Epidemiology/Population
Fruit and Vegetable Consumption and the Incidence
of Hypertension in Three Prospective Cohort Studies
Lea Borgi,* Isao Muraki,* Ambika Satija, Walter C. Willett, Eric B. Rimm, John P. Forman
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
Abstract—Increased fruit and vegetable intake lowers blood pressure in short-term interventional studies. However, data on
the association of long-term intake of fruits and vegetables with hypertension risk are scarce. We prospectively examined
the independent association of whole fruit (excluding juices) and vegetable intake, as well as the change in consumption
of whole fruits and vegetables, with incident hypertension in 3 large longitudinal cohort studies: Nurses’ Health Study
(n=62 175), Nurses’ Health Study II (n=88 475), and Health Professionals Follow-up Study (n=36 803). We calculated
hazard ratios and 95% confidence intervals for fruit and vegetable consumption while controlling for hypertension risk
factors. Compared with participants whose consumption was ≤4 servings/week, the pooled hazard ratios among those
whose intake was ≥4 servings/day were 0.92(0.87–0.97) for total whole fruit intake and 0.95(0.86–1.04) for total vegetable
intake. Similarly, compared with participants who did not increase their fruit or vegetable consumption, the pooled
hazard ratios for those whose intake increased by ≥7 servings/week were 0.94(0.90–0.97) for total whole fruit intake and
0.98(0.94–1.01) for total vegetable. Analyses of individual fruits and vegetables yielded different results. Consumption
levels of ≥4 servings/week (as opposed to <1 serving/month) of broccoli, carrots, tofu or soybeans, raisins, and apples
was associated with lower hypertension risk. In conclusion, our results suggest that greater long-term intake and increased
consumption of whole fruits may reduce the risk of developing hypertension. (Hypertension. 2016;67:288-293.
DOI: 10.1161/HYPERTENSIONAHA.115.06497.) Online Data Supplement
•
Key Words: epidemiology
■
fruit
■
hypertension
H
■
incidence
■
prospective studies
■
vegetables
Methods
ypertension, a major risk factor for cardiovascular and
renal diseases, continues to represent a growing public
health concern nationwide and worldwide. It is estimated that
41% of adult Americans will have a diagnosis of hypertension by the year 2030.1,2 The Dietary Approach to Stopping
Hypertension (DASH) diet emphasizes the importance of
increasing fruit and vegetable consumption while decreasing the intake of red meat.3 Also, in a 6-month interventional
trial, participants who were educated to increase their fruit
and vegetable consumption had a 4 mm Hg average drop in
their systolic blood pressure (BP) when compared with the
control group.4
Several prospective studies assessed the long-term intake
of fruits and vegetables with hypertension risk.5–10 However,
these studies differ in their design, dietary assessment, and
length of follow-up. Only one study analyzed individual
fruits,9 but to our knowledge, individual vegetables have
not been studied prospectively. We, therefore, examined the
associations of individual fruit and vegetable intake with the
risk of developing hypertension in 3 large prospective cohort
studies consisting of 187 453 participants with >20 years of
follow-up.
Study Population
Participants consisted of the Nurses’ Health Study (NHS, N=121 700
women, aged 30–55 years in 1976), the Nurses’ Health Study II
(NHS II, N=116 430 women, aged 25–42 years in 1989), and the
Health Professionals Follow-up Study (HPFS, N =51 529 men, aged
40–75 years in 1986). Participants returned a questionnaire every
2 years reporting a diagnosis of hypertension by a healthcare provider. Participants also answered semiquantitative food frequency
questionnaires (FFQs) every 4 years, reporting intake of >130 foods
and beverages. Reproducibility and validity of these FFQs were
described in previous work.11,12 Participants who reported a diagnosis
of hypertension at the baseline questionnaire were excluded from the
analysis (1984 in NHS, 1991 in NHS II, and 1986 in HPFS). The
resulting study population consisted of 62 175 women from NHS,
88 475 women from NHS II, and 36 803 men from HPFS. To analyze
the change in fruit and vegetable consumption, we set two 8-year
hypothetical intervention periods with subsequent 8-year followup periods in 1986 and 1994 for NHS and HPFS and in 1991 and
1999 for NHS II. Participants with a diagnosis of hypertension at or
before 1994 for NHS and HPFS and 1999 for NHS II were excluded
from our analysis. The resulting study population for this analysis of
long-term change in intake was 123 059 participants (39 164 in NHS,
63 885 in NHS II, and 20 010 in HPFS). The Institutional Review
Received September 14, 2015; first decision October 5, 2015; revision accepted November 5, 2015.
From the Renal Division, Brigham and Women’s Hospital, Boston, MA (L.B., J.P.F.); Channing Division of Network Medicine, Department of Medicine,
Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (W.C.W., E.B.R., J.P.F.); Department of Nutrition, Harvard T.H. Chan School of Public
Health, Boston, MA (I.M., A.S., W.C.W., E.B.R.); and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (W.C.W., E.B.R).
*These authors contributed equally to this work.
The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.
115.06497/-/DC1.
Correspondence to Lea Borgi, 41 Ave Louis Pasteur, 121-C, Boston, MA 02115. E-mail [email protected]
© 2015 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.115.06497
288
Borgi et al Hypertension Risk With Fruit and Vegetable Intake 289
Board of Brigham and Women’s Hospital approved the study. By
virtue of voluntarily returning their questionnaires, participants provided implied consent. All procedures followed were in accordance
with institutional guidelines.
Assessment of Hypertension
Hypertension was self-reported on the baseline and biennial questionnaires. This method of reporting a diagnosis of hypertension was
shown to be valid in the 3 cohorts.13–15 In NHS, for example, 77% of
51 cases of self-reported hypertension had a BP >160/95 mm Hg.13
A participant was considered to have prevalent hypertension if she
or he reported this diagnosis on any questionnaire up to and including the 1984 (NHS), 1991 (NHS II), or 1986 (HPFS) questionnaire.
Participants were determined to be cases if they reported a diagnosis
of hypertension on subsequent questionnaires, with a date of diagnosis that was after the date of the baseline questionnaire.
Assessment of Fruits and Vegetables Intake
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A detailed dietary questionnaire was sent in 1984, 1986, and every 4 years
thereafter. Similar FFQs were mailed every 4 years beginning in 1991
and 1986 for NHS II and HPFS, respectively. Participants answered how
often, on average, they consumed a specific food; 9 different response
categories could be selected, ranging from never or <1 serving/month to
≥6 serving/day. Multiple questions on the FFQ ascertained whole fruits:
raisins (1 oz)/grapes (half cup), fresh apples/pears (1), bananas (1), strawberries (half cup), blueberries (half cup), prunes (half cup), avocado (half
fruit), cantaloupe (one fourth melon), oranges (1), and peaches/apricots/
plums (1 or half cup canned). As for juices, we analyzed apple juice,
orange juice, and other fruit juices (small glass). Vegetables consisted of
raw and cooked spinach (half cup), kale (half cup), lettuce (per serving),
broccoli (half cup), cauliflower (half cup), brussel sprouts (half cup), cabbage/cole slaw (half cup), raw carrot (half carrot or 2–4 sticks) or cooked
carrot (half cup), string beans (half cup), beans or lentils (half cup), peas/
lima beans (half cup), corn (1 ear or half cup), yams/sweet potatoes
(half cup), eggplant/zucchini (half cup), celery (4″ stick), green peppers
(3 slices), tomatoes (1), and onions (1). The reproducibility and validity
of the FFQ were evaluated in the 3 cohorts. As examples, the deattenuated correlation coefficients between FFQs and a 7-day dietary records
in 173 women from NHS were 0.74 for apples and bananas and 0.53
for cabbage.16 In the HPFS, a similar validation study was conducted;
deattenuated Pearson correlation coefficients were 0.38 for tomatoes and
0.67 for all fruits.17
Assessment of Covariates
On biennial questionnaires, participants reported updated information about weight, smoking status, body mass index, and physical
activity (estimated as metabolic equivalent tasks). The FFQs were
also used to ascertain participants’ consumption of alcohol, whole
grains, animal flesh (red and processed meat, poultry, and fish), and
others. These covariates have been validated with questionnairederived information (correlation coefficients of 0.97 for weight and
0.79 for physical activity).18,19
Statistical Methods
To decrease within-person variation, we used a cumulative average of
an individual’s fruit and vegetable intake beginning with the baseline
FFQ and including subsequent FFQs through the censoring event.
Person-time of follow-up was calculated from the date of return of
the baseline questionnaire to the date of hypertension diagnosis, the
date of death, or the end of follow-up, whichever came first.
Total whole fruits and total vegetables were grouped into 5 categories
from ≤4 servings/month (reference group) to ≥4 servings/day. Individual
fruits and vegetables were grouped into 4 categories, from ≤1 serving/
month (reference group) to 4 to 6 servings/week. Participants’ fruit and
vegetable intake was summed to create a new, combined variable of total whole fruits plus total vegetables; this variable was categorized into
4 categories from ≤1 serving/day (reference group) to ≥6 servings/day.
