LIPID RESEARCH CLINICS (LRC) PROGRAM PREVALENCE STUDY

Visit 1 & Visit 2

# Table of Contents

[I. STUDY DESCRIPTION 3](#i.-study-description)

[A. Introduction 3](#introduction)

[B. Study Design and Populations 3](#study-design-and-populations)

[C. Data Collection Methods 4](#data-collection-methods)

[D. Procedures for Lipid Determinations
4](#procedures-for-lipid-determinations)

[E. Sampling Procedure for Recall to Visit 2 from Visit 1
7](#sampling-procedure-for-recall-to-visit-2-from-visit-1)

[F. Clinical Chemistries 11](#f.-clinical-chemistries)

[G. Procedures for Graded Exercise Test
13](#g.-procedures-for-graded-exercise-test)

[H. Procedures for Collecting and Processing Dietary Recall Data
16](#h.-procedures-for-collecting-and-processing-dietary-recall-data)

[I. General Data Editing and Correction Procedures
17](#i.-general-data-editing-and-correction-procedures)

[II. REFERENCES 26](#ii.-references)

# Table of Figures

[Figure 1 Flow Chart of the Selection Procedure for Visit 2
19](#__RefHeading___Toc88640362)

[Figure 2 Table 1: Population Description
20](#__RefHeading___Toc88640363)

[Figure 3 Table 2: Age-Specific Cutpoints Used in Selecting Subjects for
Visit 2 21](#__RefHeading___Toc88640364)

[Figure 4 Table 3: Grey Zone Numbers 22](#__RefHeading___Toc88640365)

[Figure 5 Table 4: Exclusion Criteria for GXT Protocol
24](#__RefHeading___Toc88640366)

[Figure 6 Table 5: Graded Exercise Test: Target Heart Rate (beats/min)
by Age and Physical Activity 25](#__RefHeading___Toc88640367)

#   {#section .unnumbered}

# I. STUDY DESCRIPTION

# Introduction

The purpose of this document is to provide users of the Lipids Research
Clinics (LRC) Program Prevalence data with an overview of study design,
data collection procedures, and data editing procedures. It also
contains overview information about the Limited Access Data sets (LAD)
created from the project. The LADs accompanying this document contain
the scientifically useful information collected from the Prevalence
study (including the related Family and Mortality Follow-Up components).
Data related to the identity of the participants and their relatives and
a variety of administrative information have been excluded or masked.
Data from the LRC Coronary Primary Prevention Trial (LRC-CPPT) are
documented and archived separately.

# Study Design and Populations

The LRC Program began in 1971 under the aegis of the National Heart,
Lung, and Blood Institute, National Institutes of Health. Part of this
program was the Lipid Research Clinics Prevalence Study, a standardized
series of cross-sectional surveys of various North American populations
designed to determine the prevalence of dyslipidemias and to describe
the distributions of lipids and lipoproteins in major ethnic and social
groups. In addition to contributing to the aggregate analysis, each
independent population-based study was designed with capabilities for
separate analyses of lipid and lipoprotein distributions. The
participating populations were not selected to be a probability sample
representative of the North American population per se, but by virtue of
their size and economic and geographical diversity, they provide a
useful cross-sectional group.

A description of these populations is summarized in Table 1, which also
provides the number of participants screened and response rates for
Visit 1 and Visit 2.

The populations of the study fall into three categories: occupational
groups, household or residential groups, and school children and their
parents. The occupational groups were ascertained through their
employers; the household groups typically were ascertained through
canvassing of residential areas; and children and their parents were
screened by determining the children in school and contacting their
parents.

All collaborative activities within the LRC Program have undergone
extensive standardization. Strict adherence to common protocols,
detailed documentation of procedures, personnel training, and regular
monitoring of data quality was enforced (1,2).

The Prevalence Study involved two sequential examinations. Visit 1 was a
brief screen to collect information on sociodemographic variables and
utilization of five types of lipid-altering medication, and to measure
plasma cholesterol and triglyceride levels in fasting participants ( \>=
12 hours). Visit 2 was a more extensive examination, recording medical
and family histories including a detailed drug history, blood pressure
measurements, lipid and lipoprotein determinations, nutrient intake
evaluation by means of a 24-hour dietary recall, resting and exercise
electrocardiograms, clinical chemistries, and anthropometric
measurements. Participants were not informed of the results of the Visit
1 lipid examinations prior to the completion of Visit 2. Data collection
occurred from 1972 to 1976. The median time between Visit 1 and Visit 2
was 96 days.

Some cautions should be reiterated in order to keep a proper perspective
on these data. First, the data from this Prevalence Study should not be
interpreted as representative of the total U.S. or Canadian populations.
The sampling strategy was not designed to provide representative
national samples. Further, the individual populations in the aggregate
sample were selected because of their differences; therefore, it is not
surprising that these differences carry over to the lipid and
lipoprotein distributions.

Some considerations of potential biases for study-wide estimates should
also be addressed. The first is a form of measurement error attributable
to the fact that five of the clinic populations (Baylor, Johns Hopkins,
La Jolla, Seattle, and Stanford) had their lipid and lipoprotein
cholesterol determinations measured using the Technicon AutoAnalyzer I
(AA-I) laboratory procedure, while the remaining determinations were
ascertained using the Technicon AutoAnalyzer II (AA-II) procedure
(Section II C). These two procedures give slightly different results,
and though not statistically significant, this factor is one of the
elements of difference among the populations.

Another consideration is the differential non-response among clinics.
Response rates for Visit 1 ranged from 64-86 percent, with an overall
rate of about 74 percent (Table 1). While the nonresponders are
difficult to characterize in general terms, the potential exists for the
probability of response to be correlated with characteristics measured
at Visits 1 and/or 2, which could introduce non-response bias in
study-wide estimates.

# Data Collection Methods

The methods of data collection for the different populations were
identical, with the exception of participant selection procedures. Table
1 lists the various populations interviewed. Although not required to be
identical, the participant selection procedures were all carefully
reviewed to ensure that the comparability of findings was preserved
across study populations. After collection at each clinic, data were
forwarded to one or more of a group of central agencies for coding,
further processing, and analyses.

The procedures used to enhance data quality were an important part of
the data collection process. Previous LRC publications have described
the details of these procedures (3,4). In general, all data were
collected or measured by trained and formally certified personnel.
Standard procedures included training sessions, periodic surveillance
through on-site reviews, and data reviews at the statistical center.
Data collection personnel were also required to initial sections of data
forms that they completed and record their personal code number. With
these code numbers, data could be reviewed, per interviewer, for
quality. Such reviews were conducted and did result in the deletion of
some data which were of questionable quality. The interviewer code
numbers and initials are not included in this data file. Visit 1 data
provide the bases for sociodemographic, sex, ethnic, and serum lipid
classifications. These participants served as the source population for
the more extensive Visit 2 examination and were selected according to
sampling criteria described below. Descriptive statistics for the Visit
1 and Visit 2 samples have been published previously (5,6).

