ORIGINAL RESEARCH COMMUNICATION
Intake of fruit and vegetables and the risk of ischemic stroke in a cohort ofDanish men and women1,2,3
Søren P Johnsen, Kim Overvad, Connie Stripp, Anne Tjønneland, Steen E Husted and Henrik T Sørensen
1 From the Department of Clinical Epidemiology, Aarhus University Hospital and Aalborg Hospital, Aarhus, Denmark (SPJ and HTS); the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark (SPJ and KO); the Danish Cancer Society, Instituteof Cancer Epidemiology, Copenhagen (CS and AT); and the Department of Cardiology and Internal Medicine, Aarhus County Hospital and Aarhus University Hospital, Aarhus, Denmark (SEH).
2 Supported by The Danish Cancer Society, Europe Against Cancer, The Danish Heart Foundation (grants 99-1-4-77-22703 and 99-2-4-95-22771), Hjernesagen, and The Danish Medical Research Council through Vestdansk Sundhedsvidenskabeligt Forskningsforum.
3 Reprints not available. Address correspondence to SP Johnsen, Department of Clinical Epidemiology, University of Aarhus, VennelystBoulevard 6, DK-8000 Aarhus C, Denmark. E-mail: spj@soci.au.dk.
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION
REFERENCES
Background: Previous studies have suggested that a high dietary intake of fruit and vegetables is associated with a reduced risk ofischemic stroke. The magnitude of the effect is uncertain, and only one study reported data on the intake of specific fruit and vegetables and the risk of stroke.
Objective: We examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke, with particular attention paid to specific fruit and vegetables and subtypes of ischemic stroke.
Design: In a prospective cohort study of 54 506 men and women who were included in the Danish Diet, Cancer, and Health study from 1993 to 1997, estimated total intakes of fruit and vegetables (in g/d) were extracted from a semiquantitative food-frequency questionnaire completed at baseline. Data about subjects hospitalized with ischemic stroke were obtained from the Danish National Registry of Patients and were verified later by record reviews. The follow-up for ischemic stroke ended on the date of a first hospital admission for stroke or transient ischemic attack, the date of death or emigration, or the end of the study, whichever came first.
Results: We identified 266 cases of ischemic stroke involving hospitalization during 168 388 person-years of follow-up (median follow-up: 3.09 y; range: 0.02–5.10 y). After adjustment for potential confounders, persons in the top quintile of fruit and vegetable intake (median: 673 g/d) had a risk ratio of ischemic stroke of 0.72 (95% CI: 0.47, 1.12) relative to persons in the bottom quintile of intake (median: 147 g/d) (P for trend = 0.04). When comparing the top quintile with the bottom quintile, an inverse association was most evident for fruit intake (risk ratio: 0.60; 95% CI: 0.38, 0.95; P for trend = 0.02). Similar risk estimates were seen for most types of fruit and vegetables, although the risks were significant only for citrus fruit.
Conclusion: An increased intake of fruit may reduce the risk of ischemic stroke.
Key Words: Nutrition • diet • fruit • vegetables • ischemic stroke • prospective study • epidemiology • cerebrovascular disorders • Diet • Cancer • and Health study
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION
REFERENCES
Stroke is a leading cause of death and disability, with major global public health implications. Observational studies have provided strong evidence that lifestyle factors, possibly including diet, may play an important role in the etiology of stroke (1–3).
The relation between diet and the risk of stroke has been extensively examined. However, most studies focused on specific dietarycomponents rather than on foods (4–13). Intakes of antioxidants (ie, vitamin C, ß-carotene, and flavonoids), potassium, and fiber have been associated with a reduced risk of stroke (4–8). These findings have generated an increased interest in foods that are rich in these substances, such as fruit, vegetables, and other plant foods (12–15). This interest is further stimulated by previous experiences, which have taught us that, when trying to unravel the complexity of nutrient interactions in the relation between foods and health, focusing on single nutrients may be too simple an approach (16).
The few prospective studies on the intake of fruit and vegetables and the risk of stroke (6, 12, 13, 17, 18) have shown either inverse associations or no associations. Thus, there is still uncertainty regarding the magnitude of any preventive effect. Furthermore, most of the studies had several limitations because they were based on crude assessments of diet and limited adjustment for confounding factors and because they included only a few outcomes, with no distinction between subtypes ofstroke. At present, only one study has reported on the association between the intake of specific fruit and vegetables and the risk of stroke (13). The reduced risk ofstroke in that study was most evident for the intakes of cruciferous vegetables; green, leafy vegetables; citrus fruit including juice; and citrus fruit juice alone (13). On the basis of data from a prospective study on diet and health, we examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke,with special reference to specific fruit and vegetables and different subtypes of ischemic stroke.
SUBJECTS AND METHODS
TOP
ABSTRACT
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION
REFERENCES
Design and study population
The Diet, Cancer, and Health study is a prospective cohort study with the primary aim of studying the etiological role of diet in cancer risk. The study design is described in detail elsewhere (19). From December 1993 through May 1997, 80 996 men and 79 729 women aged 50–64 y were invited to participate in the study; 27 177 men and 29 876 women accepted the invitation. Eligible cohort members were born in Denmark, were living in the Copenhagen and Aarhus areas, and had no previous cancer diagnosis in the Danish Cancer Registry. The baseline data were linked to the Danish Cancer Registry and other nationwide population-based registries, including the National Registry ofPatients and the Civil Registration System, by using the civil registry number, which is the unique number given to every Danish citizen at birth. Information on death or emigration was obtained through record linkage with the Civil Registration System, which has kept electronic records of all changes in vital status, including change in address, date of emigration, and date of death, for the entire Danish population since 1968.
The Danish National Registry of Patients, established in 1977, records 99.4% of all discharges from nonpsychiatric hospitals in Denmark (20). The data include the civil registry number, dates of admission and discharge, surgical procedures performed, and up to 20 discharge diagnoses, which were classified until 1993 according to the Danish version of the International Classification of Diseases, 8th revision (ICD-8), and subsequently according to the corresponding national version of ICD-10 (20). All discharge diagnoses are assigned exclusively by the physician who discharges the patient. To study incident cases of stroke, we excluded participants who had been hospitalized before enrollment with cardiovascular disease, ie, stroke, transient ischemic attack, ischemic heart disease, or peripheral arteriosclerosis, as recordedin the National Registry of Patients (ICD-8 codes: 410–414, 430–438, and 440, and ICD-10 codes G45, I20–25, and I60–70). Both the Diet, Cancer, and Health study and the present substudy were approved by the Regional Ethics Committees in Copenhagen and Aarhus and by The Danish Data Protection Agency.
Baseline data
All cohort members completed a detailed 192-item semiquantitative food-frequency questionnaire (FFQ). Descriptions of the development and validation of the questionnaire were published previously (21, 22). All the participants also completed a questionnaire about other lifestyle factors, such as smoking habits, alcohol intake, physical activity, health, education, and, for women, use of hormone replacement therapy. Height, weight, waist and hip circumferences, blood pressure, and total serum cholesterol concentrations were also measured at baseline.
Intake of fruit and vegetables
We estimated intakes of fruit and vegetables from the FFQ, in which the participants reported their average intake of different food items over the previous year within 1of 12 possible intake categories, which ranged from never to ≥ 8 times/d. Daily intakes of specific foods and nutrients, including 42 different types of fruit and vegetables, were calculated from the FFQ for each participant by using the software program Food Calc (23). Standard recipes and sex-specific portion sizes were applied to calculate intake in grams per day by using data from different sources, ie, the 1995 Danish National Dietary Survey (24), 24-h diet recall interviews from 3818 of the study participants (25), and various cookery books.
Fruit and vegetables were grouped into the following 10 categories according to the classifications of the American Institute for Cancer Research (26): leafy vegetables (eg, lettuce and spinach), fruiting vegetables (ie, avocados, cucumbers, aubergines, peppers, peas, pumpkins, zucchini, green beans, and tomatoes), root vegetablesother than potatoes (eg, carrots), cruciferous vegetables (eg, broccoli, Brussels sprouts, cauliflower, and cabbage), mushrooms, onion and garlic, stalk vegetables (eg, leeks and asparagus), citrus fruit (eg, oranges and grapefruit), other fruit (eg, apples and pears), and fruit and vegetable juices. Thus, fruit and vegetables were grouped by using a combination of botanical and culinary criteria. Potatoes were not included in the analyses.
Stroke data
A detailed description of the assessment of cases of stroke in the cohort was published previously (26). We identified probable cases of ischemic stroke within the cohort from The Danish National Registry of Patients; these were cases with ICD-10 discharge diagnoses of I60–69.8 and G45 through 1998 for persons living in the Copenhagen area and through 1999 for persons living in the Aarhus area. Medical records and hospital discharge letters were retrieved and reviewed by a single reviewer using a detailed standardized form (26).
