Abstract
Background/Objectives
There is convincing evidence that a high dietary fiber intake may lower the risk of coronary heart disease. However, the role of fiber in the prevention of stroke is unclear. We examined the associations of dietary fiber and fiber-rich food intake with risk of stroke within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.
Subjects/Methods
Between 1985 and 1988, 26 556 Finnish male smokers aged 50–69 years who had no history of stroke completed a dietary questionnaire. During a mean follow-up of 13.6 years, 2702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained.
Results
After adjustment for cardiovascular risk factors and folate and magnesium intakes, there was no significant association between intake of total fiber, water-soluble fiber, water-insoluble fiber, or fiber derived from fruit or cereal sources and risk of any stroke subtype. Vegetable fiber intake as well as consumption of fruit, vegetables, and cereals were inversely associated with risk of cerebral infarction; the multivariate relative risks (RR) for the highest quintile of intake compared with the lowest were 0.86 (95% confidence interval (CI): 0.76–0.99) for vegetable fiber, 0.82 (95% CI: 0.73–0.93) for fruit, 0.75 (95% CI: 0.66–0.85) for vegetables, and 0.87 (95% CI: 0.74–1.03) for cereals. Vegetable consumption was inversely associated with risk of subarachnoid hemorrhage (RR for highest versus lowest quintile: 0.62; 95% CI: 0.40–0.98) and cereal consumption was inversely associated with risk of intracerebral hemorrhage (RR: 0.64; 95% CI: 0.41–1.01).
Conclusions
These findings suggest a beneficial effect of consumption of fruits, vegetables, and cereals on stroke risk.
Keywords: cereals, dietary fiber, fruits, prospective studies, stroke, vegetables
Introduction
Diets high in fiber may reduce the risk of cardiovascular disease through several mechanisms. Experimental studies in humans have shown that dietary fiber, especially water-soluble fiber, favorably affects blood pressure, serum lipid profile, insulin sensitivity, and inflammation (Hallfrisch et al, 1995; Brown et al, 1999; Chandalia et al, 2000; Whelton et al, 2005; Weickert et al, 2006; King et al, 2007). Whereas compelling epidemiologic evidence indicates that a high dietary fiber intake may decrease the risk of coronary heart disease (Pereira et al, 2004), few studies have examined the role of dietary fiber in the prevention of stroke (Ascherio et al, 1998; Mozaffarian et al, 2003; Oh et al, 2005). Furthermore, no study has to our knowledge examined water-soluble and water-insoluble fiber in relation to risk of stroke.
We have previously found an inverse association between dietary fiber intake and risk of coronary heart disease among Finnish male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort (Pietinen et al, 1996). The purpose of the present study was to examine whether dietary fiber intake is associated with risk of stroke in this cohort. Besides total fiber intake, we assessed intakes of water-soluble and water-insoluble fiber as well as fiber from fruit, vegetable, and cereal sources. We also extended our previous analysis (Hirvonen et al, 2000) and examined the relation between fruit and vegetable consumption and stroke risk.
Subjects and Methods
Study population
The ATBC Study was established between 1985 and 1988 when 29 133 male smokers, aged 50–69 years and residing in southwestern Finland, were recruited to participate in a prevention trial (ATBC Cancer Prevention Study Group 1994). The study was a randomized, double-blinded, placebo-controlled primary prevention trial that was designed to determine whether supplementation with alpha-tocopherol, beta-carotene, or both would reduce the incidence of lung or other cancers. The trial ended in 1993, with registry-based followed thereafter. At baseline, men were excluded from the trial if they smoked fewer than five cigarettes per day; had a history of cancer, severe angina on exertion, chronic renal insufficiency, liver cirrhosis, chronic alcoholism, or other medical conditions that might limit long-term participation; or if they received anticoagulant therapy or used supplements containing vitamin E, vitamin A, or beta-carotene in excess of predefined doses. Information on dietary intake was provided by 26 556 (93%) of the randomized men who had no history of stroke at baseline.
Written informed consent was obtained from each participant before randomization. The study was approved by the institutional review boards of the National Public Health Institute of Finland and the US National Cancer Institute.
Baseline data collection
At baseline, participants provided information on background characteristics and medical, smoking, and physical activity histories (ATBC Cancer Prevention Study Group, 1994). Body weight, height, and blood pressure were measured using standard methods. Serum samples were collected and stored at −70°C for later analyses. Serum total cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were determined enzymatically (CHOD-PAP method, Boehringer Mannheim).
Dietary assessment
Diet was assessed at baseline with a validated self-administered food frequency questionnaire that included 276 food items and mixed dishes commonly consumed in Finland (Pietinen et al, 1988). The questionnaire was used with a portion-size picture booklet of 122 photographs of foods, each with three to five different portion sizes. Each man was asked to indicate his usual frequency of consumption and usual portion size of foods during the past year. Frequencies were reported as the number of times per month, week, or day. Dietary fiber and nutrient intakes were estimated using food composition data obtained from the National Public Health Institute in Finland. Data on fiber consumption was based on analyses of Finnish foods (Varo et al, 1984a; Varo et al, 1984b).
