European Journal of Clinical Nutrition (2015) 69, 392–398 © 2015 Macmillan Publishers Limited All rights reserved 0954-3007/15 www.nature.com/ejcn

ORIGINAL ARTICLE Dietary phytochemical index is inversely associated with the occurrence of hypertension in adults: a 3-year follow-up (the Tehran Lipid and Glucose Study)

M Golzarand1,2, Z Bahadoran1,2, P Mirmiran3, S Sadeghian-Sharif1 and F Azizi4

BACKGROUND/OBJECTIVE: The epidemiological association of phytochemical-rich foods with the risk of hypertension is unclear. This study aimed to determine the association of dietary phytochemical index (PI) with the occurrence of hypertension (HTN) after 3 years of follow-up in Tehranian adults. SUBJECTS/METHODS: This prospective study was conducted on 1546 nonhypertensive subjects, aged 20–70 years. Dietary intake was collected by validated semiquantitative food frequency questionnaire (FFQ). Dietary PI was calculated as (dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)) × 100. Blood pressure was measured at baseline and after 3 years of follow-up and HTN was defined by Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure criteria. The odds of HTN after 3 years in each quartile category of dietary PI were estimated by logistic regression model and adjusted for potential variables. RESULTS: The mean age of participants was 38.0 ± 12.0 years and 43% were male. The mean dietary PI was 29.1 ± 11.8. After 3 years of follow-up, 265 (17.1%) new cases of HTN were identified. No significant changes were observed in the systolic and diastolic blood pressure across quartile categories of dietary PI. After adjustment for confounders, the odds (95% confidence interval) of HTN across quartiles of dietary PI were 1.00, 0.97 (0.62–1.38), 0.69 (0.45–1.07) and 0.52 (0.32–0.84) (P for trend = 0.004). CONCLUSIONS: Consumption of phytochemical-rich foods may prevent the development of HTN. Further investigations are, however, recommended. European Journal of Clinical Nutrition (2015) 69, 392–398; doi:10.1038/ejcn.2014.233; published online 12 November 2014

INTRODUCTION pressure in hypertensive patients.10,11 However, results of a trial on Hypertension (HTN), a chronic disease, is one of the underlying spontaneously hypertensive rats has reported that using the DASH causes of cardiovascular disease and renal disease.1 The global diet nutrients model without phytochemicals has no effect on 12 burden of HTN in adults was ~ 40% (1 billion) in 2008.2 In a blood pressure, indicating that phytochemicals may be essential 13 national study conducted by the Ministry of Health of Iran, the for the blood pressure-lowering effect of the DASH diet. burden of HTN was 25% (6.6 million) among Iranian adults, aged Phytochemicals are non-nutritive active compounds in plant 25–64 years.3 Insulin resistance, oxidative stress, disorders of foods and include flavonoids, phenolic acids, indoles, glucosino- renin–angiotensin system, low production of nitric oxide (NO), lates, phytoesterogens and isothiocyanates that may protect high production of advanced glycation end products and renal against diseases such as cancer, cardiovascular disease and disability to excrete sodium are the main causes of hypertension degenerative disease and increase the quality of life.14,15 However, development.4 Previous studies have demonstrated that lifestyle determination of the quantity of phytochemical intake in diets is manipulation can prevent hypertension and its outcome results.5,6 difficult among large populations, necessitating alternative Several recommendations including lower intakes of sodium, methods for estimating the phytochemical content of foods and , sugar, saturated fatty acid and higher intakes of dietary their health effects. The phytochemical index (PI), proposed for the potassium have been developed to decrease the risk of HTN,7,8 first time by McCarty16 is a simple and practical tool for the suggesting that food and dietary pattern may have more calculation of dietary phytochemical intake. Previous cross- important roles in the management of HTN than nutrients sectional studies have examined the association between PI and per se. Hence, the Dietary Approach to Stop Hypertension (DASH), cardiovascular disease risk factors including obesity, inflammation, high in fruits, vegetables and low-fat dairy, moderate in whole oxidative stress, lipid profile and blood pressure.17,18 In a Middle grains, fish, poultry and nuts, and low in red meats, sweets and Eastern population, no prospective population-based studies saturated fatty acids, was developed to reduce blood pressure.9 investigating the relationship between dietary PI and blood Clinical trials have indicated that the DASH diet decreases blood pressure have been published. This study therefore aimed to

1Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran and 4Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Correspondence: Dr P Mirmiran, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology ResearchInstitute, No. 46, Arghavan-e-gharbi St, Farahzadi Blvd, Shahrak-e-qods, Tehran 19395-4741, Iran. E-mail: [email protected] Received 19 March 2014; revised 11 August 2014; accepted 24 September 2014; published online 12 November 2014 Dietary PI and the occurrence of HTN in adults M Golzarand et al 393 determine the association between dietary PI and the occurrence Definitions of HTN in Tehranian adults. HTN was defined on the basis of the seventh report of Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-VII) criteria;23 subjects were considered SUBJECTS AND METHODS hypertensive if they had systolic blood pressure (SBP) ⩾ 140 mm Hg Study population and/or diastolic blood pressure (DBP) ⩾ 90 mm Hg and/or currently 19 using antihypertensive drugs. The percentage of 3-year changes in This prospective study is a part of Tehran Lipid and Glucose Study, an ð Þ – ð Þ SBP after three years SBP at baseline ´ 100 ongoing population-based study being conducted in district 13 of Tehran, SBP and DBP was calculated as SBP at baseline and ðDBP after three yearsÞ – ðDBP at baselineÞ ´ initiated in 1999 to detect and prevent noncommunicable disease risk DBP at baseline 100,respectively. factors. At baseline 15 005 subjects were selected by cluster random Use of antihypertensive drugs was obtained using questionnaire at sampling methods and have been followed up every 3 years. This study baseline and after 3 years. Antihypertensive drugs included (ATC has been approved by the research council of the Research Institute for code C03), vasodilators (ATC code C04), beta-blockers (ATC code C07), – Endocrine Sciences, Shahid Beheshti University of Medical Sciences and all blockers (ATC code C08) and agents acting on the renin angiotensin system (ATC code C09). participants gave written informed consent. fi For the current study, baseline was third phase of Tehran Lipid and Obesity was de ned using World Health Organization criteria as body mass index ⩾ 30 kg/m2.24 Hyperglycemia was defined using World Health Glucose Study (2006–2008) where 2799 subjects, aged 19–74 years, Organization criteria as fasting blood sugar ⩾ 126 mg/dl.25 completed food frequency questionnaires (FFQs) and were reassessed after 3 years (2009–2011). Participants who had HTN at baseline (n = 392), under- (o800 kcal/d) or over-reported (44200 kcal/d) dietary energy Statistical analysis intake (n = 232) (Fung et al.20) and those who dropped out before 2009– All analyses were conducted using SPSS software (version 16.0, Chicago, IL, 2011 (n = 629) were excluded from the analysis. The main reason for USA). Dietary PI was categorized on the basis of quartile ranges. General dropping out was either personal or migration. There were no differences linear model for continuous variables and Chi-square for noncontinuous between characteristics of the participants who completed the study and variables were used to compare the general characteristics and dietary those who dropped out. The final sample size included 1546 subjects. intakes of participants across the quartile categories of dietary PI. Mean SBP and DBP at baseline and after 3 years and the 3-year changes were compared across quartile categories of dietary PI using general linear Assessment of lifestyle factors and blood pressure measures model adjusted for sex, age, BMI, smoking, physical activity, SES and Weight was measured using digital scale (seca 707, Hamburg, Germany) energy intake. To estimate the odds ratio (OR; (95% confidence interval and height was measured using a tape meter. Body mass index was (CI))) of HTN in each quartile category of dietary PI and major calculated as weight (kg) divided by square of the height (m2). Physical phytochemical-rich food groups, multivariable logistic regression models activity levels were calculated using the Kriska et al.21 questionnaire and adjusted for confounding variables. In the first model, age and sex were expressed as metabolic equivalent hours per week (MET h/wk). Information adjusted and BMI, smoking status, physical activity and socioeconomic fi on smoking status was obtained using questionnaire; subjects who status in the second model. The nal model was additionally adjusted for fi smoked daily or occasionally were considered as current smoker and those dietary factors