For the change in consumption of total whole fruits and total vegetables, we calculated 8-year change in dietary intake by subtracting
median value of initial intake level assessed 8 years before baseline
survey from the median value of intake at baseline (for these analyses, baseline refers to 1994 in NHS and HPFS and 1999 in NHS
II). The 8-year change in consumption was divided into 7 categories
ranging from a ≥7 servings/week decrease in intake to a ≥7 servings/
week increase in intake (with no change [±0.9 serving/week] as the
reference group).
We used Cox proportional hazards regression to calculate the
hazard ratios (HRs) and 95% confidence intervals for incident hypertension. HRs were adjusted for potential confounders: age; body
mass index; change in weight; race/ethnicity; family history of hypertension; smoking status; physical activity (metabolic equivalent
tasks per week); postmenopausal; oral contraceptive use (in NHS II);
non-narcotic analgesic; total energy intake; and intakes of alcohol,
animal flesh (in 5 categories), whole grains, and sugar-sweetened and
artificially sweetened beverage. Adjusted multivariable HRs for the 3
cohorts were pooled using fixed effects meta-analysis.
We then created continuous variables to analyze the multivariable
HRs per additional serving per day of total whole fruit, total vegetable, and total fruit and vegetable consumption.
A variety of secondary analyses were also performed. First, we
added intake of micronutrients (potassium, calcium, magnesium, sodium, and fiber) to our multivariable models. Second, we removed
weight change from our models because this could be a causal intermediate. Third, we investigated whether the associations varied
significantly according to age and body mass index by creating stratified models and introducing multiplicative interaction terms to our
unstratified multivariable models. Finally, we repeated our analyses
using simple updating instead of cumulative averaging. All analyses
were performed with SAS software (version 9.4; SAS Institute Inc,
Cary, NC). All P values are 2-sided.
Results
Association of Fruits and Vegetables With Incident
Hypertension
Among 187 453 participants free from hypertension at the
baseline questionnaire, 77 373 participants were diagnosed
with hypertension in 2 939 124 person-years of follow-up
(35 375 cases/1 034 421 person-years in NHS, 25 246/1 344 475
in NHS II, and 16 752/560 228 in HPFS).
Table S1 in the online-only Data Supplement reports the
baseline characteristics of participants in the 3 cohorts for
different intake categories of total whole fruits and total vegetables. In all 3 cohorts, those with higher intakes of fruits and
vegetables were older, more physically activity, had a higher
daily caloric intake, and were less likely to be current smokers.
Participants who consumed ≥4 servings/day of total whole
fruits and total vegetables, as compared with ≤4 servings/
week, had multivariable pooled HRs for incident hypertension of 0.92 (95% confidence interval 0.87–0.97) and 0.95
(0.86–1.04), respectively (Table 1). When fruits and vegetables
were combined into one intake category, higher consumption
(≥ 6servings/day) was associated with a lower risk of developing hypertension (HR=0.89 [0.86–0.93]) when compared to ≤1
serving/day (Table 2).
Table 3 reports the pooled HRs for most individual fruits
and vegetables and the risk of incident hypertension (complete
tables in Table S2 and S3). Higher intakes of raisins/grapes
and apples/pears, when consumed ≥4 servings/week, were
associated with a decreased risk of hypertension; multivariable pooled HRs were 0.92 (0.89–0.96) and 0.91 (0.88–0.95),
respectively. Blueberries and avocados were also associated
with a significant trend toward a lower risk of hypertension;
290 Hypertension February 2016
Table 1. Pooled Hazard Ratios (95% Confidence Intervals) of Incident Hypertension for Total Whole Fruits and Total
Vegetables Consumption in Nurses’ Health Study, Nurses’ Health Study II, and Health Professional Follow-up Study
Consumption Levels
Fruits and Vegetables
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Total Fruits*
NHS†
Adjusted hazard ratio‡
NHS II§
Adjusted hazard ratio‡
HPFS║
Adjusted hazard ratio‡
Pooled Results¶
Total Vegetables*†
NHS†
Adjusted hazard ratio‡
NHS II§
Adjusted hazard ratio‡
HPFS║
Adjusted hazard ratio‡
Pooled results¶
≤4 per Week
5–6 per Week
1 per Day
2–3 per Day
≥4 per Day
4943/154 025
1.00 (reference)
5228/272 299
1.00
2827/91 348
1.00
1.00
4283/128 106
0.97 (0.93–1.01)
4125/200 643
1.03 (0.99–1.07)
1914/63 222
0.95 (0.89–1.00)
0.99 (0.96–1.01)
12 732/366 100
0.95 (0.92–0.99)
9372/488 469
0.97 (0.94–1.01)
5330/177 585
0.92 (0.88–0.97)
0.95 (0.93–0.97)
12 548/359 298
0.94 (0.91–0.98)
6193/360 225
0.91 (0.87–0.95)
5941/200 187
0.92 (0.87–0.97)
0.93 (0.90–0.95)
869/26 892
0.96 (0.88–1.03)
328/22 839
0.91 (0.81–1.02)
740/27 887
0.88 (0.81–0.97)
0.92 (0.87–0.97)
137/4225
1.00
237/14 685
1.00
126/4325
1.00
1.00
341/10 250
0.95 (0.77–1.16)
446/25 753
1.01 (0.86–1.18)
234/8182
0.96 (0.77–1.19)
0.98 (0.88–1.09)
3250/99 574
0.90 (0.76–1.07)
3290/187 949
0.96 (0.84–1.09)
1944/68 410
0.92 (0.77–1.11)
0.93 (0.85–1.02)
20 298/589 705
0.89 (0.75–1.05)
14 198/750 828
0.97 (0.85–1.11)
9490/312 925
0.94 (0.79–1.13)
0.94 (0.86–1.03)
11 349/330 667
0.87 (0.73–1.03)
7075/365 261
1.01 (0.88–1.15)
4958/166 386
0.93 (0.78–1.12)
0.95 (0.86–1.04)
Linear P Trend
0.06
<0.001
0.01
<0.001
0.02
0.04
0.68
0.59
HPFS indicates Health Professionals Follow-up Study; and NHS, Nurses’ Health Study.
*Multivariable model, including total vegetables, was adjusted for total fruits intake (quintiles) and vice versa.
†Follow-up in Nurses’ Health Study was from 1984 to 2010 (cases/persons-years).
‡Adjusted for age, race/ethnicity (white, African American, Asian, Hispanic, other), body mass index, current smoking status, physical activity, weight
change per food frequency questionnaire cycle, menopausal status (NHS and NHS II), alcohol intake, current oral contraceptive use (NHS II), analgesic
use (nonsteroidal antiinflammatory drugs, acetaminophen, aspirin), family history of hypertension, total energy intake, animal flesh intake (combination of
processed and unprocessed red meat, poultry and seafood), whole grains, sugar-sweetened beverage intake, artificially sweetened diet beverage intake.
§Follow-up in Nurses’ Health Study II was from 1991 to 2011.
║Follow-up in Health Professionals Follow-up study was from 1986 to 2010.
¶Pooled hazard ratios of the three cohorts using a fixed effects model.
HRs were 0.92 (0.83–1.03; P trend=0.01) and 0.94(0.77–1.14;
P trend <0.001), respectively. In contrast to these fruits, higher
cantaloupe intake was associated with an increased risk of
hypertension (HR=1.07 [1.01–1.13]).
Broccoli, carrots, and tofu/soybeans were associated with
a decreased risk of incident hypertension when consumed ≥4
servings/week as compared with <1 serving/month, with multivariable pooled HRs of 0.94 (0.90–0.99), 0.95 (0.91–0.99),
and 0.88 (0.79–0.99), respectively (Table 3). In contrast, eating more string beans and brussel sprouts was associated
with an increased risk of hypertension with pooled HRs of
1.11 (1.05–1.17) and 1.23 (1.04–1.46), respectively. In addition, higher consumption of both corn and cauliflower were
associated with an increased trend toward a higher risk of
hypertension with multivariable pooled HRs of 1.05 (0.98–
1.12; P trend <0.004) and 1.06 (0.99–1.14; P trend<0.001),
respectively.
Furthermore, in a separate analysis, there was no association between fruit juices and hypertension (data not shown).
When continuous variables were used, every one additional serving per day of total whole fruit was associated with
a lower risk of hypertension (HR= 0.97 [0.96–0.98]).
Association of 8-Year Change of Fruits and
Vegetables Consumption With Subsequent
Hypertension Risk
In our analyses of 8-year change in intake with the subsequent
development of hypertension, we defined a new baseline year
of 1994 (for NHS and HPFS) and 1999 (for NHS II) to permit
the calculation of change in consumption before baseline. After
excluding participants who reported a diagnosis of hypertension at baseline, 44 032 participants were diagnosed with hypertension in 1 517 157 person-years of follow-up (20 147 cases in
566 278 person-years in NHS, 15 972/683 702 in NHS II, and
8183/267 177 in HPFS). Increasing total whole fruit consumption by ≥7 servings/week in the preceding 8 years was associated with a lower risk of hypertension with a pooled HR 0.94
(0.90–0.97; Table S4, please see http://hyper.ahajournals.org)
during the subsequent 5 years, whereas there was no association with incident hypertension when participants increased
their total vegetable consumption (HR=0.98 [0.94–1.01]).
