American Journal of Epidemiology
© The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of
Public Health. All rights reserved. For permissions, please e-mail: [email protected].
Vol. 176, No. 7
DOI: 10.1093/aje/kws266
Original Contribution
Physical Activity Reduces Salt Sensitivity of Blood Pressure
The Genetic Epidemiology Network of Salt Sensitivity Study
Casey M. Rebholz, Dongfeng Gu, Jing Chen, Jian-Feng Huang, Jie Cao, Ji-Chun Chen,
Jianxin Li, Fanghong Lu, Jianjun Mu, Jixiang Ma, Dongsheng Hu, Xu Ji, Lydia A. Bazzano,
Depei Liu, and Jiang He*, for the GenSalt Collaborative Research Group
* Correspondence to Dr. Jiang He, Department of Epidemiology, Tulane University School of Public Health and Tropical
Medicine, 1440 Canal St. SL18, New Orleans, LA 70112 (e-mail: [email protected]).
Initially submitted October 18, 2011; accepted for publication May 14, 2012.
Salt sensitivity of blood pressure (BP) is influenced by genetic and environmental factors. A dietary feeding
study was conducted from October 2003 to July 2005 that included a 7-day low-sodium intervention (51.3 mmol
sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) among 1,906 individuals
who were 16 years of age or older and living in rural northern China. Salt sensitivity of BP was defined as mean
BP change from the low-sodium intervention to the high-sodium intervention. Usual physical activity during the
past 12 months was assessed at baseline using a standard questionnaire. The multivariable-adjusted means of
systolic BP responses to high-sodium intervention were 5.21 mm Hg (95% confidence interval (CI): 4.55, 5.88),
4.97 mm Hg (95% CI: 4.35, 5.59), 5.02 mm Hg (95% CI: 4.38, 5.67), and 3.96 mm Hg (95% CI: 3.29, 4.63)
among participants from the lowest to the highest quartiles of physical activity, respectively (P = 0.003 for linear
trend). The multivariable-adjusted odds ratio of high salt sensitivity of systolic BP was 0.66 (95% CI: 0.49, 0.88)
for persons in the highest quartile of physical activity compared with those in the lowest quartile. Physical activity
is significantly, independently, and inversely related to salt sensitivity of BP and may be particularly effective in
lowering BP among salt-sensitive individuals.
blood pressure; dietary sodium; physical activity; salt sensitivity
Abbreviations: BP, blood pressure; MET, metabolic equivalent.
An increase in physical activity and a reduction in
dietary sodium have been recommended as important lifestyle modifications for the prevention and treatment of hypertension (1, 2). Observational epidemiologic studies have
reported an independent and inverse association between
physical activity and the risk of hypertension (3). Randomized controlled trials have documented that physical activity
lowers blood pressure (BP) in normotensive and hypertensive individuals (4). Observational epidemiologic studies
and clinical trials also documented an independent and
positive association between dietary sodium intake and BP
(5–9). For example, the International Study of Salt and
Blood Pressure (INTERSALT), a large cross-sectional
study in 10,074 adults from 32 countries, reported that a
100-mmol higher level of urinary sodium excretion was associated with 6-mm Hg increase in systolic BP and a 3-mm
Hg increase in diastolic BP (7). In a meta-analysis of clinical trials, Cutler and colleagues estimated that an average
reduction in dietary sodium intake of 100 mmol/day resulted in 5.8-mm Hg and 2.5-mm Hg decrements in systolic
and diastolic BP, respectively, in hypertensive individuals
and 2.3-mm Hg and 1.4-mm Hg decrements in normotensive individuals (9).