including energy intake, total ber, sodium, potassium, fi who had never smoked or had quit smoking as non-smokers. Socio- vitamin A, E and C. The lowest quartile was de ned as the reference group. P valueso0.05 were defined as a considered significant. economic status (SES) was assessed on the basis of education and occupation and categorized as low, middle and high SES. Education was classified as three levels: (1) illiterate (score 0), (2) up to diploma (score 1) RESULTS and (3) college graduate (score 2). Difficult jobs with low wages such as laborers were considered as low-class occupation (score 0), jobs such as The mean age of participants at baseline was 38.0 ± 12.0 years. shopkeepers and housekeepers were considered as middle-class occupa- Forty-three percent of participants were male. Mean dietary PI was tion (score 1) and prestigious occupations such as physicians and 29.1 ± 11.8, and median dietary PI was 16.2, 24.0, 31.3 and 42.6 in engineers were considered as high-class occupation (score 2). On the the first, second, third and fourth quartile categories, respectively. basis of the sum of the education and occupation scores, subjects were Participants in the highest compared to the lowest quartile of PI categorized as low SES (score = 0–1), middle SES (score = 2–3) and high SES were older; the distribution of the women in the upper quartile of (score = 4). Blood pressure was measured by a trained physician at baseline PI was significantly higher than the lower quartile categories. and again after 3 years; briefly, after 15 min rest and in a sitting position There were no differences between physical activity level, blood pressure was measured twice on the right arm using a standard smoking status and co-morbidities across quartile categories of mercury sphygmomanometer (Riester, Jungingen, Germany) with at least dietary PI (Table 1). 30 s interval. Subject's blood pressure was estimated based on the average Mean (s.e.m.) dietary intakes of participants across quartile of the two separate measurements. categories of dietary PI are shown in Table 2. Total energy intake did not differ across quartiles of dietary PI. There was an increasing Dietary assessment and phytochemical index calculation trend in dietary intakes of fiber, whole grains, fruits, vegetables, To assess dietary intake over the past year, a 168-item validated nuts, soy and seeds across quartile categories of dietary PI. semiquantitative FFQ22 was used at baseline. All FFQs were administered As shown in Table 3, there was no fluctuation in mean (s.e.m.) by trained nutritionists. Reported portion sizes of consumed foods were SBP and DBP at baseline and after 3 years across quartiles of converted to grams. Energy and nutrient intakes were calculated using the dietary PI. Subjects in the highest quartile category of PI had lower US Department of Agriculture food composition table (FCT); for some elevation in SBP (3.5 ± 1.3% vs 6.6 ± 1.3%) and DBP (6.5 ± 1.1% vs national foods that are not listed in the US Department of Agriculture FCT, 8.9 ± 1.1%) compared with the lowest quartile, difference was not the Iranian FCT was used. significant. 16 To estimate dietary phytochemical index, the McCarty equation was Mean (s.e.m.) SBP and DBP at baseline and after 3 years across dietary energy derived from phytochemical - rich foods ðkcalÞ used; PI ¼ ð Þ ´ 100 . quartiles of major phytochemical-rich food groups are shown in total daily energy intake kcal fi Phytochemical-rich foods included whole grains (whole wheat bread, Table 4; there were no signi cant differences between SBP and oat and bulgur), fruits (red, yellow and orange fruits), vegetables (dark DBP across the quartiles of whole grains, fruits, vegetables and green vegetables, red/orange vegetables, starchy vegetables and other legumes at baseline and after 3 years. However, elevation in DBP vegetables), natural fruit and vegetable juices, tomato sauces, soy products in the highest quartile of whole grains was significantly lower than (soy bean), nuts (peanut, almond, walnut, pistachio and hazelnut), legumes that in the lowest quartile (6.7 ± 1.1% vs 9.8 ± 1.1%). (lentil, beans, chickpea, split bean, mung bean and vicia faba), olive and After 3 years of follow-up, 265 (17.1%) new cases were olive oil. Potato was not considered as a vegetable group due to its low identified for HTN. The OR (95% CI) of HTN in each quartile phytochemical content. category of dietary PI is presented in Table 5. After adjustment for

