Download Dietary Approaches to Stop Hypertension Diet and Incidence of Stroke

Dietary Approaches to Stop Hypertension Diet
and Incidence of Stroke
Results From 2 Prospective Cohorts
Susanna C. Larsson, PhD; Alice Wallin, MSc; Alicja Wolk, DMSc
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Background and Purpose—High adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated
with lower risk of hypertension, the major risk factor for stroke. We examined whether adherence to the DASH diet is
inversely associated with the incidence of stroke.
Methods—The study population comprised 74 404 men and women (45–83 years of age), without stroke at baseline, from the
Cohort of Swedish Men and the Swedish Mammography Cohort. Diet was assessed with a food-frequency questionnaire.
A modified DASH diet score was created based on consumption of vegetables, fruits, legumes and nuts, whole grains,
low-fat dairy, red meat and processed meat, and sweetened beverages. Stroke cases were identified through linkage to
the Swedish National Patient and Cause of Death Registers. Relative risks and 95% confidence intervals were estimated
using Cox proportional hazards regression model.
Results—During 882 727 person-years (mean, 11.9 years) of follow-up, 3896 ischemic strokes, 560 intracerebral
hemorrhages, and 176 subarachnoid hemorrhages were ascertained. The modified DASH diet score was statistically
significantly inversely associated with the risk of ischemic stroke (P for trend=0.002), with a multivariable relative risk
of 0.86 (95% confidence interval, 0.78–0.94) for the highest versus the lowest quartile of the score. The modified DASH
diet score was nonsignificantly inversely associated with intracerebral hemorrhage (corresponding relative risk=0.81;
95% confidence interval, 0.63–1.05) but was not associated with subarachnoid hemorrhage.
Conclusions—These findings indicate that high adherence to the DASH diet is associated with a reduced risk of ischemic
stroke.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01127698 and NCT01127711 for
the Swedish Mammography Cohort and the Cohort of Swedish Men, respectively. (Stroke. 2016;47:986-990. DOI: 10.1161/STROKEAHA.116.012675.)
Key Words: epidemiology ◼ food ◼ proportional hazards models ◼ prospective studies ◼ risk factors ◼ stroke
T
he Dietary Approaches to Stop Hypertension (DASH)
diet is rich in vegetables, fruits, and low-fat dairy products and has reduced amounts of saturated fat, total fat, and
cholesterol.1,2 This diet considerably reduces blood pressure in
hypertensive and normotensive individuals.1 Because hypertension is the major risk factor for stroke, the DASH diet may
lower stroke risk. Few studies have examined this hypothesis.3,4 Therefore, we assessed the association between adherence to the DASH diet and incidence of stroke in Swedish
middle-aged and older adults.
between 1918 and 1952 (n=100 303) received, by mail, a 350-item
questionnaire that sought information on diet and other risk factors
for chronic diseases; 48 850 men (49%) completed the questionnaire.
The Swedish Mammography Cohort was established in 1987 to 1990
with the aim to assess the association of dietary and hormonal factors
with the risk of breast cancer.5 In the late autumn of 1997, Swedish
Mammography Cohort participants who were still alive and living
in the study area received a new questionnaire that was identical,
except for some sex-specific questions, to the questionnaire used in
the Cohort of Swedish Men. A total of 39 227 women (70% response
rate) answered the 1997 questionnaire. Because the 1987 to 1990
questionnaire did not include information on major risk factors for
stroke, we used the 1997 questionnaire as baseline for this study. We
excluded men and women with an incorrect or a missing personal
identification number (n=540), those who died before the start of follow-up (n=81), those with stroke or ischemic heart disease (n=7790)
or cancer (n=4403) before baseline, and those who had inadequately
completed the dietary questionnaire (n=859). This left 74 404 participants (39 969 men [age, 45−79 years] and 34 435 women [age, 49−83
years]) for analysis. Ethical approval was acquired from the Regional
Ethical Review Board at Karolinska Institutet in Stockholm, Sweden.
Methods
Study Population
We used data from 2 Swedish population–based prospective studies:
the Cohort of Swedish Men and the Swedish Mammography Cohort.
The Cohort of Swedish Men began in the late autumn of 1997 when
all men who resided in Västmanland or Örebro County and were born
Received January 6, 2016; final revision received January 26, 2016; accepted January 28, 2016.
