Hiroyasu Iso

Daily Total Physical Activity Level and Premature Death in Men and Women: Results From a Large-Scale Population-Based Cohort Study in Japan (JPHC Study)

PURPOSE The impact of daily total physical activity level on premature deaths has not been fully clarified in non-Western, relatively lean populations. We prospectively examined the association between daily total physical activity level (METs/day) and subsequent risk of all-cause mortality and mortalities from cancer, heart disease, and cerebrovascular disease. METHODS A total of 83,034 general Japanese citizens ages 45-74 years who responded to the questionnaire in 1995-1999 were followed for any cause of death through December 2005. Mutlivariate-adjusted hazard ratios were calculated with a Cox proportional hazards model controlling for potential confounding factors. RESULTS During follow-up, a total of 4564 deaths were recorded. Compared with subjects in the lowest quartile, increased daily total physical activity was associated with a significantly decreased risk of all-cause mortality in both sexes (hazard ratios for the second, third, and highest quartiles were: men, 0.79, 0.82, 0.73 and women, 0.75, 0.64, 0.61, respectively). The decreased risk was observed regardless of age, frequency of leisure-time sports or physical exercise, or obesity status, albeit with a degree of risk attenuation among those with a high body mass index. A significantly decreased risk was similarly observed for death from cancer and heart disease in both sexes, and from cerebrovascular disease in women. CONCLUSION Greater daily total physical activity level, either from occupation, daily life, or leisure time, may be of benefit in preventing premature death.

Serum Cholesterol Levels and Six-Year Mortality from Stroke in 350,977 Men Screened for the Multiple Risk Factor Intervention Trial

We examined the relation between the serum total cholesterol level and the risk of death from stroke during six years of follow-up in 350,977 men, 35 to 57 years of age, who had no history of heart attack and were not currently being treated for diabetes mellitus. The diagnosis of stroke and the type of stroke were obtained from death certificates. Using proportional-hazards regression to control for age, cigarette smoking, diastolic blood pressure, and race or ethnic group, we found that the six-year risk of death from intracranial hemorrhage (International Classification of Diseases, ninth edition [ICD-9], categories 431 and 432) was three times higher in men with serum cholesterol levels under 4.14 mmol per liter (160 mg per deciliter) than in those with higher cholesterol levels (P = 0.05 by omnibus test across five cholesterol levels). On the other hand, a positive association was observed between the serum cholesterol level and death from nonhemorrhagic stroke (P = 0.007). The inverse association of the serum cholesterol level with the risk of death from intracranial hemorrhage was confined to men with diastolic blood pressure greater than or equal to 90 mm Hg, in whom death from intracranial hemorrhage is relatively common. We conclude that there is an inverse relation between the serum cholesterol level and the risk of death from hemorrhagic stroke in middle-aged American men, but that its public health impact is overwhelmed by the positive association of higher serum cholesterol levels with death from nonhemorrhagic stroke and total cardiovascular disease (ICD-9 categories 390 through 459).

Report of the Conference on Low Blood Cholesterol: Mortality Associations.

BackgroundA National Heart, Lung, and Blood Institute (NHLBI) Conference was held October 9–10, 1990, to review and discuss existing data on U-shaped relations found between mortality rates and blood total cholesterol levels (TC) in some but not other studies. Presentations were given from 19 cohort studies from the United States, Europe, Israel, and Japan. A representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry TC levels in regard to death, and these were incorporated into a formal statistical overview adjusted for age, diastolic blood pressure, cigarette smoking, body mass index, and alcohol intake, as available. Methods and ResultsThe U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residual deaths. Risk for combined noncardiovascular, noncancer causes of death decreased steadily across the range of TC. The conference considered possible explanations for the statistical associations found between low TC levels or active TC lowering and certain causes of death. One is that TC is lowered by some disease conditions themselves, such as wasting in chronic pulmonary disease or reduced production and secretion of cholesterol-bearing lipoproteins with liver disease. In this sort of situation, the TC: mortality association found in observational studies may be due to preexisting disease. This was addressed by excluding early deaths from the analysis, which did not change the results. The conference considered as well the biological function of cholesterol, which, if seriously deranged, might hypothetically cause a wide variety of diseases and dysfunction. The conference also considered the biological functions that might provide plausible mechanisms for the associations found. ConclusionsDefinitive interpretation of the associations observed was not possible, although most participants considered it likely that many of the statistical associations of low or lowered TC level are explainable by confounding in one form or another. The conference focused on the apparent existence and nature of these associations and on the need to understand their source rather than on any pertinence of the findings for public health policy. Further research is recommended to explain the observed associations of low TC levels (and TC lowering) with certain noncardiovascular diseases. This includes studies of the time course of TC change in disease, the relation of TC to morbidity, further studies of possible epidemiological confounding, monitoring of population trends in TC and mortality, further studies of the relations in women, auditing of noncardiovascular events in trials, studies of cell membrane, genetic and molecular links to cholesterol metabolism, TC level and disease, studies of disease manifestations in specific lipid disorders, and further study of the proposed causal mechanisms linking low TC and hemorrhagic stroke.

