729
Body Mass Index and Associations
of Sodium and Potassium
With Blood Pressure in INTERSALT
Alan R. Dyer, Paul Elliott, Martin Shipley, Rose Stamler, Jeremiah Stamler, on behalf of the
INTERSALT Cooperative Research Group
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Abstract This report further examines the relation of body
mass index (BMI) to associations of 24-hour urinary sodium,
potassium, and sodium-potassium ratio with blood pressure in
INTERSALT, a 52-center international study of electrolytes
and blood pressure. Analyses without adjustment for BMI
indicated average systolic pressure greater by 6.00 mm Hg per
100 mmol higher sodium and diastolic by 2.52 mm Hg. With
adjustment for BMI, these values were reduced to 3.14 and
0.14 mm Hg, respectively. For the sodium-potassium ratio,
blood pressure associations were stronger when not adjusted
for BMI, and for potassium, adjustment generally had little
effect. To explore possible interactions of these variables with
BMI in relation to blood pressure, the 52 centers were divided
into two groups of 26 based on whether the center median for
BMI was less than or greater than or equal to 24.5 kg/m2, and
individuals within each of the 52 centers were classified into
lower- or higher-BMI groups based on individual BMI less
than or greater than or equal to 24.1 kg/m2. Sodium and the
sodium-potassium ratio were positively and significantly and
potassium inversely and significantly related to systolic pressure in all four of these subgroups, and the sodium-potassium
ratio and potassium were related to diastolic pressure in two
and three subgroups, respectively. Electrolyte-blood pressure
associations did not differ significantly between the two subgroups of centers or between the two subgroups based on
individuals. Although these results indicate that adjustment
for BMI has an important effect on INTERSALT associations
of sodium and the sodium-potassium ratio with blood pressure
and may represent an overadjustment, they also indicate that
each of the three variables is related to blood pressure
throughout the BMI range. Thus, they do not support the
concept of important interactions of sodium and potassium
with BMI in relation to blood pressure. (Hypertension.
1994;23 [part l]:729-736.)
Key Words • blood pressure • body mass index • sodium
• potassium
I
Intervention studies of the effects of weight loss,
reduced sodium intake, and potassium supplementation
on blood pressure have been inconsistent as to whether
weight loss leads to lower blood pressure with or
without reduced sodium intake 414 and in at least one
study with or without increased potassium intake.5
Furthermore, although sodium reduction lowers blood
pressure,15 it is unclear whether lower sodium intake
reduces blood pressure equally in overweight and nonoverweight individuals1617; also, combined effects of
weight and sodium reduction on blood pressure have
not yet been quantified.14
This report uses INTERSALT data to further examine BMI and associations of sodium, potassium, and
sodium-potassium ratio with blood pressure by quantifying the effects of adjustment for BMI on these associations and by exploring possible interactions of these
variables with BMI in relation to blood pressure.
NTERSALT is an international study of the relations of electrolyte excretion and other factors to
blood pressure carried out in 52 centers from 32
countries. Previous reports from INTERSALT indicated that body mass index (BMI), 24-hour urinary
sodium and potassium excretions, and the sodiumpotassium ratio were all independently related to blood
pressure of individuals13 and that sodium and potassium excretions of individuals were both positively correlated with BMI.2 In addition, pooled regression coefficients for sodium, potassium, and sodium-potassium
ratio with blood pressure that were adjusted only for age
and sex when compared with the coefficients also
adjusted for alcohol intake and BMI (as well as potassium for sodium, and sodium for potassium) suggested
that adjustment for BMI had a substantial effect on
observed electrolyte-blood pressure associations in
INTERSALT.1
Received January 24, 1994; accepted in revised form March 30,
1994.
From the Department of Preventive Medicine, Northwestern
University Medical School, Chicago, 111 (A.R.D., R.S., J.S.); the
Department of Public Health and Policy (P.E.) and Department of
Epidemiology and Population Sciences (P.E., M.S.), London (UK)
School of Hygiene and Tropical Medicine; and the Department of
Epidemiology and Public Health, University College and Middlesex School of Medicine, University College, London (M.S.).
Correspondence to Dr Alan R. Dyer, Department of Preventive
Medicine, Northwestern University Medical School, 680 N Lake
Shore Dr, Suite 1102, Chicago, IL 60611.
Methods
Details of the INTERSALT study design and methods have
been published.1819 Briefly, each of the 52 centers recruited
200 men and women aged 20 to 59 years, with 25 in each of
eight age-sex groups. Samples were selected randomly from
population lists or by chunk sampling of defined populations.
Local investigators were trained to implement a common
standardized protocol at one of five training meetings, based
on a detailed Manual of Operations.19 Data forms were sent to
the Coordinating Center in London for review, editing, coding,
data entry, and analysis.
730
Hypertension
Vol 23, No 6, Part 1 June 1994
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Participants in each of the 52 centers provided written or
verbal (if not literate) informed consent after approval of all
study procedures by local institutional review boards. All
procedures were conducted in accordance with institutional
guidelines.
Blood pressure (sitting) was measured twice with the use of
a random-zero sphygmomanometer (Hawksley) after participants had emptied their bladders and sat quietly for 5 minutes.
Systolic blood pressure was recorded as the appearance of
sound (phase I) and diastolic as the disappearance of sound
(phase V). Blood pressure of individual participants was the
mean of the two readings.