# Procedures for Lipid Determinations

1.  Total Cholesterol and Triglycerides

Plasma cholesterol and triglyceride levels were determined in five LRCs
by use of the AA-I analytical system. This system used the ferric
chloride-sulfuric acid method to determine total cholesterol and a
fluorometric procedure for triglyceride. The other LRCs used the AA-II
system, which uses the same fluorometric procedure for triglyceride but
the Liebermann-Burchard procedure for cholesterol. The AA-II procedure
became available only after the first five clinics were well into
screening. Differences in the results obtained on fresh samples by the
two cholesterol methods were not statistically significant.

The procedures used to prepare plasma were the same in all laboratories
(7). Blood was drawn into an evacuated tube containing sufficient
disodium ethylenediaminetetraacetate (EDTA) to provide a final
concentration of 1-1.5 mg/ml. Samples were immediately mixed and cooled
to 4°C. Within 3 hours, cells were removed by centrifugation at 1500 x g
for 30 minutes. Plasma was then stored at 4°C.

Plasma, or the appropriate plasma fractions (500 ul), were mixed with
99% isopropanol (9.50 ml) and then treated with a zeolite-containing
mixture (2 g) to remove interfering substances. The solids were
sedimented by centrifugation (1500 x g, 30 min), and the cholesterol and
triglyceride concentrations of the supernatants were determined
simultaneously by either the AA-I or AA-II. In both cases, the
instruments were calibrated with solutions or primary standard grade
cholesterol or triolein that were prepared to contain H2O in a quantity
equivalent to that in the sample extracts, and that had been similarly
treated with zeolite mixture.

The AA-II method employed a serum calibration technique (8) to correct
the observed cholesterol values to equivalent reference values. The AA-I
method did not require serum calibration. The triglyceride method used
for both instruments required the hydrolysis of triglycerides and
measurement of glycerol that was released.

Due to quality control problems at some of the clinics in the early
stages of the Visit 1 screening phase of the study, some serum samples
were frozen and shipped to other LRC laboratories for analysis. The
cholesterol and triglyceride levels obtained from analyses of these
frozen serum samples were used in the selection of subjects recalled to
Visit 2, although freezing may affect the measurement of serum lipids.
Subjects with serum lipid measurements obtained from frozen serum
samples are identified in the data file by the variable INFR. A value of
INFR equal to 1 indicates that lipid measurements were obtained from
frozen serum, and a value of 0 indicates that lipid measurements were
obtained from non-frozen serum.

2.  Separation of HDL Lipoprotein

HDL cholesterol was measured in plasma after precipitation of the apo B
containing lipoproteins with heparin and manganese chloride.
Occasionally, the heparin-Mn2+-lipoprotein complex did not sediment
completely, as evidenced by slightly turbid heparin-Mn2+ supernatants.
When this occurred, plasma was centrifuged to remove VLDL and the
heparin-Mn2+ precipitation was performed in the d \< 1.006 g/ml
infranatant. Alternatively, the plasma was first diluted two to
threefold with 0.15 M NaCl before treatment with heparin-Mn2+.

3.  Other Lipoproteins

Lipoproteins were separated by ultracentrifugation at d = 1.006 g/ml.
The floating VLDL-containing layer and the infranatant LDL +
HDL-containing fraction were recovered by a tube slicing technique. The
infranatant fraction was reconstituted to original plasma volume. The
cholesterol concentration of the LDL + HDL-containing fraction was
measured. VLDL and LDL cholesterol concentrations were calculated as
follows:

VLDL chol = (total chol) - (d \> 1.006 fraction chol)

LDL chol = (d \> 1.006 g/ml fraction) - (HDL chol)

4.  Lipoprotein Electrophoresis

Paper or agarose gel electrophoresis was used qualitatively to identify
subjects with significant amounts of beta-VLDL or floating beta in their
plasma. This cholesterol-rich lipoprotein is found in the VLDL density
range, but has an electrophoretic mobility similar to LDL. When present,
it was detected as a beta-migrating band in the d \< 1.006 g/ml
fraction.

The details of the paper and agarose electrophoretic procedures (7) are
summarized as follows. Paper electrophoresis was performed at room
temperature. The samples were applied to paper strips (Whatman No. 1)
that had been equilibrated with 0.12 M barbital buffer, pH 8.6,
containing EDTA (1 x 10^-3^M) and bovine serum albumin (1%, w/v) and
allowed to migrate for 16 hours at constant voltage (120 v). The
electropherograms were dried at 90°C, stained for approximately 1.5
hours with a solution of Oil Red 0 (0.4 g/l) in 60% (v/v) ethanol, and
then allowed to dry at room temperature. Agarose gel electrophoresis was
based on the method of Noble and was performed at room temperature using
either gel plates that were prepared in the laboratory or precast plates
that were available commercially. Samples were applied to 0.5% (w/v)
agarose gel that had been equilibrated with 0.05 M barbital buffer, pH
8.6, containing 0.05% (w/v) BSA. The time of electrophoresis and current
flow varied somewhat in the different laboratories depending on the
particular system in use, but in general, the lipoproteins were allowed
to migrate for 20-40 minutes at constant voltage (about 20 v/cm). The
plates were then fixed and stained with either Sudan Black or Fat Red
7B, both of which produced intensely stained lipoprotein bands against a
colorless transparent background.

To ensure that results were comparable across all clinics, all
participating laboratories followed standardized procedures specified
for the LRC Program (7). Technicians were thoroughly trained in the use
of the equipment as well as in the correct analytic procedures. The
first five clinics entering the program began analyzing samples using
AA-I instruments. The subsequent five clinics used the AA-II.
Eventually, all clinics in the LRC Program adopted the use of the AA-II,
but the original five clinics completed the Prevalence Study with the
AA-I instruments to ensure consistency of measurement within each clinic
during the Visit 2 phase of the Prevalence Study. Each laboratory
successfully completed a standardization program designed specifically
for the LRC Program and administered by the Lipids Section, Center for
Disease Control, before analyzing study samples. Thereafter,
laboratories continued to analyze both internal (bench) control pools
and external (blind) surveillance pools for the duration of the study.
The overall performance of the laboratories has been reported (9,10).

# Sampling Procedure for Recall to Visit 2 from Visit 1

1\. Description of Sampling Procedure

A sample to be further studied at Visit 2 was selected from all of the
attendees of Visit 1. The Visit 2 sample was drawn from those
individuals whose cholesterol and triglyceride levels were properly
measured at Visit 1. From this group of eligible participants, subjects
were recalled to Visit 2 using a complex sampling algorithm described in
the Reference Manual for the Lipid Research Clinics Program Prevalence
Study (2). A simplified version of this algorithm is illustrated in
Figure 1. Approximately 25% of Visit 1 attendees were selected for Visit
2.

As illustrated in the figure, the selection of Visit 2 participants was
made in a hierarchical fashion. First, all Visit 1 participants were
assigned a random number from 1 to 100 and those with a random number
less than or equal to 15 were recalled to Visit 2. Next, from the
unselected participants those taking lipid lowering medications were
selected.

