Detection
`
`Third Report of the
`National Cholesterol
`Education Program (NCEP)
`Expert Panel on
`
`Detection,
`Evaluation,
`and Treatment
`of High Blood
`Cholesterol
`in Adults
`(Adult Treatment
`Panel III)
`
`Evaluation
`
`Final Report
`
`Treatment
`
`National Cholesterol Education Program
`
`National Heart, Lung, and Blood Institute
`
`National Institutes of Health
`
`NIH Publication No. 02-5215
`
`CFAD Ex. 1031 (1 of 280)
`
`

`
`CFAD Ex. 1031 (2 of 280)
`
`

`
`3145
`
`Acknowledgments
`
`National Cholesterol Education Program Expert Panel
`on Detection, Evaluation, and Treatment of High Blood
`Cholesterol in Adults (Adult Treatment Panel III)
`
`National Cholesterol Education Program Coordinating
`Committee
`
`Members: Scott M. Grundy, M.D., Ph.D. (Chair
`of the panel), Diane Becker, Sc.D., M.P.H., R.N.,
`Luther T. Clark, M.D., Richard S. Cooper, M.D.,
`Margo A. Denke, M.D., Wm. James Howard, M.D.,
`Donald B. Hunninghake, M.D., D. Roger Illingworth,
`M.D., Ph.D., Russell V. Luepker, M.D., M.S.,
`Patrick McBride, M.D., M.P.H., James M. McKenney,
`Pharm.D., Richard C. Pasternak, M.D., F.A.C.C.,
`Neil J. Stone, M.D., Linda Van Horn, Ph.D., R.D.
`
`Ex-officio Members: H. Bryan Brewer, Jr., M.D.,
`James I. Cleeman, M.D. (Executive Director of the panel),
`Nancy D. Ernst, Ph.D., R.D., David Gordon, M.D.,
`Ph.D., Daniel Levy, M.D., Basil Rifkind, M.D.,
`Jacques E. Rossouw, M.D., Peter Savage, M.D.
`
`Consultants: Steven M. Haffner, M.D.,
`David G. Orloff, M.D., Michael A. Proschan, Ph.D.,
`J. Sanford Schwartz, M.D., Christopher T. Sempos, Ph.D.
`
`Staff: Susan T. Shero, M.S., R.N., Elaine Z. Murray,
`Susan A. Keller, M.P.H., M.S., B.S.N.
`
`Manuscript Preparation: Angela J. Jehle
`
`Executive Committee Advisor and Reviewers
`
`Executive Committee Advisor to the Panel:
`Stephen Havas, M.D., M.P.H., M.S.
`
`Reviewers: Eugene Braunwald, M.D., W. Virgil Brown,
`M.D., Alan Chait, M.D., James E. Dalen, M.D.,
`Valentin Fuster, M.D., Ph.D., Henry N. Ginsberg, M.D.,
`Antonio M. Gotto, M.D., D.Phil., Ronald M. Krauss,
`M.D., John C. LaRosa, M.D., F.A.C.P., Thomas H. Lee,
`Jr., M.D., Linda Meyers, Ph.D., Michael Newman, M.D.,
`Thomas Pearson, M.D., Ph.D., Daniel J. Rader, M.D.,
`Frank M. Sacks, M.D., Ernst J. Schaefer, M.D.,
`Sheldon G. Sheps, M.D., Lynn A. Smaha, M.D., Ph.D.,
`Sidney C. Smith, Jr., M.D., Jeremiah Stamler, M.D.,
`Daniel Steinberg, M.D., Ph.D., Nanette K. Wenger, M.D.