The dietary method was validated in a pilot study carried out among 189 men before the ATBC study (Pietinen et al., 1988). The men completed the food frequency questionnaire at the beginning and end of a 6-month period, and they kept food-consumption records for 24 days (2 × 12 days) in the interim period. The correlation coefficients between the dietary questionnaire and the food records were the following: total fiber 0.7, water-soluble fiber 0.7, water-insoluble fiber 0.7, fruit fiber 0.6, vegetable fiber 0.5, cereal fiber 0.7, fruits 0.6, vegetables 0.5, and cereals 0.7.
Ascertainment of end points
The endpoint was first-ever stroke that occurred between the date of randomization and December 31, 2004. The strokes were further divided into cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage and unspecified stroke. The end points were identified by record linkage with the National Hospital Discharge Register and the National Register of Causes of Death. Both registers used the codes of the International Classification of Diseases (ICD): the 8th edition was used until the end of 1986, the 9th edition through the end of 1996, and the 10th edition thereafter. The end points comprised ICD-8 codes 430–434 and 436, ICD-9 codes 430–431, 433–434 and 436, and ICD-10 codes I60, I61, I63, and I64, excluding ICD-8 codes 431.01 and 431.91 representing subdural hemorrhage and ICD-9 codes 4330X, 4331X, 4339X, and 4349X denoting occlusion or cerebral or precerebral artery stenosis without cerebral infarction. In a reviewed sample, the diagnoses of cerebral infarction, subarachnoid hemorrhage, and intracerebral hemorrhage proved correct by strict preset criteria (Walker et al, 1981) in 90%, 79%, and 82% of the discharge diagnoses and in 92%, 95%, and 91% of the causes of death, respectively (Leppälä et al, 1999).
Statistical analysis
Person-time for each participant was calculated from the date of randomization until the date of occurrence of first stroke, death from any cause, or the end of follow-up (December 31, 2004), whichever occurred first. Dietary fiber intake was adjusted for total energy intake using the residual method (Willett and Stampfer, 1986). Participants were categorized into quintiles of energy-adjusted dietary fiber intake. We used Cox proportional hazards models (Cox, 1972) to estimate relative risks with 95% confidence intervals for different quintiles of fiber intake, with simultaneous adjustment for age at baseline and supplementation group. In multivariate analysis, we additionally controlled for cardiovascular risk factors (body mass index, total number of cigarettes smoked daily, systolic and diastolic blood pressure, serum total and HDL cholesterol, histories of diabetes and coronary heart disease, and alcohol intake) and energy intake. In a second multivariate model, we further adjusted for dietary folate and magnesium intakes because these nutrients have been found to be inversely associated with risk of cerebral infarction in the ATBC Study (Larsson et al, 2008a; Larsson et al, 2008b) and are correlated with fiber intake.
Tests of linear trend across quintiles of fiber intake were conducted by assigning the median value for each quintile and treating this variable as a continuous variable. Effect modification was examined in stratified analyses and was statistically tested by including the cross-product term of fiber intake and the effect modifier. The statistical analyses were performed using Stata software, version 9.2 (StataCorp, College Station, Texas). All statistical tests were two-sided and P-values less than 0.05 were considered statistically significant.
Results
Baseline characteristics of the study population according to quintiles of total fiber intake are shown in Table 1. There was more than a 2-fold difference in the median fiber intake between the highest (35.8 g/day) and the lowest quintile (16.1 g/day) of the population. Men with a high fiber intake smoked slightly less cigarettes daily, were more likely to have a history of diabetes or coronary heart disease and to be physically active at leisure-time compared with those with a low fiber intake. Moreover, men with a high fiber intake consumed less alcohol and had higher intakes of folate, magnesium, fruits, vegetables, cereals, and rye products. The correlations between different types of fiber, fiber sources, and foods rich in fiber showed that in this population, water-soluble and water-insoluble fibers are highly correlated (r = 0.89) (Table 2). The main sources of fiber were cereals, particularly rye bread.
Table 1.
