterolemia-in-primary-prevention
3. Aafp.org. Hyperlipidemia - American Family Physician. 2015.
Available at:
http://www.aafp.org/afp/topicModules/viewTopicModule.htm?to
picModuleId=13
4. Falleroni A. Pharmacologic Treatment of Hyperlipidemia -
American Family Physician. Aafporg. 2015. Available at:
http://www.aafp.org/afp/2011/0901/p551.html