There has been no study with regard to the association between dietary fibers and the incidence of stroke and coronary heart disease (CHD) in Asia. We investigated the association between dietary fiber and the risk of cardiovascular disease (CVD), which we defined as stroke or CHD, in a Japanese population.
We studied 86 387 Japanese subjects (age 45–65 years, without CVD or cancer in 1995 as Cohort I and in 1998 as Cohort II) and used a self-administered questionnaire to follow-up the participants until the end of 2004. Dietary fiber intake was estimated from food-frequency questionnaires comprising 138 food items.
After 899 141 person-years of follow-up, we documented the incidence of 2553 strokes and 684 cases of CHD. Multivariable-adjusted hazard ratios (95% confidence intervals (CIs)) of CVD for the third to fifth quintiles of total fiber were 0.79 (0.63–0.99), 0.70 (0.54–0.89) and 0.65 (0.48–0.87) in women, respectively, compared with the lowest quintile. Total fiber intake was inversely associated with the incidence of stroke, either cerebral infarction or intracerebral hemorrhage in women. The results for insoluble fiber in women were similar to those for total fiber, whereas those for soluble fiber were weak. An inverse association of total fiber with CVD was observed primarily in non-smokers (P for trend=0.045 and 0.001) and not in smokers (probability values for interaction between total fiber and smoking were 0.06 and 0.01 in men and women, respectively).
Higher total dietary fiber was associated with reduced risk of CVD in Japanese non-smokers.
Prospective studies have revealed dietary fiber to be inversely associated with the risks of coronary heart disease (CHD) (Pietinen et al., 1996; Rimm et al., 1996; Wolk et al., 1999; Bazzano et al., 2003; Mente et al., 2009) and of stroke (Oh et al., 2005). Total fiber may provide the benefits of both water-soluble and -insoluble fiber. Water-soluble fiber may exert a cholesterol-lowering effect (Brown et al., 1999), especially on low-density lipoprotein cholesterol, without affecting the concentration of high-density lipoprotein cholesterol. Insoluble fiber may reduce the risk of CHD by slowing intestinal absorption of foods and by reducing clotting factors (Marckmann et al., 1990). However, most of these cohort studies were conducted in Western populations and targeted for CHD. The evidence for an inverse association between dietary fiber and stroke has been limited (Oh et al., 2005), especially in Asia. No study has comprehensively evaluated the effects of soluble and insoluble fiber on the incidence of stroke and CHD in Asia. In this study, we examined the effect of the dietary intake of total fiber and its components on the incidences of cardiovascular disease in the Japanese population.
Subjects and methods
Study design and samples
The Japan Public Health Center-based prospective study is an ongoing cohort study focusing on cardiovascular disease and cancer (Mannami et al., 2004; Baba et al., 2006; Otani et al., 2006; Kokubo et al., 2007). The study participants were residents of 27 cities and towns served by nine Public Health Centers (PHCs), located in Akita, Iwate, Nagano, Ibaraki, Niigata, Kochi, Nagasaki and Okinawa Prefectures. The age distributions at the time of entry were 40–59 years for Cohort I and 40–69 years for Cohort II, started in 1990 and 1993, respectively. Participants were identified using the population registry in each city or town without overlap (65 803 men and 67 520 women).
Baseline data collection
We assessed the dietary habits of participants using a food-frequency questionnaire in 1995 and 1998 for Cohorts I and II, respectively. The questionnaires were returned by 47 400 men (72%) and 53 538 women (79%). We estimated the dietary intake of each individual based on 138-food-item questionnaire, which was previously validated for estimating various nutrients and food groups (Ishihara et al., 2006). The questionnaire also collected data on demographics, lifestyle factors, occupation, height, weight, smoking, alcohol consumption, physical activity, working hours and mental stress. Cohort members were excluded from the analyses if they reported CHD, stroke or cancer in the questionnaires, moved out of the area before the baseline survey or incompletely answered the food-frequency questionnaire. After applying these exclusions, 40 046 men and 46 341 women in total were included in the analyses. This study was approved by the institutional review board of the National Cancer Center, Tokyo and the University of Tsukuba, Ibaraki, Japan. Each participant provided informed consent upon completion of the baseline questionnaire, which described the study purposes and follow-up. The study design was described in detail elsewhere (Watanabe et al., 2001).