Clinical trials have also documented that BP responses to
dietary sodium intake vary among individuals, a phenomenon called “salt sensitivity” (10). Heterogeneity in salt
S106
Am J Epidemiol. 2012;176(Suppl):S106–S113
Physical Activity and Salt Sensitivity
sensitivity is influenced by age, race, sex, hypertension
status, body weight, alcohol intake, and genetic factors
(10–13). To our knowledge, the relation between physical
activity level and salt sensitivity of BP has not been reported in the previous literature. Elucidating the interrelation
between physical activity and BP responses to dietary
sodium intervention could improve our knowledge of hypertension etiology and inform clinical guidelines and
public health policy by identifying high-risk groups of
people who will benefit most from intervention. We undertook a large dietary feeding study to examine the association of genetic and other risk factors with salt sensitivity of
BP among a rural population residing in northern China. In
the present article, we report the relation between physical
activity and salt sensitivity of BP.
MATERIALS AND METHODS
Study participants
Details of the study population and methods for the
Genetic Epidemiology Network of Salt Sensitivity
(GenSalt) Study have been published elsewhere (14). In
brief, the study was conducted in rural areas of northern
China from October 2003 to July 2005. A communitybased BP screening was conducted among people 18–60
years of age who resided in the study villages to identify
potential probands and their families. Probands with a
mean systolic BP of 130–160 mm Hg and/or a mean diastolic BP of 85–100 mm Hg and no use of antihypertensive
medications were recruited for the dietary feeding study,
along with their siblings, spouses, and offspring who were
16 years of age or older. Exclusion criteria included stage
2 hypertension (BP 160/100 mm Hg), secondary hypertension, clinical cardiovascular disease, diabetes mellitus
(fasting plasma glucose 7.0 mmol/L), chronic kidney
disease (positive urine albumin test by dipstick measurement), pregnancy, heavy alcohol consumption, a low-sodium
diet, or use of antihypertensive or antidiabetic medications
or insulin.
Institutional review boards or ethics committees at all
participating institutions approved the study protocol.
Written informed consent was obtained from each participant before baseline data collection and intervention.
Data collection
A standardized questionnaire was administered to participants by trained staff at the baseline examination to obtain
information about demographic characteristics, personal
and family medical history, and lifestyle risk factors (including cigarette smoking, alcohol consumption, and physical activity level). For the measurement of physical activity
level, we adapted the Paffenbarger Physical Activity Questionnaire (15). Data were collected on the number of hours
spent in vigorous and moderate activity on a usual day
during the previous 12 months for weekdays and weekends
separately to account for anticipated daily variability in
energy expenditure. Examples provided for vigorous activity included shoveling, digging, heavy farming, jogging,
Am J Epidemiol. 2012;176(Suppl):S106–S113
S107
brisk walking, heavy carpentry, and bicycling on hills, and
examples of moderate activity included housework, regular
walking, yard work, light carpentry, and bicycling on level
ground.
Three BP measurements were obtained every morning
during the 3-day baseline observation period and on days
5, 6, and 7 of each intervention period by trained and certified individuals using a random-zero sphygmomanometer
according to a standard protocol adapted from procedures
recommended by the American Heart Association (16). BP
was measured with the participant in the sitting position
after they had rested for 5 minutes. Participants were advised
to avoid consumption of alcohol, coffee, or tea, cigarette
smoking, and exercise for at least 30 minutes before their
BP measurements. BP observers were blinded to the participants’ dietary interventions. Body weight, height, and waist
circumference were measured twice with the participants in
light indoor clothing without shoes during their baseline examination. Waist circumference was measured 1 cm above
the participants’ navel during light breathing.
Intervention
Study participants received a low-sodium diet (3 g
sodium chloride or 51.3 mmol sodium per day) for 7 days
followed by a high-sodium diet (18 g sodium chloride or
307.8 mmol sodium per day) for an additional 7 days.
In previous studies in which salt sensitivity was assessed,
10–70 mmol sodium/day was used for low-sodium interventions and 180–345 mmol sodium/day was used for
high-sodium interventions (17). Dietary total energy intake
varied according to the baseline energy intake of each participant. All foods were cooked without salt, and prepackaged salt was added to the individual study
participant’s meal when it was served by the study staff.