`
`The Third Report of the Expert Panel on Detection,
`Evaluation, and Treatment of High Blood Cholesterol
`in Adults was approved by the National Cholesterol
`Education Program Coordinating Committee, which
`comprises the following organizational representatives:
`
`Member Organizations: National Heart, Lung, and
`Blood Institute – Claude Lenfant, M.D., (Chair),
`James I. Cleeman, M.D. (Coordinator), American
`Academy of Family Physicians – Theodore G. Ganiats,
`M.D., American Academy of Insurance Medicine –
`Gary Graham, M.D., American Academy of Pediatrics –
`Ronald E. Kleinman, M.D, American Association of
`Occupational Health Nurses – Pamela Hixon, B.S.N.,
`R.N., C.O.H.N-S, American College of Cardiology –
`Richard C. Pasternak, M.D., F.A.C.C., American College
`of Chest Physicians – Gerald T. Gau, M.D., American
`College of Nutrition – Harry Preuss, M.D., American
`College of Obstetricians and Gynecologists –
`Thomas C. Peng, M.D., American College of
`Occupational and Environmental Medicine –
`Ruth Ann Jordan, M.D., American College of Preventive
`Medicine – Lewis H. Kuller, M.D., Dr.P.H., American
`Diabetes Association, Inc. – Alan J. Garber, M.D., Ph.D.,
`American Dietetic Association – Linda Van Horn, Ph.D.,
`R.D., American Heart Association – Scott M. Grundy,
`M.D., Ph.D., American Hospital Association –
`Sandra Cornett, Ph.D., R.N., American Medical
`Association – Yank D. Coble, Jr., M.D., American Nurses
`Association – To be named, American Osteopathic
`Association – Michael Clearfield, D.O., American
`Pharmaceutical Association – James M. McKenney,
`Pharm.D., American Public Health Association –
`Stephen Havas, M.D., M.P.H., M.S., American Red
`Cross – Donald Vardell, M.S., Association of Black
`Cardiologists – Karol Watson, M.D., Ph.D., Association
`of State and Territorial Health Officials – Joanne Mitten,
`M.H.E., Citizens for Public Action on Blood Pressure and
`Cholesterol, Inc. – Gerald J. Wilson, M.A., M.B.A.,
`National Black Nurses Association, Inc. –
`Linda Burnes-Bolton, Dr.P.H., R.N., M.S.N., F.A.A.N.,
`National Medical Association – Luther T. Clark, M.D.,
`Society for Nutrition Education – Darlene Lansing,
`M.P.H., R.D., Society for Public Health Education –
`Donald O. Fedder, Dr.P.H., M.P.H.
`
`CFAD Ex. 1031 (3 of 280)
`
`

`
`3146
`
`Circulation December 17/24, 2002
`
`Associate Member Organization: American Association of
`Office Nurses – Joyce Logan.
`
`Federal Agencies: NHLBI Ad Hoc Committee on
`Minority Populations – Yvonne L. Bronner, Sc.D., R.D.,
`L.D., Agency for Healthcare Research and Quality –
`Francis D. Chesley, Jr., M.D., Centers for Disease Control
`and Prevention – Wayne Giles, M.D., M.P.H.,
`Coordinating Committee for the Community
`Demonstration Studies – Thomas M. Lasater, Ph.D.,
`Department of Agriculture – Alanna Moshfegh, M.S.,
`R.D., Department of Defense – Col. Robert Dana
`Bradshaw, M.D., M.P.H., Food and Drug Administration
`– Elizabeth Yetley, Ph.D., Health Resources and Services
`Administration – Celia Hayes, M.P.H., R.D., National
`Cancer Institute – Carolyn Clifford, Ph.D., National
`Center for Health Statistics – Clifford Johnson, M.P.H.,
`Office of Disease Prevention and Health Promotion –
`Elizabeth Castro, Ph.D., Department of Veterans Affairs –
`Pamela Steele, M.D.
`
`CFAD Ex. 1031 (4 of 280)
`
`

`
`Contents
`
`Contents
`
`3147
`
`I. Background and Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1. Development of an evidence-based report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2. Features of ATP III similar to those of ATP I and II . . . . . . . . . . . . . . . . . . . . . . . . .
`3. New features of ATP III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4. Relation of ATP III to NCEP’s public health approach . . . . . . . . . . . . . . . . . . . . . . .
