Dairy Consumption and Incidence of Hypertension

Transcript

Dairy Consumption and Incidence of Hypertension
Dairy Consumption and Incidence of Hypertension
A Dose-Response Meta-Analysis of Prospective Cohort Studies
Sabita S. Soedamah-Muthu,* Lisa D.M. Verberne,* Eric L. Ding,
Mariëlle F. Engberink, Johanna M. Geleijnse
Abstract—Observational and clinical studies suggest that dairy intake, particularly low-fat dairy, could have a beneficial
effect on blood pressure. We performed a dose-response meta-analysis of prospective cohort studies on dairy intake and
risk of hypertension in the general population. A systematic literature search for eligible studies was conducted until July
2011, using literature databases and hand search. Study-specific dose-response associations were computed according
to the generalized least squares for trend estimation method, and linear and piecewise regression models were created.
Random-effects models were performed with summarized dose-response data. We included 9 studies with a sample
size of 57 256, a total of 15 367 incident hypertension cases, and a follow-up time between 2 and 15 years. Total dairy
(9 studies; range of intake, ≈100–700 g/d), low-fat dairy (6 studies; ≈100–500 g/d), and milk (7 studies; ≈100–500 g/d)
were inversely and linearly associated with a lower risk of hypertension. The pooled relative risks per 200 g/d were
0.97 (95% CI, 0.95–0.99) for total dairy, 0.96 (95% CI, 0.93–0.99) for low-fat dairy, and 0.96 (95% CI, 0.94–0.98) for
milk. High-fat dairy (6 studies), total fermented dairy (4 studies), yogurt (5 studies), and cheese (8 studies) were not
significantly associated with hypertension incidence (pooled relative risks of ≈1). This meta-analysis of prospective
cohort studies suggests that low-fat dairy and milk could contribute to the prevention of hypertension, which needs
confirmation in randomized controlled trials. (Hypertension. 2012;60:1131-1137.) ● Online Data Supplement
Key Words: dairy products ◼ milk ◼ hypertension ◼ blood pressure ◼ meta-analysis ◼ prospective studies
H
ypertension (HTN) contributes to approximately half of
all cardiovascular diseases.1 In 2000, the worldwide prevalence of HTN was estimated to be 26%, affecting ≈1 billion
people. It is expected that 29% of the world population will be
experiencing HTN in 2025, mainly because of the expected
increase in hypertensive people in economically developing
regions.2
American and European guidelines emphasize the importance of weight control, regular physical activity, moderate
alcohol intake, and reduced sodium intake for the prevention
of HTN and cardiovascular diseases.3,4 A diet low in saturated and total fat and rich in fruit, vegetables, and low-fat
dairy products substantially lowered blood pressure (BP) in
the Dietary Approaches to Stop Hypertension (DASH) Trial.5
Dairy products contain protein, minerals (eg, calcium, potassium, magnesium, and phosphorus), and vitamins (eg, folate
and vitamin D, if fortified) that may individually or in combination reduce BP.6–8
A recent meta-analysis of 5 prospective cohort studies
showed significant inverse associations of total dairy, low-fat
dairy, and fluid dairy foods with BP.9 However, large variation
in the types of dairy intake and serving sizes exists among
populations, which has not yet been fully explored. Therefore,
we conducted a dose-response meta-analysis of 9 populationbased cohort studies in which we examined total dairy, low-fat
dairy, high-fat dairy, and different types of dairy products in
relation to incidence of HTN.
Methods
Study Selection
A systematic literature search was conducted for articles on dairy
consumption and BP or HTN, which were published until July 2011,
using the databases of PubMed (www.ncbi.nlm.nih.gov/pubmed),
Embase (www.embase.com), and Scopus (www.scopus.com). Titles
and abstracts were screened to select prospective studies on dairy
intake and HTN or BP changes over time. We identified a total of
1709 unique articles, from which we excluded animal studies, in
vitro studies, comments, letters, editorials, ecological studies, and
randomized controlled trials. Studies in children, adolescents and
pregnant women, patients, and hypertensive populations were also
excluded. Additional articles were found by checking bibliographies
of cohort studies and reviews.
Received March 12, 2012; first decision March 21, 2012; revision accepted August 14, 2012.