With regard to the remaining non-pregnant Visit 1 participants,
eligibility for recall to Visit 2 was based on elevated serum
cholesterol and triglyceride values. Some comments regarding the study
protocol and definitions of "elevated" serum lipid levels are necessary
to understand the selection process. Since pregnancy affects serum lipid
levels, only non-pregnant women were eligible for recall due to elevated
serum lipids. Also, since serum triglycerides are elevated in
non-fasting persons, only persons with fasting serum triglyceride
measurements were eligible for recall due to elevated serum
triglycerides. A person was determined to have "high" serum cholesterol
or triglyceride values if their serum cholesterol or triglycerides were
greater than or equal to the age-specific cutpoints CU, TU shown in
Table 2. A person was determined to have "Grey Zone" serum cholesterol
or triglycerides if their respective serum lipid levels fell

between the upper and lower age-specific cutpoints presented in Table 2,
i.e., greater than or equal to the lower age-specific cutpoints CL, TL
and less than the upper age-specific cutpoints CU, TU.

From the non-pregnant participants not selected to this point those with
"high" cholesterol were selected to participate in Visit 2. Further, a
sample of those with "Grey Zone" cholesterol levels was selected. This
was done by choosing "Grey Zone" participants with random numbers less
than or equal to the age/race/sex/clinic specific "Grey Zone" numbers
provided in Table 3. Then, from the remaining non-pregnant fasting
participants, all of those with "high" triglycerides were selected.
Finally, from the remaining non-pregnant fasting participants, a sample
of those with "Grey Zone" triglycerides was selected by the same means
as the cholesterol "Grey Zone" sample was chosen.

The variable V2RECALL on the data file indicates the status of each
Visit 1 subject according to his selection for participation in Visit 2.
A V2RECALL value of:

0 indicates a subject was not selected for recall to Visit 2;

1 indicates the subject was selected for recall to Visit 2 as part of
the random sample;

2 indicates the subject was selected for recall, but not as part of the
random sample.

V2RECALL indicates only whether a person was invited to return for the
Visit 2 examination, and not whether they actually participated in the
Visit 2 examination.

2\. Special Sampling Issues

The following issues regarding measurement of serum lipids should be
noted. The triglyceride measurement technique used by the LRCs required
the hydrolysis of triglycerides and measurement of glycerol that was
released. At high levels of serum triglyceride, the absolute amount of
free glycerol in the serum may be high. In order to adjust for the
amount of free glycerol in the serum, "triglyceride blank" measurements
of free glycerol were made for persons with serum triglyceride values
over 300 mg/dl. This triglyceride blank value was subtracted from the
raw (unblanked) triglyceride value to give a corrected (blanked) value.
However, in the early stages of Visit 1 screening, triglyceride blank
measurements were not obtained for subjects with triglyceride levels
over 300 mg/dl. A missing value on the data file for the triglyceride
blank for a subject with an unblanked triglyceride value greater than
300 mg/dl indicates that a triglyceride blank was not obtained. In this
case, sampling decisions were made using the unblanked triglyceride
value; in cases where a triglyceride blank was obtained and the
unblanked value was greater than 300 mg/dl, the blanked value (unblanked
triglyceride minus the triglyceride blank) was used. Since some clinics
began screening participants earlier than others, the use of unblanked
triglyceride values occurred more frequently in some of the LRC
populations. This issue does not affect the sampling probabilities;
however, some subjects were recalled using a positively biased
measurement of triglyceride.

Due to quality control problems at some of the clinics early in the
study, some serum samples were frozen and shipped to other LRC
laboratories for analysis. The cholesterol and triglyceride levels
obtained from analysis of these frozen serum samples were used in the
selection of subjects recalled to Visit 2, although freezing may affect
the measurement of serum lipids. Subjects with serum lipid measurements
obtained from frozen serum samples are identified in the data file by
the variable INFR. A value of INFR of 1 indicates that the Visit 1 lipid
measurements were obtained from frozen serum; a value of 0 indicates
that the Visit 1 lipid measurements were obtained from nonfrozen serum.

Some participants came to Visit 1 having fasted less than 12 hours.
According to the Visit 1 protocol, a subject was to be recalled to Visit
1 for a fasting serum lipid measurement only if they were not recalled
to Visit 2:

1\) as part of the random sample, or

2\) due to use of lipid-lowering medications, or

3\) due to hypercholesterolemia or "Grey Zone" hypercholesterolemia, and
if the serum triglyceride measurement was greater than or equal to the
lower age-specific cutpoint.

This may lead to error in estimating sampling probabilities. For
example, a nonfasting subject with elevated serum triglycerides who was
recalled to Visit 2 as part of the random sample would appear to have a
sampling probability of 100 percent. However, the actual sampling
probability may be lower (e.g., 15 percent) since their fasting
triglyceride level may be in the normolipidemic range. For this reason,
the LRC has routinely excluded nonfasters at Visit 1 from computations
of weights based on sampling probabilities, as well as from analyses of
serum lipid levels.

A similar problem exists for women who were pregnant at Visit 1, since
serum lipid levels may be increased during pregnancy. Since pregnant
Visit 1 subjects could have been recalled to Visit 2 as part of the
random sample, but were not eligible to be recalled to Visit 2 due to
hyperlipidemia, their apparent sampling probabilities may be in error.
The LRC has routinely excluded women who were pregnant at Visit 1 from
computations of sampling probabilities. Note that according to the Visit
2 protocol, women who were pregnant when appearing for the Visit 2
interview were not to be examined, but were to be recalled three months
postpartum. However, there were three pregnant women who were examined
at Visit 2.

3\. Sampling Weights

From the description of the sampling procedures for the Visit 2 study
given in section E.1, it is clear that individuals in the Visit 2 study
are selected with unequal probabilities of selection. For example,
normolipidemic subjects (i.e., subjects with both cholesterol and
triglyceride levels at Visit 1 below the age-specific cutpoints C~L~,
T~L~ shown in Table 2) were selected with a 15 percent sampling
probability, whereas all nonpregnant hyperlipidemics (i.e., subjects
having a fasting triglyceride or cholesterol level greater than or equal
to the age-specific cutpoints C~U~, T~U~ shown in Table 2 or having a
current prescription for a lipid lowering medication) were selected with
100 percent sampling probability. In addition, subjects with "Grey Zone"
lipid levels (i.e., subjects whose lipid levels fall between the upper
and lower age-specific cutpoints presented in Table 2) were selected
with different selection probabilities that depended on the
age/race/sex/clinic category of the subject.

In analyzing data from the Visit 2 study, users may want to weight the
data to take into account these unequal sampling probabilities in order
to make inferences regarding the Visit 1 population. An appropriate
weight for a subject is the inverse of the sampling probability for that
subject. However, given the complex sampling scheme used in selecting
subjects for the Visit 2 examination, the exact sampling probabilities
are difficult to determine. The discussion below briefly outlines the
general issues regarding the construction of sampling weights. Users not
familiar with sampling issues are advised to consult sampling
statisticians for proper analysis of the data.

One may recall that the Visit 2 study initially selected all Visit 1
participants with a random number less than or equal to 15. This
selection procedure means that one can form a Visit 2 study population
with all subjects selected from the Visit 1 attendees with a selection
probability of 15 percent. The 15 percent random sample can be easily
identified on the data file by the variable V2RECALL. The variable
V2RECALL on the data file is coded as follows:

0 = the subject was not recalled to Visit 2,

1 = the subject was recalled as part of the 15 percent random sample,

2 = the subject was recalled, but not as a part of the 15 percent random
sample.

