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Is there statistical evidence for a blood lead-blood pressure relationship?
Journal of Health Economics 8 (1989) 173-184. North-Holland
IS THERE STATISTICAL EVIDENCE FOR A BLOOD LEAD-BLOOD PRESSURE RELATIONSHIP? Douglas COATE National
Rutgers University, Newark, Bureau of Economic Research,
NJ 07102. USA Cambridge, MA 02138.
USA
Richard FOWLES Rutgers
University,
Newark, NJ 07102, USA
Received April 1987, final version received August 1988 In this paper we show that there is weak statistical evidence for a blood relationship in the second National Health and Nutrition Examination significance and magnitude of this relationship for 40-59 year old white reported by Pirkle, Schwartz, Landis, and Harlan does not characterize samples and is sensitive to the use of blood pressure data of questionable
lead-blood pressure Survey data. The males as originally other age and sex quality.
1. Introduction The gradual elimination of lead from automobile gasoline in the United States is resulting from tighter federal government regulation of the lead content of leaded gasoline and from the more than decade old federal government requirement that new cars sold in the U.S. burn unleaded gasoline. Because lead has substantial cost advantages over other additives that increase gasoline octane and lower engine knock, its elimination is increasing average gasoline prices by several cents per gallon. In addition some engines, such as the older engines in farm machinery, depreciate more rapidly when burning low lead or unleaded gasoline. Before 1985, the primary rationale for the regulation of the lead content of gasoline was the association between lead exposure and retarded intellectual development and poorer health among children, particularly black children, in the U.S. [for example, Schwartz et al. (1984)]. Although it was known that continuous exposure to high levels of airborne lead could lead to brain disease, anemia, palsy, and damage to the kidneys and reproductive systems among adults, such exposure levels were rare in the U.S. and the effects of lead in the ambient air on the health of adults in the U.S. was uncertain. The publication in 1985 of the seminal work by Pirkle, Schwartz, Ol67-6?96/89/S3.50 1% 1989, Elsevier Science Publishers B.V. (North-Holland)
171
D. Coole
and R. Fowles,
Blood
lead-blood
pressure
relationship
Landis, and Harlan (PSLH) on the relationship between blood lead levels and blood pressure in white adult males in the U.S. reduced this uncertainty. PSLH used the second National Health and Nutrition Examination Survey (NHANES II) data to analyze the effect of blood levels on the blood pressure of white males, 40 to 59 years of age. They concluded that the 37% decrease in mean blood lead levels that occurred in adult white males in the 1976 to 1980 period (calculated from the NHANES II data) resulted in a 4.7% decrease in the incidence of fatal and non-fatal myocardiai infarction, a 6.7% decrease in the incidence of fatal and non-fatal strokes, a 5.5% decrease in the incidence of death from all causes, and a 17.5% decrease in hypertension. These health benefit calculations were based on blood lead coefficients from diastolic blood pressure regressions for 40 to 59 year old white males in NHANES II and on empirical estimates of blood pressurehealth outcome relationships from other studies. The PSLH research had substantial impact and was used by the U.S. Environmental Protection Agency in their successful 1984-1985 campaign for more stringent regulation of lead levels in leaded gasoline. New EPA rules resulted that stipulated an allowable lead level of 0.5 grams per gallon of leaded gasoline effective July 1, 1985 and 0.1 grams of lead per gallon effective January 1, 1986. The prior allowed lead level was 1.1 grams per gallon of leaded gasoline [Shabecoff (1985)]. Our purpose in this paper is to show that the relationship between blood lead levels and adult blood pressure in the NHANES II data is not as strong as reported in the PSLH research. An important part of our argument is the identification of irregularities in the NHANES II blood pressure data. Because NHANES II is the primary data source for the evaluation of the health and nutritional status of the U.S. population and because blood pressure may be the most important adult health indicator collected in the survey, the latter analysis is an important one. In the next section of this paper we describe the irregularities in the NHANES II blood pressure data. In section 3 we show that the results of PSLH are weakened considerably when the sample is broadened beyond 40 to 59 year old white males and when observations from PSUs in NHANES II with suspicious blood pressure distributions are deleted from the working sample.
2. The NHANES
II data
NHANES II is a national probability sample of the U.S. noninstitutionalized civilian population, aged 6 months through 74 years, conducted between
D. C’oute and R. Fowles. Blood lead-blood pressure relationship
175
February 1976 and February 1980 by the National Center for Health Statistics. Approximately 20.000 individuals were examined in the survey. Persons with low income, preschool children, and the elderly were oversampled. Each individual in the sample was given a detailed physical examination that emphasized potential problems in the cardiovascular, respiratory, and neurological systems and included the measurement of systolic and diastolic blood pressure. Medical history, dietary, and socioeconomic characteristics questionnaires were also administered to each subject. Blood samples were taken from half of the subjects and analyzed for lead concentrations and other hematological and biochemical factors. There were 64 primary sampling units (PSUs) or sampling sites in NHANES II in 60 metropolitan areas or counties. The NHANES II survey was administered to subjects at an examination site (consisting of three connected trailers) at a central location in the PSU. Three to six hundred people were surveyed and examined at each site in a three or four week period. Blood pressure was usually measured by a physician, although a nurse performed this task in some instances. A detailed description of survey design and sampling procedures is in National Center for Health Statistics (1981). Problems with the blood pressure data in NHANES II have recently been acknowledged by the National Center for Health Statistics (1986). In their description of trends in blood pressure in the United States from 1960 to 1980, it is pointed out that the large proportion of diastolic blood pressure measures with an end digit of zero in NHANES II may be indicative of hearing impairment or lack of concentration among the examining physicians during the measurement of diastolic blood pressure. This is possible because the examining physicians in NHANES II were almost all retired practitioners and because hearing acuity diminishes with age. Diastolic blood pressure measurement requires the identification of a marked diminution or disappearance of a muffling sound. A failure to identify the ‘difficult end point of the fifth phase (would) probably result in diastolic readings biased upward’. [National Center for Health Statistics (1986, p. 68)]. Systolic blood pressure measurement was thought not to be adversely affected by physician hearing loss or carelessness. If this was the extent of the problem with the blood pressure data in NHANES II the PSLH results would still stand. In fact, their reported blood lead - diastolic blood pressure effect would be downward biased because the end digit zero problem characterized the latter part of the NHANES II period and the upward bias in the diastolic blood pressure data would be associated with the low blood lead levels in 1979 and 1980. In table 1 NHANES II PSUs are listed chronologically with the follwoing data for the first and second diastolic blood pressure readings for all NHANES II
176
D. Coate and R. Fowfes. Blood lead-blood pressure relationship
Table 1 Summary statistics for the tirst and second sitting diastolic blood pressure readings and for related variables, ages 12-74, by PSU. NHANES II.
PSU 1 : 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
Exam date mid point 3-08-76 3-09-76 4-16-76 4-20-76 5-25-76 6-02-76 6-30-76 7-20-76 g-02-76 8-26-76 9-02-76 9-26-76 10-13-76 10-26-76 11-29-76 1l-30-76 2-01-77 2-10-77 3-10-77 3-28-77 4-29-77 5-12-77 6-05-77 6-20-77 7-22-77 g-02-77 8-29-77 9-06-77 10-28-77 1I-01-77 12-03-77 12-07-77 2-02-78 2-02-78 3-10-78 3-12-78 4-17-78 4-21-78 6-01-78 6-07-78 7-17-78 7-22-78 8-29-78 9-03-78 10-16-78 10-27-78 I l-30-78 12-01-78
Mean diastolic blood pressure
Percent end digit zero
Percent equal 70mm Hg.
