Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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Cigarette smoking as a risk factor for stroke death in Japan NIPPON DATA80

Ueshima Hirotsugu, Choudhury Sohel Reza, Okayama Akira, Hayakawa Takehito, Kita Yoshikuni, Kadowaki Takashi, Okamura Tomonori, Minowa Masumi, Iimura Osamu

Stroke 35 ( 8 ) 1836 - 1841 2004.08

ISSN 0039-2499

Background and Purpose - Some previous Japanese cohort studies failed to show an association between smoking and stroke risk. Because such an association has been noted in other populations, this issue should be re-examined in a recent representative Japanese cohort with a higher total cholesterol level. Methods - A total of 9638 men and women aged 30 years and older without a history of cardiovascular disease (CVD) at baseline in 1980 were followed-up for 14 years. Results - We observed 203 stroke deaths (107 cerebral infarctions, 45 cerebral hemorrhages, and 51 others), 191 heart disease deaths, and 413 CVD deaths. The average serum total cholesterol level was ≈4.91 mmol/L. Cox proportional hazard ratios were calculated adjusting for age, systolic blood pressure, and other conventional risk factors. The hazard ratios for men who smoked 1 to 20 cigarettes/day for all strokes, cerebral infarction, and cerebral hemorrhage were 1.60 (95% CI, 0.91 to 2.79), 2.97 (CI, 1.27 to 6.98), and 0.42 (CI, 0.16 to 1.09), respectively, and for those who smoked ≥21 cigarettes/day, they were 2.17 (CI, 1.09 to 4.30), 3.26 (CI, 1.11 to 9.56), and 0.68 (CI, 0.20 to 2.33), respectively. For women who smoked ≥21 cigarettes/day, the hazard ratio for all strokes was 3.91 (CI, 1.18 to 12.90). For CVD, all heart disease, and ischemic heart disease, the hazard risks of smoking were significant (1.49 to 4.25) for men but not significant for women. Conclusions - Smoking in a cohort with moderate serum total cholesterol level was a potent risk factor for stroke, especially cerebral infarction, for both men and women, and for CVD and ischemic heart disease for men.

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Methodological issues for a large-scale intervention trial of lifestyle modification

Okamura Tomonori, Tanaka Taichiro, Takebayashi Toru, Nakagawa Hideaki, Yamato Hiroshi, Yoshita Katsushi, Kadowaki Takashi, Okayama Akira, Ueshima Hirotsugu

Environmental Health and Preventive Medicine 9 ( 4 ) 137 - 143 2004.07

ISSN 1342-078X

Objective: To clarify the methodological issues for the High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP study), which is a 4-year non-randomized control trial, an interim assessment of male participants was performed 3 years after the baseline survey. Methods: We had approximately 2,500 and 4,000 participants in the intervention and control groups, respectively. The population measures and prevalence of risk factors at each year, and between the baseline and 4th examinations were compared between the two groups. The personal trends of returning participants who were in the study at the 1st and 4th examinations were also evaluated. Results: During the 3 years, an increase in serum HDL cholesterol (2.7 mg/dl), and a reduction in the prevalence of hypertriglycemia detected with fasting blood samples (3.6%) and current smokers (5.4%) were observed in the intervention group. The mean HDL cholesterol level was significantly higher in the intervention group than in the control group at the 4th examination, reversed from the baseline survey. The serum non-HDL cholesterol level was significantly increased only in the control group. There was also a significant increase in the prevalence of hypertriglycemia and high plasma glucose detected with fasting blood samples in the control group. The return participation rate after 3 years was 72.2% for the intervention group and 74.9% for the control group. The above-mentioned changes for risk factors were mainly due to returning participants at each examination. Conclusion: These interventional methods may be effective in improving overall cardiovascular risk factors in the population. However, the low return participation rate will dilute the effect of the intervention.

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Egg consumption, serum cholesterol, and cause-specific and all-cause mortality

Nakamura Yasuyuki, Okamura Tomonori, Tamaki Shinji, Kadowaki Takashi, Hayakawa Takehito, Kita Yoshikuni, Okayama Akira, Ueshima Hirotsugu