Study participants were not blinded to their dietary sodium
intake because it was not possible to blind the taste. To
ensure compliance with the intervention program, participants were required to eat breakfast, lunch, and dinner at
the study kitchen under the supervision of study staff
during the entire study. Study participants were instructed
to avoid consumption of any foods or beverages that were
not provided by the study. Three timed urinary specimens
(one 24-hour specimen and two 8-hour overnight specimens) were obtained during the 3 days of baseline examination and the last 3 days of each intervention period to
monitor compliance with the dietary sodium intervention.
Overnight urinary sodium excretion was converted to 24hour values based on formulas developed from data obtained in a subgroup of study participants. Three separate
formulas were developed for baseline, low-sodium intervention, and high-sodium intervention using a simple linear
regression of 24-hour values on 8-hour overnight values.
The results from the 24-hour urinary excretions of
sodium and potassium showed excellent compliance with
the study diet. The mean of 24-hour urinary excretions of
sodium and potassium were 242.4 mmol and 36.9 mmol at
baseline, 47.5 mmol and 31.4 mmol during the low-sodium
intervention, and 244.3 mmol and 35.7 mmol during the
high-sodium intervention, respectively.
S108 Rebholz et al.
Statistical analysis
BP levels at baseline and during the dietary sodium intervention were calculated as the mean of 9 measurements
from 3 clinical visits during the 3-day baseline observation
or on days 5, 6, and 7 of each intervention phase. Salt
sensitivity of BP was defined as the mean BP during the
high-sodium intervention minus the mean BP during the
low-sodium intervention. High salt sensitivity was defined
as an increase in BP of 5% or more during the highsodium intervention relative to the BP level during the
low-sodium intervention ((BP on high-sodium diet − BP
on low-sodium diet)/BP on low-sodium diet). In this study
population, a 5% change corresponded to a mean absolute
change of 5.57 mm Hg in systolic BP and 3.55 mm Hg in
diastolic BP.
The physical activity information obtained from the
questionnaire was converted to metabolic equivalent
(MET) hours per day. The MET is a ratio of the metabolic
rate while performing a given task to the metabolic rate
while seated and resting. One MET represents an expenditure of 1 kilocalorie per kilogram of body weight per hour
and is equivalent to sitting quietly. MET-hours per day
were calculated by weighting the number of hours spent in
each activity intensity category by a MET value that corresponded to the occupation group represented in that activity
intensity category. The MET weight for vigorous activity
was 3.67 for farming and the MET weight for moderate activity was 2.56 for working within the household (18). The
average MET-hours per day were calculated by weighting
MET-hours for weekdays and weekends and were then
divided into quartiles for analysis.
The associations between physical activity and salt sensitivity of BP were assessed using linear and logistic
regression models. Generalized estimation equations were
used to fit linear and logistic models with empirical estimates of standard errors. All analyses included a term for
family cluster and accounted for nonindependence of
family members with an exchangeable correlation structure.
Age- and sex-adjusted mean BP responses to the highsodium intervention and percentages of high salt sensitivity
of BP were calculated by quartiles of MET-hours per day,
and the statistical significance of differences in these characteristics across quartiles was tested using linear or logistic
regression analyses. In addition, age, sex, educational level,
cigarette smoking, alcohol consumption, body mass index
(weight (kg)/height (m)2), baseline BP, and 24-hour
urinary excretion of sodium and potassium were further adjusted in the multivariable linear and logistic regression
analyses. The quartile with the lowest physical activity
level was used as the reference group. To test for linear
trend, the median MET-hours per day in each physical activity quartile were treated as a continuous variable in regression models. Unless otherwise stated, P < 0.05 was
considered statistically significant and all tests were
2-sided. Statistical analyses were performed using SAS,
version 9.2 (SAS Institute, Inc., Cary, North Carolina).