The frequency response choices were as follows: ‘never’, ‘1–3 times per month’, ‘1–2 times per week’, ‘3–4 times per week’, ‘5–6 times per week’, ‘once/day’, ‘2–3 times per day’, ‘4–6 times per day’ and ‘⩾7 times per day’. A standard portion was shown for each food item, for example, 30 g per cabbage intake. The relative portion sizes were as follows: small (∼50% smaller than the standard size), medium (approximately the same as the standard) and large (∼50% larger than the standard size). Questions on white rice intake asked the relative sizes of rice bowls and the frequency of intake, and provided nine choices ranging from ‘<1 bowl per day’ to ‘10 bowls per day’ (Sasaki et al., 2003). The frequency for miso soup intake provided six choices: ‘almost never’, ‘1–3 times per month’, ‘1–2 times per week’, ‘3–4 times per week’, ‘5–6 times per week’ or ‘daily’.
We computed daily food intakes by multiplying the frequency by the relative portion of each food item from the food-frequency questionnaire. Daily intakes of individual nutrients were calculated using the food composition table developed for each questionnaire based on the fifth revised edition of the Standard Tables of Food Composition in Japan (The Council for Science and Technology, Ministry of Education, Culture, Sports, Science and Technology, Japan, 2005). Using this table, the dietary fiber content of each food can be estimated by employing the method of Prosky et al. (1985).
The rank correlations between dietary fiber estimates from dietary records and those from the food-frequency questionnaire were 0.41 and 0.57 in Cohorts I and II for men, and 0.41 and 0.53 in Cohorts I and II for women, respectively, all of which were assessed in our validation study (Tsubono et al., 1996). For both men and women, the major sources of dietary fiber consisted of natto (fermented soybeans; 7.9 and 7.3%), rice (7.4 and 5.1%), miso (fermented soybean paste; 6.2 and 4.4%), bread (4.4 and 4.9%), carrots (3.9 and 4.4%), shiitake (oriental black mushroom; 3.4 and 3.8%) and radish (2.9 and 2.9%), respectively (Otani et al., 2006).
Confirmation of stroke and ischemic heart disease
In total, 54 hospitals in the nine PHC areas were capable of computer tomographic scanning and/or magnetic resonance imaging (Kokubo et al., 2007). All were major hospitals that admitted acute stroke and CHD cases. Medical records were reviewed by registered hospital workers, PHC physicians or research physicians who were blinded to the baseline data. Incidences of stroke and CHD were registered during the follow-up period. To complete surveillance for fatal stroke and CHD, we also conducted a systematic search for death certificates. We obtained information on the underlying cause of death by checking against death certificate files, with permission to confirm mortality from cardiovascular diseases according to the International Classification of Death, 10th Revision: I00 to I99. All fatal strokes and CHD based on death certificates only have been registered as death certificate only cases.
Strokes were confirmed according to the National Survey of Stroke criteria. These criteria require the rapid onset of a constellation of neurological deficits lasting at least 24 h (or until death). For each stroke subtype, that is, ischemic stroke (thrombotic or embolic stroke), intracerebral hemorrhage and subarachnoid hemorrhage, a definite diagnosis was established based on the examination of computer tomographic scans, magnetic resonance images or autopsy findings (Iso et al., 2000). CHD indicated in the medical records was confirmed according to the criteria of the MONICA project, which requires chest pain, electrocardiographic evidence, cardiac enzyme abnormalities and/or autopsy findings (Tunstall-Pedoe et al., 1994). In this study, cardiovascular disease was defined as stroke or CHD.
For each subject, we calculated person-days of follow-up from the baseline to whichever of the following came first: the first end point, death, emigration or 31 December 2004. Changes in residential status were identified through the residential registry in each area. Subjects who moved from their original residence (2% of the total participants) were censored at that time.
