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`National Cholesterol
`Education Program ·
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`Adult Treatment Panel· III ·
`Report
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`2001
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`ATP III Outline
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`Acknowledgments ............................................• .' .......................................•...•..•.........•••..............• ix
`National Cholesterol Education Program Expert Panel on Detection, Evaluation, and
`Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) .................. .' ...... ix
`Executive Committee Advisor and Reviewers ........................................................................ ix
`National Cholesterol Education Program Coordinating Committee ....................................... ix
`
`I. Background and Introduction .........•..........•.....•..........••..••..•.•.•.•.•.•.............. · ...........••••.•....... I-1
`1. Development of an evidence-based report ........................................................................ I-1
`2. Features of ATP III similar to those of ATP I and II ........................................................ I-2
`3. New features of ATP III ................................................................................................... I-3
`4. Relation of ATP III to NCEP's public health approach ................................................... I-4
`5. Relation of ATP III to other clinical guidelines ................................................................ 1-5
`
`. II. Rationale for Intervention .............•...... ~ ............................................................................ 11-1
`l. Basic description oflipids and lipoproteins ..................................................................... II-I
`2. LDL cholesterol as the primary target of therapy .... : ....................................................... II-I
`a. Serum LDL cholesterol as a major cause of CHD ..................................................... II-2
`b. Serum LDL cholesterol as target of therapy .............................................................. 11-4
`c. Categories and classification of total cholesterol and LDL cholesterol.. ................. ;.Il-7
`3. Other lipid risk factors ........................................................ , ........ · .............................. : ..... II-8
`a. Triglycerides .............................................................................................................. Il-8
`I) Elevated serum triglycerides (and triglyceride-rich lipoproteins) as a risk
`factor ........................................................................ ~ ................................................ 11-8
`2) Lipoprotein remnants as atherogenic lipoproteins ............................................... II-8
`3) VLDL cholesterol as a marker for remnant lipoproteins ..................................... II-9
`4) Causes of elevated serum triglyceride ........................................................... : ..... 11-9
`5) Categories of serum triglycerides ........................................................................ II-9
`6) Elevated serum triglycerides and triglyceride-rich lipoproteins as targets of
`therapy ........................... : ................................................ : .................. , ..................... II-I 0
`b. Non-HDL cholesterol. ......................................... ; .................................. " ................. II-I I
`I) Non-HDL cholesterol as a risk factor .............................................. : ................. 11-11
`2) Non-HDL cholesterol as a secondary target of therapy .................................... 11-12
`c. High density lipoproteins (HDL) ........................... ; ................................................. 11-13
`I) Low HDL cholesterol as an independent risk factor for CHD .......................... II-13
`2) Causes oflow HDL cholesterol.. ....................................................................... 11-14
`3) Classification of serum HDL cholesterol .......................................................... II-15
`4) Low HDL cholesterol as a potential target oftherapy ....................................... 11-16
`d. Atherogenic dyslipidemia ........................................................................................ 11-16
`I) Atherogenic dyslipidemia as a "risk factor" ...................................................... 11-16
`2) Atherogenic dyslipidemia as a target of therapy ......................................... ~ ..... 11-17
`4. Nonlipid risk factors ...................................................................................................... 11-22
`a. Modifiable risk factors ....................... : ......................................................... · ............ II-23
`I) Hypertension ...................................................................................................... 11-23
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`2) Cigarette smoking .............................................................................................. 11-24
`3) Diabetes ................................ : ............................................................................... 11-24
`4) Overweight/obesity ............................................................................................ ll-25
`5) Physical inactivity ............................................................................................... 11-26.