RESULTS
A total of 1,906 study participants met all eligibility criteria and took part in the dietary sodium intervention. Of
these, 1,860 (97.6%) subjects completed the low-sodium
and high-sodium interventions. Participants who did not
complete the study did not differ in terms of baseline characteristics from those who did complete the study. The majority of subjects engaged in work activity of moderate
Table 1. Age- and Sex-Adjusteda Baseline Characteristics by Physical Activity Quartile for Entire Study Population, Genetic Epidemiology
Network of Salt Sensitivity Study, China, 2003–2005
Physical Activity Level, MET-hours per day
Characteristic
<15.1 (n = 440)
Mean (SE)
Age, years
%
35.2 (0.66)
15.1–22.9 (n = 506)
23.0–34.4 (n = 471)
Mean (SE)
Mean (SE)
%
38.6 (0.43)
%
39.9 (0.43)
P for Trend
>34.4 (n = 489)
Mean (SE)
%
40.5 (0.42)
<0.0001
Male sex
40.4
48.4
52.4
71.0
<0.0001
High school education or higher
20.6
12.9
14.5
11.8
<0.0001
4.1
6.0
6.5
5.4
0.18
16.9
0.54
Current smoker
Current drinker
15.9
15.8
18.2
Body mass indexb
23.3 (0.16)
23.6 (0.15)
23.4 (0.15)
23.1 (0.15)
Waist circumference, cm
80.6 (0.50)
80.5 (0.42)
80.8 (0.46)
79.1 (0.48)
0.04
238.2 (3.21)
244.6 (2.92)
241.5 (2.99)
243.1 (3.06)
0.39
36.8 (0.47)
36.6 (0.40)
36.5 (0.39)
37.0 (0.40)
0.87
Baseline systolic BP, mm Hg
117.1 (0.67)
118.6 (0.61)
117.3 (0.71)
115.9 (0.63)
0.09
Baseline diastolic BP, mm Hg
73.9 (0.49)
74.8 (0.47)
74.0 (0.48)
72.5 (0.45)
24-hour urinary sodium, mmol
24-hour urinary potassium, mmol
BP 140/90 mm Hg
9.9
10.6
7.5
0.20
0.01
5.5
0.002
Abbreviations: BP, blood pressure; MET, metabolic equivalent; SE, standard error.
Age was adjusted for sex and sex was adjusted for age. All other variables were adjusted for age and sex.
b
Weight (kg)/height (m)2.
a
Am J Epidemiol. 2012;176(Suppl):S106–S113
Physical Activity and Salt Sensitivity
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absolute and percentage changes in systolic and diastolic
BP from the low-sodium intervention to the high-sodium
intervention. For example, in the multivariable-adjusted
model including baseline BP, a 1-standard deviation increase in physical activity level (11.5 MET-hours) was associated with a 0.46-mm Hg (95% confidence interval:
−0.74, −0.19; P = 0.001) lower increase in systolic BP. The
inverse relation was consistent for all models, systolic and
diastolic BP, and absolute and percentage change in BP (all
P values ≤0.006).
Age- and sex-adjusted proportions of high salt sensitivity
of systolic and diastolic BP by physical activity quartile are
presented in Figure 1. The proportion of subjects with high
salt sensitivity decreased with increasing physical activity
levels. For systolic BP, 45.7% of the least physically active
participants were highly salt sensitive, whereas 35.4% of
the most active were highly salt sensitive (P value for trend
= 0.003). For diastolic BP, 40.5% of the least active participants were highly salt sensitive compared with 36.8% of
the most active (P value for trend = 0.15).
