Download Dietary Magnesium Intake and Risk of Incident Hypertension Among

Dietary Magnesium Intake and Risk of Incident Hypertension
Among Middle-Aged and Older US Women in a
10-Year Follow-Up Study
Yiqing Song, MD, ScDa,*, Howard D. Sesso, ScDa, JoAnn E. Manson, MD, DrPHa,b,
Nancy R. Cook, ScDa,b, Julie E. Buring, ScDa,b,c, and Simin Liu, MD, ScDa,b,d
To assess the hypothesis that magnesium intake is beneficial in the primary prevention of
hypertension, 28,349 female United States health professionals aged >45 years participating in the Women’s Health Study (WHS), who initially reported normal blood pressure
(systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg, no history of
hypertension or antihypertensive medications), were prospectively studied. A semi-quantitative food frequency questionnaire was used to estimate magnesium intake. During a
median follow-up of 9.8 years, 8,544 women developed incident hypertension. After adjustment for age and randomized treatment, magnesium intake was inversely associated
with the risk for developing hypertension; women in the highest quintile (median 434
mg/day) had a decreased risk for hypertension (relative risk 0.87, 95% confidence interval
[CI] 0.81 to 0.93, p for trend <0.0001) compared with those in the lowest quintile (median
256 mg/day). This inverse association was attenuated but remained significant after further
adjustment for known risk factors. In the fully adjusted model, the relative risks were 1.00
(95% CI 0.95 to 1.10), 1.02 (95% CI 0.95 to 1.10), 0.96 (95% CI 0.89 to 1.03), and 0.93 (95%
CI 0.86 to 1.02) (p for trend ⴝ 0.03). Similar associations were observed for women who
never smoked and reported no history of high cholesterol or diabetes at baseline. In
conclusion, the results suggest that higher intake of dietary magnesium may have a modest
effect on the development of hypertension in women. © 2006 Elsevier Inc. All rights
reserved. (Am J Cardiol 2006;98:1616 –1621)
Magnesium intake from either diet or supplements is believed to be important in maintaining body magnesium
status and thereby maximizing its potentially antihypertensive effects. Results from some, although not all, crosssectional studies suggest that magnesium intake is associated with lower blood pressure (BP) levels.1,2 Many small
controlled trials have examined the possible effects of magnesium supplementation on the treatment of hypertension
but yielded apparently conflicting results.1,3 A recent metaanalysis of randomized clinical trials found that oral magnesium supplementation resulted in small overall reductions
in BP in a dose-dependent manner in hypertensive patients.3
However, a fairly small number of prospective cohort studies have focused on the health effects of dietary magnesium
intake for the primary prevention of hypertension with weak
a
Division of Preventive Medicine, Department of Medicine, Brigham
and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; bDepartment of Epidemiology, Harvard School of Public Health,
Boston, Massachusetts; cDepartment of Ambulatory Care and Prevention,
Harvard Medical School, Boston, Massachusetts; dDepartment of Epidemiology, School of Public Health, University of California, Los Angeles,
Los Angeles, California. Manuscript received March 31, 2006; revised
manuscript received and accepted July 3, 2006.
This study was supported by Grants DK66401, DK62290, CA-47988,
HL-43851, and HL-65727 from the National Institutes of Health, Bethesda,
Maryland.
*Corresponding author: Tel: 617-278-0913; fax: 617-731-3843.
E-mail address: [email protected] (Y. Song).
0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjcard.2006.07.040
or equivocal results.4 –7 We therefore investigated the association between magnesium intake and the incidence of
hypertension in apparently healthy women participating in
the Women’s Health Study (WHS), a large cohort of middle-aged and older United States female professionals.