`5. Relation of ATP III to other clinical guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`II. Rationale for Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1. Basic description of lipids and lipoproteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2. LDL cholesterol as the primary target of therapy . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Serum LDL cholesterol as a major cause of CHD . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Serum LDL cholesterol as target of therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. Categories and classification of total cholesterol and LDL cholesterol . . . . . . . . .
`3. Other lipid risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Triglycerides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Elevated serum triglycerides (and triglyceride-rich lipoproteins) as
`a risk factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Lipoprotein remnants as atherogenic lipoproteins . . . . . . . . . . . . . . . . . . . . . .
`3) VLDL cholesterol as a marker for remnant lipoproteins . . . . . . . . . . . . . . . . .
`4) Causes of elevated serum triglycerides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5) Categories of serum triglycerides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`6) Elevated serum triglycerides and triglyceride-rich lipoproteins
`as targets of therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Non-HDL cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Non-HDL cholesterol as a risk factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Non-HDL cholesterol as a secondary target of therapy . . . . . . . . . . . . . . . . . .
`c. High density lipoproteins (HDL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Low HDL cholesterol as an independent risk factor for CHD . . . . . . . . . . . .
`2) Causes of low HDL cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Classification of serum HDL cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Low HDL cholesterol as a potential target of therapy . . . . . . . . . . . . . . . . . . .
`d. Atherogenic dyslipidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Atherogenic dyslipidemia as a “risk factor” . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Atherogenic dyslipidemia as a target of therapy . . . . . . . . . . . . . . . . . . . . . . .
`4. Nonlipid risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Modifiable risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Cigarette smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Overweight/obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5) Physical inactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`6) Atherogenic diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Nonmodifiable risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Male sex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Family history of premature CHD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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`CFAD Ex. 1031 (5 of 280)
`
`

`
`3148
`
`Circulation December 17/24, 2002
`
`5. Emerging risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Emerging lipid risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Triglycerides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Lipoprotein remnants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Lipoprotein (a) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Small LDL particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5) HDL subspecies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`6) Apolipoproteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a) Apolipoprotein B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b) Apolipoprotein A-I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`7) Total cholesterol/HDL-cholesterol ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Emerging nonlipid risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Homocysteine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Thrombogenic/hemostatic factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Inflammatory markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Impaired fasting glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. Subclinical atherosclerotic disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Ankle-brachial blood pressure index (ABI) . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Tests for myocardial ischemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Tests for atherosclerotic plaque burden . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a) Carotid intimal medial thickening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b) Coronary calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`6. Metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Metabolic syndrome as multiple, interrelated factors that raise risk . . . . . . . . . .
`b. Diagnosis of metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. Metabolic syndrome as a target of therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`7. Primary prevention: persons without established CHD . . . . . . . . . . . . . . . . . . . . . .
`a. Scope of primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Clinical strategy in primary prevention effort . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. Concepts of short-term and long-term prevention . . . . . . . . . . . . . . . . . . . . . . .
`d. Role of LDL lowering in short-term and long-term primary prevention . . . . . .
`e. Risk assessment in primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`f. Primary prevention with lifestyle changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Basis for lifestyle recommendations for primary prevention . . . . . . . . . . . . .
`2) Dietary clinical trials of cholesterol lowering . . . . . . . . . . . . . . . . . . . . . . . .
`3) Linkage of public health approach and clinical approach in
`primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`g. Effectiveness of LDL-lowering drugs in primary prevention . . . . . . . . . . . . . . . .
`h. Selection of persons for short-term risk reduction with LDL-lowering drugs . . .
`i. Selection of older persons for short-term, primary prevention . . . . . . . . . . . . . .
`j. Selection of persons for long-term primary prevention in the clinical setting . . .