There was a statistically significant and independent
dose-response association between physical activity and
high salt sensitivity (Table 4). The odds ratio of high salt
sensitivity of systolic BP decreased significantly with
higher physical activity levels as compared with the lowest
physical activity level. The relation was consistent for all 3
models predicting high sensitivity of systolic BP (all P
values for trend ≤0.005). For example, in the multivariable-adjusted model, the odds ratio for high salt sensitivity
was 0.65 (95% confidence interval: 0.49, 0.86) for systolic
BP when comparing subjects in the highest activity level
with those in the lowest activity level. In contrast, the mean
intensity (50.3%) or vigorous intensity (37.9%). During
leisure time, most subjects engaged in activities of light intensity (51.1%) or were sedentary (28.7%). On a usual day,
participants spent an average of 3.3 hours in vigorous activity and 4.6 hours in moderate activity.
Table 1 presents the age- and sex-adjusted baseline characteristics of study participants by physical activity quartile.
Participants who were more physically active were older,
were more likely to be male, attained a lower level of education, had lower baseline BP levels, and were less likely to
have hypertension. There was not a statistically significant
difference in sodium and potassium excretion by physical
activity quartile.
Table 2 shows an inverse association between the adjusted mean absolute and percent change in BP from the lowsodium intervention to the high-sodium intervention and
quartile of physical activity. The multivariable-adjusted
average increase in systolic BP was 5.26 mm Hg among
persons in the lowest quartile of physical activity compared
with 3.92 mm Hg in persons in the highest quartile of physical activity. There was an average increase of 2.20 mm Hg
in diastolic BP among those in the lowest physical activity
level quartile compared with a 1.19-mm Hg increase in the
highly physically active group. This statistically significant
linear trend was preserved after additional adjustment for
baseline BP (all P values for trend ≤0.01). The same
inverse association was observed for the mean percent
change in BP from the low-sodium intervention to the
high-sodium intervention and the level of physical activity
(all P values for trend ≤0.03).
Table 3 shows an inverse association between physical
activity level as a continuous variable and the adjusted
Table 2. Mean Absolute and Percentage Blood Pressure Responses to the High-Sodium Intervention by Physical Activity Levels, Genetic
Epidemiology Network of Salt Sensitivity Study, China, 2003–2005
Physical Activity
Level, MET-hours
per day
Multivariable-Adjusteda
Age- and Sex-Adjusted
Systolic
Diastolic
95% CI
Systolic
Mean
95% CI
Multivariable-Adjustedb
Diastolic
Mean
95% CI
Mean
Mean
<15.1
5.30
4.73, 5.87
2.34
1.85, 2.82
5.26
4.60, 5.93
2.20
15.1–22.9
5.21
4.71, 5.70
2.23
1.74, 2.72
5.13
4.50, 5.77
23.0–34.4
5.12
4.56, 5.67
2.11
1.63, 2.58
5.09
4.43, 5.74
>34.4
3.94
3.40, 4.48
1.35
0.81, 1.88
3.92
3.24, 4.61
95% CI
Systolic
Diastolic
Mean
95% CI
Mean
95% CI
1.63, 2.76
5.21
4.55, 5.88
2.15
1.59, 2.71
2.07
1.49, 2.66
4.97
4.35, 5.59
2.00
1.41, 2.58
1.97
1.38, 2.57
5.02
4.38, 5.67
1.92
1.33, 2.51
1.19
0.56, 1.82
3.96
3.29, 4.63
1.21
Absolute Blood Pressure Responses, mm Hg
P for trend
0.0009
0.006
0.001
0.007
0.003
0.59, 1.84
0.01
Percentage Blood Pressure Responses
<15.1
4.81
4.28, 5.34
3.48
2.76, 4.20
4.79
4.17, 5.41
3.28
2.47, 4.09
4.76
4.14, 5.39
3.24
2.43, 4.05
15.1–22.9
4.67
4.22, 5.11
3.37
2.65, 4.10
4.62
4.05, 5.19
3.16
2.31, 4.01
4.53
3.97, 5.10
3.10
2.25, 3.96
23.0–34.4
4.65
4.14, 5.15
3.19
2.49, 3.89
4.62
4.03, 5.22
2.98
2.09, 3.86
4.59
4.00, 5.18
2.94
2.06, 3.83
>34.4
3.65
3.15, 4.13
2.27
1.48, 3.07
3.61
2.99, 4.23
2.01
1.08, 2.94
3.63
3.02, 4.25
2.02
1.09, 2.95
P for trend
0.002
0.02
0.002
0.02
0.004
0.03
Abbreviations: CI, confidence interval; MET, metabolic equivalent.