The Cox proportional hazards ratios (HRs) were fitted to the categorized consumption (the reference group is the first quartile of dietary fiber) after adjusting for age, sex and other potential confounding factors, that is, smoking status (never, ex-smoker or current smoker of 1–19 or ⩾20 cigarettes per day); alcohol intake (non-drinkers (<1 day per month), occasional drinkers (1–3 days per month), weekly ethanol intake of 1–149, 150–299, 300–449 or ⩾450 g per week); body mass index (in quintiles); history of diabetes (yes or no); medication use for hypertension or hypercholesterolemia (yes or no); quintiles of energy-adjusted dietary intakes of fruits, vegetables, fish, sodium and isoflavone; leisure time spent engaged in exercise (<1 day per month, 1–3 days per month or ⩾1 day per week); and proximity to the nearest PHC. The Cox proportional HRs were fitted to the combination of categorized consumption and current smoking (yes or no) after adjusting for age, sex and other potential confounding factors, including interactive terms for the categorized dietary fiber intake and current smoking. We conducted tests for trends in confounding variables and HRs across increasing quintiles of dietary fiber intake by assigning a median value of each quintile. All statistical analyses were conducted using the SAS statistical package (version 8.2; SAS Institute Inc., Cary, NC, USA).
Table 1 shows the cardiovascular risk factors and intake of selected foods according to quintiles of dietary total fiber. In the food frequency questionnaire, both men and women in the higher quintiles of total dietary fiber intake were older, had lower prevalence of current smoking and drinking, had higher prevalence of engaging in exercise during leisure time (⩾1 time per week) and of taking antihypertensive and/or antihyperlipidemic drugs and had higher rates of diabetes. As for the daily intake of nutrients, both men and women, in the higher quintiles of dietary total fiber intake, had a higher intake of vegetables, fruits, fish, sodium and isoflavones. The findings were similar for water-soluble and -insoluble fibers (not shown in the table).
During a follow-up period that averaged 10.4 years, we documented 2553 strokes (1499 in men and 1054 in women) and 684 CHD events (485 in men and 199 in women). The strokes included 1428 cerebral infarctions (910 in men and 518 in women), 766 intracerebral hemorrhages (456 in men and 310 in women) and 359 subarachnoid hemorrhages (133 in men and 226 in women). Of the CHD events, 383 were confirmed clinically or by autopsy and 14 were sudden cardiac deaths. In total, 3237 cardiovascular disease events (1984 in men and 1253 in women) were documented.
Multivariable-adjusted HRs (95% confidence intervals) of cardiovascular disease for the second to fifth quintiles of total fiber were 0.88 (0.78–0.99), 0.93 (0.81–1.07) and 0.77 (0.65–0.92) in men and women combined, respectively, compared with the lowest quintile (P for trend=0.02; data not shown). In the age-adjusted analysis, total fiber intake was inversely associated with cardiovascular diseases (stroke and CHD combined) in both men (P for trend<0.001) and women (P for trend=0.004) (Table 2). After further adjustment for confounding factors, these relationships in women persisted. Likewise, there were inverse associations in women, although no statistically significant association in men between total fiber and the incidences of cardiovascular diseases, stroke and either cerebral infarction or intracerebral hemorrhage, but not CHD.
We observed inverse associations between insoluble fiber and the incidences of cardiovascular disease, total stroke, cerebral infarction and intracerebral hemorrhage in women, whereas the inverse associations for soluble fiber in women were weak (Table 3). In men, these relationships were not statistically significant for either soluble or insoluble fiber (not shown in the table).
The inverse associations of total dietary fiber intake with incidence of cardiovascular diseases were statistically significant for both men and women who had never smoked (trend P=0.045 and 0.001, respectively), but not in smokers of either gender (Table 4). Interactions between total, water soluble and water-insoluble dietary fiber intake and smoking with regard to cardiovascular diseases were highly significant in women (P=0.01, 0.01 and 0.002, respectively), and weakly significant in men (P=0.06, 0.79 and 0.04).
In this study of middle-aged Japanese individuals, dietary intake of total fiber was found to be inversely associated with cardiovascular diseases in men and women who had never smoked. However, the association was not statistically significant in smokers of either gender. To the best of our knowledge, this is the first study on the association between dietary fiber intakes and the incidences of CHD and stroke in Asia.