We used the World Health Organization’s definition of stroke, ie, an acute disturbance of focal or global cerebral function with symptoms lasting more than 24 h or leading to death of presumed vascular origin (27). A computed tomography or magnetic resonance scan, a spinal fluid examination, or an autopsy or operation description was necessary to distinguish between ischemic infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. All cases of ischemic stroke included in this study were verified by a computed tomography or magnetic resonance scan.
We subclassified all cases of ischemic stroke on the basis of the presumed etiology according to the following Trial of Org 10172 (a low-molecular-weight heparinoid) in Acute Stroke Treatment (TOAST) classifications: large-artery atherosclerosis, cardioembolism, small-vessel occlusion, stroke of other determined etiology, andstroke of undetermined etiology (28). These classifications are based on clinical features, ie, cortical or cerebellar dysfunction and lacunar syndrome, and on data (eg, location and size of infarct) collected by tests such as brain imaging, cardiac imaging, duplex imaging of extracranial arteries, arteriography, and laboratory assessments for a prothrombotic state.
Data analysis
Follow-up for ischemic stroke began on the date on which the subjects visited one of the study centers and ended on the date of their first hospital admission for ischemic stroke, the date of a censoring event (ie, hospitalization for intracerebral hemorrhage, subarachnoid hemorrhage, unspecified stroke, or transient ischemic attack; death; or emigration), or 31 December 1998 for participants living in the Copenhagen area or 31 December 1999 for participants living in the Aarhus area, whichever came first. We categorized the intake of fruit and vegetables (in g/d) into quintiles, and the risk of ischemic stroke was compared between the quintiles by using the lowest quintile as the reference. We used the nonparametric test developed by Cuzick (29) to test for trends in the distribution of the potentially confoundingvariables across the quintiles. A chi-square test was used for categorical variables.
We used Cox proportional hazards regression to obtain risk ratios (RRs) adjusted for possible confounders, ie, sex, total energy intake, smoking status, blood pressure, serum cholesterol, diabetes mellitus, body mass index, alcohol intake, intake of red meat and n-3 polyunsaturated fatty acids, physical activity, and education. We used 2 approaches for fitting the multivariate models to first identify the most important confounding factors and then to adjust for all available possible confounders. First, to adjust for confounding, we used the change-in-estimate method, in which variables were selected on the basis of changes in the risk estimates of interest (adjusted model) (30). Besides diet, the variables included in these models were sex, total energy intake, and smoking. Second, we extended this adjusted model with the additional variables (full model), ie, systolic and diastolic blood pressure, serum cholesterol at baseline, diabetes mellitus, body mass index, alcohol intake, intake of red meat and n-3 polyunsaturated fatty acids, physical activity, and education. Age was used as the time axis, ie, for subjects who entered the study in December 1993, age at the time of inclusion in the study and age at the time of censoring were equal to chronological age at those time points. However, for subjects who entered the study later, we adjusted for their delayed entry at the time of enrollment because the age at which the participants became at risk (ie, the length of time from birth to the startof the study) was not identical with the age at which they came under observation (ie, the length of time from birth to inclusion in the study). We thus adjusted for delayed entry by defining the age at which the participants became at risk and the age at which they came under observation as separate time points, ie, time from birth to the start of the study and time from birth to inclusion in the study, respectively. The assumption of proportional hazards in the Cox models was evaluated by usinggraphical assessment and was found to be appropriate in all models.
We adjusted for energy intake by using the residual method (31), ie, residuals were computed from a linear regression model with fruit and vegetable intake as the dependent variable and total energy intake as the independent variable. The predicted fruit and vegetable intake for a person having an energy intake equal to the mean value for the study population was added as a constant. The total energy intake was also included in the models.
Present tobacco consumption (in g/d) was calculated by equating a cigarette with 1 g tobacco, a cheroot or pipe with 3 g, and a cigar with 4.5 g. Smoking status was included in the models at 5 levels: never smoker, former smoker, and current smoker of 1–14, 15–24, or ≥ 25 g tobacco/d. Systolic and diastolic blood pressure at baseline, body mass index at baseline, intake of red meat and n-3 polyunsaturated fatty acids (in g/d), and recreational physical activity (in h/wk) were included as continuous variables, whereas total serum cholesterol concentration was included as a dichotomized variable (≤ 6 compared with > 6 mmol/L), and length of education after elementary school was included with 4 categories (0, <> 4 y).
We also used separate Cox models to carry out analyses stratified by sex and smoking status and analyses that included product terms to assess possible effect modification by these variables. Finally, the analyses were repeated according to different subtypes of ischemic stroke, ie, large-artery atherosclerosis, cardioembolism,small-vessel occlusion, and stroke of undetermined etiology; official Danish recommendations (daily intake of fruit and vegetables ≥ 600 g); and length of follow-up (< class="blsp-spelling-error" id="SPELLING_ERROR_4">CIs throughout the analyses. All analyses were performed with the use of STATA statistical software (release 7.0; Stata Corporation, College Station, TX). RESULTS TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES The cohort included 57 053 persons at baseline. We excluded 2500 persons (4.4%) who were previously registered with cardiovascular disease in the Danish National Registry of Patients and 47 persons (0.08%; including 2 persons with stroke) who left ≥ 10 items blank on the FFQ or who had ≥ 7 items with implausible values. The study population thus included 54 506 persons, who provided a total of 168 388 person-years of risk (median: 3.09 y; range: 0.02–5.10 y). Information on all variables was available for 53 035 persons (97.3% of the persons included in the present study). Characteristics of the study participants by quintile of total fruit and vegetable intake (in g/d) are shown in Table 1 . The median intake of fruit and vegetables ranged from 147 g/d in the lowest quintile to 673 g/d in the highest quintile. Total intake of fruit and vegetables was positively associated with the proportion of women (ie, 39.7% of the subjects in the lowest quintile were women, whereas 67.7% of the subjects in the highest quintile were women), with the proportions of subjects having a higher education and diabetes mellitus, and with total energy intake. By contrast, total intake of fruit and vegetables was negatively associated with the proportion ofcurrent smokers (ie, 53.2% of the subjects in the lowest quintile were current smokers, whereas 25.1% of the subjects in the highest quintile were current smokers) and with the proportions of subjects having hypertension, high cholesterol, and high alcohol intake. View this table: [in this window] [in a new window] TABLE 1 . Characteristics of study participants by quintile of total fruit and vegetable intake (in g/d)1 We verified 266 instances of first-time acute ischemic stroke among the study participants during follow-up. These events included 27 (10.2%) instances of stroke due to large-artery atherosclerosis, 24 (9.0%) instances of stroke due to cardioembolism, 115 (43.2%) instances of stroke due to small-vessel occlusion, 2 (0.8%) instances of stroke due to other determined etiology, and 98 (36.8%) instances of stroke of undetermined etiology. RRs of acute ischemic stroke by quintile of fruit and vegetable intake are shown in Table 2 . The total combined intake of fruit and vegetables, as well as the total separate intakes of fruit and of vegetables, was associated with a reduced risk of acute ischemic stroke in the unadjusted models; relative to the lowest quintile, the RRs for the highest quintile were between 0.40 and 0.63. Adjustment for sex, total energy intake, and smoking status weakened the association (RRs: 0.52–0.85); however,the directions of the associations remained unchanged. Whether energy intake was adjusted for by residuals of the dietary exposure variable alone or by residuals and total energy intake in combination had no influence on the estimates. The RRs were further weakened after additional adjustment for systolic and diastolic bloodpressure, serum cholesterol at baseline, diabetes mellitus, body mass index, alcohol intake, intake of red meat and n-3 polyunsaturated fatty acids, physical activity, and education; however, the effect of adjustment for these factors was modest in most of the models. The lowest RR in the full model was seen in the highest quintile of fruit intake (RR = 0.60; 95% CI: 0.38, 0.95; P = 0.03). View this table: [in this window] [in a new window] TABLE 2 . Risk ratios and 95% CIs of ischemic stroke by quintile (Q) of fruit and vegetable intake1 Regarding specific types of fruit and vegetables, the results indicated a reduced risk of acute ischemic stroke for most of the items except mushrooms, onion and garlic, and stalk vegetables: relative to the lowest quintiles, crude RRs for the highest quintiles were between 0.45 and 0.69 (Table 3 ). Adjustment for the most influential confounding factors weakened these associations, making most of them nonsignificant. Additional adjustment for potentially confounding factors had a minor effect on the risk estimates. We found the lowest RRs in the full model in the highest quintiles of intake of citrus fruit (RR = 0.63; 95% CI: 0.41, 0.96; P = 0.03) and other fruit (RR = 0.67; 95% CI: 0.43, 1.04; P = 0.08). View this table: [in this window] [in a new window] TABLE 3 . Risk ratios and 95% CIs of ischemic stroke by quintile (Q) of intake of specific groups of fruit and vegetables1 Some variation in the risk estimates, eg, when comparing the highest and the lowest quintiles of total fruit and vegetable intake, was seen when we stratified by smoking status (never or former smokers compared with current smokers [the RRs (and 95% CIs) for the nonsmokers and the smokers were 0.93 (0.47, 1.82) and 0.65 (0.35, 1.20), respectively (P = 0.37)]) and sex [the RRs (and 95% CIs) for the men and the women were 0.88 (0.49, 1.60) and 0.68 (0.34, 1.40), respectively (P = 0.62)]. However, none of these differences was significant. The associations between fruit and vegetable intake and ischemic stroke were also evaluated separately for different subtypes of ischemic stroke because the pathophysiologic mechanisms involved in the different subtypes are likely to be different. No differences were found; however, some of the risk estimates were imprecise because of the relatively low number of outcomes, particularly for large-artery atherosclerosis and cardioembolism (data not shown). The lowest RRs were found in the highest quintile of fruit intake for strokes due to small-vessel occlusion [RR = 0.67 (95% CI: 0.34, 1.31)] and for strokes of undetermined etiology [RR = 0.50 (95% CI: 0.23, 1.08)]. However, inverse, nonsignificant associations were found for all types of ischemic stroke. Relative to the participants with a daily intake of < rr =" 0.90)" trend =" 0,04)." trend =" 0.02)."> 6 mmol / L), dan panjang setelah pendidikan sekolah dasar yang termasuk dalam 4 kategori (0, <3,> 4 y).