Multivariable model A included age, sex, body mass index, educational level, cigarette smoking, alcohol consumption, and baseline urinary
excretion of sodium and potassium.
b
Multivariable model A plus baseline systolic or diastolic blood pressure.
a
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S110 Rebholz et al.
Table 3. Association Between a 1-Standard-Deviation Increase in Physical Activity Level (11.5 Metabolic Equivalent-Hours) and Blood
Pressure Responses, Genetic Epidemiology Network of Salt Sensitivity Study, China, 2003–2005
Systolic Blood Pressure
Model
Regression Coefficient
95% CI
Diastolic Blood Pressure
P Value
Regression Coefficient
95% CI
P Value
Absolute Blood Pressure Responses, mm Hg
Age- and sex-adjusted
−0.53
−0.81, −0.26
0.0001
−0.41
−0.65, −0.16
0.001
Multivariable-adjusteda
−0.52
−0.80, −0.24
0.0003
−0.41
−0.66, −0.16
0.001
Multivariable-adjustedb
−0.46
−0.74, −0.19
0.001
−0.38
−0.63, −0.13
0.003
Percentage Blood Pressure Responses
Age- and sex-adjusted
−0.46
−0.71, −0.21
0.0003
−0.52
−0.88, −0.16
0.005
Multivariable-adjusteda
−0.45
−0.70, −0.20
0.0005
−0.54
−0.91, −0.17
0.004
Multivariable-adjustedb
−0.42
−0.67, −0.17
0.001
−0.52
−0.89, −0.15
0.006
Abbreviation: CI, confidence interval.
a
Multivariable model A included age, sex, body mass index, educational level, cigarette smoking, alcohol consumption, and baseline urinary
excretion of sodium and potassium.
b
Multivariable model A plus baseline systolic or diastolic blood pressure.
percent change in diastolic BP across physical activity quartiles was only marginally statistically significant (P values
for trend = 0.09) in the multivariable-adjusted models.
DISCUSSION
The present large population-based dietary feeding study
identified a strong, consistent dose-response relation
between level of physical activity and salt sensitivity of BP.
Salt sensitivity of BP decreased progressively with higher
levels of physical activity. This association was statistically
significant and independent of important covariables.
These findings have important clinical and public health
implications. Hypertension is a prevalent disorder and
leading cause of premature deaths in the United States and
Figure 1. Age- and sex-adjusted proportions of high salt sensitivity
(5% blood pressure (BP) increase from low-sodium to high-sodium
intervention) by quartile of physical activity levels, Genetic
Epidemiology Network of Salt Sensitivity Study, China, 2003–2005.
P for systolic blood pressure trend = 0.003; P for diastolic blood
pressure trend = 0.15. MET, metabolic equivalent.
worldwide (19, 20). In addition, high salt sensitivity of BP
has been shown to increase the risk of cardiovascular
disease and premature mortality (21, 22). An increase in
physical activity level and a reduction in dietary sodium
have been identified as 2 major approaches for the prevention and treatment of hypertension (1, 2). Our findings
suggest that high levels of physical activity protect against
salt sensitivity of BP, as evidenced by participants in the
highest quartile of physical activity having much lower BP
responses than the participants in the lower 3 quartiles of
physical activity. However, sodium consumption impacts
BP across all levels of physical activity. Because of this, a
low-dietary-sodium intervention could be beneficial to all
people. Moreover, these findings also provide further
support for the recommendations to increase physical activity for the prevention and treatment of hypertension, especially among those with a high dietary sodium intake.
