Published papers

Background: Although light and moderate alcohol drinkers are likely to have better subjective health, the sub-scales for subjective health have not been well documented. Methods: We studied 4,521 male workers aged 25 yr and older with no history of cancer or cardiovascular disease, in 12 occupational groups in Japan. Data were from the High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP). Drinking status was classified according to daily alcohol intake or frequency of drinking. We assessed the health-related quality of life (HRQOL) based on scores for five scales of the SF-36. Results: Decreased odds ratios of sub-optimal HRQOL conditions, defined as less than the median SF-36 scores, for Role-Physical and General Health were found among persons who consumed 1.0 to 22.9 g/d of alcohol. Odds ratios for sub-optimal Vitality conditions were lowered according to increased levels of alcohol intake. Role-Emotional scores were not associated with alcohol drinking. People who drank 5 to 6 d/wk had higher levels of Role-Physical and Vitality, and those who drank 1 to 2 d/wk had better Vitality and Mental Health scores than non-drinkers. When adjusted for age, marital status, working hours, physical activity at work, self-reported job stress, smoking, regular exercise, hypertension, hyperlipidemia, and diabetes, the associations were almost unchanged except for General Health. Conclusions: Associations of drinking patterns with subjective health varied in five sub-scales of the SF-36. Overall, alcohol drinkers rated their health as good in comparison with non-drinkers.

We examined the interactions between lifestyle and polymorphisms of salt-sensitive genes and their effects on hypertension in a general Japanese sample (The Shigaraki Study). The study group consisted of 2,902 subjects who underwent a medical examination in 1999 in Shigaraki, a suburban area in Shiga. Among 1,647 subjects not receiving antihypertensive medication, in a combined analysis of angiotensinogen (AGT) and adducin (ADD1) polymorphisms, double homozygosity of 235Trp or 460Trp was not found to be associated with hypertension. A multiple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [95% CI]: 1.06-1.08), body mass index (BMI) (OR: 1.18, 95% CI: 1.13-1.23), alcohol consumption (OR: 1.39, 95% CI: 1.16-1.66), family history of hypertension (OR: 1.57, 95% CI: 1.18-2.07), and combined AGT M235T Thr/Thr and ADD1 Trp/Trp polymorphisms (OR: 1.37, 95% CI: 1.03-1.82) were associated with hypertension. However, there was no interaction between eating salty food and combined AGT and ADD1 polymorphisms. Furthermore, eating salty food was not associated with hypertension in a multivariate analysis. Therefore, a combination of the AGT and ADD1 polymorphisms appears to be associated with hypertension. However, a simple questionnaire regarding salt intake was not sufficient to confirm the relationship between salt intake and hypertension and/or salt-sensitive genes.

Heavy alcohol drinking is an important risk factor for some lifestyle-related diseases. However, the relationship between drinking habits and medical care expenditures has not been elucidated in a Japanese general population. We examined this relationship in a 9-year cohort study. Study participants were 2039 National Health Insurance beneficiaries aged 40-69 years living in a rural Japanese community. The baseline survey, with medical check-up, was performed in 1989 or 1990 and the subjects' drinking habits were estimated by questionnaire. Medical care use and costs were monitored by linkage with the National Health Insurance claim history files at baseline survey through the end of March 2000. Men who were daily heavy drinkers (ethanol intake > or =69 g per day) had significantly higher medical costs compared to participants who drank less, within 5 years after baseline. This difference was 2000 yen per month after adjusting for age, body mass index, smoking, systolic blood pressure, glycosuria, serum total cholesterol and alanine aminotransferase. Daily heavy male drinkers also had a higher hazard ratio for total mortality compared to occasional drinkers, by the Cox proportional hazard model (hazard ratio: 1.81), although it did not reach statistical significance (P = 0.153). In women, medical costs were almost the same for occasional and daily drinkers. Total medical costs among Japanese men aged 20 years and over may be decreased by about 8400 billon yen per year if we assume a 20% decrease in daily heavy drinkers. To reduce national medical costs, it is important to promote a program for heavy drinkers, as described in the "Health Japan 21" initiative, the Japanese national health promotion guidelines for the first 10 years of the 21st century.