Associations between change in the consumption level of individual fruits and vegetables with incident hypertension were
generally similar to those associations observed with long-term
intake (Tables S5, please see http://hyper.ahajournals.org)).
Overall, our secondary analyses had no substantial impact
on the findings. Adjusting for potassium and other micronutrients (including calcium, magnesium, sodium, and fiber) did not
materially change the results. We also examined more extreme
categories of total fruit and vegetable consumption, and the
results were mostly unchanged. There were no consistent interactions between fruit and vegetable intake and either age or body
mass index with hypertension risk. Removing weight change
from our models did not change our findings. We also found
similar results when the analyses were repeated with simple
updating of dietary intake (rather than cumulative averaging).
Borgi et al Hypertension Risk With Fruit and Vegetable Intake 291
Table 2. Pooled Hazard Ratios (95% Confidence Intervals) of Incident Hypertension for Combined Total
Fruits and Total Vegetables Consumption in Nurses’ Health Study, Nurses’ Health Study II ,and Health
Professional Follow-up Study
Total Fruits and Vegetables
NHS*
Adjusted hazard ratio†
NHS II‡
Adjusted hazard ratio†
HPFS§
Adjusted hazard ratio†
Pooled results‖
Linear P
Trend
≤1 per Day
2–3 per Day
4–5 per Day
≥6 per Day
1052/31 868
1.00 (reference)
1427/79 840
1.00
666/22 176
1.00
1.00
11 318/339 541
0.90 (0.84–0.95)
10 019/528 610
0.97 (0.92–1.03)
5711/190 017
0.93 (0.85–1.01)
0.94 (0.90–0.97)
13 914/396 152
0.88 (0.83–0.94)
8785/462 410
0.95 (0.89–1.00)
6085/201 161
0.91 (0.83–0.98)
0.91 (0.88–0.95)
9091/266 861
0.85 (0.80–0.91)
5015/273 616
0.94 (0.88–0.99)
4290/146 874
0.89 (0.81–0.97)
0.89 (0.86–0.93)
<0.001
0.02
0.02
<0.001
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HPFS indicates Health Professionals Follow-up Study; and NHS, Nurses’ Health Study.
*Follow-up in Nurses’ Health Study was from 1984 to 2010 (cases/persons-years).
†Adjusted for age, race/ethnicity (white, African American, Asian, Hispanic, other), body mass index, current smoking status,
physical activity, weight change per food frequency questionnaire cycle, menopausal status (NHS and NHS II), alcohol intake, current
oral contraceptive use (NHS II), analgesic use (nonsteroidal antiinflammatory drugs, acetaminophen, aspirin), family history of
hypertension, total energy intake, animal flesh intake (combination of processed and unprocessed red meat, poultry and seafood),
whole grains, sugar-sweetened beverage intake, artificially sweetened diet beverage intake.
‡Follow-up in Nurses’ Health Study II was from 1991 to 2011.
§Follow-up in Health Professionals Follow-up study was from 1986 to 2010.
‖Pooled hazard ratios of the 3 cohorts using a fixed effects model.
Discussion
In 3 prospective cohort studies of US women and men, longterm intake of total whole fruit was associated with a decreased
risk of developing hypertension, whereas total vegetable intake
was not. The association of whole fruit intake with hypertension incidence was independent of other known and potential
risk factors for hypertension. Some vegetables (ie, broccoli,
carrots, tofu) and some fruits (ie, raisins or grapes and apples
or pears) were associated with a lower risk of hypertension,
whereas some vegetables (ie, string beans, Brussels sprouts)
and cantaloupe were associated with an increased risk of developing hypertension. To our knowledge, our study is the first to
prospectively analyze individual vegetables and has the longest
follow-up period of any study of diet and hypertension.
Our finding that total whole fruit but not total vegetable intake is associated with a lower risk of developing
Table 3. Pooled Hazard Ratios (95% Confidence Intervals) of Incident Hypertension for Several
Individual Fruit and Individual Vegetable Consumption in Nurses’ Health Study, Nurses’ Health
Study II, and Health Professional Follow-up Study
Individual Fruits and
Vegetables
Raisins or grapes*
Apples or pears*
Strawberries*
Blueberries*
Avocado*
Spinach*
String beans*
Corn*
Broccoli*
Cauliflower
Brussel Sprouts*
Carrots*
Tofu or soybeans*
Cantaloupe*
Consumption Levels
<1 per Month
1–3 per Month
1–3 per Week
≥4 per Week
P Trend
1.00 (reference)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
0.98 (0.96–1.00)
0.94 (0.90–0.97)
0.98 (0.96–1.00)
0.97 (0.95–0.98)
0.97 (0.95–0.99)
0.99 (0.97–1.01)
1.02 (0.99–1.05)
1.02 (0.99–1.05)
0.99 (0.96–1.03)
1.00 (0.98–1.02)
1.02 (1.00–1.04)
0.99(0.95–1.03)
0.95 (0.93–0.98)
1.03 (1.01–1.05)
0.94 (0.92–0.97)
0.95 (0.91–0.98)
0.99 (0.97–1.02)
0.95 (0.92–0.98)
0.92 (0.87–0.96)
0.99 (0.97–1.01)
1.05 (1.02–1.09)
1.03 (1.00–1.07)
0.97 (0.93–1.00)
1.04 (1.01–1.07)
1.04 (1.00–1.08)
0.97 (0.93–1.01)
1.01 (0.97–1.07)
1.06 (1.03–1.08)
0.92 (0.89–0.96)
0.91 (0.88–0.95)
1.01 (0.95–1.07)
0.92 (0.83–1.03)
0.94 (0.77–1.14)
0.98 (0.93–1.02)
1.11 (1.05–1.17)
1.05 (0.98–1.12)
0.94 (0.90–0.99)
1.06 (0.99–1.14)
1.23 (1.04–1.46)
0.95 (0.91–0.99)
0.88 (0.79–0.99)
1.07 (1.01–1.13)
<0.001
<0.001
0.79
0.01
<0.001
0.32
<0.001
0.004
<0.001
<0.001
0.03
0.003
0.001
0.002
NHS indicates Nurses’ Health Study.
*Pooled hazard ratios of the 3 cohorts using a fixed effects model. Adjusted for age, race/ethnicity (white, African
American, Asian, Hispanic, other), body mass index, current smoking status, physical activity, weight change per food
frequency questionnaire cycle, menopausal status (in NHS I and NHS II), alcohol intake, current oral contraceptive use (in
NHS II), analgesic use (nonsteroidal antiinflammatory drugs, acetaminophen, aspirin), family history of hypertension, total
energy intake, animal flesh intake (combination of processed and unprocessed red meat, poultry and seafood), whole
grains (quintiles), sugar-sweetened beverage intake, artificially-sweetened diet beverage intake. All vegetables were
adjusted for each other, with a reference group of < 1 serving/month.
292 Hypertension February 2016
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hypertension is consistent with some earlier studies. The largest prior experience comes from the Women’s Health Study,
a prospective cohort of 28 082 female US health professionals
with baseline semiquantitative FFQ and 12.9 years of followup.5 Those participants who consumed more dark-yellow
vegetables had a lower adjusted risk of incident hypertension
(HR=0.88; 95 confidence interval 0.82–0.95), whereas similar comparisons for cruciferous vegetables (such as brussel
sprouts) yielded an increased risk of hypertension (HR=1.14;
1.06–1.23).5 Also similar to our study, greater intake of apples
and raisins were associated with lower risks of developing
hypertension, with HRs of 0.91 (0.85–0.99) and 0.90 (0.85–
0.96), respectively.5
Other studies are considerably smaller or are cross-sectional.
In the Ohasama study, for example, 745 nonhypertensive women
and men aged ≥35 years were followed for 4 years.6 Participants
in the highest compared with lowest quintile of fruit intake had
a lower adjusted hypertension risk (odds ratio=0.40; 0.21–0.74,
P trend=0.03).6 The mechanisms by which fruits and vegetables
may be associated with hypertension are probably multiple.