Both "spot" and 24-hour urine collections were made to
estimate electrolyte excretion. The start and end of each
24-hour collection were supervised by clinic staff, and completeness was assessed by a standardized interview. Urine
aliquots were stored locally at -20°C before being shipped
frozen to the Central Laboratory at St Raphael University in
Leuven, Belgium, where all urine analyses were performed
with strict internal and external quality control. Sodium and
potassium excretions were measured by atomic absorption
flame photometry.20 Individual sodium and potassium excretion values were the products of concentrations in the urine
and urinary volume corrected to 24 hours.
Height and weight were each measured twice using a
stadiometer and beam balance scale where possible. BMI was
calculated as weight divided by height squared (kilograms per
meter squared). Daily intake of alcoholic drinks over the
preceding 7 days was assessed by questionnaire and, based on
local information, converted into volume (milliliters) of absolute alcohol.
Repeat urine collections and blood pressure measurements
were obtained at a second visit in a random 8% of participants
to estimate intraindividual variability.
To quantify the effect of adjustment for BMI on electrolyteblood pressure associations, center-by-center linear regressions of blood pressure on sodium, potassium, and sodiumpotassium ratio were calculated with and without adjustment
for BMI. All regressions included adjustment for age, sex, and
alcohol intake. The regressions of blood pressure on sodium
excretion also included 24-hour potassium excretion, and
those for potassium included sodium. To adjust for alcohol,
7-day intakes were stratified into three groups (0,1 to 299, and
300+ mL of absolute alcohol per week) with two 0-1 variables,
ie, no alcohol intake versus 1 to 299 mL/wk (0,1) and no intake
versus 300+ mL/wk (0,1). Five of 10 079 people were excluded
from these analyses because of missing data on alcohol intake.
In addition, the results for diastolic blood pressure with
adjustment for age, sex, alcohol intake, and BMI differ slightly
from those previously reported1 because of the exclusion from
regression analyses for diastolic pressure of 17 people with
diastolic blood pressures recorded as less than 30 mm Hg.
Within-center regression coefficients were averaged (pooled)
across centers to yield study-wide estimates of associations
between blood pressure and each electrolyte variable with and
without adjustment for BMI. Each center coefficient was
weighted by the inverse of its variance.
Regression coefficients for sodium are expressed as millimeters of mercury per 100 mmol (1 mmol = l mEq=23 mg)
sodium, coefficients for potassium as millimeters of mercury
per 30 mmol (1 mmol = l mEq=39 mg) potassium, and coefficients for the sodium-potassium ratio as millimeters of mercury per 2 U. These values for sodium, potassium, and the
sodium-potassium ratio were chosen for two reasons. First, 100
mmol (mEq) sodium, 30 mmol (mEq) potassium, and 2 U of
the sodium-potassium ratio are approximately the interquartile ranges for these variables in the INTERSALT sample of
10 074 people used in these analyses, ie, 97 mmol (mEq) for
sodium, 32 mmol (mEq) for potassium, and 2.13 U for the
sodium-potassium ratio. Second, these values also generally
reflect the changes that would be required in sodium and
potassium intake in the US population and/or the INTERSALT sample to achieve the goals for intake suggested by the
National Research Council.21-22 For sodium, the National
Research Council recommends a reduction in daily intake
from the current US consumption of 10 to 14.5 g salt (171 to
248 mmol sodium intake) to no more than 6.0 g salt (103 mmol
sodium), with a goal of 4.5 g (77 mmol sodium).21 Hence, the
average reduction in sodium intake from current levels required to achieve this goal is approximately 100 mmol (mEq).
For potassium, the National Research Council recommends an
intake of 3500 mg (90 mmol),22 which represents an average
increase of approximately 35 mmol (mEq) over current INTERSALT levels of intake. Changes of this magnitude in
sodium and potassium intake would reduce the average sodium-potassium ratio in INTERSALT by approximately 2 U.
To explore possible interactions of electrolyte variables and
BMI in relation to blood pressure, two sets of analyses were
performed. First, the 52 centers were divided into two groups
of 26 centers based on whether the median BMI at the center
was less than 24.5 kg/m2 (lower-BMI centers) or greater than
or equal to 24.5 kg/m2 (higher-BMI centers). There were 2518
men and 2492 women in the 26 lower-BMI centers and 2524
men and 2540 women in the 26 higher-BMI centers. Within
each center, linear regressions of blood pressure on each
electrolyte variable were calculated and adjusted for age, sex,
alcohol intake, and BMI. Regressions for sodium also included
potassium, and those for potassium included sodium. Withincenter regression coefficients, weighted by the inverse of their
variances, were averaged across centers to yield estimates of
the associations between blood pressure and each variable
within each set of 26 centers.
In the second set of analyses for interactions, individuals
within the 52 centers were classified as lower-BMI if their BMI
was less than 24.1 kg/m2 and higher-BMI if their BMI was
greater than or equal to 24.1 kg/m2. (The cut point for
determining higher- and lower-BMI individuals was chosen to
approximately equalize the number of individuals in each
subgroup after exclusion of any subgroup in a center with
fewer than 20 individuals.) Within each center, linear regressions of blood pressure on each electrolyte variable were
calculated for individuals in each group. Regressions were not
run for any BMI subgroup in a center if that subgroup
contained fewer than 20 people. This resulted in 4 centers and
57 people being excluded from analyses in the higher-BMI
groups. There were 2349 men and 2661 women included in the
analyses for the lower-BMI groups and 2658 men and 2349
women included in the analyses for the higher-BMI groups. In
these analyses, adjustment was also made for age, sex, alcohol
intake, and BMI within each BMI subgroup. Potassium excretion was also included in regressions of blood pressure on
sodium, and sodium in those for potassium. Regression coefficients were averaged across centers for all higher-BMI
groups and all lower-BMI groups, with weights equal to the
inverse of the variance.