To evaluate the relationship between blood pressure and cerebrovascular death depending on body mass index (BMI) levels, we analysed a database of 9338 subjects from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged, which was originally conducted a baseline survey in 1980 and followed up in 1999. Relative risk (RR) and a 95% confidence interval (CI) of death from total stroke, cerebral infarction, and intracerebral haemorrhage after adjusting for age, sex, serum cholesterol, albumin, glucose, the use of anti-hypertensive agents, a past history of diabetes, BMI, smoking, and drinking were estimated with the Cox-proportional hazard model in the BMI tertile groups of a representative Japanese population. Cutoff points of BMI tertiles are 21.2 and 23.8 kg/m2. The results indicated that a 10 mmHg systolic blood pressure (SBP) increase was associated with mortality from intracerebral haemorrhage at low and middle BMI groups (RR= 1.38 and 1.23; 95% CI=1.17-1.62 and 1.03-1.47, respectively). SBP was positively associated with mortality from cerebral infarction in middle and high BMI groups (RR=1.19 and 1.21; 95% CI=1.06-1.33 and 1.06-1.38, respectively). The effects of diastolic blood pressure on intracerebral haemorrhage and infarction had the same tendency as those of SBP. These results suggested that the causal effect of blood pressure on stroke subtypes might be modified by BMI. © 2005 Nature Publishing Group All rights reserved.

Since 1969, community-based stroke prevention programs have been conducted in N town, Kochi prefecture. To clarify factors related to participation in medical checkups including social networks, a cross-sectional questionnaire survey was performed on 6,704 residents aged 40 and over in N town in 1996. 1. Location of the workplace, types of medical insurance and interest in health were significantly associated with participation in medical checkups. 2. Participation in medical examinations provided at the workplace was significantly, inversely related with participation rates in community checkups in the group aged 40 to 59 years. 3. Low independence level in daily activities was inversely associated with participation rates for medical checkups in groups aged 60 years and older. 4. Visiting medical facilities was inversely associated with the participation rate for medical checkups in female groups. 5. The group with the highest social networks score (5 points) had the highest participation rate for medical checkups. After adjusting for other participation related factors, social networks scores had a significantly positive association with the participation rate for medical checkups provided by the Health Services for the Elderly Act.

Purpose: To examine the risk factors for subarachnoid hemorrhage, for few prospective data have been available on risk factors of subarachnoid hemorrhage among Japanese. Methods: A 9.4-year cohort study was conducted on 12,372 men and women, aged 40-69 years, free of history of stroke in six communities in Japan. Results: During the follow-up, seventy-one incidents of subarachnoid hemorrhage occurred. After adjusting for age, serum total cholesterol, body mass index, history of diabetes mellitus, blood pressure category and drinking category, current smokers had a significantly increased risk of subarachnoid hemorrhage compared with 'never-smokers': multivariate relative risk (RR) [95% confidence interval (95%CI)] = 3.1(1.4-6.9) for women, 1.5(0.4-5.3) for men and 2.7(1.3-5.5) for men and women. Hypertensives had a significantly increased risk of subarachnoid hemorrhage compared with normotensives: multivariate RR(95%CI) = 3.1(1.6-6.0) for women, 4.3(1.5- 12.0) for men and 3.4(2.0-5.9) for men and women. For men, heavy drinkers (>=69 g per day ethanol), had a significantly increased risk of subarachnoid hemorrhage compared with 'never-drinkers': multivariate RR(95%CI) = 4.3(1.1- 16.8). For women, the relationship between heavy drinking and risk was not examined due to the small number of heavy drinkers (n=13). Multivariate RR(95%CI) for men who smoked currently and drank heavily compared with men who did not smoke currently nor drink heavily was 6.0(1.8-20.1). Multivariate RR(95%CI) for hypertensive men who drank heavily compared with normotensive or borderline hypertensive men who did not drink heavily was 13.0(3.9-43.9). Multivariate RR(95%CI) for hypertensive men and women who smoked currently compared with normotensive or borderline hypertensive men and women who did not smoke currently was 6.1(1.3-28.7) for men and 6.3(1.4-28.0) for women. Furthermore, the combination of smoking, hypertension and heavy drinking raised the risk of subarachnoid hemorrhage substantially: multivariate RR(95%CI) = 17.5(3.4-90.2). Conclusion: Smoking and hypertension appeared to increase the risk of subarachnoid hemorrhage. For men, although the association of smoking with the risk of subarachnoid hemorrhage was weak compared with women, the combination of smoking, hypertension and heavy drinking increased the risk substantially. For women, smoking appeared to be an independent risk of subarachnoid hemorrhage, and the combination of smoking and hypertension increased the risk in additive fashion.