One hypothesis pertains to the high flavonoid content of several fruits and vegetables, such as berries, apples, broccoli, and
others.20 In a prospective study of the NHS I, NHS II, and the
HPFS, participants in the highest quintile intake of anthocyanins
(mostly from blueberries and strawberries) had an 8% lower risk
of hypertension.21 Also, in a randomized controlled trial of men
at risk for cardiovascular disease, a diet rich with high-flavonoid
fruits and vegetables increased endothelium-dependent microvascular reactivity and plasma nitric oxide, as well as decreased
C-reactive protein and E-selectin.22 Furthermore, grape polyphenols were found to potentiate vasorelaxation and decrease
BP, as well as endothelial dysfunction markers, in a small,
placebo-controlled, double-blind study of 24 men with metabolic syndrome.23 Endothelial dysfunction, inflammation, and
oxidative stress are potential important factors in the development of hypertension.24–26 Also, quercetin, a flavonoid found in
apples, was found to decrease systolic BP by 3 mm Hg (P<0.01)
when compared with placebo in a double-blind crossover trial.27
Similarly, soy isoflavones were found to decrease BP in a metaanalysis of randomized controlled trials.28
As with the Women’s Health Initiative study,5 we found a
variable association of cruciferous vegetables with hypertension.
Although broccoli was associated with a lower risk of hypertension, brussel sprouts seemed to increase hypertension risk when
consumed ≥4 servings/week. In a recent meta-analysis of fruit
and vegetable intake and the incidence of pancreatic cancer in 14
cohort studies, brussel sprouts were associated with an increased
risk of pancreatic cancer; this association could be related to the
use of pesticides or its carcinogenic abilities.29 However, this
association was not seen with broccoli, cauliflower, or cabbage.
Another possible explanation for these differences is the
cooking methods used when eating vegetables. While broccoli is commonly eaten steamed or raw, brussel sprouts (and
string beans) are usually roasted, fried, or baked and mixed
with seasonings. However, additionally adjusting for total fats
and micronutrients (including sodium) in our analyses did not
materially alter our findings (data not shown). The effect of
different cooking methods on flavonoids, other phenolic compounds, and the total antioxidant capacity of vegetables in the
Brassica corps group is controversial.30 In one study, for example, microwave cooking decreased broccoli’s flavonoid content
by 97%.31 In another study, however, precooking and cooking
methods did not alter the antioxidant capacities of broccoli.32
There are several limitations to our study. First, the diagnosis of hypertension was self-reported and participants’ BPs
were not directly measured. However, all participants are
health professionals, and this method of hypertension diagnosis in these cohorts has been validated in multiple studies.14–16
Second, our participants were mostly nonhispanic white men
and women, and this analysis should be replicated in other
populations. Third, the FFQ is an imperfect tool for assessing food intake, and therefore, random misclassification of
fruit and vegetable consumption may have occurred; this random error was likely to have been amplified in our analyses
of change in intake over time. Yet, this type of error would
have the effect of moving our hazard ratios toward the null
(ie, toward finding no associations). Thus, it is possible that
the associations we report are underestimates of the true relationships. Fourth, the associations that we found were modest; however, even these modest associations, if considered
at the population level, could have important public health
ramifications. Finally, as in any observational study, we cannot exclude the possibility that our findings are the result of
residual confounding. Food preferences could also result in
residual confounding.
However, we controlled for multiple known and potential
risk factors for the development of hypertension in a prospective fashion.
In conclusion, we found a prospective, independent association between higher whole fruit intake, as well as a longitudinal increase in fruit intake, and a decreased risk of incident
hypertension. No such association was noted with higher vegetable intake. Although our study supports the hypothesis that
specific fruits and vegetables may have important effects on
BP, these findings should be confirmed by randomized trials.
Several unexpected results in this study, including disparate
relations with different vegetables, merit further investigation.
Perspectives
In summary, our observed findings continue to stress on the
importance of dietary intake on diseases, especially cardiovascular diseases. Given the increasing prevalence of hypertension in
the United States and around the world, these data have important public health implications. Future studies are needed to
assess the potential mechanisms underlying these associations.
Acknowledgments
Borgi, Muraki, Rimm, and Forman contributed to the conception and
design of the study. All authors were involved in the analysis and interpretation of the data. Borgi and Muraki designed and conducted the
statistical analysis. Borgi and Muraki worked on the drafting of the
article, which was thoroughly reviewed and approved by all authors.
Sources of Funding
This study was funded by research grants P01 CA87969, UM1
CA176726, and UM1 CA167552. Dr Borgi was funded by an
American Heart Association fellowship award (14POST20380070).
Disclosures
None.
Borgi et al Hypertension Risk With Fruit and Vegetable Intake 293
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Novelty and Significance
What Is New?
Summary
• First study with >20 years of follow-up.
• New findings about individual fruits and vegetables consumption and
Not all vegetables are associated with a lower risk of hypertension.
We found an increased risk of hypertension with an increased consumption of string beans, brussel sprouts, and cantaloupe.
incidence of hypertension.
What Is Relevant?
• Not all fruits and vegetables prevent hypertension.
Fruit and Vegetable Consumption and the Incidence of Hypertension in Three Prospective
Cohort Studies
Lea Borgi, Isao Muraki, Ambika Satija, Walter C. Willett, Eric B. Rimm and John P. Forman
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
Hypertension. 2016;67:288-293; originally published online December 7, 2015;
doi: 10.1161/HYPERTENSIONAHA.115.06497
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FRUIT AND VEGETABLE CONSUMPTION AND THE INCIDENCE OF HYPERTENSION IN THREE PROSPECTIVE COHORT STUDIES
Lea Borgi MD, MMSc*1, Isao Muraki, MD, PhD*3, Ambika Satija, BA3, Walter C. Willett MD, Dr.P.H 2,3 , Eric B. Rimm, ScD 2,3, John P. Forman MD,
MSc1,2
1
Renal Division, Brigham and Women’s Hospital, Boston.
2
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston
3
Departments of Nutrition and Epidemiology, Harvard T.H. School of Public Health
*equal contribution
Short title: Hypertension Risk with Fruit and Vegetable Intake
Word Count: 6,000 for manuscript and 228 for abstract. 5 tables in online supplement.
Corresponding Author: Lea Borgi, 41 Avenue Louis Pasteur, 121-C, Boston, MA 02115.
Phone/fax numbers: 617 264 3068, 617 264 5975. Email: [email protected].
Supplementary Table S1: Baseline characteristics of participants in the Nurses’ Health Study, Nurses’ Health Study II and the Health Professionals
Follow-up Study. Values are median (interquartile range) or percentages unless stated
Nurses’ Health Study*
Age (years)
White (%)
Body Mass Index
Total daily calories (kcal)
Alcohol (serving/day)
Animal Flesh§(serving/day)
Physical Activity (METs/w)
Current Smokers (%)
Family History of HTN (%)
Total Fruits (servings)
≤4 per week
1 per day
50(44-56)
95
23.5(21.6-26.4)
1693(1388-2043)
2.1(0.0-8.5)
1.3(0.9-1.8)
8.0(2.9-19.0)
21
43
53 (47-58)
92
23.4 (21.3-26.4)
2162(1779-2566)
1.8(0.0-5.5)
1.4(0.9-1.9)
12.6 (4.5-29.0)
15
38
≤4 per week
1 per day
≥4 per day
42 (37-47)
43(38-48)
42 (37-48)
39 (34-44)
41(36-46)
44 (39-49)
White (%)
Body Mass Index
Total daily calories (kcal)
Alcohol (serving/day)
Animal Flesh§(serving/day)
Physical Activity (METs/w)
Current Smokers (%)
Family History of HTN (%)
93
24.0 (21.5-27.9)
1505(1224-1832)
1.0(0.0-4.9)
1.1(0.8-1.5)
7.9 (2.7-19.0)
17
49
94
24.1(21.7-27.8)
1764(1480-2089)
1.5(0.0-5.3)
1.2(0.9-1.6)
13.0(5.3-26.4)
8
48
90
23.2 (21.0-26.6)
2302(1966-2667)
1.1(0.0-4.3)
1.3(0.9-1.9)
25.2 (10.6-49.6)
5
48
91
23.7 (21.3-27.5)
1285(1015-1628)
0.0(0.0-2.0)
0.8(0.5-1.2)
7.1 (2.3-18.4)
17
50
93
23.8(21.5-27.5)
1467(1209-1773)
0.9(0.0-3.0)
1.0(0.7-1.3)
8.4(3.2-19.5)
12
48
94
24.2 (21.7-28.0)
2033(1714-2382)
1.9(0.0-6.7)
1.4(1.0-1.9)
18.3 (7.8-35.9)
9
49
Health Professionals
Follow-up Study‡
≤4 per week
1 per day
≥4 per day
Age (years)
White (%)
Body Mass Index
Total daily calories (kcal)
Animal Flesh§(serving/day)
Physical Activity (METs/w)
Current Smokers (%)
Family History of HTN (%)
49 (43-57)
91
25.1 (23.3-26.9)
1716(1366-2134)
1.5(1.0-2.0)
7.8 (2.2-21.3)
17
32
52(61-44)
92
25.0(23.3-26.6)
1891(1540-2318)
1.5(1.0-2.0)
12.4(4.2-28.8)
9
32
56 (47-64)
91
23.0 (23.0-26.5)
2355(1933-2891)
1.4(0.9-2.0)
22.2 (8.3-46.0)
3
30
Nurses’ Health Study 2†
Age (years)
47 (42-53)
95
23.2 (21.3-25.8)
1507(1203-1863)
2.9(0.0-12.2)
1.2(0.9-1.7)
5.0 (1.7-13.6)
37
42
≥4 per day
Total Vegetables (servings)
≤4 per week
1 per day
≥4 per day
49 (43-55)
92
23.1 (21.2-26.0)
1217(972-1611)
0.9(0.0-3.9)
0.9(0.5-1.2)
3.9 (0.9-10.9)
39
40
≤4 per week
≤4 per week
51 (43-61)
88
25.1 (23.3-26.7)
1503(1191-1909)
1.1(0.7-1.6)
6.7 (1.8-20.1)
16
30
48(43-54)
94
26.1(21.3-26.1)
1426(1144-1746)
1.5(0.0-6.3)
1.1(0.7-1.5)
4.6(1.6-13.9)
28
43
1 per day
1 per day
51(43-59)
90
25.1(23.3-26.7)
1641(1309-2023)
1.2(0.8-1.7)
9.0(2.8-24.1)
12
32
51 (45-57)
95
23.5 (21.9-26.3)
1917(1578-2310)
2.9(0.0-11.0)
1.6(1.1-2.1)
10.4 (3.7-23.6)
21
42
≥4 per day
≥4 per day
53 (45-62)
92
24.7 (23.1-26.6)
2188(1781-2674)
1.7(1.2-2.6)
16.8 (6.1-35.6)
7
32
* Baseline for Nurses’ Health Study is 1984.