American Journal of Clinical Nutrition 80 ( 1 ) 58 - 63 2004.07

ISSN 0002-9165

Background: Because egg yolk has a high cholesterol concentration, limited egg consumption is often suggested to help prevent ischemic heart disease (IHD). Objective: We epidemiologically examined the validity of this recommendation. Design: We analyzed the relations of egg consumption to serum cholesterol and cause-specific and all-cause mortality by using the NIPPON DATA80 (National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged, 1980) database. At the baseline examination in 1980, a nutritional survey was performed by using the food-frequency method in Japanese subjects aged ≥30 y. We followed 5186 women and 4077 men for 14 y. Results: The subjects were categorized into 5 egg consumption groups on the basis of their responses to a questionnaire (≥2/d, 1/d, 1/2 d, 1-2/wk, and seldom). There were 69, 1396, 1667, 1742, and 315 women in each of the 5 groups, respectively. Age-adjusted total cholesterol (5.21, 5.04, 4.95, 4.91, and 4.92 mmol/L in the 5 egg consumption categories, respectively) was related to egg consumption (P < 0.0001, analysis of covariance). In women, unadjusted IHD mortality and all-cause mortality differed significantly between the groups [IHD mortality: 1.1, 0.5, 0.4, 0.5, and 2.0 per 1000 person-years, respectively (P = 0.008, chi-square test); all-cause mortality: 14.8, 8.0, 7.5, 7.5, and 14.5 per 1000 person-years, respectively (P < 0.0001, chi-square test)]. In men, egg consumption was not related to age-adjusted total cholesterol. Cox analysis found that, in women, all-cause mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group, whereas no such relations were noted in men. Conclusion: Limiting egg consumption may have some health benefits, at least in women in geographic areas where egg consumption makes a relatively large contribution to total dietary cholesterol intake. © 2004 American Society for Clinical Nutrition.

The evaluation of materials to provide health-related information as a population strategy in the worksite

Yoshita Katsushi, Tanaka Taichiro, Kikuchi Yuriko, Takebayashi Toru, Chiba Nagako, Tamaki Junko, Miura Katsuyuki, Kadowaki Takashi, Okamura Tomonori, Ueshima Hirotsugu

Environmental Health and Preventive Medicine 9 ( 4 ) 144 - 151 2004.07

ISSN 1342-078X

Objective: To examine the effectiveness of newly developed materials for providing health-related information to the worksite population, we compared the amount of attention that employees paid to the materials. Methods: Study subjects were 2,361 employees in six companies partcipating in an intervention program between 2002 and 2003. Three kinds of media were used as tools for providing health information: [1] Point Of Purchase advertising menus (POP menus) were placed on all tables in company restaurants, [2] posters were put on walls and [3] leaflets were distributed at health-related events. One year or more after the introduction of these media, we compared the amount of attention paid to each type of medium. Results: Amongst the three types of media, the POP menu drew the most attention, although results were not consistent in all gender and company groups. Every piece of information provided by the POP menus was "always" or "almost always " read by 41% of the men and 51% of the women surveyed. The corresponding rate for posters was 30% in men and 32% in women. For leaflets, only 16% of men and 22% of women read almost all of the leaflets. More attention was paid to the POP menu when the sample was women, older, and ate at the company restaurant at least three times a week. Conclusion: The POP menu may provide health-related information to a broader range of people than posters and leaflets, therefore, it is an effective material for population strategy.

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Effectiveness of annual interventions for smoking cessation in an occupational setting in Japan

Kadowaki Takashi, Okamura Tomonori, Funakoshi Tsutae, Okayama Akira, Kanda Hideyuki, Miyamatsu Naomi, Kita Yoshikuni, Ueshima Hirotsugu

Environmental Health and Preventive Medicine 9 ( 4 ) 161 - 164 2004.07

ISSN 1342-078X

Objective: To examine the effectiveness of a small-scale smoking cessation intervention program conducted annually for ten years in an occupational setting in Japan. Methods: We conducted an annual intervention program promoting smoking cessation in male smokers from 1993 to 2002 in an occupational setting in Hyogo, Japan. Trends in smoking prevalence in this worksite were compared with a control group from two similar worksites of the same company. The intervention program was carried out by medical students (the fourth year of a six-year course) who received training on the protocol prior to the intervention. This protocol consisted of one initial group session, followed by periodical correspondence for two months. Successful cessation of smoking was determined by self-declaration of abstinence for longer than four weeks after intervention, confirmed by an expiratory carbon monoxide concentration of less than nine ppm. Smoking prevalence was determined by a self-administered questionnaire provided at the annual health checkup. Results: The proportion of smokers who participated in the program was 3.47% on average. Abstinence rates following each intervention ranged from 13.3% to 60.0%, with the prevalence of male smokers at the intervention worksite decreasing from 56.2% in 1993 to 47.0% in 2002. In contrast, the smoking prevalence of the control worksites remained largely unchanged, being 60.2% in 1995 and 57.6% in 2002. At the end of the study, the intervention worksite had a significantly lower prevalence of smokers in either the crude or age-adjusted rate. Conclusion: A small-scale but repeated smoking cessation intervention program at a worksite can reduce smoking prevalence more efficiently than the natural trend.

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The high-risk and population strategy for occupational health promotion (HIPOP-OHP) study

Okamura T., Tanaka T., Babazono Akira, Yoshita Katsushi, Chiba Nagako, Takebayashi Toru, Nakagawa Hideaki, Yamato Hiroshi, Miura Katsuyuki, Tamaki J., Kadowaki T., Okayama Akira, Ueshima Hirotsugu, Nishi Nobuo, Tsuji Keiko, Kikuchi Yuriko, Yanagita Masahiko, Kodama Kazunori, Kasagi Fumiyoshi, Kusaka Yukinori, Saitoh Shigeyuki, Sakata Kiyomi, Tanaka Hideo, Nakamura Masakazu, Naito Yoshihiko, Nakamura Yasuyuki, Watanabe Makoto, Nakamura Yoshikazu, Tamura Unai, Minai Junko, Yamagata Zentaro, Urano Sumio, Kinoshita Fujihisa, Saitoh Isao, Tanihara Shinichi, Tamaki Junko, Tochikubo Osamu

Journal of Human Hypertension 18 ( 7 ) 475 - 485 2004.07

ISSN 0950-9240

In order to establish the methodology of a population strategy for improving cardiovascular risk factors, we have planned the High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP study). This study is a nonrandomized control trial in approximately 6500 participants in six intervention and six control companies. Our population strategy is based on three factors, nutrition, physical activity, and smoking. For each factor, a researcher's working team was organized and has been supporting the intervention. A standardized method to obtain comparable data has also been established. In the baseline survey, urinary sodium excretion in male subjects was higher, and urinary potassium excretion was lower in both genders in the intervention group compared to the control group. The prevalence of hypertension for both genders was also higher in the intervention group. Male subjects in the intervention group had higher serum total cholesterol than controls, while high-density lipoprotein cholesterol was lower in both genders in the intervention group compared to the control group. These differences were reflected by our finding that the predicted relative risk of coronary heart disease for male subjects was significantly higher in the intervention group (relative risk, RR: 1.17; 95% confidence interval, 95% CI.: 1.09, 1.25) and significantly lower in the control group (RR: 0.93; 95% CI.: 0.89, 0.98) compared to a model Japanese population. Similar results were observed in the female subjects. Taken together, these findings indicate that it is possible to compare trends of predicted relative risk for coronary heart disease between two groups. © 2004 Nature Publishing Group All rights reserved.

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Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese

Iso Hiroyasu, Moriyama Yuri, Sato Shinichi, Kitamura Akihiko, Tanigawa Takeshi, Yamagishi Kazumasa, Imano Hironori, Ohira Tetsuya, Okamura Tomonori, Naito Yoshihiko, Shimamoto Takashi

Circulation 109 ( 22 ) 2766 - 2772 2004.06

ISSN 0009-7322

Background - To date, no prospective studies have examined the association between serum homocysteine levels and the risk of stroke and stroke subtypes in Asian populations. Methods and Results - A prospective, nested, case-control study of Japanese subjects 40 to 85 years of age was conducted by using frozen serum samples from 11 846 participants in cardiovascular risk surveys collected from 1984 to 1995 for one community and 1989 to 1995 for the other two communities. By the end of 2000, we identified 150 incident strokes, the subtypes of which were confirmed by imaging studies. Three control subjects per case were selected by matching for sex, age, community, year of serum storage, and fasting status. Serum total homocysteine levels were measured by high-performance liquid chromatography. Compared with control subjects, total (n=150), hemorrhagic (n=52), and ischemic (n=98) strokes had higher geometric mean values of total homocysteine and higher proportions of homocysteine ≥11.0 μmol/L. The multivariate odds ratios (95% CI) for highest (≥11.0 μmol/L) versus lowest quartiles (<7.0 μmol/L) of homocysteine after adjustment for body mass index, smoking, alcohol intake, hypertension, serum total cholesterol, and other cardiovascular risk factors were 2.99 (1.51 to 5.93) for total stroke, 3.89 (1.60 to 9.46) for ischemic stroke, 3.36 (1.27 to 8.90) for lacunar infarction, and 1.63 (0.44 to 6.00) for hemorrhagic stroke. The respective multivariate odds ratios associated with a 5-μmol/L increase in homocysteine were 1.40 (1.09 to 1.80), 1.52 (1.07 to 2.14), 1.48 (1.01 to 2.18), and 1.10 (0.76 to 1.59). The excess risk of total and ischemic strokes did not vary significantly according to sex, age, smoking status, or hypertensive status. Conclusions - High total homocysteine concentrations were associated with the increased risk of total stroke, more specifically ischemic stroke and lacunar infarction, among Japanese men and women.