Background: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. Design: A community-based cross-sectional design. Methods: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). Results: The prevalence of thickening was 10.7% for the lowest fertile of homocysteine level and 21.1% for the highest fertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest fertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. Conclusions: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.

The purpose of this study was to obtain the overall characteristics and outcome in stroke patients in an urban area of Japan, in order to develop some strategies for a community-based care system for improvement of the prognosis and activities of daily life in stroke patients. The present study, based on 4 hospitals in Yao city in Osaka, showed results as follows: 1) The number of stroke patients discharged from 4 hospitals during a recent one year period was 377 (216 men and 161 women). 2) The proportion of patients who died was 27%. Of the living patients, the proportions of patients who had motor paralysis or speech disturbance at discharge were 54% and 27%, respectively. 3) The proportion of patients who were to return to their home was 77% for all living patients. The proportion of patients who were not able to walk by themselves, or needed assistance in at least one of the activities of daily life was 31% and 28%, respectively, for all living patients who were to return to their home. This study showed that stroke registry from major hospitals in an urban area is useful for obtaining the overall characteristics of stroke patients in the area and promote community-wide programs in the prevention and home care of stroke.

PURPOSE: We conducted an epidemiological study of survival and disability in stroke in three Japanese communities to seek community strategies for improvement in survival and disability. METHODS: A total of 297 first-ever strokes were identified between 1988 and 1992 in three rural communities (total population = 47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of daily living by sex, age-group and stroke subtypes. Successful review of computed tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and the data were used for subtype analyses. RESULTS: For all strokes (n = 297) survival rates were 85% for 30 day, 70% for one year, 62% for three year. The rates tended to be lower in women than in men. The rates were lowest in ages less than 60 at thirty day, and in ages 80 and older at the end of the first and third year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage and cortical cerebral infarction had lower survival rates than intracerebral hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80 in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar infarction. The proportion of stroke survivors who need assistance from others in the first and third years tended to be higher in women than in men. The proportion was higher in older patients than in the younger, and higher for intracerebral hemorrhage with ventricular rupture and cortical cerebral infarction than in other subtypes of stroke. From logistic regression analysis, the odds ratio for disability in the first year was 6.55 for ages 80 and older compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage with ventricular rupture, 4.53 for cortical cerebral infarction compared with lacunar infarction. In the third year the odds ratio was significant for ages 70-79, and decreased for intracerebral hemorrhage with ventricular rupture (odds ratio = 2.98), and increased for cortical cerebral infarction (odds ratio = 6.06). CONCLUSIONS: Survival and disability in stroke depended on age and stroke subtypes. Even after age adjustment, stroke subtypes with large cerebral involvement had worse prognosis than stroke subtypes. Community-based hypertension control programs are important to prevent any subtypes of stroke. Stroke subtypes as well as age should be taken into account to develop effective care and medical treatments for strokes.

To examine the relation between alcohol intake and the incidence of coronary heart disease among Japanese, the authors analyzed data from a prospective study of 8,476 Japanese male employees, who were 40-59 years old at baseline (between 1975 and 1984) and worked for 13 urban companies in Osaka, Japan. These men were followed until the end of 1993, on average, an 8.8-year follow-up. Eighty-three coronary heart disease events (54 myocardial infarction, 32 angina pectoris) occurred during the employment period under study. Compared with the risk of coronary heart disease for never drinkers, the age-adjusted relative risk for those with an increased ethanol intake was lower, but the risk did not appear to be reduced further with the intake of ≤69 g of ethanol per day. The multivariate relative risk adjusted for age, serum total cholesterol, cigarette smoking, body mass index, left ventricular hypertrophy, and a history of diabetes mellitus was 0.83 (95% confidence interval (CI) 0.24-2.86) in exdrinkers, 0.69 (95% CI 0.37-1.29) in drinkers of 1-22 g/day of ethanol, 0.55 (95% CI 0.29-1.05) in drinkers of 23-45 g/day, 0.41 (95% CI 0.19-0.88) in drinkers of 46-68 g/day, and 0.59 (95% CI 0.23- 1.51) in drinkers of ≤69 g/day. The inverse association with alcohol intake was similar between myocardial infarction and angina pectoris. Alcohol intake seemed to prevent the premature incidence of coronary heart disease among urban Japanese middle-aged men.

Background. Use of genetic analysis may improve the predictive value of risk factors for disease. A high plasma level of high-density lipoprotein (HDL) cholesterol is a strong negative risk factor for coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) deficiency causes increased levels of HDL cholesterol. However, recent studies suggest that CETP deficiency is a risk factor for CHD despite elevated HDL cholesterol levels. Methods. Plasma lipid levels, CHD prevalence, resting electrocardiograms, and common CETP gene mutations were analyzed cross-sectionally in a population of 19,044 male and 29,487 female Japanese subjects (ages 45-79 years). Results. High HDL cholesterol levels (serum HDL cholesterol ≤80 mg/dl, ≤95th percentile) were found in 6 and 5% of Japanese men and women, respectively. In the group with HDL cholesterol ≤80 mg/dl, common CETP gene mutations were identified in 23-24% of men and 31-49% of women. The prevalence of CHD in the group with high HDL cholesterol (≤80 mg/dl) was low among both men (1.0%) and women (1.3%). There was no difference in CHD prevalence between hyper- HDL-cholesterolemic subjects with and without CETP mutations. Conclusions. Subjects with very high HDL levels (HDL cholesterol ≤80 mg/dl) as well as mild-to-moderate HDL elevations (60-79 mg/dl) appear to be protected against CHD, whether or not they have CETP deficiency, a genetic cause of elevated HDL.

To investigate the contribution of the platelet aggregation in the development of cardiovascular diseases, we examined the relation of constitutional and lifestyle variables with platelet aggregation for a total of 306 males aged 50 to 70 in Ikawa town, Akita prefecture (n = 163) and Noichi town, Kochi prefecture (n = 143). The examination of platelet aggregation was completed within 3 hours of obtaining blood samples. We used ADP (Adenosine 5'-diphosphate) as an agonist and obtained PATI (the platelet aggregatory threshold index) by nephelometry. Platelet count, mean platelet volume, white blood cell count, serum fatty acid compositions were also examined and dietary intake of fish, seafood and soy bean foods were inquired using one-week dietary records. PATI indicated a logarithmic normal distribution in both Ikawa and Noichi. The mean of logarithmic transformed PATI (log PATI) was higher in Ikawa than in Noichi. Thus platelet aggregation was lower in Ikawa than in Noichi. According to multiple regression analysis, age, platelet count in platelet rich plasma, mean platelet volume in platelet rich plasma, and white blood cell count were inversely associated with log PATI. Serum arachidonic acid composition tended to be inversely related with log PATI. Serum n3-polyunsaturated fatty acid composition was positively related with log PATI, and log gamma-GTP tended to be positively associated with log PATI. Soy protein intake and cigarette smoking showed no consistent associations with log PATI. This cross-sectional study suggests that serum n3-polyunsaturated fatty acid, and gamma-GTP, as an index of alcohol intake, reduce platelet aggregation while age, white blood cell count, platelet count, mean platelet volume, and serum arachidonic acid raise platelet aggregation.

To investigate associations of alcohol intake to constitutional and biochemical variables, cross-sectional studies of men aged 40-59 years from six geographical and occupational populations with varied lifestyles were conducted in the 1990's. Systolic and diastolic blood pressures, glutamic oxaloacetic transaminase, gamma glutamyl transpeptidase, HDL-cholesterol, and uric acid were linearly associated with alcohol intake in all six populations. Drinkers of 2+ drinks (46 g ethanol or more) per day showed higher levels of triglyceride, glutamic pyruvic transaminase than never-drinkers. In two urban occupational populations, men who mainly drank beer had higher uric acid levels; men mainly drinking sake had higher blood pressures and lower serum total cholesterol; men mainly drinking whiskey had higher obesity indices. These differences in constitutional and biochemical variables related to type of alcoholic beverage consumed may be due to differences in lifestyles such as diet and physical activity.