Intake of Fish and n3 Fatty Acids and Risk of Coronary Heart Disease Among Japanese The Japan Public Health Center-Based (JPHC) Study Cohort I

Background— Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk. Methods and Results— To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41 578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990–1992 to 2001. After 477 325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]). Conclusions— Compared with a modest fish intake of once a week or ≈20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.

Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease

BackgroundAccurate estimation of the glomerular filtration rate (GFR) is crucial for the detection of chronic kidney disease (CKD). In clinical practice, GFR is estimated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) study equation or the Cockcroft-Gault (CG) equation instead of the time-consuming method of measured clearance for exogenous markers such as inulin. In the present study, the equations originally developed for a Caucasian population were tested in Japanese CKD patients, and modified with the Japanese coefficient determined by the data.MethodsThe abbreviated MDRD study and CG equations were tested in 248 Japanese CKD patients and compared with measured inulin clearance (Cin) and estimated GFR (eGFR). The Japanese coefficient was determined by minimizing the sum of squared errors between eGFR and Cin. Serum creatinine values of the enzyme method in the present study were calibrated to values of the noncompensated Jaffé method by adding 0.207 mg/dl, because the original MDRD study equation was determined by the data for serum creatinine values measured by the noncompensated Jaffé method. The abbreviated MDRD study equation modified with the Japanese coefficient was validated in another set of 269 CKD patients.ResultsThere was a significant discrepancy between measured Cin and eGFR by the 1.0 × MDRD or CG equations. The MDRD study equation modified with the Japanese coefficient (0.881 × MDRD) determined for Japanese CKD patients yielded lower mean difference and higher accuracy for GFR estimation. In particular, in Cin 30–59 ml/min per 1.73 m2, the mean difference was significantly smaller with the 0.881 × MDRD equation than that with the 1.0 × MDRD study equation (1.9 vs 7.9 ml/min per 1.73 m2; P <?0.01), and the accuracy was significantly higher, with 60% vs 39% of the points deviating within 15%, and 97% vs 87% of points within 50%, respectively (both P <?0.01). Validation with the different data set showed the correlation between eGFR and Cin was better with the 0.881 × MDRD equation than with the 1.0 × MDRD study equation. In Cin less than 60 ml/min per 1.73 m2, the accuracy was significantly higher, with 85% vs 69% of the points deviating within 50% (P <?0.01), respectively. The mean difference was also significantly smaller (P <?0.01). However, GFR values calculated by the 0.881 × MDRD equation were still underestimated in the range of Cin over 60 ml/min per 1.73 m2.ConclusionsAlthough the Japanese coefficient improves the accuracy of GFR estimation of the original MDRD study equation, a new equation is needed for more accurate estimation of GFR in Japanese patients with CKD stages 3 and 4.

Trends for coronary heart disease and stroke and their risk factors in Japan.

