Vital and
`Health Statistics
`Serum Lipids of
`Adults 20–74 Years:
`United States,
`1976-80
`
`Series 11:
`Data From the National Health Survey
`Not 242
`This report presents descriptive and analytic data for serum total cholesterol,
`cholesterol
`lipoproteins, and triglycerides for adults 20–74 years of age by age,
`sex, and selected subgroups of the population at risk of developing coronary
`heart disease, This information is frorm the second National Health and Nutrition
`Examination Survey, which was conducted during the years 1976-80,
`
`US. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`Public Health Service
`Centers for Disease Control and Prevention
`National Center for Health Statistics
`
`Hyaitsville, Maryland
`March 1993
`DHHS Publication No. [PHS) 93-1692
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 1 of 113
`
`

`

`Trade Name Diecleimer
`
`The use of trade names is for identiicetion onfy and does not imply
`endorsement by the Public Health Service, U.S. Department of Health and
`Human Sewices.
`
`Copyright
`
`information
`
`All material appearing in this report is in the public domain and may be
`reproduced or copied without permission: citation as to source, however,
`appreciated.
`
`is
`
`Suggeeted Cftetlon
`
`Carroll M, Sempos C, Briefel R, et al. Serum lipids of adults 2G74 years,
`United States, 1976-60. National Center for Health Statistics. Vital Health Stat
`11(242). 1S93.
`
`Library of Congrese Cataloging-in-Publication
`
`Data
`
`*
`
`Serum lipids and lipoproteins of adults, 1976-60.
`p. cm. – (Vkel and health statistics. Series 11, Data from the National
`Health Survefi no. 242)
`(DHHS publication: no. (PHS) 93–1 692)
`Authors, Margaret Carroll... [et al.].
`“From the second National Health and Nutriion Examination Survey.”
`Includes bibliographical references.
`ISBN O-640WJ462-9
`2. Blood cholesterol- United
`1. Blood lipids– United States-Statistics.
`States- Statistics. 3. Blood lipoproteins – United States – Statistics. 4. Coronary
`heart disease–United
`States– Risk factors -Statistics. L Carroll, Margaret T.
`Il.
`National Center for Health Statistics (U.S.)
`Ill. National Health and Nutrition
`Examination Survey (U.S.)
`IV. Series. V. Series: DHHS publication no. (PHS)
`93-1692.
`[DNLM: 1. Cholesterol– blood –sbtisfics. W2 A N146vk: no. 242]
`RA407.3.A347
`no. 242
`[QP99.3.L5]
`362.1 ‘0S73’021 s–dc20
`[614.5’9123’00973]
`DNLM/DLC
`for Library of Congress
`
`92–1 6913
`CIP
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 2 of 113
`
`

`

`National Center
`
`for Health Statistics
`
`Manning Feinleib, M.D., Dr. P.H., Director
`
`Jack R, Anderson, Acting Depu@ Director
`
`Jacob J. Feldman, Ph. D., Associate Direc/or for Analysis
`and Epidemiology
`
`Gail F. Fisher, Ph. D., Associate Director for Planning and
`Extramural Program
`
`Peter L. Hurley, Associate Director for Vital and Health
`Statistics Systems
`Robert A. Israel, Associate Director for International Statistics
`
`Stephen E. Nieberding, Associate Direcror for Management
`Charles J. Rothwell, Associate Director for Data Processing
`and Services
`
`Monroe G. Sirken, Ph. D., Associate Director for Research
`and Methodology
`
`David L. Larson, Assistant Director, Atlanta
`
`Division of Health Examination Statistics
`
`Robert S. Murphy, M.S.P.H., Direc(or
`
`Kurt R, Maurer, Ph. D., Depufy Director
`Ronette R. Briefel, Dr. P.H,, R. D., Direc[or, Nutrition
`Monitoring and Related Research Program
`
`Clifford L. Johnson, M.S.P.H., Special Assistant of
`Analysis and Information Managenvmt
`
`Vicki L. Burt, SC.M,, R. N., Chief Survey Planning and
`Development Branch
`Jean Findlay, M.S., ChieJ Survey Operations Branch
`
`Katherine M. Flegal, Ph. D., Chiej Medical Statistics
`Branch
`Anne C. Looker, Ph. D., ChieJ Nutrition Statistics Branch
`
`Robert S. Krasowski, M.A., M.S., ChieJ Computer
`Systems and Programming Branch
`
`Christopher T. Sempos, Ph. D., Chief Longitudinal
`Statistics Branch
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 3 of 113
`
`