BMI was included as a possible confounder in these two sets
of analyses for two reasons. First, adjustment for BMI within
BMI subgroups allows comparison of the results reported here
with previously reported results.1 Second, analyses in individuals classified as lower and higher BMI constitutes an adjustment for BMI that was not present in analyses in lower- and
higher-BMI centers. Hence, to make these two sets of analyses
comparable, BMI was included as an independent variable in
all BMI subgroup analyses.
Pooled regression coefficients for electrolyte variables were
corrected for reliability ("regression dilution bias") according
to methods previously described for INTERSALT.23-24 The
estimates of reliability used in these corrections were 0.3747
for 24-hour sodium excretion, 0.4717 for 24-hour potassium
excretion, and 0.3422 for the sodium-potassium ratio. The
corrections for models containing both sodium and potassium
also require an estimate of the proportion of the covariance
Dyer et al
BMI, Sodium, Potassium, and Blood Pressure
731
TABLE 1. Pooled Regression Coefficients Relating 24-Hour Urinary Sodium and Potassium Excretions and
Sodium-Potassium Ratio to Blood Pressure With and Without Adjustment for Body Mass Index
Systolic Pressure
Variable
Dlastollc Pressure
With BMI
Adjustment
Without BMI
Adjustment
With BMI
Adjustment
Without BMI
Adjustment
24-Hour urinary sodium
1.001
2.051
0.037
0.858
Standard error
0.264
0.266
0.187
0.190
Z score
3.788)1
7.709||
0.198
4.528||
3.138
6.002
0.140
2.522
-0.761
-0.560
-0.507
-0.308
0.210
0.214
0.156
0.159
-3.633||
-2.622§
-3.252§
-1.933
-2.015
-1.973
-1.119
-0.987
1.242
1.685
0.343
0.681
Coefficient, mm Hg/100 mmol sodium
Corrected coefficient*
24-Hour urinary potassium
Coefficient, mm Hg/30 mmol potassium
Standard error
Z score
Corrected coefficient*
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
24-Hour urinary sodium-potassium ratio
Coefficient, mm Hg/2 U
Standard error
0.209
0.214
0.148
0.151
Z score
5.941||
7.878H
2.323+
4.500||
3.692
4.942
1.019
2.056
Corrected coefficientt
BMI indicates body mass index.
*Corrected for reliability of both 24-hour sodium and potassium excretions and intraindividual correlation of sodium and potassium.
tCorrected for reliability of 24-hour sodium-potassium ratio.
tP<.05, §P<.01, ||P<.001.
between sodium and potassium that is due to true covariation
between them. The estimate used in these analyses was 0.5110.
(This estimate indicates that approximately 49% of the observed covariance between sodium and potassium excretions
in INTERS ALT was due to their measurement on the same
24-hour urine collection.)
Results
Electrolyte-Blood Pressure Associations With and
Without Adjustment for BMI
Table 1 gives the pooled regression coefficients relating 24-hour sodium (millimeters of mercury per 100
mmol) and potassium (millimeters of mercury per 30
mmol) excretions and sodium-potassium ratio (millimeters of mercury per 2 U) to systolic and diastolic blood
pressure with and without adjustment for BMI. The
table also gives the standard error of each coefficient,
the coefficient divided by its standard error (Z score),
and the coefficient corrected for reliability ("regression
dilution bias").
Without adjustment for BMI, the pooled regression
coefficient relating sodium to systolic blood pressure
without correction for reliability was twice as large as
the coefficient from the analysis that included BMI, ie,
2.05 mm Hg for sodium intake higher by 100 mmol
(mEq) versus 1.00 mm Hg per 100 mmol (mEq). With
correction for reliability, the coefficients were 6.00 and
3.14 mm Hg per 100 mmol (mEq) sodium, respectively.
For sodium and diastolic pressure, a regression coefficient that was positive and significant without adjustment for BMI became nonsignificant when BMI was
added to the model. With correction for reliability, the
regression coefficient relating sodium to diastolic blood
pressure indicated average pressure greater by 2.52
mm Hg for sodium higher by 100 mmol (mEq) without
adjustment for BMI and 0.14 mm Hg per 100 mmol
(mEq) with adjustment.
For potassium, unlike for sodium, the unconnected
regression coefficients for both systolic and diastolic
blood pressures were smaller without adjustment for
BMI than with adjustment, and the coefficient for
diastolic pressure from the model without BMI did not
differ significantly from zero. However, when corrected
for regression dilution bias, the difference due to inclusion of BMI in the model essentially disappeared for
systolic pressure and was reduced for diastolic. For
systolic blood pressure, the corrected regression coefficients indicated average pressure less by 2.02 and 1.97
mm Hg for potassium excretion higher by 30 mmol
(mEq) for the models with and without BMI adjustment, respectively. For diastolic blood pressure, the
corrected coefficients indicated average pressure less by
1.12 and 0.99 mm Hg per 30 mmol (mEq) higher
potassium excretion, respectively.
Adjustment for BMI also had a substantial effect on
the regression coefficients for the sodium-potassium
ratio and blood pressure. For systolic blood pressure,
both the corrected and uncorrected regression coefficients were approximately 33% larger in the model
without than with adjustment for BMI, whereas for
diastolic pressure, coefficients were twice as large
without adjustment for BMI. With correction for
reliability and no adjustment for BMI, the regression
coefficient for systolic blood pressure indicated average pressure greater by 4.94 mm Hg for the sodiumpotassium ratio higher by 2 U and average diastolic
pressure greater by 2.06 mm Hg. With adjustment for
732
Hypertension
TABLE 2.