Kami juga digunakan terpisah Cox model untuk melakukan analisis bertingkat oleh jenis kelamin dan status merokok dan analisis produk yang menyertakan persyaratan untuk menilai kemungkinan efek modifikasi oleh variabel-variabel tersebut. Terakhir, analisis yang diulang menurut subtypes berbeda dari ischemic stroke, yaitu besar-artery atherosclerosis, cardioembolism, kecil-kapal kemacetan, dan stroke yg tak dpt ditentukan dari etiologi; resmi Denmark rekomendasi (harian asupan buah-buahan dan sayuran ≥ 600 g), dan panjang tindak lanjut (<1 dibandingkan dengan 1 ≥ y).
Kami diperkirakan P untuk tren risiko stroke menurut asupan buah-buahan dan sayuran berdasarkan pada uji Wald, setelah masuknya individu eksposur variabel kontinu sebagai tindakan. Kami dihitung 95% CIS di seluruh analisis. Semua analisis yang dilakukan dengan menggunakan perangkat lunak statistik STATA (release 7.0; Stata Corporation, College Station, TX).
Kelompok yang termasuk 57 053 orang di dasar. Kami dikecualikan 2500 orang (4,4%) yang sebelumnya terdaftar dengan penyakit cardiovascular di Denmark yang Pasien Registry Nasional dan 47 orang (0,08%; termasuk 2 orang dengan stroke) yang kiri ≥ 10 item kosong pada FFQ atau yang telah ≥ 7 item implausible dengan nilai-nilai. Studi populasi sehingga termasuk 54 506 orang, yang disediakan total 168 388 orang-tahun risiko (median: 3,09 y; kisaran: 0,02-5,10 y). Informasi tentang semua variabel yang tersedia untuk 53 035 orang (97,3% dari orang yang termasuk dalam kajian ini).
Karakteristik kajian oleh peserta dari total quintile buah dan sayuran intake (dalam g / d) yang akan ditampilkan pada Tabel 1. The median asupan buah-buahan dan sayuran berkisar antara 147 g / d terendah di quintile ke 673 g / d tertinggi di quintile. Total asupan buah-buahan dan sayuran yang positif berkaitan dengan proporsi perempuan (yakni, 39,7% dari mata pelajaran di quintile terendah adalah perempuan, sedangkan 67,7% dari mata pelajaran di tingkat quintile adalah perempuan), dengan proporsi mata pelajaran yang memiliki pendidikan tinggi dan diabetes mellitus, dan dengan total asupan energi. Dengan kontras, total asupan buah-buahan dan sayuran adalah negatif yang terkait dengan proporsi ofcurrent perokok (yakni, 53,2% dari mata pelajaran di quintile terendah adalah perokok aktif, sedangkan 25,1% dari mata pelajaran di tingkat quintile adalah perokok saat ini) dan dengan proporsi mata pelajaran yang memiliki hipertensi, kolesterol tinggi, dan asupan alkohol tinggi.
Kami diverifikasi 266 kasus yang pertama kali ischemic stroke akut di kalangan peserta studi selama tindak lanjut. Acara ini termasuk 27 (10,2%) kasus stroke karena besar-artery atherosclerosis, 24 (9,0%) kasus stroke akibat cardioembolism, 115 (43,2%) kasus stroke akibat kemacetan kapal kecil, 2 (0,8%) kejadian stroke karena etiologi lainnya ditentukan, dan 98 (36,8%) dari kasus stroke yg tak dpt ditentukan etiologi.
RRs dari ischemic stroke akut oleh quintile dari asupan buah dan sayuran yang akan ditampilkan pada Tabel 2. Total gabungan dari asupan buah dan sayuran, serta total intakes terpisah dari buah-buahan dan sayuran, yang terkait dengan mengurangi risiko ischemic stroke akut di unadjusted model; relatif ke terendah quintile, maka untuk RRs tertinggi adalah quintile antara 0,40 dan 0,63. Penyesuaian untuk jenis kelamin, asupan energi total, dan status merokok melemah asosiasi (RRs: 0.52-0.85), namun arahnya dari asosiasi tetap tidak berubah. Apakah asupan energi untuk disesuaikan oleh residuals dari diet eksposur variabel sendiri atau oleh residuals dan asupan energi total dikombinasikan tidak memiliki pengaruh pada perkiraan. RRs yang telah melemah lebih lanjut setelah penyesuaian tambahan untuk systolic dan diastolic bloodpressure, di dasar serum kolesterol, diabetes mellitus, body mass index, asupan alkohol, asupan daging merah dan n-3 polyunsaturated fatty acid, aktivitas fisik, dan pendidikan, namun yang efek penyesuaian untuk faktor-faktor ini adalah yang paling sederhana dalam model. Terendah di RR penuh model yang terlihat dalam buah-buahan tertinggi quintile asupan (RR = 0,60; 95% CI: 0,38, 0,95; P = 0,03).
Spesifik mengenai jenis buah-buahan dan sayuran, hasil menunjukkan penurunan risiko stroke ischemic akut untuk sebagian besar item kecuali jamur, bawang merah dan bawang putih, dan sayur-sayuran tangkai: relatif ke terendah quintiles, crude RRs untuk quintiles adalah yang tertinggi di antara 0,45 dan 0,69 (Tabel 3). Penyesuaian untuk yang paling berpengaruh confounding faktor melemah asosiasi ini, sehingga kebanyakan mereka nonsignificant. Tambahan untuk penyesuaian potensial confounding faktor yang kecil terhadap perkiraan resiko. Kami menemukan terendah di RRs penuh model tertinggi dari asupan quintiles dari buah jeruk (RR = 0,63; 95% CI: 0,41, 0,96; P = 0,03) dan buah (RR = 0,67; 95% CI: 0,43, 1,04 ; P = 0,08). Beberapa variasi dalam perkiraan resiko, misalnya, ketika membandingkan tertinggi dan terendah quintiles dari total asupan buah dan sayuran, yang terlihat ketika kita bertingkat oleh status merokok (atau tidak pernah mantan perokok dibandingkan dengan perokok saat ini [yang RRs (CIS dan 95%) untuk nonsmokers dan perokok adalah 0,93 (0,47, 1,82) dan 0,65 (0,35, 1,20), masing-masing (P = 0,37)]) dan jenis kelamin [yang RRs (CIS dan 95%) untuk laki-laki dan perempuan adalah 0,88 (0,49, 1,60) dan 0,68 (0,34, 1,40), masing-masing (P = 0,62)]. Namun, tidak ada yang perbedaan yang signifikan.
Asosiasi di antara buah-buahan dan sayuran dan asupan ischemic stroke juga dievaluasi secara terpisah untuk berbagai subtypes dari ischemic stroke pathophysiologic karena mekanisme yang terlibat dalam berbagai subtypes yang mungkin berbeda. Tidak ada perbedaan yang ditemukan, namun beberapa risiko perkiraan yang tepat karena yang relatif rendah jumlah hasil, terutama untuk besar-artery atherosclerosis dan cardioembolism (data tidak ditampilkan). RRs terendah yang ditemukan dalam buah-buahan tertinggi quintile asupan untuk Strokes karena kecil-kapal kemacetan [RR = 0,67 (95% CI: 0,34, 1,31)], dan untuk Strokes yg tak dpt ditentukan dari etiologi [RR = 0,50 (95% CI: 0,23 , 1,08)]. Namun, terbalik, nonsignificant asosiasi yang ditemukan untuk semua jenis ischemic stroke.