`

`Contents
`
`1 3 3 3 5 8 8 8 8 8 9g 9 9 1
`
`0
`12
`
`Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Source of data and analytic issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Source of data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Methods of measurement
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Analytic issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Selected tindings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Total cholesterol
`(TC)
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`High density lipoprotein (HDL) cholesterol
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Non-high density lipoprotein (non-HDL)
`cholesterol . . . . . . . . . . . . . . . . . . .
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Ratio of TCto HDL-C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Serum triglyceride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Low density lipoprotein (LDL-C)cholesteroI
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`LDL-C:HDL-C ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`The National Cholesterol Education Program Adult Treatment Panel Guidelines
`. . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`List of detailed tables
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Appendixes
`
`1,
`H.
`III.
`W.
`
`97
`Statistical notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...4....
`and reliability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
`Data presentation
`Definition ofvariables
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...105
`Definitions of risk factorvariables.
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...106
`
`Text tables
`
`A.
`
`B.
`
`c.
`
`D,
`
`ages
`for Health Statistics, by years ofsurvey,
`Health examination surveys conducted by the National Center
`of target population,
`and lipid determinations:
`1960–80 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Number and percent ofpersons20–74
`years ofagewlm wereinterviewed
`and examinedby
`age, sex,and
`race: Second National Health and Nutrition Examination Survey, 1976–80 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Number and percent of persons 20-74 years of age interviewed and examined inthe
`fasting sample, by age,
`sex, and race: Second National Health an
`dNutritio nExamination Survey, 1976–S0 . . . . . . . . . . . . . . . . . . . . . . . .
`Number ofpersons
`ages 20–74 years with known serum lipid determinationsby
`race: Second National
`Health and Nutrition Examination Survey, 1976-S0 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`2
`
`3
`
`4
`
`4
`
`...
`Ill
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 4 of 113
`
`

