Table of Contents

• STEP 1: Determine lipoprotein levels - obtain complete lipoprotein profile after 9- to 12-hour fast
• STEP 2: Identify presence of clinical atherosclerotic disease that confers high risk for coronary heart disease (CHD) events (CHD risk equivalent)
• STEP 3: Determine presence of major risk factors (other than LDL)
• STEP 4: If 2+ risk factors (other than LDL) are present without CHD or CHD risk equivalent, assess 10-year (short-term) CHD risk
• STEP 5: Determine risk category
• STEP 6: Initiate therapeutic lifestyle changes (TLC) if LDL is above goal
• STEP 7: Consider adding drug therapy if LDL exceeds levels shown in Step 5 table
• STEP 8: Identify metabolic syndrome and treat, if present, after 3 months of TLC
• STEP 9: Treat elevated triglycerides

STEP 1:  Determine lipoprotein levels - obtain complete lipoprotein profile after 9- to 12-hour fast.

ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)

• LDL Cholesterol - Primary Target of Therapy
  
  

  <100	Optimal
  100-129	Near Optimal/Above Optimal
  130-159	Borderline High
  160-189	High
  190	Very high

  
  
  
• Total Cholesterol
  
  

  <200	Desirable
  200-239	Borderline High
  240	High

  
  
  
• HDL Cholesterol
  
  

  <40	Low
  60	High

STEP 2: Identify presence of clinical atherosclerotic disease that confers high risk for coronary heart disease (CHD) events (CHD risk equivalent):

• Clinical CHD
• Symptomatic carotid artery disease
• Peripheral arterial disease
• Abdominal aortic aneurysm.

STEP 3: Determine presence of major risk factors (other than LDL):

Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals

• Cigarette smoking
• Hypertension (BP 140/90 mmHg or on antihypertensive medication)
• Low HDL cholesterol (<40 mg/dl)*
• Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years)
• Age (men 45 years; women 55 years)

* HDL cholesterol 60 mg/dL counts as a "negative" risk factor; its presence removes one risk factor from the total count.

Note: in ATP III, diabetes is regarded as a CHD risk equivalent.

STEP 4: If 2+ risk factors (other than LDL) are present without CHD or CHD risk equivalent, assess 10-year (short-term) CHD risk (see Framingham tables).

Three levels of 10-year risk:

• >20% -- CHD risk equivalent
• 10-20%
• <10%

STEP 5: Determine risk category:

• Establish LDL goal of therapy
• Determine need for therapeutic lifestyle changes (TLC)
• Determine level for drug consideration

LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy in Different Risk Categories.

Risk Category	LDL Goal	LDL Level at Which to Initiate Therapeutic Lifestyle Changes (TLC)	LDL Level at Which to Consider Drug Therapy
CHD or CHD Risk Equivalents (10-year risk >20%)	<100 mg/dL	100 mg/dL	130 mg/dL (100-129 mg/dL: drug optional)*
2+ Risk Factors (10-year risk 20%)	<130 mg/dL	130 mg/dL	10-year risk 10-20%: 130 mg/dL 10-year risk <10%: 160 mg/dL
0-1 Risk Factor**	<160 mg/dL	160 mg/dL	190 mg/dL (160-189 mg/dL: LDL-lowering drug optional)

* Some authorities recommend use of LDL-lowering drugs in this category if an LDL cholesterol <100 mg/dL cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify triglycerides and HDL, e.g., nicotinic acid or fibrate. Clinical judgment also may call for deferring drug therapy in this subcategory.

** Almost all people with 0-1 risk factor have a 10-year risk <10%, thus 10-year risk assessment in people with 0-1 risk factor is not necessary.

STEP 6: Initiate therapeutic lifestyle changes (TLC) if LDL is above goal.

TLC Features

• TLC Diet:
• Saturated fat <7% of calories, cholesterol <200 mg/day
• Consider increased viscous (soluble) fiber (10-25 g/day) and plant stanols/sterols (2g/day) as therapeutic options to enhance LDL lowering
• Weight management
• Increased physical activity

STEP 7: Consider adding drug therapy if LDL exceeds levels shown in Step 5 table:

• Consider drug simultaneously with TLC for CHD and CHD equivalents
• Consider adding drug to TLC after 3 months for other risk categories.