To clarify characteristics of participants in community-based rehabilitation programs provided by local municipalities (cities, towns, and villages) and effect of the program on their levels of independence in activities of daily living (ADL), a cross-sectional study was performed on 422 participants in 49 municipalities in Kochi Prefecture. 1. Mean age of participants was 68.3 +/- 9.0, and 77.7% of them were stroke patients. 2. The mean interval between disease onset and program participation was 40.4 months, and the mean duration of program participation was 54.5 months. 3. At the start of rehabilitation programs and at the time of the investigation (December 1993), about 90% of the participants had good levels of independence in ADL (Rank A and over according to the standard of the Ministry of Health and Welfare). 4. The frequency of rehabilitation programs and the presence of occupational therapists were positively associated with the improvement of levels of independence in ADL. In particular, the frequency of rehabilitation programs was associated with improvement of quality of life in self-supporting participants (Rank J2), and the presence of occupational therapists was associated with the improvement of ADL in semi-bed-ridden participants (Rank A). 5. After adjusting for age and sex, using multiple logistic regression analysis, type of diseases (non-stroke), hospital rehabilitation immediately after onset, higher levels of independence in ADL at the start of rehabilitation programs, and higher frequency of rehabilitation programs were significantly associated with improvements in levels of independence in ADL. Shorter interval between disease onset and program participation, and the presence of occupational therapists were also associated with improvements in levels of independence in ADL, although the relation did not reach statistical significance.

Kochi Prefecture had a higher admission rate for patients with cardiovascular disease, particularly for stroke, than Shimane Prefecture which has a similar socio-economic level. Kochi Prefecture had a smaller average number of persons in a household, a lower proportion of three generation households, and a lower proportion of households with six persons or more than Shimane Prefecture. The decline in number of persons in a household was greater in Kochi Prefecture than in Shimane Prefecture from 1960 to 1985, especially between 1970 and 1975. The association between family make-up and hospital discharge one year after stroke was examined in a rural community in Kochi Prefecture. Two hundred forty nine patients aged 40 years and older who were admitted immediately after stroke events were registered between 1969 and 1988, and they were followed for one year. According to family make-up, the subjects were divided into four groups: 1) persons who lived with spouse and daughter-in-law, 2) persons who lived with spouse, 3) persons who lived with daughter-in-law, 4) persons who lived without spouse and daughter-in-law. Although mean age and the proportion of serious cases were not different between group 1 and group 4, the proportion of admitted patients of group 1 was significantly lower than that of group 4. About 60% of group 1 had households with six persons or more. Group 2 had the lowest proportion of admitted patients, but this group was significantly younger than other groups. Within group 3, the proportion of admitted patients was higher in households in which the daughter-in-law had a job than in households in which she did not. These results suggest that the high admission rate in Kochi Prefecture is attributable to households which are short of personnel for home care.

Trends for stroke incidence and prognosis were investigated in a southwest rural town in Japan, where a community-based stroke prevention program has been conducted since 1969. Four hundred forty-nine stroke patients aged 40 years and older were registered from 1969 to 1988. From among these, 405 (90%) were followed for 3 years to examine prognosis. 1. Age-adjusted stroke incidence in each 5 year interval decreased from 1969 to 1988 with stroke incidence decreasing in almost all age groups 40 years and older for both men and women. A small increase in incidence was observed for women aged 70 years and older between 1979-1983 and 1984-1988. 2. While there was a 46% increase in the population aged 40 years and older, the number of stroke patients decreased between 1969-1973 and 1984-1988. 3. Mortality rates between one week and three years after a stroke have shown a decrease from 1969-1978 to 1979-1988. The proportion of those not requiring nursing care between one week years after stroke has increased. The proportion of all patients requiring nursing care however did not change. 4. After adjusting for age, sex, type of stroke, and loss of consciousness, the blood pressure level within 5 years prior to the stroke was positively associated with death between one week and three years after the event, and was negatively associated with the proportion of those not requiring nursing care. 5. Despite a 31% increase in the census population of all ages between 1969-1978 and 1979-1988, the number of those requiring nursing care has increased only 6% at one year after stroke. If the population had remained constant, the number of those requiring nursing care would have decreased by 10% at one year after the event. These results suggest that a long-term community-based stroke prevention program can decrease both the number of those requiring nursing care and mortality after stroke, as well as stroke incidence and the number of stroke patients.