`

`Serum Lipids of Adults
`
`Sempos, Ph. D.,
`Margaret Carroll, M. S. P.H., Christopher
`Ronette Briefel, Dr. P. H., R. D., Shirley Gray, M. B.A., and
`Clifford Johnson, M. S. P. H., Division of Health
`Examination Statistics
`
`Introduction
`lipopro-
`the cholesterol
`(TC),
`Serum total cholesterol
`teins, and serum triglyceride
`are all associated with the
`development of coronary heart disease (CHD)
`(l-3). Both
`TC and low density lipoprotein
`cholesterol
`(LDL-C)
`are
`directly related to the development
`of CHD (1,2). High
`density lipoprotein cholesterol
`(HDL-C)
`is inversely asso-
`ciated with CHD development
`and high levels of HDL
`cholesterol may be protective
`(4,5). Serum triglyceride,
`although directly associated with CHD, has not consis-
`tently been shown to be an independent CHD risk factor
`(6,7).
`data on serum
`This report presents basic reference
`lipids and lipoproteins
`for adults 20-74 years of age,
`including TC, HDL-C,
`the difference
`between TC and
`HDL-C or non-HDL-C, TC:HDL-C ratio, serum triglycer-
`ide, calculated LDL-C, LDL-C.HDL-C ratio, and detailed
`estimates
`of
`the percent
`of persons with high blood
`cholesterol
`as defined by the Adult Treatment
`Panel of
`the National Cholesterol Education Program (2).
`for
`The data were collected by the National Center
`Health Statistics
`(NCHS)
`through
`the second National
`Health and Nutrition Examination Survey (NHANES II),
`conducted
`during the years 1976–SO (S). NHANES
`II
`included a variety of measures of nutritional
`status and
`related health information.
`The NHANES is an expansion of the National Health
`Examination Survey (NHES). The surveys are designed to
`collect data by direct standardized
`examinaticm of a sam-
`ple of the population. Direct examinations,
`coupled with
`cIinical
`tests and measurements,
`are the ordy source of
`prevalence
`data
`regarding
`previously
`undiagnosed
`and
`
`to the
`the contributions
`The authors acknovdcdgc with apprcciatimr
`]abordtory analysis, data collection, datti processing ami editing, and
`manuscript
`review made by the following individuals from various Gov-
`ernment and non-Govcmmcnt
`agcncics:
`The George Washington University Lipid Research Clinic:
`John C. La Rosa, M.D.
`Richard Mucsing, Ph.D.
`The National Heart Lung mrd Blood lnstitutc, Nation:ll
`Health:
`Basil Rifkind, M.D.
`Kenneth Lippcl, Ph.D.
`Robinson Fuhvood, M. S.P.H.
`The National Center for Health Statistics:
`Robert S. Murphy, M.S.P.H.
`
`Institutes of
`
`diseases. They are the best source of standard-
`untreated
`ized clinical, physical, and physiological data on the subject.
`The three programs of the NHES (1959-70)
`(9-11)
`focused on selected aspects of illness and health,
`each
`targeting a particular
`age group of the population.
`In 1971, responsibility for monitoring the nutritional
`status of the population was added to the National Health
`Examination Survey, which then became the first National
`Health and Nutrition Examination Survey (NHANES I).
`Conducted
`from April 1971-June
`1974, NHANES I was
`designed to assess overall health status, with particular
`emphasis on dental health, skin problems, eye conditions,
`and the nutritional
`status of the population
`1–74 years of
`age (12).
`Adults 25–74 years of age were examined to deter-
`mine the prevalence
`of chronic
`lung disease; disabling
`arthritis of the hip, knee, or Iower spine; cardiovascular
`disease; and hearing levels. In addition,
`information was
`obtained
`on health care needs
`and general well-being.
`This segment of the NHANES I program was followed by
`a 15-month period (July 1974-October
`1975) during which
`an additional national
`sample of persons 25–74 years of
`
`to augmentthesizeof the
`age \vas examined in order
`original NHANES I sample. This study is referred to as
`the National Health and Nutrition Examination Survey,
`Augmentation Cycle (13).
`report,
`this
`for
`of data
`NHANES
`II,
`the
`source
`provides an opportunity
`to assess the population’s health
`and nutritional
`status cross-sectionally and to assess some
`aspects of change over time (14), Components
`of nutri-
`tional status measurement were included in a physician’s
`examination,
`a medical history questionnaire,
`body meas-
`urements,
`laboratory assessments of blood samples, and a
`dietary interview’.
`Also included in NHANES II were tests and proce-
`dures
`that provided data on diabetes, kidney and heart
`disease, hypertension,
`certain allergies, disc degeneration,
`pulmonary
`function, hearing and speech problems,
`and
`exposure to certain potentiality toxic substances.
`from
`TotaI
`serum cholesterol
`has been determined
`sera collected in each health examination
`survey except
`the second National Health Examination Survey (NHES
`II)
`(table A). During NHANES H,
`the NCHS and the
`National Heart, Lung and Blood Institute of the National
`Institutes
`of Health collected and analytically processed
`
`1
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 5 of 113
`
`