From the Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands (S.S.S.-M., L.D.M.V., M.F.E., J.M.G.); Department of
Nutrition, Harvard School of Public Health, Boston, MA (E.L.D.); and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital
and Harvard Medical School, Boston, MA (E.L.D.).
The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.
112.195206/-/DC1.
*S.S.S.-M. and L.D.M.V. contributed equally to this study.
Correspondence to Dr Sabita S. Soedamah-Muthu, Wageningen University, Division of Human Nutrition, PO Box 8129, 6700 EV Wageningen, the
Netherlands. E-mail [email protected]
© 2012 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI:10.1161/HYPERTENSIONAHA.112.195206
1131
1132 Hypertension November 2012
From the 18 studies that met the inclusion criteria, the full text was
retrieved. Of these, we excluded 9 articles for the following reasons:
no specific exposure data presented for dairy but only dairy included in
dietary patterns or dairy micronutrients,10–12 data on metabolic syndrome
and not HTN or BP,13,14 no relative risks (RRs) available for incident
HTN by type of dairy,15 cross-sectional design,16 hypertensive population,17 and 1 article for the same study population, Coronary Artery Risk
Development in Young Adults (CARDIA) Study.18 If insufficient data
were reported in the article (eg, no specific risk estimates for different
dairy products and HTN incidence), additional information was requested from the authors.19–23 Eventually, 9 studies19–27 were included in the
meta-analysis. For 3 of these studies that used BP change as the primary
outcome,20–22 additional data on HTN incidence during follow-up were
supplied by the authors. Figure S1 in the online-only Data Supplement
provides a flow chart for the selection of studies for meta-analysis.
types of dairy and incident HTN, where each noodle of the Spaghetti
Plot represents the data contribution of each study. Study-specific doseresponse associations were computed for all types of dairy according to
the generalized least squares for trend estimation method of Greenland
and Longnecker.30 Random-effects weighted pooling was conducted
using DerSimonian and Laird random-effects models.31 Forest plots
were made to visualize and summarize the associations of the different
types of dairy and HTN incidence. Pooled estimates were expressed
in round numbers that approximated a normal portion size and fitted
within the range of dairy intake of all studies (ie, 200 g for milk, total,
low-fat, and high-fat dairy; 150 g for fermented dairy; 50 g for yogurt;
and 30 g for cheese). In addition, spline knots were created to check
for potential nonlinear dose-response associations between the intake
of different types of dairy and HTN incidence. In case of a nonlinear
association, piecewise spline regression models were used to express
varying dose-response relationships within different intake intervals.
We assessed the I2 statistic to represent the percentage of total variation
attributable to between-study heterogeneity.32
Stratified analyses were performed (only linearly) by mean age
of study cohorts (≤50 and >50 years), continent (Europe and United
States), mean body mass index (BMI) of study cohorts (normal
weight and overweight; BMI <25 and ≥25 kg/m2), and follow-up duration (≤6 and >6 years), if ≥3 studies were available per subgroup.
Meta-regression was used to examine effect measure modification for
these subgroup variables, and P values for interaction are presented.
An additional sensitivity analysis was performed excluding the large
Women’s Health Study,23 because that study included only women
and provided no data on total cheese and total milk (but only cottage
cheese and skim milk). The funnel plot was made for total dairy intake and HTN incidence to visualize publication bias, and the Egger
test was used to assess publication bias.33
Statistical Methods
We defined 7 dairy categories for the present meta-analysis, namely
total dairy, milk, low-fat dairy, high-fat dairy, total fermented dairy,
yogurt, and cheese. For each category of dairy intake, the total
number of subjects, number of cases, dairy intake data, and RR with
SE or 95% CI were extracted from the selected articles. In 3 studies,
findings were presented as odds ratios, whereas incident HTN
occurred in >10% of the study participants.21,24,26 Because of the
high HTN incidence, the odds ratios may present an overestimation
of the true RR in these studies, and we, therefore, attenuated the
odds ratios using a previously published correction method.28 In
the American studies, dairy intakes were presented in servings per
day20,23 or in times per day.27 To convert these intakes in grams per
day, conversions from the US Food Guide Pyramid were used (eg,
247 g for 1 serving of milk and 245 g for 1 serving of yogurt).29 From
each publication, results from the final multivariable model was used,
which included adjustments for lifestyle and dietary variables (Table
S1 in the online-only Data Supplement). We used STATA version
11.0 (STATA Corp, College Station, TX) for statistical analyses.
