1 Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
2 Institute of Health Science, Kyushu University, Fukuoka, Japan.
3 Cancer Research UK Epidemiology Unit, Oxford University, Oxford, UK.
Dr Catherine Sauvaget, Department of Epidemiology, Radiation Effects Research Foundation, 52 Hijiyama Park, Minami-ku, 7320815 Hiroshima, Japan. E-mail: sauvaget{at}rerf.jp
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Methods A self-administered questionnaire, including questions on dietary habits, was mailed to the members of the Life Span Study, a cohort of people exposed and non-exposed to atomic bomb radiation, who were alive as of 1 September 1979. Animal products included frequency intake of beef/pork, chicken, ham/sausage, milk, dairy products, eggs, fish, and broiled fish. Responses were obtained from 40 349 people (72%): 15 350 men (mean age 54 years) and 24 999 women (mean age 58 years). The subjects were followed for 16 years, and deaths were ascertained by linkage to the nationwide family registration system of Japan. The associations between diet and stroke mortality were examined using a Cox proportional hazard model.
Results During the follow-up period, 1462 stroke deaths occurred. Four animal products comprising eggs, dairy products, fish, and broiled fish were independently associated with a decreased risk of stroke mortality; while beef/pork, chicken, ham/ sausage, and milk consumption were not associated with stroke death. A composite measure of eggs, dairy products, fish, and broiled fish intake was calculated, and the highest tertile was significantly inversely associated with total stroke mortality (Hazards Ratio [HR] = 0.80, 95% CI: 0.68, 0.93) compared with the lowest tertile. The protective effect of animal product intake on total stroke death was largely confined to intracerebral haemorrhage death; the RH of intracerebral haemorrhage death for the highest tertile of consumption was 0.72 (95% CI: 0.530.98) compared with the lowest tertile; animal products intake was not related to cerebral infarction mortality (HR = 0.84; 95% CI: 0.671.06).
Conclusions Intake of animal products such as eggs, dairy products, and fish may be protective against intracerebral haemorrhage, but is not related to cerebral infarction mortality.
Accepted 12 February 2003
Stroke was the leading cause of death in Japan for the 30-year period ending in 1980 and is currently the third, following cancer and coronary heart disease. In the 1960s, the age-adjusted mortality rate from stroke in Japan was twice that in Western countries,1 although international comparison might be difficult due to different diagnostic criteria and methodology used. During that period, in Japan, intracerebral haemorrhage was the predominant sub-type; this has been a common feature of East Asian countries.2 Since the mid 1960s, there has been a steady and dramatic reduction in the stroke mortality rate,3 declining by 30% in men and 20% in women between 1965 and 2000.4 Recent data show that the age-standardized stroke mortality rate in Japan (56.7 per 100 000 population) is now similar to that in Germany (52.4) and the UK (51.8), although is still higher than that in the US (34.8);5 death rates being standardized to the WHO World Standard Population.
Interestingly, while the decline in total stroke mortality largely represented that of intracerebral haemorrhage subtype,4 cerebral infarction rates increased nearly fivefold in men and threefold in women between 1951 and 1984.4 Since 1975, the cerebral infarction mortality rate is higher than that of intracerebral haemorrhage and is now the predominant subtype. This indicates that intracerebral haemorrhage and cerebral infarction are affected differently by lifestyle factors. Available data to date suggest that, other than age and hypertension, cerebral haemorrhage and infarction do not share the same risk factors.6 Suggested risk factors for intracerebral haemorrhage include a history of coronary artery disease, low total cholesterol level, and a low intake of animal protein and fat.7,8 High alcohol intake, high physical activity at work, and poor home heating may also be associated with stroke mortality, and together these three factors may contribute as much as high systolic blood pressure alone.1 Risk factors for cerebral infarction include atrial fibrillation, smoking, high total cholesterol levels, low high-density lipoprotein cholesterol levels, and possibly, a low fish intake.9,10
It has been suggested that the observed change in stroke mortality rate may be explained by both improvements in preventive and medical care, and the acceleration of the westernization or modernization of Japanese lifestyles from the end of World War II.11,12 Nationwide community-based hypertension control programmes, nutrition education campaigns to reduce salt intake, and improvements in hypotensive agents were clearly associated with a dramatic decline in average blood pressure levels and subsequent stroke incidence.13,14 In addition, the extended period of strong economic growth from 1960 to 1975 brought about a series of socioeconomic changes including better working conditions, the mechanization of farming, improvements in household heating systems, changes in dietary habits, and developments of refrigeration and marketing.15 Westernization of the diet included an increased consumption of meat, milk, eggs, dairy products, and fruit.3,16
A previous study conducted in the whole of Japan between 1965 and 1982 among 223 170 men and women suggested that an increased consumption of animal products might be protective against cerebrovascular disease mortality.17 The aim of the present study is to examine whether a high intake of animal products estimated from a food frequency questionnaire (FFQ) is associated with a subsequent reduction in total stroke mortality, and whether the associations are different between the two main subtypes intracerebral haemorrhage and cerebral infarction, using a cohort of more than 55 000 Japanese atomic bomb-survivors men and women living in the community.