`

`Table A: Health examination surveys conducted by the National
`Center
`for Health Statistics, by years of survey, age of target
`population, and lipid determinations:
`1960-60
`
`Survey
`
`Years
`conducted
`
`Age of
`target
`popu/afion
`
`Lipid
`determinations
`
`First National Health Examination
`Survey ...,,........,,..
`
`1960-62
`
`18-79 years
`
`TC
`
`Second National Health
`Examination Survey.
`
`Third National Health
`Examination Survey,
`
`1963-65
`
`6-11 years
`
`none
`
`1966-70
`
`12-17 years
`
`TC
`
`First National Health and Nutrition
`Examination Survey.
`.
`
`Second National Health
`and Nutrition Examination
`Survey . . . . . . . . . . . . . . . . .
`
`1971-74
`
`1-74 years
`
`TC
`
`1976-80
`
`6 months–
`74 years
`
`TC
`HDL-C serum
`triglyceride
`
`for HDL-C and
`
`serum specimens
`time)
`the first
`(for
`triglycerides in addition to TC.
`Lipid analyses for NHANES H were performed at the
`George Washington University according to protocol used
`by the Lipid Research Clinic Program (LRC). The blood
`determinations
`underwent numerous quality control and
`editing procedures
`in both the data collection and data
`processing phases of the survey. All unusual values were
`checked and verified by the laboratory.
`Data for TC, HDL-C,
`and serum triglyceride were
`determined only for adults ages 20-74 years in NHANES
`11, TC and HDL-C were scheduled to be measured in all
`adults 20–74 years old who were examined in NHANES II
`and serum triglyceride was scheduled to be measured only
`in the randomly selected half of the examined adults 20-74
`years old who were to receive the oral glucose tolerance test
`(OGTT). The “half sample” was also designed to represent
`the adult population of the United States.
`Estimates of the mean, standard error of the mean,
`and selected percentiles
`are shown for serum lipid and
`lipoprotein
`determinations
`by race,
`sex, and age, and
`for women 20-44 years of age by race, age, and use of
`oral contraceptives.
`These
`include TC, HDL-C,
`non-
`HDL-C,
`and the TC:HDL-C ratio. This latter compos-
`ite variable,
`first used in the Framingham Study,
`is a
`useful measure
`of
`the joint
`contribution
`of TC and
`HDL-C to CHD risk (15).
`for persons
`are presented
`In addition,
`estimates
`20-74 years old who fasted at least 12 hours prior to veni-
`puncture for serum triglyceride, calculated values of LDL-C
`(16) and the LDL-C:HDL-C ratio by race, sex, and age.
`Cumulative
`percent
`distributions
`for
`these
`seven
`variables are also presented by race, sex, and age. Selected
`results from these tables are highlighted in other
`tables
`showing the percent distributions by selected cutpoints of
`importance
`to CHD. These results include:
`
`.
`.
`
`The percent with HDL–C less than 35 mg/dl
`The percent with a TC:HDL–C ratio greater
`equal
`to 4.5 (17)
`
`than or
`
`The percent of persons with serum triglyceride levels between
`250 and 500 mg/dl and the percent with serum triglyceride
`levels of 500 mg/dl or more (6) are not highlighted in a special
`table. However,
`these percents can be obtained from the
`tables showing cumulative percents (18).
`In addition,
`the guidelines proposed by the National
`Cholesterol Education
`Program’s
`(2) Expert Panel on
`Detection,
`Evaluation,
`and Treatment
`of High Blood
`Cholesterol
`in Adults or Adult Treatment
`Panel
`(ATP)
`are applied to all adults 20–74 years,
`to women 20–44
`years,
`to hypertensives,
`and to normotensives
`in summary
`tables showing:
`
`.
`
`.
`
`The percent with desirable, borderline-high
`serum TC
`analysis with
`lipoprotein
`for
`referred
`The percent
`risk and high risk LDL-C
`desirable, borderline-high
`(not presented for women 20-44 years)
`
`and high
`
`The percent of hypertensives and normotensives with
`desirable, borderline-high,
`and high TC as well as the
`percent of hypertensive
`and normotensives
`referred for
`lipoprotein
`analysis with desirable,
`borderline-high-risk,
`and high-risk LDL-C are also presented. Moreover,
`the
`percent
`of hypertensives
`and normotensives within the
`desirable, borderline-high-risk,
`and high-risk TC catego-
`ries, and the percent
`referred
`for
`lipoprotein
`analysis
`within the desirable,
`borderline-high-risk,
`and high-risk
`LDL-C categories
`are presented. Similar
`tables are pre-
`sented for percent with HDL-C less than 35 mgldl and
`persons with a ratio of TC to HDL-C greater
`than, or
`equal
`to 4.5 in the various categories of the guidelines,
`Two additional
`tables
`show the percent with desir-
`able,, borderline-high-risk,
`and high-risk LDL-C for adults
`20-74 years–one
`as a percent of the total population and
`one as a percent of those not needing treatment
`for high
`blood cholesterol.
`Important
`findings derived from these
`tables have been published (19), as are other
`important
`findings concerning NHANES II lipid data (19-23).
`are
`All serum lipid and lipoprotein
`determinations
`shown in milligrams per deciliters (mg/dl). To convert TC,
`HDL-C, non-HDL-C,
`and LDL-C to rnillimoles per
`liter
`(mmol/L), multiply the value expressed in milligrams per
`deciliters
`by .02586. To convert
`serum triglyceride
`to
`mmol/L, multiply the value expressed in milligrams per
`deciliters by .01129.
`Sample sizes for most subgroups are large enough to
`meet NCHS requirements for statistically reliable results (see
`appendix II). In instances where these requirements are not
`satisfied, an asterisk (*) is shown instead of the estimates.
`The lipid data from this survey have been coded,
`edited,
`and
`released
`on microdata
`tape
`(PB. No.
`PB90-500943). Persons interested in more detailed analy-
`ses can purchase
`this tape from the National Technical
`Information
`Service, 5285 Port Royal Road, Springfield,
`Virginia (24),
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 6 of 113
`
`