First
First
First
8:.37 78.43 81.40 80.81 76.60 78.56 75.50 8 1.54 83.31 78.51 81.06 78.67 83.47 83.85 84.33 81.59 83.46 78.84 83.40 84.20 80.35 80.11 86.74 84.99 81.23 81.50 75.97 80.97 81.34 79.29 81.04 80.08 76.02 78.80 8 1.47 75.50 83.51 80.19 77.88 84.83 76.04 80.32 83.08 78.81 79.87 90.01 75.00 74.71
Second 78.01 75.94 78.97 79.17 76.80 76.8 1 73.60 80.54 81.67 78.34 79.57 78.45 83.14 83.48 82.84 80.22 83.13 76.90 83.28 82.68 80.18 79.86 86.49 82.18 78.76 79.32 74.64 79.19 81.03 79.71 82.34 78.2 1 74.58 78.10 78.48 74.69 81.49 80.24 76.86 82.16 75.02 77.06 82.86 78.00 79.65 87.17 73.23 72.15
3 1.97 33.08 52.84 28.88 59.64 33.33 56.72 20.52 54.49 22.58 59.71 22.47 76.47 25.00 66.15 34.20 23.36 31.19 22.18 32.78 22.87 48.12 47.18 64.90 30.28 47.72 28.17 65.30 21.69 54.24 26.13 48.97 55.35 33.33 50.00 51.44 72.42 26.85 22.93 74.71 54.15 47.36 32.96 24.13 60.99 47.28 95.28 67.78
Second 50.29 29.04 50.83 32.47 69.00 33.86 47.89 29.19 50.29 21.55 60.18 20.11 74.20 23.57 55.81 35.44 25.54 29.23 21.05 29.87 27.12 47.31 47.14 63.75 28.84 44.00 24.17 57.85 22.75 55.66 24.50 51.70 52.07 24.73 46.85 50.00 61.76 22.22 17.80 74.14 54.81 49.02 28.51 22.22 47.48 44.91 88.62 65.10
6.93 9.55 12.00 6.61 16.09 5.61 17.64 5.17 12.57 6.84 14.21 7.82 18.91 4.28 11.92 7.40 5.43 7.17 5.24 6.22 6.34 10.63 7.04 13.07 4.76 13.88 5.66 15.78 5.26 17.45 1.42 13.60 12.35 9.13 11.80 15.78 14.96 7.87 6.36 12.35 15.89 14.21 6.25 7.27 24.64 3.72 43.92 19.33
Second 15.02 10.66 15.00 9.92 12.64 9.27 15.54 6.89 8.38 7.30 20.37 7.82 16.66 5.00 8.07 8.14 5.43 7.59 3.37 7.46 6.87 14.36 9.85 15.03 5.23 20.00 4.71 17.00 6.84 15.56 3.96 10.88 17.64 8.60 14.58 13.87 14.59 5.09 5.45 14.60 18.54 17.53 7.35 6.51 13.38 9.57 36.91 16.66
Chi-sqr. test stat.’
Blood lead ug,‘dL
7.35 9.66 5.70 32.76 10.50 5.54 38.58 7.29 12.58 12.82 3.67 8.76 18.10 11.99 32.21 6.59 13.14 7.17 24.65 15.36 3.84 5.38 46.94 29.84 4.99 5.42 21.37 10.29 2.47 14.03 3.80 8.52 12.28 11.18 9.40 37.92 19.86 11.34 14.20 42.73 35.27 2.34 10.24 14.67 23.46 80.51 74.00 35.75
14.73 16.29 13.93 15.43 18.77 16.82 16.60 16.18 16.65 15.92 16.26 15.03 18.06 19.13 15.27 13.90 16.70 12.79 10.86 11.99 13.59 13.97 18.30 15.44 14.86 14.17 14.50 15.45 15.54 13.75 13.53 14.10 13.88 12.86 14.74 13.18 13.95 13.20 16.98 13.61 13.19 14.58 14.06 14.68 17.37 15.44 14.09 14.05
D. Coare
and R. Fowles.
Blood lead-blood
49 50
. 51 52 53 54 55 56 57 58 59 60 61 62 63 64
relarionship
Exam date mid point
.Mean diastolic blood pressure
Percent end digit zero
Percent equal 70mm Hg.
First
Second
First
Second
First
2-04-79 2-08-79 3-22-79 3-23-79 S-03-79 5-06-79 6- 17-79 6- 19-79 8- 17-79 8-23-79 9-23-79 10-09-79 11-l 1-79 1l-24-79 2-05-80 2- 14-80
81.06 78.04 83.28 81.76 15.54 77.30 72.20 85.00 14.18 78.68 79.48 77.3 1 72.24 79.79 82.06 71.83
80.43 78.27 80.79 80.28 74.38 75.29 71.20 84.46 73.78 78.48 77.21 76.55 71.38 78.61 79.32 71.68
64.00 23.95 63.58 71.72 91.14 25.57 99.47 87.60 99.10 45.19 82.97 84.88 99.25 51.56 55.34 99.15
56.00 25.95 62.08 62.28 91.75 25.51 97.93 86.63 98.2 1 42.12 91.91 80.00 95.89 33.18 48.65 98.72
14.75 7.61 12.43 15.42 46.41 7.14 55.67 13.67 53.77 14.28 18.29 44.44 55.55 10.61 15.84 54.8 1
Table Number Of
PSU
subjects
Mean age
I 2 3 4 5 6 7 8 9 IO 11 12 13 14 15 16 17 18 19 20 21 22
172 269 300 270 173 192 238 346 167 218 211 178 221 140 260 269 184 235 267 241 188 187
39.39 47.70 38.50 40.55 41.06 40.89 41.68 47.06 40.6 1 39.32 38.12 36.39 42.90 38.74 44.65 40.24 46.85 36.66 45.29 42.57 42.42 42.43
177
1 (continued)
Table
PSU
pressure
Second
Chi-sqr. test stat.’
Blood lead ug/dL
15.30 10.38 12.43 15.71 41.75 8.76 54.63 16.23 56.88 14.92 29.78 43.63 51.85 8.40 13.96 50.20
13.76 20.62 10.06 4.47 137.91 35.67 156.66 29.84 135.74 16.13 40.88 il.61 214.14 2.68 10.36 188.66
15.24 11.39 11.02 11.13 12.26 12.36 14.37 12.78 12.00 11.49 10.79 11.85 9.34 12.08 10.66 9.20
1 (continued) Mean body mas?
Percent male
24.90 25.10 24.84 24.58 24.27 26.21 24.54 25.32 24.25 24.48 23.98 23.80 24.54 24.50 24.77 24.89 25.16 24.24 24.84 24.04 24.62 25.93
49.13 48.46 51.67 44.12 52.30 44.85 50.84 45.11 41.92 48.40 47.39 52.5 1 49.10 56.43 46.15 44.81 51.09 54.01 46.82 45.64 48.15 41.49
Percent white 91.90 75.00 90.00 55.51 91.95 55.15 97.89 90.5 1 84.61 94.06 95.26 98.32 66.21 95.71 98.07 67.03 88.04 75.10 94.38 92.11 58.20 62.23
Percent black 1.73 22.05 6.00 44.48 3.44 44.84 0.00 9.48 4.19 5.02 3.79 0.00 32.88 2.85 1.92 32.96 11.41 23.20 5.61 7.88 33.33 36.17