Methods
Study population: The WHS is an ongoing randomized,
double-blind, placebo-controlled trial of low-dose aspirin
and vitamin E in the primary prevention of cardiovascular
disease and cancer.8 In 1992, a total of 39,876 female
United States health professionals aged ⱖ45 years without
previous myocardial infarction, stroke, transient ischemic
attack, or cancer (except for nonmelanoma skin cancer)
were enrolled and randomized into the study. Of these, 98%
provided detailed information about their diets, completing
a 131-item semi-quantitative food frequency questionnaire
(SFFQ) in 1993.8 We excluded patients with ⬎70 items left
blank on their SFFQs and with energy intakes outside the
range of 2,514 kJ (600 kcal) to 14,665 kJ (3,500 kcal). The
study population was then restricted to 28,349 women with
complete data on magnesium intake and other major lifestyle variables and without hypertension at baseline. The
presence of hypertension at baseline was defined as having
no self-reported history of hypertension, no history of antihypertensive treatment, reported systolic BP ⬍140 mm Hg,
and diastolic BP ⬍90 mm Hg at study entry. Baseline BP
was reported in 1 of 9 ordinal systolic BP categories ranging
www.AJConline.org
Systemic Hypertension/Magnesium and Hypertension in Women
1617
Table 1
Age-adjusted (in 5-year categories) baseline characteristics according to quintiles of total and dietary magnesium intakes in 28,349 women in the
Women’s Health Study
Characteristic
Dietary Magnesium
Q1
No. of participants
Median intake (mg/d)
Mean age (yrs)
Mean body mass index (kg/m2)
Alcohol consumption (g/d)
Systolic blood pressure (mm Hg)
⬍110
110–119
120–129
130–139
Diastolic blood pressure (mm Hg)
⬍65
65–74
75–84
85–89
Current smoker
Vigorous exercise (ⱖ4 times/wk)
Postmenopausal hormones (current user)
Multivitamin use (current user)
Parental history of MI at ⬍60 yrs
History of hyperlipidemia
Diabetes mellitus
Mean total calorie (kcal/d)
Mean total fat (g/d)
Mean protein (g/d)
Mean total cholesterol (mg/d)
Mean glycemic load*
Q3
Q5
Total Magnesium
p Value
5,668
253
53
26
4.8
5,669
320
54
25
5.0
5,671
400
55
25
4.2
19%
36%
30%
15%
19%
38%
30%
14%
10%
39%
42%
8.7%
18%
6.3%
37%
25%
12%
24%
1.0%
1,696
64
74
238
165
12%
41%
39%
8.3%
14%
11%
41%
29%
12%
24%
1.2%
1,742
58
82
227
165
Q1
Q3
Q5
p Value
⬍0.0001
⬍0.0001
0.005
5,669
256
52
26
4.8
5,669
330
54
25
4.9
5,670
434
55
25
4.2
⬍0.0001
⬍0.0001
0.0006
25%
38%
26%
12%
⬍0.0001
0.09
⬍0.0001
⬍0.0001
19%
36%
30%
15%
19%
39%
29%
14%
25%
38%
27%
11%
⬍0.0001
0.18
⬍0.0001
⬍0.0001
15%
44%
35%
6.7%
10%
19%
42%
34%
13%
25%
1.9%
1,692
49
86
200
176
⬍0.0001
0.0001
⬍0.0001
0.0004
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
0.71
0.70
0.002
0.39
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
10%
39%
42%
8.5%
17%
6.4%
36%
18%
13%
24%
1.1%
1,669
64
74
238
164
11%
41%
39%
8.3%
14%
11%
41%
24%
12%
25%
1.2%
1,764
58
82
226
165
15%
43%
35%
6.8%
10%
18%
45%
55%
13%
25%
1.5%
1,680
50
85
204
175
⬍0.0001
0.0002
⬍0.0001
0.004
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
0.30
0.52
0.07
0.04
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
All covariate values are according to the quintiles of total magnesium intake. All the means of nutrients are energy adjusted.
* Glycemic load was defined as an indicator of blood glucose induced by a subject’s total carbohydrate intake. Each unit of glycemic load represents the
equivalent of 1 g carbohydrate from white bread.
MI ⫽ myocardial infarction; Q ⫽ quintile.
from ⬍110 to ⱖ180 mm Hg and 7 ordinal diastolic BP
categories ranging from ⬍65 to ⱖ105 mm Hg.
This study was conducted according to the ethical guidelines of Brigham and Women’s Hospital. Written informed
consent was obtained from all participants.
Assessment of magnesium intake: On the SFFQ, participants were asked how often on average they had consumed individual foods of a commonly used portion size
during the previous year. Nine possible responses ranging
from “never” to “6 or more times per day” were recorded.