`

`Source of data and
`analytical
`issues
`
`Source of data
`
`The second National Health and Nutrition Examina-
`tion Survey (NHANES) was conducted February 1976-Feb-
`ruary 1980 by NCHS. The study population for the survey
`was the civilian noninstitutionalized
`population 20–74 years
`of age in the United States. The NHANES
`II sample
`consisted of 17,390 persons 20-74 years of age, SS percent
`of whom were interviewed. Of these, 11,S64 were inter-
`viewed and examined,
`resulting
`in a response
`rate of
`68 percent. The sampIe sizes and response rates for adults
`20-74 years by race,
`sex, and age in NHANES
`II are
`shown in tables B and C; sample sizes available for each
`lipid determination
`are shown in table D. More detail on
`the sample design and conduct of the survey is shown in
`appendix L Other data collection and analytic issues are
`described in appendixes
`II-IV.
`and
`tests, procedures,
`All
`interviews,
`examinations,
`laboratory determinations
`followed standardized
`protocol.
`NHANES II, like previous examination surveys, consisted
`of
`two components.
`The first component
`consisted
`of
`household interviews and the second component consisted
`of physical examinations
`and additional
`interviews in mo-
`bile examination centers.
`
`Table B. Number and percent of persons 20-74 years of age who
`and examined by age, sex, and race: Second
`were intewiewed
`National Health and Nutrition Examination Survey, “[976-S0
`
`Age, sex, and race
`
`Total
`sample
`
`Number
`
`Percent
`
`Number
`
`Percent
`
`Interviewed
`
`Examined
`
`Total
`
`. .
`
`. . . . . . . .
`
`17,390
`
`15,364
`
`86.35
`
`11,864
`
`68.22
`
`Age
`
`20-24 years.
`25-34 years.
`35-44 years..
`45-54 years.
`55–64 years.
`65-74 years.
`
`. . . . .
`. . . . .
`. . .
`. . . . .
`. . . . .
`. . . . .
`
`Sex
`
`1,894
`3,031
`2,236
`2,149
`3,868
`4,212
`
`1,758
`2,773
`2,005
`1,866
`3,330
`3,632
`
`92.82
`91.49
`89.67
`66.83
`86.09
`86.23
`
`1,414
`2,237
`1,589
`“1,453
`2,556
`2,615
`
`74.66
`73.80
`71.06
`67.61
`66.08
`62.08
`
`Female . . . . . . . . .
`Male . . . . . . . . . .
`
`9,316
`8,074
`
`8,286
`7,078
`
`68.94
`87.66
`
`6,260
`EI,604
`
`67.20
`69.41
`
`Race
`
`. . . . . .
`White . . . .
`. . . . . .
`Black,
`,,,
`Other
`. . . . . . . . . .
`
`15,103
`1,955
`332
`
`13,316
`1,764
`284
`
`88.17
`90.23
`85.54
`
`10,301
`1,336
`227
`
`68.20
`68.34
`68.37
`
`involved collect-
`The househoId interview component
`ing socioeconomic
`and demographic
`information from the
`family and sample persons within the family and complet-
`ing a medical history questionnaire
`for sample persons.
`Staff from the U.S. Bureau of the Census performed
`the
`initial household
`interviews
`and assisted in scheduling
`appointments
`for examinations.
`The examination component was performed in mobile
`examination centers specially designed for this study. The
`examination,
`environment,
`and equipment were standard-
`ized to minimize differences
`in findings among sample
`locations. Examination
`teams were trained to follow the
`study protocol, which in turn provided for standardization
`and evaluation
`of
`their performance.
`The examination
`consisted of:
`
`.
`
`and screening by a
`examination
`. A general medical
`physician and additional medical histo~
`Laboratory
`tests of whole blood,
`serum and urine
`specimens, and lipid determinations
`Body measurements
`.
`. A dietary interview
`.
`Selected diagnostic tests, such as electrocardiogranls
`and x rays, and tests on speech and hearing, allergies,
`and pulmonary function
`
`Thus, NHANES II provided the opportunity to assess key
`aspects of the population’s
`health and nutritional
`status
`during a 4-year period, and to assess changes in the U.S.
`population over time by comparison with other NHANES.
`
`Methods of measurement
`
`NHANES H was staffed by two trained examination
`teams and equipped with three mobile examination cen-
`ters which could be moved to a central
`location in each of
`the examination
`sites or primary sampling units. At
`the
`mobile examination center, examinees changed from their
`street clothing to disposable paper examination uniforms
`and foam rubber
`slippers designed to facilitate and stan-
`dardize various elements of the examination.
`
`Serum lipid determinations
`
`from
`Blood samples were obtained by venipuncture
`both fasting and nonfasting subjects. The cells were al-
`lowed to clot and the samples were then centrifuged. The
`
`3
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 7 of 113
`
`