D. Coupe und R. Fades.
178
Blood
Table
leud-blood
pressure
relationship
1 (continued)
PSU
Number of subjects
\lean age
Mean body ma&
‘3 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64
142 152 208 177 212 245 189 212 200 147 168 186 142 208 273 216 218 356 301 209 271 261 I41 185 213 149 175 288 I85 336 310 306 189 234 223 313 235 312 268 225 262 236
40.23 At.83 43.24 42.49 39.46 39.56 43.28 40.45 39.94 34.69 40.85 42.2 I 44.44 43.25 41.87 44.86 41.57 51.42 45.43 41.36 41.15 37.60 45.13 42.57 40.66 42.17 38.57 40.10 41.32 44.51 38.32 36.78 39.65 41.23 42.20 43.9 I 42.9 1 44.24 40.73 42.73 43.10 40.30
24.4 I 24.68 25.37 24.69 24.5 I 25.28 24.8 I 25.14 24.48 23.84 24.67 24.65 23.69 24.39 24.72 25.32 24.37 25.83 25.71 25.13 25.49 25.13 25.36 24.93 25.1 I 24.52 24.92 24.84 24.38 25.09 24.40 24.27 24.63 24.37 24.38 25.07 25.03 24.94 25.58 24.84 24.95 24.97
-
Percent male
Percent white
Percent black
52.1 I 47.06 54.29 46.: 1 45.75 48.58 50.00 50.47 42.57 45.58 45.29 47.3 1 56.25 42.58 47.08 50.00 48.18 47.19 44.70 50.24 52.57 45.98 47.18 44.15 47.20 51.33 50.27 50.87 48.11 48.57 49.04 49.35 47.94 44.44 47.1 I 46.35 47.66 48.09 48.89 50.00 49.06 46.03
95.77 96.07 96.66 98.88 99.52 99.19 82.63 97.64 92.57 61.90 72.94 91.93 25.69 94.25 93.06 99.53 90.00 100.00 99.33 86.72 100.00 55.55 82.39 88.82 74.76 96.66 55.73 95.84 94.59 92.28 98.07 95.12 69.07 76.49 78.22 98.73 91.91 99.68 99.25 21.68 76.60 97.07
2.1 I 3.92 2.38 0.55 0.47 0.40 16.84 2.35 5.94 37.41 17.64 5.37 0.69 3.34 2.18 0.00 8.63 0.00 0.00 12.79 0.00 43.29 16.90 10.63 23.36 2.66 42.62 3.46 2.70 7.71 1.92 3.57 29.89 23.07 21.33 1.26 8.08 0.3 1 0.37 73.89 23.39 2.92
“The chi-square statistic tests the tirst sitting diastolic blood pressure distribution of each PSU against the diastolic blood pressure of all subjects 12 and over in the first National Health and Nutrition Examination Survey. See footnote 2. bBody mass is the ratio of weight in kilograms to the square of height in meters.
D. Coute und R. Fonfes. Blood lead-blood pressure relarionship
179
subjects over 12 years of age:’ means, proportion of readings with end digit zero. proportion of readings equal to 70, and Pearson’s chi-square statistic to evaluate the equivalence of the diastolic blood pressure distribution (first reading) for each PSU in NHANES II to the NHANES I diastolic blood pressure distribution.’ Also shown in table 1 are the number of readings and the mean PSU values for age and body mass and the percent of subjects male, white and black.3 It is clear from table 1 that the end digit zero phenomenon intensified in 1979. PSUs 53, 5.5. 57, 61, and 64 have the largest percentages of end digit zeros in the first and second diastolic blood pressure readings in 1979 and 1980. These percentages for the first sitting diastolic blood pressure readings are 98, 99, 99, 99, and 99, respectively. For the second measure they are 98, 98, 98, 95, and 97, respectiveiy.4 Because blood pressure was to be recorded in only even digits, zeros should appear about 20 percent of the time. It is also clear from table 1 that high end digit zero percentages are associated with high chi-square test statistics, with lower mean diastolic blood pressure readings, and with higher proportions of readings at 70. Figs. 1. 2, and 3 verify the association by PSU between end digit zero and chi-square statistic and end digit zero and mean diastolic blood pressure for the whole sample and for the 1979-1980 period.s They ‘In NHANES 11, blood pressure was measured in the sitting position at the beginning of the physical examination and in the sitting and recumbent positions at the end of the physical examination. Summary statistics are presented for both of the sitting diastolic readings because the first reading corresponds to the diastolic measure in the first National Health and Nutrition Examination Survey, which is the reference distribution for the chi-square tests described below. and the second reading was emphasized by PSLH. Also, regression results are sensitive to the measure used (see section 3). *The reference distribution for Pearson’s chi-square statistic is the diastolic blood pressure distribution of all subjects I2 and over in the first National Health and Nutrition Examination Survey. 1971-1974. Like NHANES II. it is a near representative sample for the U.S. population with over 20.000 examined subjects. One blood pressure reading at the beginning of the physical exam was administered by a physician (not retired) to all subjects I2 years and over. For the chi-square calculations, blood pressure readings were grouped into eight uniform categories after deleting readings below 55 mm hg. and above 125 mm hg. The latter adjustment eliminates the possibility that an HNANES II PSU with a few extreme observations will necessarily have a high chi-square statistic. 3Blood pressure generally increases with age and body mass (weight/height**2) and is higher for males and adult blacks [Fortmann et al. (1983) and Gordon and Kannel (1983)]. ‘The corresponding ligures for the recumbent diastolic blood pressure reading for these PSUs are 98, 99, 97. and 100. respectively. The systolic blood pressure measures were also characterized by an end digit zero problem that trends with the frequency of end digit zero in the diastolic blood pressure data. Percent end digit zero for the first-and second sitting systolic measures and for the recumbent svstolic measure are 95. 91, and 95 for PSU 53; 92. 96, and 97 for PSU 55; 96. 95, and 98 for PSU 57; 98, 99. and 99 for PSU 61; and 99, 98, 99 for PSU 64. ‘Note that the first sitting diastolic blood pressure measure is used in fig. I and the second sitting diastolic blood pressure measure is used in figs. 2 and 3. We switch to the second measure in tigs. 2 and 3 because this measure is used by PSLH. Fig. I requires the first measure because of its match with the NHANES I diastolic reading that is used as the reference distribution in the chi-square calculations.
IHE.
B
180
D. Coale and R. Foowies. Blood lead-blood pressure relationship
57 55 l ‘. 53
.
64 .
61 .
.
.
CHI-SQUARE
Fig.
1. Percent
end
digit
zero
TEST
STATISTIC
and chi-square statistic, first sitting reading, by PSU, NHANES II.
diastolic
blood
pressure
. .
l
. . .
. l
0. : .
.
:. .
. .
.
. .
.
.
70
Fig. 2. Percent
end
digit
.
$3
, MEAN
zero
DIASTOLIC
BLOOD
and mean diastolic blood NHANES II, 1976-1978.
PRESSURE
pressure,
second
sitting,
by
PSU,
D. Coate
‘O”
and R. Fwles,
55*
-064 61
5;
Blood
lead-blood
;3
pressure
181
relationship
. .
0ct
.
ii:_ P c_ 3
.
3 zw
. .
.
8
.
. . I
207
70
MEAN
I
DIASTOLIC
. I
BLOOD
1
I
PRESSURE
Fig. 3. Percent end digit zero and mean diastolic blood pressure, second sitting, by PSU, NHANES II. 1979-1980.
also highlight PSUs 53, 55, 57, 61, and 64 as the most severe outliers by the joint criteria of proportion end digit zero and chi-square statistic. It appears then that data of questionable quality characterize the blood pressure readings for some PSUs in 1979 and 1980. Furthermore, the recorded measurements may be biased downward and may have contributed to an artificial robustness in the PSLH research because blood lead levels in NHANES II were falling in 1979 and 1980.
3. Regression results In table 2 blood lead coefficients and r values are sumarized from blood pressure regression models for different NHANES II samples. The purpose of the table is to show the sensitivity of the blood lead coefficient to the blood pressure measure used, to the age, sex, and race characteristics of the sample chosen, and to the blood pressure data of questionable quality in 1979 and 1980. The model specifications are from PSLH. Independent variables in the diastolic blood pressure specification include age, age squared, the natural log of blood lead, body mass (weight/height**2), dietary potassium, hemoglobin, albumin, and the natural log of dietary vitamin C. The PSLH systolic blood pressure equation includes the aforementioned independent variables with the exception of hemoglobin and dietary potas-
D. Coarv und R. Fades,
182
Bid
Table
pressurr
relationship
2
coefficients and I statistics for the natural log of blood lead for selected NHANES samples. generalized least squares. PSLH blood pressure specification.”