Because dietary sodium intake in the US population is well
above recommended levels (23), increased physical activity
should play an important role in programs aimed at BP reduction in the US general population.
The protective effect of increased levels of physical activity on BP responses to high sodium intake might occur
through several potential mechanisms, such as reduction of
insulin resistance, improvement of endothelial function,
and inhibition of sympathetic nervous system activity.
Physical activity has been shown to be associated with
reduced insulin resistance (24), and insulin resistance decreases renal sodium excretion, leading to extracellular
fluid volume expansion and salt-sensitive hypertension (25,
26). The shear stress associated with physical activity has
been shown to improve vascular endothelial function
through increased nitric oxide production, reduce pathologic constriction, and improve blood flow (27, 28). The association between inhibition of nitric oxide synthesis and salt
sensitivity of BP was shown in an animal study (29). The
physiologic response to exercise is a reduction of sympathetic nervous system activity potentially through altered
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Physical Activity and Salt Sensitivity
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Table 4. Odds Ratios for the Association Between High Salt Sensitivity and Physical Activity Levels, Genetic Epidemiology Network of Salt
Sensitivity Study, China, 2003–2005
Model
Physical Activity,
MET-hours per day
Multivariable-Adjusteda
Age- and Sex-Adjusted
OR
P Value
95% CI
OR
95% CI
P Value
Multivariable-Adjustedb
OR
95% CI
P Value
Systolic Blood Pressure Increase 5%
<15.1
1
15.1–22.9
0.99
0.77, 1.29
0.99
0.98
0.75, 1.27
0.85
0.96
0.73, 1.25
0.74
23.0–34.4
0.93
0.70, 1.25
0.64
0.93
0.70, 1.24
0.63
0.93
0.69, 1.25
0.62
>34.4
0.65
0.49, 0.86
0.003
0.65
0.49, 0.86
0.003
0.66
0.49, 0.88
0.004
P value for trend
Referent
1
0.003
Referent
1
0.003
Referent
0.005
Diastolic Blood Pressure Increase 5%
<15.1
1
15.1–22.9
1.02
0.79, 1.31
0.88
0.99
0.77, 1.28
0.95
0.99
0.77, 1.28
0.95
23.0–34.4
0.86
0.67, 1.12
0.26
0.84
0.65, 1.09
0.19
0.84
0.65, 1.09
0.19
>34.4
0.86
0.66, 1.12
0.26
0.82
0.62, 1.08
0.15
0.82
0.63, 1.08
0.15
P value for trend
Referent
1
0.15
Referent
0.09
1
Referent
0.09
Abbreviations: CI, confidence interval; MET, metabolic equivalent; OR, odds ratio.
Multivariable model A included age, sex, body mass index, educational level, cigarette smoking, alcohol consumption, and baseline urinary
excretion of sodium and potassium.
b
Multivariable model A plus baseline systolic or diastolic blood pressure.
a
gene expression in the brain (30). Excessive salt consumption can lead to impaired central sympathetic system inhibition, followed by increased peripheral sympathetic activity,
which affects renal hemodynamics and ultimately results in
the observed salt sensitivity of BP (31). Studies have suggested the role of the sympathetic nervous system in salt
sensitivity of BP as indicated by increased response to the
cold pressor test (32), higher plasma norepinephrine levels
(33), higher dopamine levels (34), and decreased number
of β2-adrenergic receptors (35).
The present study has several strengths. To our knowledge, this investigation is the largest population-based
feeding study in which salt sensitivity was examined. The
compliance of subjects to the dietary intervention was excellent, as evidenced by multiple 24-hour urinary excretion
assessments. Strict data quality control was enforced to
ensure the validity of the results. Careful measurement of
study variables, and the outcome variable in particular,
allowed for precise and accurate estimation of the association. To minimize measurement bias during the assessment
of BP, a minimum of 9 readings were obtained from multiple clinical visits by the same trained observers using the
same random-zero sphygmomanometer during each phase
of the study. This study not only assessed leisure-time activity but also incorporated work-related activity.