Drugs Affecting Lipoprotein Metabolism

Drug Class	Agents and Daily Doses	Lipid/Lipoprotein Effects	Side Effects	Contraindications
HMG CoA reductase inhibitors (statins)	Lovastatin (20-80 mg), Pravastatin (20-40 mg), Simvastatin (20-80 mg), Fluvastatin (20-80 mg), Atorvastatin (10-80 mg), Cerivastatin (0.4-0.8 mg)	LDL-C   18-55% HDL-C   5-15% TG         7-30%	Myopathy Increased liver enzymes	Absolute: Active or chronic liver disease Relative: Concomitant use of certain drugs*
Bile acid Sequestrants	Cholestyramine (4-16 g) Colestipol (5-20 g) Colesevelam (2.6-3.8 g)	LDL-C   15-30% HDL-C   3-5% TG        No change or increase	Gastrointestinal distress Constipation Decreased absorption of other drugs	Absolute: dysbeta-lipoproteinemia TG >400 mg/dL Relative: TG >200 mg/dL
Nicotinic acid	Immediate release (crystalline) nicotinic acid (1.5-3 gm), extended release nicotinic acid (Niaspan ®) (1-2 g), sustained release nicotinic acid (1-2 g)	LDL-C   5-25% HDL-C   15-35% TG       20-50%	Flushing Hyperglycemia Hyperuricemia (or gout) Upper GI distress Hepatotoxicity	Absolute: Chronic liver disease Severe gout Relative: Diabetes Hyperuricemia Peptic ulcer disease
Fibric acids	Gemfibrozil (600 mg BID) Fenofibrate (200 mg) Clofibrate (1000 mg BID)	LDL-C   5-20% (may be increased in patients with high TG) HDL-C   10-20% TG       20-50%	Dyspepsia Gallstones Myopathy	Absolute: Severe renal disease Severe hepatic disease

* Cyclosporine, macrolide antibiotics, various anti-fungal agents, and cytochrome P-450 inhibitors (fibrates and niacin should be used with appropriate caution).

STEP 8: Identify metabolic syndrome and treat, if present, after 3 months of TLC.

Clinical Identification of the Metabolic Syndrome - Any 3 of the Following:

Risk Factor	Defining Level
Abdominal obesity*  Men  Women	Waist circumference**  >102 cm (>40 in)  >88 cm (>35 in)
Triglycerides	150 mg/dL
HDL cholesterol  Men  Women	<40 mg/dl <50 mg/dl
blood pressure	130/85 mmHg
Fasting glucose	110 mg/dL

* Overweight and obesity are associated with insulin resistance and the metabolic syndrome. However, the presence of abdominal obesity is more highly correlated with the metabolic risk factors than is an elevated body mass index (BMI). Therefore, the simple measure of waist circumference is recommended to identify the body weight component of the metabolic syndrome.

** Some male patients can develop multiple metabolic risk factors when the waist circumference is only marginally increased, e.g., 94-102 cm (37-39 in). Such patients may have a strong genetic contribution to insulin resistance. They should benefit from changes in life habits, similarly to men with categorical increases in waist circumference.

Treatment of the metabolic syndrome

• Treat underlying causes (overweight/obesity and physical inactivity):
• Intensify weight management
• Increase physical activity
• Treat lipid and non-lipid risk factors if they persist despite these lifestyle therapies:
• Treat hypertension
• Use aspirin for CHD patients to reduce prothrombotic state
• Treat elevated triglycerides and/or low HDL (as shown in Step 9 below)

STEP 9: Treat elevated triglycerides.

ATP III Classification of Serum Triglycerides (mg/dL)

< 150	Normal
150-199	Borderline high
200-499	High
500	Very high

Treatment of elevated triglycerides (150 mg/dL)

• Primary aim of therapy is to reach LDL goal.
• Intensify weight management.
• Increase physical activity.
• If triglycerides are 200 mg/dL after LDL goal is reached, set secondary goal for non-HDL cholesterol (total - HDL) 30 mg/dL higher than LDL goal.

Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals for Three Risk Categories

Risk Category	LDL Goal (mg/dL)	Non-HDL Goal (mg/dL)
CHD and CHD Risk Equivalent (10-year risk for CHD >20%)	<100	<130
Multiple (2+) Risk Factors and 10-year risk 20%	<130	<160
0-1 Risk Factor	<160	<190

If triglycerides 200-499 mg/dL after LDL goal is reached, consider adding drug if needed to reach non-HDL goal:

• intensify therapy with LDL-lowering drug, or
• add nicotinic acid or fibrate to further lower VLDL.

If triglycerides 500 mg/dL, first lower triglycerides to prevent pancreatitis:

• very low-fat diet (15% of calories from fat)
• weight management and physical activity
• fibrate or nicotinic acid
• when triglycerides <500 mg/dL, turn to LDL-lowering therapy.

Treatment of low HDL cholesterol (<40 mg/dL)

• First reach LDL goal, then:
• Intensify weight management and increase physical activity.
• If triglycerides 200-499 mg/dL, achieve non-HDL goal.
• If triglycerides <200 mg/dL (isolated low HDL) in CHD or CHD equivalent, consider nicotinic acid or fibrate.