Disease surveillance and population surveys of risk characteristics in a northeast rural community of Japan (1965 census population, 7,030) are combined in an attempt to relate morbidity and risk factor trends for coronary heart disease and stroke during the last 2 decades. Between 1964 and 1983, the incidence of coronary heart disease (i.e., combined myocardial infarction, angina pectoris, and sudden death) did not change significantly among men and women ages 40-69, and was lower than that for stroke. The incidence of all stroke declined about 60% for both men and women, ages 40-69, with a significant decrease in cerebral hemorrhage for both sexes and in cerebral infarction for men. Between 1963-1966 and 1980-1983, significant upward shifts occurred in the means and distributions of serum total cholesterol and serum total protein in every age and sex group, primarily during the 1st decade. Age-adjusted mean cholesterol levels rose 22 mg/dl to the 1980-1983 mean of 179 mg/dl in men ages 40-69. In women ages 40-69, the mean rose 29 mg/dl to 192 mg/dl. Among nutrients, animal fat intake doubled in men ages 40-59 from 4.5% of daily calories in 1969 to 9.6% in 1980-1983. Animal protein intake also increased, from 5.8% to 7.1%. Most of this increase occurred between 1969 and 1972-1975 and may be attributable to an increased intake of meat, eggs and dairy products. From 1963-1966 to 1980-1983, mean relative weight index rose significantly for all age-sex groups except men ages 50-69. Mean systolic and diastolic blood pressure levels declined for every age-sex group, with a 15-mm Hg age-adjusted decrease in systolic, 4-mm Hg decrease in diastolic pressure among men ages 40-69, and a 11-mm Hg systolic and 4-mm Hg diastolic decrease for women. Two cohorts of men and women ages 40-69 at baseline were followed for disease incidence: an early cohort (2,257 persons) followed from 1963-1966 to 1973 and a later cohort (2,711 persons) followed from 1972-1975 to 1983. In these cohorts, significant risk prediction for cerebral hemorrhage and infarction was obtained with blood pressure level and end organ effects in the electrocardiogram and fundus photographs. Serum cholesterol was inversely associated with cerebral hemorrhage in the early cohort but not in the later.(ABSTRACT TRUNCATED AT 400 WORDS)

The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults.