† Baseline for Nurses’ Health Study II is 1991.
‡ Baseline for Health Professionals Follow-up Study is 1986.
§Animal flesh: combination of processed and unprocessed red meat, poultry and seafood.
Supplementary Table S2: Pooled hazard ratios (95% confidence intervals) of incident hypertension for individual vegetable consumption in Nurses’
Health Study, Nurses’ Health Study II and Health Professional Follow-up Study
Consumption Levels
Individual Vegetables
Corn
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
<1 per month
1-3 per month
1-3 per week
≥4 per week
3116/95386
1.00
1374/84357
1.00
1407/46707
1.00
1.00
19904/559107
1.02(0.98-1.06)
12051/607741
1.07(1.01-1.14)
8938/290405
0.97(0.91-1.02)
1.02(0.99-1.05)
12052/370557
1.03(0.98-1.07)
11185/621231
1.09(1.03-1.16)
6112/214656
0.99(0.93-1.06)
1.03(1.00-1.07)
303/9371
0.93(0.82-1.05)
636/31146
1.12(1.01-1.23)
295/8460
1.09(0.95-1.25)
1.05(0.98-1.12)
18397/558078
1.00
14105/780227
1.00
8209/280882
1.00
1.00
15491/432591
1.01(0.99-1.03)
9934/500078
1.02(0.99-1.05)
7267/235236
1.00(0.97-1.04)
1.01(1.00-1.03)
1453/42670
1.01(0.95-1.07)
1174/62225
1.11(1.04-1.18)
1234/42378
0.99(0.93-1.07)
1.03(1.00-1.07)
34/1082
0.88(0.62-1.24)
33/1945
0.99(0.70-1.41)
42/1732
0.77(0.56-1.05)
0.86(0.71-1.05)
4130/127431
1.00
5589/313111
1.00
1680/57877
1.00
1.00
18576/524237
0.99(0.96-1.03)
11781/592964
1.00(0.96-1.03)
8158/261754
1.02(0.96-1.08)
1.00(0.98-1.02)
12315/373364
1.00(0.96-1.04)
7588/422732
1.01(0.97-1.05)
6579/230309
1.01(0.95-1.08)
1.01(0.98-1.04)
354/9390
1.13(1.01-1.27)
876/34486
0.98(0.86-1.11)
335/10287
1.06(0.93-1.21)
1.06(0.99-1.14)
205/6375
1.00
252/16310
1.00
317/10472
1.00
1.00
1784/52793
1.07(0.92-1.24)
1827/96482
1.02(0.89-1.17)
1458/49343
0.89(0.78-1.01)
0.98(0.91-1.06)
9544/280483
1.05(0.91-1.21)
8986/503597
0.99(0.87-1.12)
4976/167741
0.86(0.76-0.97)
0.95(0.88-1.02)
23842/694771
1.03(0.89-1.19)
14181/728086
0.99(0.87-1.13)
10001/332672
0.85(0.76-0.96)
0.94(0.88-1.02)
P Trend
0.27
0.03
0.10
0.004
Yams or sweet potatoes
NHS*
Adjusted hazard ratio§
NHS II†
Adjusted hazard ratio§
HPFS‡
Adjusted hazard ratio§
Pooled results||
0.78
0.01
0.83
0.12
Peas or lima beans
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.24
0.53
0.52
0.17
Lettuce
NHS*
Adjusted hazard ratio§
NHS II†
Adjusted hazard ratio§
HPFS‡
Adjusted hazard ratio§
Pooled results||
0.74
0.83
0.29
0.56
Broccoli
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
1311/41124
1.00
1369/71841
1.00
1317/43027
1.00
1.00
12029/344916
1.03(0.97-1.09)
8851/458751
0.98(0.92-1.04)
6517/210667
0.96(0.90-1.03)
0.99(0.96-1.03)
20165/594694
1.00(0.94-1.07)
13443/738131
0.95(0.89-1.01)
8162/283077
0.95(0.89-1.02)
0.97(0.93-1.00)
1870/53687
0.95(0.88-1.03)
1583/75751
0.94(0.86-1.02)
756/23457
0.94(0.84-1.05)
0.94(0.90-0.99)
5990/182513
1.00
6628/380064
1.00
3656/123183
1.00
1.00
19538/566227
1.01(0.98-1.05)
12316/650023
0.99(0.96-1.02)
8878/290967
0.99(0.95-1.03)
1.00(0.98-1.02)
9372/272291
1.06(1.01-1.10)
5926/296961
1.06(1.02-1.11)
3966/138605
0.97(0.92-1.03)
1.04(1.01-1.07)
475/13391
1.10(0.99-1.22)
376/17426
1.04(0.92-1.17)
252/7473
1.02(0.88-1.19)
1.06(0.99-1.14)
21906/643071
1.00
18042/987538
1.00
9032/306509
1.00
1.00
11482/332501
1.02(1.00-1.05)
6060/300486
1.01(0.98-1.04)
6348/206186
1.03(0.99-1.06)
1.02(1.00-1.04)
1968/57570
1.07(1.02-1.13)
1094/54212
1.03(0.97-1.10)
1315/46229
0.99(0.93-1.06)
1.04(1.00-1.08)
49/1280
1.31(0.98-1.75)
50/2239
0.98(0.73-1.30)
57/1303
1.46(1.10-1.93)
1.23(1.04-1.46)
5453/176998
1.00
6954/423378
1.00
3141/115504
1.00
1.00
20769/585447
1.00(0.97-1.04)
14222/717365
1.02(0.99-1.05)
9424/308701
1.00(0.96-1.05)
1.01(0.99-1.03)
8824/262693
1.02(0.98-1.06)
3883/194805
1.03(0.98-1.08)
3902/128119
1.00(0.95-1.05)
1.02(0.99-1.04)
329/9284
1.01(0.90-1.14)
187/8928
1.03(0.88-1.20)
285/7903
1.15(1.00-1.31)
1.06(0.98-1.14)
1022/33785
1.00
990/56661
1.00
743/26137
1.00
9216/281293
1.01(0.94-1.08)
4533/226825
0.98(0.92-1.06)
4948/167557
0.97(0.90-1.06)
16651/481173
0.98(0.91-1.05)
11831/631911
0.96(0.89-1.03)
7531/255127
0.96(0.89-1.05)
8486/238170
0.97(0.90-1.04)
7892/429078
0.94(0.87-1.01)
3530/111406
0.94(0.86-1.03)
0.01
0.01
0.36
<0.001
Cauliflower
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.002
0.01
0.73
<0.001
Brussel Sprouts
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.05
0.56
0.18
0.03
Cabbage
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.47
0.18
0.48
0.11
Carrots
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
0.28
0.01
0.16
Pooled Results||
1.00
0.99(0.95-1.03)
0.97(0.93-1.01)
0.95(0.91-0.99)
9471/288351
1.00
6019/343499
1.00
3257/112284
1.00
1.00
20693/586063
1.00(0.97-1.03)
12874/647498
1.01(0.97-1.04)
8551/279173
0.97(0.92-1.01)
1.00(0.98-1.01)
5016/153415
0.98(0.94-1.02)
5890/325553
1.02(0.98-1.07)
4610/156620
0.99(0.94-1.04)
1.00(0.97-1.02)
195/6592
0.90(0.77-1.04)
463/27926
0.98(0.89-1.09)
334/12150
0.90(0.79-1.01)
0.94(0.87-1.00)
32442/937828
1.00
22127/1160624
1.00
13984/464662
1.00
1.00
2295/74142
0.93(0.89-0.97)
2255/128107
0.93(0.89-0.97)
2101/71111
1.01(0.96-1.06)
0.95(0.93-0.98)
553/19369
0.90(0.82-0.98)
737/46004
0.94(0.87-1.02)
575/20966
1.02(0.93-1.11)
1.01(0.97-1.07)
85/3083
0.90(0.73-1.13)
127/9740
0.82(0.68-0.99)
92/3489
0.96(0.77-1.18)
0.88(0.79-0.99)
7402/213926
1.00
8108/421768
1.00
4408/145982
1.00
1.00
15689/459963
0.98(0.95-1.01)
10028/506893
0.97(0.94-1.00)
7736/257029
0.99(0.95-1.03)
0.98(0.96-1.00)
10868/314164
0.99(0.96-1.03)
6433/376467
0.95(0.91-0.99)
3993/134219
0.99(0.94-1.04)
0.95(0.93-0.97)
1416/46368
1.00(0.94-1.07)
677/39347
0.97(0.89-1.06)
615/22998
0.99(0.90-1.08)
0.99(0.95-1.04)
9543/285613
1.00
5794/320095
1.00
4234/150851
1.00
1.00
14224/399084
1.02(0.99-1.05)
10111/527647
1.02(0.98-1.05)
6319/205303
0.99(0.96-1.04)
1.01(0.99-1.03)
8168/207480
1.02(0.98-1.05)
7627/412032
1.01(0.97-1.05)
5157/172544
1.02(0.97-1.06)
1.01(0.99-1.04)
1234/33513
0.98(0.92-1.04)
1714/84701
0.99(0.93-1.05)
1042/31530
1.04(0.97-1.13)
1.00(0.96-1.04)
796/25263
1.00
1748/101648
5850/180783
0.97(0.90-1.05)
6236/347973
19073/561111
1.01(0.93-1.08)
12380/668622
9655/267264
1.00(0.93-1.08)
4882/226232
0.003
Beans or lentils
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.03
0.58
0.48
0.31
Tofu or soybeans
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
<0.001
0.01
0.71
0.001
Eggplant or zucchini
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.13
0.11
0.91
0.97
Green Pepper
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled results||
0.87
0.45
0.11
0.65
Tomatoes
NHS*
Adjusted hazard ratio§
NHS II †
0.37
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
1.00
556/18773
1.00