For visualizing dose-response relationships across all data, Spaghetti
Plots, developed by coauthor Eric L. Ding, were created to illustrate the
direction and shape of the associations between the intake of different
Results
Study Characteristics
The Table shows the characteristics of the 9 prospective cohort
studies that were included in the meta-analysis. In total, data
Table. Characteristics of 9 Prospective Cohort Studies That Were Included in a Meta-Analysis of Dairy Intake and Incident Hypertension
Study
Population
Reference
Country
Men, Mean Mean BMI,
% Age, y kg/m2
Follow-Up
Time, y
Subjects (Cases) Dietary Assessment Baseline Period HTN Assessment
19
Alonso et al
SUN cohort
Spain
39
37
23.1
2
5880 (180)
136-item FFQ
1999–2002
Self-report*
Alonso et al20
ARIC Study
United States
43
53
26.4
9
8204 (2399)
66-item FFQ
1987–1989
Physical
examination*
Dauchet et al21
SU.VI.MAX
cohort
France
36
50
24.8
5
2341 (606)
6-d dietary records
1994
Physical
examination*
Engberink et al24 MORGEN
Study
The Netherlands 45
50
24.9
5
3454 (713)
178-item FFQ
1993–1997
Physical
examination*
Engberink et al25 Rotterdam
Study
The Netherlands 43
65
25.7
6
2245 (984)
170-item FFQ
1990–1993
Physical
examination*
Snijder et al22
Hoorn Study
The Netherlands 46
59
25.4
5
755 (319)
92-item FFQ
1989
Physical
examination*
Steffen et al27
CARDIA Study United States
43
25
25.2
15
4304 (997)
Dietary history,
average y 0 and 7
1985–1986,
1992–1993
Physical
examination†
Wang et al23
Women’s
United States
Health Study
0
54
25.1
10
28 886 (8 710)
131-item FFQ
1992–1995
Self-report*
47
43
24.8
10
1187 (459)
5-day dietary records
1989
Physical examination*
Heraclides et al26 1946 National United Kingdom
Birth Cohort
BMI indicates body mass index; HTN, hypertension; FFQ, food-frequency questionnaire; SUN, Seguimiento University of Navarra; ARIC, Atherosclerosis Risk in
Communities Study; SU.VI.MAX, SUpplementation en VItamines et Mineraux Anti-oXydants; MORGEN, Monitoring van Risicofactoren en Gezondheid in Nederland;
CARDIA, Coronary Artery Risk Development in Young Adults.
*Definition of HTN was SBP ≥140 mm Hg or DBP ≥90 mm Hg or use of antihypertensive medication.
†Definition of HTN was SBP ≥130 mm Hg or DBP ≥85 mm Hg or use of antihypertensive medication.
Soedamah-Muthu et al Meta-Analysis of Dairy and Hypertension 1133
from 57 256 individuals were available for analysis. Apart
from the Women’s Health Study,23 studies were performed in
both sexes, with the percentage of men ranging from 39% to
47%. The mean age of study populations was 48±12 years
(range, 25–65 years), and follow-up lasted 5 to 15 years.
Three studies were conducted in the United States20,23,27 and 6
in Europe.19,21,22,24–26 The types of dairy intake that were examined and definitions of dairy categories differed across studies,
as described in Table S2.
Apart from 1 study,27 all studies used the same definition for
HTN, that is, systolic BP (SBP) ≥140 mm Hg or diastolic BP
(DBP) ≥90 mm Hg or use of antihypertensive medication. In
the CARDIA Study, HTN was defined as SBP ≥130 mm Hg or
DBP ≥85 mm Hg or use of antihypertensive medication.27 In
2 studies, HTN incidence was based on self-report.19,23 In the
remaining studies, HTN cases were confirmed during physical examination. Table S3 shows the characteristics of metaanalyses per dairy category .