If the analysis is restricted to the random sample, one need not do any
weighting in the analysis of data. However, restricting analysis to the
random sample results in the loss of approximately one-half of the data.

In the full Visit 2 sample, the selection probabilities depend on the
subjects' age, sex, race, clinic, medication use status, and serum lipid
levels. Hence, the sampling weights are computed for each stratum
defined by its sample design variables. For each stratum, the sampling
weight can be computed as the ratio of the number of Visit 1 subjects
falling in a specified stratum to the number of those who participated
in the Visit 2 screening in the same stratum. This ratio is a
satisfactory approximation of the inverse of the sampling probability
for a subject. Note that the sampling weight defined above is based on
the persons who actually participated in the Visit 2 study.

Although it is simple to compute sampling weights in a specified
stratum, care should be taken in the construction of strata and in the
analysis of data that takes into account the sampling weights. A number
of such issues are discussed below.

In the actual selection process, the sampling probabilities depend on
seven age groups (\<10, 10-19, 20-29, 30-39, 40-49, 50-59, 60+), two
race groups (whites and other nonblacks, and blacks), two sex groups
(male, female), and ten clinics. These sample design characteristics
form 280 (7 x 2 x 2 x 10) strata. There is another stratum defined by
hyperlipidemia and lipid lowering medication use for which 100 percent
of the subjects were selected. In addition, there is another stratum
containing normolipidemics who were part of the 15% random sample. In
distributing all Visit 2 participants into these 282 strata, there will
be several strata with less than two participants so that meaningful
weights and variances cannot be computed. Because of the sparseness of
data, it is often necessary to collapse strata to obtain meaningful
weights. The collapsing of strata depends on the type of analysis, the
subgroups under analysis and exclusions. The process of collapsing
strata is generally accomplished by identifying strata with few subjects
and then merging strata with similar sampling probabilities. The
sampling weights are computed as the ratio of the number of Visit 1
subjects to the number of Visit 2 subjects within the collapsed strata.
Strata containing large numbers of subjects with similar sampling
probabilities may also be combined to simplify the computation of
weights and to reduce the number of strata. Since the decisions
regarding collapsing of strata are analysis specific, sampling weights
have not been provided on this data file. Note that it is necessary to
use the Lipid Research Clinics Prevalence Study Visit 1 Limited Access
Dataset to obtain the number of subjects at Visit 1 within sampling
strata.

Sometimes, dropping a very small number of subjects can be done to
minimize the number of strata. For example, if one is interested in
studying white male children under twelve years of age, dropping several
clinics with no or a very small number of children and dropping the
oversampled "Grey Zone" subjects results in minimum loss of subjects.
Thus, one needs to form only two strata: all hyperlipidemics and
nonhyperlipidemics.

If one wants to use larger groups of Visit 2 subjects (such as white
males ages 20 and above) in the analysis, reduction of strata can be
done by collapsing strata with similar sampling probabilities based on a
sample defining variable (such as clinic or age group) and deleting
subjects in strata containing small numbers of oversampled "Grey Zone"
subjects. Users are advised to consult a sampling statistician in
creating the optimal number of strata.

Statistical summary measures, such as means and proportions, that take
into account sample weights can be easily computed using standard
statistical packages (e.g., SAS, SPSS, BMDP). However, computation of
standard errors that take into account sampling design requires special
computational formulas and greater care in collapsing strata. Also,
fitting of statistical models, such as linear regression, logistic
regression, or proportional hazards models that account for sample
design requires special procedures. Users are advised to examine some of
the special computer program developed for this purpose (e.g., SUPERCARP
(11), SURREGR (12), SESUDAAN (13), etc.).

#  F. Clinical Chemistries

1.  Introduction

The clinical chemistries measured were: glucose, aspartate
aminotransferase (AST), alkaline phosphatase, thyroxine, total
bilirubin, total globulin, uric acid, and creatinine. These chemistries
were chosen because they are indicators of conditions or metabolic
abnormalities associated with lipid and lipoprotein levels.

One source of potential bias for study-wide estimates is unique to the
clinical chemistry determinations. The laboratory originally designated
to be the Central Clinical Chemistry Laboratory (CCCL), the Laboratory
Procedures Division of the Upjohn Company, did not meet all the quality
control criteria set forth in the study protocol. Therefore, early on in
the study, the CCCL was moved to BioScience Laboratories (BSL) in Van
Nuys, California.

Since most of the values obtained by the first laboratory were deemed to
be either unreliable or not comparable to BSL's measurements, the
clinical chemistry measurements analyzed at Laboratory Procedures have
not been included on this data set. Laboratory Procedures' plasma
glucose measurements, however, were judged to be acceptable and
comparable and are included in a special variable in this data set.

Overall, the effect of this problem should be modest, since Laboratory
Procedures analyzed 1,656 samples out of nearly 14,000. Still, since the
proportion of missing records differs by clinic, this situation should
be considered when using these data.

2.  Quality Control

Quality control of the clinical chemistries evaluations was rigorous.
Commercial lyophilized control sera at two concentration levels were
included in each analytical run. Precision limits for this internal
monitoring system had to be satisfied before the run was accepted.
Additionally, both internal and external blind resubmission programs for
monitoring performance were in effect during the course of this study.
These programs assessed precision and methodological drift.

The external surveillance program consisted of submitting two types of
blind samples to the central laboratory. Twice monthly, two times the
usual amount of blood was drawn from a randomly selected Visit 2 subject
at each LRC. These samples were equally divided, one half was given the
subject's identification number and, according to protocol, mailed to
the central laboratory the week it was drawn. The other half was
assigned a dummy identification number, stored at -20°C, and mailed one
week later. Upon completion of the analyses, the laboratories forwarded
all results to the coordinating center. After receipt of the results,
the coordinating center checked values of split specimens for
comparability.

In addition to these split samples, on a weekly basis, each LRC
submitted to the central laboratory one "pool" sample prepared by the
Centers for Disease Control (CDC) and distributed to the LRCs. The
sample was given a dummy identification number and submitted in the same
manner as Visit 2 subject samples. Prior to instituting a pool, reliable
reference values were established by the CCCL and CDC. The CCCL employed
the study test methods, performing replicate analyses over a period of
30 days. The CDC performed 6 to 12 replicate analyses using reference
procedures for initial value assignment. Subsequently, pool reference
values were established using the weighted average of analyses done at
the CCCL on blind and open samples during a 10-week period. Each month,
the results of that month's analyses were compared to the reference
values in order to monitor precision and drift over time.

Outliers were monitored using two methods, analysis of split samples and
analysis of pooled sera. If a value for a given constituent measured in
the two halves of a split sample did not agree sufficiently with one
another or if analysis of pooled sera yielded a value for one of the
constituents that was unacceptably divergent from the target value for
the pooled sample, the value was considered to be an outlier.