`k. LDL goals in primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`8. Secondary prevention: persons with CHD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Secondary prevention of recurrent CHD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Effects of lipid-lowering therapy on stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`9. Total mortality considerations and therapeutic safety . . . . . . . . . . . . . . . . . . . . . . .
`10. Magnitude of reduction in CHD risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`11. CHD as a risk indicator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`12. Concept of CHD risk equivalents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Other forms of clinical atherosclerotic disease . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Peripheral arterial disease (PAD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Carotid artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Abdominal aortic aneurysm (AAA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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`CFAD Ex. 1031 (6 of 280)
`
`

`
`Contents
`
`3149
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`b. Diabetes as a CHD risk equivalent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. High-risk persons with multiple risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . .
`13. Models for clinical intervention: role of multidisciplinary team . . . . . . . . . . . . . . .
`14. Cost-effectiveness issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Purpose of cost-effectiveness analysis of LDL-lowering therapy . . . . . . . . . . . . .
`b. Approaches to estimating cost-effectiveness of cholesterol-lowering therapies . .
`c. Criteria for cost-effectiveness therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`d. Cost-effectiveness analysis for LDL lowering for secondary prevention
`(persons with established CHD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`e. Cost-effectiveness analysis in persons with CHD risk equivalents . . . . . . . . . . .
`f. Cost-effectiveness of primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Cost-effectiveness of dietary therapy for primary prevention . . . . . . . . . . . .
`2) Cost-effectiveness of drug therapy for short-term primary prevention . . . . .
`3) Cost-effectiveness for primary prevention based on WOSCOPS results . . . .
`4) Cost-effectiveness of primary prevention based on the
`AFCAPS/TexCAPS trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5) Cost-effectiveness in long-term primary prevention . . . . . . . . . . . . . . . . . . .
`g. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`III. Detection and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1.
`Identification of risk categories for setting of LDL-cholesterol goals . . . . . . . . . . .
`a. Identification of persons with CHD and CHD risk equivalents . . . . . . . . . . . . .
`b. Risk assessment in persons without CHD or CHD risk equivalents
`(starting with risk factor counting) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1)
`Identification of persons with multiple (2+) risk factors . . . . . . . . . . . . . . . .
`2) Calculation of 10-year CHD risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2. Determination and classification of LDL cholesterol . . . . . . . . . . . . . . . . . . . . . . . .
`a. Who should be tested for cholesterol and lipoproteins? . . . . . . . . . . . . . . . . . . .
`b. Procedures of measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. Classification of lipid and lipoprotein levels . . . . . . . . . . . . . . . . . . . . . . . . . . .
`d. Secondary dyslipidemias (see Section VII) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3. Atherogenic dyslipidemia and the metabolic syndrome . . . . . . . . . . . . . . . . . . . . . .
`a. Atherogenic dyslipidemia and classification of serum triglycerides . . . . . . . . . .
`b. Diagnosis of the metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4. Role of emerging risk factors in risk assessment . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Appendix III–A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Distributions of Total Cholesterol, LDL Cholesterol,
`HDL Cholesterol, and Triglycerides in the U.S. Adult
`Population, NHANES III Data (1988-1994)(Serum) . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`3212
`3216
`3216
`3216
`3217
`3217
`3219
`
`3219
`3220
`3220
`3220
`3220
`3220
`
`3221
`3221
`3222
`
`3227
`3227
`3227
`
`3227
`3228
`3228
`3232
`3232
`3232
`3233
`3233
`3233
`3233
`3234
`3234
`
`3237
`
`3237
`
`IV. General Approach to Treatment—Goals and Thresholds . . . . . . . . . . . . . . . . . . . . .
`1. Therapeutic goals for LDL cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2. Management of LDL Cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. CHD and CHD risk equivalents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Baseline LDL cholesterol ≥130 mg/dL . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Baseline LDL cholesterol 100–129 mg/dL . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Baseline LDL cholesterol <100 mg/dL . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`3243
`3243
`3244
`3244
`3244
`3244
`3245
`
`CFAD Ex. 1031 (7 of 280)
`
`

`
`3150
`
`Circulation December 17/24, 2002
`
`b. Multiple (2+) risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Multiple risk factors, and 10-year risk >20 percent . . . . . . . . . . . . . . . . . . . .