Total Dairy
Nine studies assessed the association between total dairy
intake and HTN incidence.19–27 These studies included a total
of 57 256 individuals, of whom 15 367 developed HTN, and
mean (or median) dairy intakes in the different studies varied
between 257 and 458 g/d. Total dairy intake was linearly associated with HTN incidence (Figure 1A and 1B), with a pooled
RR for HTN of 0.97 (95% CI, 0.95–0.99) per 200 g/d and no significant statistical heterogeneity (I2=28%; P=0.19). Excluding
the Women’s Health Study and stratification by continent, age,
and follow-up time did not alter the results. Stratification by
BMI showed a slightly stronger association in overweight versus normal-weight populations. The pooled RR per intake of
200 g/d was 1.00 (95% CI, 0.96–1.04) for the 4 studies, with
a mean BMI <25 kg/m2,19,21,24,26 and 0.96 (95% CI, 0.94–0.98)
for the 5 studies, with a mean BMI ≥25 kg/m2.20,22,23,25,27
The funnel plot for the studies of total dairy with HTN incidence showed reasonable symmetry (Figure S2), with no evidence for publication bias (P=0.17).
Low- and High-Fat Dairy
Intake of low-fat dairy and high-fat dairy was assessed in 6
studies,19,22–26 including a total of 42 407 individuals (11 365
HTN cases). Mean intakes in the different studies were 205 to
271 g/d for low-fat dairy and 98 to 228 g/d for high-fat dairy.
Low-fat dairy was linearly and inversely associated with HTN
incidence, with a pooled RR of 0.96 (95% CI, 0.93–0.99)
per intake of 200 g/d (Figure 2A and 2B). Intake of high-fat
dairy was not associated with HTN incidence (RR per 200
g/d, 0.99; 95% CI, 0.95–1.03) (Figure S3A and S3B). There
was no significant heterogeneity for the associations with
low-fat (I2=25%; P=0.25) or high-fat dairy (I2=0%; P=0.44).
Excluding the Women’s Health Study did not change the
pooled RR for low-fat dairy but yielded a slightly different
estimate for high-fat dairy (RR per 200 g/d, 1.03; 95% CI,
0.95–1.11). Stratification by age or BMI did not change the
results. For continent and follow-up time, subgroups were too
small to perform stratified analyses.
Milk
Seven studies20–23,25–27 assessed the intake of milk and incident
HTN, including 47 647 individuals (14 398 HTN cases), with
mean milk intakes of 117 to 264 g/d. A significant inverse linear association was found, with a pooled RR of 0.96 (95%
CI, 0.94–0.98) per increment of 200 g/d (Figure S4A and
S4B). Spline models did not reveal significant nonlinearity.
Excluding the Women’s Health Study (data for skim milk
only) and stratification by continent and follow-up time did
not alter the results. For age and BMI, subgroups were too
small to perform stratified analyses.
Total Fermented Dairy, Cheese, and Yogurt
Four studies reported data for total fermented dairy
intake.22,24–26 These studies were composed of 7641 individuals (2475 HTN cases) and mean total fermented dairy intake
of 84 to 201 g/d. The pooled RR for HTN incidence was 0.99
(95% CI, 0.94–1.04) per 150 g/d. Stratified analyses could not
be performed because of the limited number of studies.
Associations with yogurt intake were assessed in 5
studies20,22–24,27 that included 45 088 individuals (12 959 HTN
cases), with mean yogurt intakes of 10 to 79 g/d. Yogurt intake
was not associated with HTN incidence. The pooled RR for
HTN incidence was 0.99 (95% CI, 0.96–1.01) per 50 g/d
(Figure S5A). Stratified analyses could not be performed
because of the limited number of studies. Excluding the
Women’s Health Study did not essentially change the results.
Associations with cheese intake were assessed in 8 studies,20–27 which included 51 007 individuals (15 066 HTN cases)
with mean cheese intakes of 10 to 43 g/d. The pooled RR for
association of cheese intake with HTN incidence was 1.00
(95% CI, 0.98–1.03) per 30 g/d (Figure S6A and S6B). After
exclusion of the Women’s Health Study (assessing cottage
cheese only), the RR for HTN incidence increased to 1.02
(95% CI, 0.99–1.05) per 30 g/d. Stratification by continent,
age, BMI, and follow-up time did not change the results.
No heterogeneity was observed in the analyses of total fermented dairy, yogurt, and cheese.
Discussion
This meta-analysis showed that total dairy intake was associated with a 3% lower risk of HTN per 200 g/d. When examining different types of dairy products in relation to HTN risk,
we found significant inverse associations with low-fat dairy and
milk. For high-fat dairy, total fermented dairy products, yogurt,
and cheese, no significant associations with HTN were found.