Nutrient intakes were computed by multiplying the frequency of consumption of each unit of food from the SFFQ
by the nutrient content of the specified portion size according to food composition tables from the Harvard Food
Composition Database.9 Data on use of multivitamin supplements were taken into account to assess the intake of
supplemental magnesium. Total magnesium represented the
sum of magnesium intake from dietary and supplemental
sources. Each nutrient was adjusted for total energy using
the residual method.10 In populations of nurses and health
professionals, this SFFQ has demonstrated reasonably good
validity as a measure of long-term average dietary intakes.11
Pearson’s correlation coefficient between magnesium intake
assessed by the SFFQ and 2 weeks of diet records was 0.76.12
Outcome ascertainment: As described previously,13 incident hypertension was based on self-reported BP, treatment, and/or physician diagnosis in our cohort. Incident
cases of hypertension were defined by meeting ⱖ1 of 4
criteria: self-reports of a new physician diagnosis on
follow-up questionnaires at years 1 or 3 or on 1 of the
annual questionnaires thereafter; self-reports of newly
initiated antihypertensive treatment at years 1, 3, or 4;
self-reported systolic BP ⱖ140 mm Hg; or self-reported
diastolic BP ⱖ90 mm Hg. Women reporting new physician
diagnoses of hypertension also provided the month and year
of their diagnoses. Those patients developing hypertension
after the development of major concomitant diseases, including myocardial infarction, stroke, pulmonary embolism,
and peripheral vascular disease, were not considered as
having incident cases of hypertension. On the basis of this
definition, 8,544 cases of incident hypertension developed
during a median follow-up of 9.8 years (mean 8.0). Selfreported BP in health professionals has been shown to be
highly correlated with measured systolic BP (r ⫽ 0.72) and
diastolic BP (r ⫽ 0.60).14 We performed a separate study in
which an 86% validation rate for self-reported hypertension
was observed, consistent with other studies.15,16 In a comparable population in the Nurses’ Health Study, 99% of
1618
The American Journal of Cardiology (www.AJConline.org)
Table 2
Relative risks (RR) (95% confidence intervals [CI]) of incident hypertension according to magnesium intake in 28,349 women in the Women’s Health
Study
Variable
Total magnesium intake
Median (interquartile range) (mg/d)
No. of cases
Age-adjusted RR (95% CI)*
Multivariate-adjusted RR (95% CI)†
Multivariate-adjusted RR (95% CI)‡
Multivariate-adjusted RR (95% CI)§
Dietary magnesium intake
Median (interquartile range) (mg/d)
No. of cases
Age-adjusted RR (95% CI)
Multivariate-adjusted RR (95% CI)†
Multivariate-adjusted RR (95% CI)‡
Multivariate-adjusted RR (95% CI)§
Quintile of Magnesium Intake
p Value for
Trend
1
2
3
4
5
256 (238–269)
1,727
1.00
1.00
1.00
1.00
298 (290–306)
1,753
0.99 (0.93–1.06)
1.01 (0.94–1.09)
1.02 (0.95–1.10)
1.02 (0.95–1.10)
330 (322–338)
1,739
0.97 (0.90–1.03)
0.99 (0.91–1.07)
1.03 (0.95–1.10)
1.02 (0.95–1.10)
367 (356–378)
1,676
0.91 (0.85–0.97)
0.93 (0.86–1.00)
0.96 (0.89–1.03)
0.96 (0.89–1.03)
434 (411–472)
1,649
0.87 (0.81–0.93)
0.89 (0.83–0.97)
0.94 (0.87–1.01)
0.93 (0.86–1.02)
⬍0.0001
0.0003
0.02
0.03
253 (236–265)
1,760
1.00
1.00
1.00
1.00
292 (284–299)
1,739
0.96 (0.90–1.02)
0.99 (0.93–1.07)
1.00 (0.93–1.07)
1.00 (0.93–1.07)
320 (313–327)
1,794
0.98 (0.92–1.05)
1.01 (0.94–1.08)
1.03 (0.96–1.11)
1.02 (0.95–1.10)
350 (342–359)
1,618
0.85 (0.79–0.91)
0.87 (0.81–0.94)
0.90 (0.84–0.97)
0.89 (0.83–0.97)
400 (383–428)
1,633
0.84 (0.78–0.89)
0.88 (0.81–0.94)
0.92 (0.85–0.99)
0.91 (0.83–0.99)
⬍0.0001
⬍0.0001
0.002
0.002
* Adjusted for age and randomized treatment.
†
Further adjusted for family history of MI before 60 years of age (yes/no), exercise (rarely/never, ⬍1 time/week, 1 to 3 times/week, and ⱖ4 times/week),
alcohol use (rarely/never, 1 to 3 drinks/month; 1 to 6 drinks/week, and ⱖ1 drink/day), postmenopausal hormone use (never, past, and current), multivitamin
use (never, past, and current), smoking (never, past, and current), and total energy intake (quintiles).
‡
Multivariate model additionally adjusted for body mass index, history of diabetes mellitus, and high cholesterol.