From the Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Correspondence to Susanna C. Larsson, PhD, Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77
Stockholm, Sweden. E-mail [email protected]
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.116.012675
986
Larsson et al DASH Diet and Stroke Risk 987
Diet Assessment and DASH Score
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A food-frequency questionnaire (FFQ), designed to measure the
Swedish diet, was used to assess diet. Participants were asked to report
their average intake of 96 foods/food items during the past year. Eight
predefined frequency categories, ranging from never to ≥3 times per
week, were provided for most foods. For frequently consumed foods
(eg, milk, yogurt, and bread), participants were asked to indicate their
exact consumption per day or per week. The validity and reproducibility of the FFQ have been described previously.6,7 For example, the
mean correlation coefficient between fourteen 24-hour recall interviews and FFQ-based estimates was 0.65 for macronutrients.
The DASH diet used in this study was adapted from the DASH
diet score created by Fung et al.3 The score by Fung et al3 included
vegetables, fruits and fruit juices, legumes and nuts, whole-grain
products, low-fat dairy foods, red meat and processed meat, sweetened beverages, and sodium. We modified this score by excluding
sodium because the FFQ used in the Swedish Mammography Cohort
and Cohort of Swedish Men cohorts did not include salt used in cooking or at the table, and therefore, total dietary sodium intake could
not be estimated. Sodium restriction was not included in the original DASH diet.1 Participants were classified into quintiles by their
consumption of each food component. For the first 5 components,
participants were provided a score from 1 to 5 for being in the lowest
to the highest quintiles of intake. Scores were reversed (5–1 for the
lowest to the highest quintiles) for red meat and processed meat and
sweetened beverages for which low consumption was desired. The
modified DASH (mDASH) diet score ranged from 7 (minimal adherence) to 35 (maximal adherence).
Assessment of Covariates
The baseline (1997) questionnaire contained information about education, weight, height, physical activity (including walking/bicycling
and exercise over the preceding year), smoking status and history,
aspirin use, family history of myocardial infarction before 60 years
of age, alcohol consumption, and history of hypertension, high cholesterol levels, and diabetes mellitus. Data on atrial fibrillation were
acquired from the Swedish National Patient Register. We defined
diabetes mellitus as a diagnosis of diabetes mellitus in the Swedish
National Patient Register or the Swedish National Diabetes Register
and complemented with self-reported history of diabetes mellitus.
Body mass index was calculated as weight divided by the square of
height (kg/m2). Pack-years of smoking history were calculated by
multiplying the number of packs of cigarettes smoked per day by the
number of years of smoking.
Case Ascertainment and Follow-Up
Incident stroke cases were ascertained by linkage with the Swedish
National Patient Register (includes inpatient and outpatient [nonprimary care] data) and the Swedish Cause of Death Register (also
includes nonhospitalized cases). Stroke cases were classified according
to the International Classification of Diseases, 10th Revision codes:
I63 for ischemic stroke, I61 for intracerebral hemorrhage, and I60 for
subarachnoid hemorrhage. Validation studies of the Swedish National
Patient Register have found that 96% of stroke cases are identified via
this register8 and that 92% of the patients with stroke are correctly classified.9 Participants contributed person-time of follow-up from January
1, 1998, to the date of diagnosis of stroke, death from any cause, or
censoring date (December 31, 2010), whichever came first.
Statistical Analysis
Participants were classified into quartiles according to their adherence to the mDASH diet. We also analyzed the mDASH diet score as
a continuous variable (per 5-U increment; about 1 SD). Cox proportional hazards regression models stratified on age (in months), and
sex was used to estimate hazard ratios (hereafter referred to as relative risk) with 95% confidence intervals (CIs). Multivariable models
included education (less than high school, high school, or university),
family history of myocardial infarction before 60 years of age (yes
or no), smoking (never; past <20 or ≥20 pack-years; and current <20
or ≥20 pack-years), aspirin use (never, 1–6 tablets per week, and ≥7
tablets/wk), walking/bicycling (quintiles), exercise (quintiles), body
mass index (kg/m2; continuous), and history of hypertension (yes or
no), hypercholesterolemia (yes or no), diabetes mellitus (yes or no),
and atrial fibrillation, as well as total energy intake (kcal/d; continuous) and alcohol consumption (g/d; sex-specific quintiles). The proportional hazards assumption (tested using Schoenfeld residuals) was
satisfied.