A test procedure was declared "out of control" due to (1) bias of the
pool samples, (2) too many pool sample outliers, (3) poor precision for
the pool samples, (4) too many split sample outliers, or (5) poor
precision for the split samples. Specific statistical criteria were
developed for each of the above problems. If a procedure's performance
was declared "out of control," the samples associated with the
respective analytical runs were retested.

A report summarizing the CCCL's performance was prepared monthly by the
coordinating center. This report was evaluated by the Lipid Metabolism
Branch, NHLBI, and also by an advisory group of clinical chemistries
consultants.

3\. Procedures for Clinical Chemistry Determinations

a.  Conditions of blood collection

At Visit 2, participants reported to the LRC after an overnight fast of
at least 12 hours. After participants remained seated for at least 5
minutes, a tourniquet was applied to distend the antecubital vein. The
tourniquet was released just prior to removal of the blood sample. Blood
was drawn through a 1.5" 20-gauge needle into either plain evacuated
tubes or evacuated tubes containing anticoagulant (heparin/fluoride).
Tubes were labeled and anticoagulated samples mixed promptly by
inverting 8 times. Tubes with no anticoagulant were left standing 0.5 to
2 hours at room temperature, while tubes with anticoagulant were placed
in wet ice. After centrifugation at 1500 x g for 15 minutes, serum and
plasma to be used for the analyses were frozen at -20°C.

b.  Processing of samples

The Visit 2 serum (7.5 mL minimum) and plasma (3.0 mL minimum) aliquots,
stored at -20°C, were packed in dry ice and shipped frozen, either to
BSL, Van Nuys, CA, or to Laboratory Procedures Division of the Upjohn
Company, King of Prussia, PA. Laboratory Procedures served as the CCCL
from the beginning of the Prevalence Study to September 1973. BSL served
as the CCCL from September 1973 to the completion of the Prevalence
Study in June 1976 (see Section F.1).

Upon arrival at the laboratory, serum and plasma samples were thawed at
room temperature, mixed on a rotating wheel, examined visually for
hemolysis, turbidity, or lipemia and aliquoted for analysis.

Serum was used for all tests except glucose, which was determined from a
plasma sample. Alkaline phosphatase activity was determined by a
p-nitrophenylphosphate method (14). Serum thyroxine levels were measured
by a competitive protein-binding technique (15,16). Serum uric acid
levels were determined on the AutoAnalyzer I (AA-I) by a
phosphotungstate method (17). Serum bilirubin was determined by the
method of Jendrassik and Grof, modified for the AutoAnalyzer II (AA-II)
(18). Serum aspartate aminotransferase (AST) activity was determined by
a modification of the method of Karmen (19,20). Serum globulins were
measured by a colorimetric method (21). Serum creatinine was measured by
a colorimetric picrate method (17,22). At Laboratory Procedures, plasma
glucose was measured by the ferricyanide method in a single channel
AutoAnalyzer (23). At BSL, plasma glucose was measured on the ABA-100 by
a hexokinase method (24).

#  G. Procedures for Graded Exercise Test

Each study participant recalled to Visit 2 was invited to take a graded
exercise test. Those participants who gave informed consent and were not
excluded for health reasons were given the test according to the LRC
protocol requirements. Electrocardiograph technicians from each LRC
attended special training programs and were certified for standardized
performance of all phases of the procedure. Treadmill testing was
usually performed in the morning; subjects were told not to eat within
the two hours prior to testing. A physician was present during all
tests. Before the treadmill test was undertaken, a standardized physical
examination, with emphasis on the cardiopulmonary system, was performed
by the attending physician. Those with contraindications were either
rescheduled or excluded. Contraindications to exercise testing were
either temporary in nature and resulted in rescheduling of the test to a
later date, or of a more serious nature, leading to the exclusion of the
participant. Temporary exclusions included that the participant had
taken food in the past two hours, or that the subject reported symptoms
indicative of a possible recent infarction, recent fainting, or acute
illness. Reasons for exclusion outright from the protocol can be seen in
Table 4. Overall, 616 persons were excluded from exercise testing on the
basis of contraindications.

Each eligible patient was disrobed to the waist and chest hair was
removed from electrode sites, which were then marked with ink, cleansed
with acetone, and lightly touched with a #6 spherical dental burr spun
by a Dremel MotoTool. (Some laboratories used other acceptable means of
reducing skin resistance.) Fluid column electrodes fitted with
disposable self-adhering disks were then applied for 15 standard leads
(I, II, III, aVR, aVL, aVF, V1 through V6, X, Y, Z). Limb electrodes
were applied to the torso as described by Mason and Likar (25). The
electrocardiograph (ECG) cable was draped over the left shoulder; an
eight-inch wide, disposable elastic bandage was wrapped around the chest
and over the electrodes and cable, with just enough tension to hold them
in place and to stabilize the subcutaneous tissues during exercise.

EGG recordings were made on paper and magnetic tape using a Hewlett-
Packard model #1516A recorder. A resting 15-lead EGG was recorded in the
supine, sitting, and standing positions. The ECG was then examined by
the physician for evidence of myocardial ischemia, hypertrophy,
tachycardia, arrhythmia, or advanced intracardiac conduction block.
While this was being done, blood pressure was measured in the left arm
and recorded.

The treadmill procedure was then explained to the subjects found
suitable for exercise testing. The test was performed on a motor-driven
and electrically controlled treadmill (Quinton model #1849C) in
uninterrupted three-minute stages. The treadmill exercise schedule was
adapted from the Bruce multistage exercise test. Exercise was performed
at the following speeds (mph) and slopes (% grade): stage 0-1.7, 0%;
stage one-half-1.7, 5%; stage one-1.7, 10%; stage two-2.5, 12%; stage
three-3.4, 14%; stage four-4.2, 16%; stage five-5.0, 18%; stage six-5.5,
20%; stage seven-6.0, 22%. The exercise test was begun at stage one,
unless the subject's appearance and demeanor suggested that walking
capacity was limited. For each subject, a target heart rate of 90% of
predicted maximal was selected on the basis of age and physical activity
(see Table 5) (26). A person was considered physically active if he/she
regularly engaged in hard physical labor or exercised strenuously at
least three times a week.

During the test, subjects were repeatedly questioned about their
subjective responses, especially in regard to chest discomfort, other
pain or discomfort, shortness of breath, fatigue, dizziness, and visual
disturbances. Their expressions, posture, and gait were observed. There
was periodic palpation of the arms, shoulders, and forehead for
estimation of skin temperature and sweating. Heart rate was monitored
continuously during exercise using an electrocardiographic
cardiotachometer and was recorded at the end of every three-minute stage
and at the time the subject stopped during the last stage attained.
Blood pressure was measured once near the end of each three-minute
treadmill stage. Subjects were allowed to touch the treadmill handrails
for balance, but were not allowed to pull or lean on them.

The ECG was monitored carefully and continuously on an oscilloscope.
During exercise, leads X, Y, and Z were recorded for the first two and
one-half minutes of each stage on magnetic tape for processing. During
the last thirty seconds of each stage, the recording was switched to
leads V4, V5, and V6. Recording was interrupted whenever exercise was
terminated, and a few seconds after the end of exercise, recording of
leads V4, V5, and V6 was begun for thirty seconds. Alternate recording
of lead groups X, Y, and Z and V4, V5, and V6 continued for six minutes
postexercise, with the V4, V5, and V6 groups only recorded for thirty
second intervals at the end of the second and fifth minutes
postexercise. Several seconds of each lead group during each stage were
recorded on paper strips as a back-up if the computer tape was damaged
or lost. Cardiac resuscitation equipment was always readily available.