Regression
White male JO-59
Race Sex Ages Data
lead-blood
White male 21-39
White male 60-74
White female 40-59
White female 21-39
White female 60-74
All Both 12-39 60-74
-0.87 (- 1.00)
1.41 (1.35)
1.28 (3.05)
from all PSUs
Diastolic (0
1
Diastolic (0
2
I.20
2.75 (2.27)
0.62 (0.62)
(1.06)
3.93 (3.34)
1.90 (1.98)
1.32 (1.16)
- 0.28 (-0.27)
- 0.49 (-0.55)
1.04 (1.07)
1.43 (3.49)
3.21 (1.57)
2.66 (3.92)
1.77 ( 1.55)
Systolic (rl
1
5.3 1 (2.991
2.20 (1.68)
1.25 (0.62)
- 0.02 (-0.01)
-0.18 (-0.16)
Systolic (rl
2
6.78 (3.71)
3.00 (2.19)
2.93 (1.53)
- 1.33 (-0.77)
(- 1.09)
I .08 (0.54)
2.60 (3.85)
794
620
815
891
5039
Sample sizeb _____ Data from all PSUs
574
1
1.62 (1.30)
Diastolic (r)
2
2.73 (2.24) 3.85
1
787
- 1.25
but 53, 55. 57, 61, 64
Diastolic (1)
Systolic (0
II
(2.05)
-0.55 (-0.51)
0.58 (0.48)
0.40 (0.33)
- 2.77 (-2.96)
0.58 (0.53)
0.4 1 (0.91)
0.50 (0.48)
0.66 (0.56)
- 1.20 (-1.06)
- 2.02 (-2.12)
0.32 (0.31)
0.54 (1.23)
0.98 (0.69)
0.27 (0.12)
- 1.08 (-0.53)
-2.33 (- 1.84)
3.16 (1.43)
1.84 (2.48)
2.08 5.06 1.64 - 1.48 2 - 3.55 0.65 1.59 4591 827 525 694 741 556 726 sizeb -__ “Means and standard deviations for the second sitting blood pressure measures for all subjects 12 to 74 years in all PSUs are 78.8 and 12.5 (diastolic) and 125.6 and 21.8 (systolic). The mean and standard deviation of the natural log of blood lead are 2.54 and 0.41. %ample size from blood presure models for the second diastolic reading. Systolic
Sample
plus the natural logs of dietary riboflavin, dietary oleic acid, and serum vitamin C. We have added sex and race variables to the basic PSLH specifications when appropriate, that is when models are estimated over samples including different races and both sexes. Because these models have a strange assortment of linear and nonlinear terms, diastolic and systolic blood pressure models were also estimated with the following independent variables: age, body mass, blood lead, and race and sex when relevant. The blood lead coefficients from these models followed the same pattern as those in table 2, confirming the PSLH conclusion that the results for the blood lead coefficient are not sensitive to model specification.6 sium,
‘JRegression results for the NHANES II samples identified in table 2 are available from the authors on request. The coefficients of the natural log of blood lead for the recumbent blood pressure measures are generally bounded by the coefficients for the two sitting measures for the samples in table 2.
D. Courr and R. Fowlrs, Blood
lead-blood pressure relarionship
183
The evidence in table 2 indicates the level and statistical significance of the blood lead coefficient are sensitive to the age, race, and sex characteristics of the sample, to the blood pressure measure selected, and to the inclusion of the questionable blood pressure data from the 1979-1980 period. The regressions are estimated by generalized least squares to take account of within PSU variance.’ Ignoring the questionable data issue for a moment, it is clear that the blood pressure-blood lead association is strongest for the original PSLH sample of 40-59 year old white males and for the second sitting blood pressure measurement. The association weakens considerably for males if the first sitting blood pressure measurement is used rather than the second and if the sample is expanded to other age groups. The association is weak in the case of females and sometimes negative. In the absence of plausible biological explanations, the sensitivity of the blood pressure-blood lead results to the different age and sex groupings is a strong challenge to the PSLH results. The results are weakened even further if data from PSUs 53, 55, 57, 61, and 64 are deleted from the samples. In the lower part of table 2 it can be seen that the magnitude of the blood lead coefficients fall by one-third to one-half for the male samples if these questionable data are excluded. Statistical significance falls markedly also. Estimating the blood pressure relationships separately for each PSU gives a wide range of coefficients for the natural logarithm of lead. For example. the mean of the 64 coefficients and the 25th and 75th percentile values of the distribution of coefficients for 12 to 74 year olds, second sitting diastolic blood pressure measure, are 0.37, -2.08. and 1.81. The same measures for the 21 to 74 year old white males are 1.23, -3.72, and 5.75. It should also be pointed out that even the original PSLH coefficients do not indicate that reductions in blood lead result in substantial falls in blood pressure. The 37% reduction in blood lead claimed by PSLH as characteristic of the 1976-1980 period would reduce diastolic blood pressure at the mean by only 1.8 mm. hg, according to their regression results.* The big payoff in improved cardiovascular health and lower death rates that they report comes from the sensitivity of these health outcomes to reductions in ‘OLS estimates of the PSLH diastolic blood pressure model over the 40-59 year old white male sample yield a coefticient of 4.3 (r=3.5) for the natural log of blood lead for the all PSU sample and a coefficient of 3.1 (1=?.4) for the sample with data deleted from the tive problem PSUs. The reported results of PSLH, which are adjusted for sample design, show a natural log of blood lead coeflicient of 3.95 (1=2.8). We have not adjusted for sample design because the sampling weights provided with the NHANES II data are not appropriate for the various subsamples considered in table 2. 8Using the NHANES II data to detect trends within the sample period. as PSLH did for blood lead levels can be misleading. Although the sample is near representative of the U.S. population throughout the sample period it is not necessarily representative in any year or sub-period.
I84
D. Coare
and R. Fonles,
Blood
lead-blood
pressure
relationship
blood pressure according to the Pooling Project (1978) and Framingham (Shurtleff, 1974; McGee and Gordon, 1976) studies. 4. Conclusion In this paper we have shown that there is weak statistical evidence for a blood lead-blood pressure relationship in the second National Health and Nutrition Examination Survey data. The significance and magnitude of this relationship for 40-59 year old white males as originally reported by Pirkle, Schwartz, Landis, and Harlan does not characterize other age and sex samples and is sensitive to the use of blood pressure data of questionable quality. References Fortmann, S.P. et al., 1983, The association of blood pressure and dietary alcohol: Differences by age, sex, and estrogen use, American Journal of Epidemiology 118, 497-507. Gordon, Tavia and William B. Kannel, 1983, Drinking and its relation to smoking. BP, blood lipids, and uric acid: The Framingham Study, Archives of Internal Medicine 143, July, 13661375. McGee. D. and T. Gordon. 1976, The results of the Framingham Study applied to four other U.S. based epidemiological studies of coronary heart disease, The Framingham Study, Sec. 31, (NIH) 76-1083. National Center for Health Statistics, 1981, Plan and operation of the second national health and nutrition examination survey, U.S. Dept. of Health and Human Services, vital and health statistics, series I. no. 15, July. National Center for Health Statistics. 1986, Blood pressure levels in persons IS-74 years of age in 1976-1980, and trends in blood pressure from 1960 to 1980 in the United States, U.S. Dept. of Health and Human Services, Vital and Health Statistics, series II, no. 234, July. Pirkle, James L., Joel Schwartz. J. Richard Landis and William R. Harlan, 1985, The relationship between blood lead levels and blood pressure and its cardiovascular risk implications, American Journal of Epidemiology 121. no. 2. 1978, Relationship of blood pressure, serum cholesterol, Pooling Project Research Group. smoking habit, relative weight, and ECG abnormalities to incidence of major coronary events. Journal of Chronic Diseases 31, 201-306. Schwartz, Joel et al.. 1984. Costs and benefits of reducing lead in gasoline, Draft final report (Office of Policy Analysis. U.S. Environmental Protection Agency, Washington, D.C., EPA23@-03-84005). Shabecoff, Phillip. 1985, EPA orders 90 percent cut in lead content of gasoline by 1986, New York Times, March 5, 20. Shurtleff. D., 1974. Some characteristics related to the incidence of cardiovascular disease and death, The Framingham Study, Sec. 30, (NIH) 76-1083.