`6) Atherogenic diet ................................................................................................ 11-27
`b. Nonmodifiable risk factors ...................................................................................... Il-28
`1) Age ..................................................................................................................... 11-28
`2) Male sex ............................................................................ : ................................. 11-28
`3) Family history of premature CHD ..................................................................... 11-29
`5. Emerging risk factors .................................................................................................. , .... 11-30
`a. Emerging lipid risk factors ....................... , ............................................................... 11-31
`1) Triglycerides ...................................................................................................... ll-31
`2) Lipoprotein remnants ......................................................................................... 11-31
`3) Lipoprotein (a) ................................................................................................... 11-32
`4) Small LDL particles ................................... c ••••••••••••••••••••••••••••••••••••••••••••••••••••••• 11-33
`5) HDL subspecies ....................................................... ; ......................................... 11-33
`6) Apolipoproteins ................................................................................................. 11-33
`a) Apolipoprotein B ........................................................................................... 11-33
`b) Apolipoprotein Al ........................................................................................ 11-34
`7) Total cholesterol/HDL-cholesterol ratio ............................................................ II-34
`b. Emerging nonlipid risk factors ................ : ........................... ~ .................................... II-34
`1) Homocysteine .................................................................................................... 11-34
`2) Thrombogenic/hemostatic factors ..................................................................... II-35
`3) Inflammatory markers ....................................................................................... 11-36
`4) Impaired fasting glucose .................................................................................... II-36
`c. Subclinical atherosclerotic disease ........................................................................... II-3 7
`1) Ankle-brachial blood pressure index (ABl) ...................................................... 11-37
`2) Tests for myocardial ischemia ........................................................................... II-37
`3) Tests for atherosclerotic plaque burden .............................. ~ .............................. II-38
`a) Carotid intimal medial thickening ................................................... : ........... II-38
`b) Coronary cal.cium ........................................................................................ 11-38
`6. Metabolic syndrome ....................................................................................................... ll-39
`a. Metabolic syndrome as multiple, interrelated factors that raise risk ....................... II-39
`b. Diagnosis of metabolic syndrome ............................................................................ II-40
`c. Metabolic syndrome as a target of therapy .............................................................. IJ-41
`7. Primary prevention: persons without established CHD ...................................... : .......... II-42
`a. Scope of primary prevention .................................................................................... 11-42
`b. Clinical strategy in primary. prevention effort ......................................................... 11-42
`c. Concepts of short-term and long-term prevention ................................................... 11-43
`d. Role of LDL lowering in short-term and long-term primary prevention ................. II-43
`e. Risk assessment in primary prevention ............... '. .................................................... II-44
`f. Primary preventi1:m with lifestyle changes ............................................................... II-46
`I) Basis for lifestyle recommendations for primary prevention ............................ II-46
`2) Dietary clinical trials of cholesterol lowering ................................................... 11-46
`3) Linkage of public health approach and clinical approach in
`primary prevention .................................................................................................. Il-46
`g. Effectiveness ofLDL-lowering drugs in primary prevention .................................. 11-46
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`h. Selection of persons for short-term risk reduction with LDL-lowering drugs ........ II-47
`i. Selection of older persons for short-term, primary prevention ................................. 11-48
`j. Selection of persons for long-term primary prevention in the clinical setting ......... 11-49
`k. LDL goals in primary prevention ............................................................................ 11-54
`8. Secondary prevention: persons with CHD ..................................................................... 11-56
`a. Secondary prevention of recurrent CHD ................................................... , .............. II-56
`b .. Effects of lipid-lowering therapy on stroke ............................................................. II-62
`9. Total mortality considerations and therapeutic safety ................................................... Il-62
`J 0. Magnitude of reduction in CHO risk ........................................................................... II-65
`i· 1. CHO as a risk indicator ................................................................................................ II-66
`12. Concept of CHO risk equivalents ................................................................................ 11-67
`a. Other forms of clinical atherosclerotic disease ............. ~ .......................................... 11-67
`l) Peripheral arterial disease (PAD) ...................................................................... II-67
`2) Carotid artery disease ........................................................................................ II-70
`3) Abdominal aortic aneurysm (AAA) .................................................................. 11-73
`b. Diabetes as a CHO risk equivalent ...................... , ................................................... II-74
`c. High-risk persons with multiple risk factors ............................................................ 11-78
`13. Models for clinical intervention: role of multidisciplinary team ............. : ................... II-79
`14. Cost-effectiveness issues ................................. : ........................................................... II-80
`a. Purpose of cost-effectiveness analysis ofLDL-lowering therapy ........................... II-80
`b. Approaches to estimating cost-effectiveness of cholesterol-lowering therapies ..... II-81
`c. Criteria for cost-effectiveness therapies ................................................................... II-84
`d. Cost effectiveness analysis for LDL lowering for secondary prevention
`(persons with established CHO) ................................................................................... II-84
`e. Cost effectiveness analysis in persons with CHD risk equivalents .......................... 11-85
`f. Cost effectiveness of primary prevention .......................................................... : ...... II-85
`I) Cost effectiveness of dietary therapy for primary prevention ........................... 11-85
`2) Cost effectiveness of drug therapy for short-term primary prevention ............. II-85
`3) Cost-effectiveness for primary prevention based on WOSCOPS results .......... II-86
`4) Cost effectiveness of primary prevention based on the