§
A full model with additional adjustment for dietary intakes of saturated fat (quintiles) and cholesterol (quintiles), glycemic load (quintiles), and sodium
intake (quintiles).
women who reported high BP had confirmation of their
diagnoses by medical record review.15
Statistical analysis: Participants were divided into quintiles according to their intake of total magnesium from diet
and supplements. We used Cox proportional-hazards models to estimate the rate ratios (described as relative risks)
and 95% confidence intervals (CIs) of incident hypertension
for each quintile of magnesium intake, with the lowest
quintile as the referent. Models were first adjusted for age
and randomized treatment assignment (vitamin E and aspirin). The second multivariate model added total energy
intake (quintiles), smoking (never, past, and current), vigorous exercise (rarely or never, ⬍1 time/week, 1 to 3 times/
week, and ⱖ4 times/week), alcohol intake (rarely or never,
1 to 3 drinks/month, 1 to 6 drinks/week, and ⱖ1 drink/day),
postmenopausal hormone use (never, past, and current), the
use of multivitamin supplements (never, past, and current),
and parental history of myocardial infarction before 60
years of age (yes or no). The third model made additional
adjustment for body mass index (in kilograms per square
meter; continuous), history of diabetes mellitus (yes or no),
and high cholesterol (yes or no), and the final multivariateadjusted model further controlled for dietary factors, including intakes of saturated fat, cholesterol, sodium, and dietary
glycemic load (all categorized as quintiles). Tests of linear
trend across increasing quintiles of magnesium intake were
conducted by assigning the medians of intakes in quintiles
(in milligrams per day), treated as a continuous variable.
The same analytic approach was used for analyses of
dietary magnesium intake (from diet alone). Because magnesium intake from supplements alone contributed a small
proportion of total magnesium intake (⬍4%), limited variation of supplemental magnesium intake did not allow us to
have sufficient statistical power to perform a separate analysis of magnesium supplements.
All statistical analyses were conducted using SAS version 8.0 (SAS Institute Inc., Cary, North Carolina). All
p values were 2 tailed.
Results
In the present study, dietary sources accounted for about
97% of the total intake of magnesium. The median intake of
magnesium was 330 mg/day for our cohort of middle-aged
women, close to the recommended dietary allowance of 320
mg/day for adult women.17 Age-standardized characteristics
of the study population by total and dietary magnesium
intakes are listed in Table 1. At baseline in 1993, women
with high magnesium intakes were slightly older and leaner,
less likely to be current smokers or alcohol drinkers, and
more likely to exercise and to take multivitamins or postmenopausal hormones than those with lower magnesium
intakes (Table 1). Magnesium intake was also positively
associated with dietary protein and glycemic load and negatively associated with dietary fat and cholesterol. Notably,
baseline systolic BP and diastolic BP were inversely associated with total or dietary magnesium intake (Table 1).
In the age- and randomized treatment-adjusted models,
there was a significant inverse association between magnesium
intake and the risk for developing hypertension (Table 2).
After adjustment for total energy intake, smoking, exercise,
alcohol intake, postmenopausal hormone use, use of multivitamin supplements, and parental history of myocardial
infarction before 60 years of age, this inverse association
was attenuated but remained statistically significant (p for
linear trend ⫽ 0.0003). Additional adjustment for body
mass index, history of diabetes mellitus, and high choles-
Systemic Hypertension/Magnesium and Hypertension in Women
1619
Table 3
Relative risks (RR) (95% confidence intervals [CI]) of incident hypertension according to magnesium intake in 10,799 women who were nonsmokers
and had no histories of diabetes mellitus and high cholesterol levels at baseline in the Women’s Health Study
Variable
Total magnesium intake*
Median (interquartile range) (mg/d)
No. of cases
Age-adjusted RR (95% CI)
Multivariate-adjusted RR (95% CI)†
Multivariate-adjusted RR (95% CI)‡
Multivariate-adjusted RR (95% CI)§
Dietary magnesium intake
Median (interquartile range) (mg/d)
No. of cases
Age-adjusted RR (95% CI)
Multivariate-adjusted RR (95% CI)†
Multivariate-adjusted RR (95% CI)‡
Multivariate-adjusted RR (95% CI)§
Quintile of Magnesium Intake*
p Value for
Trend
1
2
3
4
5
256 (238–269)
671
1.00
1.00
1.00
1.00
297 (289–306)
618
0.96 (0.86–1.07)
1.01 (0.90–1.13)
1.03 (0.92–1.16)
1.03 (0.92–1.16)
330 (322–337)
562
0.87 (0.78–0.98)
0.90 (0.80–1.02)
0.95 (0.84–1.08)
0.96 (0.84–1.09)
366 (356–378)
573
0.83 (0.74–0.93)
0.86 (0.76–0.98)
0.91 (0.81–1.03)
0.91 (0.80–1.04)
433 (410–470)
543
0.80 (0.72–0.90)
0.82 (0.72–0.93)
0.90 (0.79–1.03)
0.90 (0.78–1.04)
⬍0.0001
0.0002
0.04
0.06
253 (236–265)
677
1.00
1.00
1.00
1.00
291 (284–299)
629
0.93 (0.84–1.04)
0.99 (0.88–1.11)
1.00 (0.89–1.12)
1.00 (0.89–1.13)
320 (313–328)
607
0.93 (0.84–1.04)
0.98 (0.87–1.11)
1.02 (0.91–1.15)
1.02 (0.90–1.16)
351 (342–359)
528
0.76 (0.68–0.85)
0.79 (0.70–0.90)
0.85 (0.75–0.96)
0.85 (0.74–0.97)
399 (383–427)
526
0.77 (0.68–0.86)
0.82 (0.72–0.93)
0.90 (0.79–1.02)
0.89 (0.77–1.02)
⬍0.0001
⬍0.0001
0.01
0.02
* Adjusted for age and randomized treatment.
