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
<100 100-129 130-159 160-189 > 190 Optimal Near optimal Borderline high High 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 CHD & CHD risk eq. Multiple (2+) RFs 0 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 Goals
Risk Category LDL Goal CHD/risk eq. <100mg/dl 2+ RFs <130mg/dl Drug Rx level >130mg/dl -10yr risk high >130mg/dl -10yr risk low >160mg/dl >190mg/dl

0-1 RF

<160mg/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 5 0 -5 -10 -15 -20 -25 -30 -35 -40 Atorvastatin 10 Fluvastatin 40 LDL Lovastatin 20 HDL Pravastatin 20 TGs Simvastatin 20 -39 -19 -24 -14 -24 -32 -38 -10 -11 6 NA 7 2 8

-15

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: • • • • <150 150-199 200-499 >500 normal borderline high high 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 nonHDL 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

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