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Hyperlipidemia

Presentation Objectives
• State the major goals of the Adult Treatment
Panel (ATP) III Guidelines.
• Describe the new risk stratification process,
low density lipid (LDL) goals and the
Framingham assessment.
• State the major medications used to lower
cholesterol and their common side effects.
• Describe the management of low high
density lipids (HDL), elevated triglycerides
(TGs) and the metabolic syndrome.
National Cholesterol
Education Program (NCEP)
• Adult treatment Panel I (1988)
– primary prevention in those with high LDL
• Adult treatment panel II(1993)
– reaffirmed the above, plus emphasis on
intensive management of LDL in those
with established coronary heart disease
(CHD)
• Adult treatment panel III (2001)
New features of ATP III

• Focus on multiple risk factors
• Modification of lipid and lipoprotein
classification
• Support for implementation
ATP III: Focus on Multiple Risk
Factors
• Diabetes becomes equivalent in risk to
CHD
• Uses Framingham criteria to intensify
treatment in some of those with
multiple risk factors
• Identifies those with the metabolic
syndrome for intensive lifestyle
changes
ATP III: Modification of Lipid
Classification
• Identifies LDL cholesterol of < 100
mg/dl as optimal
• Raises limit of low HDL from 35mg/dl
to 40mg/dl.
• Lowers the triglyceride classification
levels to give more attention to
moderate elevations.
ATP III: Support for
Implementation
• Recommends a complete lipoprotein
profile as the preferred initial test
• Presents strategies for promoting
adherence to treatment
• Recommends treatment beyond LDL
lowering for persons with triglycerides
>200mg/dl.
What is a Lipid profile?
• Total cholesterol
• LDL cholesterol
• HDL cholesterol
• Triglycerides
Targets of therapy
• Primary target of therapy is LDL cholesterol.
Relationship between LDL level and CHD risk
is continuous
• HDL cholesterol
• Non-HDL cholesterol (this includes the
atherogenic remnant lipoprotein portion
measured by very low density lipids [VLDL],
which is calculated by total cholesterol-HDL
or LDL + VLDL. Normal value for VLDL <30.)
• Triglycerides
Lipid Profile calculations

• TC = LDL + HDL + VLDL
• VLDL = TG/5
• LDL = TC – (HDL + VLDL)
Who Should be Screened?
• All adults > 20 years
– Fasting Lipid profile ( 9-12 hr fast)
– Once every 5 years
– If non fasting sample obtained, then only
total cholesterol and HDL cholesterol are
usable. Further testing with fasting Lipid
profile if cholesterol > 200 and HDL <40.
ATP III Classification of LDL
cholesterol
<100 Optimal

100-129 Near optimal

130-159 Borderline high

160-189 High

> 190 Very high
ATP III Classification of Total
and HDL cholesterol
Total cholesterol
<200 Desirable
200-239 Borderline high
>240 High

HDL cholesterol
<40 Low
>60 High
Identify Conditions that confer high
risk for CHD (CHD risk equivalents)
• Clinical CHD
• Symptomatic carotid artery disease
• Peripheral arterial disease
• Abdominal aortic aneurysm
• Diabetes Mellitus
• Multiple risk factors that confer 10
year risk for CHD > 20%
Major Risk Factors
• Major risk factors other than LDL cholesterol
that modify LDL goals
– Cigarette smoking
– Hypertension ( with or without medication)
– Low HDL Cholesterol
– Family history of premature CHD (<55 M, <65F)
– Age (M>45, F>55)
• HDL cholesterol >60 removes one risk factor
from the total count
Categories of Risk that Modify
LDL Goals
Risk Category LDL Goal (mg/dl)

CHD & CHD risk eq. <100
Multiple (2+) RFs <130
0 to 1 RFs <160
Risk Assessment
• Two steps
– 1. Count risk factors
– 2. If 2+ risk factors present then calculate
10yr risk using Framingham risk scoring.
This allows better targeting of intensive
therapy to those that will benefit most
from it.
– Framingham assessment (age, total
cholesterol, systolic blood pressure,
treatment for hypertension, cigarette
smoking)
Secondary hyperlipidemia
• Need to exclude the following, prior to
initiation of treatment:
– Diabetes
– Hypothyroidism
– obstructive liver disease
– Chronic renal failure
– Drugs eg. progestins, anabolic steroids,
corticosteroids.
LDL Cholesterol Goals
Risk Category LDL Goal Drug Rx level

CHD/risk eq. <100mg/dl >130mg/dl

2+ RFs <130mg/dl -10yr risk high
>130mg/dl
-10yr risk low
>160mg/dl

0-1 RF <160mg/dl >190mg/dl
LDL Cholesterol Lowering
Therapy
• 1. Therapeutic Lifestyle changes

– Reduced intake of saturated fats (< 7%
calories)
– Increased soluble fiber
– Weight reduction
– Increased physical activity (decreases
VLDL, blood pressure, insulin resistance &
LDL in some people, increases HDL)
LDL Cholesterol Lowering
Therapy
• 2. Drug Therapy

• Statins
• Fibrates
• Bile Acid Sequestrants
• Nicotinic Acid
The Statins
• HMG CoA reductase inhibitors
– Reduce LDL & triglycerides (TG) , raise HDL
• Side effects
– Gastrointestinal (GI), myopathy, elevated liver
enzymes
• Contraindications
– absolute - liver disease (acute or chronic)
– Relative - concomitant use of cyclosporine,
macrolides, various antifungals, cytochrome p-450
inhibitors.
Relative efficacy of Statins
10 7 8
6
5 2
NA
0
-5
-10 -11
-10 -14 -15
-15 -19 -24
-39 -24 -32
-20 -38
-25
-30
-35
-40
Atorvastatin 10 Fluvastatin 40 Lovastatin 20 Pravastatin 20 Simvastatin 20