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Resting heart rate and cause-specific death in a 16.5-year cohort study of the Japanese general population

Okamura Tomonori, Hayakawa Takehito, Kadowaki Takashi, Kita Yoshikuni, Okayama Akira, Elliott Paul, Ueshima Hirotsugu

American Heart Journal 147 ( 6 ) 1024 - 1032 2004.06

ISSN 0002-8703

Background Several prospective studies have reported resting heart rate (HR) to be a risk factor for certain cause-specific death, together with sex- or age-specific differences in the effects of HR on death. However, there have been few prospective data from non-Western populations. Methods Cohort study, over 16.5 years to date of death or end of follow-up (November 15, 1998) involving 8800 men and women ≥30 years of age randomly selected throughout Japan, who participated in the National Survey on Circulatory Disorders in 1980. Resting HR was determined from 3 consecutive intervals between R waves on the 12-lead electrocardiogram. Results For middle-aged men (30 to 59 years of age), in the highest quartile of HR, there was a significant positive association with cardiovascular (RR, 2.55; 95% CI, 1.22 to 5.31) and all-cause death (RR, 1.45; 95% CI, 1.06 to 2.00). For middle-aged women, in the highest quartile, there was a significant positive association with noncancer, noncardiovascular (RR, 2.41; 95% CI, 1.04 to 5.59), and all-cause death (RR, 1.94; 95% CI, 1.26 to 3.01). Resting HR also showed a significant positive association with cardiac events but not to stroke. These relations were not evident for elderly subjects (≥60 years of age). Results were not affected when deaths within the first 5 years of follow-up were excluded, except for noncancer, noncardiovascular death. Conclusions High resting HR is an independent predictor of long-term death in the Japanese general population.

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Non-invasive measurement of brachial-ankle pulse wave velocity is associated with serum C-reactive protein but not with α-tocopherol in Japanese middle-aged male workers

Okamura Tomonori, Moriyama Yuri, Kadowaki Takashi, Kanda Hideyuki, Ueshima Hirotsugu

Hypertension Research 27 ( 3 ) 173 - 180 2004.03

ISSN 0916-9636

Pulse wave velocity (PWV) is an indicator of arterial stiffness, especially in the aorta, and a marker for vascular damage. We examined the association of brachial-ankle PWV (baPWV) with serum α-tocopherol and C-reactive protein (CRP) levels in addition to the traditional risk factors. Study subjects were 178 Japanese male workers aged 50-59 without past histories of cardiovascular diseases. The relation of baPWV with serum α-tocopherol and CRP levels was cross-sectionally analyzed after adjusting for other cardiovascular risk factors. The arithmetic mean of serum α-tocopherol was 38.9 μmol/l, and the geometric mean of serum CRP was 0.47 mg/l. Multiple linear regression analysis indicated that serum CRP levels were associated with an elevation of baPWV, in addition to age, systolic blood pressure and heart rate. However, serum α-tocopherol, serum lipids (triglyceride, low and high density lipoprotein cholesterol), fasting plasma glucose, body mass index, smoking and alcohol drinking did not significantly correlate to baPWV. Multivariate-adjusted means of baPWV according to serum CRP quartile were 1,431, 1,436, 1,507 and 1,508 cm/s (p=0.033). The serum CRP level might be an important marker for arterial stiffness in Japanese middle-aged males. However, no relation was observed between α-tocopherol and baPWV.

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Stages of change for salt intake and urinary salt excretion

Tamaki Junko, Kikuchi Yuriko, Yoshita Katsushi, Takebayashi Toru, Chiba Nagako, Tanaka Taichiro, Okamura Tomonori, Kasagi Fumiyoshi, Minai Junko, Ueshima Hirotsugu

Hypertension Research 27 ( 3 ) 157 - 166 2004.03

ISSN 0916-9636

We investigate the relationship of urinary salt excretion to the stage of change to decrease salt intake in the Japanese diet. The data reported here were obtained from a baseline survey of the High-Risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study that was conducted as a non-randomized control trial at 12 worksites in Japan. A total of 6,816 subjects (5,410 male, 1,406 female) were used in 1999 and 2000 for the analysis. We used three categories of stage of change: precontemplation or contemplation (P/C), preparation (P), and action or maintenance (A/M). Urinary salt excretion was estimated from the sodium and creatinine concentrations in spot urine samples. Multivariate analysis indicated that urinary salt excretion among males was 0.3 g/day greater in the P/C stage than in the A/M stage (p<0.05). For non-obese females, urinary salt excretion in the P/C stage was 0.6 g/day greater than in the A/M stage (p<0.05). Multivariate analysis showed that diastolic blood pressure in males not taking antihypertensive agents was 1.3 mmHg lower in the P/C stage than in the A/M stage (p<0.05). A similar but statistically insignificant tendency was observed among non-obese females. A significant association was demonstrated between stage of change for dietary salt intake and urinary salt excretion for both males and non-obese females. There may be a potential application of the stage of change model for reducing dietary salt intake in a health promotion program.

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Specific alcoholic beverage and blood pressure in a middle-aged Japanese population

Okamura T., Tanaka T., Yoshita K., Chiba N., Takebayashi T., Kikuchi Y., Tamaki J., Tamura U., Minai J., Kadowaki T., Miura K., Nakagawa H., Tanihara S., Okayama A., Ueshima H.