`AFCAPS/TexCAPS trial ......................................................................................... II-86
`5) Cost-effectiveness in long-term primary prevention ......................................... II-87
`g. Summary .................................................................................................................. II-87
`
`III. Detection and Evaluation .......................................................................................... ~ ..... 111-1
`1. Identification of risk categories for setting of LDL-cholesterol goals ........................... III-I
`a. Identification of persons with CHD and CHO risk equivalent.. .............................. III-I
`b. Risk assessment in persons without CHO or CHO risk equivalents
`(starting with risk factor counting) ............................................................................... III-2
`l) Identification of persons with multiple (2+) risk factors ................................... III-3
`2) Calculation of 10-year CHO risk ....................................................................... III-3
`2. Determination and classification of LDL cholesterol.. .................................................. lll-8
`a. Who should be tested for cholesterol and lipoproteins? .......................................... III-8
`b. Procedures of measurement ..................................................................................... 111-9
`c. Classification oflipid and lipoprotein levels ......................................................... III-I 0
`d. Secondary dysJipidemias (see Section VII) ........................................................... III-I 0
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`3. Atherogenic dyslipidemia and the metabolic syndrome .............................................. III-11
`a. Atherogenic dyslipidemia and classification of serum triglycerides ..................... III-11
`b. Diagnosis of the metabolic syndrome .................................................................... III-11
`4. Role of emerging risk factors in risk assessment ......................................................... III-11
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`IV. General Approach to Treatment-Goals and Thresholds .......................................... IV-1
`1. Therapeutic goals for LDL cholesterol .......................................................................... IV-1
`2. Management of LDL Cholesterol ................................................ : ................................. IV-2
`a. CHO and CHO risk equivalents ........................................ , ...................................... IV-2
`1) Baseline LDL cholesterol ~130 mg/dL ............................................................. IV-3
`2) Baseline LDL cholesterol 100-129 mg/dL ....................................................... IV-3
`3) Baseline LDL cholesterol <IOO mg/dL ............................................................. IV-3
`b. Multiple (2+) risk factors .......................................................... : ............................... IV-4
`1) Multiple risk factors, IO-year risk >20 percent~ ................................................ IV-4
`2) Multiple risk factors, IO-year risk I 0-20 percent.. ............................................ IV-4
`3) Multiple risk factors, 10-year risk <l 0 percent ................................................. IV-4
`c. Zero to one risk factor ........................................................... · .................................... IV-5
`d. Management of LDL cholesterol when risk assessment begins with
`Framingham scoring (Table IV.2-4) ............................................................................ IV-5
`e. Recommendations for persons whose LDL cholesterol levels are below goal.. ...... IV-6
`f. LDL-lowering therapy in older persons ............................................................. : ..... IV-7
`3. Management of atherogenic dyslipidemia and the metabolic syndrome ....................... IV-7
`a. Atherogenic dyslipidemia ....................................... : ................................................ IV-7
`b. Metabolic syndrome ................................................................................................. IV-7
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`V. Adopting Healthful Lifestyle Habits to Lower LDL Cholesterol and Reduce
`CHD Risk ................................................................................................................................... V-1
`1. Population approach: promoting a base of healthy life habits ......................................... V-1
`2. General approach to therapeutic lifestyle changes (TLC) ............................................... V-5
`3. Components of the TLC diet. ......................................................................................... V-13
`a. Major nutrient components ...................................................................................... V-13
`1) Saturated fatty acids ....................................................................................... '. ... V-13
`2) Trans fatty acid .................................................................................................. V-15
`3) Dietary cholesterol. ....................................... : ..................................................... V-15
`4) Monounsaturated fatty acids .............................................................................. ¥-16
`5) Polyunsaturated fatty acids ................................................................................ V-17
`6) Total fat. ............................................................................................................. V-18
`7) Carbohydrate ............................................................. ~ ....................................... V-19
`8) Protein ................................................................................................................ V-20
`b. Additional dietary options for LDL lowering .......................................................... V-20
`I) Increasing viscous fiber in the diet. ................................................................... V-20
`2) Plant stanols/sterols ................................................. : .......................................... V-21
`3) Soy protein ......... : ............................................................................................... V-22
`c .. Other dietary factors that may reduce baseline risk for CHO .................................. V-22
`1) n-3 (omega-3) polyunsaturated fatty acids ........................................................ V~23
`2) Vitamins/antioxidants ......................................................................... ~ .............. V-24
`a) Folic acid and vitamins B6 and Bl2 ............................................................ V-24
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`b) Antioxidants ................................................................................................. V-25
`3) Moderate intakes of alcohol .......................................................................... : ... V-26
`4) Dietary sodium, potassium, and calcium ........................................................... V-27
`5) Herbal or botanical dietary supplements ........................................................... V-28
`6) High protein, high total fat and saturated fat weight loss regimens .................. V-28
`4. Management of the metabolic syndrome through.life habit changes ............. ; .............. V-29
`a. Weight control. ......................................................................................................... V-29
`b. Increased regular physical activity ........................................................................... V-30
`5. Practical approach to life habit changes ......................................................................... V-30
`a. Role of the physician ............................. : .................................................................. V-30
`1) Visit 1: Risk assessment, diet assessment, and initiation of therapeutic
`lifestyle change ...................................................... ~ ................................................ V-31 .