Age-standardized baseline characteristics by quintiles of total dietary fiber intake among 26 556 men in the ATBC Study a
| Quintiles of fiber intake
|
|||||
|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | |
| Median fiber intake, g/d | 16.1 | 20.9 | 24.7 | 28.9 | 35.8 |
| Age, y | 57.4 | 57.6 | 57.7 | 57.7 | 57.8 |
| Smoking, cigarettes/d | 22.8 | 21.0 | 20.1 | 19.4 | 18.9 |
| Body mass index, kg/m2 | 26.0 | 26.2 | 26.3 | 26.3 | 26.4 |
| Systolic blood pressure, mm Hg | 142.0 | 142.5 | 142.7 | 142.6 | 142.8 |
| Diastolic blood pressure, mm Hg | 88.3 | 87.8 | 87.4 | 87.2 | 87.3 |
| Serum total cholesterol, mmol/L | 6.20 | 6.25 | 6.27 | 6.24 | 6.25 |
| Serum HDL cholesterol, mmol/L | 1.24 | 1.20 | 1.19 | 1.18 | 1.16 |
| Diabetes, % | 4.9 | 4.9 | 5.7 | 5.9 | 7.6 |
| History of coronary heart disease, % | 10.0 | 10.8 | 11.2 | 10.8 | 12.1 |
| Physically active, % b | 56.9 | 57.6 | 60.4 | 63.5 | 66.9 |
| Daily intake | |||||
| Energy, kcal | 2656 | 2723 | 2716 | 2711 | 2651 |
| Alcohol, g | 29.3 | 19.6 | 16.4 | 13.9 | 11.1 |
| Folate, g | 288 | 314 | 333 | 350 | 384 |
| Magnesium, g | 411 | 442 | 469 | 498 | 558 |
| Water-soluble fiber, g | 3.7 | 4.8 | 5.6 | 6.3 | 7.8 |
| Water-insoluble fiber, g | 11.8 | 16.0 | 19.1 | 22.6 | 29.5 |
| Fruit fiber, g | 2.0 | 2.8 | 3.3 | 3.6 | 4.3 |
| Vegetable fiber, g | 4.1 | 4.7 | 5.2 | 5.2 | 5.4 |
| Cereal fiber, g | 9.2 | 13.4 | 16.5 | 20.4 | 28.2 |
| Fruits, g | 59.1 | 84.4 | 96.5 | 104.2 | 119.5 |
| Vegetables, g | 64.1 | 77.7 | 85.0 | 89.3 | 94.7 |
| Cereals, g | 158 | 193 | 214 | 237 | 277 |
| Rye products, g | 30.2 | 60.4 | 85.0 | 89.3 | 94.7 |
Values are means unless otherwise indicated.
Moderate or heavy activity at leisure time.
Table 2.
Correlations among different fiber types, sources of fiber, and foods rich in fibera
| Variable | Correlation
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
| Total fiber (1) | 1.00 | 0.93 | 0.99 | 0.33 | 0.27 | 0.91 | 0.26 | 0.19 | 0.50 | 0.77 |
| Water-soluble fiber (2) | … | 1.00 | 0.89 | 0.56 | 0.39 | 0.73 | 0.49 | 0.35 | 0.45 | 0.61 |
| Water-insoluble fiber (3) | … | … | 1.00 | 0.26 | 0.23 | 0.94 | 0.19 | 0.15 | 0.50 | 0.81 |
| Fruit fiber (4) | … | … | … | 1.00 | 0.23 | 0.04 | 0.81 | 0.37 | 0.05 | 0.01 |
| Vegetable fiber (5) | … | … | … | … | 1.00 | 0.00 | 0.19 | 0.55 | −0.01 | 0.03 |
| Cereal fiber (6) | … | … | … | … | … | 1.00 | 0.02 | −0.02 | 0.51 | 0.85 |
| Fruits (7) | … | … | … | … | … | … | 1.00 | 0.40 | 0.19 | 0.09 |
| Vegetables (8) | … | … | … | … | … | … | … | 1.00 | 0.17 | 0.06 |
| Cereals (9) | … | … | … | … | … | … | … | … | 1.00 | 0.57 |
| Rye products (10) | … | … | … | … | … | … | … | … | … | 1.00 |
Dietary fiber variables are adjusted for total energy intake.
During a mean follow-up of 13.6 years (360 187 person-years), we identified 2702 cerebral infarctions, 383 intracerebral hemorrhages, 196 subarachnoid hemorrhages, and 84 unspecified strokes. In analysis adjusted for age and supplementation group, total fiber, water-soluble fiber, and water-insoluble fiber intakes were significantly inversely associated with risk of cerebral infarction but not of intracerebral or subarachnoid hemorrhage (Table 3). The inverse associations were attenuated but remained statistically significant after further adjustment for cardiovascular risk factors and total energy intake. However, neither total fiber, soluble fiber, nor insoluble fiber remained significantly protective after additional adjustment for folate and magnesium intakes. The association between fiber intake and stroke was not significantly modified by age, cardiovascular risk factors (alcohol intake, cigarettes/day, smoking years, BMI, hypertension, serum total cholesterol, serum HDL cholesterol, physical activity) or by supplementation group (data not shown).
Table 3.