The exercise test was terminated for any of the following reasons:

1\. Subjective response: the subject was unwilling or unable to continue
exercise because of dyspnea or fatigue (subjective maximal test).

2\. Development of potential hazards to the subject (e.g. ventricular
arrhythmia, leg pain, chest pain, ST changes, supraventricular
tachycardia, other arrythmias, hypotension, cerebral symptoms,
intracardiac block, excessive hypertension).

3\. Attainment of near-maximal exercise: exercise was stopped if the
subject attained age-predicted target heart rate and maintained it for
one minute, if the subject maintained it until the end of the ongoing
exercise stage, or if subject's heart rate exceeded target heart rate by
8 beats/min., whichever occurred first.

At the instant of treadmill exercise termination, the participants were
helped to chairs where blood pressure was recorded, cardiac ausculation
was performed, and ECG monitoring continued. Blood pressures were
recorded at two, four, and six minutes postexercise, and subjects were
questioned about symptoms present at the time or about those they may
have failed to report in the final moments of exercise. The results of
the test were then discussed with the subject.

The ECGs of the exercise tests were processed and coded at the Central
Electrocardiographic Laboratory (CEL), University of Alabama,
Birmingham. At the CEL, all resting electrocardiograms were classified
uniformly, according to the Minnesota code, by two rigorously trained
coders and reviewed by a supervisor (27). The latter adjudicated any
discrepancies between the coders, in consultation with two CEL
cardiologists, when necessary. The coders adhered to carefully defined
visual coding criteria which included an internal quality control
system. The resting ECG was also analyzed by the Mayo Clinic computer
program and the results compared with the visual coding. Any
discrepancies were adjudicated by CEL cardiologists. The exercise ECG
was also visually coded and computer analyzed by the CEL's own EKAP-III
program (28). Differences between visual and computer coding were
adjudicated by the coding supervisor, in consultation with one of the
two cardiologists at the CEL, if necessary. These results were forwarded
to the LRC Central Patient Registry (CPR), University of North Carolina,
Chapel Hill.

#  H. Procedures for Collecting and Processing Dietary Recall Data 

1\. Procedures for Coding Raw Food Data

Dietary recall data were coded centrally at the Nutrition Coding Center,
University of Minnesota, Minneapolis. Coding involved conversion of each
completely described food item to the appropriate NHLBI food code. This
involved completion of dietary recall columns labeled NHLBI food code,
Frequency, Food unit, Prep code, and Fat code. The food code selected
was selected from the most recent edition of the NHLBI codebook and was
to match as closely as possible the food description provided. Frequency
and food unit columns were used to describe quantity consumed relative
to serving sizes in the NHLBI codebook. Prep codes were used to
designate computerized coding rules whereby the computer added a
standard amount of fat per food unit. The amount of fat added for
various preparation methods was determined by experimentation and
represented the average amounts of fat absorbed by foods when prepared
by a particular method. If the dietary interviewer had information to
indicate that an individual actually consumed more or less fat per food
unit than would be added by the computerized food preparation code, food
item and fat used were entered and coded separately. Four-letter code
words were used in the Fat code column to indicate the kind of fat added
in the preparation of a food item. Fat codes were included for all foods
with a Prep code designation. If the kind of fat used was unknown,
computerized fat coding rules were used to either represent the fat most
likely to be used in recipes made commercially or at home (APF items) or
fats typically used when foods were prepared by selected Prep codes.
More complete instructions appear in Sections III.A through III.I of the
manual titled "Instructions for Dietary Recall, March 1976" included in
this release of the limited access data.

2\. Peripheral Coding of Dietary Recalls

A five percent sample of all recalls taken by a given nutritionist were
coded locally. This procedure was required to maintain the awareness of
the nutritionist of the detail required in dietary interviewing.
Applicants for certification as dietary recall interviewers participated
in pre-training which reviewed not only use of specific forms and
dietary interviewing, but also exercises to familiarize the individual
with the concepts of coding and the NHLBI codebook. Sections III.A
through 111.1 of the manual titled "Instructions for Dietary Recall,
March 1976" contain explicit instructions given to dietary recall
interviewers for peripheral coding.

3\. Editing and Processing of Dietary Recall Data

Dietary data coded at the NCC were sent to the LRC Central Patient
Registry at Chapel Hill for keypunching, processing into nutrient
values, and editing. Tables provided by the NCC included the NHLBI Food
Table, and fat and preparation code reference tables. At the LRC, these
tables of information were used by the nutrition edit program (NUEDUP)
and the nutrient calculation program (NUCRANK) to calculate nutrient
totals from the dietary recall forms, and check for data correctness.
The edit procedures were used to check for out of range nutrient values
for macronutrients, keypunch error, NCC error, or LRC error.

When per day calculated nutrient values exceeded selected thresholds,
the dietary recall was flagged for further attention. Flagged recalls
were checked for keypunch errors by nutrition data processing staff.
Nutrient totals for corrected recalls were recalculated. Out of range
values were checked against foods consumed to determine the correctness
of coding relative to foods consumed (e.g., subject consumed 10 cokes
resulting in out of range carbohydrate, but recall was coded correctly).
Recalls were edited to determine correctness of other NCC coding, e.g.,
"frequency" coding, etc. Recalls were recalculated based on corrections
made. Finally, a small number of flagged recalls were determined to be
permanently questionable if resolution of an out of range value could
not be determined.

Although in-house informal descriptive statistics have been estimated
for all micronutrients, calculated nutrient variables have not been
subjected to the same threshold out of range edit checks that have been
done for the macronutrients.

4\. Dietary Data Quality Control

Internal quality control procedures were established within the NCC to
insure maintenance of a high level of coding quality. In addition, an
external quality control program was established 1) to track coding
accuracy, defined as the percent deviation in the coding of a recall
from the "official" coding of that same recall, 2) to estimate between
coder variability, and 3) to measure system drift. To meet these
objectives, 50 "standards" were selected at random from regularly coded
recalls, excluding those with seasonal or other food items that were
potentially unbinding. These standards were sent to the clinics where
they were transcribed onto new forms with current dates. They then
entered the normal data flow, e.g., transcribed recalls sent from clinic
to CPR, batches of recalls sent to NCC from CPR for coding, coded recall
returned to CPR for keypunch, and processing through edit, calculations,
and analysis. Thus, quality control standards were indistinguishable
from current recalls. Provision of internal and external quality control
procedures has provided a high quality of LRC Prevalence Study nutrition
data.