© 2015 Macmillan Publishers Limited European Journal of Clinical Nutrition (2015) 392 – 398 Dietary PI and the occurrence of HTN in adults M Golzarand et al 394

Table 1. Baseline characteristics of participants by categories of dietary phytochemical index: Tehran Lipid and Glucose Study

Q1 (n = 385) Q2 (n = 388) Q3 (n = 386) Q4 (n = 387)

Dietary phytochemical index Range o20.7 20.7–27.7 27.7–36.1 436.1 Mean 15.6 24.0 31.6 45.0 Median 16.2 24.0 31.3 42.6 Age (years) 35.2 ± 11.5 36.5 ± 11.4 38.3 ± 12.0 41.9 ± 11.9* Men (%) 52.5 42.6 42.6 34.6* Physical activity (Met-h/wk) 37.9 ± 2.8 31.9 ± 2.7 38.0 ± 2.8 39.3 ± 2.8 Current smoker (%) 15.1 11.2 11.4 7.8

Socioeconomic status (%) Low 15.4 26.9 19.2 21.4 Medium 47.6 54.1 51.8 50.0 High 23.0 29.0 29.0 28.6 Weight (kg) 72.4 ± 0.7 71.4 ± 0.7 71.6 ± 0.7 71.6 ± 0.7 Hyperglycemia (%) 7.8 9.6 9.8 12.7 Obesity (%) 31.1 29.1 25.8 32.0 Abbreviation: Q, quartile. Data are shown as mean ± s.e.m. To compare the general characteristics across quartiles of phytochemical index, Chi-square test or age-adjusted general linear models were used. *Po0.05.

Table 2. Mean dietary intake of participants according to quartiles of dietary phytochemical index: Tehran Lipid and Glucose Study

Dietary intake Q1 (n = 385) Q2 (n = 388) Q3 (n = 386) Q4 (n = 387)

Median of PI (g/d) 16.3 24.1 31.3 42.6 Energy intake (kcal/d) 2286 ± 33 2280 ± 32 2252 ± 32 2381 ± 33 Carbohydrate (%) 55.0 ± 0.3 56.1 ± 0.3 57.3 ± 0.3 60.8 ± 0.3* Fat (%) 33.1 ± 0.3 32.4 ± 0.3 31.8 ± 0.3 29.0 ± 0.3* Protein (%) 13.1 ± 0.1 13.4 ± 0.1 13.6 ± 0.1 14.2 ± 0.1* Total fiber (g/d) 34.6 ± 1.0 36.4 ± 1.0 36.5 ± 1.0 42.9 ± 1.0* Whole grains (g/d) 34.9 ± 4.4 63.7 ± 4.4 92.6 ± 4.3 180 ± 4.4* Legumes (g/d) 11.9 ± 1.1 16.5 ± 1.1 15.1 ± 1.1 20.2 ± 1.1* Fruits (g/d) 191 ± 12 312 ± 12 420 ± 12 548 ± 12* Vegetables (g/d) 220 ± 9 275 ± 9 311 ± 9 350 ± 9* Meats (g/d) 87.8 ± 2.7 86.1 ± 2.7 82.7 ± 2.6 80.2 ± 2.7 Nuts (g/d) 4.1 ± 0.5 6.2 ± 0.4 7.1 ± 0.4 10.9 ± 0.5* Dairy (g/d) 492 ± 15 494 ± 15 483 ± 15 458 ± 15 Seed (g/d) 0.9 ± 0.3 1.4 ± 0.3 2.2 ± 0.3 3.3 ± 0.3* Soy bean (g/d) 1.0 ± 0.2 1.8 ± 0.2 1.7 ± 0.2 2.1 ± 0.2* Abbreviation: Q, quartile. Data are shown as mean ± s.e.m. To compare the dietary intakes of participants across quartiles of PI, general linear model with adjustment for sex, age, body mass index, smoking, energy intakes, physical activity and socioeconomic status were used. *P for trendo0.05.

Table 3. Blood pressure of participants by categories of dietary phytochemical index at baseline and after 3-year of follow-up: Tehran Lipid and Glucose Study

Q1 (n = 385) Q2 (n = 388) Q3 (n = 386) Q4 (n = 387) P for trend

Systolic blood pressure (mm Hg) Baseline 107.6 ± 0.5 107.9 ± 0.5 107.4 ± 0.5 107.8 ± 0.9 0.92 After 3 years 111.6 ± 0.6 112.5 ± 0.6 111.8 ± 0.6 111.2 ± 0.6 0.76 3-year change (%) 6.6 ± 1.3 4.8 ± 1.3 4.5 ± 1.3 3.5 ± 1.3 0.81

Diastolic blood pressure (mm Hg) Baseline 71.6 ± 0.4 71.3 ± 0.4 71.6 ± 0.4 70.8 ± 0.4 0.49 After 3 years 76.5 ± 0.4 76.4 ± 0.4 76.0 ± 0.4 74.9 ± 0.4 0.21 3-year change (%) 8.9 ± 1.1 8.1 ± 1.0 6.9 ± 1.0 6.5 ± 1.1 0.55 Abbreviation: Q, quartile. Data are shown as mean ± s.e.m. To compare systolic blood pressure and diastolic blood pressure and their 3-year changes across quartiles of PI general linear models were used with adjustment for age, sex, body mass index, smoking, physical activity, socioeconomic status and energy intake.