`2) Multiple risk factors, and 10-year risk 10–20 percent . . . . . . . . . . . . . . . . . .
`3) Multiple risk factors, 10-year risk <10 percent . . . . . . . . . . . . . . . . . . . . . . .
`c. Zero to one risk factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`d. Management of LDL cholesterol when risk assessment begins with
`Framingham scoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`e. Recommendations for persons whose LDL cholesterol levels are
`below goal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`f. LDL-lowering therapy in older persons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3. Management of atherogenic dyslipidemia and the metabolic syndrome . . . . . . . . . .
`a. Atherogenic dyslipidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`V. Adopting Healthful Lifestyle Habits to Lower LDL Cholesterol and Reduce
`CHD Risk
` . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1. Population approach: promoting a base of healthy life habits . . . . . . . . . . . . . . . . .
`2. General approach to therapeutic lifestyle changes (TLC) . . . . . . . . . . . . . . . . . . . . .
`3. Components of the TLC Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Major nutrient components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Saturated fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Trans fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Dietary cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Monounsaturated fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5) Polyunsaturated fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`6) Total fat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`7) Carbohydrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`8) Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Additional dietary options for LDL lowering . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1)
`Increasing viscous fiber in the diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Plant stanols/sterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Soy protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`c. Other dietary factors that may reduce baseline risk for CHD . . . . . . . . . . . . . . .
`1) n-3 (omega-3) polyunsaturated fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Vitamins/antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a) Folic acid and vitamins B6 and B12 . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b) Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) Moderate intakes of alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Dietary sodium, potassium, and calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5) Herbal or botanical dietary supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`6) High protein, high total fat and saturated fat weight loss regimens . . . . . . . .
`4. Management of the metabolic syndrome through life habit changes . . . . . . . . . . . .
`a. Weight control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Increased regular physical activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5. Practical approach to life habit changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Role of the physician . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Visit 1: Risk assessment, diet assessment, and initiation of
`therapeutic lifestyle change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Visit 2: Intensifying the TLC diet for LDL cholesterol lowering . . . . . . . . . .
`3) Visit 3: Decision about drug therapy; initiating management
`of the metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`3245
`3245
`3245
`3245
`3245
`
`3246
`
`3246
`3247
`3247
`3247
`3247
`
`3253
`3253
`3254
`3258
`3258
`3260
`3261
`3261
`3262
`3263
`3263
`3264
`3265
`3265
`3265
`3265
`3266
`3266
`3266
`3268
`3268
`3268
`3269
`3270
`3270
`3271
`3271
`3271
`3271
`3272
`3272
`
`3272
`3272
`
`3273
`
`CFAD Ex. 1031 (8 of 280)
`
`

`
`Contents
`
`3151
`
`4) Visit N: Long-term follow-up and monitoring adherence to
`therapeutic lifestyle changes (TLC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b. Role of nurses, physician assistants, and pharmacists . . . . . . . . . . . . . . . . . . . . .
`c. Specific role of registered dietitians and other qualified nutrition
`professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Role of the nutrition professional in LDL-lowering therapy . . . . . . . . . . . . .
`a) First: dietary assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`b) Dietary guidance on adopting the TLC diet . . . . . . . . . . . . . . . . . . . . . .
`c) Specific foods and preparation techniques . . . . . . . . . . . . . . . . . . . . . . . .
`d) Recommendations by food group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`e) Other eating tips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Role of the dietitian in management of the metabolic syndrome . . . . . . . . . .
`Improving patient adherence to life habit changes . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`3274
`3275
`
`3275
`3275
`3276
`3276
`3277
`3277
`3279
`3279
`3280
`
`6.