Journal of Human Hypertension 18 ( 1 ) 9 - 16 2004.01

ISSN 0950-9240

The purpose of this study was to clarify the effects of popular Japanese alcoholic beverages on blood pressure. We performed a cross-sectional study on 4335 Japanese male workers using baseline data from an intervention study. We defined six groups according to the type of alcoholic beverage that provided two-thirds of the subject's total alcohol consumption: beer, sake (rice wine), shochu (traditional Japanese spirits), whiskey, wine and others. The partial regression coefficients of daily alcohol intake (1 drink = 11.5 g of ethanol) to systolic blood pressure (SBP) and diastolic blood pressure (DBF) were 0.87(P < 0.001, standard error (s.e.) = 0.09) and 0.77(P < 0.001, s.e. = 0.06), respectively. A comparison among the types of alcoholic beverages mainly consumed revealed significant differences in SBP and DBP. Both SBP and DBP were highest in the shochu group. However, an analysis of covariance adjusting for total alcohol consumption resulted in the disappearance of these differences. Although after adjustment for total alcohol consumption, the shochu group exhibited a significant positive association with 'high-normal blood pressure or greater' (odds ratio 1.43, 95% confidence interval 1.06-1.95) compared with the beer group, this significant relation disappeared after adjusting for the body mass index (BMI), urinary sodium and potassium excretion. The pressor effect, per se, of popular Japanese alcoholic beverages on blood pressure may not be different among the types of alcoholic beverages after adjusting for other lifestyle factors.

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Weight-control intervention in overweight subjects at high risk of cardiovascular disease

Okuda Nagako, Okamura Tomonori, Kadowaki Takashi, Tanaka Taichiro, Ueshima Hirotsugu

[Nippon kōshū eisei zasshi] Japanese journal of public health 51 ( 7 ) 552 - 560 2004

ISSN 0546-1766

OBJECTIVE: To evaluate the effectiveness of a weight-control intervention for overweight subjects at high risk of cardiovascular disease (CVD) at a worksite conducted by medical students as a public health practical training program. METHODS: A total of 45 men and women who were obese (BMI > or = 24.0 kg/m2) and found to be hypertensive (SBP > or = 140 mmHg or DBP > or = 90 mmHg) or suffering from hypercholesterolemia (total serum cholesterol > or = 220 mg/dl) in an annual health check up in November 2001 were invited to participate in a weight-control intervention program. Eight individuals agreed (intervention group) and other sixteen control subjects whose sex and age (+/- 3 years) were matched to the intervention subjects were selected. The duration of the program was three months (from July to October 2002) and a 2 kg weight reduction in that period was set as the goal. The baseline survey consisted of a dietary questionnaire and a health quiz. Subjects had two counseling sessions and received four personal letters in the three months. A semi-quantitative food frequent questionnaire, a photograph method (Diet Agent Service, Matsushita Electric Works, Ltd.) and three day food records were conducted for dietary surveys. Changes in bodyweight, BMI, blood pressure, and serum total cholesterol concentration from November 2001 to November 2002 were compared between the intervention and control groups. Food group intakes and nutrient intakes were compared between weight reduction achievers and non-achievers. RESULTS: Mean bodyweight changes from November 2001 to November 2002 were -2.3 kg (SD 3.3 kg) for the intervention group and +0.3 kg (SD 1.5 kg) for the control group, the difference being significant (p = 0.013). For the intervention group mean bodyweight change from July to October 2002 was -1.5 kg (SD 2.4 kg). For total serum cholesterol, the mean changes were -32.1 mg/dl vs. +0.5 mg/dl (p = 0.005), for SBP -9.5 mmHg vs. +4.7 mmHg (p = 0.083) and for DBP -2.8 mmHg vs. +1.4 mmHg (p = 0.438). These were thought to be consequences of weight-control intervention. From dietary surveys, weight reduction achievers increased fish intake and decreased fats, snacks and sweets. Those who answered the health quiz more correctly demonstrated more reduction of bodyweight. CONCLUSIONS: Effectiveness of a weight-control intervention for reduction of CVD risk factors was found in the present public health practical training program for medical students. Dietary advice based on various dietary surveys was indicated to be effective in the weight-control program. A population strategy to distribute health information appeared necessary for effective health education programs for high-risk subjects.

Haplotype analyses of cholesteryl ester transfer protein gene promoter

Lu Hong, Inazu Akihiro, Moriyama Yuri, Higashikata Toshinori, Kawashiri Masa Aki, Yu Wenxin, Huang Zhiping, Okamura Tomonori, Mabuchi Hiroshi