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Ascertainment of dietary habits
The questionnaire included items on age, anthropometric measurements, smoking, and other lifestyle factors, and a 22-item FFQ. Details on the FFQ have been reported elsewhere.20 The FFQ included questions on the consumption frequency of nine animal products: beef and pork, pork products such as ham/sausage, chicken, milk, eggs, dairy products (butter and cheese, excluding margarine), fish excluding broiled and dry fish, broiled fish, and dry fish. Subjects were asked to state how frequently they ate each food item, based on four categories: never, once/week, 24 times/week, and almost daily.
A previous validation study found the mean daily intakes of animal foods estimated from the FFQ to be significantly associated with intake as estimated from a 24-hour dietary record, with Spearman correlation coefficients ranging from 0.17 to 0.32 across categories of intake. However, intake of dry fish from the FFQ was not correlated with intake from the 24-hour dietary record, and was therefore excluded from the present analysis.20
First, the relationship between stroke mortality and each animal product intake was analysed separately. The FFQ validation study showed that the mean intake in weight of a food item that was recorded as missing on the questionnaire was similar to that of the never, or once/week frequencies. We concluded that those who did not report their intake in the FFQ scarcely or never ate the food.20 We therefore grouped those with missing values together with the lowest frequency category, and were thus able to include the entire study population in the analysis.
Second, mortality risks were related to a composite variable of total intake of animal products and of their subsets. First, the intake of each food product was categorized into three groups: missing, never and once/week (scored as 0), 24 times/week (scored as 1), and almost daily (scored as 2). All animal product intake was then defined as the sum of scores (012) of beef and pork, chicken, pork products, milk, egg, dairy products, fish excluding broiled/dry fish, and broiled fish. Another composite variable included the animal products significantly inversely associated with stroke mortality. Fish product intake was defined as the sum of scores of fish excluding broiled/dry fish, and broiled fish. The three composite variables were then categorized into three levels of consumptionlow, moderate, and highwith the number of subjects in each category equally distributed. The mean daily intake of animal foods in each category was estimated by multiplying the frequency of consumption from the FFQ with an average portion size according to the mean intake derived the 24-hour diaries.
Follow-up and ascertainment of stroke death cases
Stroke death cases were ascertained by linkage to the nationwide family registration system of Japan.18,21 Copies of death certificates are regularly obtained by RERF for all deceased LSS cohort members, and trained coders enter the appropriate codes into the database. The ascertainment is virtually complete, since the death certificates are available as long as the subjects reside within Japan, and the number of emigrants is small. Causes of deaths were coded according to the International Classification of Diseases codes.22 Follow-up was started on 1 January 1980 for men and 1 February 1981 for women, and continued until the date of stroke death, death from other causes, or 31 December 1996, whichever came earliest.