European Journal of Clinical Nutrition (2015) 392 – 398 © 2015 Macmillan Publishers Limited Dietary PI and the occurrence of HTN in adults M Golzarand et al 395

Table 4. Blood pressure of participants by categories of phytochemical-rich food groups at baseline and after 3-year of follow-up: Tehran Lipid and Glucose Study

Q1 (n = 385) Q2 (n = 388) Q3 (n = 386) Q4 (n = 387) P for trend

Whole grains Systolic blood pressure (mm Hg) Baseline 108 ± 0.6 107 ± 0.6 108 ± 0.6 108 ± 0.6 0.82 After 3 years 112 ± 0.6 111 ± 0.6 112 ± 0.6 112 ± 0.6 0.84 3-year change (%) 6.6 ± 1.3 4.4 ± 1.3 4.7 ± 1.3 3.7 ± 1.4 0.14 Diastolic blood pressure (mm Hg) Baseline 71.6 ± 0.4 70.8 ± 0.4 71.5 ± 0.4 71.4 ± 0.4 0.49 After 3 years 77.0 ± 0.4 75.2 ± 0.4 75.8 ± 0.4 75.8 ± 0.4 0.01* 3-year change (%) 9.8 ± 1.1 7.2 ± 1.0 6.8 ± 1.0 6.7 ± 1.1 0.02*

Vegetables Systolic blood pressure (mm Hg) Baseline 108 ± 0.6 108 ± 0.6 108 ± 0.5 107 ± 0.6 0.67 After 3 years 112 ± 0.6 112 ± 0.6 112 ± 0.6 112 ± 0.6 0.53 3-year change (%) 4.3 ± 1.4 6.9 ± 1.3 3.9 ± 1.3 4.3 ± 1.4 0.57 Diastolic blood pressure (mm Hg) Baseline 70.9 ± 0.4 71.5 ± 0.4 71.9 ± 0.4 71.1 ± 0.4 0.20 After 3 years 75.5 ± 0.4 76.4 ± 0.4 76.5 ± 0.4 75.4 ± 0.4 0.24 3-year change (%) 7.1 ± 1.1 7.5 ± 1.0 8.6 ± 1.0 7.3 ± 1.1 0.57

Fruits Systolic blood pressure (mm Hg) Baseline 107 ± 0.6 108 ± 0.6 108 ± 0.6 108 ± 0.6 0.47 After 3 years 112 ± 0.6 112 ± 0.6 112 ± 0.6 112 ± 0.6 0.72 3-year change (%) 4.3 ± 1.4 4.2 ± 1.3 6.3 ± 1.3 4.6 ± 1.4 0.64 Diastolic blood pressure (mm Hg) Baseline 71.3 ± 0.4 71.5 ± 0.4 71.3 ± 0.4 71.3 ± 0.4 0.93 After 3 years 76.4 ± 0.5 75.8 ± 0.5 76.0 ± 0.5 75.7 ± 0.5 0.32 3-year change (%) 7.9 ± 1.1 8.2 ± 1.0 7.4 ± 1.0 6.9 ± 1.1 0.78

Legumes Systolic blood pressure (mm Hg) Baseline 108 ± 0.6 108 ± 0.6 108 ± 0.6 107 ± 0.6 0.91 After 3 years 112 ± 0.6 112 ± 0.6 112 ± 0.6 111 ± 0.6 0.57 3-year change (%) 4.7 ± 1.3 4.1 ± 1.3 6.6 ± 1.3 4.0 ± 1.4 0.89 Diastolic blood pressure (mm Hg) Baseline 71.5 ± 0.4 71.9 ± 0.4 71.3 ± 0.4 70.7 ± 0.4 0.78 After 3 years 76.4 ± 0.5 75.9 ± 0.5 75.7 ± 0.5 75.8 ± 0.5 0.31 3-year change (%) 9.0 ± 1.1 6.2 ± 1.0 7.1 ± 1.0 8.2 ± 1.1 0.14 Abbreviation: Q, quartile. Data are shown as mean ± s.e.m. To compare systolic blood pressure and diastolic blood pressure and their 3-year changes across the quartiles of dietary whole grains, vegetables, fruits and legumes, general linear models were used with adjustment for age, sex, body mass index, smoking, physical activity, socioeconomic status and energy intake.