Our results are based on data from prospective cohort
studies, in which dairy intake was mostly assessed by foodfrequency questionnaires. In several studies, validation of the
food-frequency questionnaires showed good correlations of
≈0.7 for milk or (if not assessed) for protein and calcium,
which are good indicators for milk intake.19,22–24 Dietary
intake data in the different studies were collected between
1985 and 2002. In earlier studies,20,22,26,27 high-fat milk was
a major contributor to total milk intake, whereas in later
studies19,21,23–25 this was more often low-fat milk. In spite
of variations in types of dairy intake between populations
(Table S2) and over time, no statistical heterogeneity was
1134 Hypertension November 2012
A
Author
Year Country
Study Population
Relative Risk % Weight
(95% CI)
Alonso
2005
ES
SUN cohort
0.91 (0.80–1.03) 2.83
Steffen
2005
USA
CARDIA Study
0.93 (0.88–0.99) 9.80
Engberink 2009
NL
Rotterdam Study
0.94 (0.89–0.99) 12.65
Wang
2008
USA
Women’s Health Study
0.96 (0.94–0.98) 30.81
Alonso
2009
USA
ARIC Study
0.97 (0.93–1.01) 18.06
Heraclides 2012
UK
1946 National Birth Cohort
1.01 (0.92–1.12) 4.25
Engberink 2009
NL
MORGEN Study
1.01 (0.96–1.07) 12.18
Dauchet
2007
FR
SU.VI.MAX cohort
1.02 (0.93–1.12) 4.88
Snijder
2008
NL
Hoorn Study
1.04 (0.95–1.14) 4.54
Overall
0.97 (0.95–0.99) 100.00
(I2=28.3%, P=0.193)
NOTE: Weights are from random-effects analysis
0.1
B
Relative Risk
0.5
1.0
2.0
Relative Risk
1.2
1.0
0.8
0.6
0
200
400
600
800
Total Dairy (grams per day)
Figure 1. A, Forest plot for the linear dose-response relationship between total dairy intake (per increment of 200 g/d) and hypertension
(HTN) incidence from 9 studies. Shown are author names, year of publication, country, study population, relative risks (RRs), 95%
CIs, and weight to the overall meta-analysis. Study-specific RRs and 95% CIs are visualized in squares. The area of the squares
is proportional to the specific study weight to the overall meta-analysis. The diamond presents the pooled RR and a 95% CI. The
percentage of heterogeneity because of between-study variation is shown by I2. B, Ding Spaghetti plot for the linear dose-response
relationship between total dairy intake and HTN incidence from 9 studies. Each gray (thin) line represents a study. The circles are placed
at the study-specific RRs that are related to the corresponding quantity of intake. The area of the circle is proportional to the studyspecific weight. The solid black line represents the pooled RR at each quantity of intake and the dashed line the corresponding 95% CI.
SUN indicates Seguimiento University of Navarra; CARDIA, Coronary Artery Risk Development in Young Adults; ARIC, Atherosclerosis
Risk in Communities Study; MORGEN, Monitoring van Risicofactoren en Gezondheid in Nederland; SU.VI.MAX, SUpplementation en
VItamines et Mineraux Anti-oXydants (trial with daily supplementation with antioxidant vitamins and minerals).
present, and stratified analysis by continent, age, BMI, and
follow-up time did not show substantially different results.
Our meta-analyses covered a broad range of dairy products.
Data on dairy intake were converted into grams per day for all
studies, using country-specific conversions, and pooled RRs
for incident HTN were obtained using an advanced statistical
approach.30 For zero intakes and intakes >700 g/d (total dairy)
or >500 g/d (milk, low-fat dairy), we had insufficient data to
draw conclusions. Our results are in line with the results from
a recent systematic review8 and with a pooled meta-analysis
by Ralston et al,9 which showed significant inverse associations for high versus low intake of total dairy (RR, 0.87), lowfat dairy (RR, 0.84), and fluid dairy (ie, milk and yogurt; RR,
0.92) with incident HTN, whereas no significant associations
were found for high-fat dairy and cheese.