#  I. General Data Editing and Correction Procedures

Errors in data items on the LRC master and analysis files have been
detected through a variety of mechanisms, both during file creation and
data analysis. During the creation of the master data files, data
editing identified values of variables which were out of their allowable
range and values that were inconsistent with other measurements. For
each variable, the status\--acceptable value, possible keypunch error,
value out of range, etc.\--was recorded on the master data files. Error
correction forms were sent to the clinics to either verify or correct
potentially erroneous values. In many cases errors were identified,
corrections made on the master files, and the status of the variables
reset to acceptable. However, some values were identified as "correct"
by the clinics and were retained on the master files, some with a
"non-acceptable" value of the status indicator. Unsolicited error
correction forms were also submitted by clinics as a result of their own
internal review and data editing.

During analysis file creation and data analysis, checks of the data
revealed other possible errors. Procedures performed at the Central
Patient Registry and Coordinating Center (CPR) to identify possible
errors included examination of extreme values of continuous variables,
frequency distribution checks of discrete variables for permissible
values, bivariate plots of related variables, and checks for consistency
among related variables. Records of persons with invalid, unusual, or
inconsistent values were printed and compared to microfilmed copies of
the original paper forms to check for data processing errors. When the
reason for a potential error was not readily apparent, the clinic was
contacted to determine if an error existed. In some instances, the
clinics responded by submitting a correction form. However, in many
cases, the clinic verified that the suspicious value agreed with the
value on the clinic file.

During preparation of previous LRC Prevalence Public Use data files in
1986-90, an attempt was made to correct all known data errors. Data
values were corrected when possible and set to missing when the true
values could not be determined. Since a few of these errors have been
documented as late as 1986-90, only, the data in this file do not
correspond exactly with the data and sample sizes presented in previous
LRC publications. These recent corrections involve changes to a few
records/subjects only:

-   Visit 1 data: Changes to data for 111 subjects, deletion of 5
    duplicate records, and addition of 1 record.

-   Visit 2 Interview data: Changes to data for 242 subjects and
    addition of 1 record.

-   Clinical Chemistries data: Changes to data for 13 subjects.

-   Graded Exercise Test data: Change to 238 data values for 167
    subjects and addition of 1 record.

-   Nutrition data: No new corrections.

An additional source of discrepancy in sample size between this data
file and the LRC Population Studies Data Books (5,6) is caused by the
erroneous duplication of three records during the preparation of tables
for the Data Books. The algorithm for the computation of age has been
revised to include day of birth, which has resulted in Visit 1 age
changes to five subjects and Visit 2 age changes (reduction in age by
one year) for 594 subjects..

Prior to the formal start of the Visit 1 screening program, a pilot
phase was conducted. Volunteers for this pilot phase were not
specifically recruited from the target population identified by the
clinic. Data for these persons are not included on this data file,
unless they were subsequently selected as part of a clinic's target
population.

Some Visit 1 subjects were recalled to obtain a fasting serum lipid
sample. To avoid duplicate records for individual subjects, only data
from the last Visit 1 interview for these subjects has been retained on
this file.

[]{#__RefHeading___Toc88640362 .anchor}Figure 1 Flow Chart of the
Selection Procedure for Visit 2

(Detailed in the Reference Manual for Lipid

Research Clinics Program Prevalence Study)

![](media/image1.png){width="6.577083333333333in"
height="8.016666666666667in"}

[]{#__RefHeading___Toc88640363 .anchor}Figure 2 Table 1: Population
Description

Number of Eligible Subjects, and

Percent of Subjects Screened at Prevalence Study Visit 1 (in
parentheses) and Visit 2

+-----------------+-------------+-----------+-------------+-------------+
| Sampling Frame  | Clinic Name | Number    | Number      | Percent     |
|                 |             | Eligible  | Screened    | Response    |
+-----------------+-------------+-----------+-------------+-------------+
|                 |             |           |             |             |
+-----------------+-------------+-----------+-------------+-------------+
| Occupational    | (SE)        | (6,046)   | (4,999)     | \(83\)      |
| Groups          |             |           |             |             |
|                 |             | 1,388     | 1,191       | 86          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (ST)        | (6,028)   | (4,280)     | \(71\)      |
|                 |             |           |             |             |
|                 |             | 1,189     | 1,074       | 90          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (TR)        | (11,968)  | (8,208)     | \(69\)      |
|                 |             |           |             |             |
|                 |             | 2,182     | 1,781       | 82          |
+-----------------+-------------+-----------+-------------+-------------+
| Households      | (IA)        | (5,594)   | (3,918)     | \(70\)      |
|                 |             |           |             |             |
|                 |             | 1,099     | 999         | 91          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (JH)        | (5,075)   | (4,389)     | \(86\)      |
|                 |             |           |             |             |
|                 |             | 1,146     | 1,041       | 91          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (LJ)        | (7,791)   | (6,086)     | \(78\)      |
|                 |             |           |             |             |
|                 |             | 1,644     | 1,459       | 89          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (MN)        | (8,392)   | (6,750)     | \(80\)      |
|                 |             |           |             |             |
|                 |             | 1,779     | 1,380       | 78          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (KC)        | (9,522)   | (7,179)     | \(75\)      |
|                 |             |           |             |             |
|                 |             | 1,958     | 1,638       | 84          |
+-----------------+-------------+-----------+-------------+-------------+
| School-children | (BA)        | (5,939)   | (3,795)     | \(64\)      |
| and their       |             |           |             |             |
| parents         |             | 902       | 637         | 71          |
+-----------------+-------------+-----------+-------------+-------------+
|                 | (CN)        | (15,571)  | (10,891)    | \(70\)      |
|                 |             |           |             |             |
|                 |             | 3,049     | 2,652       | 87          |
+-----------------+-------------+-----------+-------------+-------------+
| TOTAL           |             | (81,926)  | (60,495)    | \(74\)      |
|                 |             |           |             |             |
|                 |             | 16,336    | 13,852      | 85          |
+-----------------+-------------+-----------+-------------+-------------+

[]{#__RefHeading___Toc88640364 .anchor}Figure 3 Table 2: Age-Specific
Cutpoints Used in Selecting Subjects for Visit 2

+--------------+------------+------------+------------+--------------+
| Age          | C          |            | TR         |              |
|              | HOLESTEROL |            | IGLYCERIDE |              |
+--------------+------------+------------+------------+--------------+
|              | Lower      | Upper      | Lower      | Upper        |
|              |            |            |            |              |
|              | CL         | CU         | TL         | TU           |
+--------------+------------+------------+------------+--------------+
| 0-19         | 175        | 205        | 75         | 150          |
+--------------+------------+------------+------------+--------------+
| 20-29        | 190        | 210        | 125        | 200          |
+--------------+------------+------------+------------+--------------+
| 30-39        | 220        | 240        | 150        | 250          |
+--------------+------------+------------+------------+--------------+
| 40-49        | 225        | 260        | 150        | 300          |
+--------------+------------+------------+------------+--------------+
| 50-59        | 245        | 280        | 150        | 300          |
+--------------+------------+------------+------------+--------------+
| 60+          | 245        | 280        | 150        | 300          |
+--------------+------------+------------+------------+--------------+

Source: Reference Manual for Lipid Research Clinics Program Prevalence
Study, July 1974.