Vol 23, No 6, Part 1 June 1994
Medians (25th and 75th Percentlles) of Study Variables for Body Mass Index Subgroups
Lower-BMI
Variable
Hlgher-BMI
Individuals from lower- and higher-BMI centers
No. of centers
26
26
5010
5064
113.0 (104.0,124.0)
119.0 (110.0,130.0)
No. of men and women
Systolic pressure, mm Hg
Diastolic pressure, mm Hg
71.0 (63.0,79.0)
75.0 (67.0,82.0)
Urinary Na excretion, mmol
148.0 (94.7,203.0)
152.0 (112.3,201.2)
49.1 (34.8,68.2)
53.6 (39.6,69.8)
Urinary K excretion, mmo)
2.98(1.89,4.46)
2.90(2.18,3.83)
BMI, kg/m2
22.9 (20.8,25.2)
25.7 (23.0, 29.0)
Moderate drinkers, %*
37.7
48.0
Heavy drinkers, %t
12.2
13.5
Urinary Na-K ratio
Lower- and higher-BMI individuals
52
No. centers
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
5010
5007
112.0 (103.0,121.0)
122.0 (112.0,133.0)
No. men and women
Systolic pressure, mm Hg
48*
Diastolic pressure, mm Hg
69.0 (61.0, 76.0)
77.0 (70.0,84.0)
Urinary Na excretion, mmol
139.0 (92.8,187.6)
161.7 (118.8,213.7)
47.5 (34.4,64.4)
55.5 (40.9, 72.4)
2.91 (1.94,4.16)
2.95 (2.19,3.99)
Urinary K excretion, mmol
Urinary Na-K ratio
2
21.7 (20.2,22.9)
27.2 (25.5,30.0)
Moderate drinkers, %*
41.4
44.7
Heavy drinkers, %t
11.7
14.0
BMI, kg/m
BMI indicates body mass index. Fifty-two centers were divided into 26 with median BMI <24.5 kg/m2 (lower-BMI
centers) and 26 with median BMI 2:24.5 kg/m2 (higher-BMI centers). Individuals in each center were divided into
those with BMI <24.1 kg/m 2 (lower-BMI) and those with BMI 2:24.1 kg/m2 (higher-BMI).
*1 to 299 mL absolute alcohol per week.
t300+ mL absolute alcohol per week.
tFifty-seven higher-BMI individuals from four centers were excluded (see "Methods").
BMI and correction for reliability, the regression
coefficients indicated average pressure greater by 3.69
and 1.02 mm Hg per 2 U for systolic and diastolic
blood pressures, respectively.
Descriptive Statistics for BMI Subgroups
Table 2 gives the medians and 25th and 75th percentiles for systolic and diastolic blood pressures, 24-hour
urinary sodium and potassium excretions, sodium-potassium ratio, and BMI for participants from higherand lower-BMI centers as well as for all higher- and
lower-BMI individuals. Table 2 also gives the percentages of participants in these BMI subgroups who reported consuming 1 to 299 mL absolute alcohol in the
week before the exam and the percentage who reported
consuming 300+ mL. Medians for blood pressure, sodium and potassium excretions, and BMI (as expected)
were all greater in higher-BMI centers and individuals
than in lower-BMI centers and individuals. However,
the differences in blood pressure and electrolytes were
larger for higher- and lower-BMI individuals than for
higher- and lower-BMI centers, reflecting the inclusion
of both higher- and lower-BMI individuals in the higher- and lower-BMI centers.
Sodium and Blood Pressure in BMI Subgroups
Table 3 gives the results of the regression analyses to
assess possible interactions of sodium with BMI in
relation to blood pressure. With multivariate adjustment, 24-hour sodium excretion was positively and
significantly related to systolic pressure in both higherand lower-BMI centers and individuals.
For analyses based on centers, the regression coefficient was larger for lower-BMI centers compared with
higher-BMI centers. Without correction for reliability,
the pooled regression coefficients indicated average systolic pressure greater by 1.32 mm Hg for each 100-mmol
(mEq) increment in sodium excretion in lower-BMI
centers and 0.73 mm Hg greater in higher-BMI centers, a
difference that was not statistically significant. With
correction for reliability, the coefficients indicated average systolic pressure greater by 3.98 and 2.41 mm Hg,
respectively, for sodium higher by 100 mmol (mEq).
For analyses based on classification of individuals, the
regression coefficient was larger in higher-BMI compared with lower-BMI individuals. The pooled regression coefficients indicated average systolic pressure
greater by 1.22 and 1.00 mm Hg, respectively, per 100
mmol (mEq) sodium. This difference was also not
Dyer et al
BMI, Sodium, Potassium, and Blood Pressure
733
TABLE 3. Pooled Regression Coefficients (mm Hg per 100 mmol) Relating 24-Hour Urinary Sodium Excretion to
Blood Pressure in Body Mass Index Subgroups
Dlastollc Pressure
Systolic Pressure
Variable
Lower-BMI
Higher-BMI
Lower-BMI
Higher-BMI
Lower- and higher-BMI centers
Coefficient*
Standard error
Z score
Corrected coefficient!
