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Department of Preventive Medicine and Public Health, Medical School, Clnica Universidad de Navarra, Irunlarrea 1,
E 31080 Pamplona, Navarra, Spain
b
Department of Maternal and Child Nursing and Public Health, Nursing School, Universidade Federal de Minas Gerais,
Avenida Alfredo Balena, 190. Belo Horizonte, Minas Gerais, CEP 30130-100 Brazil
Received 5 November 2008; received in revised form 7 March 2009; accepted 23 April 2009
KEYWORDS
Hypertension;
Nuts;
Nutrition;
Epidemiology;
Cohort studies
Abstract Background and aims: The consumption of tree nuts could reduce the risk of hypertension, but scarce research has been done to evaluate this potential association. We assessed
the association between nut consumption and the incidence of hypertension among 9919
Spanish university graduates followed-up biennially for a median of 4.3 years.
Methods and results: Food habits were assessed with a validated 136-item food-frequency
questionnaire. Nut consumption was classified into four categories: rarely/never, 1e3/month,
1/week, and 2/week. A participant was classified as an incident case of hypertension when,
being free of hypertension at baseline, he/she subsequently reported a physician-made diagnosis of hypertension in at least one of the follow-up questionnaires. The incidence of hypertension was 12.4 per 1000 person-years. We found no association between nut consumption
and incidence of hypertension after adjusting for sex, age and other dietary and non-dietary
potential confounders (hazard ratio [HR] for those in the highest vs. lowest nut consumption
category Z 0.77 [IC 95%: 0.46e1.30] p Z 0.795). Results were not modified when we stratified
them analyses according to sex or to body mass index.
Conclusion: Our data do not provide evidence for an inverse association between nut consumption and incident hypertension in our cohort. Further results from cohorts and trials with a higher baseline risk of hypertension should be obtained to test this relationship.
2009 Elsevier B.V. All rights reserved.
Abbreviations: CVD, cardiovascular disease; IHD, ischemic heart disease; BP, blood pressure; PHS, Physicians Health Study; SUN Project,
Seguimiento Universidad de Navarra (University of Navarra Follow-up Study); BMI, body mass index; HR, hazard ratio; MET, metabolic
equivalent index; DASH, Dietary Approaches to Stop Hypertension; MDP, Mediterranean dietary pattern.
*
The SUN Study has received funding from the Spanish Government, Instituto de Salud Carlos III (Grants PI030678, PI040233, PI070240,
RD06/0045, and G03/140), the Navarra Regional Government (PI141/2005) and the University of Navarra.
* Corresponding author. Tel.: 34 948 425 600; fax: 34 948 425 649.
E-mail address: mamartinez@unav.es (M.A. Martnez-Gonza
lez).
0939-4753/$ - see front matter 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.numecd.2009.04.013
360
Introduction
Hypertension is a major public health problem, affecting
approximately 1 billion individuals,[1] causing 7.6 million
premature deaths and 6% of all cases of disability-adjusted
life years worldwide [2]. In European countries hypertension prevalence is increasing [3]. Ischemic heart disease
(IHD) and stroke are the two main cardiovascular causes of
mortality around the world, and hypertension explains 47%
and 54% of deaths by IHD and stroke, respectively [2].
Lifestyle modification may lower blood pressure (BP)
[4,5] and reduce the incidence of hypertension. Lifestyle
modification includes weight lost among overweight/obese
individuals [4,5]; increased physical activity [4]; reduced
alcohol consumption [4,5]; adoption of a diet rich in fresh
fruit, vegetables,[5,6] potassium [5] and a reduced sodium
content [4,5,7]. For instance, the DASH diet (Dietary
Approaches to Stop Hypertension) has similar BP lowering
effects to a single drug therapy [7]. In addition, a DASHtype diet has been shown to be associated with a lower
cardiovascular risk in the Nurses Health Study [8].
As is known, nuts are an integral part of the Mediterranean Dietary Pattern (MDP) [9]. MDP has been shown to be
protective against age-related changes in blood pressure
[10]. Results from the PREDIMED randomized trial showed
that a Mediterranean diet enriched with mixed nuts was
able to reduce BP levels to a larger extent than a low-fat
diet during a 3-month follow-up [11]. Moreover, during a 1year follow-up of the PREDIMED trial the arm of the trial
allocated to the Mediterranean diet plus free provision of
nuts exhibited a significant reduction in the prevalence of
the metabolic syndrome, with a small reduction in hypertension prevalence after 1 year [12]. However, in that trial
most participants initially had hypertension at baseline.