A higher intake of dietary fiber, particularly water-soluble fiber, was associated with reduced risk of CHD in the NHANES I Study (Bazzano et al., 2003). In men, stronger inverse associations have been observed between cereal fiber and the risk of CHD than between vegetable or fruit fiber (mainly insoluble fiber) and the risk of CHD (Pietinen et al., 1996; Rimm et al., 1996). However, the evidence of stroke has been limited. In women, dietary fiber, especially cereal fiber, has also been inversely associated with the risk of stroke, particularly hemorrhagic stroke, but not with cerebral infarction (Oh et al., 2005). In Asia, recently, dietary intake of total fiber has been inversely associated with the risk of mortality from CHD (Eshak et al., 2010). In this study, dietary intake of total and insoluble fiber was inversely associated in Japanese women with the incidence of cardiovascular diseases, particularly cerebral infarction and intracerebral hemorrhage.
Insoluble fiber affects intestinal absorption of foods, reducing clotting factors (Marckmann et al., 1990; Anderson, 2000), fibrinolysis (Pereira and Pins, 2000) and coagulation (Jenkins et al., 2000). It also reduces the levels of inflammatory markers, such as C-reactive protein (Ajani et al., 2004; Ma et al., 2006). On the other hand, dietary water-soluble fiber reduces cholesterol levels (Brown et al., 1999; Pereira and Pins, 2000), improves glycemic control and lowers triglyceride levels (Anderson and Tietyen-Clark, 1986). However, based on a meta-analysis of 20 studies in which oat bran was added to the diet, the effects of water-soluble fiber on serum cholesterol appeared relatively modest (Ripsin et al., 1992) and could not account for the substantial effect of fiber on CHD incidence. A meta-analysis of 45 prospective cohort studies showed no association between blood cholesterol levels and stroke, except in those under 45 years of age when screened (Prospective Studies Collaboration, 1995). Although water-soluble fiber moderately reduces cholesterol levels, it may not contribute to the reduction of incident stroke.
A meta-analysis of randomized placebo-controlled trials has shown that dietary and supplementary fiber intakes (average dose, 11.5 g per day) lowers systolic and diastolic blood pressure by approximately −1 mm Hg, especially in older and hypertensive populations (Streppel et al., 2005). In prospective studies, dietary fiber was significantly and inversely associated with blood pressure (Ascherio et al., 1996) and the incidence of hypertension (Ascherio et al., 1992). As hypertension is the strongest risk factor for stroke (Kokubo et al., 2008), dietary fiber may moderately reduce the risk of stroke through a blood pressure-lowering effect.
In both men and women, there were inverse associations of total fiber with cardiovascular diseases only for those who had never smoked. The incidence of smoking is an established risk factor for stroke (Mannami et al., 2004) and coronary heart disease (Baba et al., 2006; Higashiyama et al., 2009) and seems to diminish the benefit of dietary fiber as was also shown previously (Liu et al., 2002). In women, the persistent inverse association between dietary fiber and cardiovascular diseases after the adjustment for cardiovascular risk factors was probably due to the very low prevalence of women smokers (5% of women versus 45% of men). The increased requirement for antioxidants among smokers may offset the protective effect of dietary fiber against cardiovascular disease (Jimenez et al., 2008). Habitual smoking may lead to other lifestyle changes, especially in dietary patterns: smokers consumed more calories, fat, alcohol and caffeine than did non-smokers (Liu et al., 2002). These dietary patterns may also diminish the benefit of dietary fiber. However, the mechanisms by which these factors interact to offset these benefits remain to be determined.
This study has certain methodological strengths compared with previous investigations. First, we evaluated a large prospective cohort (n=86 387) enrolled from the Japanese general population. A prospective study has little recall bias, and results obtained from the general population are more relevant than data obtained from an occupational, hospital-based cohort and/or volunteers. Second, incidence is a more direct measure of strokes risk than death because treatment influences stroke death. Third, we estimated dietary fiber intakes using a validated questionnaire. Our participants came from different areas of Japan and these populations consumed a sufficient variety of fiber types.
Our study has several limitations. First, data regarding present illnesses were self-reported, raising the problem of potential misclassification. However, our self-reported data may be reasonably accurate because nationwide annual health screenings, conducted since 1992 in Japan, produced similar results (Kawada and Suzuki, 2005). Second, measurement errors concerning nutrient intake are inevitable when using the food frequency questionnaire. However, the reproducibility of fiber intake measurements in the questionnaire was good, as documented previously (Tsubono et al., 1996). In this study, the reproducibility of fiber intake estimates suggests that any over- or under-estimates are likely to cancel each other out and result in an accurate overall estimate. Third, as we studied dietary fiber intake, our results are not relevant to the association between fiber supplements and stroke risk.