Relatif terhadap para peserta dengan harian asupan dari <100 g buah-buahan dan sayuran, para peserta dengan asupan harian yang ≥ 600 g, yang sesuai dengan rekomendasi resmi Denmark, memiliki RR dari ischemic stroke akut dari 0,63 (95% CI: 0,33, 1,22) (full model). Kami mencari segala penyakit di preclinical dasar yang mungkin terpengaruh diet gaya hidup atau faktor lainnya, namun ketika kasus yang melibatkan potensi preclinical penyakit yang dikeluarkan dari tahun pertama dari tindak lanjut, resiko estimatesdid tidak berubah (data tidak ditampilkan).
DISKUSI
TOP
ABSTRAK
PENDAHULUAN
Subjek dan metode
HASIL
DISKUSI
REFERENSI
Dalam hal ini besar kelompok belajar, termasuk orang yang berusia 50-64 y di dasar, maka asupan buah-buahan, terutama buah jeruk dan lainnya, adalah terkait dengan mengurangi risiko ischemic stroke akut. Kami tidak menemukan jelas asosiasi antara asupan dari sayuran dan riskof akut ischemic stroke. Berkurangnya risiko yang paling jelas untuk Strokes karena-kapal kecil dan kemacetan Strokes ofundetermined etiologi. Kekuatan utama kita adalah belajar banyak hal, yang divalidasi dan komprehensif assessmentof asupan makanan, dan informasi lengkap tentang berbagai potensi confounding faktor; lengkap tindak lanjut melalui nasional, penduduk berbasis registries, yang membatasi risiko seleksi dan surveilans bias, dan standar penilaian semua hasil kegiatan terdaftar.
Untuk identifikasi potensi kejadian stroke, kami diandalkan di coding dari cerebrovascular diagnosa oleh dokter rumah sakit pada saat pasien telah habis. Oleh karena itu, kami dapat hanya untuk menyertakan Strokes yang dipimpin ke rumah sakit. Namun, mengingat usia profil kami belajar kelompok, ada kemungkinan bahwa kebanyakan pasien dengan gejala klinis akut stroke dirujuk ke rumah sakit untuk evaluasi lebih lanjut dan kerugian untuk tindak lanjut yang mungkin nondifferential dan sederhana karena ofthe singkat ikuti up periode.
Walaupun kita disesuaikan untuk confounding beberapa faktor dalam analisis, kemungkinan masih sisa confounding. Yang tinggi asupan buah-buahan dan sayuran, khususnya yang tinggi dan asupan buah-buahan, mungkin juga menjadi indikator keseluruhan lebih dari gaya hidup sehat (32) itu, selain termasuk diukur perilaku elemen seperti menjadi nonsmoker yang moderat dan asupan alkohol, juga mencakup berbagai perilaku yang lebih halus dan psikososial elemen. Selain itu, pengetahuan tentang diet dan sikap terhadap kesehatan dan makanan yang cenderung dikaitkan dengan asupan buah dan sayuran (33). Sebaliknya, mungkin juga akan berpendapat bahwa potensi untuk penyesuaian antara faktor kausal jalan di antara buah-buahan dan sayuran dan asupan risiko ischemic stroke, misalnya, tekanan darah dan serum kolesterol, adalah sulit dan dapat berakibat risiko perkiraan yang terlalu konservatif .
Akhirnya, baik eksposur dan confounder data mungkin telah terganggu misclassification, yang, karena sifat yang prospektif kami belajar desain, mungkin independen dari penilaian stroke, yaitu nondifferential. Nondifferential misclassification dari eksposur data, misalnya, karena dari imprecision dari dietaryquestionnaire di dasar atau karena perubahan dalam praktek diet di antara para peserta selama tindak lanjut, kami akan mengurangi kemampuan untuk mendeteksi setiap asosiasi antara asupan sayur dan buah-buahan dan risiko akut ischemic stroke, sedangkan nondifferential misclassification dari variabel confounder dapat mengakibatkan sisa confounding dan dapat berakibat baik attenuation dan risiko inflasi dari perkiraan.
Temuan kami ini sesuai dengan mereka yang sebelumnya beberapa calon studi (6, 12, 13, 17, 18). Berdasarkan pada Perawat Kesehatan Studi dan Kesehatan Professionals' Follow-up Study, Joshipura dkk (13) yang dilaporkan dari RR 0,69 (95% CI: 0,52, 0,91) untuk tingkat quintile buah intake (median servings / d: laki-laki, 4,54; perempuan 4,33) relatif ke bawah quintile (median servings / d: laki-laki, 0,86; perempuan 0,72), yang mirip dengan RR 0,60 yang ditemukan di studi kami jika servings dianggap menjadi 100 g tiap. Mereka juga menemukan lebih lemah kalak asosiasi antara asupan dari sayuran sendiri dan risiko ischemic stroke (RR = 0,90) bila dibandingkan mereka yang tertinggi dari quintiles intake (median servings / d: laki-laki, 6,21; perempuan, 5,37) dengan terendah quintiles (median servings / d: laki-laki, 1,60; perempuan 1,36). Dengan kontras, dalam studi Framingham berdasarkan kelompok, Gillman et al (12) tidak menemukan bahwa efek perlindungan dari buah yang lebih kuat dibandingkan dengan sayur-sayuran. Namun, mereka hanya belajar termasuk 97 kasus stroke atau transient ischemic serangan. Namun, setiap kenaikan dari 3 harian servings buah atau sayuran yang berkaitan dengan RR untuk sementara ischemic stroke atau serangan 0,81 (95% CI: 0,56, 1,19) dan 0,74 (95% CI: 0,54, 1,02), masing-masing.
Dalam hal tertentu untuk jenis buah dan sayuran, perhatikan bahwa mengurangi risiko ischemic stroke yang paling nyata untuk item yang biasanya dimakan mentah, misalnya, rimbun, sayuran, buah jeruk, dan buah-buahan lainnya. Efek yang berpotensi perlindungan dari buah jeruk dalam studi ini juga sesuai dengan temuan sebelumnya pada buah dan sayuran yang kaya vitamin C (13) dan mungkin menunjukkan berperan untuk vitamin C. Sebaliknya, sedangkan lainnya studi menunjukkan bahwa bawang putih mungkin memiliki bermanfaat efek kesehatan dalam kaitannya dengan penyakit cardiovascular dan kanker (34), kami tidak menemukan pengurangan resiko di antara para peserta dengan nilai asupan bawang merah dan bawang putih. Namun, bawang putih wasvery asupan rendah kami belajar penduduk, yang kita tidak dapat belajar hal ini dengan lebih terperinci.
Beberapa mekanisme mungkin terlibat dalam perlindungan terlihat efek buah dan sayuran pada risiko ischemic stroke. Beberapa buah dan sayuran konstituen, termasuk micronutrients, antioksidan, phytochemicals, dan serat, telah menurun yang terkait dengan risiko stroke dan penyakit lainnya di cardiovascular hewan model dan pengamatan epidemiologic studi (4-8). Namun, bukti yang ada pada peran masing-masing konstituen yang selama ini sudah tak meyakinkan, dan hasil dari beberapa pengujian ini berpotensi bioactive compounds sendiri atau dikombinasikan dalam persidangan di randomized cardiovascular dan penyakit kanker telah mengecewakan, terutama pada orang yang memakan Barat diet (15, 35-39). Mungkin ada penjelasan untuk berbagai temuan-temuan, misalnya, tak berguna dosis singkat dan belajar lama. Selain itu, peran satu gizi mungkin tidak mudah terisolasi dari kompleks biochemical konten tanaman pangan. Selain itu, upaya membuat sebab-musabab di inferences innutritional konstituen epidemiologi spesifik antara buah-buahan dan sayur-sayuran dan kemudian risiko penyakit yang terhambat oleh berbagai konten konstituen biologis aktif, misalnya, vitamin C, ß-carotene, dan flavonoids, dalam buah dan sayuran, yang tergantung pada asal geografis, musim tahun, metode penyimpanan dan memasak, dll masalah ini sulit untuk mempelajari gizi spesifik, dan mereka juga sulit untuk mencoba untuk membagi buah-buahan dan sayuran oleh ofspecific jumlah konstituen dan micronutrients.
Kesimpulannya, sebelumnya telah diusulkan suatu efek perlindungan dari asupan tinggi buah dan sayuran pada risiko ischemic stroke. Dari hasil ini kami besar Denmark kelompok belajar yang mendukung hipotesa asupan makanan yang tinggi adalah buah dari independen terkait dengan pengurangan risiko ischemic stroke.