`
`Diet Appendix A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Sample Dietary Assessment Questionaire MEDFICTS . . . . . . . . . . . . . . . . . . . . . . . . .
`
`3283
`3283
`
`Diet Appendix B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`TLC Sample Menus: Traditional American Cuisine: Male, 25–49 Years . . . . . . . . . . .
`Traditional American Cuisine: Female, 25–49 Years . . . . . . . .
`Lacto Ovo Vegetarian Cuisine: Male, 25–49 Years . . . . . . . . . .
`Lacto Ovo Vegetarian Cuisine: Female, 25–49 Years . . . . . . . .
`Southern Cuisine: Male, 25–49 Years . . . . . . . . . . . . . . . . . . . .
`Southern Cuisine: Female, 25–49 Years . . . . . . . . . . . . . . . . .
`Asian Cuisine: Male, 25–49 Years . . . . . . . . . . . . . . . . . . . . . . .
`Asian Cuisine: Female, 25–49 Years . . . . . . . . . . . . . . . . . . . . .
`Mexican-American Cuisine: Male, 25–49 Years . . . . . . . . . . . .
`Mexican-American Cuisine: Female, 25–49 Years . . . . . . . . . .
`
`Diet Appendix C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Saturated Fat, Total Fat, Cholesterol, and Omega-3 Content of Meat,
`Fish, and Poultry in 3-Ounce Portions Cooked Without Added Fat . . . . . . . . . . . . . . .
`
`VI. Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1. Thresholds and goals for drug treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Drug therapy to achieve treatment goals: overview . . . . . . . . . . . . . . . . . . . . . . .
`b. Cholesterol management in persons with CHD or CHD risk equivalents . . . . . .
`1) Baseline LDL cholesterol ≥130 mg/dL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) On-treatment LDL cholesterol 100–129 mg/dL . . . . . . . . . . . . . . . . . . . . . . .
`3) Baseline LDL cholesterol 100–129 mg/dL . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Baseline LDL cholesterol <100 mg/dL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`5)
`Initiating cholesterol-lowering drugs in hospitalized patients . . . . . . . . . . . .
`6) Special considerations for drug therapy in CHD patients . . . . . . . . . . . . . . .
`c. General principles of primary prevention with drug therapy . . . . . . . . . . . . . . . .
`d. Drug considerations for persons with multiple (2+) risk factors . . . . . . . . . . . . .
`1) 10-year risk >20 percent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) 10-year risk 10–20 percent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`3) 10-year risk <10 percent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`e. Drug considerations for persons with 0–1 risk factor,
`10-year risk <10 percent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2. Available drug therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`a. Overview and general approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`3287
`3287
`3288
`3289
`3290
`3291
`3292
`3293
`3294
`3295
`3296
`
`3299
`
`3299
`
`3303
`3303
`3303
`3304
`3305
`3305
`3305
`3306
`3306
`3307
`3307
`3307
`3307
`3307
`3308
`
`3308
`3308
`3308
`
`CFAD Ex. 1031 (9 of 280)
`
`

`
`3152
`
`Circulation December 17/24, 2002
`
`b. Major drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) HMG CoA reductase inhibitors (statins)—lovastatin,
`pravastatin, simvastatin, fluvastatin, atorvastatin . . . . . . . . . . . . . . . . . . . . .
`2) Bile acid sequestrants—cholestyramine, colestipol, colesevelam . . . . . . . . . . .
`3) Nicotinic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`4) Fibric acid derivatives (fibrates): gemfibrozil, fenofibrate, clofibrate . . . . . . .
`c. Other drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`d. n-3 (omega) fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`e. Hormone replacement therapy (HRT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1) Selective estrogen receptor modulators (SERM)—Raloxifene . . . . . . . . . . . .
`f. Miscellaneous drugs and therapeutic approaches . . . . . . . . . . . . . . . . . . . . . . . .
`1)
`Investigational drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`2) Other approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . .