Relationship of Dietary Intake to Subsequent Incidence of Stroke and Ischemic Heart Disease

To test a hypothesis that Japanese traditional dietary habits may be associated positively with risk of stroke and inversely with that of ischemic heart disease, a 13.5-year prospective study was conducted among residents aged 40 years and over in A-I district, Shibata City, Niigata Prefecture, Japan. Their baseline intake of nutrients and foods was assessed in July, 1977, by a food frequency method which was newly developed by the authors. Even during the follow-up period when Japanese dietary habits were considerably westernized, neither hypercholesterolemia nor obesity was related to development of stroke or ischemic heart disease. The risk of ischemic heart disease had a tendency to be low among the persons whose vegetable intake was high, and the risk of cerebral hemorrhage tended to be low among those whose intake of animal foods was high, although these relations did not reach statistical significance. This may be due to residual effects from the national privation period to the present day.


INTRODUCTION
Several ecological and cross-sectional studies have suggested that the traditional Japanese dietary habits, characterized by unbalanced diets, extremely high carbohydrates and salt, and low fat and animal protein, were associated with the development of cerebral hemorrhage (CH) and angionecrotic cerebral infarction (CI) (1)(2)(3).To test this hyothesis, a prospective cohort study was conducted in the Akadani-Ijimino district (hereinafter referred to as A-I district) of Shibata City, Niigata Prefecture, Japan.In addition to clinical examinations, baseline dietary intake was assessed in July, 1977.The persons initially free of stroke or ischemic heart disease (IHD) have been followed up ever since.In this paper, we report the results of 13.5 years of observation for the relationship between dietary intake at entry and the subsequent incidence of stroke and IHD.

Study District
Shibata City is located in the northern part of Niigata Prefecture, Japan.The A-I district is an agricultural area where rice and fruits are produced in the plains on a relatively large scale, whereas in the mountainous area several hundred meters above sea level only a small scale of agriculture if practiced.The majority of the families in the A-I district are farmers who supplement their income with side jobs in other occupations.The rise in the income of individual farmers in the district has been remarkable.The annual income per farming household has already surpassed that of wage-earners in city areas.

Baseline Examination
Details of study methodology have been reported elsewhere 11.5).Briefly, an initial examination was conducted in July, 1977, with all the A-I residents 40 years of age and over.In addition to clinical examinations, the baseline intake of nutrients and foods, as well as physical activities, were assessed by a new method developed by the authors.Each subject or interviewee was asked to recall the pattern of food consumption during the preceding one-year period and provide information about the frequency of intake per week, its quantity at one time, and the method of cooking each food as listed in the Japanese Food Composition Table .The questions concerned staple foods, side dishes and snacks, in that order.At present, there are 97 food items in the questionnaire.Based on the data concerning the food intake frequency and its quantity, each subject's daily food intake amount and nutrient intake was estimated.The main advantage of this food intake frequency questionnaire method is that it reveals information on the food intake tendencies of individual persons over a long period of time, namely, their habitual patterns of dietary intake.
The authors have developed another questionnaire and interview form in order to estimate the mean value of physical activities that individual persons engaged in during the preceding year.The evaluation method for physical activities is based on a simple estimation method devised for this purpose.This method deals specifically with types of activities, the period per month, working hours per day, and sleeping hours.In the questionnaire, there are a few other questions on whether each physical activity was done in a sedentary position or standings whether strenuous muscular effort was required, and whether they subject participated in sports in his or her leisure time.

Follow-up
The observational cohorts for stroke had no history of stroke, and the ischemic heart disease (IHD) cohorts had no history of myocardial infarction (MI) or angina pectoris on effort.Both cohorts were followed up for 13.5 years, from July 1977 through December 1990.To identify S-113 possible cases of stroke and IHD, follow-up examinations were conducted annually during the follow-up period, and active surveillance was also used.
In surveillance of stroke, and acute MI and sudden death, appropriate information was obtained from physicians, death certificates, public health nurse reporting, reports from council residents, reports of emergency services, records of social insurance and hospital records.Details of the follow-up methods and the methods for identifying stroke and IHD are described elsewhere (5,6).

Analyses
There was the loss of some cohorts due to death, moving, or other reasons during the 13.5 years of follow-up.To make maximum use of the data, the person-year method of incidence determination was employed.
The cohort members were divided into two groups according to the presence (+) and absence (-) of a factor confirmed in the baseline examination.In the case of a continuous variable, a factor was defined as present when the value exceeded the 75-percentile.For each subgroup, the sex-and age-standardized incidence ratio (SIR) of cerebral hemorrhage (CH), cerebral infarction (CI) and IHD (acute MI and sudden death) was calculated.The SIR is the ratio of the observed number to the expected number of cases.The expected number is the sum of products of the sex-and age-specific person-year incidence rate in the cohorts and the person-years by sex and age in the subgroup under study.The sex-and age-adjusted risk ratio was computed by the equation of Rothman and Boice (7).The statistical significance was determined by the method of Mantel and Haenszel (8,9) .In addition, the dose-response relationships between some of the continuous variables and the incidence of stroke (CH and CI) or IHD were measured.For systolic blood pressure, diastolic blood pressure and serum total cholesterol, the cohort members were divided into four groups according to 25-percentile values (quartiles).Sex-and age-adjusted person-year incidences of each quartile were calculated by the indirect method.

Response Rate and Observational Cohorts
There were 1,182 men and 1,469 women residents aged 40 years and over in the A-I district in July, 1977.Among them, 998 men (84.5% of the male population), and 1,360 women (92.6% of the female population) responded to the initial examination.Excluding those who had clinical evidence of a previous history of stroke, 960 men and 1,339 women were followed up as cohort members from July, 1977 through December, 1990 (Table 1).
As to ischemic heart disease, another cohort group was set up, using 984 men and 1,342 women who were initially free from myocardial infarction and angina pectoris on effort (Table 2).

Incidence
Table 3 shows the number of stroke cases.During the 13.5-year observation, 105 new cases of stroke were confirmed: 44 men and 61 women.Among the stroke cases, six men and 14 women were subclassified as CH, and 26 men and 34 women as CI.The number of cases of IHD is shown in

Dose-response Relationship
The relation of blood pressure to subsequent incidence of CH, CI and IHD is shown in Fig. 1.The cohort members were divided into four groups according to quartile.The doseresponse relationship between the initial blood pressure level and incidence is observed to be most prominent with respect to diastolic blood pressure and CI.
The relationship between serum total cholesterol and the subsequent incidence of the three diseases is shown in Fig. Analysis of SIR Fig. 3 shows the sex-and age-adjusted risk ratio of vegetable nutrient intake for CH, CI and IHD.The risk ratio of carbohydrate and vegetable fat with regard to CH is almost 1, and that of CI and IHD is less than 1.As for the caloric percent of vegetable nutrients, the relationship between risk ratios and nutrient shows the same tendency.On the whole, the authors find that the risk ratios of IHD are generally less than 1.
The same type of analysis was carried out with vegetable food intake.Some risk ratios for IHD show less than 1.Most of the risk ratios for CH and CI are around 1 (Fig. 4).

S-117
The analysis of animal nutrient intake is shown in Fig. 5.The risk ratio of animal fat with the three diseases is less than 1.The risk ratio of caloric percent of animal fat with regard to IHD is more than 1, almost 1 with regard to CI, and less than 1 with regard to CH .However, they are not statistically significant.
Fig. 6 shows animal food intake.The risk ratio of meat and milk for IHD is less than 1 .
Except fish for CI, the risk ratios of all the foods for CH, CI and IHD are less than 1 .
Fig. 7 shows the relationship between energy input and output and obesity , and the risk for the subsequent incidence of stroke and IHD.The risk ratios of energy expenditure and labor intensity for CH are greater than 1.However, those of the obesity index are less than 1 .On the other hand, as for IHD, the risk ratio of labor intensity is less than 1, and those of the obesity index are greater than 1.A birth cohort analysis indicated that the experience with the period of national privation was closely associated with death rate from cerebrovascular disease (1).According to the National Nutrition Survey conducted in 1946, the average intake of fat was 13.3 g/day, that of animal protein was 12.9 g/day and that of carbohydrated was 248.7 g/day in Tokyo.Some surveys during the privation and reconstruction periods reported that the amount of salt taken per adult per day was 26 g in Akita and 14 g in Hiroshima by Dahl (10), 27.3 g for males and 21.5 g for females in Yamagata by Suzuki et al. (11), and 18.1 g (range of 12.0 g -30.4 g) in Akita by Sasaki (12).The Japanese in those days consumed much steamed rice, soybean paste soup (Misoshiru) and salted vegetables.Animal foods such as beef, pork and chicken, each of which were taken several times in a year, were considered to be healthy foods that prevented infectious diseases.Eggs were taken once a week or less.Figure 4 Sex-, age-adjusted risk ratio of vegetable food intake for cerebral hemorrhage, cerebral infarction, and ischemic heart disease Figure 5 Sex-, age-adjusted risk ratio of animal nutrient intake for cerebral hemorrhage, cerebral infarction, and ischemic heart disease Figure 6 Sex-, age-adjusted risk ratio of animal food intake for cerebral hemorrhage, cerebral infarction, and ischemic heart disease had a tendency to raise risk of stroke and westernaization to decrease risk of stroke and increase risk of IHD, these associations were not statistically significant.It seems that there are two reasons for such conflicting results.One of them is the period of assessment of dietary intake (1977).As the dietary habits of Japanese had already changed before 1975 through the westernization process, the authors could not assess earlier traditional dietary patterns.In this study we have observed the tendency for incidence of both stroke and IHD to be low among the people who experienced the period of privation before, during and just after World War II, and whose dietary habits became relatively westernized after reaching middle age.Among the population aged 40 years or more investigated in this study, the greatest risk factor for stroke and IHD was hypertension, and the involvement of hypercholesterolemia in these diseases was less marked.The high dietary intake level we have cited in this study does not signify excessive intake but optimum intake.The other reason is gradual changes in lifestyle and subsequently those in risk factors and the incidence of subclassified CI that have occurred during the 13.5year period of our follow-up studies.
In this study, stroke (excluding subarachinoid hemorrhage) was classified as CH or CI.As the use of computer tomography (CT) has spread, stroke has recently started to be further subclassified, based on CT findings, into cerebral thrombosis of the cortical branches, cerebral thrombosis of the perforating branches and cerebral embolism.
According to some case-control studies (14,15), cerebral thrombosis of the cortical branches is regarded as affected primarily by hypercholesterolemia and secondarily by hypertension.Conversely, CI of the perforating branches appears to be closely associated with hypertension, but not with hypercholesterolemia.
In this study, because the authors analyzed CI only per se, without dividing it into different types, the effects of different types of CI could not be shown.
In Europe and the United States, as well as in large cities in Japan, CI of the cortical branches seems to be a predominant type.In agricultural districts in Japan such as the A-I district in this study, CH has been decreasing, and two types of CI now seem to be mixed.These findings indicate that Japan on the whole is moving away from the condition that existed prior to 1965 towards a state similar to that seen in Europe and the United States today.
Acute myocardial infarction (MI) is pathologically divided into two types, transmural and subendcardial myocardial infarctions.According to a case-control study, transmural MI was associated with three risk factors hypercholesterolemia, hypertension and smoking while subendcardial MI was affected by hypertension and aging (16).Konishi et al. (17) reported that, in Japan, transmural MI was more frequently seen than subendcardial MI in large cities, although the incidence of subendcardial MI was relatively high in rural areas like the A-I district investigated in this study.Thus, it seems that the relation between high intake of animal fat or hypercholesterolemia and IHD did not reach statistical significance.
Changes in lifestyles and subsequent changes in risk factors may have brought about the decreases in CH, CI of the perforating branches and subendcardial MI, and a slight increase of CI of the cortical branches and transmural MI.However, such Japanese under 40 years of age were born and brought up at the time the westernization process was fairly well entrenched, having no experience with the war-affected period of privation, and the authors can not rule out the possibility that the incidence of CI of the cortical branches and IHD, accompanied by hypercholesterolemia, will increase in the future.This trend has already started to be seen in large cities.It will be necessary to put these under close surveillance for cardiovascular

Figure 3
Figure3Sex-, age-adjusted risk ratio of vegetable nutrient intake for cerebral hemorrhage, cerebral infarction, and ischemic heart disease

Figure 7
Figure 7 Sex-, age-adjusted risk ratio of energy input and output and obesity for cerebral hemorrhage, cerebral infarction and ischemic heart disease

Table 4 .
There were 19 new cases of IHD among men and 23 such cases among women.

Table 1
Population, number of persons examined at initial examination and number of cohort members for strokes in A-I district, Japan, 1977.