IS THERE STATISTICAL EVIDENCE FOR A BLOOD LEAD-BLOOD PRESSURE RELATIONSHIP? Douglas COATE National
Rutgers University, Newark, Bureau of Economic Research,
NJ 07102. USA Cambridge, MA 02138.
USA
Richard FOWLES Rutgers
University,
Newark, NJ 07102, USA
Received April 1987, final version received August 1988 In this paper we show that there is weak statistical evidence for a blood relationship in the second National Health and Nutrition Examination significance and magnitude of this relationship for 40-59 year old white reported by Pirkle, Schwartz, Landis, and Harlan does not characterize samples and is sensitive to the use of blood pressure data of questionable
lead-blood pressure Survey data. The males as originally other age and sex quality.
1. Introduction The gradual elimination of lead from automobile gasoline in the United States is resulting from tighter federal government regulation of the lead content of leaded gasoline and from the more than decade old federal government requirement that new cars sold in the U.S. burn unleaded gasoline. Because lead has substantial cost advantages over other additives that increase gasoline octane and lower engine knock, its elimination is increasing average gasoline prices by several cents per gallon. In addition some engines, such as the older engines in farm machinery, depreciate more rapidly when burning low lead or unleaded gasoline. Before 1985, the primary rationale for the regulation of the lead content of gasoline was the association between lead exposure and retarded intellectual development and poorer health among children, particularly black children, in the U.S. [for example, Schwartz et al. (1984)]. Although it was known that continuous exposure to high levels of airborne lead could lead to brain disease, anemia, palsy, and damage to the kidneys and reproductive systems among adults, such exposure levels were rare in the U.S. and the effects of lead in the ambient air on the health of adults in the U.S. was uncertain. The publication in 1985 of the seminal work by Pirkle, Schwartz, Ol67-6?96/89/S3.50 1% 1989, Elsevier Science Publishers B.V. (North-Holland)
171
D. Coole
and R. Fowles,
Blood
lead-blood
pressure
relationship
Landis, and Harlan (PSLH) on the relationship between blood lead levels and blood pressure in white adult males in the U.S. reduced this uncertainty. PSLH used the second National Health and Nutrition Examination Survey (NHANES II) data to analyze the effect of blood levels on the blood pressure of white males, 40 to 59 years of age. They concluded that the 37% decrease in mean blood lead levels that occurred in adult white males in the 1976 to 1980 period (calculated from the NHANES II data) resulted in a 4.7% decrease in the incidence of fatal and non-fatal myocardiai infarction, a 6.7% decrease in the incidence of fatal and non-fatal strokes, a 5.5% decrease in the incidence of death from all causes, and a 17.5% decrease in hypertension. These health benefit calculations were based on blood lead coefficients from diastolic blood pressure regressions for 40 to 59 year old white males in NHANES II and on empirical estimates of blood pressurehealth outcome relationships from other studies. The PSLH research had substantial impact and was used by the U.S. Environmental Protection Agency in their successful 1984-1985 campaign for more stringent regulation of lead levels in leaded gasoline. New EPA rules resulted that stipulated an allowable lead level of 0.5 grams per gallon of leaded gasoline effective July 1, 1985 and 0.1 grams of lead per gallon effective January 1, 1986. The prior allowed lead level was 1.1 grams per gallon of leaded gasoline [Shabecoff (1985)]. Our purpose in this paper is to show that the relationship between blood lead levels and adult blood pressure in the NHANES II data is not as strong as reported in the PSLH research. An important part of our argument is the identification of irregularities in the NHANES II blood pressure data. Because NHANES II is the primary data source for the evaluation of the health and nutritional status of the U.S. population and because blood pressure may be the most important adult health indicator collected in the survey, the latter analysis is an important one. In the next section of this paper we describe the irregularities in the NHANES II blood pressure data. In section 3 we show that the results of PSLH are weakened considerably when the sample is broadened beyond 40 to 59 year old white males and when observations from PSUs in NHANES II with suspicious blood pressure distributions are deleted from the working sample.
2. The NHANES
II data
NHANES II is a national probability sample of the U.S. noninstitutionalized civilian population, aged 6 months through 74 years, conducted between
D. C’oute and R. Fowles. Blood lead-blood pressure relationship
175
February 1976 and February 1980 by the National Center for Health Statistics. Approximately 20.000 individuals were examined in the survey. Persons with low income, preschool children, and the elderly were oversampled. Each individual in the sample was given a detailed physical examination that emphasized potential problems in the cardiovascular, respiratory, and neurological systems and included the measurement of systolic and diastolic blood pressure. Medical history, dietary, and socioeconomic characteristics questionnaires were also administered to each subject. Blood samples were taken from half of the subjects and analyzed for lead concentrations and other hematological and biochemical factors. There were 64 primary sampling units (PSUs) or sampling sites in NHANES II in 60 metropolitan areas or counties. The NHANES II survey was administered to subjects at an examination site (consisting of three connected trailers) at a central location in the PSU. Three to six hundred people were surveyed and examined at each site in a three or four week period. Blood pressure was usually measured by a physician, although a nurse performed this task in some instances. A detailed description of survey design and sampling procedures is in National Center for Health Statistics (1981). Problems with the blood pressure data in NHANES II have recently been acknowledged by the National Center for Health Statistics (1986). In their description of trends in blood pressure in the United States from 1960 to 1980, it is pointed out that the large proportion of diastolic blood pressure measures with an end digit of zero in NHANES II may be indicative of hearing impairment or lack of concentration among the examining physicians during the measurement of diastolic blood pressure. This is possible because the examining physicians in NHANES II were almost all retired practitioners and because hearing acuity diminishes with age. Diastolic blood pressure measurement requires the identification of a marked diminution or disappearance of a muffling sound. A failure to identify the ‘difficult end point of the fifth phase (would) probably result in diastolic readings biased upward’. [National Center for Health Statistics (1986, p. 68)]. Systolic blood pressure measurement was thought not to be adversely affected by physician hearing loss or carelessness. If this was the extent of the problem with the blood pressure data in NHANES II the PSLH results would still stand. In fact, their reported blood lead - diastolic blood pressure effect would be downward biased because the end digit zero problem characterized the latter part of the NHANES II period and the upward bias in the diastolic blood pressure data would be associated with the low blood lead levels in 1979 and 1980. In table 1 NHANES II PSUs are listed chronologically with the follwoing data for the first and second diastolic blood pressure readings for all NHANES II
176
D. Coate and R. Fowfes. Blood lead-blood pressure relationship
Table 1 Summary statistics for the tirst and second sitting diastolic blood pressure readings and for related variables, ages 12-74, by PSU. NHANES II.
PSU 1 : 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
Exam date mid point 3-08-76 3-09-76 4-16-76 4-20-76 5-25-76 6-02-76 6-30-76 7-20-76 g-02-76 8-26-76 9-02-76 9-26-76 10-13-76 10-26-76 11-29-76 1l-30-76 2-01-77 2-10-77 3-10-77 3-28-77 4-29-77 5-12-77 6-05-77 6-20-77 7-22-77 g-02-77 8-29-77 9-06-77 10-28-77 1I-01-77 12-03-77 12-07-77 2-02-78 2-02-78 3-10-78 3-12-78 4-17-78 4-21-78 6-01-78 6-07-78 7-17-78 7-22-78 8-29-78 9-03-78 10-16-78 10-27-78 I l-30-78 12-01-78
Mean diastolic blood pressure
Percent end digit zero
Percent equal 70mm Hg.