Relative risks (95% confidence intervals) of stroke subtypes by quintiles of total fiber and water-soluble and water-insoluble fiber intake among 26 556 men in the ATBC Study, 1985–2004
| Quintiles of fiber intake
|
P for trend | |||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | ||
| Total fiber | ||||||
| Median, g/d | 16.1 | 20.9 | 24.7 | 28.9 | 35.8 | |
| Cerebral infarction | ||||||
| Cases, n | 578 | 524 | 560 | 523 | 517 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.85 (0.75–0.95) | 0.88 (0.79–0.99) | 0.80 (0.71–0.90) | 0.80 (0.71–0.90) | <0.001 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.89 (0.79–1.00) | 0.95 (0.84–1.07) | 0.87 (0.77–0.98) | 0.86 (0.76–0.98) | 0.03 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.92 (0.82–1.04) | 1.01 (0.89–1.15) | 0.95 (0.83–1.10) | 1.01 (0.85–1.19) | 0.83 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 68 | 86 | 87 | 77 | 65 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.19 (0.86–1.63) | 1.17 (0.85–1.60) | 1.00 (0.72–1.38) | 0.85 (0.61–1.20) | 0.15 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.27 (0.92–1.76) | 1.30 (0.94–1.80) | 1.11 (0.79–1.56) | 0.94 (0.66–1.35) | 0.37 |
| Multivariate RR 2 (95% CI)c | 1.00 | 1.29 (0.92–1.79) | 1.32 (0.93–1.87) | 1.13 (0.77–1.63) | 0.97 (0.61–1.54) | 0.63 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 39 | 41 | 37 | 35 | 44 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.02 (0.66–1.58) | 0.91 (0.58–1.43) | 0.84 (0.53–1.33) | 1.07 (0.70–1.65) | 0.95 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.02 (0.65–1.59) | 0.92 (0.58–1.46) | 0.85 (0.53–1.37) | 1.09 (0.69–1.71) | 0.87 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.97 (0.62–1.53) | 0.84 (0.51–1.37) | 0.74 (0.44–1.26) | 0.86 (0.47–1.59) | 0.49 |
| Water-soluble fiber | ||||||
| Median, g/d | 3.8 | 4.8 | 5.5 | 6.3 | 7.7 | |
| Cerebral infarction | ||||||
| Cases, n | 590 | 530 | 549 | 547 | 484 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.85 (0.76–0.96) | 0.86 (0.76–0.96) | 0.83 (0.74–0.93) | 0.73 (0.64–0.82) | <0.001 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.91 (0.81–1.03) | 0.93 (0.82–1.04) | 0.91 (0.80–1.02) | 0.79 (0.69–0.89) | 0.001 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.93 (0.82–1.05) | 0.96 (0.85–1.10) | 0.96 (0.83–1.10) | 0.86 (0.73–1.02) | 0.17 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 66 | 98 | 88 | 65 | 66 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.40 (1.03–1.92) | 1.23 (0.89–1.69) | 0.88 (0.62–1.24) | 0.89 (0.63–1.25) | 0.06 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.55 (1.12–2.13) | 1.38 (0.99–1.92) | 0.98 (0.68–1.39) | 0.99 (0.69–1.42) | 0.35 |
| Multivariate RR 2 (95% CI)c | 1.00 | 1.55 (1.12–2.15) | 1.38 (0.97–1.97) | 0.98 (0.65–1.46) | 0.99 (0.62–1.59) | 0.60 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 37 | 37 | 41 | 38 | 43 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.96 (0.61–1.52) | 1.05 (0.67–1.63) | 0.96 (0.61–1.51) | 1.07 (0.69–1.67) | 0.75 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.97 (0.61–1.55) | 1.06 (0.67–1.68) | 0.98 (0.61–1.58) | 1.11 (0.69–1.77) | 0.66 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.94 (0.59–1.51) | 1.00 (0.61–1.63) | 0.90 (0.53–1.54) | 0.95 (0.51–1.79) | 0.86 |
| Water-insoluble fiber | ||||||
| Median, g/d | 12.2 | 16.0 | 19.1 | 22.6 | 28.3 | |
| Cerebral infarction | ||||||
| Cases, n | 577 | 537 | 534 | 528 | 526 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.86 (0.76–0.97) | 0.84 (0.74–0.94) | 0.81 (0.72–0.91) | 0.81 (0.72–0.91) | 0.001 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.90 (0.80–1.02) | 0.90 (0.80–1.02) | 0.88 (0.78–0.99) | 0.88 (0.76–0.99) | 0.06 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.94 (0.80–1.03) | 0.97 (0.85–1.10) | 0.97 (0.84–1.11) | 1.03 (0.87–1.21) | 0.61 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 72 | 89 | 76 | 80 | 66 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.14 (0.84–1.56) | 0.95 (0.69–1.32) | 0.98 (0.71–1.34) | 0.81 (0.58–1.14) | 0.11 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.22 (0.89–1.68) | 1.05 (0.75–1.46) | 1.08 (0.78–1.51) | 0.89 (0.63–1.26) | 0.29 |
| Multivariate RR 2 (95% CI)c | 1.00 | 1.22 (0.89–1.69) | 1.05 (0.74–1.50) | 1.08 (0.74–1.57) | 0.88 (0.56–1.39) | 0.43 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 38 | 39 | 41 | 35 | 43 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.99 (0.63–1.55) | 1.04 (0.67–1.61) | 0.86 (0.55–1.37) | 1.08 (0.70–1.67) | 0.89 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.02 (0.64–1.58) | 1.06 (0.67–1.66) | 0.88 (0.55–1.42) | 1.10 (0.70–1.75) | 0.80 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.96 (0.60–1.52) | 0.97 (0.60–1.57) | 0.78 (0.46–1.32) | 0.89 (0.49–1.64) | 0.58 |
Adjusted for age and supplementation group.
Adjusted further for number of cigarettes smoked daily, body mass index, systolic and diastolic blood pressures, serum total cholesterol, serum high-density lipoprotein cholesterol, histories of diabetes and coronary heart disease, leisure-time physical activity, and intakes of alcohol and total energy.
Adjusted further for intakes of folate and magnesium.
We also evaluated the associations of fiber derived from fruit, vegetable, and cereal sources with stroke risk (Table 4). After adjustment for age, supplementation group, cardiovascular risk factors, and intakes of total energy, folate, and magnesium, only intake of vegetable fiber was statistically significantly inversely associated with risk of cerebral infarction; the multivariate relative risk for the highest compared with the lowest quintile was 0.86 (95% CI: 0.76–0.99). When vegetable intake was included in the model in place of folate and magnesium intakes, the corresponding relative risks were 0.90 (95% CI: 0.78–1.04).