Table 5. Odds ratio (95% CI) for hypertension incidence according to quartiles of phytochemical index: Tehran Lipid and Glucose Study

Phytochemical index Q1 (n = 385) Q2 (n = 388) Q3 (n = 386) Q4 (n = 387) P for trend

Hypertension incident Crude model Reference 1.04 (0.72–1.51) 0.92 (0.63–1.35) 0.96 (0.65–1.39) +Age and sex Reference 0.99 (0.67–1.46) 0.67 (0.51–1.14) 0.65 (0.43–0.97) +Lifestyle factorsa Reference 1.00 (0.67–1.47) 0.76 (0.51–1.13) 0.64 (0.43–0.97) +Dietary factorsb Reference 0.97 (0.62–1.38) 0.69 (0.45–1.07) 0.52 (0.32–0.84) 0.004 Abbreviations: CI, confidence interval; Q, quartile. Data are shown as odds ratio and 95% CI. aIn addition to age and sex, this model is adjusted for lifestyle factors incliding: smoking status, physical activity, socioeconomic status and body mass index. bIn additional to age, sex and lifestyle factors, this model is adjusted for energy intake, total fiber, sodium, potassium, vitamins A, C and E.

age, sex, lifestyle factors and dietary factors in the multivariate Table 6 shows the OR (95% CI) of HTN in each quartile model, compared with the lowest quartile category of dietary PI, of major phytochemical-rich food groups. After adjustment for the odds of HTN were 0.97 (95% CI: 0.62–1.38), 0.69 (95% CI: 0.45– confounding variables, no association between HTN occurrence 1.07) and 0.52 (95% CI: 0.32–0.84) in the second, third and fourth and dietary intake of whole grains, legumes, vegetables and fruits quartiles, respectively (P for trend = 0.004). was found.

© 2015 Macmillan Publishers Limited European Journal of Clinical Nutrition (2015) 392 – 398 Dietary PI and the occurrence of HTN in adults M Golzarand et al 396

Table 6. Odds ratio (95% CI) for hypertension incidence according to quartiles of major phytochemical-rich food groups: Tehran Lipid and Glucose Study

Phytochemical-rich food groups Q1 (n = 385) Q2 (n = 388) Q3 (n = 386) Q4 (n = 387) P for trend

Whole grains +Age and sex Reference 0.88 (0.60–1.28) 0.74 (0.50–1.09) 0.77 (0.53–1.14) +Lifestyle factorsa Reference 0.87 (0.59–1.28) 0.74 (0.50–1.09) 0.78 (0.53–1.16) +Dietary factorsb Reference 0.89 (0.60–1.30) 0.75 (0.50–1.12) 0.71 (0.47–1.07) 0.100

Vegetables +Age and sex Reference 0.90 (0.61–1.34) 0.94 (0.64–1.40) 0.80 (0.53–1.19) +Lifestyle factorsa Reference 0.89 (0.60–1.32) 0.91 (0.61–1.35) 0.74 (0.49–1.11) +Dietary factorsb Reference 0.88 (0.59–1.33) 0.88 (0.57–1.35) 0.68 (0.44–1.15) 0.161

Fruits +Age and sex Reference 0.86 (0.58–1.27) 0.94 (0.64–1.38) 0.87 (0.59–1.28) +Lifestyle factorsa Reference 0.85 (0.57–1.26) 0.93 (0.63–1.37) 0.86 (0.59–1.27) +Dietary factorsb Reference 0.86 (0.57–1.30) 0.93 (0.60–1.44) 0.86 (0.48–1.54) 0.712

Legumes +Age and sex Reference 0.83 (0.55–1.25) 1.12 (0.76–1.65) 1.25 (0.85–1.83) +Lifestyle factorsa Reference 0.84 (0.55–1.26) 1.09 (0.73–1.62) 1.22 (0.84–1.81) +Dietary factorsb Reference 0.87 (0.57–1.31) 1.12 (0.75–1.67) 1.23 (0.82–1.84) 0.149 Abbreviations: CI, confidence interval; Q, quartile. Data are shown as odds ratio and 95% CI. aIn addition to age and sex, this model is adjusted for lifestyle factors incliding: smoking status, physical activity, socioeconomic status and body mass index. bIn additional to age, sex and lifestyle factors, this model is adjusted for energy intake, total fiber, sodium, potassium, vitamins A, C and E.