Also, recently the Physicians Health Study (PHS) reported
a lower risk of hypertension for those who consumed nuts
on a daily basis [13]. This is plausible since raw nuts have
a high content of magnesium, potassium and unsaturated
fatty acids, and only small amounts of sodium. However,
with the exception of the PREDIMED trial [11,12] and the
PHS cohort [13] there is scarce information about the
ability of a nut-rich diet to prevent the incidence of
hypertension.
The aim of our study was to assess the association
between the consumption of tree nuts and the incidence of
hypertension in a large prospective cohort of university
graduates in Spain.
Methods
Subjects
The SUN project (Seguimiento Universidad de Navarra) is
a dynamic cohort comprised exclusively of Spanish university graduates. The recruitment of participants started in
December 1999 and it is permanently open. Information is
collected using self-administered questionnaires mailed
every 2 years. The objectives and methods of this project
have been detailed elsewhere [14].
By April 2008, 19,519 participants were recruited and
had answered the baseline questionnaire. Those
Dietary assessment
The baseline questionnaire included a 136-item semiquantitative food-frequency questionnaire that was previously validated in Spain, it also included open-label questions for information about use of dietary supplements [15].
The questionnaire was adapted from the Willetts questionnaire and it was based on typical portion sizes. Participants selected one of 9 options for the frequency of intake
in the previous year for each food item (rarely/never, 1e3/
month, 1/week, 2e4/week, 5e6/week, daily, 2e3/day,
4e6/day, 6/day). We asked the participants how often,
on average, they had consumed nuts during the previous
year. Information on nut consumption was collected in
a single aggregated question, which included walnuts,
almonds, hazelnuts or peanuts. These varieties represent
more than 95% of the total nut consumption in the Spanish
population [16]. Due to the small number of subjects in the
categories corresponding to a higher frequency of nut
consumption, we merged the upper categories to obtain
more stable estimates as has been previously reported in
similar studies [17,18]. Thus, in all our analyses, we classified nut consumption into four categories: rarely/never,
1e3/month, 1/week, and 2/week.
The food-frequency questionnaire was also used to
obtain information on other nutrients that could act as
potential confounders. Nutrient intake scores were
computed using an ad hoc computer program. A trained
dietitian updated the nutrient data bank using the most upto-date food composition tables for Spain [19,20]. We
calculated the amount of each of these nutrients without
taking into account the share allocated to nut consumption,
and adjusted the estimates for these new variables.
The intakes of foods and nutrients (other than nut
consumption) were adjusted for total energy intake applying
the residual method, and separate regression models were
run to obtain the residuals for men and women [21].
Hypertension ascertainment
The baseline questionnaire inquired about the most recent
systolic and diastolic blood pressure, use of antihypertensive drugs and whether the participant had received
a medical diagnosis of hypertension. A participant was
considered to have hypertension at baseline if he/she
reported a medical diagnosis of hypertension, was under
antihypertensive medication, or reported a systolic blood
pressure 140 mmHg and/or a diastolic blood pressure
90 mmHg [1].
New cases of hypertension were defined as those individuals reporting a physician-made diagnosis of hypertension in the follow-up questionnaire and who did not have
hypertension at baseline.
A validation study showed an adequate validity for the
self-reported diagnosis of hypertension in this highly
educated cohort [25].
361
Statistical analysis
For each participant we computed person-time of follow-up
from the date of return of the baseline questionnaire to the
date of return of the last follow-up questionnaire or to the
date of the physician-made diagnosis of hypertension,
whichever occurred first.
Hazard ratios (HRs) for the three upper categories of nut
consumption and their 95% CIs were estimated with Cox
proportional hazard models, adjusting for potential
confounders and taking as the reference category those
subjects who consumed nuts never or rarely.
The initial model included only age and sex as covariates
(model 1). We fitted an additional model adding universally
accepted risk factors for hypertension (family history of
hypertension [yes, no] and hypercholesterolemia [yes, no])
and variables closely associated with lifestyle and healthrelated habits (smoking [never, past, current, not specified], educational level [degree 1: 3 years of university
study, degree 2: 4e5 years of university study, degree 3:
6e9 years of university study], and physical activity [MET
hour/week, continuous]) (model 2). To assess the possibility of confounding by other dietary variables, we fitted
an additional model adding several dietary factors that
have been related to the risk of hypertension in some
studies (total energy intake, alcohol intake, the intake of
polyunsaturated fatty acids, monounsaturated fatty acids,
saturated fatty acids, proteins, carbohydrates, sodium,
magnesium, potassium, calcium, folic acid, vitamin E,
mineral supplements, caffeine intake, and fiber intake)
(model 3). Finally, we fitted a last model adding BMI (body
mass index) at baseline, and weight change during followup [lost, gain, equal] (model 4).
