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Case Control Study of Nonfatal Myocardial Infarction in Relation to Selected Foods in Japanese Men and Women

Jpn Circ J 2001; 65: Case Control Study of Nonfatal Myocardial Infarction in Relation to Selected Foods in Japanese and Shizuka Sasazuki, MD, and the Fukuoka Heart Study Group* Most studies of
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Jpn Circ J 2001; 65: Case Control Study of Nonfatal Myocardial Infarction in Relation to Selected Foods in Japanese and Shizuka Sasazuki, MD, and the Fukuoka Heart Study Group* Most studies of diet and coronary heart disease (CHD) have focused on constituents rather than on whole foods. The present study examined the relationship of selected foods to nonfatal acute myocardial infarction (AMI) in Japan, with special reference to vegetables, fruits, fish, and tofu. A total of 660 cases with their first episode of AMI aged years living in Fukuoka City or adjacent areas and 1,277 controls matched for age, sex, and residence were surveyed on lifestyle, including dietary factors. Participation rates were 87% of cases and 52% of controls. Consumption frequencies of 19 food/beverages items and daily amounts of 4 items were ascertained by interview. The final analysis was done with 632 cases and 1,214 controls. Although consumption of vegetables showed no clear association with the risk of AMI, fruit consumption appeared to reduce the risk of AMI in both men and women. The results also suggested that fish consumption was related to a decreased risk of AMI in men, although the trend was not statistically significant. In women only, tofu consumption was inversely related to the risk of AMI; relative risks for eating tofu 2, 2 3, and 4+ times per week were 1.0, 0.8, and 0.5, respectively, after adjustment for non-dietary factors (p for trend = 0.01). Further adjustment for consumption of fruit, fish and tofu did not alter the findings generally. The findings suggest that, in women at least, tofu consumption may be protective against the risk of AMI. Further studies are needed to corroborate the relationship of consumption of fish and fruit to AMI risk in Japanese men and women. (Jpn Circ J 2001; 65: ) Key Words: Acute myocardial infarction; Case control study; Foods Hypercholesterolemia is an important cause of coronary heart disease (CHD) and much emphasis has been placed on the role of dietary fat, especially saturated fats and cholesterol, in the epidemiology of CHD. 1 3 Most studies on diet and CHD have thus focused on constituents rather than on whole foods, and such constituent-based analysis may underestimate or overlook the role for specific foods in the development of CHD. For instance, dietary fiber is consistently shown to be related to a reduced risk of CHD, 4 but fiber-rich foods also contain high amounts of other protective compounds. 3,4 Interestingly, of vegetables, fruits and cereals, cereal fiber has been most strongly or exclusively associated with a decreased risk of CHD in prospective studies of men and women in the United States. 5,6 Further, whole-grain intake was shown to be associated with a reduced risk of CHD independent of total dietary fiber in the Iowa s Health Study. 7 Thus studies of foods and CHD risk will be very useful for further understanding of the diet CHD relationship. Because food is a unit of the actual diet, food-based analysis also provides more practical information in the prevention of CHD, as illustrated in recent studies that investigated the role of eggs 8 and food sources of saturated fat. 9 Several foods and food groups have recently drawn much interest because of their potential cardioprotective effect. (Received August 9, 2000; revised manuscript received October 23, 2000; accepted November 27, 2000) Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, and Epidemiology and Biostatistics Division National Cancer Center Research Institute East, Chiba, Japan *Members of the Study Group are listed in Appendix Mailing address: Shizuka Sasazuki, MD, Epidemiology and Biostatistics Division National Cancer Center Research Institute East, Kashiwanoha, Kashiwa City, Chiba , Japan Fish oil has an antithrombotic effect and lowers serum triglyceride levels, 10 as well as having an antiarrhythmic effect. 11 Although some prospective studies have shown an inverse association between fish consumption and CHD risk, 12,13 it still remains controversial whether fish consumption is related to decreased risk of CHD Randomized controlled trials showed that high intake of fish oil resulted in a reduction in all-cause mortality 17 or cardiovascular deaths 18 among patients surviving myocardial infarction (MI). The consumption of soy or soy products reduces serum total or low-density lipoprotein (LDL) cholesterol levels and the high content of phytoestrogen in soy has led to the hypothesis that soy consumption may confer protection from CHD. 22 To our knowledge, there has not been a study directly addressing the relationship between soy consumption and CHD risk. Vegetable and fruit consumption is related to reduced risk of CHD, 23,24 although it is uncertain to what extent this reduction is attributable to antioxidative constituents or dietary fiber. Despite a westernized diet being generally related to increased risk of CHD in Japan, 25,26 there is sparse epidemiologic evidence regarding the relationship between foods and CHD risk in Japan. By means of a case control study, we examined the relationship between selected foods and the risk of nonfatal acute MI (AMI) in Japanese men and women. Our particular interest was the role of fish, soy products, vegetables and fruits in the development of AMI. Methods Subjects Consecutive cases of a first episode of AMI that were admitted within 1 month of onset were identified in 22 collaborating hospitals during the period September 1996 Foods and MI to September Cases were restricted to residents of Fukuoka City at the inception of the study, and extended to include those in 21 adjacent municipalities after June Thirteen hospitals were originally selected to cover Fukuoka City, and 9 hospitals subsequently joined the study. These collaborating hospitals were staffed with one or more expert cardiologists and equipped with the facilities for treating AMI. The cardiologists made the diagnosis of AMI, which was based on ECG, ischemic cardiac pain and enzyme changes, in accordance with the criteria used in the Lipid Research Clinical Program. 27 Trained nurses visited each hospital weekly and checked all admissions with a diagnosed or suspected AMI. They asked eligible patients to participate in the study with the permission of the attending doctors. A total of 660 of 756 eligible patients (87%; age range, years) were surveyed with regard to lifestyle and other factors. Community controls were recruited by referring to the resident registers of the municipalities where the corresponding cases resided. For each case, we selected at most 2 controls matched for birth year (within 2 years), sex, and proximity in residence. Candidates were first approached by mail. Two reminders were sent, and contact by telephone was attempted last if the telephone number was listed in the telephone directory. Of 2,613 subjects approached, 53 were returned as undeliverable mail, 22 were dead, 26 were found to be non-residents, 79 had prior history of MI; 889 refused, 267 did not have a telephone; and 1,277 cooperated. Thus a net participation rate was calculated as 52% (1,277/2,433). The final analysis included 632 sets of 632 cases and 1,214 controls excluding one case for whom no matched control was selected, 27 cases with incomplete data and their matched 52 controls, and 11 controls with incomplete data. Interview Survey A questionnaire-based interview ascertained personal characteristics such as smoking habit, alcohol consumption, occupational and leisure time physical activities, dietary habits and history of hypertension, hyperlipidemia, diabetes mellitus, or angina pectoris. The questionnaire was distributed to the patients with AMI before interview and was completed with the assistance of research nurses during the hospital admission. The median time from admission to interview was 14 days. Control subjects also received the questionnaire by mail beforehand, and research nurses and members of the working group (physicians and a public health nurse) interviewed them at a clinic, medical office or the subject s workplace or home (72.7%, 8.7%, 6.8%, and 11.7%, respectively). Control subjects under medical treatment were usually interviewed at their own doctor s clinic. Dietary questions measured the average habitual consumption of 23 food and dish items during the year prior to the onset of AMI in cases and for the year prior to the interview in controls. Daily consumption of green tea, coffee, rice, and miso (soy paste) soup were ascertained by precoded answers (0, 1, 2 3, 4 6, 7 9, or 10+ cups or bowls). Only the frequencies of consumption were determined for the other 19 items by using a precoded category of 6 levels (none or 1, 1, 2 3, or 4 6 times per week, almost once per day, and 2 3 times per day): bread for breakfast, pickled vegetables, fresh vegetables/salad, boiled vegetables, fried vegetables, deep fried vegetables, fish, poultry as main dish, poultry mixed with vegetables, meat (beef/pork) as main dish, meat (beef/pork) mixed with vegetables, ham/sausage, 201 egg, tofu, garlic as a sole food, garlic included in mixed dish, fruit, milk, and yogurt. Three types of vegetable dishes (boiled, fried, and deep fried) were combined to create a score of the total consumption of cooked vegetables from the weekly frequencies of each item. The score for total vegetable consumption was also calculated from 5 types of vegetable dishes; a coefficient of 0.2 was used for pickled vegetables based on the typical serving size. Meat consumption was estimated as a composite score of meat as main dish and meat mixed with vegetables, and ham/sausage; a coefficient of 0.5 was used for each of the latter 2. Consumption frequencies of poultry as main dish and poultry mixed with vegetables were also added, with a coefficient of 0.5 given to the latter, to obtain a composite score of poultry consumption. Likewise, consumption of sole garlic and garlic as a constituent were combined with a coefficient of 0.5 to the latter; and consumption of milk and yogurt were simply added. The coefficients representing serving size were empirically determined with reference to recipe books of common dishes. Cigarette smokers were defined as those who had ever smoked daily for 1 year or longer, and alcohol drinkers were defined as those who had drunk at least once per week for 1 year or more. Former smokers (or former alcohol drinkers) were those who had ceased smoking (or alcohol drinking) for 1 or more years before the onset of AMI or the interview. Ethanol intake (ml/day) was assessed for current drinkers based on reported consumption frequencies and amounts of 4 alcoholic beverages (sake, shochu, beer, and spirits). Occupational and leisure time physical activities were each categorized dichotomously. Subjects who were unemployed or who had a sedentary job were classified as occupationally inactive. Questions on leisure time physical activities ascertained the number of days on which subjects had exercised per week on weekdays and per month on weekends or holidays on average during the past year, the type of the activity, and the average amount of time spent on each activity. Reported activities were categorized into light, moderate, hard, and very hard intensities with reference to published data. 28 Subjects were regarded as physically active in leisure time if they participated in moderate or more strenuous activities for at least 30min per week. Clinical Data Clinical and laboratory data, as well as the medical history of the patients with AMI, were extracted from the medical records. When blood had not been taken within 24 h of the onset of AMI, we inquired of the primary physicians about the levels of serum lipids immediately after, or alternatively before, the onset of AMI. Serum total cholesterol concentrations measured during the 24-h period after the occurrence of AMI were used with 153 cases (24%) because the relevant information was not available. Blood samples were drawn from each control subjects for determination of serum lipids, unless serum total cholesterol had been measured within the 6 months prior to the interview, in which case the recorded data were used. The subjects were not required to be fasting. The serum samples were sent to the Clinical Laboratory of the Fukuoka City Medical Association. Height and weight were measured for most of the controls, but self-reported values were used with those interviewed at their workplace or home. Current medication was also elicited by referring to to medical records at clinics. Body mass index (BMI) (ie, weight (kg)/ height(m) 2 ) was calculated as an index of obesity, and a BMI 202 SASAZUKI S et al. Table 1 Tertile Categories of the Consumption of Selected Foods in and Food items Low Intermediate High Low Intermediate High Pickled vegetables 1 Fresh vegetables 1 Cooked vegetables 2 Total vegetables 2 Fruit 1 Meat 2 Poultry 2 Fish 1 Rice 3 Miso soup 3 Egg 1 Tofu 1 Milk or yogurt 1 Frequency per week; 2 total score of consumption based on an approximate portion size and frequency per week of each food (see text); 3 servings per day. Table 2 Characteristics of Cases and Controls in the Fukuoka Heart Study, September 1996 September 1998 Characteristics Cases Controls p for difference Cases Controls p for difference No Regular job 283 (61.8) 589 (66.8) (21.8) 58 (17.5) 0.23 Smoking status Never 66 (14.4) 187 (21.2) 131 (75.3) 284 (85.5) Past 112 (24.5) 303 (34.4) ( 3.4) 15 ( 4.5) Current 280 (61.1) 392 (44.4) 37 (21.3) 33 ( 9.9) Alcohol drinking Never 186 (40.6) 213 (24.1) 148 (85.1) 249 (75.0) Past 68 (14.8) 83 ( 9.4) ( 5.7) 12 ( 3.6) Current (44.5) 586 (66.4) 16 ( 9.2) 71 (21.4) Physically active job 102 (22.3) 247 (28.0) (10.9) 51 (15.4) 0.17 Leisure time activity (31.9) 336 (38.1) (27.6) 97 (29.2) 0.70 Hyperlipidemia 172 (37.6) 225 (25.5) (47.7) 154 (46.4) 0.78 Hypertension 137 (29.9) 165 (18.7) (47.7) 87 (26.2) Diabetes mellitus 72 (15.7) 69 ( 7.8) (20.1) 18 ( 5.4) Angina pectoris 35 ( 7.6) 22 ( 2.5) ( 8.0) 10 ( 3.0) 0.01 Overweight (25.8) 223 (25.3) (25.3) 85 (25.6) At least once per week; 2 moderate or more strenuous activity in leisure time for 30 min or more per week; 3 body mass index of 25 or greater was defined as overweight. Hypertension and angina pectoris were each determined if a subject was under pharmacological therapy. Hyperlipidemia was defined if a subject had a serum total cholesterol level of 220 mg/dl or greater or was under hypolipidemic medication. Diabetes mellitus was defined if they were under dietary or pharmacological therapy for the disease. Survey of Non-Participant Control Candidates To examine the characteristics of control candidates who did not participate in this study, we did a supplementary survey with 456 non-participant candidates, accumulated until December 1997, using an abbreviated version of the questionnaire. This short questionnaire included questions regarding 5 items of vegetables, fruit, and total consumption of meat. Of 217 respondents (47.6%), 4 subjects reported a history of MI. The comparison was made between 213 non-participant candidates and 1,214 controls. As compared with non-participants, male controls were found to have consumed deep-fried vegetables more frequently, and female controls were younger, consumed fried vegetables more frequently, and had a higher prevalence of hyperlipidemia that was being treated with medication. There was no remarkable difference between the non-participant candidates and controls as regards smoking, alcohol use, leisure-time physical activity, the consumption of pickled, fresh/salad, boiled, or fried vegetables, fruit consumption, and meat consumption. Statistical Analysis Matched relative risks (RRs) and 95% confidence intervals (CIs) were calculated to indicate the relation between each dietary factor and the risk of AMI. Multiple conditional logistic regression analysis was conducted to control for the potential confounding effects of selected factors. Trend of the association was assessed by the Wald statistic for a variable representing a specific food; median values were assigned to the consumption levels of each food. Spearman s rank correlation coefficients were calculated to investigate the interrelationships of selected foods. The frequencies of consumption of each dietary factor were categorized into 3 groups so that each category included as equal numbers of male and female controls as possible (Table 1). Smoking status was categorized into 4 levels in men (never, past, and current smoking of 20 or 20+ cigarettes per day) and into 2 levels in women (never, and past Foods and MI 203 Table 3 Adjusted Relative Risks (RRs) and 95% Confidence Intervals (CIs) of Acute Myocardial Infarction for the Low, Intermediate, and High Consumption of Selected Foods* Food items Low Intermediate High p for trend Low Intermediate High p for trend Pickled vegetables ( ) 0.7 ( ) ( ) 1.0 ( ) 0.96 Fresh vegetables ( ) 0.9 ( ) ( ) 1.0 ( ) 0.92 Cooked vegetables ( ) 1.0 ( ) ( ) 0.9 ( ) 0.79 Total vegetables ( ) 1.2 ( ) ( ) 1.1 ( ) 0.84 Fruit ( ) 0.7 ( ) ( ) 0.7 ( ) 0.17 Meat ( ) 1.0 ( ) ( ) 0.7 ( ) 0.12 Poultry ( ) 0.9 ( ) ( ) 1.0 ( ) 0.80 Fish ( ) 0.6 ( ) ( ) 1.2 ( ) 0.27 Rice ( ) 0.7 ( ) ( ) 0.6 ( ) 0.49 Miso soup ( ) 0.8 ( ) ( ) 1.0 ( ) 0.99 Egg ( ) 0.9 ( ) ( ) 0.8 ( ) 0.66 Tofu ( ) 0.9 ( ) ( ) 0.5 ( ) 0.01 Milk or yogurt ( ) 1.0 ( ) ( ) 0.7 ( ) 0.25 *Adjusted for smoking, alcohol use, sedentary job, leisure-time physical activity, hyperlipidemia, hypertension, diabetes mellitus, angina pectoris, and obesity. Table 4 Adjusted Relative Risks (RRs) and 95% Confidence Intervals (CIs) of Acute Myocardial Infarction for the Low, Intermediate, and High Consumption of Selected Foods With Mutual Adjustment for Dietary Factors* Food Low Intermediate High p for trend Fruit ( ) 0.7 ( ) 0.22 Fish ( ) 0.7 ( ) 0.51 Tofu ( ) 1.0 ( ) 0.82 Fruit ( ) 0.6 ( ) 0.08 Fish ( ) 1.3 ( ) 0.09 Tofu ( ) 0.5 ( ) *Adjusted for smoking, alcohol use, sedentary job, leisure-time physical activity, hyperlipidemia, hypertension, diabetes mellitus, angina pectoris, obesity, and two other listed foods. combined and current smoking). Alcohol use was classified into 4 categories in men (never, past, and current drinking of 30 or 30+ ml of alcohol per day) and 2 categories in women (never, and past combined and current drinking). Indicator variables were created to represent categories of these covariates. Dichotomous variables were used for occupational physical activity, leisure-time physical activity, hypertension, angina pectoris, hyperlipidemia, diabetes mellitus, and obesity. Reported p values were 2-sided, and all statistical analyses were done with the Statistical Analysis System (SAS) version 6.12 (SAS Institute, Inc, Cary, NC, USA). Results The characteristics of the cases and controls are presented in Table 2. More controls compared with cases in men (66.8% vs 61.8%) had a regular job and more cases compared with controls in women (21.8% vs 17.5%) were employed. Traditional coronary risk factors were more frequent among cases than among controls in both men and women except for obesity. Table3 shows the RRs of nonfatal AMI in relation to the consumption of selected foods with adjustment for the nondietary coronary risk factors in men and women separately. Vegetable consumption showed no measurable association with AMI risk in either men or women. Although the RRs of AMI for the intermediate and high consumption of pickled vegetables were 0.8 (95% CI ) and 0.7 ( ), respectively, as compared with the lowest consumption in men, total, cooked and fresh vegetables were virtually unrelated to AMI risk in both men and women. The risk of AMI was significantly decreased in men with the intermediate and high consumption of fruits and fish each, although the trends were not statistically significant
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