DISCUSSION was inversely associated with HTN occurrence. There is insufficient Our findings from this prospective study indicated that partici- evidence regarding whether the phytochemical content of pants who consumed higher amount of phytochemical-rich foods different foods has synergistic effects or interaction in the mixed had lower risk for the occurrence of HTN. diets. In the present study, however, it seems that phytochemical Experimental studies have documented that the effectiveness content in fruits, vegetables, whole grains, legumes and seeds of lifestyle modification and single-drug therapy on blood have synergistic effects that are responsible for the inverse pressure is similar.26 Recent guidelines of the European Society association observed between dietary PI intake and the occur- of Hypertension (2013) and of the European Society of Cardiology rence of HTN. Moreover, no significant reduction in the SBP and for the management of arterial HTN recommended that higher DBP after 3 years in the highest quartile of dietary PI compared intakes of fruits, vegetables, dietary and soluble fiber and whole with the lowest quartile may be related to the normal or grains have favorable effects on blood pressure.26 borderline blood pressure of participants at baseline. Previous studies have shown that consumption of fruits and Several mechanisms have been proposed for the antihyperten- vegetables,27,28 legumes,29,30 nuts31,32 and whole grains33,34 are sive properties of phytochemicals; habitual intake of inversely associated with blood pressure. A cross-sectional study phytochemical-rich foods could modulate several metabolic of 4025 German adults shows that subjects in the highest processes and intracellular signaling pathways.40 It has been compared with the lowest quintiles of a health-conscious pattern hypothesized that oxidative stress through reactive oxygen rich in whole grains, vegetables, fruits, legumes, fish and species production contributes to the pathogenesis of HTN and vegetables oil had 30% (95% CI: 0.74–0.90) lower risk of HTN.35 antioxidant intake may prevent the development of HTN.41 Principle bioactive components of plant foods are phytochemicals, Phytochemicals are the main components of diet that exhibit fibers, vitamin C and potassium.36 Phytochemicals are related to antioxidant properties42 and may prevent HTN development health status and lower the risk of several chronic diseases.15 The through modulation of inflammatory processes and endothelial Moli-sani study of 13 771 men and women (aged 55 ± 12 years) function.43 indicate that there was an inverse association between higher In addition, phytochemicals enhance and maintain endothelial- intake of high-antioxidant vitamins and phytochemicals and derived NO concentrations through stimulation of endothelial decrease in SBP (β = − 0.5, Po0.02), DBP (β = − 0.3, Po0.02) and nitric oxide synthase activity and expression and inhibition of the risk of HTN (OR = 0.94 (95% CI: 0.91–0.98)) in men, but not in NADPH oxidase activity and decline endothelial-derived endothe- women, findings suggesting that the amount of phytochemical lin-1 level. Hence they relax vascular smooth muscle tone and – intake is critical for preventing hypertension.37 It is estimated that reduce blood pressure.44 47 Previous investigations indicate that the DASH diet, developed for lowering blood pressure, provides increment in NO production is more important than antioxidant 73 mg of phytochemicals per 1000 kcal.38 In the PREDIMED trial, activity of phytochemicals in reduction of blood pressure and patients who consumed high amounts of Gazpacho, a prevention of HTN.48 phytochemical-rich vegetable soup, had lower SBP (−2.6 mm Hg, This study has several strengths and limitations. The population- Po0.05), DBP (−1.9 mm Hg, Po0.05) levels and the risk of HTN in based design was the most important strength of the current these subjects was also lower (OR = 0.73 (95% CI: 0.55–0.98)) than study. In addition, dietary intake was not assessed by using a self- nonconsumers; it has been suggested that phytochemicals in administered questionnaire. Main limitations of this study are vegetable components used for preparation of Gazpacho had a inherent limitations of PI. First, PI is a complex of caloric synergistic effect on attenuation of blood pressure.39 phytochemical-rich food groups including whole grains, fruits, In the present study, there was no association between HTN vegetables, legumes, seed, fruit and vegetable juice, olive and and major phytochemical-rich food groups alone, but dietary PI olive oil and does not consider non-caloric phytochemical-rich