LDL HDL TGs
Precautions with use of
Statins
• Monitor liver function tests (LFTs)
– Baseline, 6 weeks, 12 weeks, 6 months, 1 yr and
semiannually thereafter.
– May need to check more often if dosage adjusted
– Stop statin therapy if LFTs become >3 times the
upper limit of normal.
• Monitor for myalgia
Bile Acid Sequestrants
• Cholestyramine most commonly used
• Decreases LDL (15-30%), minimal effects on
HDL and TG may actually rise.
• Side effects
– GI distress, constipation, decreased absorption of
other drugs.
• Contraindications
– Raised triglycerides (TGs)
Nicotinic acid (Niacin)
• Decreases LDL (5-25%), and TGs (20-50%)
• Increases HDL (15-35%)
• Side Effects
– Flushing, hyperglycemia, hyperuricemia, upper GI
distress and hepatotoxicity.
• Contraindications
– absolute - chronic liver disease, severe gout
– relative – diabetes mellitus, peptic ulcer disease,
hyperuricemia
Fibrates
• Most common gemfibrozil 600mg twice a day.
• Decreases LDL (5-20%) unless high TG
• Decreases TG (20-50%)
• Raises HDL (10-20%)
• Side effects
– Dyspepsia, gallstones, myopathy
• Absolute contraindications
– severe hepatic and severe renal disease
Ezetimibe (Zetia®)
• Appears to inhibit cholesterol absorption in
the small intestine at the level of the brush
border.
• Can add up to 25% additional reduction in
LDL when added to a statin or about 18%
alone.
• Up to 10% decrease in TGs and minor
increases in HDL when added to a statin.
• May be used alone in patients intolerant of
statins (up to 12% reduction in total
cholesterol).
Ezetimibe (Zetia®)
• Dosage: 10mg once daily with or without food.
• Liver function tests should be performed when
ezetimibe is added to a statin according to statin
recommendations.
• Effects of ezetimibe in patients with moderate or
severe hepatic insufficiency are unknown, so
ezetimibe is not recommended in these patients.
• In clinical trials, there was no excess of myopathy or
rhabdomyolysis associated with ezetimibe compared
with statin or placebo alone.
Management of Specific
Conditions
• 1. Very High LDL cholesterol
(>190mg/dl)

– Often genetic
– Important to screen for in early adulthood
– Need to screen families
– May require combined drug therapy.
Management of Specific
Conditions
• 2. Low HDL Cholesterol

– Strong independent predictor of CHD
– ATP III does not specify a goal of therapy
– Several possible causes e.g.: obesity, physical
inactivity, metabolic syndrome, cigarette
smoking and drugs e.g.: beta blockers and
steroids.
Management of Specific
Conditions
• 2. Low HDL Cholesterol continued:
– First reach LDL goal
– Intensify weight management and increase
physical activity
– If TGs are 200-500 mg/dl achieve non HDL goal
(essentially LDL goal + 30 for upper limit of
normal VLDL)
– If TGS<200 (isolated low HDL) and patient has
CHD or risk equivalent consider nicotinic acid or
fibrate
Management of Specific
Conditions
• 3. Elevated Triglycerides
– recent meta-analysis reveals this is an
independent risk factor for CHD
– Causes
• obesity, physical inactivity, excess alcohol
intake, cigarette smoking, meds such as beta
blockers and steroids and genetic disorders of
lipid metabolism, other diseases eg type 2
diabetes, chronic renal failure. Metabolic
syndrome most common in practice.
Management of Specific
conditions
• ATP III Classification of elevated
triglycerides:

• <150 normal
• 150-199 borderline high
• 200-499 high
• >500 very high
Management of specific
conditions
• Treatment of elevated triglycerides:
– when TGS > 500 then need to lower triglycerides
first to prevent pancreatitis.

– Otherwise need to reach LDL goal first, then non-
HDL goal (LDL goal + 30 for VLDL).

– Increase physical activity, intensify weight
management first, then use fibrates or nicotinic
acid to reduce VLDL and triglycerides.
The Management of Specific
Conditions
4. The Metabolic Syndrome:
• Any three of the following:
– 1. Abdominal Obesity
• Waist circumference ( >40 in M, >35 in F)
– 2. Triglycerides >150mg/dl
– 3. HDL Cholesterol
• <40 mg/dl in M, <50mg/dl in F
– 4. Blood Pressure >130/>85 mmHg
– 5. Fasting Glucose >110mg/dl
The Management of Specific Conditions
Treatment of the Metabolic Syndrome:
• Recognized as secondary target of risk
reduction therapy after LDL cholesterol.
– 1. Treat underlying causes
• intensify weight management
• increase physical activity
– 2. Treat risk factors if they persist after
lifestyle therapies.
• Treat HTN, Use ASA for CHD, Treat increased
triglycerides &/or Low HDL.
Interventions to Improve
Adherence
• Simplify medication regimes.
• Use good counseling techniques with patients.
• Involve patients and their families in their
care.
• Increase visits / access to achieve goals.
• Reinforce and reward compliance.
• Multidisciplinary approach within the clinic.
• Physician reminders to prompt attention to
lipid management.
Take Home Messages
• Focus on Multiple Risk Factors
• New Lipid and Lipoprotein
Classification
• New recommendations for screening
• More intensive tender loving care
• New strategies for compliance