Table 4.
Relative risks (95% confidence intervals) of stroke subtypes by quintiles of fruit, vegetable, and cereal fiber intake among 26 556 men in the ATBC Study, 1985–2004
| Quintiles of fiber intake
|
P for trend | |||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | ||
| Fruit fiber | ||||||
| Median, g/d | 0.7 | 1.8 | 2.7 | 3.9 | 6.2 | |
| Cerebral infarction | ||||||
| Cases, n | 590 | 521 | 521 | 555 | 515 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.85 (0.75–0.95) | 0.82 (0.73–0.92) | 0.86 (0.77–0.97) | 0.78 (0.69–0.88) | 0.001 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.90 (0.80–1.01) | 0.88 (0.78–0.99) | 0.93 (0.83–1.05) | 0.86 (0.76–0.97) | 0.05 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.91 (0.81–1.03) | 0.90 (0.80–1.02) | 0.96 (0.85–1.09) | 0.91 (0.80–1.04) | 0.83 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 77 | 78 | 78 | 84 | 66 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.97 (0.71–1.33) | 0.93 (0.68–1.28) | 1.00 (0.73–1.36) | 0.76 (0.55–1.06) | 0.12 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.06 (0.77–1.45) | 1.00 (0.73–1.38) | 1.06 (0.78–1.46) | 0.82 (0.58–1.15) | 0.21 |
| Multivariate RR 2 (95% CI)c | 1.00 | 1.07 (0.78–1.48) | 1.04 (0.75–1.43) | 1.11 (0.80–1.55) | 0.88 (0.61–1.26) | 0.44 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 39 | 35 | 32 | 42 | 48 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.88 (0.56–1.39) | 0.79 (0.49–1.25) | 1.03 (0.67–1.60) | 1.18 (0.77–1.80) | 0.20 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.90 (0.57–1.42) | 0.79 (0.49–1.27) | 1.05 (0.67–1.64) | 1.23 (0.80–1.91) | 0.15 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.91 (0.57–1.45) | 0.81 (0.50–1.31) | 1.08 (0.68–1.71) | 1.28 (0.80–2.06) | 0.14 |
| Vegetable fiber | ||||||
| Median, g/d | 2.9 | 3.9 | 4.7 | 5.6 | 7.1 | |
| Cerebral infarction | ||||||
| Cases, n | 571 | 621 | 533 | 493 | 484 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.04 (0.93–1.17) | 0.89 (0.79–1.01) | 0.81 (0.72–0.92) | 0.79 (0.70–0.89) | <0.001 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.06 (0.94–1.18) | 0.92 (0.82–104) | 0.84 (0.74–095) | 0.82 (0.73–0.93) | <0.001 |
| Multivariate RR 2 (95% CI)c | 1.00 | 1.07 (0.95–1.20) | 0.94 (0.83–1.06) | 0.86 (0.76–0.98) | 0.86 (0.76–0.99)4 | 0.001 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 88 | 73 | 63 | 91 | 68 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.80 (0.58–1.08) | 0.69 (0.50–0.95) | 0.98 (0.73–1.31) | 0.73 (0.53–1.00) | 0.21 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.81 (0.59–1.10) | 0.70 (0.51–0.98) | 1.00 (0.74–1.35) | 0.76 (0.55–1.05) | 0.35 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.82 (0.60–1.11) | 0.72 (0.52–1.00) | 1.04 (0.76–1.41) | 0.81 (0.57–1.14) | 0.62 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 47 | 40 | 38 | 32 | 39 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.81 (0.53–1.23) | 0.76 (0.49–1.16) | 0.62 (0.40–0.97) | 0.74 (0.48–1.13) | 0.11 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.81 (0.53–1.23) | 0.77 (0.50–1.18) | 0.62 (0.39–0.97) | 0.74 (0.48–1.14) | 0.12 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.79 (0.52–1.20) | 0.73 (0.47–1.13) | 0.59 (0.37–0.93) | 0.63 (0.43–1.07)d | 0.06 |
| Cereal fiber | ||||||
| Median, g/d | 8.9 | 13.1 | 16.5 | 20.6 | 27.5 | |
| Cerebral infarction | 74 | 89 | 64 | 85 | 71 | |
| Cases, n | 563 | 531 | 525 | 549 | 534 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.87 (0.78–0.98) | 0.85 (0.76–0.96) | 0.87 (0.77–0.98) | 0.86 (0.77–0.97) | 0.04 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.93 (0.82–1.05) | 0.91 (0.80–1.02) | 0.95 (0.84–1.07) | 0.92 (0.82–1.04) | 0.36 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.95 (0.84–1.08) | 0.95 (0.84–1.08) | 1.03 (0.90–1.17) | 1.06 (0.91–1.23) | 0.25 |
| Intracerebral hemorrhage | ||||||
| Cases, n | ||||||
| Age-adjusted RR (95% CI)a | 1.00 | 1.11 (0.82–1.51) | 0.79 (0.56–1.10) | 1.02 (0.75–1.39) | 0.87 (0.63–1.20) | 0.31 |
| Multivariate RR 1 (95% CI)b | 1.00 | 1.18 (0.86–1.61) | 0.85 (0.61–1.20) | 1.12 (0.81–1.54) | 0.93 (0.66–1.30) | 0.55 |
| Multivariate RR 2 (95% CI)c | 1.00 | 1.18 (0.86–1.62) | 0.86 (0.60–1.22) | 1.13 (0.80–1.59) | 0.94 (0.63–1.42) | 0.71 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 44 | 35 | 39 | 33 | 45 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.77 (0.50–1.20) | 0.86 (0.56–1.32) | 0.72 (0.46–1.13) | 1.00 (0.66–1.52) | 0.93 |
| Multivariate RR 1 (95% CI)b | 1.00 | 0.77 (0.49–1.21) | 0.87 (0.56–1.34) | 0.73 (0.46–1.15) | 1.02 (0.66–1.57) | 0.84 |
| Multivariate RR 2 (95% CI)c | 1.00 | 0.75 (0.47–1.17) | 0.81 (0.52–1.28) | 0.66 (0.40–1.08) | 0.86 (0.50–1.46) | 0.60 |
Adjusted for age and supplementation group.