One potential limitation of our study is the short duration
of the intervention period. Exposure to a 1-week lowsodium intervention and 1-week high-sodium intervention
is the standard procedure for studying salt sensitivity. The
relation of such a relatively short intervention to future
health effects is not known definitively. However, in the
Olivetti Heart Study, BP response to a short-term (3-day)
Am J Epidemiol. 2012;176(Suppl):S106–S113
dietary sodium intervention was associated with incidence
of hypertension in long-term follow-up (36). Furthermore,
previous clinical studies have shown that the methodology
used to estimate salt sensitivity in this study is reproducible
(37, 38). Another potential limitation is the generalizability
of study findings. This study was conducted in a farming
population in China who had a relatively high overall level
of physical activity. Whereas the majority of this study population engaged in work-related activity of moderate
(50.3%) or vigorous intensity (37.9%), the prevalence of
moderate-intensity work in the United States is estimated to
be 20% (39). On average, Genetic Epidemiology Network
of Salt Sensitivity Study participants spent 3.3 hours in vigorous activity and 4.6 hours in moderate activity per day,
and US adults spent less than 2 hours in vigorous activity
and 1.5–2.2 hours in moderate activity per week (40).
Because of this, we might not be able to see the extent of
the protective effect of physical activity on sodium sensitivity. However, we should expect an even larger effect of
dietary sodium intake on BP in a much less physically
active population. Lastly, we were unable to assess potential confounding of the relation between physical activity
and salt sensitivity of BP by diet characteristics because of
a lack of detailed information collected on usual diet from
standard measurement tools, such as food frequency questionnaires or 24-hour dietary recalls.
In summary, our study indicates that physical activity is
significantly, independently, and inversely related to salt
sensitivity of BP, with a graded dose-response association
between lower level of physical activity and higher salt sensitivity. Among the study participants who were physically
inactive, BP response to high salt consumption was greater
S112 Rebholz et al.
than that among persons who were physically active.
However, BP response to salt consumption was observed at
every level of physical activity. Our findings suggest that
physical activity may be particularly effective in lowering
BP among salt-sensitive individuals.
ACKNOWLEDGMENTS
Author affiliations: Department of Epidemiology, School
of Public Health and Tropical Medicine, Tulane University,
New Orleans, Louisiana (Casey M. Rebholz, Lydia
A. Bazzano, Jiang He); Cardiovascular Institute and Fuwai
Hospital, Chinese Academy of Medical Sciences and
Peking Union Medical College, and National Center for
Cardiovascular Disease, Beijing, China (Dongfeng Gu,
Jian-Feng Huang, Jie Cao, Ji-Chun Chen, Jianxin Li);
Department of Medicine, School of Medicine, Tulane University, New Orleans, Louisiana (Jing Chen, Lydia
A. Bazzano, Jiang He); Institute of Basic Medicine, Shandong Academy of Medical Sciences, Shandong, China
(Fanghong Lu); Department of Medicine, Xi’an Jiaotong
University School of Medicine, Shanxi, China (Jianjun
Mu); Shandong Center for Diseases Control and Prevention, Shandong, China (Jixiang Ma); School of Public
Health, Zhengzhou University, Henan, China (Dongsheng
Hu); Xinle Traditional Chinese Medicine Hospital, Hebei,
China (Xu Ji); and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese
Academy of Medical Sciences and Peking Union Medical
College, Beijing, China (Depei Liu).
This work was supported by the National Heart, Lung, and
Blood Institute of the National Institutes of Health (grants
U01HL072507, R01HL087263, and R01HL090682).
Conflict of interest: none declared.
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