We performed tests for trend by creating a variable containing the
median value for each quartile of the mDASH diet score. This variable
was entered as a continuous variable in the model. Stratified analyses
by smoking status (ever or never) and history of hypertension (yes or
no), hypercholesterolemia (yes or no), diabetes mellitus (yes or no),
and atrial fibrillation (yes or no) were conducted to assess potential
effect modification. Multiplicative interaction was tested by including
an interaction term into the multivariable model that also included the
stratification variable and the mDASH diet score (in quartiles). The
likelihood ratio test that compared models with and without the interaction terms was used to test the statistical significance of the interactions. All P values were 2-tailed (α=0.05). The statistical analyses
were performed using SAS (version 9.4; SAS Institute, Cary, NC).
Results
Compared with participants with low adherence to the
mDASH diet score, those with high adherence were slightly
older and were more likely to be have a postsecondary education but less likely to be current smokers and overweight
(Table 1). Furthermore, they were more physically active and
consumed less alcohol.
During 882 727 person-years (mean, 11.9 years) of followup, 3896 ischemic strokes (2223 in men and 1673 in women),
560 intracerebral hemorrhages (348 in men and 212 in
women), and 176 subarachnoid hemorrhages (80 in men and
96 in women) were ascertained. The associations between the
mDASH diet score and the risk of stroke types are presented
in Table 2. The mDASH diet score was statistically significantly inversely associated with the risk of ischemic stroke.
Compared with men and women in the lowest quartile of the
mDASH diet score, those in the highest quartile had a 14%
(95% CI, 6–22) reduced risk of ischemic stroke. Each 5-U
(≈1 SD) increment of the mDASH diet score was associated
with 7% (95% CI, 3–10) reduced risk of ischemic stroke. The
association between the mDASH diet score and the ischemic
stroke did not differ by sex (P for interaction=0.81). High
adherence to the mDASH diet was associated with a statistically nonsignificant lower risk of intracerebral hemorrhage
but was not associated with subarachnoid hemorrhage.
When we stratified the analysis by selected risk factors, the
inverse association between the mDASH diet score and the
ischemic stroke was stronger in never smokers (multivariable
relative risk for the highest versus the lowest quartile=0.80;
95% CI, 0.70–0.92) than in ever smokers (corresponding relative risk=0.89; 95% CI, 0.78–1.01; P for interaction=0.02).
The association was not modified by history of hypertension,
hypercholesterolemia, diabetes mellitus, or atrial fibrillation
at baseline (P for interaction>0.18 for all).
Discussion
In this prospective study of middle-aged and older adults,
adherence to the DASH diet was inversely associated with
the incidence of ischemic stroke. Individuals in the highest
988 Stroke April 2016
Table 1. Age-Standardized Baseline Characteristics According to the Modified Dietary Approaches to Stop
Hypertension Diet in 74 404 Swedish Adults
Quartile of the mDASH Diet Score, Range (Median)
Characteristics*
7–18 (16)
19–21 (20)
21–23 (23)
24–35 (27)
18 171
18 521
18 312
19 400
60.0±9.7
60.1±9.5
60.2±9.3
60.5±9.0
Postsecondary education, %
12
16
20
25
Family history of myocardial infarction, %
15
15
15
16
Current smokers, %
31
26
22
18
No. of participants
Age, y
Aspirin use ≥7 tablets per wk, %
6.4
6.6
6.6
6.9
Walk/bicycle ≥40 min/d, %
29
32
35
40
Exercise ≥2 h/wk, %
48
55
60
67
Overweight (BMI≥25 kg/m ), %
53
51
49
46
Hypertension, %
22
21
21
20
Hypercholesterolemia, %
10
11
11
11
Diabetes mellitus, %
5.9
5.7
5.8
6.2
Atrial fibrillation, %
1.8
1.7
1.6
1.7
Alcohol intake, g/d
12±22
10±16
10±17
8.6±12
Vegetables, servings
1.7±1.1
2.4±1.4
3.1±1.7
4.0±2.2
Fruits and juices, servings
0.9±0.7
1.4±1.0
1.9±1.2
2.7±1.4
Legumes and nuts, servings
0.1±0.1
0.1±0.1
0.1±0.2
0.2±0.3
Whole grains, servings
2.4±1.9
3.3±2.1
3.8±2.2
4.7±2.3
Low-fat dairy, servings
0.8±1.3
1.3±1.6
1.8±1.9
2.7±2.3
Red and processed meat, servings
1.4±0.8
1.2±0.8
1.2±0.8
1.0±0.8
Sweetened beverages, servings
1.1±1.5
0.6±1.1
0.4±0.8
0.2±0.6
2
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Daily food consumption
BMI indicates body mass index; and mDASH, modified Dietary Approaches to Stop Hypertension.