1.00
0.99(0.93-1.04)
2725/90927
0.97(0.88-1.06)
0.98(0.94-1.02)
1.04(0.98-1.09)
8910/307983
0.95(0.87-1.04)
1.01(0.97-1.05)
1.03(0.97-1.10)
4561/142545
0.96(0.87-1.06)
1.01(0.97-1.05)
12451/316424
1.00
9004/522242
1.00
5630/180698
1.00
1.00
10894/263324
0.98(0.96-1.01)
10066/506040
1.01(0.98-1.04)
6121/178794
1.03(0.99-1.07)
1.00(0.98-1.02)
4336/100943
0.97(0.93-1.01)
5069/263935
0.98(0.95-1.02)
2309/62679
1.03(0.97-1.09)
0.99(0.96-1.01)
565/13840
0.92(0.84-1.01)
1107/52259
0.99(0.93-1.06)
257/7152
0.94(0.82-1.07)
0.96(0.92-1.01)
0.08
0.71
0.14
Onions
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.05
0.39
0.92
0.10
*Follow-up in Nurses’ Health Study was from 1984 to 2010 (cases/persons-years).
† Follow-up in Nurses’ Health Study II was from 1991-2011
‡ Follow-up in Health Professionals Follow-up study was from 1986 to 2010.
§ Adjusted for age, race/ethnicity (white, African-American, Asian, Hispanic, other), body mass index, current smoking status, physical activity,
weight change per food frequency questionnaire cycle, menopausal status (NHS and NHS II), alcohol intake, current oral contraceptive use (NHS II),
analgesic use (nonsteroidal antiinflammatory drugs, acetaminophen, aspirin), family history of hypertension, total energy intake, animal flesh
intake (combination of processed and unprocessed red meat, poultry and seafood), whole grains, sugar-sweetened beverage intake, artificiallysweetened diet beverage intake.
|| Pooled hazard ratios of the three cohorts using a fixed effects model.
Supplementary Table S3: Pooled hazard ratios (95% confidence intervals) of incident hypertension for individual fruit consumption in Nurses’
Health Study, Nurses’ Health Study II and Health Professional Follow-up Study
Individual Fruits
Raisins or grapes
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
||
Pooled Results
<1 per month
Consumption Levels
1-3 per month
1-3 per week
≥4 per week
10178/294047
1.00(reference)
8875/432559
1.00
5053/164791
1.00
1.00
16772/487292
0.97(0.94-0.99)
11704/612722
0.99(0.96-1.02)
6799/223815
0.99(0.96-1.04)
0.98(0.96-1.00)
7140/212014
0.93(0.90-0.96)
4099/254714
0.94(0.91-0.98)
3744/131080
0.98(.93-1.02)
0.94(0.92-0.97)
1285/41068
0.92(0.86-0.97)
568/44480
0.82(0.75-0.90)
1156/40542
1.00(0.93-1.07)
0.92(0.89-0.96)
1578/44977
1.00
1770/92667
1.00
1199/38653
1.00
1.00
9704/290095
0.94(0.89-0.99)
7978/397011
0.96(0.91-1.02)
4591/149223
0.97(0.91-1.04)
0.94(0.90-0.97)
14719/417845
0.93(0.88-0.99)
11077/608919
0.95(0.90-1.01)
7041/239658
0.96(0.89-1.03)
0.95(0.91-0.98)
9374/281504
0.90(0.85-0.96)
4421/245878
0.93(0.87-0.99)
3921/132694
0.93(0.86-1.00)
0.91(0.88-0.95)
2723/90470
1.00
2229/123798
1.00
1633/55083
1.00
1.00
10024/317214
1.01(0.97-1.06)
8247/431346
1.01(0.97-1.06)
4023/137001
0.95(0.89-1.01)
1.00(0.97-1.03)
16045/455721
1.03(0.98-1.07)
11311/603134
1.03(0.98-1.08)
6778/228793
0.95(0.89-1.01)
1.01(0.98-1.04)
6583/171016
1.03(0.98-1.08)
3459/186197
0.99(0.93-1.04)
43318/139350
0.95(0.89-1.01)
0.99(0.96-1.03)
5657/165795
1.00
21106/613507
0.96(0.93-0.99)
8010/237646
0.96(0.92-0.99)
602/17473
0.99(0.91-1.09)
P Trend
<0.001
<0.001
0.73
<0.001
Apples or pears
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
0.003
0.07
0.03
<0.001
Bananas
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
||
Pooled Results
0.65
0.28
0.43
0.46
Strawberries
NHS*
Adjusted hazard ratio§
0.47
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
3800/205254
1.00
5188/167653
1.00
1.00
14031/720867
1.03(0.99-1.07)
9062/306494
0.98(0.94-1.02)
0.98(0.96-1.00)
6762/381876
1.02(0.98-1.07)
2329/80359
1.03(0.97-1.09)
0.99(0.97-1.02)
653/36478
1.02(0.93-1.12)
173/5723
1.00(0.85-1.18)
1.01(0.95-1.07)
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
19275/555984
1.00
14159/740832
1.00
13442/395363
0.98(0.96-1.00)
8786/469293
0.96(0.93-0.99)
2520/78823
0.94(0.89-0.98)
2148/124999
0.95(0.90-0.99)
138/4252
0.89(0.75-1.07)
153/9351
0.90(0.76-1.07)
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
10156/331043
1.00
1.00
5542/192300
0.95(0.92-0.99)
0.97(0.95-0.98)
970/34108
0.97(0.90-1.05)
0.95(0.92-0.98)
84/2777
1.03(0.81-1.30)
0.92(0.83-1.03)
5644/167350
1.00
5439/291361
1.00
2573/84536
1.00
1.00
13069/384701
1.01(0.97-1.04)
11451/605132
0.93(0.90-0.97)
5559/183363
0.98(0.93-1.03)
0.97(0.95-0.99)
12973/376109
1.01(0.98-1.05)
7237/387572
0.95(0.91-0.99)
6312/214668
0.98(0.92-1.03)
0.98(0.96-1.01)
3689/106260
1.00(0.96-1.06)
1119/60410
0.89(0.83-0.96)
2308/77661
0.96(0.90-1.02)
0.97(0.93-1.00)
6122/185505
1.00
6133/324975
1.00
473/154738
1.00
1.00
18155/524919
1.01(0.98-1.05)
12283/632052
1.01(0.98-1.05)
8216/271786
1.00(0.96-1.04)
1.02(0.99-1.04)
9979/290092
1.03(0.99-1.07)
6148/349298
1.03(0.99-1.08)
3377/118507
0.99(0.94-1.05)
1.02(1.00-1.05)
1119/33905
1.00(0.93-1.07)
682/38152
1.06(0.97-1.15)
426/15197
0.95(0.85-1.06)
1.01(0.96-1.06)
27319/802498
1.00
21481/1130042
5928/171971
1.02(0.99-1.05)
3023/166336
1628/45532
0.98(0.93-1.03)
605/39632
500/14420
1.01(0.92-1.10)
137/8466
0.76
0.22
0.79
Blueberries
0.01
0.01
0.46
0.01
Oranges
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results¶
0.68
0.02
0.25
0.17
Peaches, apricots or
plums
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
||
Pooled Results
0.68
0.09
0.54
0.30
Prunes
NHS*
Adjusted hazard ratio§
NHS II †
0.77
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
1.00
14065/476649
1.00
1.00
1.00(0.96-1.04)
2007/61753
0.98(0.94-1.030
1.01(0.99-1.03)
0.94(0.86-1.02)
519/16423
0.94(0.86-1.03)
0.96(0.93-1.00)
1.05(0.89-1.25)
161/5402
0.86(0.73-1.02)
0.99(0.92-1.06)
28895/799042
1.00
20442/1068957
1.00
11682/387039
1.00
1.00
3951/116154
0.98(0.95-1.02)
4227/237179
0.95(0.92-0.98)
4189/140513
0.99(0.95-1.02)
0.97(0.95-0.99)
303/9843
0.85(0.76-0.95)
557/36621
0.91(0.84-0.99)
817/30551
0.95(0.88-1.02)
0.92(0.87-0.96)
20/651
0.99(0.64-1.54)
20/1718
0.77(0.49-1.19)
64/2124
0.98(0.76-1.26)
0.94(0.77-1.14)
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
5431/165133
1.00
6053/340890
1.00
19041/537365
1.02(0.98-1.05)
14423/735796
1.03(0.99-1.06)
9725/292373
1.06(1.02-1.10)
4585/257086
1.04(1.00-1.09)
1178/39551
1.10(1.03-1.18)
185/10703
0.93(0.80-1.08)
HPFS ‡
Adjusted hazard ratio§
Pooled Results||
3820/130649
1.00
1.00
9305/303121
1.05(1.01-1.10)
1.03(1.01-1.05)
3148/107455
1.08(1.02-1.14)
1.06(1.03-1.08)
497/19002
1.08(0.97-1.19)
1.07(1.01-1.13)
0.68
0.02
0.16
Avocado
NHS*
Adjusted hazard ratio§
NHS II †
Adjusted hazard ratio§
HPFS ‡
Adjusted hazard ratio§
||
Pooled Results
0.01
<0.001
0.24
<0.001
Cantaloupe
0.01
0.59
0.09
0.002
*Follow-up in Nurses’ Health Study was from 1984 to 2010 (cases/persons-years).