Our results also corroborate data from a prospective study of
2290 older participants at high cardiovascular risk by Toledo
et al,17 which was excluded from our meta-analysis, because
80% of their participants already had HTN at baseline. They
found an inverse association of low-fat dairy, but not high-fat
dairy, with BP change during 1 year of follow-up, with a significant −4.2 mm Hg difference in SBP for the highest versus
lowest quintile of low-fat dairy. Low-fat and high-fat dairy
intakes were also examined in relation to 4-year incidence of
HTN in 30 681 predominantly white US men who participated
in the Health Professionals Study, and it was reported that no
statistically significant associations were found.10 Specific
data on dairy intake, however, could not be obtained, and
we, therefore, had to exclude this study. If RRs for increasing
levels of dairy intake in the Health Professionals Study were
Soedamah-Muthu et al Meta-Analysis of Dairy and Hypertension 1135
A
Author
Year Country Study population
Alonso
2005
ES
SUN cohort
0.81 (0.68–0.97) 3.43
Engberink 2009
NL
Rotterdam Study
0.94 (0.88–1.00) 19.28
Engberink 2009
NL
MORGEN Study
0.94 (0.87–1.02) 14.22
Wang
2008
USA
Women’s Health Study
0.96 (0.93–0.98) 45.73
Snijder
2008
NL
Hoorn Study
1.01 (0.92–1.10) 11.32
Heraclides 2012
UK
1946 National Birth Cohort
1.03 (0.91–1.18) 6.01
Relative Risk
(95% CI)
Overall
% Weight
0.96 (0.93–0.99) 100.00
2
(I =25.1%, P=0.246)
NOTE: Weights are from random-effects analysis
0.1
B
Relative Risk
0.5
1.0
2.0
1.2
Relative Risk
1.0
0.8
0.6
0.4
0
200
400
Low−Fat Dairy (grams per day)
600
Figure 2. A, Forest plot for the linear dose-response relationship between low-fat dairy intake (per increment of 200 g/d) and
hypertension (HTN) incidence from 6 studies. Shown are author names, year of publication, country, study population, relative risks
(RRs), 95%CIs, and weight to the overall meta-analysis. Study-specific RRs and 95% CIs are visualized in squares. The area of the
squares is proportional to the specific study weight to the overall meta-analysis. The diamond presents the pooled RR and a 95% CI.
The percentage of heterogeneity because of between-study variation is shown by I2. B, Ding Spaghetti plot for the linear dose-response
relationship between low-fat dairy intake and HTN incidence from 6 studies. Each gray (thin) line represents a study. The circles are
placed at the study-specific RRs that are related to the corresponding quantity of intake. The area of the circle is proportional to the
study-specific weight. The solid black line represents the pooled RR at each quantity of intake and the dashed line the corresponding
95% CI. SUN indicates Seguimiento University of Navarra; MORGEN, Monitoring van Risicofactoren en Gezondheid in Nederland (study
set up to examine risk factors and health in the Netherlands)
close to or >1, the beneficial associations as reported in the
present meta-analysis could be overestimated.
Randomized trials of dairy intake and BP in healthy individuals, with follow-up periods ranging from 8 to 40 weeks,
showed inconsistent results.34–40 In overweight and obese subjects, dairy intake (combining milk, cheese, and yogurt) lowered SBP only,34 DBP only,35 both,36 or none.37–39 In a study of
young normal-weight adults (mean BP, 118/69 mm Hg), highfat dairy increased SBP but not DBP, and no benefit was found
for low-fat dairy.40 The DASH trial among 459 US adults, on
the other hand, showed that BP can be substantially reduced by
an 8-week diet rich in fruits, vegetables, and low-fat dairy products compared with a typical US diet, with reductions in SBP up
to −11 mm Hg in hypertensive participants. Because of the multifactorial intervention, it is, however, not clear to what extent
the inclusion of low-fat dairy products contributed to the DASH
effect.5 To the best of our knowledge, no long-term trials (>1
year) of dairy intake and incident HTN have been conducted.
Dairy is a major source of dietary calcium and potassium,
2 minerals that could lower BP. An intake of 200 g of
nonfortified milk provides ≈250 mg of calcium and 300 mg
of potassium.41,42 A meta-analysis of 40 randomized controlled
trials showed a small but significant effect of ≈1 g/d of calcium
supplementation on SBP and DBP (−1.9/−1.0 mm Hg).43
Significant reductions in BP (−2.4/−1.6 mm Hg) were also
found for ≈2 g/d of potassium supplementation in a metaanalysis of 27 trials.44 In addition, it has been suggested that
other nutrients in dairy, such as magnesium, phosphorus, and
proteins, could improve BP.8 From our observational data, we
cannot conclude to what extent these different components in
dairy contributed to the inverse associations with incident HTN
and whether the relationship is causal.