†
Further adjusted for family history of MI before 60 years of age (yes/no), exercise (rarely/never, ⬍1 time/week, 1 to 3 times/week, and ⱖ4 times/week),
alcohol use (rarely/never, 1 to 3 drinks/month, 1 to 6 drinks/week, and ⱖ1 drink/day), postmenopausal hormone use (never, past, and current), multivitamin
use (never, past, and current), and total energy intake (quintiles).
‡
Multivariate model additionally adjusted for body mass index.
§
A full model with additional adjustment for dietary intakes of saturated fat (quintiles) and cholesterol (quintiles), glycemic load (quintiles), and sodium
intake (quintiles).
terol appeared to further attenuate the inverse association
(p for linear trend ⫽ 0.02). Similar associations were observed after additional adjustment for dietary intake of saturated fat, cholesterol, sodium, and glycemic load (p for
linear trend ⫽ 0.03). The same analyses restricting to dietary magnesium intake (without supplements) resulted in
similar but more significant associations and trends.
Women with major coronary risk factors may have modified their diets to reduce their risk. To evaluate the robustness of our findings, we limited analyses to women who were
nonsmokers and did not have diabetes and hypercholesterolemia at baseline (n ⫽ 10,799; 2,967 incident cases of hypertension) (Table 3). The results were not materially altered in all
models.
Discussion
In this large prospective cohort with a median follow-up of
9.8 years, we found that high intake of magnesium at baseline was modestly associated with a lower risk for incident
hypertension in apparent healthy middle-aged and older
United States women. Similar associations were observed in
those nonsmokers without a history of diabetes mellitus or
high cholesterol levels who were less likely to change diet.
These data support the notion that higher magnesium intake
from consuming magnesium-rich foods, such as whole grains,
nuts, legumes, and green leafy vegetables, may have beneficial
effects for the primary prevention of hypertension.
Dietary magnesium intake has been associated with a
host of other metabolic disorders, including insulin resistance,18,19 systemic inflammation,20 dyslipidemia,18,19 type
2 diabetes,19,21,22 and cardiovascular disease.23 The hypothetical relation between magnesium intake and hypertension was first suggested by the results from ecologic studies
that showed a negative correlation between water hardness
and hypertension.24,25 However, the interpretation of such
comparisons at population levels is always problematic,
because ecologic correlations on the basis of grouped data at
population levels may not reflect the corresponding association at the individual level due to confounding (known as
ecologic fallacy).26 In addition, the intake of magnesium
from drinking water is negligible compared with total magnesium intake from diet.27
Most epidemiologic data relating dietary magnesium to
lower prevalence of hypertension have been provided by
numerous cross-sectional studies. The results of most, but not
all, cross-sectional studies suggest that magnesium intake may
reduce BP in diverse populations.1,2 Yet the cross-sectional
evidence does not necessarily imply any causal relation, because of the inherent limitations of this study design.