First
First
First
8:.37 78.43 81.40 80.81 76.60 78.56 75.50 8 1.54 83.31 78.51 81.06 78.67 83.47 83.85 84.33 81.59 83.46 78.84 83.40 84.20 80.35 80.11 86.74 84.99 81.23 81.50 75.97 80.97 81.34 79.29 81.04 80.08 76.02 78.80 8 1.47 75.50 83.51 80.19 77.88 84.83 76.04 80.32 83.08 78.81 79.87 90.01 75.00 74.71
Second 78.01 75.94 78.97 79.17 76.80 76.8 1 73.60 80.54 81.67 78.34 79.57 78.45 83.14 83.48 82.84 80.22 83.13 76.90 83.28 82.68 80.18 79.86 86.49 82.18 78.76 79.32 74.64 79.19 81.03 79.71 82.34 78.2 1 74.58 78.10 78.48 74.69 81.49 80.24 76.86 82.16 75.02 77.06 82.86 78.00 79.65 87.17 73.23 72.15
3 1.97 33.08 52.84 28.88 59.64 33.33 56.72 20.52 54.49 22.58 59.71 22.47 76.47 25.00 66.15 34.20 23.36 31.19 22.18 32.78 22.87 48.12 47.18 64.90 30.28 47.72 28.17 65.30 21.69 54.24 26.13 48.97 55.35 33.33 50.00 51.44 72.42 26.85 22.93 74.71 54.15 47.36 32.96 24.13 60.99 47.28 95.28 67.78
Second 50.29 29.04 50.83 32.47 69.00 33.86 47.89 29.19 50.29 21.55 60.18 20.11 74.20 23.57 55.81 35.44 25.54 29.23 21.05 29.87 27.12 47.31 47.14 63.75 28.84 44.00 24.17 57.85 22.75 55.66 24.50 51.70 52.07 24.73 46.85 50.00 61.76 22.22 17.80 74.14 54.81 49.02 28.51 22.22 47.48 44.91 88.62 65.10
6.93 9.55 12.00 6.61 16.09 5.61 17.64 5.17 12.57 6.84 14.21 7.82 18.91 4.28 11.92 7.40 5.43 7.17 5.24 6.22 6.34 10.63 7.04 13.07 4.76 13.88 5.66 15.78 5.26 17.45 1.42 13.60 12.35 9.13 11.80 15.78 14.96 7.87 6.36 12.35 15.89 14.21 6.25 7.27 24.64 3.72 43.92 19.33
Second 15.02 10.66 15.00 9.92 12.64 9.27 15.54 6.89 8.38 7.30 20.37 7.82 16.66 5.00 8.07 8.14 5.43 7.59 3.37 7.46 6.87 14.36 9.85 15.03 5.23 20.00 4.71 17.00 6.84 15.56 3.96 10.88 17.64 8.60 14.58 13.87 14.59 5.09 5.45 14.60 18.54 17.53 7.35 6.51 13.38 9.57 36.91 16.66
Chi-sqr. test stat.’
Blood lead ug,‘dL
7.35 9.66 5.70 32.76 10.50 5.54 38.58 7.29 12.58 12.82 3.67 8.76 18.10 11.99 32.21 6.59 13.14 7.17 24.65 15.36 3.84 5.38 46.94 29.84 4.99 5.42 21.37 10.29 2.47 14.03 3.80 8.52 12.28 11.18 9.40 37.92 19.86 11.34 14.20 42.73 35.27 2.34 10.24 14.67 23.46 80.51 74.00 35.75
14.73 16.29 13.93 15.43 18.77 16.82 16.60 16.18 16.65 15.92 16.26 15.03 18.06 19.13 15.27 13.90 16.70 12.79 10.86 11.99 13.59 13.97 18.30 15.44 14.86 14.17 14.50 15.45 15.54 13.75 13.53 14.10 13.88 12.86 14.74 13.18 13.95 13.20 16.98 13.61 13.19 14.58 14.06 14.68 17.37 15.44 14.09 14.05
D. Coare
and R. Fowles.
Blood lead-blood
49 50
. 51 52 53 54 55 56 57 58 59 60 61 62 63 64
relarionship
Exam date mid point
.Mean diastolic blood pressure
Percent end digit zero
Percent equal 70mm Hg.
First
Second
First
Second
First
2-04-79 2-08-79 3-22-79 3-23-79 S-03-79 5-06-79 6- 17-79 6- 19-79 8- 17-79 8-23-79 9-23-79 10-09-79 11-l 1-79 1l-24-79 2-05-80 2- 14-80
81.06 78.04 83.28 81.76 15.54 77.30 72.20 85.00 14.18 78.68 79.48 77.3 1 72.24 79.79 82.06 71.83
80.43 78.27 80.79 80.28 74.38 75.29 71.20 84.46 73.78 78.48 77.21 76.55 71.38 78.61 79.32 71.68
64.00 23.95 63.58 71.72 91.14 25.57 99.47 87.60 99.10 45.19 82.97 84.88 99.25 51.56 55.34 99.15
56.00 25.95 62.08 62.28 91.75 25.51 97.93 86.63 98.2 1 42.12 91.91 80.00 95.89 33.18 48.65 98.72
14.75 7.61 12.43 15.42 46.41 7.14 55.67 13.67 53.77 14.28 18.29 44.44 55.55 10.61 15.84 54.8 1
Table Number Of
PSU
subjects
Mean age
I 2 3 4 5 6 7 8 9 IO 11 12 13 14 15 16 17 18 19 20 21 22
172 269 300 270 173 192 238 346 167 218 211 178 221 140 260 269 184 235 267 241 188 187
39.39 47.70 38.50 40.55 41.06 40.89 41.68 47.06 40.6 1 39.32 38.12 36.39 42.90 38.74 44.65 40.24 46.85 36.66 45.29 42.57 42.42 42.43
177
1 (continued)
Table
PSU
pressure
Second
Chi-sqr. test stat.’
Blood lead ug/dL
15.30 10.38 12.43 15.71 41.75 8.76 54.63 16.23 56.88 14.92 29.78 43.63 51.85 8.40 13.96 50.20
13.76 20.62 10.06 4.47 137.91 35.67 156.66 29.84 135.74 16.13 40.88 il.61 214.14 2.68 10.36 188.66
15.24 11.39 11.02 11.13 12.26 12.36 14.37 12.78 12.00 11.49 10.79 11.85 9.34 12.08 10.66 9.20
1 (continued) Mean body mas?
Percent male
24.90 25.10 24.84 24.58 24.27 26.21 24.54 25.32 24.25 24.48 23.98 23.80 24.54 24.50 24.77 24.89 25.16 24.24 24.84 24.04 24.62 25.93
49.13 48.46 51.67 44.12 52.30 44.85 50.84 45.11 41.92 48.40 47.39 52.5 1 49.10 56.43 46.15 44.81 51.09 54.01 46.82 45.64 48.15 41.49
Percent white 91.90 75.00 90.00 55.51 91.95 55.15 97.89 90.5 1 84.61 94.06 95.26 98.32 66.21 95.71 98.07 67.03 88.04 75.10 94.38 92.11 58.20 62.23
Percent black 1.73 22.05 6.00 44.48 3.44 44.84 0.00 9.48 4.19 5.02 3.79 0.00 32.88 2.85 1.92 32.96 11.41 23.20 5.61 7.88 33.33 36.17