Adjusted further for number of cigarettes smoked daily, body mass index, systolic and diastolic blood pressures, serum total cholesterol, serum high-density lipoprotein cholesterol, histories of diabetes and coronary heart disease, leisure-time physical activity, and intakes of alcohol and total energy.
Adjusted further for intakes of folate and magnesium.
When adjusting for vegetable intake in place of folate and magnesium intakes, the RR was 0.90 (95% CI, 0.78–1.04) for cerebral infarction and 0.91 (95% CI, 0.55–1.51) for subarachnoid hemorrhage.
We considered the possibility that the effect of fiber intake on stroke risk may be mediated through reductions in serum total cholesterol levels and blood pressure and that adjustment for these factors in our multivariate models may minimize potential associations. The results were similar when we excluded serum cholesterol and systolic and diastolic blood pressure from the multivariate model (data not shown).
To address the potential for increased exposure misclassification over time, we divided the follow-time into less than 10 years and 10 or more years of follow-up. The association between fiber intake and stroke did not differ appreciably by follow-up time.
We further examined food sources of fiber in relation to risk of stroke (Table 5). Intakes of fruit and vegetables were statistically significantly inversely associated with risk of cerebral infarction after adjustment for age, supplementation group, and cardiovascular risk factors. The multivariate relative risk of cerebral infarction for the highest quintile of combined fruit and vegetable intake (median, 321 g/d) compared with the lowest quintile (median, 53 g/d) was 0.77 (95% CI: 0.68–0.87; P for trend <0.001). Vegetable consumption was inversely associated with risk of intracerebral and subarachnoid hemorrhage, but the association with intracerebral hemorrhage was not statistically significant in multivariate analysis. In multivariate analysis, cereal consumption was statistically significantly inversely associated with risk of intracerebral hemorrhage (P for trend = 0.04) and nonsignificantly inversely associated with risk of cerebral infarction (P for trend = 0.08). We observed no statistically significant association between intake of rye products and risk of any subtype of stroke; the multivariate relative risks for the highest quintile of rye product intake (172.7 g/d) compared with the lowest quintile (16.0 g/d) were 0.98 (95% CI: 0.86–1.11) for cerebral infarction, 0.82 (95% CI: 0.57–1.17) for intracerebral hemorrhage, and 0.98 (95% CI: 0.63–1.52) for subarachnoid hemorrhage.
Table 5.
Relative risks (95% confidence intervals) of stroke subtypes by quintiles of fruit, vegetable, and cereal intake among 26 556 men in the ATBC Study, 1985–2004
| Quintiles of intake
|
P for trend | |||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | ||
| Fruits | ||||||
| Median, g/d | 11.6 | 40.7 | 74.0 | 113.5 | 192.9 | |
| Cerebral infarction | ||||||
| Cases, n | 603 | 547 | 543 | 515 | 494 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.88 (0.78–0.98) | 0.86 (0.77–0.97) | 0.81 (0.72–0.91) | 0.78 (0.69–0.88) | <0.001 |
| Multivariate RR (95% CI)b | 1.00 | 0.90 (0.80–1.02) | 0.91 (0.81–1.02) | 0.85 (0.76–0.96) | 0.82 (0.73–0.93) | 0.003 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 76 | 86 | 77 | 84 | 60 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.09 (0.80–1.49) | 0.97 (0.71–1.33) | 1.05 (0.77–1.44) | 0.75 (0.54–1.06) | 0.07 |
| Multivariate RR (95% CI)b | 1.00 | 1.14 (0.84–1.55) | 1.04 (0.75–1.43) | 1.14 (0.83–1.57) | 0.84 (0.59–1.20) | 0.26 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 41 | 28 | 43 | 45 | 39 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.65 (0.40–1.06) | 1.00 (0.65–1.54) | 1.03 (0.67–1.60) | 0.88 (0.57–1.36) | 0.85 |