[]{#__RefHeading___Toc88640365 .anchor}Figure 4 Table 3: Grey Zone
Numbers

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

AGE

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

Clinic Sex Racea 0-9 10-19 20-29 30-39 40-49 50-59 60+

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

BA 1 1 29 29 30 30 15 26 30

BA 2 1 23 23 30 60 27 30 30

BA 1 2 19 19 30 30 30 30 30

BA 2 2 29 29 30 35 30 30 30

JH 1 1 48 48 15 32 24 30 30

JH 2 1 36 36 19 96 60 30 30

JH 1 2 30 30 30 30 30 30 30

JH 2 2 30 30 30 30 30 30 30

CN 1 1 23 25 30 15 15 15 30

CN 2 1 29 32 30 82 37 30 30

CN 1 2 34 31 30 16 30 30 30

CN 2 2 33 30 30 74 30 30 30

IA 1 1 30 30 15 15 24 20 30

IA 2 1 30 30 29 49 33 27 30

IA 1 2 30 30 30 30 30 30 30

IA 2 2 30 30 30 30 30 30 30

LJ 1 1 45 45 30 15 15 18 15

LJ 2 1 15 15 30 95 24 21 20

LJ 1 2 30 30 30 30 30 30 30

LJ 2 2 30 30 30 30 30 30 30

MN 1 1 40 40 15 15 17 24 30

MN 2 1 15 15 32 24 22 29 30

MN 1 2 30 30 30 30 30 30 30

MN 2 2 30 30 30 30 30 30 30

KC 1 1 19 19 15 15 15 19 32

KC 2 1 15 15 25 55 32 21 15

KC 1 2 30 30 30 30 30 30 30

KC 2 2 30 30 30 30 30 30 30

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

(Continued on next page)

Table 3 Continued

Grey Zone Numbers

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

AGE

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

Clinic Sex Racea 0-9 10-19 20-29 30-39 40-49 50-59 60+

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

SE 1 1 30 30 15 15 15 31 30

SE 2 1 30 30 18 75 21 30 30

SE 1 2 30 30 30 30 30 30 30

SE 2 2 30 30 30 30 30 30 30

ST 1 1 30 30 15 15 15 24 44

ST 2 1 30 30 15 28 34 21 51

ST 1 2 30 30 30 30 30 30 30

ST 2 2 30 30 30 30 30 30 30

TR 1 1 30 30 20 15 15 23 42

TR 2 1 19 19 15 55 17 22 15

TR 1 2 30 30 30 30 30 30 30

TR 2 2 30 30 30 30 30 30 30

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

(a): Note on race: Race codes 1, 3, 4, and 9 on Visit 1 questionnaire
are grouped as race code 1 for the purpose of simplifying this table.
These codes correspond to the responses "White", "Oriental", "American
Indian" and "Other" to Question 18 of the Visit 1 Interview; a code of 2
indicates the response "Negro or Black". A sex code of 1 indicates
"Male"; 2 indicates "Female".

[]{#__RefHeading___Toc88640366 .anchor}Figure 5 Table 4: Exclusion
Criteria for GXT Protocol

-   Possible aortic stenosis

(aortic systolic murmur and at least one of the following: angina
pectoris, exertional syncope, evidence of cardiac enlargement, dyspnea,
ventricular gallop)

-   Congestive heart failure

(evidence of cardiac enlargement and at least one of the following:
ventricular gallop, dyspnea, moist basilar rales)

-   Blood pressure

(systolic \<90 or \>200 mm Hg; diastolic \>120 mm Hg)

-   Suspected congenital heart disease

-   R-on-T type PVCs

-   Two consecutive PVCs

-   Frequent PVCs

-   Multifocal PVCs

-   Ventricular parasystole

-   Atrial flutter

-   Atrial fibrillation

-   Supraventricular tachycardia except for sinus tachycardia

-   Use of antiarrhythmic medications

-   Second or third degree heart block

-   Left bundle branch block

-   Wolff-Parkinson-White syndrome

-   Evidence of acute MI

-   Evidence of definite MI by Minnesota code

-   Possible or suspect unhealed MI by Minnesota code

-   Unstable angina

-   Coronary bypass surgery

[]{#__RefHeading___Toc88640367 .anchor}Figure 6 Table 5: Graded Exercise
Test: Target Heart Rate (beats/min) by Age and Physical Activity

Age (years)

  ------------- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- -----
                20    25    30    35    40    45    50    55    60    65    70    75    80    85    90

  Sedentary     177   175   173   172   170   168   166   164   162   160   158   157   155   153   151

  Physically\   171   169   167   166   164   162   159   158   156   154   152   150   149   147   145
  Active                                                                                            
  ------------- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- -----

# II. REFERENCES

1.  The Lipid Research Clinics Program Epidemiology Committee. Plasma
    lipid distributions in selected North American populations.
    Circulation 60: 427, 1979.

2.  Central Patient Registry and Coordinating Center for the Lipid
    Research Clinics. Reference manual for the Lipid Research Clinics
    Program Prevalence Study, Vols. 1 and 2. Chapel Hill, Department of
    Biostatistics, University of North Carolina, July 1974.

3.  Mowery RL, Williams OD. Aspects of clinic monitoring in large-scale
    multiclinic trials. Clin Pharmacol Ther 25: 717, 1979.

4.  Williams OD. A framework for the quality assurance of clinical data.
    Clin Pharmacol Ther 25: 700, 1979.

5.  The Lipid Research Clinics Population Studies Data Book, Volume I:
    The Prevalence Study. Aggregate distributions of lipids,
    lipoproteins and selected variables in 11 North American
    populations. U.S. Dept. of Health and Human Services, Bethesda, MD.
    NIH Publication No. 80-1527, July 1980.

6.  The Lipid Research Clinics Population Studies Data Book, Volume II:
    The Prevalence Study. Aggregate distributions of nutrient intake in
    10 North American populations. U.S. Dept. of Health and Human
    Services, Bethesda, MD. NIH Publication No. 82-2014, September 1982.

7.  Manual of Laboratory Operations, Lipid Research Clinics Program,
    Vol. 1. Lipid and lipoprotein analysis. Bethesda, NHLBI, NIH, DHEW
    Publication No. (NIH) 75-628, May 1974.

8.  Bachorik PS, Wood P, Williams J, Kuchmak M, Ahmed S, Lippel K,
    Albers JJ. Automated determination of total plasma cholesterol: a
    serum calibration technique. Clin Chem Acta 96: 145, 1979.

9.  Lippel K, Ahmed S, Albers JJ, Bachorik PS, Cooper G, Helms R,
    Williams J. Analytical performance and comparability of the
    determination of cholesterol by 12 Lipid Research Clinics. Clin Chem
    23: 1744, 1977.

10. Ahmed S, Lippel K, Bachorik PS, Albers JJ, Williams J, Cooper G.
    Analytical performance and comparability of the determination of
    triglycerides in 12 Lipid Research Clinics laboratories. Clin Chem
    24: 330, 1978.

11. Hidiroglov MA, Fuller WA, Hickman RD. SUPERCARP. Survey Section,
    Statistical Laboratory, Iowa State University, Sixth Edition, 1980.

12. Holt MM. SURREGR: Standard errors of regression coefficients from
    sample survey data. Research Triangle Institute, Research Triangle
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