`

`and an a[iquot was placed in a
`was recovered,
`serum
`screw-capped vial and placed in a freezer within 3
`plastic
`hours of collection, At approximately
`2-week intervals,
`serum specimens collected over the preceding period were
`placed in a styrofoam shipping container with dry ice.
`Specimens were shipped to George Washington Univer-
`sity Lipid Research Clinic Laboratory
`for analysis of
`serum cholesterol,
`triglyceride,
`and high density lipopro-
`tein (HDL) cholesterol.
`samples were
`the laboratory,
`When they arrived at
`placed in a freezer at -15° C until
`they were analyzed –
`usually within 2 weeks of receipt. Specimens were allowed
`to thaw at room temperature,
`then mixed thoroughly by
`vortexing. All measurements were performed according to
`the protocol
`described
`for
`the Lipid Research Clinics
`(LRC) program (25).
`
`Total serum cholesterol
`
`and serum triglycerides
`
`isopro-
`on zeolite-treated
`Analyses were performed
`(Techni-
`panol extracts using an Auto-Analyzer
`II (AAII)
`con Instruments, Tarrytown, N,Y.) (a), The AAII uses a
`Lieberman-Burchard
`reagent
`for cholesterol and a flouri-
`metric measurement
`of triglycerides,
`Instrumental process
`was established
`at
`the beginning of each analytical
`run
`with. cholesterol/triglyceride
`standards
`in isopropanol
`(100/50, 200/100, 300/200, and 400/300 mg/dl) provided by
`the Clinical Chemistry Standardization
`Section of
`the
`Centers for Disease Control and Prevention (CDC).
`adjust
`A serum calibrator was used to automatically
`instrumental
`response to reference AbelI-Kendall values
`(26), Extracts of a high or low serum cholesterol/triglycer-
`ide internal pool were positioned in each tray; results from
`out-of-control
`analyses were rejected
`and the analyses
`repeated. The serum calibrator and internal control pools
`
`Table C. Number and percent of persons 20-74 years of age
`interviewed and examined in the fasting sample, by age, sex, and
`race: Second National Health and Nutrition Examination Survey,
`1976-80
`
`years with known serum
`Table [). Number of persons ages 20-74
`serum lipid determinations
`by race: Second National Health and
`Nutrition Examination Survey, 1976-80
`
`Lipid determjnaticm
`
`Total
`
`White
`
`—
`Black
`
`. .
`(TC)
`Total serum cholesterol
`High density lipoprotein cholesterol
`. . . .
`(HDL-C).
`. .,,
`,,,
`,,,
`. . . . . .
`Ratio of TC/HDL-C.
`.
`. . . .
`. . . . . . .
`,,
`Serum triglyceride,
`. . . . . . . . . . . . .
`Low delwity lipoprotein cholesterol.
`
`11,864
`
`10,301
`
`9,797
`9,797
`2,753
`2,283
`
`8,562
`8,582
`2,401
`1,990
`
`1,336
`
`1,043
`1,043
`299
`251
`
`target values were
`with assigned cholesterol/triglyceride
`provided by the CDC, Serum triglyceride values are for
`the fasting sample only. There were 5,903 sample persons
