Published papers

PURPOSE: Although high consumption of fish may be one of the contributing factors for Japanese longevity, no epidemiological study using Japanese data has tested this hypothesis. SUBJECTS AND METHODS: The relationship between fish consumption and all-cause as well as cause-specific mortality was analyzed using the database of NIPPON DATA80. At baseline in 1980, history, physical, and blood biochemical measurement and a nutritional survey by the food-frequency method were performed in randomly selected community-based subjects aged 30 years and over in Japan. After exclusion of subjects with significant comorbidities at baseline, we followed 3 945 men and 4 934 women for 19 years. Men and women were analyzed comprehensively. Age- and sex-adjusted and multivariate adjusted relative risk for all-cause or cause-specific mortality was calculated using a Cox proportional hazards model with delayed entry. RESULTS: During 19 years of followup, there were 1 745 deaths. Subjects were divided into 5 groups according to fish consumption frequency. The multivariate Cox analyses showed that relative risks for subjects who ate fish more than twice daily compared with those of subjects who ate 1 to 2 times weekly were 0.99 (95% confidence intervals: 0.77-1.27) for all-cause, 1.26 (0.70-2.29) for stroke, 0.92 (0.20-4.23) for cerebral hemorrhage, 1.09 (0.48-2.43) for cerebral infarction, and 0.91 (0.35-2.35) for coronary heart disease mortality. CONCLUSION: Our results did not provide evidence in support of the fish hypothesis, perhaps because the majority of the Japanese subjects in the study ate fish more than the threshold level shown to be beneficial in the previous studies. © 2005 Elsevier Inc. All rights reserved.

There are few community-based epidemiologic studies that have dealt with risk factors for heart failure in non-Western populations. It has been reported that the measurement of plasma B-type natriuretic peptide (BNP) is useful for detecting patients with asymptomatic heart failure. To clarify the determinants of high plasma BNP level, the association of BNP with cardiovascular risk factors in community dwelling residents was examined. The plasma BNP levels were measured in 686 residents aged 35-69 years who received annual health check-up. The relationship of BNP to blood pressure, blood haemoglobin, serum cholesterol (total and high-density lipoprotein cholesterol), plasma glucose, electrocardiographic (ECG) findings, urinary salt excretion, and lifestyle factors (smoking and alcohol consumption) were cross-sectionally analysed. The plasma BNP geometric mean was 13.7 pg/ml. Both linear and logistic regression analyses indicated that the plasma BNP levels were positively associated with age, urinary salt excretion, higher blood pressure, high R-wave voltage in the 12-lead ECG (Minnesota Code 3-1 or 3-3), and female gender. Plasma BNP levels were inversely associated with blood haemoglobin levels. Gender-specific analysis showed similar results. However, plasma BNP did not correlate with other cardiovascular risk factors such as serum lipids. © 2005 Nature Publishing Group All rights reserved.

Background: Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the US and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40-49 in the US and Japan. Methods: We conducted a cross-sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography. Results: Systolic blood pressure, total cholesterol, low density lipoprotein (LDL)-cholesterol, and smoking rates were higher among the Japanese (122.6 ± 14.1 versus 113.7 ± 9.6 mmHg, P < 0.01; 5.72 ± 0.90 versus 4.99 ± 0.81 mmol/l (220.9 ± 34.6 versus 192.8 ± 31.3 mg/dl), P < 0.01; 3.52 ± 1.01 versus 3.10 ± 0.78 mmol/l (136.0 ± 39.0 versus 119.7 ± 30.0 mg/dl), P < 0.01; and 48 versus 15%, P < 0.01, respectively). Triglycerides and fibrinogen were similar. High density lipoprotein (HDL)-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score >0 was strikingly lower among the Japanese than the Americans (13% versus 47%, P < 0.01). Conclusions: Much lower prevalence of coronary calcium despite a less favourable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance. © International Epidemiological Association 2004; all rights reserved.

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.

There is no population-based prospective study concerning the relation between serum albumin and mortality in a non-Western population, and few previous studies included the subgroup analysis stratified by serum cholesterol level. A 13.7-year cohort study was conducted on 6,957 males and females aged 30-59 years from 300 randomly selected areas throughout Japan, who participated in the National Survey on Circulatory Disorders in 1980. In the group with median and above of total cholesterol, one standard deviation (SD) increment of serum albumin (2.6 g/L for males and 2.4 g/L for females) was inversely associated with all-cause mortality for both males and females (relative risk RR = 0.68 and 0.81; 95% confidence interval CI = 0.53-0.87 and 0.68-0.98), and with cancer mortality for females (RR = 0.74; 95% CI = 0.57-0.96); and the lowest category of serum albumin (≤43 g/L) showed the highest cardiovascular mortality for males (RR = 5.04; 95% CI = 1.04-24.5) among the three albumin categories. These relationships were not evident in the group with total cholesterol level below median. A combination of a low albumin level and above average cholesterol level, even both within the clinical normal range, is associated with excess mortality in the Japanese general population. © 2004 Elsevier Inc. All rights reserved.

The Stages of Change model evaluates and conceptualizes attempts to alter particular behavior patterns. To investigate the validity of this model for assessing fruit and vegetable intake, we examined the association between the stage of change in fruit and vegetable intake and urinary potassium excretion. The data were from baseline surveys taken in 1999 and 2000 from the High-Risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study in Japan. This was a non-randomized control trial at 12 worksites in Japan and aimed to decrease cardiovascular risk factors. Cross-sectional analysis was performed using data from 6,774 participants (5,364 men and 1,410 women). We used three categories of the model: precontemplation or contemplation (P/C), indicating no commitment to change; preparation (P), indicating readiness to change behavior but not actually doing so; and action or maintenance (A/M), indicating an actual change in behavior. Urinary potassium excretion was estimated from the potassium and creatinine concentrations in spot urine samples. Multivariate analysis indicated that urinary potassium excretion in the A/M stage was 1.65 mmol/day more than in the P stage, and 1.44 mmol/day more than in the P/C stage for men (p<0.05, respectively). For women, urinary potassium excretion in the A/M stage was 1.26 mmol/day more than in the P/C stage (p< 0.05) and 1.04 mmol/day more than in the P stage, although the latter result lacked statistical significance (p=0.08). This study supports the potential value of the Stages of Change model for increasing fruit and vegetable intake in the design of dietary intervention programs.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.