D. Coupe und R. Fades.
178
Blood
Table
leud-blood
pressure
relationship
1 (continued)
PSU
Number of subjects
\lean age
Mean body ma&
‘3 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64
142 152 208 177 212 245 189 212 200 147 168 186 142 208 273 216 218 356 301 209 271 261 I41 185 213 149 175 288 I85 336 310 306 189 234 223 313 235 312 268 225 262 236
40.23 At.83 43.24 42.49 39.46 39.56 43.28 40.45 39.94 34.69 40.85 42.2 I 44.44 43.25 41.87 44.86 41.57 51.42 45.43 41.36 41.15 37.60 45.13 42.57 40.66 42.17 38.57 40.10 41.32 44.51 38.32 36.78 39.65 41.23 42.20 43.9 I 42.9 1 44.24 40.73 42.73 43.10 40.30
24.4 I 24.68 25.37 24.69 24.5 I 25.28 24.8 I 25.14 24.48 23.84 24.67 24.65 23.69 24.39 24.72 25.32 24.37 25.83 25.71 25.13 25.49 25.13 25.36 24.93 25.1 I 24.52 24.92 24.84 24.38 25.09 24.40 24.27 24.63 24.37 24.38 25.07 25.03 24.94 25.58 24.84 24.95 24.97
-
Percent male
Percent white
Percent black
52.1 I 47.06 54.29 46.: 1 45.75 48.58 50.00 50.47 42.57 45.58 45.29 47.3 1 56.25 42.58 47.08 50.00 48.18 47.19 44.70 50.24 52.57 45.98 47.18 44.15 47.20 51.33 50.27 50.87 48.11 48.57 49.04 49.35 47.94 44.44 47.1 I 46.35 47.66 48.09 48.89 50.00 49.06 46.03
95.77 96.07 96.66 98.88 99.52 99.19 82.63 97.64 92.57 61.90 72.94 91.93 25.69 94.25 93.06 99.53 90.00 100.00 99.33 86.72 100.00 55.55 82.39 88.82 74.76 96.66 55.73 95.84 94.59 92.28 98.07 95.12 69.07 76.49 78.22 98.73 91.91 99.68 99.25 21.68 76.60 97.07
2.1 I 3.92 2.38 0.55 0.47 0.40 16.84 2.35 5.94 37.41 17.64 5.37 0.69 3.34 2.18 0.00 8.63 0.00 0.00 12.79 0.00 43.29 16.90 10.63 23.36 2.66 42.62 3.46 2.70 7.71 1.92 3.57 29.89 23.07 21.33 1.26 8.08 0.3 1 0.37 73.89 23.39 2.92
“The chi-square statistic tests the tirst sitting diastolic blood pressure distribution of each PSU against the diastolic blood pressure of all subjects 12 and over in the first National Health and Nutrition Examination Survey. See footnote 2. bBody mass is the ratio of weight in kilograms to the square of height in meters.
D. Coute und R. Fonfes. Blood lead-blood pressure relarionship
179
subjects over 12 years of age:’ means, proportion of readings with end digit zero. proportion of readings equal to 70, and Pearson’s chi-square statistic to evaluate the equivalence of the diastolic blood pressure distribution (first reading) for each PSU in NHANES II to the NHANES I diastolic blood pressure distribution.’ Also shown in table 1 are the number of readings and the mean PSU values for age and body mass and the percent of subjects male, white and black.3 It is clear from table 1 that the end digit zero phenomenon intensified in 1979. PSUs 53, 5.5. 57, 61, and 64 have the largest percentages of end digit zeros in the first and second diastolic blood pressure readings in 1979 and 1980. These percentages for the first sitting diastolic blood pressure readings are 98, 99, 99, 99, and 99, respectively. For the second measure they are 98, 98, 98, 95, and 97, respectiveiy.4 Because blood pressure was to be recorded in only even digits, zeros should appear about 20 percent of the time. It is also clear from table 1 that high end digit zero percentages are associated with high chi-square test statistics, with lower mean diastolic blood pressure readings, and with higher proportions of readings at 70. Figs. 1. 2, and 3 verify the association by PSU between end digit zero and chi-square statistic and end digit zero and mean diastolic blood pressure for the whole sample and for the 1979-1980 period.s They ‘In NHANES 11, blood pressure was measured in the sitting position at the beginning of the physical examination and in the sitting and recumbent positions at the end of the physical examination. Summary statistics are presented for both of the sitting diastolic readings because the first reading corresponds to the diastolic measure in the first National Health and Nutrition Examination Survey, which is the reference distribution for the chi-square tests described below. and the second reading was emphasized by PSLH. Also, regression results are sensitive to the measure used (see section 3). *The reference distribution for Pearson’s chi-square statistic is the diastolic blood pressure distribution of all subjects I2 and over in the first National Health and Nutrition Examination Survey. 1971-1974. Like NHANES II. it is a near representative sample for the U.S. population with over 20.000 examined subjects. One blood pressure reading at the beginning of the physical exam was administered by a physician (not retired) to all subjects I2 years and over. For the chi-square calculations, blood pressure readings were grouped into eight uniform categories after deleting readings below 55 mm hg. and above 125 mm hg. The latter adjustment eliminates the possibility that an HNANES II PSU with a few extreme observations will necessarily have a high chi-square statistic. 3Blood pressure generally increases with age and body mass (weight/height**2) and is higher for males and adult blacks [Fortmann et al. (1983) and Gordon and Kannel (1983)]. ‘The corresponding ligures for the recumbent diastolic blood pressure reading for these PSUs are 98, 99, 97. and 100. respectively. The systolic blood pressure measures were also characterized by an end digit zero problem that trends with the frequency of end digit zero in the diastolic blood pressure data. Percent end digit zero for the first-and second sitting systolic measures and for the recumbent svstolic measure are 95. 91, and 95 for PSU 53; 92. 96, and 97 for PSU 55; 96. 95, and 98 for PSU 57; 98, 99. and 99 for PSU 61; and 99, 98, 99 for PSU 64. ‘Note that the first sitting diastolic blood pressure measure is used in fig. I and the second sitting diastolic blood pressure measure is used in figs. 2 and 3. We switch to the second measure in tigs. 2 and 3 because this measure is used by PSLH. Fig. I requires the first measure because of its match with the NHANES I diastolic reading that is used as the reference distribution in the chi-square calculations.
IHE.
B
180
D. Coale and R. Foowies. Blood lead-blood pressure relationship
57 55 l ‘. 53
.
64 .
61 .
.
.
CHI-SQUARE
Fig.
1. Percent
end
digit
zero
TEST
STATISTIC
and chi-square statistic, first sitting reading, by PSU, NHANES II.
diastolic
blood
pressure
. .
l
. . .
. l
0. : .
.
:. .
. .
.
. .
.
.
70
Fig. 2. Percent
end
digit
.
$3
, MEAN
zero
DIASTOLIC
BLOOD
and mean diastolic blood NHANES II, 1976-1978.
PRESSURE
pressure,
second
sitting,
by
PSU,
D. Coate
‘O”
and R. Fwles,
55*
-064 61
5;
Blood
lead-blood
;3
pressure
181
relationship
. .
0ct
.
ii:_ P c_ 3
.
3 zw
. .
.
8
.
. . I
207
70
MEAN
I
DIASTOLIC
. I
BLOOD
1
I
PRESSURE
Fig. 3. Percent end digit zero and mean diastolic blood pressure, second sitting, by PSU, NHANES II. 1979-1980.
also highlight PSUs 53, 55, 57, 61, and 64 as the most severe outliers by the joint criteria of proportion end digit zero and chi-square statistic. It appears then that data of questionable quality characterize the blood pressure readings for some PSUs in 1979 and 1980. Furthermore, the recorded measurements may be biased downward and may have contributed to an artificial robustness in the PSLH research because blood lead levels in NHANES II were falling in 1979 and 1980.
3. Regression results In table 2 blood lead coefficients and r values are sumarized from blood pressure regression models for different NHANES II samples. The purpose of the table is to show the sensitivity of the blood lead coefficient to the blood pressure measure used, to the age, sex, and race characteristics of the sample chosen, and to the blood pressure data of questionable quality in 1979 and 1980. The model specifications are from PSLH. Independent variables in the diastolic blood pressure specification include age, age squared, the natural log of blood lead, body mass (weight/height**2), dietary potassium, hemoglobin, albumin, and the natural log of dietary vitamin C. The PSLH systolic blood pressure equation includes the aforementioned independent variables with the exception of hemoglobin and dietary potas-
D. Coarv und R. Fades,
182
Bid
Table
pressurr
relationship
2
coefficients and I statistics for the natural log of blood lead for selected NHANES samples. generalized least squares. PSLH blood pressure specification.”