`in the fasting sample (table C ),
`The fasting time in hours was calculated in the mobile
`examination center
`from the Glucose Challenge and Re-
`lated Diabetes Data questionnaire
`(24), Only the triglyce-
`ride values for those sample persons who fasted 12 hours
`or more were used for this report
`(n= 2,753).
`
`High density lipoprotein cholesterol
`
`by the beta quanti-
`HDL cholesterol was determined
`fication procedure, which involves a combination of pre-
`parative
`ultracentrifugation
`and
`heparin-manganese
`precipitation. The determination was made on a superna-
`tant
`fraction obtained
`after
`treatment
`of the sera with
`heparin
`and manganese
`chloride,
`to precipitate
`apo B
`containing lipoproteins. The precipitate was sedimented
`at 1,500 x g, and an
`by centrifugation
`for 30 minutes
`a]iquot of the clear supernatant was extracted with, 9.5
`volumes of 99 percent
`isopropanol, The extract was treated
`with a zeolite-containing mixture
`to remove interfering
`substances. The solids were sedimented
`by centrifuging
`for 30 minutes at 1,500 x g. The cholesterol
`content of
`the extract was measured on the AAII as described in the
`LRC program operations manual.
`
`hfervie wed
`
`Examined
`
`Non-HDL cholesterol
`
`Age, sex, and race
`
`Total
`samp/e
`
`Number
`
`Percent
`
`Number
`
`Percent
`
`Total
`
`. . . . . . . . . .
`
`8,686
`
`7,691
`
`88.54
`
`5,903
`
`67.96
`
`Age
`
`20-24 years,
`25–34 years,
`35-44 years.
`45–54 years.
`55–64 years.
`65–74 years.
`
`Sex
`
`. .
`
`.
`
`914
`1,520
`1,135
`1,075
`1,909
`2,133
`
`837
`1,390
`1,025
`926
`1,651
`1,862
`
`Female,
`Male,
`
`. . . . . . . .
`. . . .
`. . . . .
`
`4,572
`4,114
`
`4,073
`3,618
`
`Race
`
`White,
`Black,
`Other,
`
`. . . . . . . . .
`.,..,..,,
`. . . .
`
`. . . . .
`
`7,555
`962
`169
`
`6,673
`871
`147
`
`4
`
`91.58
`91.45
`90.31
`66.14
`86.49
`87,29
`
`89,09
`87.94
`
`88.33
`90.54
`86.98
`
`650
`1,129
`795
`706
`1,261
`1,340
`
`71,12
`74,28
`70,04
`65.86
`67.10
`6262
`
`3,057
`1,016
`
`66.86
`24.70
`
`5,145
`646
`112
`
`68.10
`67.15
`66.27
`
`For each sample person 20-74 years of age for whom
`TC and HDL cholesterol were determined,
`the non-HDL
`cholesterol was determined
`by subtracting
`the HDIL-C
`from the TC. The non-HDL cholesterol
`is an estimate of
`the sum of LDL-C and very low density lipoprotein
`cholesterol
`(VLDL-C).
`
`Ratio of TC to HDL-C
`
`For each sample person 20–74 years of age for whom
`TC and HDL cholesterol were determined,
`the ratio was
`obtained by dividing the TC by the HDL-C.
`
`Low-density
`
`lipoprotein cholesterol
`
`to venip-
`For persons fasting 12 hours or more prior
`uncture,
`serum LDL was calculated using the Friedewald
`equation (16) as follows:
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1011, p. 8 of 113
`
`