† Follow-up in Nurses’ Health Study II was from 1991-2011
‡ Follow-up in Health Professionals Follow-up study was from 1986 to 2010.
§ Adjusted for age, race/ethnicity (white, African-American, Asian, Hispanic, other), body mass index, current smoking status, physical activity,
weight change per food frequency questionnaire cycle, menopausal status (NHS and NHS II), alcohol intake, current oral contraceptive use (NHS II),
analgesic use (nonsteroidal antiinflammatory drugs, acetaminophen, aspirin), family history of hypertension, total energy intake, animal flesh
intake (combination of processed and unprocessed red meat, poultry and seafood), whole grains, sugar-sweetened beverage intake, artificiallysweetened diet beverage intake.
|| Pooled hazard ratios of the three cohorts using a fixed effects model.
Supplementary Table S4: Pooled hazard ratios (95% confidence intervals) of incident hypertension for 8-year change in total whole fruits and total
vegetables consumption in Nurses’ Health Study, Nurses’ Health Study II and Health Professional Follow-up Study
Change in consumption levels
Fruits and
Vegetables
No change
(±0.9 per
week)
Decreased
≥7 per week
Decreased
4.0-6.9 per week
Decreased
1.0-3.9 per week
2,354/66,202
1.01(0.95-1.08)
1,571/65,946
1.04(0.97-1.12)
816/27,039
1.02 (0.93-1.13)
1.02 (0.98-1.07)
1,748/49,574
0.99(0.94-1.06)
1,360/55,944
1.03(0.96-1.10)
632/19,260
1.09(0.99-1.20)
1.02(0.98-1.06)
3,299/94,925
0.98(0.93-1.02)
2,934/121,711
0.99(0.94-1.04)
1,314/42,010
1.00 (0.93-1.08)
0.99 (0.96-1.02)
5,077/143,288
1.02(0.96-1.07)
2,865/110,537
1.00(0.94-1.07)
1,555/49,770
1.00(0.91-1.10)
1,851/53,076
0.98(0.92-1.04)
1,139/45,945
0.98(0.91-1.06)
666/21,426
0.98(0.87-1.10)
2,658/72,338
1.03(0.97-1.09)
1,695/71,508
0.95(0.89-1.02)
1,036/32,524
0.90(0.81-1.00)
2,020/56,315
1.00
1,497/60,984
1.00
815/26,732
1.00
1.02(0.98-1.06)
0.99(0.95-1.04)
1.00(0.96-1.04)
5,869/166,514
1.01(0.95-1.07)
3,560/139,732
1.01(0.94-1.08)
1,865/59,176
1.00(0.91-1.10)
1,558/42,681
1.02(0.95-1.09)
1,048/41,284
1.01(0.92-1.09)
557/17,663
0.98(0.87-1.10)
1.01(0.97-1.05)
1.01(0.96-1.06)
Increased
1.0-3.9 per week
Increased
4.0-6.9 per week
Increased
≥7 per week
2,148/60,205
0.98(0.93-1.03)
1,492/68,459
0.92(0.87-0.98)
877/29,790
0.93(0.85-1.01)
0.95(0.92-0.98)
2,948/84,062
0.96(0.91-1.01)
1,900/89,135
0.93(0.87-0.98)
1,248/44,187
0.90(0.84-0.98)
0.94(0.91-0.97)
2,431/67,677
1.00(0.94-1.06)
1,899/80,562
0.98(0.91-1.05)
1,042/35,828
0.92(0.83-1.02)
1,623/47,420
0.95(0.89-1.01)
1,366/59,831
0.96(0.89-1.03)
779/25,268
0.87(0.78-0.97)
4,487/126,164
0.98(0.93-1.03)
5,511/254,335
0.95(0.90-1.01)
2,290/75,629
0.91(0.83-0.99)
1.00
0.98(0.94-1.02)
0.97(0.92-1.01)
0.98(0.94-1.01)
1,935/54,409
0.98(0.92-1.05)
1,390/58,467
0.96(0.88-1.03)
749/25,287
0.90(0.81-1.00)
1,476/40,911
1.00
1,129/45,326
1.00
639/19,261
1.00
1,938/53,646
1.00(0.93-1.07)
1,509/64,347
0.95(0.88-1.03)
868/28,346
0.92(0.83-1.02)
1,459/40,683
0.97(0.91-1.05)
1,189/51,779
0.95(0.87-1.03)
631/21,710
0.87(0.78-0.97)
5,912/167,435
0.96(0.90-1.02)
6,147/282,766
0.93(0.87-0.99)
2,874/95,736
0.91(0.83-0.99)
0.96(0.91-1.00)
1.00
0.97(0.92-1.01)
0.94(0.90-0.99)
0.94(0.90-0.97)
Linear
P
Trend
Total Fruits||
NHS *
§
Adjusted HR
NHS II †
Adjusted HR§
HPFS‡
Adjusted HR§
Pooled Results¶
3,838/106,256
3,812/105,055
1.00(reference) 1.00(0.96-1.05)
3,752/149,998
2,963/132,509
1.00
0.93(0.88-0.98)
1,639/51,582
1,657/53,310
1.00
0.97(0.91-1.04)
1.00
0.97(0.94-1.00)
0.17
<0.001
<0.001
<0.001
Total
Vegetables||
NHS *
Adjusted HR§
NHS II†
Adjusted HR§
HPFS‡
Adjusted HR§
Pooled results¶
Total Fruits and
Vegetables
NHS *
Adjusted HR§
NHS II†
Adjusted HR§
HPFS‡
Adjusted HR§
Pooled results¶
0.08
0.10
0.20
0.007
0.02
<0.001
0.09
<0.001
* Follow-up in Nurses’ Health Study was from 1994 to 2010 (cases/persons-years).
† Follow-up in Nurses’ Health Study II was from 1999 to 2011 (cases/persons-years).
‡ Follow-up in Health Professionals Follow-up study was from 1994 to 2010 (cases/persons-years).
§ Adjusted for age, race/ethnicity (white, African-American, Asian, Hispanic, other), body mass index at baseline, smoking status (never/never,
never/current, past/past, past/current, current/past, or current/current), physical activity, menopausal status (in NHS and NHS II), current oral
contraceptive use (in NHS II), analgesic use (acetaminophen, aspirin, other nonsteroidal anti-inflammatory drugs), family history of hypertension,
initial and change values of alcohol intake, total energy intake, animal flesh intake (combination of processed and unprocessed red meat, poultry
and seafood), whole grains, sugar-sweetened beverage intake, artificially-sweetened beverage intake (all in quintiles).
||Multivariable model including initial and change values of total vegetables was mutually adjusted for initial and change values of total fruits
intake (quintiles for variables other than change variables of total vegetable intake and total fruit intake, and five categories for change variables of
total vegetable intake and total fruit intake).
¶Pooled hazard ratios of the three cohorts using a fixed effects model.
Supplementary Table S5: Pooled hazard ratios (95% confidence intervals) of incident hypertension for change in individual fruit and vegetable consumption in
Nurses’ Health Study, Nurses’ Health Study II and Health Professional Follow-up Study
Change in consumption levels
Individual Fruits
and Vegetables
Raisins or grapes*†
Apples or pears*†
Bananas*†
Strawberries*†
Blueberries*†
Oranges*†
Peaches, apricots or
plums*†
Prunes*†
Avocado*†
Cantaloupe*†
String beans*†
Celery*†
Corn*†
Yams or sweet
potatoes*†
Peas or lima
beans*†
Lettuce*†
Kale*†
Spinach*†
Broccoli*†
Cauliflower*†
Brussel Sprouts*†
Cabbage*†
Carrots*†
Beans or lentils*†
Tofu or soybeans*†
Eggplant or
zucchini*†
Green Pepper*†
Tomatoes*†
Onions*†
Decrease
≥2 per week
Decrease
1.0-1.9 per week
Decrease
0.5-0.9 per week
No change
(±0.4 per week)
Increase
0.5-0.9 per week
Increase
1.0-1.9 per week
Increase
≥2 per week
Linear
P Trend
0.98 (0.91-1.05)
1.02 (0.98-1.07)
1.01 (0.96-1.07)
1.08 (0.97-1.21)
0.96 (0.91-1.02)
0.99 (0.95-1.04)
1.04 (1.01-1.08)
1.02 (0.98-1.05)
1.02 (0.97-1.07)
0.99 (0.92-1.07)
0.99 (0.95-1.03)
1.00 (0.97-1.03)
1.02 (0.98-1.05)
0.98 (0.94-1.02)
1.01 (0.98-1.04)
0.98 (0.95-1.02)
0.98 (0.95-1.02)
1.00(reference)
1.00
1.00
1.00
1.00
1.00
0.98 (0.95-1.00)
1.00 (0.96-1.04)
0.99 (0.95-1.02)
0.99 (0.96-1.02)
0.99 (0.97-1.02)
0.97 (0.94-1.01)
0.97 (0.94-1.01)
1.01 (0.97-1.04)
1.00 (0.97-1.03)
1.00 (0.96-1.04)
0.97 (0.93-1.02)
0.96 (0.93-0.99)
0.94 (0.90-0.99)
0.99 (0.95-1.03)
0.99 (0.96-1.02)
1.01 (0.94-1.08)
0.96 (0.89-1.03)
0.96 (0.91-1.00)
0.04
0.08
0.57
0.47
0.32
0.26
1.03 (0.95-1.13)
1.02 (0.98-1.07)
1.00 (0.98-1.04)
1.00
1.00 (0.97-1.03)
1.01 (0.98-1.05)
1.00 (0.94-1.06)
0.66
1.04 (0.92-1.17)
0.99 (0.92-1.07)
0.98 (0.86-1.11)
1.00 (0.90-1.11)
1.06 (0.94-1.19)
1.00 (0.95-1.06)
1.01 (0.96-1.06)
1.00 (0.95-1.05)
0.99 (0.94-1.04)
1.03 (0.98-1.10)
0.98 (0.94-1.03)
0.99 (0.96-1.02)
0.99 (0.95-1.02)
1.02 (0.98-1.06)
1.01 (0.98-1.05)
1.00
1.00
1.00
1.00
1.00
1.00
1.00 (0.96-1.04)
0.97 (0.94-1.01)
1.00 (0.97-1.03)
0.99 (0.95-1.03)
1.02 (0.98-1.06)
1.02 (0.98-1.06)
0.94 (0.87-1.02)
0.99 (0.93-1.07)
1.03 (0.99-1.07)
1.04 (0.99-1.09)
1.03 (0.98-1.08)
0.99 (0.95-1.04)
0.91 (0.85-0.98)
0.92 (0.81-1.05)
1.03 (0.95-1.11)
0.97 (0.90-1.04)
1.09 (1.02-1.17)
1.06 (0.94-1.19)
0.01
0.08
0.08
0.81
0.05
0.60
0.91 (0.70-1.20)
1.03 (0.93-1.13)
0.96 (0.92-1.00)
1.00
0.98 (0.95-1.01)
0.99 (0.93-1.05)
0.96 (0.83-1.10)
0.87
0.95 (0.84-1.09)
0.96 (0.91-1.01)
0.97 (0.94-1.01)
1.00
0.98 (0.95-1.02)
1.02 (0.97-1.07)
1.03 (0.90-1.17)
0.10
1.00 (0.95-1.04)
0.71 (0.50-1.01)
1.00 (0.88-1.13)
0.98 (0.88-1.09)
0.92 (0.81-1.06)
1.05 (0.83-1.34)
0.98 (0.84-1.14)
1.05 (1.00-1.11)
0.91 (0.79-1.06)
1.24 (0.97-1.58)
1.03 (0.99-1.08)
0.85 (0.71-1.01)
0.97 (0.92-1.04)
1.02 (0.97-1.06)
1.02 (0.96-1.08)
0.92 (0.83-1.02)
0.99 (0.93-1.06)
1.03 (0.99-1.08)
1.05 (0.99-1.11)
1.09 (0.94-1.27)
1.02 (0.97-1.08)
0.93 (0.85-1.01)
0.97 (0.93-1.01)
1.01 (0.97-1.05)
0.99 (0.96-1.03)
0.96 (0.91-1.01)
0.98 (0.95-1.02)
1.01 (0.97-1.06)
1.01 (0.97-1.05)
1.02 (0.93-1.12)
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.01 (0.96-1.07)
1.01 (0.96-1.06)
0.98 (0.95-1.01)
0.98 (0.94-1.03)
1.00 (0.96-1.04)
1.01 (0.97-1.05)
1.02 (0.98-1.06)
0.98 (0.94-1.03)
1.00 (0.97-1.04)
0.93 (0.88-0.98)
1.02 (0.98-1.06)
0.93 (0.85-1.02)
0.97 (0.93-1.01)
0.99 (0.95-1.03)
1.06 (1.00-1.11)
1.01 (0.92-1.10)
0.98 (0.93-1.04)
0.98 (0.94-1.02)
0.98 (0.94-1.02)
0.92 (0.85-1.00)
1.01 (0.97-1.05)
0.93 (0.79-1.10)
0.96 (0.90-1.03)
0.94 (0.85-1.04)
1.03 (0.91-1.17)
1.11 (0.93-1.32)
0.97 (0.84-1.12)
0.96 (0.91-1.00)
0.97 (0.88-1.06)
0.86 (0.79-0.94)
0.84
0.93
0.46
0.23
0.13
0.12
0.85
<0.001
0.48
<0.001
1.10 (0.98-1.23)
1.00 (0.94-1.06)
0.99 (0.96-1.03)
1.00
0.98 (0.95-1.02)
1.02 (0.97-1.08)
1.08 (0.98-1.18)
0.67
1.06 (0.97-1.16)
1.01 (0.94-1.08)
0.99 (0.91-1.08)
1.07 (1.01-1.12)
1.01 (0.97-1.05)
1.00 (0.95-1.06)
1.04 (1.00-1.08)
1.03 (0.97-1.08)
0.98 (0.94-1.02)
1.00
1.00
1.00
1.00 (0.96-1.04)
1.01 (0.96-1.06)
1.01 (0.97-1.05)
1.00 (0.96-1.05)
1.03 (1.00-1.07)
0.99 (0.94-1.03)
0.97 (0.91-1.04)
1.02 (0.97-1.08)
1.06 (1.01-1.12)
0.02
0.48
0.08
1.08 (0.85-1.36)
*Adjusted for age, race/ethnicity (white, African-American, Asian, Hispanic, other), body mass index at baseline, smoking status (never/never, never/current,
past/past, past/current, current/past, or current/current), physical activity, menopausal status (in NHS and NHS II), current oral contraceptive use (in NHS II),
analgesic use (acetaminophen, aspirin, other nonsteroidal anti-inflammatory drugs), family history of hypertension, initial value of total fruit intake (quintiles),
initial and change values of alcohol intake, total energy intake, animal flesh intake (combination of processed and unprocessed red meat, poultry and seafood),
whole grains, sugar-sweetened beverage intake, artificially-sweetened beverage intake, total vegetable intake (quintiles for variables other than change
variables of total vegetable intake, and five categories for change variables of total vegetable intake). And for fruit juices, further adjusted for change values of
total fruit intake (five categories)
†Pooled hazard ratios of the three cohorts using a fixed effects model.