Journal of Molecular Medicine 81 ( 4 ) 246 - 255 2003.04

ISSN 0946-2716

Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to triglyceride-rich lipoproteins. TaqIB polymorphism (B2 allele) identified in intron 1 is associated with lower plasma CETP concentrations and higher HDL cholesterol levels and may play an antiatherogenic role in humans, However, its molecular mechanism remains unclear. To evaluate the association between the promoter polymorphisms and CETP/HDL cholesterol levels, ten novel and three previously reported polymorphisms located within 3.3 kb of the CETP gene promoter were investigated in a sample of 357 elderly Japanese men. All the promoter polymorphisms were in linkage disequilibrium with each other and with TaqIB. The -2505A allele, the "S" allele of the [gaaa]_n repeat ("S" denotes [gaaa]_n=329 bp and longer, "L" denotes >329 bp) and TaqIB2 allele were significantly associated with both lower plasma CETP concentrations and higher HDL cholesterol levels whereas -971G/A and -629A/C were significantly associated with CETP concentrations but not with HDL-C levels. The 12-polymorphism haplotypes consisting of -2804, -2505, [gaaa]_n, -1930, -1674, -1129, -1046, -971, -875, -827, -629, and TaqIB were analyzed. These 12 polymorphisms generated eight main haplotypes, accounting for 86% of the observed haplotypes. The G/A/S/T/T/C/T/A/C/C/A/B2 haplotype was significantly associated with lower CETP concentrations (2.0±0.6 μg/ml) and higher HDL cholesterol levels (55.1±12.7 mg/dl) than the other seven main haplotypes. The 5- and 3-polymorphism haplotype analyses consisting of -2505 and the [gaaa]_n repeat indicated the -2505C/A polymorphism might explain the variation in the CETP concentrations best, and the [gaaa]_n repeat and/or the -2505C/A polymorphism may independently determine the variation in HDL cholesterol levels, whereas the -629A/C and TaqIB polymorphisms were not instrumental in determining CETP concentrations as well as HDL cholesterol levels, although the latter has been frequently examined in many association studies.

A "natural experiment" in cardiovascular epidemiology in the early 21st century

Sekikawa Akira, Horiuchi B. Y., Edmundowicz D., Ueshima H., Curb J. D., Sutton-Tyrrell K., Okamura T., Kadowaki T., Kashiwagi A., Mitsunami K., Murata K., Nakamura Y., Rodriguez B. L., Kuller L. H.

Heart 89 ( 3 ) 255 - 257 2003.03

ISSN 1355-6037

What cause of mortality can we predict by cholesterol screening in the Japanese general population?

Okamura Tomonori, Kadowaki T., Hayakawa T., Kita Y., Okayama A., Ueshima H.

Journal of Internal Medicine 253 ( 2 ) 169 - 180 2003.02

ISSN 0954-6820

Objective. In a population with a markedly lower coronary mortality such as in Japan, the benefit of cholesterol screening may be different from Western populations. We attempted to assess the importance of cholesterol screening in Japan. Design. A 13.2-year cohort study for cause-specific mortality. Setting. Three hundred randomly selected districts throughout Japan in which the National Survey on Circulatory Disorders 1980 was performed. Subjects. A total of 9216 community dwelling persons aged 30 years and over, with standardized serum cholesterol measurement and without a past history of cardiovascular disease. Results. There were 1206 deaths, which included 462 deaths due to cardiovascular disease with 79 coronary heart diseases. Hypercholesterolemia (>6.21 mmol L^-1) showed a significant positive relation to coronary mortality (relative risk; 2.93, 95% confidence interval: 1.52-5.63) but not to stroke. Although hypocholesterolemia (<4.14 mmol L^-1) was significantly associated with an increased risk of liver cancer, noncardiovascular, noncancer disease and all-cause mortality, these associations, except for liver cancer, disappeared after excluding deaths in the first 5 years of the follow-up. The multivariate adjusted attributable risk of hypercholesterolaemia for coronary disease was 0.98 per 1000 person-years, which was three-fold higher than that of hypocholesterolemia for liver cancer: 0.32 per 1000 person-years. The attributable risk percentage of hypercholesterolaemia was 66% for coronary heart disease. Conclusion. Similar to Western populations, it is recommended to provide screening for hypercholesterolaemia in Japan, especially for males, although its attributable risk for coronary disease might be small.

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Electron-beam computed tomography for identification of high-risk persons in primary prevention of coronary heart disease in the United States and its implication for Japan

Sekikawa Akira, Okamura Tomonori, Kadowaki Takashi, Mitsunami Kenichi, Murata Kiyoshi, Kashiwagi Atsunori, Nakamura Yasuyuki, Kanda Hideyuki, Edmundowicz Daniel, Sutton-Tyrrell Kim, Curb J. David, Kuller Lewis H., Ueshima Hirotsugu

[Nippon kōshū eisei zasshi] Japanese journal of public health 50 ( 3 ) 183 - 193 2003

ISSN 0546-1766

Coronary heart disease (CHD) is the leading cause of death in the United States (US). Approximately half of deaths from (CHD) occur out of hospital, most being sudden. The majority of sudden cardiac deaths occur in asymptomatic subjects. Recent lipid-lowering trials in asymptomatic subjects have demonstrated the potential for risk reduction for CHD events by primary prevention. It is, however, generally acknowledged that risk will be underestimated in asymptomatic subjects who fall into the category of intermediate risk by the traditional risk factors. Non-invasive measurements of subclinical atherosclerosis, which is the end result of risk-factor exposure, have the possibility of improving the risk stratification of asymptomatic subjects in intermediate-risk. Electron-beam computed tomography (EBCT) is a non-invasive and highly sensitive means to detect calcification within coronary arterial wall. Coronary artery calcification (CAC) is a recognized marker of atherosclerosis. Atherosclerotic burden of coronary arteries correlates strongly with the amount of CAC measured by EBCT. Studies examining the predictive value of CAC among asymptomatic subjects consistently reported that CAC is a risk for CHD. Two studies reported that unadjusted odds ratios of CAC for CHD were over 20. Incremental value of EBCT over the traditional risk assessment models, however, has not been established. Although CHD mortality in Japan remains uniquely low in industrialized countries, among men aged 30-49, risk factor profiles for CHD are similar between men in the US and Japan, except higher prevalence of cigarette smoking in Japan and higher prevalence of obesity in the US. It is reported that the declining trend in CHD mortality in Japan has recently slowed down in metropolitan areas, especially in men aged 30-49, and that the incidence has increased in middle-aged workers in a metropolitan area. A mortality validation study reported that the differences in CHD mortality between the US and Japan were not as large as suggested by vital statistics. It is, therefore, important to evaluate subclinical atherosclerosis measured by EBCT in men in recent birth cohorts in Japan and compare it to that in men in the US in order to predict future trend in CHD in Japan.

Smoking scenes in Japanese television dramas

Kanda Hideyuki, Okamura Tomonori, Kadowaki Takashi, Hayakawa Takehito, Kita Yoshikuni, Ueshima Hirotsugu

[Nippon kōshū eisei zasshi] Japanese journal of public health 50 ( 1 ) 62 - 70 2003

ISSN 0546-1766

BACKGROUND: Exposure to smoking scenes in movies and TV dramas has been known to be a trigger for young people starting habitual smoking, but it has not been clarified to what extent youth is routinely exposed to smoking scenes in television programs in Japan. OBJECTIVE: To clarify the status quo of smoking scenes and smoking-related items in serial TV dramas targeting young audience in Japan. METHOD: Seven TV dramas targeting a young audience broadcast between July and September, 2001 were analyzed. A total of 63 hours of TV programs were divided into units of three minutes (a total of 1,264 units). All the units were reviewed for smoking scenes, description of social contexts related to smoking behavior, existence of smoking and smoking-related items. FINDINGS: Among the 1,264 three-minute units, 129 (10.2%) contained smoking behavior, and 258 (20.4%) depicted smoking environment with presence of smoking-related items. Smokers were male actors (126 units, 97.7%), aged 20-40 years (118 units, 91.5%), leading actors (72 units, 55.8%), and were smoking alone (80 units, 62.0%). Smoking places mainly took place in indoor settings (56 units, 43.4%). Ashtrays were the most frequently observed smoking-related items (8.1% of the total units). The smoking scenes with actions other than smoking itself accounted for 70 units (54.3% of the smoking scenes). As for the actions other than smoking, working (28 units, 21.7%) and eating (17 units, 13.2%) were commonly observed. Regarding smoking scenes without any other actions, 32 units (24.8%) were observed in the beginning or ending telops, and 27 units (20.9%) showed a person smoking without doing anything else. There were only 3 units (0.2%) which were against smoking behavior. Approximately 30% of the Japanese serial television drama scenes featured tobacco use in story plots. As the general features of the smoking scenes, most of them do not necessarily require smoking in the story. Furthermore, there was little consideration about separation of designated smoking areas.

Determinants of platelet aggregation in 50-70-year-old men from three Japanese communities

Imano Hironori, Iso Hiroyasu, Sato Shinichi, Kitamura Akihiko, Okamura Tomonori, Tanigawa Takeshi, Ohira Tetsuya, Kudo Minako, Naito Yoshihiko, Iida Minoru, Shimamoto Takashi

Atherosclerosis 165 ( 2 ) 327 - 334 2002.12

ISSN 0021-9150

To investigate the association of lifestyle and constitutional variables with platelet aggregation, we examined the platelet aggregation, serum fatty acid composition, alcohol intake, smoking, and dietary intake of seafood and soybean estimated by a 1-week dietary record in 448 males aged 50-70 in three rural Japanese communities: Ikawa, Akita prefecture (northeast coast), Noichi, Kochi prefecture (southwest coast), and Kyowa, Ibaraki prefecture (central inland). Platelet aggregatory threshold index (PATI) was used to determine the minimum concentration of adenosine 5′-diphosphate (ADP) that caused a non-reversible aggregation of platelets. Intake of seafood and n3-polyunsaturated fatty acid and ingestion of ethanol were higher in the northeast coastal community than in the other two communities. Mean platelet and white blood cell counts were lower in northeast coastal community than in the other two communities. The geometric mean PATI was higher (i.e. platelet aggregation was lower) in the northeast coastal community than the other two communities. Within the entire sample, platelet aggregation correlated inversely with serum level of n3-polyunsaturated fatty acids and γ-glutamyl transpeptidase, an index of alcohol consumption, and positively with platelet and white blood cell counts. Platelet aggregation tended to correlate positively with serum arachidonic acid. There was no correlation between smoking and platelet aggregation. Our results suggest that seafood intake and moderate alcohol consumption reduce platelet aggregation. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

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Polymorphism of the angiotensin converting enzyme gene and blood pressure in a Japanee general population (the Shigaraki study)

Tamaki Shinji, Nakamura Yasuyuki, Tsujita Yasuyuki, Nozaki Akihiko, Amamoto Kenji, Kadowaki Takashi, Kita Yoshikuni, Okamura Tomonori, Iwai Naoharu, Kinoshita Masahiko, Ueshima Hirotsugu

Hypertension Research 25 ( 6 ) 843 - 848 2002.11

ISSN 0916-9636

Recent studies have described a linkage between angiotensin converting enzyme (ACE) gene polymorphism and hypertension in a large number of hypertensive sibs. Moreover, among Japanese, the DD genotype of the ACE gene has been reported to be a genetically predisposing factor for hypertension in a large general population. However, there is some controversy regarding the association between the ACE insertion/deletion (I/D) polymorphism and systemic hypertension. Therefore, we examined the influence of the ACE I/D polymorphism in a random Japanese population. The participants were 2,892 subjects (1,110 males: mean age, 58.4±15.5; 1,782 females: mean age, 56.2±15.7) who underwent medical examinations in 1999 in Shigaraki, a suburban town located in an urban area in Shiga prefecture. Among them, 2,395 subjects (917 males: mean age, 58.0±15.7; 1478 females: mean age, 56.3±15.6) who gave their informed consent for genetic analysis were enrolled in the present study. Every year since 1991, we have repeatedly performed medical examinations in Shigaraki. ACE genotypes were determined by polymerase chain reaction (PCR) methods. Logistic analysis revealed that age (p<0.001; odds ratio=1.091), body mass index (BMI) (p<0.001; odds ratio=1.211), and family history of hypertension (p<0.001; odds ratio=0.371) were associated with hypertension (systolic blood pressure greater than 140 mmHg and diastolic greater than 90 mmHg). There was no association between ACE polymorphism and blood pressure. There were also no significant differences in blood pressure among males or females across the three genotypes. Moreover, in an analysis of 1,484 subjects (549 males: mean age, 62.8±12.1; 935 females: mean age, 61.2±12.6) who were followed-up since 1991, there was no association between ACE polymorphism and changes in blood pressure (p=0.3905). We conclude that ACE polymorphism does not appear to have any significant association with blood pressure, changes in blood pressure or sex in Japanese subjects, who have a more homogeneous genetic background than any other group reported to date.

Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population

Amamoto Kenji, Okamura Tomonori, Tamaki Shinji, Kita Yoshikuni, Tsujita Yasuyuki, Kadowaki Takashi, Nakamura Yasuyuki, Ueshima Hirotsugu

Hypertension Research 25 ( 6 ) 857 - 864 2002.11

ISSN 0916-9636

In Japanese and other Asians, the prevalence of genetically decreased mitochondrial aldehyde dehydrogenase (ALDH2) activity is higher than in Caucasians. The aim of this study was to elucidate the relation between ALDH2 genotypes and blood pressure levels or hypertension in Japanese. After obtaining informed consent for genetic analysis from 917 men and 1,478 women who lived in a mountainous farming region near Kyoto and who were free from cardiovascular disease and liver dysfunction, the authors identified the ALDH2 genotype in all subjects. Differences in blood pressure level among genotypes were then compared by analysis of covariance, and the relation between genotypes and hypertension was also analyzed by logistic regression analysis. The frequencies of genotypes *1/*1, *1/*2, and *2/*2 were 44.7%, 46.9% and 8.4% in men, and 50.1%, 43.2% and 6.8% in women, respectively. In men, systolic and diastolic blood pressures tended to decrease in the order of *1/*1>*1/*2>*2/*2. However, adjustment for confounding factors including alcohol consumption resulted in the disappearance of significance. Logistic regression analysis adjusted for the same confounding factors for men showed that the odds ratios (OR) of being hypertensive in the *2 allele to not having *2 allele were 0.67 (95% confidence interval (CI): 0.47-0.96). However, in the subgroup analyses, this relation was not observed in the group having a below-median level of alcohol consumption (OR=0.92; 95% CI: 0.53-1.62) or in the group not taking antihypertensive agents (OR=0.77; 95% CI: 0.52-1.15). Furthermore, we did not observe any relation between the ALDH2/*2 allele and hypertension in women (OR=1.07; 95% CI: 0.80-1.42). The results suggest that there may be no causal relation between hypertension and the ALDH2 genotype per se, after excluding for some confounding factors, especially for alcohol drinking.

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