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 <200 200-239 >240 HDL cholesterol <40 >60

Desirable Borderline high High Low 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

CHD & CHD risk eq.Multiple (2+) RFs0 to 1 RFs

LDL Goal (mg/dl)

<100 <130 <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 GoalsRisk Category

CHD/risk eq.

LDL Goal

<100mg/dl

Drug Rx level

>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

-39

6

-19-24

NA

-14

-24

7

-10

-32

2

-11

-38

8

-15

-40

-35

-30

-25

-20

-15

-10

-5

0

5

10

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

• 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

4. The Metabolic Syndrome:

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.

The Management of Specific Conditions

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