1.319
0.727
0.198
-0.095
0.389
0.360
0.279
0.253
3.395P
2.019}
0.710
-0.374
3.976
2.405
0.610
-0.270
0.995
1.223
-0.200
0.338
0.374
0.378
0.285
0.259
2.660§
3.234§
-0.704
1.305
2.957
3.809
-0.548
1.083
Lower- and higher-BMI individuals
Coefficient*
Standard error
Z score
Corrected coefficientt
2
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
BMI indicates body mass index. Fifty-two centers were divided into 26 with median BMI <24.5 kg/m (lower-BMI centers) and 26 with
median BMI 2:24.5 kg/m2 (higher-BMI centers). Individuals in each center were divided into those with BMI <24.1 kg/m 2 (lower-BMI) and
those with BMI &24.1 kg/m2 (higher-BMI).
*Adjusted for age, sex, BMI, alcohol intake, and 24-hour potassium excretion.
tCorrected for reliability of both 24-hour sodium and potassium excretions and Intraindividual con-elation of sodium and potassium.
tP<.05, §P<.01, ||P<.001.
statistically significant. With correction for reliability,
the regression coefficients were 3.81 and 2.96 mm Hg
per 100 mmol (mEq).
For diastolic pressure, none of the four regression
coefficients were significantly different from zero. This
finding is consistent with results in Table 1 for the full
INTERSALT sample showing no significant association
of sodium with diastolic pressure when adjustment was
made for age, sex, alcohol intake, BMI, and potassium
excretion. The coefficients for sodium and diastolic
pressure also did not differ significantly between lowerand higher-BMI centers or individuals.
Potassium and Blood Pressure in BMI Subgroups
Table 4 gives the results of regression analyses relating 24-hour potassium excretion to blood pressure in
higher- and lower-BMI centers and individuals. With
multivariate adjustment, potassium was inversely and
significantly related to systolic pressure in both higherand lower-BMI centers and higher- and lower-BMI
individuals. Potassium was also significantly related to
diastolic pressure in higher-BMI centers and higherand lower-BMI individuals. Although these inverse associations for higher-BMI centers and individuals were
larger than those for lower-BMI centers and individuals,
the differences were not statistically significant. Without
correction for reliability, the pooled regression coefficients indicated average systolic pressure less by 0.54
mm Hg per 30-mmol (mEq) increment in potassium
excretion in lower-BMI centers and 1.13 mm Hg less for
higher-BMI centers. With correction for reliability, the
coefficients indicated average pressure less by 1.52 and
TABLE 4. Pooled Regression Coefficients (mm Hg per 30 mmol) Relating 24-Hour Urinary Potassium Excretion to
Blood Pressure In Body Mass Index Subgroups
Systolic Pressure
Variable
Dlastollc Pressure
Lower-BMI
Higher-BMI
Lower-BMI
Higher-BMI
-0.539
-1.130
-0.376
-0.690
Lower- and higher-BMI centers
Coefficient*
Standard error
Z score
Corrected coefficienrt
0.265
0.342
0.204
-2.030+
-3.310Q
-1.842
-2.857§
-1.521
-2.816
-0.874
-1.462
-0.761
-0.856
-0.507
-0.556
0.276
0.335
0.219
0.233
-2.753§
-2.5594
-2.316*
-2.386*
-1.918
-2.387
-1.051
-1.356
0.241
Lower- and higher-BMI individuals
Coefficient*
Standard error
Z score
Corrected coefficientt
Definitions are as in Table 3.
'Adjusted for age, sex, BMI, alcohol intake, and 24-hour sodium excretion.
tCorrected for reliability of both 24-hour sodium and potassium excretions and intraindividual con-elation of sodium and potassium.
#><.O5, §P<.01, |P<.001.
734
Hypertension
Vol 23, No 6, Part 1 June 1994
TABLE 5. Pooled Regression Coefficients (mm Hg per 2 U) Relating 24-Hour Urinary Sodium-Potassium Ratio to
Blood Pressure In Body Mass Index Subgroups
Systolic Pressure
Variable
Lower-BMI
Dlastollc Pressure
Higher-BMI
Lower-BMI
Higher-BMI
Lower- and higher-BMI centers
Coefficient*
Standard error
Z score
1.503
0.993
0.438
0.255
0.299
0.292
0.213
0.205
5.021||
3.402B
2.056*
1.245
4.482
2.955
1.305
0.759
1.331
1.414
0.219
0.568
Standard error
0.283
0.306
0.216
0.207
Z score
4.707||
4.620f)
1.014
2.744§
3.932
4.192
0.647
1.685
Corrected coefficient)"
Lower- and higher-BMI individuals
Coefficient*
Corrected coefficientt
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Definitions are as in Table 3.
'Adjusted for age, sex, BMI, and alcohol intake.
tCorrected for reliability of 24-hour sodium-potassium ratio.
*P<.05, §P<.01, P < . 0 0 1 .
2.82 mm Hg, respectively, per 30 mmol (mEq). The
comparable estimates for diastolic pressure were 0.38
and 0.69 mm Hg per 30 mmol (mEq) potassium without
correction for reliability and 0.87 and 1.46 mm Hg with
correction.
The differences in regression coefficients for higherand lower-BMI individuals were smaller than those for
higher- and lower-BMI centers. The regression coefficients for systolic pressure indicated average pressure
less by 0.76 and 0.86 mm Hg, respectively, in lower- and
higher-BMI individuals without correction for reliability
and 1.92 and 2.39 mm Hg per 30 mmol (mEq) with
correction. For diastolic pressure, the coefficients without correction for reliability were 0.51 and 0.56 mm Hg
and were 1.05 and 1.36 mm Hg with correction.