Intake of fruit and vegetables and the risk of ischemic stroke in a cohort ofDanish men and women1,2,3
Søren P Johnsen, Kim Overvad, Connie Stripp, Anne Tjønneland, Steen E Husted and Henrik T Sørensen
1 From the Department of Clinical Epidemiology, Aarhus University Hospital and Aalborg Hospital, Aarhus, Denmark (SPJ and HTS); the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark (SPJ and KO); the Danish Cancer Society, Instituteof Cancer Epidemiology, Copenhagen (CS and AT); and the Department of Cardiology and Internal Medicine, Aarhus County Hospital and Aarhus University Hospital, Aarhus, Denmark (SEH).
2 Supported by The Danish Cancer Society, Europe Against Cancer, The Danish Heart Foundation (grants 99-1-4-77-22703 and 99-2-4-95-22771), Hjernesagen, and The Danish Medical Research Council through Vestdansk Sundhedsvidenskabeligt Forskningsforum.
3 Reprints not available. Address correspondence to SP Johnsen, Department of Clinical Epidemiology, University of Aarhus, VennelystBoulevard 6, DK-8000 Aarhus C, Denmark. E-mail: spj@soci.au.dk.
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION
REFERENCES
Background: Previous studies have suggested that a high dietary intake of fruit and vegetables is associated with a reduced risk ofischemic stroke. The magnitude of the effect is uncertain, and only one study reported data on the intake of specific fruit and vegetables and the risk of stroke.
Objective: We examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke, with particular attention paid to specific fruit and vegetables and subtypes of ischemic stroke.
Design: In a prospective cohort study of 54 506 men and women who were included in the Danish Diet, Cancer, and Health study from 1993 to 1997, estimated total intakes of fruit and vegetables (in g/d) were extracted from a semiquantitative food-frequency questionnaire completed at baseline. Data about subjects hospitalized with ischemic stroke were obtained from the Danish National Registry of Patients and were verified later by record reviews. The follow-up for ischemic stroke ended on the date of a first hospital admission for stroke or transient ischemic attack, the date of death or emigration, or the end of the study, whichever came first.
Results: We identified 266 cases of ischemic stroke involving hospitalization during 168 388 person-years of follow-up (median follow-up: 3.09 y; range: 0.02–5.10 y). After adjustment for potential confounders, persons in the top quintile of fruit and vegetable intake (median: 673 g/d) had a risk ratio of ischemic stroke of 0.72 (95% CI: 0.47, 1.12) relative to persons in the bottom quintile of intake (median: 147 g/d) (P for trend = 0.04). When comparing the top quintile with the bottom quintile, an inverse association was most evident for fruit intake (risk ratio: 0.60; 95% CI: 0.38, 0.95; P for trend = 0.02). Similar risk estimates were seen for most types of fruit and vegetables, although the risks were significant only for citrus fruit.
Conclusion: An increased intake of fruit may reduce the risk of ischemic stroke.
Key Words: Nutrition • diet • fruit • vegetables • ischemic stroke • prospective study • epidemiology • cerebrovascular disorders • Diet • Cancer • and Health study
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION
REFERENCES
Stroke is a leading cause of death and disability, with major global public health implications. Observational studies have provided strong evidence that lifestyle factors, possibly including diet, may play an important role in the etiology of stroke (1–3).
The relation between diet and the risk of stroke has been extensively examined. However, most studies focused on specific dietarycomponents rather than on foods (4–13). Intakes of antioxidants (ie, vitamin C, ß-carotene, and flavonoids), potassium, and fiber have been associated with a reduced risk of stroke (4–8). These findings have generated an increased interest in foods that are rich in these substances, such as fruit, vegetables, and other plant foods (12–15). This interest is further stimulated by previous experiences, which have taught us that, when trying to unravel the complexity of nutrient interactions in the relation between foods and health, focusing on single nutrients may be too simple an approach (16).
The few prospective studies on the intake of fruit and vegetables and the risk of stroke (6, 12, 13, 17, 18) have shown either inverse associations or no associations. Thus, there is still uncertainty regarding the magnitude of any preventive effect. Furthermore, most of the studies had several limitations because they were based on crude assessments of diet and limited adjustment for confounding factors and because they included only a few outcomes, with no distinction between subtypes ofstroke. At present, only one study has reported on the association between the intake of specific fruit and vegetables and the risk of stroke (13). The reduced risk ofstroke in that study was most evident for the intakes of cruciferous vegetables; green, leafy vegetables; citrus fruit including juice; and citrus fruit juice alone (13). On the basis of data from a prospective study on diet and health, we examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke,with special reference to specific fruit and vegetables and different subtypes of ischemic stroke.
SUBJECTS AND METHODS
TOP
ABSTRACT
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION
REFERENCES
Design and study population
The Diet, Cancer, and Health study is a prospective cohort study with the primary aim of studying the etiological role of diet in cancer risk. The study design is described in detail elsewhere (19). From December 1993 through May 1997, 80 996 men and 79 729 women aged 50–64 y were invited to participate in the study; 27 177 men and 29 876 women accepted the invitation. Eligible cohort members were born in Denmark, were living in the Copenhagen and Aarhus areas, and had no previous cancer diagnosis in the Danish Cancer Registry. The baseline data were linked to the Danish Cancer Registry and other nationwide population-based registries, including the National Registry ofPatients and the Civil Registration System, by using the civil registry number, which is the unique number given to every Danish citizen at birth. Information on death or emigration was obtained through record linkage with the Civil Registration System, which has kept electronic records of all changes in vital status, including change in address, date of emigration, and date of death, for the entire Danish population since 1968.
The Danish National Registry of Patients, established in 1977, records 99.4% of all discharges from nonpsychiatric hospitals in Denmark (20). The data include the civil registry number, dates of admission and discharge, surgical procedures performed, and up to 20 discharge diagnoses, which were classified until 1993 according to the Danish version of the International Classification of Diseases, 8th revision (ICD-8), and subsequently according to the corresponding national version of ICD-10 (20). All discharge diagnoses are assigned exclusively by the physician who discharges the patient. To study incident cases of stroke, we excluded participants who had been hospitalized before enrollment with cardiovascular disease, ie, stroke, transient ischemic attack, ischemic heart disease, or peripheral arteriosclerosis, as recordedin the National Registry of Patients (ICD-8 codes: 410–414, 430–438, and 440, and ICD-10 codes G45, I20–25, and I60–70). Both the Diet, Cancer, and Health study and the present substudy were approved by the Regional Ethics Committees in Copenhagen and Aarhus and by The Danish Data Protection Agency.
Baseline data
All cohort members completed a detailed 192-item semiquantitative food-frequency questionnaire (FFQ). Descriptions of the development and validation of the questionnaire were published previously (21, 22). All the participants also completed a questionnaire about other lifestyle factors, such as smoking habits, alcohol intake, physical activity, health, education, and, for women, use of hormone replacement therapy. Height, weight, waist and hip circumferences, blood pressure, and total serum cholesterol concentrations were also measured at baseline.
Intake of fruit and vegetables
We estimated intakes of fruit and vegetables from the FFQ, in which the participants reported their average intake of different food items over the previous year within 1of 12 possible intake categories, which ranged from never to ≥ 8 times/d. Daily intakes of specific foods and nutrients, including 42 different types of fruit and vegetables, were calculated from the FFQ for each participant by using the software program Food Calc (23). Standard recipes and sex-specific portion sizes were applied to calculate intake in grams per day by using data from different sources, ie, the 1995 Danish National Dietary Survey (24), 24-h diet recall interviews from 3818 of the study participants (25), and various cookery books.
Fruit and vegetables were grouped into the following 10 categories according to the classifications of the American Institute for Cancer Research (26): leafy vegetables (eg, lettuce and spinach), fruiting vegetables (ie, avocados, cucumbers, aubergines, peppers, peas, pumpkins, zucchini, green beans, and tomatoes), root vegetablesother than potatoes (eg, carrots), cruciferous vegetables (eg, broccoli, Brussels sprouts, cauliflower, and cabbage), mushrooms, onion and garlic, stalk vegetables (eg, leeks and asparagus), citrus fruit (eg, oranges and grapefruit), other fruit (eg, apples and pears), and fruit and vegetable juices. Thus, fruit and vegetables were grouped by using a combination of botanical and culinary criteria. Potatoes were not included in the analyses.
Stroke data
A detailed description of the assessment of cases of stroke in the cohort was published previously (26). We identified probable cases of ischemic stroke within the cohort from The Danish National Registry of Patients; these were cases with ICD-10 discharge diagnoses of I60–69.8 and G45 through 1998 for persons living in the Copenhagen area and through 1999 for persons living in the Aarhus area. Medical records and hospital discharge letters were retrieved and reviewed by a single reviewer using a detailed standardized form (26).