`

`LDL-C = TC-(HDL-C+
`
`serum triglyceride/5).
`
`Reliability of estimates
`
`All values are expressed in mg/dl.
`
`individuals with a serum
`LDL-C was not calculated for
`triglyceride
`value greater
`than 400 mg/dl because
`the
`equation is not accurate beyond this valua (16). LDL-C
`data in this report
`are based on the values
`for 2,2S3
`sample persons.
`
`Ratio of LDL-C to HDL-C
`
`fasting 12
`The LDL-C to HDL-C ratio for persons
`hours or more prior
`to venipuncture with known HDL-C
`and serum triglyceride not exceeding 400 mg/dI was calcu-
`lated by dividing the LDL-C value by the HDL-C value.
`
`Analytic issues
`
`Weighting procedures
`
`The estimates are weighted to be national population
`estimates. Weighting was accomplished by inflating exam-
`ination findings for each examined person by the recipro-
`cal of selection probabilities adjusted to account for persons
`who were not examined and poststratifying
`by race, sex,
`and age. As a result of poststratification
`adjustments,
`the
`population estimates closely approximate
`the independent
`U.S. Bureau
`of
`the Census
`estimates
`for
`the civilian
`noninstitutionalized
`population of the United States at the
`midpoint of the survey (March 1, 197S).
`and
`Estimates of TC, HDL-C, non-HDL cholesterol
`the ratio of TC to HDL-C are based on the examined
`weights found in tape position 2S2–2S7 (24) of all NHANES
`II data release tapes.
`Estimates of serum triglyceride, LDL-C and the ratio
`of LDL-C to HDL-C are based on the OGTT weights
`found in tape positions 294-299 of all NHANES II data
`release tapes. These weights account for the fact that ordy
`half
`the adults
`examined in NHANES
`II
`received the
`OGTT test.
`A more detailed discussion of the calculation of sam-
`ple weights is in appendk
`I.
`
`Population estimates
`
`are presented
`estimates
`The 19S6 U.S. population
`by age, sex, and race in table VI of appendix
`I. The
`prevalence
`estimates
`shown
`in tables
`32-4S can be
`applied to these population
`estimates
`to obtain corre-
`sponding estimates of the number of U.S. adults affected.
`For example, 26.S percent of all persons had a high TC
`(TC >240 mg/dl) value (2)
`(table 34); multiplying that
`figure
`by the
`number
`of persons
`20-74
`years
`old
`(15S,639,000)
`from table VI
`results
`in an estimate
`of
`42,515,000 persons with high TC in 19S6.
`
`Estimates of percents, means, standard errors of the
`percents
`and means, and nine selected percentiles
`(5th,
`10th, 15th, 25th, 50th, 75th, S5th, 90th, and 95th) are
`presented
`for each lipid variable. These
`estimates
`are
`stable only if the sample
`size is sufficiently large. The
`sample size is sufficiently large for most subgroups;
`the
`exceptions are indicated with an asterisk.
`(See appendix II
`for further discussion of data presentation
`and reliabili~.)
`The number of black adults fasting 12 hours or more
`was too small
`to present
`statistically
`reliable
`sex- and
`age-specific estimates of serum triglyceride
`and LDL-C.
`Therefore,
`only unadjusted
`or crude estimates
`and age-
`adjusted estimates of these lipid variables are presented
`for black men and women. Because the number of women
`20-44 years old who fasted 12 hours or more prior
`to
`examination was insufficient
`to further
`strati~
`by oral
`contraceptive
`use, age, and race, estimates of serum trig-
`lyceride and LDL-C are not presented for these subgroups
`(table D).
`The reliability of an estimated mean or percent de-
`pends not only on the number of people upon which it is
`based but also on its relative standard error, defined as the
`ratio of the standard error of the estimate to the estimate
`times 100. The larger
`the relative standard
`error of the
`estimate
`the less reliable
`is the estimate.
`In the past,
`NCHS has recommended
`that
`the relative standard error
`of an estimate not exceed 25 percent.
`
`Percent needing lipoprotein analysis
`
`Program’s Ex-
`The National Cholesterol Education
`pert Committee on the Detection, Evaluation,
`and Treat-
`ment
`of High Blood Cholesterol
`in Adults
`has
`recommended
`a two-step process
`(2). This committee
`is
`also referred to as the Adult Treatment Panel or ATP.
`The first step in the ATP guidelines
`is based on the
`measurement
`of
`total cholesterol
`and an evaluation
`of
`CHD risk factor load. Adults with a high blood TC level of
`greater
`than or equal
`to 240 m@dl (6.21 mmol/L)
`are
`referred
`for lipoprotein
`analysis. Those with borderl