| Multivariate RR (95% CI)b | 1.00 | 0.64 (0.40–1.04) | 0.98 (0.63–1.50) | 0.98 (0.64–1.51) | 0.80 (0.51–1.26) | 0.79 |
| Vegetables | ||||||
| Median, g/d | 25.4 | 47.9 | 70.3 | 98.6 | 153.7 | |
| Cerebral infarction | ||||||
| Cases, n | 593 | 570 | 534 | 549 | 456 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.94 (0.84–1.05) | 0.88 (0.78–0.99) | 0.89 (0.80–1.01) | 0.74 (0.65–0.83) | <0.001 |
| Multivariate RR (95% CI)b | 1.00 | 0.94 (0.84–1.06) | 0.90 (0.80–1.01) | 0.91 (0.81–1.02) | 0.75 (0.66–0.85) | <0.001 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 88 | 81 | 84 | 63 | 67 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.90 (0.67–1.22) | 0.94 (0.69–1.26) | 0.70 (0.50–0.97) | 0.74 (0.54–1.02) | 0.03 |
| Multivariate RR (95% CI)b | 1.00 | 0.91 (0.67–1.23) | 0.97 (0.72–1.32) | 0.73 (0.53–1.02) | 0.80 (0.58–1.11) | 0.10 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 45 | 38 | 43 | 33 | 37 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.80 (0.52–1.24) | 0.88 (0.58–1.34) | 0.65 (0.42–1.02) | 0.70 (0.45–1.08) | 0.09 |
| Multivariate RR (95% CI)b | 1.00 | 0.76 (0.49–1.17) | 0.83 (0.54–1.26) | 0.60 (0.38–0.95) | 0.62 (0.40–0.98) | 0.04 |
| Cereals | ||||||
| Median, g/d | 116.4 | 165.6 | 205.2 | 249.9 | 327.4 | |
| Cerebral infarction | ||||||
| Cases, n | 569 | 561 | 553 | 530 | 489 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.92 (0.82–1.03) | 0.89 (0.79–1.00) | 0.85 (0.75–0.95) | 0.78 (0.69–0.88) | <0.001 |
| Multivariate RR (95% CI)b | 1.00 | 0.98 (0.87–1.10) | 0.97 (0.85–1.10) | 0.93 (0.81–1.07) | 0.87 (0.74–1.03) | 0.08 |
| Intracerebral hemorrhage | ||||||
| Cases, n | 94 | 82 | 84 | 65 | 58 | |
| Age-adjusted RR (95% CI)a | 1.00 | 0.81 (0.60–1.09) | 0.82 (0.61–1.10) | 0.63 (0.46–0.86) | 0.56 (0.41–0.78) | <0.001 |
| Multivariate RR (95% CI)b | 1.00 | 0.85 (0.63–1.16) | 0.88 (0.64–1.22) | 0.70 (0.48–1.01) | 0.64 (0.41–1.01) | 0.04 |
| Subarachnoid hemorrhage | ||||||
| Cases, n | 32 | 39 | 31 | 49 | 45 | |
| Age-adjusted RR (95% CI)a | 1.00 | 1.16 (0.73–1.85) | 0.91 (0.55–1.49) | 1.40 (0.90–2.19) | 1.27 (0.81–2.00) | 0.19 |
| Multivariate RR (95% CI)b | 1.00 | 1.12 (0.69–1.81) | 0.84 (0.50–1.42) | 1.24 (0.74–2.07) | 1.00 (0.54–1.84) | 0.91 |
Adjusted for age and supplementation group.
Adjusted further for number of cigarettes smoked daily, body mass index, systolic and diastolic blood pressures, serum total cholesterol, serum high-density lipoprotein cholesterol, histories of diabetes and coronary heart disease, leisure-time physical activity, and intakes of alcohol and total energy.
Cereals are sources of dietary magnesium, folate, and vitamin E. To evaluate whether the observed inverse association of cereal intake with risk of cerebral infarction and intracerebral hemorrhage could be attributed to increased intakes of dietary magnesium, folate, and vitamin E, we added these nutrients (contributions from food sources) to the multivariate model. When these nutrients were simultaneously included in the model, the relative risks for the highest versus the lowest quintile of cereal intake were 0.98 (95% CI: 0.82–1.18) for cerebral infarction and 0.67 (95% CI: 0.41–1.09) for intracerebral hemorrhage.
Discussion
In this prospective study of male smokers, we found no significant association between intake of total fiber, water-soluble fiber, water-insoluble fiber, or fiber derived from fruit or cereal sources with risk of stroke after adjustment for cardiovascular risk factors and other dietary variables including folate and magnesium intakes. Nevertheless, vegetable fiber intake as well as fruit and vegetable consumption were significantly inversely associated with risk of cerebral infarction. Vegetable consumption was inversely related to risk of subarachnoid hemorrhage and cereal consumption to risk of intracerebral hemorrhage.