1136 Hypertension November 2012
We found a small inverse association of low-fat, but not
high-fat dairy, with HTN incidence. People who consume
low-fat dairy may be more health conscious and have a
healthier eating and lifestyle pattern. In all studies included
in our meta-analysis, adjustment was performed for smoking,
alcohol intake, total energy intake, and several dietary confounders. However, residual confounding cannot be ruled out
in observational studies. One study did not adjust for BMI,27
and 3 studies did not adjust for physical activity,22,24,25 which
are important determinants of HTN risk. Exclusion of studies that did not adjust for physical activity,22,24,25 however,
yielded similar results for total, low-fat, and high-fat dairy.
Alternatively, the lower risk of HTN in those consuming lowfat dairy could be because of replacement of other beverages,
for example, sugar-containing soft drinks that have been associated with increased BP.45,46 The intake of high-fat dairy was
not inversely associated with HTN in our meta-analysis, in
contrast to intake of low-fat dairy. Apart from residual confounding by factors related to a more unhealthy diet or lifestyle, we have no ready explanation for this finding. High-fat
dairy products are a source of saturated and trans fatty acids,
although there has been little convincing evidence to date that
dairy fat increases the risk of HTN.47–49 Furthermore DASH
diet, low in saturated fat (rich in low-fat dairy, fruits, and vegetables), has been shown to lower BP.5 We also found no relationship with cheese, which may partly be explained by its
relatively high content of salt that is known to raise BP.44
Overall, this meta-analysis of prospective cohort studies
showed an inverse association of low-fat dairy and milk with
risk of HTN, which needs confirmation in randomized controlled trials.
Perspectives
US dietary guidelines recommend consumption of 3 cups of
dairy per day, preferably fat-free or low-fat milk or yogurt.
The results from our meta-analysis of prospective cohort studies showed that intake of dairy, in particular low-fat dairy and
milk, could reduce the risk of HTN with 3% per 200 g/d within
the range of intakes that we studied (100–700 g/d). These findings warrant confirmation in randomized, controlled trials.
Acknowledgments
We thank the authors who contributed data to this meta-analysis:
M.A. Martínez-González (SUN cohort, data on high-fat dairy intake), A. Alonso (ARIC Study, data on the associations of total dairy,
total milk, total cheese, and yogurt with HTN incidence), E. KesseGuyot and S. Hercberg (SU.VI.MAX Study, data on the associations
of total dairy, milk, and cheese with HTN incidence), M.B. Snijder
and J.M. Dekker (Hoorn Study, provision of the data set), L. Wang
(Women’s Health Study, data on milk, yogurt, and cheese intake),
and A. Heraclides (1946 National Birth Cohort, provision of his prepublication). We thank Dione Bouchaut (Wageningen University,
Netherlands) for graphical work on the Figures for this article.
Sources of Funding
S.S. Soedamah-Muthu and J.M. Geleijnse obtained an unrestricted
grant from the Dutch Dairy Association (NZO) for meta-analyses of
dairy products and cardiovascular diseases. S.S. Soedamah-Muthu
recently (May 2012) obtained a project grant from Global Dairy
Platform for meta-analyses on cheese and blood lipids. These funding organizations were not involved in the design, data collection,
data interpretation, or reporting of the present study.
Disclosures
E.L. Ding has consulted for Dairy Research Institute, unrelated to this
study. The other authors have no conflicts to report.
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Novelty and Significance
What Is New?
• A ssessment of different types of dairy in relation to hypertension risk
• Standardization among studies for levels of intake and examination of
dose-response associations by means of an advanced meta-analysis technique
What Is Relevant?
• Low-fat dairy and milk were inversely related to risk of hypertension,
whereas high-fat dairy and fermented dairy were not.
• Dairy is frequently consumed in Western societies, and the burden of hypertension is high; therefore, the results of this study could have a substantial public health impact.
Summary
The results from this meta-analysis based on data from 9 prospective
cohort studies showed a small beneficial association between dairy
intake, especially low-fat dairy and milk, and hypertension risk.