*Values are mean±SD if not otherwise indicated.
quartile of the mDASH diet had a statistically significant
14% lower risk of ischemic stroke compared with those in the
lowest quartile. There was some evidence of an inverse association between the mDASH diet and the intracerebral hemorrhage, but results were not statistically significant.
Two previous prospective studies have reported results on
the DASH diet, using the score created by Fung et al,3 in relation to the risk of stroke.3,4 The largest of these studies included
88 517 middle-aged US nurses of which 1242 and 440 women
developed ischemic stroke and hemorrhagic stroke, respectively, during 24 years of follow-up.3 In that cohort, Fung et al3
found that the DASH diet score was statistically significantly
inversely associated with the risk of total stroke (relative risk
for the highest versus the lowest quintile=0.83; 95% CI, 0.71–
0.96) but not ischemic or hemorrhagic stroke possibly because
of the smaller number of cases. In a Dutch cohort study of
33 671 adults, including 527 total stroke cases diagnosed over
12.2 years of follow-up, each 1-SD increment of the DASH
diet score was associated with a statistically significant 10%
lower risk of total stroke.4
In this study, the inverse relationship between the mDASH
diet and the risk of ischemic stroke seemed to be stronger
in never smokers. However, as several stratified analyses
were conducted, the stronger association in never smokers
may be a chance finding. In contrast to our findings, in the
Nurses’ Health Study, the DASH diet score was more strongly
inversely associated with total stroke risk in smokers than in
nonsmokers although a test for interaction was not statistically
significant.3
The DASH diet has similarities with the Mediterranean diet,
which has been associated with a lower risk of ischemic but
not hemorrhagic stroke.10,11 However, 2 studies observed no
statistically significant association between the Mediterranean
diet and the risk of ischemic12,13 or hemorrhagic stroke,12 but
the number of ischemic stroke cases (n=177) was limited in
one of those studies.13 Like the DASH diet, the Mediterranean
diet is abundant in plant foods (vegetables, fruit, nuts, and
legumes) and low in red and processed meat. A major difference between the 2 diets is that low-fat dairy products are
emphasized in the DASH diet2 but not in the Mediterranean
diet where dairy products are considered a detrimental component.14 Other main differences are that the DASH diet is
characterized by low amounts of sweets and sugar-containing beverages and, unlike the Mediterranean diet, does not
Larsson et al DASH Diet and Stroke Risk 989
Table 2. Relative Risks (and 95% Confidence Intervals) of Stroke Types According to Adherence to the Modified Dietary
Approaches to Stop Hypertension Diet in 74 404 Swedish Adults, 1998–2010
Quartile of mDASH Diet Score, Range (Median)
7–18 (16)
19–21 (20)
21–23 (23)
24–35 (27)
P Trend*
Per 5 U
Ischemic stroke
Men and women
Cases, n
1061
966
947
922
…
3896
211 158
219 049
218 877
233 643
…
882 727
Age and sex adjusted
1.00
0.90 (0.82–0.98)
0.87 (0.80–0.96)
0.81 (0.74–0.89)
<0.0001
0.91 (0.88–0.94)
Multivariable†
1.00
0.91 (0.83–1.00)
0.90 (0.83–0.99)
0.86 (0.78–0.94)
0.002
0.93 (0.90–0.97)
1.00
0.93 (0.83–1.04)
0.92 (0.82–1.03)
0.89 (0.78–1.01)
0.06
0.94 (0.89–0.99)
1.00
0.86 (0.75–1.00)
0.87 (0.75–1.01)
0.80 (0.69–0.92)
0.005
0.91 (0.86–0.97)
Cases, n
156
147
142
115
…
560
Age and sex adjusted
1.00
0.95 (0.76–1.20)
0.94 (0.75–1.18)
0.74 (0.58–0.95)
0.02
0.89 (0.81–0.98)
Multivariable†
1.00
1.00 (0.79–1.25)
0.99 (0.78–1.25)
0.81 (0.63–1.05)
0.14
0.93 (0.84–1.03)
1.00
1.04 (0.78–1.37)
1.03 (0.77–1.38)
0.87 (0.62–1.22)
0.52
0.96 (0.84–1.09)
1.00
0.91 (0.61–1.38)
0.91 (0.60–1.36)
0.69 (0.45–1.06)
0.08
0.87 (0.73–1.03)
42
51
37
46
…
176
Age and sex adjusted
1.00
1.13 (0.75–1.71)