Statistical analysis
The association between animal product intake and stroke mortality was examined using a Cox proportional hazard model, and hypothesis tests and CI were based on Wald statistics. Age was the primary time scale in all analyses and baseline rates were stratified by sex and birth cohort. All multivariate analyses were adjusted for possible confounding variables: smoking status (never, past, and current), alcohol-drinking status (never, past, and current), body mass index (BMI) calculated from the self-reported height and weight (<19, 19<22, 22<25, and 25+ kg/m2), education level (junior high school or lower, high school, and junior college/university or higher), self-reported histories (yes, no) of diabetes mellitus or hypertension, radiation dose (continuous variable in mSv), and city (Hiroshima, Nagasaki). The analyses were carried out using the SAS software version 8.23
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The analysis of the health effects of a vegetarian diet is of interest in the investigation of the health effects of meat or animal products intake. Unfortunately, the data on the rate of stroke mortality among vegans (people who consume no animal products) compared with meat-eaters is sparse and further research is clearly needed to determine whether these individuals are at an increased risk. Several studies have shown vegetarians, who consume animal protein in the form of milk, egg, and dairy products, to not have an elevated rate of stroke mortality compared with non-vegetarians,2426 despite their lower levels of cholesterol.27
In Japan, consumption of animal products has generally increased since World War II. Intakes of fish/shellfish, eggs, milk, and meats increased until 19701975 and have been constant thereafter, whilst the intake of dairy products has been constantly increasing (Figure 1).28,29 Nevertheless, the consumption in Japan is lower than that of Western countries. During the study period, the proportion of energy from animal products in Japan represented half of the estimated energy intake compared with that in Western countries (Japan 18%, UK 37%, USA 36%).30
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After Japans recent high economic growth period (1975), serum cholesterol levels in the Japanese population have been increasing along with the intakes of animal products.3335 The association between serum cholesterol concentrations and the risk of stroke mortality has been examined extensively. Hypocholesterolaemia is consistently associated with an increased risk of intracerebral haemorrhage mortality among Japanese living in Japan,15,3639 Japanese Americans,40,41 and Caucasians.42,43 A low cholesterol level, associated with severe hypertension, is thought to involve a weakening of the endothelium of cerebral arteries, and could, in part, explain the observed protective association of animal products consumption with intracerebral haemorrhage.44
Previous findings from prospective studies on the relationship between serum cholesterol levels and cerebral infarction are inconsistent: low serum cholesterol level has been associated with a decreased risk,42,45 with no association,14,15,37,38,40 and with an increased risk.13,44,46 Cerebral infarction can be classified into two types according to the size and location of responsible arteries: (1) cervical and cortical or large arteries, and (2) penetrating or small arteries.47 Recent studies suggest that the intake of animal products and related factors may have different effects on these two types of cerebral infarction. Pathogenesis of large arteries infarction involves high cholesterol levels and atherogenesis, while pathogenesis of small arteries infarction is related to a weakening of the smaller arteries endothelium due to low serum cholesterol levels associated with sustained mild or moderate hypertension.44 In a male cohort in the US, fat intake predisposed to atherosclerosis in the larger vessels, but was protectively associated with the integrity of the smaller intracranial vessels.46 An autopsy study of members of the Honolulu Heart Program showed that protein and fat from animal sources were not associated with atherosclerosis in the small cerebral vessels, while they increased the risk of atherosclerosis in large arteries.48 Infarction in small arteries used to be the most prevalent sub-type of cerebral infarction in Japan before the 1970s, opposite to that of Caucasians.44,49,50 However, concomitant with the rise in serum cholesterol levels, cerebral infarction in the region of the large arteries is increasing.47 This may suggest that animal products will not remain a somewhat protective factor of cerebral infarction in Japan, but become a risk factor of infarction through their atherogenic effects on large arteries. However, among the present population, no protective or risk factor association was observed.
Another factor that may complicate the interpretation of the results for cerebral infarction is the difference in fat composition from meat and fish. Meat products are rich in saturated fatty acids, thought to be a risk factor for cerebral infarction via its atherogenecity. Conversely, fish products are rich in polyunsaturated fatty acids and n-3 fatty acids, and are thought to protect against cerebral infarction via their hypolipidaemic, hypotensive, antiatherogenic, and antithrombotic effects.10 Unfortunately, such detailed information on the subtypes of cerebral infarction was unavailable in the present data.
Other limitations in the present study include the unavailability of data to assess the reproducibility of the FFQ, although the FFQ has been validated. The FFQ included no information on portion size and nutrient intakes could not be estimated.51 However, possible misclassifications between haemorrhage and infarction strokes were unlikely because computerized tomography diagnosis was already in use when the study was initiated and thus the quality and reliability of death certificate information was likely to be sufficient.52
Although the study population is unique in the fact that most of the people had been exposed to ionizing radiation, there is no association between stroke risk and radiation exposure in the LSS cohort.21 Moreover, diet is not known to be associated with radiation exposure.51 Therefore, the present findings are also applicable to the general population.
In conclusion, the large-scale population-based cohort study in Japan suggests that, in a country where animal product intake is generally low, a consumption of eggs, dairy products, and fish may reduce the risk of mortality from intracerebral haemorrhage.
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References |
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