European Journal of Clinical Nutrition (2015) 392 – 398 © 2015 Macmillan Publishers Limited Dietary PI and the occurrence of HTN in adults M Golzarand et al 397 food like green and black tea that are one source of 13 Seymour EM, Singer AA, Bennink MR, Parikh RV, Kirakosyan A, Kaufman PB et al. phytochemicals. Second, the type of phytochemical consumed is Chronic intake of a phytochemical-enriched diet reduces cardiac fibrosis and not considered in PI, for example, in one diet more fruits and diastolic dysfunction caused by prolonged salt-sensitive hypertension. J Gerontol vegetables may be consumed, whereas in another diet with the A Biol Sci Med Sci 2008; 63: 1034–1042. 14 Dreosti IE. Recommended dietary intake levels for phytochemicals: Feasible or same dietary PI score, more legumes and whole grains are 9 – consumed that have different type of phytochemicals. Hence, the fanciful? Asia Pac J Clin Nutr 2000; : S119 S122. 15 Holst B, Williamson G. Nutrients and phytochemicals: from bioavailability to quality of dietary phytochemicals differ among people with the bioefficacy beyond antioxidants. Curr Opin Biotechnol 2008; 19:73–82. same PI score and their effects on the blood pressure and 16 McCarty MF. Proposal for a dietary ‘phytochemical index’. Med Hypotheses 2004; occurrence of HTN are varied. Another limitation of this study is 63:813–817. that there was no measurement of dietary PI intake after 3 years, 17 Bahadoran Z, Golzarand M, Mirmiran P, Saadati N, Azizi F. The association of although a 3-year period is too short to change dietary patterns. dietary phytochemical index and cardiometabolic risk factors in adults: Tehran Furthermore, because the Iranian FCT is incomplete, the US Lipid and Glucose Study. J Hum Nutr Diet 2013; 26: 145–153. Department of Agriculture FCT was used to calculate the energy 18 Vincent HK, Bourguignon CM, Taylor AG. Relationship of the dietary phyto- chemical index to weight gain, oxidative stress and inflammation in overweight and nutrient intakes. 23 – In conclusion, our results showed that higher dietary PI was young adults. J Hum Nutr Diet 2010; :20 29. 19 Azizi F, Rahmani M, Emami H, Mirmiran P, Hajipour R, Madjid M et al. associated with the lower risk of HTN in adults after a 3-year Cardiovascular risk factors in an Iranian urban population: Tehran lipid and follow-up. It seems that the synergistic effects of phytochemicals glucose study (phase 1). Soz Praventivmed 2002; 47:408–426. from different foods are responsible for the inverse association 20 Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, Colditz GA et al. Whole-grain between high dietary PI intake and risk of HTN, and further intake and the risk of type 2 diabetes: a prospective study in men. Am J Clin Nutr investigations such as randomized clinical trials are required to 2002; 76:535–540. confirm these findings. 21 Kriska AM, Knowler WC, LaPorte RE, Drash AL, Wing RR, Blair SN et al. Development of questionnaire to examine relationship of physical activity and diabetes in Pima Indians. Diabetes Care 1990; 13: 401–411. CONFLICT OF INTEREST 22 Esfahani FH, Asghari G, Mirmiran P, Azizi F. Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran The authors declare no conflict of interest. Lipid and Glucose Study. J Epidemiol 2010; 20: 150–158. 23 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr. et al. ACKNOWLEDGEMENTS The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; We thank the Tehran Lipid and Glucose Study participants and the field investigators 289: 2560–2572. of the Tehran Lipid and Glucose Study for their cooperation and assistance in 24 Obesity: preventing and managing the global epidemic. World Health Organ Tech physical examinations, biochemical and nutritional evaluation and database Rep Ser 2000; 894:1–253. management. This study was supported by grant no. 121 from the National Research 25 WHO Consultation Definition, diagnosis and classification of diabetes mellitus Council of the Islamic Republic of Iran and the Research Institute for Endocrine and its complications. Report of a WHO consultation, Part 1: Diagnosis and Sciences of Shahid Beheshti University of Medical Sciences. We thank Ms N Shiva for classification of diabetes mellitus. 1999, World Health Organization, Geneva, critical editing of the English language of the manuscript. Switzerland. 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