Sodium-Potassium Ratio and Blood Pressure in
BMI Subgroups
Table 5 gives the results of regression analyses relating the 24-hour sodium-potassium ratio to blood pressure in BMI subgroups. With multivariate adjustment,
the sodium-potassium ratio was significantly related to
systolic pressure in both higher- and lower-BMI centers
and individuals and to diastolic pressure in lower-BMI
centers and higher-BMI individuals. Although the coefficients for both systolic and diastolic blood pressure
were larger in lower-BMI compared with higher-BMI
centers but were larger in higher-BMI than in lowerBMI individuals, none of these differences was statistically significant. Without correction for reliability, the
pooled regression coefficients indicated average systolic
pressure greater by 1.50 and 1.00 mm Hg for the sodium-potassium ratio higher by 2 U for lower- and
higher-BMI centers and by 1.33 and 1.41 mm Hg for
lower- and higher-BMI individuals. With correction for
reliability, the coefficients indicated average systolic
pressure greater by 4.48 and 2.96 mm Hg in lower- and
higher-BMI centers and by 3.93 and 4.19 mm Hg for
lower- and higher-BMI individuals. The uncorrected
coefficients for diastolic pressure ranged from 0.22
mm Hg in lower-BMI individuals to 0.57 mm Hg in
higher-BMI individuals and the corrected coefficients
from 0.65 to 1.69 mm Hg.
Discussion
The purpose of these analyses was to further examine
BMI and associations of sodium, potassium, and sodium-potassium ratio with blood pressure in INTERSALT. The relation of BMI to these associations is of
interest because of the suggested effect of adjustment
for BMI on the sodium-blood pressure relations in
INTERSALT1 and other studies 2528 and because of the
inconsistencies in the results of intervention trials on
the independent effects of sodium reduction and weight
loss on blood pressure. 4141617 These questions were
addressed by quantifying the effect of adjustment for
BMI on associations of sodium, potassium, and sodiumpotassium ratio with blood pressure and by exploring
possible interactions of these variables with BMI in
relation to blood pressure.
Adjustment for BMI had a substantial effect on the
size of regression coefficients relating sodium and the
sodium-potassium ratio to blood pressure. Adjustment
for BMI, in addition to adjustment for age, sex, alcohol
intake, and potassium excretion, reduced the uncorrected regression coefficient for sodium with systolic
blood pressure by more than 50% and the corrected
coefficient by almost 50%. For diastolic pressure, adjustment for BMI made a significant association
(P<.001) nonsignificant. For the sodium-potassium ratio, adjustment for BMI reduced both corrected and
uncorrected regression coefficients for systolic pressure
by approximately 25% and for diastolic by approximately 50%. For potassium, adjustment for BMI increased the size of uncorrected regression coefficients
but left corrected coefficients little changed from the
analyses that did not include BMI.
An important issue in regard to these and other
analyses of the sodium-blood pressure association is
whether it is really appropriate to adjust for BMI.
Although BMI is a variable measured essentially without error, this is not the case for 24-hour sodium
Dyer et al
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
excretion; indeed, for sodium excretion in INTERSALT, the intraindividual variation was greater than the
interindividual variation, as indicated by a coefficient of
reliability that was less than 0.50. Furthermore, given
the positive correlation of BMI with sodium excretion, a
portion of the association between BMI and blood
pressure may be due to the higher sodium intake in
overweight individuals. Hence, the inclusion of BMI as
a potential confounder in previous INTERSALT analyses may have resulted in an overadjustment for that
variable.
Possible interactions of these electrolytes with BMI in
relation to blood pressure were addressed by examining
electrolyte-blood pressure associations in centers classified as lower- or higher-BMI based on the median
BMI at the center being less than or greater than or
equal to 24.5 kg/m2 and by examining these same
associations in individuals classified as lower- or higherBMI based on individual BMI of less than or greater
than or equal to 24.1 kg/m2. In these analyses sodium
and the sodium-potassium ratio were positively and
significantly related to systolic pressure, and potassium
was inversely and significantly related in all four BMI
subgroups. The sodium-potassium ratio was also positively and significantly related to diastolic pressure in
two subgroups and potassium inversely and significantly
related in three. Pooled regression coefficients did not
differ significantly between higher- and lower-BMI centers or individuals for any of these electrolyte variables.
It has been suggested that the low blood pressures
found in populations with low sodium intake might
reflect lower body weight rather than low sodium intake,29 thus implying that an association between sodium and blood pressure should be absent or reduced
among lower-body-weight populations and individuals.
As indicated above, no evidence to support this assertion was found in the present study. Thus, the findings
of this report are concordant with other epidemiologic
studies showing significant associations between sodium
and blood pressure in lean Far Eastern populations30'31
and in Western populations with higher BMI.28-32-33
The combined effects of weight and sodium reduction
on blood pressure have not been quantified,14 and it is
unclear whether lower sodium intake reduces blood
pressure equally in overweight and non-overweight
individuals.16'17 In addition, it has been suggested that
weight loss without a concomitant reduction in sodium
intake does not lead to reductions in blood pressure.5
Although the present analyses cannot address these
issues directly, results from previous analyses showing
that BMI was significantly related to both systolic and
diastolic blood pressures, independent of sodium and
potassium excretion,1 and the present results showing
that sodium and potassium excretions were significantly
related to systolic pressure throughout the range of BMI
indicate that the effects of sodium intake and overweight on blood pressure are additive. Thus, for most
populations consuming salt in excess of 5.8 g/d (ie, >100
mmol/d sodium), the inference from the analyses presented here is that reduction in both salt intake and
weight will have additive effects in lowering blood
pressure. However, these cross-sectional observational
data are limited in regard to resolving the issue posed by
the apparently contradictory results of intervention
trials; ie, with maintenance of high salt intake, is weight
BMI, Sodium, Potassium, and Blood Pressure
735
reduction in obese individuals ineffective in lowering
blood pressure? Further well-designed and well-executed trials are needed to resolve this matter.