`2) Visit 2: Intensifying the TLC diet for LDL cholesterol lowering ..................... V-31
`3) Visit 3: Decision about drug therapy; initiating management of the
`metabolic syndrome ................................................................................................ V-32
`4) Visit N:Long-term follow-up and monitoring adherence to therapeutic
`lifestyle changes (TLC) ....................... : ................................................................... V-34
`b. Role of nurses, physician assistants, and pharmacists ......................... : ................... V-34
`c. Specific role ofregistered dietitians and other qualified nutrition professionals ..... V-35
`1) Role of the nutrition professional in LDL-lowering therapy ............................. V-35
`a) First: dietary assessment .............................................................................. V-36
`b) Dietary guidance on adopting the TLC Diet ............................................... V-36
`c) Specific foods and preparation techniques .................................................. V-37
`d) Recommendations by food group ................................................................ V-38
`e) Other eating tips ........................................................................................... V-40
`2) Role of the dietitian in management of the metabolic syndrome ...................... V-41
`6. Improving patient adherence to life habit changes ........................................................ V-41
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`Diet Appendix A
`Sample Dietary Assessment Questionaire (Part 1) MEDFICTS* ........................................ A-I
`Sample Dietary Assessment Questionaire (Part 2) MEDFICTS* ........................................ A-2
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`Diet Appendix B
`TLC Sample Menu-Traditional American Cuisine, Male, 25-49 Years ........................... B_;l
`TLC Sample Menu-Traditional American Cuisine, Female, 25-49 Years ........................ B-2
`TLC Sample Menu-Lacto Ovo Vegetarian Cuisine, Male, 25-49 Years .......................... B-3
`TLC Sample Menu-Lacto Ovo Vegetarian Cuisine, Female, 25-49 Years ............. : ......... B-4
`TLC Sample Menu-Southern Cuisine, Male, 25-49 Years ............................................... 8-5 ·
`TLC Sample Menu-Southern Cuisine, Female, 25-49 Years ............................................ B-6
`TLC Sample Menu-Asian Cuisine, Male, 25-49 Years ..................................................... B-7
`TLC Sample Menu-Asian Cuisine, Female, 25-49 Years ................................................. B-8
`TLC Sample Menu-Mexican-American Cuisine, Male, 25-49 Years ...... , ........................ B-9
`TLC Sample Menu-Mexican-American Cuisine, Female, 25-49 Years ......................... 8-10
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`Diet Appendix C
`Saturated Fat, Total Fat, Cholesterol, and Omega-3 Content of Meat, Fish,
`and Poultry in 3-0unce Portions Cooked Without Added Fat ............................................. C-1
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`VI. Drug Therapy ................•.........................•.............................................................•.......... VI-1
`1. Thresholds and goals for drug treatment ....................................................................... VI-I
`a. Drug therapy to achieve treatment goals: overview ................................................. VI-1
`b. Cholesterol management in persons with CHD or CHD risk equivalents ............... Vl-3
`1) Baseline LDL cholesterol ~130 mg/dL ............................................................. VI-3
`2) On-treatment LDL cholesterol 100-129 mg/dL ................................................ VI-3
`3) Baseline LDL cholesterol 100-129 mg/dL ....................................................... VI-4
`4) Baseline LDL cholesterol <100 mg/dL ............................................................. VI-5
`5) Initiating cholesterol-lowering drugs in hospitalized patients ........................... VI-5
`6) Special considerations for drug therapy in CHD patients ................................. VI-6
`c. General principles of primary prevention with drug therapy ................................... Vl-7
`d. Drug considerations for persons with multiple (2+) risk factors ............................. VI-7
`1) 10-year risk >20 percent .................................................................................... VI-7
`2) IO-year.risk 10-20 percent ................................................................................ Vl-8
`3) 10-year risk <10 percent ..................................................................................... VI-8
`e. Drug considerations for persons with 0-1 risk factor, 10-year risk <10 percent.. ... VI-8
`2. Available drug therapies ................................................................................................ Vl-8
`a. Overview and general approach ................................................................... · ............ VI-8
`b. Major drugs .............................................................................................................. VI-9