Regression
White male JO-59
Race Sex Ages Data
lead-blood
White male 21-39
White male 60-74
White female 40-59
White female 21-39
White female 60-74
All Both 12-39 60-74
-0.87 (- 1.00)
1.41 (1.35)
1.28 (3.05)
from all PSUs
Diastolic (0
1
Diastolic (0
2
I.20
2.75 (2.27)
0.62 (0.62)
(1.06)
3.93 (3.34)
1.90 (1.98)
1.32 (1.16)
- 0.28 (-0.27)
- 0.49 (-0.55)
1.04 (1.07)
1.43 (3.49)
3.21 (1.57)
2.66 (3.92)
1.77 ( 1.55)
Systolic (rl
1
5.3 1 (2.991
2.20 (1.68)
1.25 (0.62)
- 0.02 (-0.01)
-0.18 (-0.16)
Systolic (rl
2
6.78 (3.71)
3.00 (2.19)
2.93 (1.53)
- 1.33 (-0.77)
(- 1.09)
I .08 (0.54)
2.60 (3.85)
794
620
815
891
5039
Sample sizeb _____ Data from all PSUs
574
1
1.62 (1.30)
Diastolic (r)
2
2.73 (2.24) 3.85
1
787
- 1.25
but 53, 55. 57, 61, 64
Diastolic (1)
Systolic (0
II
(2.05)
-0.55 (-0.51)
0.58 (0.48)
0.40 (0.33)
- 2.77 (-2.96)
0.58 (0.53)
0.4 1 (0.91)
0.50 (0.48)
0.66 (0.56)
- 1.20 (-1.06)
- 2.02 (-2.12)
0.32 (0.31)
0.54 (1.23)
0.98 (0.69)
0.27 (0.12)
- 1.08 (-0.53)
-2.33 (- 1.84)
3.16 (1.43)
1.84 (2.48)
2.08 5.06 1.64 - 1.48 2 - 3.55 0.65 1.59 4591 827 525 694 741 556 726 sizeb -__ “Means and standard deviations for the second sitting blood pressure measures for all subjects 12 to 74 years in all PSUs are 78.8 and 12.5 (diastolic) and 125.6 and 21.8 (systolic). The mean and standard deviation of the natural log of blood lead are 2.54 and 0.41. %ample size from blood presure models for the second diastolic reading. Systolic
Sample
plus the natural logs of dietary riboflavin, dietary oleic acid, and serum vitamin C. We have added sex and race variables to the basic PSLH specifications when appropriate, that is when models are estimated over samples including different races and both sexes. Because these models have a strange assortment of linear and nonlinear terms, diastolic and systolic blood pressure models were also estimated with the following independent variables: age, body mass, blood lead, and race and sex when relevant. The blood lead coefficients from these models followed the same pattern as those in table 2, confirming the PSLH conclusion that the results for the blood lead coefficient are not sensitive to model specification.6 sium,
‘JRegression results for the NHANES II samples identified in table 2 are available from the authors on request. The coefficients of the natural log of blood lead for the recumbent blood pressure measures are generally bounded by the coefficients for the two sitting measures for the samples in table 2.
D. Courr and R. Fowlrs, Blood
lead-blood pressure relarionship
183
The evidence in table 2 indicates the level and statistical significance of the blood lead coefficient are sensitive to the age, race, and sex characteristics of the sample, to the blood pressure measure selected, and to the inclusion of the questionable blood pressure data from the 1979-1980 period. The regressions are estimated by generalized least squares to take account of within PSU variance.’ Ignoring the questionable data issue for a moment, it is clear that the blood pressure-blood lead association is strongest for the original PSLH sample of 40-59 year old white males and for the second sitting blood pressure measurement. The association weakens considerably for males if the first sitting blood pressure measurement is used rather than the second and if the sample is expanded to other age groups. The association is weak in the case of females and sometimes negative. In the absence of plausible biological explanations, the sensitivity of the blood pressure-blood lead results to the different age and sex groupings is a strong challenge to the PSLH results. The results are weakened even further if data from PSUs 53, 55, 57, 61, and 64 are deleted from the samples. In the lower part of table 2 it can be seen that the magnitude of the blood lead coefficients fall by one-third to one-half for the male samples if these questionable data are excluded. Statistical significance falls markedly also. Estimating the blood pressure relationships separately for each PSU gives a wide range of coefficients for the natural logarithm of lead. For example. the mean of the 64 coefficients and the 25th and 75th percentile values of the distribution of coefficients for 12 to 74 year olds, second sitting diastolic blood pressure measure, are 0.37, -2.08. and 1.81. The same measures for the 21 to 74 year old white males are 1.23, -3.72, and 5.75. It should also be pointed out that even the original PSLH coefficients do not indicate that reductions in blood lead result in substantial falls in blood pressure. The 37% reduction in blood lead claimed by PSLH as characteristic of the 1976-1980 period would reduce diastolic blood pressure at the mean by only 1.8 mm. hg, according to their regression results.* The big payoff in improved cardiovascular health and lower death rates that they report comes from the sensitivity of these health outcomes to reductions in ‘OLS estimates of the PSLH diastolic blood pressure model over the 40-59 year old white male sample yield a coefticient of 4.3 (r=3.5) for the natural log of blood lead for the all PSU sample and a coefficient of 3.1 (1=?.4) for the sample with data deleted from the tive problem PSUs. The reported results of PSLH, which are adjusted for sample design, show a natural log of blood lead coeflicient of 3.95 (1=2.8). We have not adjusted for sample design because the sampling weights provided with the NHANES II data are not appropriate for the various subsamples considered in table 2. 8Using the NHANES II data to detect trends within the sample period. as PSLH did for blood lead levels can be misleading. Although the sample is near representative of the U.S. population throughout the sample period it is not necessarily representative in any year or sub-period.
I84
D. Coare
and R. Fonles,
Blood
lead-blood
pressure
relationship
blood pressure according to the Pooling Project (1978) and Framingham (Shurtleff, 1974; McGee and Gordon, 1976) studies. 4. Conclusion In this paper we have shown that there is weak statistical evidence for a blood lead-blood pressure relationship in the second National Health and Nutrition Examination Survey data. The significance and magnitude of this relationship for 40-59 year old white males as originally reported by Pirkle, Schwartz, Landis, and Harlan does not characterize other age and sex samples and is sensitive to the use of blood pressure data of questionable quality. References Fortmann, S.P. et al., 1983, The association of blood pressure and dietary alcohol: Differences by age, sex, and estrogen use, American Journal of Epidemiology 118, 497-507. Gordon, Tavia and William B. Kannel, 1983, Drinking and its relation to smoking. BP, blood lipids, and uric acid: The Framingham Study, Archives of Internal Medicine 143, July, 13661375. McGee. D. and T. Gordon. 1976, The results of the Framingham Study applied to four other U.S. based epidemiological studies of coronary heart disease, The Framingham Study, Sec. 31, (NIH) 76-1083. National Center for Health Statistics, 1981, Plan and operation of the second national health and nutrition examination survey, U.S. Dept. of Health and Human Services, vital and health statistics, series I. no. 15, July. National Center for Health Statistics. 1986, Blood pressure levels in persons IS-74 years of age in 1976-1980, and trends in blood pressure from 1960 to 1980 in the United States, U.S. Dept. of Health and Human Services, Vital and Health Statistics, series II, no. 234, July. Pirkle, James L., Joel Schwartz. J. Richard Landis and William R. Harlan, 1985, The relationship between blood lead levels and blood pressure and its cardiovascular risk implications, American Journal of Epidemiology 121. no. 2. 1978, Relationship of blood pressure, serum cholesterol, Pooling Project Research Group. smoking habit, relative weight, and ECG abnormalities to incidence of major coronary events. Journal of Chronic Diseases 31, 201-306. Schwartz, Joel et al.. 1984. Costs and benefits of reducing lead in gasoline, Draft final report (Office of Policy Analysis. U.S. Environmental Protection Agency, Washington, D.C., EPA23@-03-84005). Shabecoff, Phillip. 1985, EPA orders 90 percent cut in lead content of gasoline by 1986, New York Times, March 5, 20. Shurtleff. D., 1974. Some characteristics related to the incidence of cardiovascular disease and death, The Framingham Study, Sec. 30, (NIH) 76-1083.