The related question also remains as to whether a
high salt intake is a primary, essential, necessary cause
for a population rise of blood pressure with age from
youth through middle and older age and for high
prevalence rates of hypertension, and whether other
factors (eg, obesity, high alcohol consumption, low
potassium intake) are secondary, adjuvant, contributory
causes operating only if salt intake is high. No "experiments of nature" in populations are available yielding
data to resolve this issue definitively. Data on the four
low sodium centers in INTERSALT were not consistent
as to whether BMI is directly related to blood pressure
in populations with habitual low salt intake. Thus, for
men from all four of these samples —the Yanomamo
and Xingu Indians in Brazil, Papua, New Guinea, and
Kenya—with median 24-hour sodium excretion ranging
from 0.2 to 51.3 mmol (mEq) per 24 hours,1 BMI was
positively related to blood pressure, significantly so in
the Yanomamo for both systolic and diastolic blood
pressure and in Kenya for diastolic pressure.2 However,
in women there were no significant associations between BMI and blood pressure, and three of the eight
within-center regression coefficients relating BMI to
blood pressure were negative. Moreover, for men from
these isolated low sodium samples, higher BMI could
reflect muscularity rather than adiposity, so that the
meaning of the direct BMI-blood pressure relation may
be different than in most populations, for which greater
BMI is predominantly due to greater adiposity. Hence,
the INTERSALT data are not definitive in regard to
this question.
In any case, the overall results of INTERSALT
indicate that for most populations, with high average
salt intake, effects on blood pressure of sodium reduction and weight loss should be independent and
additive.
In conclusion, these INTERSALT results do not
support the concept of important interactions of sodium
and potassium with BMI in relation to blood pressure.
Furthermore, they indicate that associations of sodium
(positive) and potassium (inverse) with blood pressure
occur across the BMI range. These findings have implications for the primary prevention of high blood pressure in populations; ie, they lend further support to
recommendations for a combined approach, including
lower sodium intake, higher potassium intake, reduction
in the prevalence of heavy drinking, and prevention and
control of obesity.34
Acknowledgments
This study was launched under the auspices of the Council
on Epidemiology and Prevention of the International Society
and Federation of Cardiology (ISFC). A full list of participating centers and investigators is given in Reference 1. The work
was supported by grants from the Wellcome Trust (United
Kingdom); the National Heart, Lung, and Blood Institute
(2R01 HL-33387) (United States); the International Society of
Hypertension; the World Health Organization; the Heart
Foundations of Canada, Great Britain, Japan, and the Netherlands; the Chicago Health Research Foundation; the
FWGO-FMRS (Belgian National Research Foundation); and
the ALSK-CGER (Parastatal Insurance Co, Brussels).
736
Hypertension
Vol 23, No 6, Part 1 June 1994
References
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
1. INTERSALT Cooperative Research Group. INTERSALT: an
international study of electrolyte excretion and blood pressure.
Results for 24-hour urinary sodium and potassium excretion. Br
MedJ. 1988;297:319-328.
2. Dyer A, Elliott P. Body mass index and blood pressure in the
INTERSALT study of urinary electrolytes, other factors and blood
pressure. J Hum Hypertens. 1989^3:299-308.
3. Dyer AR, Elliott P, Shipley MJ. Body mass index versus height and
weight in relation to blood pressure: findings for the 10,079 persons
in the INTERSALT Study. Am J Epidemiol 1990;131:589-596.
4. Dahl LK, Silver L, Christie RW. The role of salt in the fall of blood
pressure accompanying reduction in obesity. N Engl J Med. 1958;
258:1186-1192.
5. Heyden S, Tyroler HA, Hames CG, Bartel A, Thompson JW,
Knshan I, Rosenthal T. Diet treatment of obese hypertensives.
Clin Sci Mol Med. 1973;45:209-212.
6. Reisin E, Abel R, Modan M, Silverberg DS, Eliahou H, Modan B.
Effect of weight loss without salt restriction on the reduction of
blood pressure in overweight hypertensive patients. N Engl J Med.
1978;298:l-6.
7. Fagerberg B, Andersson OK, Isaksson B, Bjorntorp P. Blood
pressure control during weight reduction in obese hypertensive
men: separate effects of sodium and energy restriction. Br Med J.
1984;288:11-14.
8. Andersson OK, Fagerberg B, Hedner T. Importance of dietary salt
in the hemodynamic adjustment to weight reduction in obese
hypertensive men. Hypertension. 1984;6:814-819.
9. Tuck ML, Sower L, Kiedzick G, Maxwell M. The effect of weight
reduction on blood pressure, plasma renin activity and plasma
aldosterone levels in obese patients. N Engl J Med. 1981 ;304:
930-933.
10. Gillum RF, Prineas RJ, Jeffrey RW, Jacobs DR, Elmer PJ, Gomez
O, Blackburn H. Nonpharmacologic therapy of hypertension: the
independent effects of weight reduction and sodium restriction in
overweight borderline hypertensive patients. Am Heart J. 1983;105:
128-133.
11. Haynes BR, Harper AC, Costley SR, Johnston M, Logan AG,
Flanagan PT, Sackett DL. Failure of weight reduction to reduce
mildly elevated blood pressure: a randomized trial. / Hypertens.
1984;2:535-539.