In conclusion, our community-based prospective study showed higher dietary intakes of total and insoluble fibers to be associated with reduced risk of total strokes, cerebral infarction and intracerebral hemorrhage in women. The inverse associations between dietary total fiber intake and cardiovascular diseases were statistically significant only for non-smokers. Our results suggest that dietary fiber may be beneficial for the prevention of cardiovascular diseases in non-smokers.
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We thank all of the staff members in each study area and in the central office for their painstaking efforts in conducting the baseline survey and follow-up research. This study was supported by Grants-in-Aid for Cancer Research and the Third-Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan.
The authors declare no conflict of interest.
Additional Contributors to the Japan Public Health Center-based Prospective Study (JPHC study, principal investigator: S Tsugane) Group are as follows: S Tsugane, M Inoue, T Sobue and T Hanaoka, National Cancer Center, Tokyo; J Ogata, S Baba, T Mannami, A Okayama and Y Kokubo, National Cardiovascular Center, Osaka; K Miyakawa, F Saito, A Koizumi, Y Sano, I Hashimoto, T Ikuta and Y Tanaba, Iwate Prefectural Ninohe Public Health Center, Iwate; Y Miyajima, N Suzuki, S Nagasawa, Y Furusugi and N Nagai, Akita Prefectural Yokote Public Health Center, Akita; H Sanada, Y Hatayama, F Kobayashi, H Uchino, Y Shirai, T Kondo, R Sasaki, Y Watanabe, Y Miyagawa, Y Kobayashi and M Machida, Nagano Prefectural Saku Public Health Center, Nagano; Y Kishimoto, E Takara, T Fukuyama, M Kinjo, M Irei and H Sakiyama, Okinawa Prefectural Chubu Public Health Center, Okinawa; K Imoto, H Yazawa, T Seo, A Seiko, F Ito, F Shoji and R Saito, Katsushika Public Health Center, Tokyo; A Murata, K Minato, K Motegi, T Fujieda and S Yamato, Ibaraki Prefectural Mito Public Health Center, Ibaraki; K Matsui, T Abe, M Katagiri and M Suzuki, Niigata Prefectural Kashiwazaki and Nagaoka Public Health Center, Niigata; M Doi, A Terao, Y Ishikawa and T Tagami, Kochi Prefectural Chuo-higashi Public Health Center, Kochi; H Sueta, H Doi, M Urata, N Okamoto and F Ide, Nagasaki Prefectural Kamigoto Public Health Center, Nagasaki; H Sakiyama, N Onga, H Takaesu and M Uehara, Okinawa Prefectural Miyako Public Health Center, Okinawa; F Horii, I Asano, H Yamaguchi, K Aoki, S Maruyama, M Ichii and M Takano, Osaka Prefectural Suita Public Health Center, Osaka; Y Tsubono, Tohoku University, Miyagi; K Suzuki, Research Institute for Brain and Blood Vessels Akita, Akita; Y Honda, K Yamagishi, S Sakurai and N Tsuchiya, Tsukuba University, Ibaraki; M Kabuto, National Institute for Environmental Studies, Ibaraki; M Yamaguchi, Y Matsumura, S Sasaki and S Watanabe, National Institute of Health and Nutrition, Tokyo; M Akabane, Tokyo University of Agriculture, Tokyo; T Kadowaki, Tokyo University, Tokyo; M Noda and T Mizoue, International Medical Center of Japan, Tokyo; Y Kawaguchi, Tokyo Medical and Dental University, Tokyo; Y Takashima and Y Yoshida, Kyorin University, Tokyo; K Nakamura, Niigata University, Niigata; S Matsushima and S Natsukawa, Saku General Hospital, Nagano; H Shimizu, Sakihae Institute, Gifu; H Sugimura, Hamamatsu University, Shizuoka; S Tominaga, Aichi Cancer Center Research Institute, Aichi; H Iso, Osaka University, Osaka; M Iida, W Ajiki and A Ioka, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka; S Sato, Chiba Prefectural Institute of Public Health, Chiba; E Maruyama, Kobe University, Hyogo; M Konishi, K Okada and I Saito, Ehime University, Ehime; N Yasuda, Kochi University, Kochi; S Kono, Kyushu University, Fukuoka.
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