Prospective data investigating the relation of magnesium
intake with the development of hypertension are very limited.5–7 Our results are similar to those of the Nurses’ Health
Study and the Health Professionals Follow-Up Study, which
have reported a significant inverse association between dietary magnesium intake and BP.5,6 In a recent analysis of
the Nurses’ Health Study, Ascherio et al12 observed an
inverse relation of dietary magnesium with self-reported
BP, but not with the incidence of hypertension. After adjusting for age, body mass index, and alcohol intake, the
relative risk of incident hypertension was 1.10 (95% CI 0.92
to 1.32, p for trend ⫽ 0.56), and the average BP was 1.3/1.0
mm Hg lower in women with high magnesium intakes
(ⱖ350 mg/day) compared with those with low intakes
(⬍200 mg/day). In contrast, the Atherosclerosis Risk in
Communities (ARIC) study failed to detect a significant
association between dietary magnesium and hypertension
1620
The American Journal of Cardiology (www.AJConline.org)
but found a modest inverse association between serum magnesium levels and hypertension.7 Besides differences in
study characteristics, the use of a simple, 61-item food
frequency questionnaire in the ARIC study might have
resulted in nondifferential misclassification of dietary intake
and thus biased the associations toward the null. Moreover,
the correlation between serum and dietary magnesium in
this study was very small (correlation coefficient 0.053).7
Overall, available evidence for the role of magnesium in the
primary prevention of hypertension is not compelling, but
one should not rule out a small effect of high magnesium
intake in reducing blood pressure in normotensive subjects.
A body of evidence from in vitro studies and animal
models has suggested a pivotal role of magnesium intake in
regulating BP.28 Numerous small clinical trials have assessed the therapeutic effect of magnesium supplements in
hypertension but yielded conflicting results.1,3 A recent
meta-analysis of 20 clinical trials showed that magnesium
supplementation led to a small overall reduction in BP in a
dose-dependent manner.3 The pooled results of 14 doubleblind, randomized trials showed that a 10 mmol/day (240
mg/day) increase in magnesium intake was associated with
a nonsignificant decrease in systolic BP (⫺3.3 mm Hg 95%
CI ⫺0.1 to 6.8) and a decrease in diastolic BP (⫺2.3 mm
Hg, 95% CI ⫺1.0 to 5.6) in hypertensive patients.3 Notably,
small sample sizes, incomplete randomization, the lack of
blind designs, variable durations of follow-up, high rates of
noncompliance, and differences in magnesium treatment
protocols, magnesium formulas and concentrations, and
study populations have contributed to the inconsistency in
previous trials. The long-term benefits and safety of magnesium treatment on reducing BP remain to be determined
in future large well-designed controlled trials.
Some limitations of the present study warrant consideration. First, measurement errors of dietary intakes and
other factors are inevitable. However, because the data
were prospectively collected, the misclassification of dietary intake was likely to be nondifferential, which would
lead to an underestimation of the observed association in
this study. Second, diet was assessed once, at baseline.
The lack of repeated measurement would fail to address
the changes in dietary intake over time. However, excluding participants who had ever smoked or had a history of high cholesterol and diabetes mellitus, which
allows the reduction of the possibility of bias from diet
change, yielded a similar association in this cohort.
Third, because magnesium coexisted with many nutrients
in the diet, it would be difficult to completely separate the
independent effect of magnesium from those of other
dietary nutrients, such as fiber, folate, calcium, and potassium. Fourth, our observed modest association might
be explained by residual confounding due to some lifestyle and dietary factors. Yet our results were unlikely to
be explained by recall or selection bias because of the
prospective study design and high follow-up rate. Of
note, the inverse association between magnesium intake
and risk for incident hypertension was not independent of
baseline systolic BP and diastolic BP. Adjustment for
baseline systolic BP or diastolic BP or both in any models
eliminated the observed inverse associations, because
baseline BP is most likely to be influenced by long-term
magnesium intake assessed by an SFFQ at baseline,
which would be an intermediate variable between dietary
intake of magnesium and future risk for hypertension.
Controlling for baseline systolic and diastolic BP would
not be appropriate for evaluating the impact of dietary
magnesium on the development of hypertension in the
absence of a study design involving an acute dietary
intervention. Finally, because our study population included only female health professionals who were predominantly white, the results of the present study may
not be generalizable to those in the general United States
population. However, because the ranges of basic characteristics are comparable to those of the general population, the associations found in this study most likely are
relevant to women in this age range.
We conclude that higher magnesium intake from consuming magnesium-rich foods, such as whole grains, nuts,
legumes, and green leafy vegetables, may be beneficial for
the primary prevention of hypertension.
Acknowledgment: We are indebted to the 39,876 dedicated
and committed participants of the WHS. We also acknowledge the contributions of the entire staff of the WHS.
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