`1) HMG CoA reductase inhibitors (statins}-lovastatin, pravastatin,
`simvastatin, fluvastatin, atorvastatin ........................................... : ........................... Vl-9
`2) Bile acid sequestrants~holestyramine, colestipol, colesevelam ................... VI-13
`3) Nicotinic acid ...................................................... · ..... ~ ....................................... VI-15
`4) Fibric acid derivatives (fibrates): gemfibrozil, fenofibrate, clofibrate ............ VI-18
`c. Other drugs ............................................................................................................. VI-22
`d. n-3 fatty acids ....... ; .................................................................................................. VI-22
`e. Hormone replacement therapy (HRT) ................................................................... VI-23
`1) Selective estrogen receptor modulators (SERM}-Raloxifene ....................... VI-24
`f. Miscellaneous drugs and therapeutic approaches ................................................... VI-25
`1) Investigational drugs ........................................................................................ VJ.."'·25
`2) Other approaches ............................................................................................. VI-25
`3. Selection of drugs for elevated LDL cholesterol ......................................................... VI-25
`a. Practical advice on combined drug therapy ........................................................... VI-27
`1) Statin-bile acid sequestrant combination ...................................................... VI-i7
`2) Statin-fibrate combination therapy ............................................................... VI-28
`3) Statin-nicotinic acid combination therapy .................................................... VI-30
`4) Fibrate-nicotinic acid combination therapy .................................................. VI-30
`4. Initiation, monitoring and followup of drug treatment ................................................. VI-30
`a. Initiation ofLDL-lowering drug therapy ............................................................... VI-30
`b. Baseline measurements .......................................................................................... VI-31
`c. Interval of follow up ............................................................................................... VI-32
`d. Followup treatment decisions ........................................... _ ..................................... VI-33
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`VII. Management of Specific Dyslipidemias ...................................................................... VIl-1
`I. Very high LDL cholesterol ........................................................................................... VII-I
`a. Familial hypercholesterolemia (FH) ................. ; ..................................................... VII-3
`b. Familial defective apolipoprotein B-100 (FDB) ..................................................... VII-4
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`c. Polygenic hypercholesterolemia ............................................................................. VII-4
`2. Elevated triglycerides .................................................................................................. · .. VII-4
`a. Classification, causation, and clinicahignificance .. : .............................................. VII-4
`1) Classification of serum triglycerides ................................................................ VII-4
`2) Causes of elevated triglycerides ....................................................................... VII-5
`3) Relation of elevated triglycerides to CHD and other conditions ....................... VII-7
`b. Therapeutic considerations for persons with elevated triglycerides ....................... VII-9
`1) Non-HDL cholesterol: secondary target for persons with elevated
`triglycerides ............................ · ................................................................................ VII-9
`2) Changes in life habits are primary therapy for elevated triglycerides .............. VII-9
`3) Special treatment considerations for different triglyceride
`categories {Table VII.2-4) ..................................... : ............................................. VII-11
`3. Low HDL cholesterol (without hypertriglycerid~mia) ............................................... VII-13
`a. Definition, causes and relationship to CHD .......................................................... VII-13
`b.. Therapeutic considerations in persons with low HDL cholesterol ....................... VIl-16
`1) Clinical trial evidence ............................ ~ ..... : ...................................... .' ........... VII-16
`2) Recommendations for low HDL cholesterol in persons with CHD
`or CHD risk equivalents, I 0-year risk >20 percent ............................ : ................ VII-17
`3) Considerations for persons with low HDL cholesterol in other risk
`categories, IO-year risk :S20 percent.. ...................... ; ........................................... VII-17
`4. Diabetic dyslipidemia ................................................................................................