We also included a separate model adjusting for other
food groups instead of macro and micronutrients to avoid
the possibility of over-adjustment bias (model 5).
To assess whether a multiplicative interaction existed
between nut consumption and sex, we introduced
a product-term (nut sex) in the fully adjusted model. We
also assessed interaction between nut consumption and
overweight status (nut BMI), dichotomizing BMI (<25 or
25 kg/m2) and nut consumption (never or else). To assess
multiplicative interactions, we introduced interaction
terms and then compared both models, the one with and
the one without the product-term using the likelihood ratio
test.
Analyses were performed with SPSS version 15.0 (SPSS
Inc, Chicago, IL). All p values are 2-tailed. Statistical
significance was set at p < 0.05.
Results
We observed five hundred and forty two new cases of hypertension (341 men and 201 women) during a median follow-up
of 4.3 years (mean Z 4.5 years). The incidence of hypertension in our population was 12.4 per 1000 person-years.
Table 1 shows the non-dietary and dietary characteristics of participants according to their categories of nut
consumption. Participants belonging to the highest category of nut consumption were more likely to be men, older,
non-smokers, physically more active and reported a higher
362
Table 1
1e3/month
1/week
2/week
N Z 2089
N Z 4572
N Z 1972
N Z 1286
1463 (70.0)
34.6 10.2
2859 (62.5)
35.9 10.5
1121 (56.8)
36.4 10.5
698 (54.3)
39.6 11.4
515 (24.7)
528 (25.3)
22.9 20.8
1205 (26.4)
1093 (23.9)
23.7 21.2
504 (25.6)
487 (24.7)
24.6 20.7
415 (32.3)
246 (19.1)
28.2 26.0
800 (38.3)
373 (17.9)
23.0 3.3
1710 (37.4)
918 (20.1)
23.2 3.2
739 (37.5)
390 (19.8)
23.2 3.1
493 (38.3)
341 (26.5)
23.2 3.2
351 (16.8)
590 (28.2)
1148 (55.0)
2166 594
10 9
59 41
712 (15.6)
1296 (28.3)
2564 (56.1)
2350 582
10 9
56 39
323 (16.4)
479 (24.3)
1170 (59.3)
2523 564
11 9
55 38
241 (18.7)
344 (26.7)
701 (54.5)
2665 581
11 11
52 40
37 8
43 9
16 4
273 44
109 17
24 9
4691 2198
4509 1107
398 75
1199 391
371 151
72
391 237
603 322
10 16
381 198
293 261
187 58
59 33
119 61
37 9
43 9
16 4
274 45
107 17
25 10
4641 2064
4480 1135
398 71
1159 357
363 141
72
414 280
587 285
9 14
381 193
259 244
187 56
57 32
118 53
37 9
44 9
17 4
270 43
107 15
26 9
4786 2218
4548 1005
408 70
1159 367
376 139
82
406 205
610 262
9 13
372 185
238 231
184 57
55 29
121 58
34 9
45 9
19 4
264 48
107 17
30 11
4411 2622
4909 1133
458 81
1194 389
421 136
11 3
467 286
649 272
10 15
340 196
244 247
166 64
53 31
128 62
Sex [n (%)]
Female
Age
Smoking status [n (%)]
Former smokers
Current smokers
Physical activity during leisure
time (MET s-h/w)
Family history of hypertension [n (%)]
Hypercholesterolemia [n (%)]
BMI (kg/m2)
363
Hazard ratios (HRs) and 95% CIs of hypertension according to nut consumption.
Nut consumption
New cases
of hypertension
Person-years
Rate (cases per
1000 person-years)
Model 1a
Model 2b
Model 3c
Model 4d
Model 5e
Never/rarely
1e3/Month
1/Week
2/Week
91
250
128
73
9136
9.9
20 404
12.2
8633
14.8
5476
13.3
1
1
1
1
1
0.98
0.98
0.98
0.99
1.08
1.17
1.19
1.16
1.17
1.23
(ref.)
(ref.)
(ref.)
(ref.)
(ref.)
(0.71e1.35)
(0.71e1.35)
(0.71e1.36)
(0.72e1.38)
(0.85e1.38)
(0.83e1.66)
(0.84e1.68)
(0.81e1.67)
(0.81e1.68)
(0.93e1.63)
0.84
0.87
0.73
0.77
0.91
(0.57e1.24)
(0.59e1.29)
(0.44e1.21)
(0.46e1.30)
(0.66e1.26)
P for trend
0.673
0.833
0.565
0.795
0.746
Discussion
In this prospective cohort study, we found no evidence for
an inverse association between nut consumption and incident hypertension. These results are in agreement with
a randomized clinical trial that evaluated the effects of nut
consumption on selected markers of the metabolic
syndrome, and found that mean blood-pressure values only
slightly decreased, but the observed changes were not
statistically significant [26].
On the other hand, in the PREDIMED randomized trial,
a reduction in mean BP was observed in both interventional groups using either a nut-enriched or an olive oilenriched Mediterranean diet [11]. In the group allocated
to a Mediterranean diet plus free provision of tree nuts,
the PREDIMED trial participants received 30 g/d of raw
tree nuts (15 g/d of walnuts, 7.5 g/d of hazelnuts and
7.5 g/d of almonds). In addition to its experimental design
(different from the observational nature of the present
cohort), the PREDIMED trial differs methodologically from
the SUN cohort. First of all, subjects in the PREDIMED trial
consumed more nuts than those belonging to the highest
category of nut consumption in the SUN cohort; in addition, the PREDIMED trial only included participants at high
cardiovascular risk and many participants were taking
antihypertensive drug treatment. Any potential synergism
between lifestyle factors and pharmacological agents for
management of hypertension would have contributed to
a stronger effect [27]. The PREDIMED trial did not evaluate nut consumption separately from the overall
364
vitamin E, but a lower intake of carbohydrate and saturated
fatty acids.
In Spain the varieties of nuts most widely consumed are
peanuts, walnuts, hazelnuts and almonds [16]. The last two
are rich in oleic acid that offers a lowering effect on BP as
has already been reported [11]. Walnuts are rich in alinolenic acid, and its anti-inflammatory properties are
being evaluated. This feature could prevent the progression
of atherosclerosis, which is an important risk factor for
hypertension [29]. Fiber intake could protect against
hypertension through weight reduction due to the influence
on satiety and energy intake [30]. Potassium [5] also offers
a lowering effect on BP.
Other explanations make it also likely that a high nut
consumption might be able to reduce BP, but this BP
lowering effect may be insufficient to prevent the development of hypertension in our study. This fact could be
occurring because: (1) nut consumption might have been
underestimated since we did not compute the amount
included in sauces, cheeses, cereals, and desserts[16]; (2)
information about nut consumption was collected only in
the baseline questionnaire and we were not able to assess
changes in nut consumption during follow-up; (3) we were
not able to isolate the role of each specific type of nut; so if
only some kind of nut were protective against the development of hypertension, the aggregation of consumption
data in a single question would very probably underestimate its specific effect; (4) we could not examine the
influence of the preparation method (salted, roasted or raw
nuts) on the risk of hypertension; (5) the case ascertainment for hypertension was based on self-reported data and
it is well known that about one third of hypertensive individuals are not aware of their status [1]; however, we have
shown an adequate validity of this self-report of a physician-made diagnosis of hypertension in this highly educated
cohort [25]; (6) and, especially, because the incidence of
hypertension was relatively low in our cohort and this
scarcity in the number of observed new cases could hinder
the finding of a statistically significant association between
nut consumption and hypertension. We acknowledge that
our statistical power might be too low to detect an association of small magnitude. We observed 542 cases of
hypertension over 9919 subjects. Assuming an alfa error
(bilateral) equal 0.05, a power of 0.80 and a relative risk of
0.75 for a dichotomized exposure, we would need 3947
exposed and 3947 unexposed subjects to detect a protective effect at that level.
The strengths of this study are the large sample size, long
duration of follow-up (4.3 years median), its prospective
design that could avoid inverse causation bias, and the control
for a wide variety of potential confounders. Additionally, both
dietary exposure and outcome were ascertained through
standardized and validated questionnaires [15,25].
In conclusion, though our estimated confidence intervals
are compatible with some degree of protection of nut
consumption against hypertension, our data do not support
an inverse association between nut consumption and incidence of hypertension in this cohort of Spanish university
graduates. Larger cohorts and trials including participants
initially free of hypertension and with greater statistical
power and ability to differentiate between raw nuts and
salted nuts would contribute to clarifying this association.
Acknowledgements
We thank all members of the SUN Study Group for administrative, technical and material support. We thank
participants of the SUN Study for their continued cooperation and participation. Adriano Marc
al Pimenta would also
like to thank the Coordenac
a
oamento de
o de Aperfeic
Pessoal de Nvel Superior e CAPES, Brazil for their scholarship for studies at the University of Navarra, Spain.
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