We used the World Health Organization’s definition of stroke, ie, an acute disturbance of focal or global cerebral function with symptoms lasting more than 24 h or leading to death of presumed vascular origin (27). A computed tomography or magnetic resonance scan, a spinal fluid examination, or an autopsy or operation description was necessary to distinguish between ischemic infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. All cases of ischemic stroke included in this study were verified by a computed tomography or magnetic resonance scan.
We subclassified all cases of ischemic stroke on the basis of the presumed etiology according to the following Trial of Org 10172 (a low-molecular-weight heparinoid) in Acute Stroke Treatment (TOAST) classifications: large-artery atherosclerosis, cardioembolism, small-vessel occlusion, stroke of other determined etiology, andstroke of undetermined etiology (28). These classifications are based on clinical features, ie, cortical or cerebellar dysfunction and lacunar syndrome, and on data (eg, location and size of infarct) collected by tests such as brain imaging, cardiac imaging, duplex imaging of extracranial arteries, arteriography, and laboratory assessments for a prothrombotic state.
Data analysis
Follow-up for ischemic stroke began on the date on which the subjects visited one of the study centers and ended on the date of their first hospital admission for ischemic stroke, the date of a censoring event (ie, hospitalization for intracerebral hemorrhage, subarachnoid hemorrhage, unspecified stroke, or transient ischemic attack; death; or emigration), or 31 December 1998 for participants living in the Copenhagen area or 31 December 1999 for participants living in the Aarhus area, whichever came first. We categorized the intake of fruit and vegetables (in g/d) into quintiles, and the risk of ischemic stroke was compared between the quintiles by using the lowest quintile as the reference. We used the nonparametric test developed by Cuzick (29) to test for trends in the distribution of the potentially confoundingvariables across the quintiles. A chi-square test was used for categorical variables.
We used Cox proportional hazards regression to obtain risk ratios (RRs) adjusted for possible confounders, ie, sex, total energy intake, smoking status, blood pressure, serum cholesterol, diabetes mellitus, body mass index, alcohol intake, intake of red meat and n-3 polyunsaturated fatty acids, physical activity, and education. We used 2 approaches for fitting the multivariate models to first identify the most important confounding factors and then to adjust for all available possible confounders. First, to adjust for confounding, we used the change-in-estimate method, in which variables were selected on the basis of changes in the risk estimates of interest (adjusted model) (30). Besides diet, the variables included in these models were sex, total energy intake, and smoking. Second, we extended this adjusted model with the additional variables (full model), ie, systolic and diastolic blood pressure, serum cholesterol at baseline, diabetes mellitus, body mass index, alcohol intake, intake of red meat and n-3 polyunsaturated fatty acids, physical activity, and education. Age was used as the time axis, ie, for subjects who entered the study in December 1993, age at the time of inclusion in the study and age at the time of censoring were equal to chronological age at those time points. However, for subjects who entered the study later, we adjusted for their delayed entry at the time of enrollment because the age at which the participants became at risk (ie, the length of time from birth to the startof the study) was not identical with the age at which they came under observation (ie, the length of time from birth to inclusion in the study). We thus adjusted for delayed entry by defining the age at which the participants became at risk and the age at which they came under observation as separate time points, ie, time from birth to the start of the study and time from birth to inclusion in the study, respectively. The assumption of proportional hazards in the Cox models was evaluated by usinggraphical assessment and was found to be appropriate in all models.
We adjusted for energy intake by using the residual method (31), ie, residuals were computed from a linear regression model with fruit and vegetable intake as the dependent variable and total energy intake as the independent variable. The predicted fruit and vegetable intake for a person having an energy intake equal to the mean value for the study population was added as a constant. The total energy intake was also included in the models.
Present tobacco consumption (in g/d) was calculated by equating a cigarette with 1 g tobacco, a cheroot or pipe with 3 g, and a cigar with 4.5 g. Smoking status was included in the models at 5 levels: never smoker, former smoker, and current smoker of 1–14, 15–24, or ≥ 25 g tobacco/d. Systolic and diastolic blood pressure at baseline, body mass index at baseline, intake of red meat and n-3 polyunsaturated fatty acids (in g/d), and recreational physical activity (in h/wk) were included as continuous variables, whereas total serum cholesterol concentration was included as a dichotomized variable (≤ 6 compared with > 6 mmol/L), and length of education after elementary school was included with 4 categories (0, <> 4 y).
We also used separate Cox models to carry out analyses stratified by sex and smoking status and analyses that included product terms to assess possible effect modification by these variables. Finally, the analyses were repeated according to different subtypes of ischemic stroke, ie, large-artery atherosclerosis, cardioembolism,small-vessel occlusion, and stroke of undetermined etiology; official Danish recommendations (daily intake of fruit and vegetables ≥ 600 g); and length of follow-up (< class="blsp-spelling-error" id="SPELLING_ERROR_4">CIs throughout the analyses. All analyses were performed with the use of STATA statistical software (release 7.0; Stata Corporation, College Station, TX). RESULTS TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES The cohort included 57 053 persons at baseline. We excluded 2500 persons (4.4%) who were previously registered with cardiovascular disease in the Danish National Registry of Patients and 47 persons (0.08%; including 2 persons with stroke) who left ≥ 10 items blank on the FFQ or who had ≥ 7 items with implausible values. The study population thus included 54 506 persons, who provided a total of 168 388 person-years of risk (median: 3.09 y; range: 0.02–5.10 y). Information on all variables was available for 53 035 persons (97.3% of the persons included in the present study). Characteristics of the study participants by quintile of total fruit and vegetable intake (in g/d) are shown in Table 1 . The median intake of fruit and vegetables ranged from 147 g/d in the lowest quintile to 673 g/d in the highest quintile. Total intake of fruit and vegetables was positively associated with the proportion of women (ie, 39.7% of the subjects in the lowest quintile were women, whereas 67.7% of the subjects in the highest quintile were women), with the proportions of subjects having a higher education and diabetes mellitus, and with total energy intake. By contrast, total intake of fruit and vegetables was negatively associated with the proportion ofcurrent smokers (ie, 53.2% of the subjects in the lowest quintile were current smokers, whereas 25.1% of the subjects in the highest quintile were current smokers) and with the proportions of subjects having hypertension, high cholesterol, and high alcohol intake. View this table: [in this window] [in a new window] TABLE 1 . Characteristics of study participants by quintile of total fruit and vegetable intake (in g/d)1 We verified 266 instances of first-time acute ischemic stroke among the study participants during follow-up. These events included 27 (10.2%) instances of stroke due to large-artery atherosclerosis, 24 (9.0%) instances of stroke due to cardioembolism, 115 (43.2%) instances of stroke due to small-vessel occlusion, 2 (0.8%) instances of stroke due to other determined etiology, and 98 (36.8%) instances of stroke of undetermined etiology. RRs of acute ischemic stroke by quintile of fruit and vegetable intake are shown in Table 2 . The total combined intake of fruit and vegetables, as well as the total separate intakes of fruit and of vegetables, was associated with a reduced risk of acute ischemic stroke in the unadjusted models; relative to the lowest quintile, the RRs for the highest quintile were between 0.40 and 0.63. Adjustment for sex, total energy intake, and smoking status weakened the association (RRs: 0.52–0.85); however,the directions of the associations remained unchanged. Whether energy intake was adjusted for by residuals of the dietary exposure variable alone or by residuals and total energy intake in combination had no influence on the estimates. The RRs were further weakened after additional adjustment for systolic and diastolic bloodpressure, serum cholesterol at baseline, diabetes mellitus, body mass index, alcohol intake, intake of red meat and n-3 polyunsaturated fatty acids, physical activity, and education; however, the effect of adjustment for these factors was modest in most of the models. The lowest RR in the full model was seen in the highest quintile of fruit intake (RR = 0.60; 95% CI: 0.38, 0.95; P = 0.03). View this table: [in this window] [in a new window] TABLE 2 . Risk ratios and 95% CIs of ischemic stroke by quintile (Q) of fruit and vegetable intake1 Regarding specific types of fruit and vegetables, the results indicated a reduced risk of acute ischemic stroke for most of the items except mushrooms, onion and garlic, and stalk vegetables: relative to the lowest quintiles, crude RRs for the highest quintiles were between 0.45 and 0.69 (Table 3 ). Adjustment for the most influential confounding factors weakened these associations, making most of them nonsignificant. Additional adjustment for potentially confounding factors had a minor effect on the risk estimates. We found the lowest RRs in the full model in the highest quintiles of intake of citrus fruit (RR = 0.63; 95% CI: 0.41, 0.96; P = 0.03) and other fruit (RR = 0.67; 95% CI: 0.43, 1.04; P = 0.08). View this table: [in this window] [in a new window] TABLE 3 . Risk ratios and 95% CIs of ischemic stroke by quintile (Q) of intake of specific groups of fruit and vegetables1 Some variation in the risk estimates, eg, when comparing the highest and the lowest quintiles of total fruit and vegetable intake, was seen when we stratified by smoking status (never or former smokers compared with current smokers [the RRs (and 95% CIs) for the nonsmokers and the smokers were 0.93 (0.47, 1.82) and 0.65 (0.35, 1.20), respectively (P = 0.37)]) and sex [the RRs (and 95% CIs) for the men and the women were 0.88 (0.49, 1.60) and 0.68 (0.34, 1.40), respectively (P = 0.62)]. However, none of these differences was significant. The associations between fruit and vegetable intake and ischemic stroke were also evaluated separately for different subtypes of ischemic stroke because the pathophysiologic mechanisms involved in the different subtypes are likely to be different. No differences were found; however, some of the risk estimates were imprecise because of the relatively low number of outcomes, particularly for large-artery atherosclerosis and cardioembolism (data not shown). The lowest RRs were found in the highest quintile of fruit intake for strokes due to small-vessel occlusion [RR = 0.67 (95% CI: 0.34, 1.31)] and for strokes of undetermined etiology [RR = 0.50 (95% CI: 0.23, 1.08)]. However, inverse, nonsignificant associations were found for all types of ischemic stroke. Relative to the participants with a daily intake of < rr =" 0.90)" trend =" 0,04)." trend =" 0.02)."> 6 mmol / L), dan panjang setelah pendidikan sekolah dasar yang termasuk dalam 4 kategori (0, <3,> 4 y).