12. The Trials of Hypertension Prevention Collaborative Research
Group. The effects of nonpharmacologic interventions on blood
pressure of persons with high normal levels: results of the Trials of
Hypertension Prevention, Phase I. JAMA. 1992;267:1213-1220.
13. Wassertheil-Smoller S, Blaufox MD, Oberman AS, Langford HC,
Davis BR, Wylie-Rosset J. The Trial of Antihypertensive Interventions and Management (TAIM) Study: adequate weight loss,
alone and combined with drug therapy in the treatment of mild
hypertension. Arch Intern Med. 1992;152:131-136.
14. Prineas RJ. Clinical interaction of salt and weight change on blood
pressure level. Hypertension. 1991;17(suppl I):I-143-I-149.
15. Cutler JA, Follmann D, Elliott P, Suh I. An overview of randomized
trials of sodium restriction. Hypertension. 1991;17(suppl I):I-27-I-33.
16. Cooper R, Van Horn L, Liu K, Trevisan M, Nanas S, Ueshima H,
Larbi E, Yu CS, Sempos C, LeGrady D, Stamler J. A randomized
trial on the effect of decreased dietary sodium intake on blood
pressure in adolescents. J Hypertens. 1984;2:361-366.
17. Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V,
Martin M. The effect of weight loss on the sensitivity of blood
pressure to sodium in obese adolescents. N Engl J Med. 1989^21:
580-585.
18. INTERSALT Co-operative Research Group. INTERSALT Study:
an international co-operative study on the relation of blood
pressure to electrolyte excretion in populations, I: design and
methods. / Hypertens. 1986;4:781-787.
19. Elliott P, Stamler R. Manual of Operations for 'INTERSALT,' an
international cooperative study on the relation of sodium and
potassium to blood pressure. Controlled Clm Trials. 1988;9(suppl):
ls-118s.
20. American Association of Clinical Chemists. Standard Methods of
Clinical Chemistry, Volume 3. New York, NY: Academic Press;
1961.
21. National Research Council, Committee on Diet and Health, Food
and Nutrition Board, Committee on Life Sciences. Diet and Health:
Implications for Reducing Chronic Disease. Washington, DC:
National Academy Press; 1989:678.
22. National Research Council, Subcommittee on the Tenth Edition of
the RDAs, Food and Nutrition Board, Commission on Life
Sciences. Recommended Dietary Allowances. 10th ed. Washington,
DC: National Academy Press; 1989:253.
23. Dyer AR, Shipley M, Elliott P, for the INTERSALT Cooperative
Research Group. 24-hour urinary electrolyte excretion and blood
pressure in the INTERSALT Study, I: estimates of reliability. Am
J Epidemiol 1994;139:927-939.
24. Dyer AR, Elliott P, Shipley M, for the INTERSALT Cooperative
Research Group. 24-hour urinary electrolyte excretion and blood
pressure in the INTERSALT Study, II: estimates of electrolyteblood pressure associations corrected for regression dilution bias.
Ami Epidemiol 1994;139:940-951.
25. Watson RL, Langford HG, Abernethy J, Barnes TY, Watson MJ.
Urinary electrolytes, body weight, and blood pressure: pooled
cross-sectional results among four groups of adolescent females.
Hypertension. 1980;2(suppl I):I-93-I-98.
26. Connor SL, Connor WE, Henry H, Sexton G, Keenan EJ. The
effects of familial relationships, age, body weight, and diet on blood
pressure and the 24 hour urinary excretion of sodium, potassium,
and creatinine in men, women, and children of randomly selected
families. Circulation. 1984;70:76-85.
27. M'Buyamba-Kabangu JR, Fagard R, Lijnen P, Mbuy wa Mbuy R,
Staessen J, Amery A. Blood pressure and urinary cations in urban
Bantu of Zaire. Am J Epidemiol 1986;124:957-968.
28. Pietinen PI, Wong O, Altschul AM. Electrolyte output, blood
pressure, and family history of hypertension. Am J Clin Nutr.
1979;32:997-1005.
29. Dustan HP. Obesity and hypertension. Ann Intern Med. 1985;103:
1047-1049.
30. Kesteloot H, Huang DX, Li Y, Geboers J, Joossens J. The relationship between cations and blood pressure in the People's
Republic of China. Hypertension. 1987;9:654-659.
31. Kesteloot H, Park BC, Lee CS, Brems-Heyns E, Claessens J,
Joossens JV. A comparative study of blood pressure and sodium
intake in Belgium and in Korea. EurJ Cardiol. 1980;ll:169-182.
32. Strazzullo P, Trevisan M, Farinaro E, Cappuccio FP, Ferrara LA,
De Campora E, Mancini M. Characteristics of the association
between salt intake and blood pressure in a sample of a male
working population in Southern Italy. Eur Heart J. 1983;4:608-613.
33. Elliott P, Forrest RD, Jackson CA, Yudkin JS. Sodium and blood
pressure: positive associations in a north London population with
consideration of the methodological problems of within-population
surveys. / Hum Hypertens. 1988;2:89-95.
34. Stamler R. Implications of the INTERSALT Study. Hypertension.
1991;17(suppl I):I-16-I-2O.
Body mass index and associations of sodium and potassium with blood pressure in
INTERSALT.
A R Dyer, P Elliott, M Shipley, R Stamler and J Stamler
Hypertension. 1994;23:729-736
doi: 10.1161/01.HYP.23.6.729
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1994 American Heart Association, Inc. All rights reserved.
Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://hyper.ahajournals.org/content/23/6_Pt_1/729
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial
Office. Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Hypertension is online at:
http://hyper.ahajournals.org//subscriptions/