Three previous prospective studies have examined the association between fiber intake and risk of stroke. In the Nurses’ Health Study, with 18-years of follow-up and 1020 stroke cases, a high intake of cereal fiber was associated with a statistically significant 34% and 49% lower risk of total stroke and hemorrhagic stroke, respectively (Oh et al., 2005). No association was observed for total fiber or vegetable or fruit fiber intake (Oh et al., 2005). In the Cardiovascular Health Study among 3588 elderly men and women, with 8.6 years of follow-up and 392 stroke cases, those in the 80th percentile of cereal fiber intake had a statistically significant 22% and 24% lower risk of total stroke and ischemic stroke, respectively, compared to those in the 20th percentile of intake (Mozaffarian et al., 2003). Results from the Health Professionals Follow-up Study, with 8 years of follow-up and 328 stroke cases, also indicated an inverse association between intake of cereal fiber, but not fruit or vegetable fiber, and risk of total stroke but only among hypertensive men (Ascherio et al., 1998).
The discrepant findings for cereal fiber between our results and those of other studies may be due to different study populations. Cereal fiber intake in this population of Finnish men was substantially higher (median intake, 16.5 g/d) than in the three previous cohorts of US men and women (median intake ranging from about 3 g/d to 5 g/d) (Ascherio et al, 1998; Mozaffarian et al, 2003; Oh et al, 2005). The possibility of a threshold value so that cereal fiber intakes above a certain level do not provide any additional protective effect may explain our failure to detect an association between cereal fiber intake and stroke.
Our findings for fruit and vegetable consumption are consistent with results from previous prospective studies. In a meta-analysis of nine prospective studies (with a total of 4917 stroke events), compared with those who consumed less than three servings of fruit and vegetables per day, the relative risk of stroke was 0.74 (95% CI 0.69–0.79) for those who consumed more than five servings per day (He et al, 2006).
Fruit and vegetables are one of the main components of the Dietary Approaches to Stop Hypertension (DASH) diet, which has been shown to substantially lower blood pressure (Appel et al, 1997). Raised blood pressure is a potent risk factor for stroke (Lewington et al, 2002). In our study, systolic and diastolic blood pressures were similar at all levels of fruit and vegetable intake and removing blood pressure from the multivariate model did not appreciably change the results for fruit and vegetable intake (data not shown). Hence, blood pressure may not explain the observed inverse association between fruit and vegetable intake and stroke risk in our study. Fruits and vegetables are rich sources of many potentially protective compounds such as folate, which is a determinant of blood homocysteine concentrations. There is ample evidence linking elevated blood homocysteine concentrations to increased risk of stroke (Homocysteine Studies Collaboration, 2002b). Elevated homocysteine concentrations affect both the vascular wall structure and the blood coagulation system (Selhub, 1999). Fruits and vegetables are also rich in antioxidants. However, intervention studies of vitamin C, vitamin E, and beta-carotene have not shown a beneficial effect on stroke incidence or mortality (Leppälä et al, 2000; Heart Protection Study Collaborative Group, 2002a).
Although we observed no independent association between cereal fiber intake and risk of stroke, cereal consumption was significantly inversely associated with risk of intracerebral hemorrhage and nonsignificantly inversely associated with risk of cerebral infarction. This may suggest that other factors than fiber in cereals may be beneficial. Cereals are an important source of dietary magnesium and folate; one third of magnesium and one fifth of folate was derived from cereals in the ATBC Study population. We have previously found that high intakes of magnesium and folate are associated with a lower risk of cerebral infarction in the ATBC Study (Larsson et al., 2008a; Larsson et al., 2008b). In addition, cereals contain many other compounds which may play a role in reducing the risk of stroke (Slavin et al, 1999). In our secondary analyses, we investigated whether the observed inverse association between cereal intake and risk of stroke could be attributed to magnesium, folate, and vitamin E. After adjustment for these nutrients, the inverse association between cereal intake and intracerebral infarction remained (although it was not statistically significant) but not the inverse association between cereal intake and cerebral infarction.
Our study has certain strengths and limitations. Strengths include its prospective design and the large number of stroke cases, which provided high statistical power to detect associations. Furthermore, we had detailed information on cardiovascular risk factors, including body mass index, smoking, blood pressure, and serum cholesterol, which enabled us to comprehensively control for potential confounding by these factors. A limitation of this study is that diet was assessed with a self-administered dietary questionnaire and at baseline only. Therefore, some measurement error leading to misclassification of dietary fiber intake was inevitable, and this would tend to attenuate any true association between fiber intake and stroke risk. On the other hand, the correlation coefficient between total fiber intake based on the dietary questionnaire and the food records was 0.7 in the validation study. With this degree of validity along with the size of the study, we should have been able to detect important associations. Another limitation is that our study population consists entirely of male smokers. Smokers tend to have a slightly lower blood pressure (Omvik, 1996) as well as increased serum total cholesterol and reduced HDL (Krupski, 1991) compared with nonsmokers. The associations of fiber and fiber-rich food intake with stroke risk could therefore differ in nonsmoking populations. There are, however, no studies to show different associations between intakes of fiber and risk of stroke in different smoking categories.
In summary, findings from this prospective study do not support the hypothesis that a high intake of dietary fiber is independently inversely associated with risk of stroke. However, our results indicate that high consumption of fruits, vegetables, and cereals may reduce the risk of stroke.
Acknowledgments
The ATBC Study was supported by Public Health Service contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004 from the US National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Md. Dr Larsson’s postdoctoral research at the National Public Health Institute in Helsinki, Finland, was supported by a grant from the Swedish Council for Working Life and Social Research.
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