Kami juga digunakan terpisah Cox model untuk melakukan analisis bertingkat oleh jenis kelamin dan status merokok dan analisis produk yang menyertakan persyaratan untuk menilai kemungkinan efek modifikasi oleh variabel-variabel tersebut. Terakhir, analisis yang diulang menurut subtypes berbeda dari ischemic stroke, yaitu besar-artery atherosclerosis, cardioembolism, kecil-kapal kemacetan, dan stroke yg tak dpt ditentukan dari etiologi; resmi Denmark rekomendasi (harian asupan buah-buahan dan sayuran ≥ 600 g), dan panjang tindak lanjut (<1 dibandingkan dengan 1 ≥ y).
Kami diperkirakan P untuk tren risiko stroke menurut asupan buah-buahan dan sayuran berdasarkan pada uji Wald, setelah masuknya individu eksposur variabel kontinu sebagai tindakan. Kami dihitung 95% CIS di seluruh analisis. Semua analisis yang dilakukan dengan menggunakan perangkat lunak statistik STATA (release 7.0; Stata Corporation, College Station, TX).
Kelompok yang termasuk 57 053 orang di dasar. Kami dikecualikan 2500 orang (4,4%) yang sebelumnya terdaftar dengan penyakit cardiovascular di Denmark yang Pasien Registry Nasional dan 47 orang (0,08%; termasuk 2 orang dengan stroke) yang kiri ≥ 10 item kosong pada FFQ atau yang telah ≥ 7 item implausible dengan nilai-nilai. Studi populasi sehingga termasuk 54 506 orang, yang disediakan total 168 388 orang-tahun risiko (median: 3,09 y; kisaran: 0,02-5,10 y). Informasi tentang semua variabel yang tersedia untuk 53 035 orang (97,3% dari orang yang termasuk dalam kajian ini).
Karakteristik kajian oleh peserta dari total quintile buah dan sayuran intake (dalam g / d) yang akan ditampilkan pada Tabel 1. The median asupan buah-buahan dan sayuran berkisar antara 147 g / d terendah di quintile ke 673 g / d tertinggi di quintile. Total asupan buah-buahan dan sayuran yang positif berkaitan dengan proporsi perempuan (yakni, 39,7% dari mata pelajaran di quintile terendah adalah perempuan, sedangkan 67,7% dari mata pelajaran di tingkat quintile adalah perempuan), dengan proporsi mata pelajaran yang memiliki pendidikan tinggi dan diabetes mellitus, dan dengan total asupan energi. Dengan kontras, total asupan buah-buahan dan sayuran adalah negatif yang terkait dengan proporsi ofcurrent perokok (yakni, 53,2% dari mata pelajaran di quintile terendah adalah perokok aktif, sedangkan 25,1% dari mata pelajaran di tingkat quintile adalah perokok saat ini) dan dengan proporsi mata pelajaran yang memiliki hipertensi, kolesterol tinggi, dan asupan alkohol tinggi.
Kami diverifikasi 266 kasus yang pertama kali ischemic stroke akut di kalangan peserta studi selama tindak lanjut. Acara ini termasuk 27 (10,2%) kasus stroke karena besar-artery atherosclerosis, 24 (9,0%) kasus stroke akibat cardioembolism, 115 (43,2%) kasus stroke akibat kemacetan kapal kecil, 2 (0,8%) kejadian stroke karena etiologi lainnya ditentukan, dan 98 (36,8%) dari kasus stroke yg tak dpt ditentukan etiologi.
RRs dari ischemic stroke akut oleh quintile dari asupan buah dan sayuran yang akan ditampilkan pada Tabel 2. Total gabungan dari asupan buah dan sayuran, serta total intakes terpisah dari buah-buahan dan sayuran, yang terkait dengan mengurangi risiko ischemic stroke akut di unadjusted model; relatif ke terendah quintile, maka untuk RRs tertinggi adalah quintile antara 0,40 dan 0,63. Penyesuaian untuk jenis kelamin, asupan energi total, dan status merokok melemah asosiasi (RRs: 0.52-0.85), namun arahnya dari asosiasi tetap tidak berubah. Apakah asupan energi untuk disesuaikan oleh residuals dari diet eksposur variabel sendiri atau oleh residuals dan asupan energi total dikombinasikan tidak memiliki pengaruh pada perkiraan. RRs yang telah melemah lebih lanjut setelah penyesuaian tambahan untuk systolic dan diastolic bloodpressure, di dasar serum kolesterol, diabetes mellitus, body mass index, asupan alkohol, asupan daging merah dan n-3 polyunsaturated fatty acid, aktivitas fisik, dan pendidikan, namun yang efek penyesuaian untuk faktor-faktor ini adalah yang paling sederhana dalam model. Terendah di RR penuh model yang terlihat dalam buah-buahan tertinggi quintile asupan (RR = 0,60; 95% CI: 0,38, 0,95; P = 0,03).
Spesifik mengenai jenis buah-buahan dan sayuran, hasil menunjukkan penurunan risiko stroke ischemic akut untuk sebagian besar item kecuali jamur, bawang merah dan bawang putih, dan sayur-sayuran tangkai: relatif ke terendah quintiles, crude RRs untuk quintiles adalah yang tertinggi di antara 0,45 dan 0,69 (Tabel 3). Penyesuaian untuk yang paling berpengaruh confounding faktor melemah asosiasi ini, sehingga kebanyakan mereka nonsignificant. Tambahan untuk penyesuaian potensial confounding faktor yang kecil terhadap perkiraan resiko. Kami menemukan terendah di RRs penuh model tertinggi dari asupan quintiles dari buah jeruk (RR = 0,63; 95% CI: 0,41, 0,96; P = 0,03) dan buah (RR = 0,67; 95% CI: 0,43, 1,04 ; P = 0,08). Beberapa variasi dalam perkiraan resiko, misalnya, ketika membandingkan tertinggi dan terendah quintiles dari total asupan buah dan sayuran, yang terlihat ketika kita bertingkat oleh status merokok (atau tidak pernah mantan perokok dibandingkan dengan perokok saat ini [yang RRs (CIS dan 95%) untuk nonsmokers dan perokok adalah 0,93 (0,47, 1,82) dan 0,65 (0,35, 1,20), masing-masing (P = 0,37)]) dan jenis kelamin [yang RRs (CIS dan 95%) untuk laki-laki dan perempuan adalah 0,88 (0,49, 1,60) dan 0,68 (0,34, 1,40), masing-masing (P = 0,62)]. Namun, tidak ada yang perbedaan yang signifikan.
Asosiasi di antara buah-buahan dan sayuran dan asupan ischemic stroke juga dievaluasi secara terpisah untuk berbagai subtypes dari ischemic stroke pathophysiologic karena mekanisme yang terlibat dalam berbagai subtypes yang mungkin berbeda. Tidak ada perbedaan yang ditemukan, namun beberapa risiko perkiraan yang tepat karena yang relatif rendah jumlah hasil, terutama untuk besar-artery atherosclerosis dan cardioembolism (data tidak ditampilkan). RRs terendah yang ditemukan dalam buah-buahan tertinggi quintile asupan untuk Strokes karena kecil-kapal kemacetan [RR = 0,67 (95% CI: 0,34, 1,31)], dan untuk Strokes yg tak dpt ditentukan dari etiologi [RR = 0,50 (95% CI: 0,23 , 1,08)]. Namun, terbalik, nonsignificant asosiasi yang ditemukan untuk semua jenis ischemic stroke.