0.78 (0.50–1.23)
0.85 (0.55–1.31)
0.25
0.91 (0.77–1.09)
Multivariable†
1.00
1.17 (0.77–1.78)
0.84 (0.53–1.33)
0.95 (0.60–1.50)
0.55
0.96 (0.80–1.16)
Person-years
Men
Multivariable†
Women
Multivariable†
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Intracerebral hemorrhage
Men and women
Men
Multivariable†
Women
Multivariable†
Subarachnoid hemorrhage
Men and women‡
Cases, n
mDASH indicates modified Dietary Approaches to Stop Hypertension.
*Calculated by assigning the median value to each quartile and treating this variable as a continuous variable.
†The Cox proportional hazards regression model is stratified on age (months) and sex and includes education, family history of myocardial infarction before 60 years
of age, smoking status, and pack-years of smoking, aspirin use, walking/bicycling, exercise, body mass index, history of hypertension, hypercholesterolemia, diabetes
mellitus, and atrial fibrillation and intakes of total energy and alcohol.
‡Analyses by sex were not conducted because of the small number of cases.
emphasize moderate alcohol consumption. Furthermore, the
Mediterranean diet is characterized by a high intake of olive
oil or a high ratio of monounsaturated to saturated fat, whereas
the DASH diet is low in fat. Besides a blood pressure–lowering effect, the DASH and Mediterranean diets may lower the
risk of ischemic stroke through potential antiatherosclerotic
effects as these diets are rich in antioxidants from plant foods
and are low in saturated fatty acids and cholesterol.
Strengths of this study are the prospective design, objective information on stroke diagnoses obtained via linkage with
Swedish registers, and the large number of stroke cases, in
particular ischemic stroke. A limitation is the lack of information on salt used in cooking and at the table. We could, therefore, not include dietary sodium in the mDASH diet score. The
DASH-Sodium trial showed that additional sodium restriction
resulted in even greater blood pressure reduction than the
DASH diet without sodium restriction.15 Another limitation is
the observational design. Hence, the possibility that residual
confounding may have affected our findings cannot be ruled
out. Because dietary intake was self-reported through a single
FFQ, some misclassification of diet was inevitable. This study
is further limited by the lack of data on cardioembolic, largeartery, and lacunar ischemic stroke subtypes. We could, therefore, not investigate whether the DASH diet is more strongly
associated with a certain subtype. Finally, as participants were
middle-aged and older Swedish adults who were relatively
healthy, the generalizability of our results to younger adults,
nonwhites, and less healthy populations is unclear.
In conclusion, results from this prospective study of generally healthy adults indicate that a diet that resembles the
DASH diet, which is widely promoted by the National Heart,
Lung, and Blood Institute for the prevention and treatment of
990 Stroke April 2016
hypertension,2 is associated with a reduced risk of ischemic
stroke.
Sources of Funding
This work was supported by grants from the Swedish Stroke
Association, the Swedish Research Council for Health, Working
Life and Welfare, and the Swedish Research Council/Council for
Infrastructures. The funders had no role in the design, implementation, analysis, or interpretation of the data, or in the decision to submit the paper for publication.
Disclosures
None.
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Dietary Approaches to Stop Hypertension Diet and Incidence of Stroke: Results From 2
Prospective Cohorts
Susanna C. Larsson, Alice Wallin and Alicja Wolk
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Stroke. 2016;47:986-990; originally published online February 11, 2016;
doi: 10.1161/STROKEAHA.116.012675
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