Relatif terhadap para peserta dengan harian asupan dari <100 g buah-buahan dan sayuran, para peserta dengan asupan harian yang ≥ 600 g, yang sesuai dengan rekomendasi resmi Denmark, memiliki RR dari ischemic stroke akut dari 0,63 (95% CI: 0,33, 1,22) (full model). Kami mencari segala penyakit di preclinical dasar yang mungkin terpengaruh diet gaya hidup atau faktor lainnya, namun ketika kasus yang melibatkan potensi preclinical penyakit yang dikeluarkan dari tahun pertama dari tindak lanjut, resiko estimatesdid tidak berubah (data tidak ditampilkan).
DISKUSI
TOP
ABSTRAK
PENDAHULUAN
Subjek dan metode
HASIL
DISKUSI
REFERENSI
Dalam hal ini besar kelompok belajar, termasuk orang yang berusia 50-64 y di dasar, maka asupan buah-buahan, terutama buah jeruk dan lainnya, adalah terkait dengan mengurangi risiko ischemic stroke akut. Kami tidak menemukan jelas asosiasi antara asupan dari sayuran dan riskof akut ischemic stroke. Berkurangnya risiko yang paling jelas untuk Strokes karena-kapal kecil dan kemacetan Strokes ofundetermined etiologi. Kekuatan utama kita adalah belajar banyak hal, yang divalidasi dan komprehensif assessmentof asupan makanan, dan informasi lengkap tentang berbagai potensi confounding faktor; lengkap tindak lanjut melalui nasional, penduduk berbasis registries, yang membatasi risiko seleksi dan surveilans bias, dan standar penilaian semua hasil kegiatan terdaftar.
Untuk identifikasi potensi kejadian stroke, kami diandalkan di coding dari cerebrovascular diagnosa oleh dokter rumah sakit pada saat pasien telah habis. Oleh karena itu, kami dapat hanya untuk menyertakan Strokes yang dipimpin ke rumah sakit. Namun, mengingat usia profil kami belajar kelompok, ada kemungkinan bahwa kebanyakan pasien dengan gejala klinis akut stroke dirujuk ke rumah sakit untuk evaluasi lebih lanjut dan kerugian untuk tindak lanjut yang mungkin nondifferential dan sederhana karena ofthe singkat ikuti up periode.
Walaupun kita disesuaikan untuk confounding beberapa faktor dalam analisis, kemungkinan masih sisa confounding. Yang tinggi asupan buah-buahan dan sayuran, khususnya yang tinggi dan asupan buah-buahan, mungkin juga menjadi indikator keseluruhan lebih dari gaya hidup sehat (32) itu, selain termasuk diukur perilaku elemen seperti menjadi nonsmoker yang moderat dan asupan alkohol, juga mencakup berbagai perilaku yang lebih halus dan psikososial elemen. Selain itu, pengetahuan tentang diet dan sikap terhadap kesehatan dan makanan yang cenderung dikaitkan dengan asupan buah dan sayuran (33). Sebaliknya, mungkin juga akan berpendapat bahwa potensi untuk penyesuaian antara faktor kausal jalan di antara buah-buahan dan sayuran dan asupan risiko ischemic stroke, misalnya, tekanan darah dan serum kolesterol, adalah sulit dan dapat berakibat risiko perkiraan yang terlalu konservatif .
Akhirnya, baik eksposur dan confounder data mungkin telah terganggu misclassification, yang, karena sifat yang prospektif kami belajar desain, mungkin independen dari penilaian stroke, yaitu nondifferential. Nondifferential misclassification dari eksposur data, misalnya, karena dari imprecision dari dietaryquestionnaire di dasar atau karena perubahan dalam praktek diet di antara para peserta selama tindak lanjut, kami akan mengurangi kemampuan untuk mendeteksi setiap asosiasi antara asupan sayur dan buah-buahan dan risiko akut ischemic stroke, sedangkan nondifferential misclassification dari variabel confounder dapat mengakibatkan sisa confounding dan dapat berakibat baik attenuation dan risiko inflasi dari perkiraan.
Temuan kami ini sesuai dengan mereka yang sebelumnya beberapa calon studi (6, 12, 13, 17, 18). Berdasarkan pada Perawat Kesehatan Studi dan Kesehatan Professionals' Follow-up Study, Joshipura dkk (13) yang dilaporkan dari RR 0,69 (95% CI: 0,52, 0,91) untuk tingkat quintile buah intake (median servings / d: laki-laki, 4,54; perempuan 4,33) relatif ke bawah quintile (median servings / d: laki-laki, 0,86; perempuan 0,72), yang mirip dengan RR 0,60 yang ditemukan di studi kami jika servings dianggap menjadi 100 g tiap. Mereka juga menemukan lebih lemah kalak asosiasi antara asupan dari sayuran sendiri dan risiko ischemic stroke (RR = 0,90) bila dibandingkan mereka yang tertinggi dari quintiles intake (median servings / d: laki-laki, 6,21; perempuan, 5,37) dengan terendah quintiles (median servings / d: laki-laki, 1,60; perempuan 1,36). Dengan kontras, dalam studi Framingham berdasarkan kelompok, Gillman et al (12) tidak menemukan bahwa efek perlindungan dari buah yang lebih kuat dibandingkan dengan sayur-sayuran. Namun, mereka hanya belajar termasuk 97 kasus stroke atau transient ischemic serangan. Namun, setiap kenaikan dari 3 harian servings buah atau sayuran yang berkaitan dengan RR untuk sementara ischemic stroke atau serangan 0,81 (95% CI: 0,56, 1,19) dan 0,74 (95% CI: 0,54, 1,02), masing-masing.
Dalam hal tertentu untuk jenis buah dan sayuran, perhatikan bahwa mengurangi risiko ischemic stroke yang paling nyata untuk item yang biasanya dimakan mentah, misalnya, rimbun, sayuran, buah jeruk, dan buah-buahan lainnya. Efek yang berpotensi perlindungan dari buah jeruk dalam studi ini juga sesuai dengan temuan sebelumnya pada buah dan sayuran yang kaya vitamin C (13) dan mungkin menunjukkan berperan untuk vitamin C. Sebaliknya, sedangkan lainnya studi menunjukkan bahwa bawang putih mungkin memiliki bermanfaat efek kesehatan dalam kaitannya dengan penyakit cardiovascular dan kanker (34), kami tidak menemukan pengurangan resiko di antara para peserta dengan nilai asupan bawang merah dan bawang putih. Namun, bawang putih wasvery asupan rendah kami belajar penduduk, yang kita tidak dapat belajar hal ini dengan lebih terperinci.
Beberapa mekanisme mungkin terlibat dalam perlindungan terlihat efek buah dan sayuran pada risiko ischemic stroke. Beberapa buah dan sayuran konstituen, termasuk micronutrients, antioksidan, phytochemicals, dan serat, telah menurun yang terkait dengan risiko stroke dan penyakit lainnya di cardiovascular hewan model dan pengamatan epidemiologic studi (4-8). Namun, bukti yang ada pada peran masing-masing konstituen yang selama ini sudah tak meyakinkan, dan hasil dari beberapa pengujian ini berpotensi bioactive compounds sendiri atau dikombinasikan dalam persidangan di randomized cardiovascular dan penyakit kanker telah mengecewakan, terutama pada orang yang memakan Barat diet (15, 35-39). Mungkin ada penjelasan untuk berbagai temuan-temuan, misalnya, tak berguna dosis singkat dan belajar lama. Selain itu, peran satu gizi mungkin tidak mudah terisolasi dari kompleks biochemical konten tanaman pangan. Selain itu, upaya membuat sebab-musabab di inferences innutritional konstituen epidemiologi spesifik antara buah-buahan dan sayur-sayuran dan kemudian risiko penyakit yang terhambat oleh berbagai konten konstituen biologis aktif, misalnya, vitamin C, ß-carotene, dan flavonoids, dalam buah dan sayuran, yang tergantung pada asal geografis, musim tahun, metode penyimpanan dan memasak, dll masalah ini sulit untuk mempelajari gizi spesifik, dan mereka juga sulit untuk mencoba untuk membagi buah-buahan dan sayuran oleh ofspecific jumlah konstituen dan micronutrients.
Kesimpulannya, sebelumnya telah diusulkan suatu efek perlindungan dari asupan tinggi buah dan sayuran pada risiko ischemic stroke. Dari hasil ini kami besar Denmark kelompok belajar yang mendukung hipotesa asupan makanan yang tinggi adalah buah dari independen terkait dengan pengurangan risiko ischemic stroke.
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