Context Caffeine intake from coffee has been associated with a lower incidence of diabetes. Researchers have not studied the relationship of green tea, a popular beverage in Japan, where the incidence of diabetes is increasing rapidly. Contributions The authors estimated the intake of caffeine-containing beverages in a community-based survey in Japan and measured the 5-year incidence of diabetes. Greater intake of green tea or coffee was associated with a reduced incidence of diabetes. The effect of green tea was largely observed in women, was dose-related, and reflected caffeine intake. Implications Higher intake of caffeine, whether from coffee or green tea, is associated with a lower incidence of diabetes. The Editors The prevalence of type 2 diabetes has increased worldwide, particularly in Asian countries where it was previously low (1). In Japan, population-based studies have shown a 2-fold increase in the prevalence of diabetes during the past 2 decades, from 5% to 10% to 10% to 15% (2). Several cohort studies done in Europe and in the United States reported an association between coffee consumption, a major source of caffeine, and reduced risk for diabetes (3-7). Although these studies did not show any association between consumption of black tea and the risk for diabetes, they did not examine the effect of green or oolong teas, major sources of caffeine in Asian countries. Consumption of green tea is common in Japan; 80% of the population drinks green tea, and the average consumption per capita is 2 cups per day (8). We wanted to determine whether there is a relationship between consumption of green tea and the risk for type 2 diabetes and, if so, whether caffeine fully accounts for this relationship. To examine these questions, we analyzed data from a large cohort study of 19487 middle-aged men and women in 25 communities across Japan. We also examined the effect of age, sex, body mass index (BMI), family history, smoking status, alcohol use, magnesium intake, and physical activity on the association between this mode of caffeine consumption and risk for diabetes. Methods The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) started between 1988 and 1990. A total of 110792 individuals (46465 men and 64327 women) who were 40 to 79 years of age and living in 45 communities across Japan participated in municipal health screening examinations and completed self-administered questionnaires regarding lifestyle and medical history of cardiovascular disease and cancer (9). Informed consent was obtained before the completion of the questionnaire. Participants from 25 of the 45 communities completed 5-year follow-up surveys. Among 35690 participants (15177 men and 20513 women) who were 40 to 65 years of age at baseline without a history of type 2 diabetes, stroke, coronary heart disease, or cancer, 17413 individuals (49%; 6727 men and 10686 women) completed the 5-year follow-up questionnaire and provided valid responses on tea or coffee consumption and history of type 2 diabetes. The data from these 17413 individuals were used for the analyses. The mean age of the nonrespondents was 1 year younger for men (52.3 vs. 53.3 years of age) and did not differ for women (53.1 vs. 53.0 years of age) compared with the respondents. The mean BMI and the prevalence of a BMI of 25.0 kg/m2 or greater did not differ between the respondents and nonrespondents. Mean BMI was 22.7 kg/m2 versus 22.8 kg/m2 for men and 22.8 kg/m2 versus 22.9 kg/m2 for women, respectively; the prevalence of overweight was 18% versus 19% for men and 21% versus 22% for women, respectively. The ethical committees at Nagoya University and the University of Tsukuba approved the study. Assessment of Consumption of Tea and Coffee and Caffeine Intake At baseline, consumption of tea and coffee was assessed by using a self-administered dietary questionnaire. Participants were asked to state their average consumption of green tea, black tea, oolong tea, and coffee during the previous year. They could select any of 4 frequency responses: less than once a week, about 1 to 2 times a week, about 3 to 4 times a week, and almost every day. Participants who selected the response of almost every day were also asked to state their average consumption of these beverages in number of cups per day. We classified the categories of consumption as less than 1 cup per week, 1 to 6 cups per week, 1 to 2 cups per day, 3 to 5 cups per day, and 6 or more cups per day. The highest 2 or 3 consumption categories were combined for coffee, black tea, and oolong tea because of the small number of participants in these categories. The consumption of decaffeinated coffee or tea was not recorded because these products were not commercially available in Japan in the early 1990s. The total intake of caffeine was calculated by adding the caffeine content from each specific beverage (1 cup for coffee or tea) and multiplying it by the participants weight proportional to the frequency of caffeine use. We estimated the size of the cup for each beverage from a validation study (10) and the caffeine content per 100 mL of each beverage from the Japan Food Tables (11). The estimated caffeine content was 153 mg per cup (170 mL) of coffee, 30 mg per cup (200 mL) of green tea, 51 mg per cup (170 mL) of black tea, and 38 mg per cup (190 mL) of oolong tea. The mean caffeine intake was 229 mg/d for men and 215 mg/d for women. Relative proportions of caffeine intake by beverage were 46% from green tea, 44% to 47% from coffee, 3% from black tea, and 4% to 5% from oolong tea. For reproducibility, the Spearman correlation coefficients between the 2 questionnaires, administered 1 year apart for 85 participants (8 men and 77 women), were 0.79 for green tea, 0.87 for coffee, 0.77 for black tea, and 0.56 for oolong tea (10). The validity of the data was confirmed for the 85 participants by comparing the data from the questionnaire with those from four 3-day dietary records collected approximately 3 to 4 months apart (10). The mean frequency of consumption of green tea was 25.4 cups per week according to the questionnaire and 30.1 cups per week according to four 1-week dietary records (Spearman correlation coefficient, 0.47). The respective mean frequencies were 8.0 cups and 7.1 cups per week with a correlation coefficient of 0.79 for coffee, 1.4 cups and 1.6 cups per week with a correlation coefficient of 0.70 for black tea, and 1.8 cups and 1.2 cups per week with a correlation coefficient of 0.55 for oolong tea. When we restricted the data to the 77 women, the results were essentially the same. Assessment of Diabetes Cases Participants who reported having diabetes newly diagnosed by physicians on the 5-year follow-up questionnaire were considered to have incident diabetes. To examine the validity of self-reporting of diabetes, we compared self-report data with laboratory findings and treatment status in a sample of 1230 men and 1837 women. We considered elevated glucose concentrations (fasting serum glucose concentration 7.8 mmol/L [140 mg/dL] or a randomly measured concentration of 11.1 mmol/L [200 mg/dL]) or treatment with oral hypoglycemic agents or insulin to indicate new cases of diabetes. Recent criteria from the American Diabetes Association (12) were not used because the cases in our study were diagnosed before 1995. The sensitivity of self-reporting was 70% for men and 75% for women; the specificity was 95% for men and 98% for women. Statistical Analysis To examine potential confounding variables reported from previous studies (3-7), we presented baseline characteristics according to the frequency of consumption for each beverage. Tests for trends were conducted by using the median values of confounding variables in each category of beverage; the linear regression model was used for continuous variables, and the logistic regression model was used for categorical variables. The odds ratios for incident type 2 diabetes were calculated in each category of beverage consumption and in each quartile of caffeine intake; less than 1 cup per week or the lowest quartile was used as the reference category. We estimated age, sex, and BMI-adjusted odds ratios and multivariable odds ratios using the logistic regression model, adjusting for age (in years), sex, sex-specific quintiles of BMI (weight in kilograms divided by the square of height in meters), parental history of diabetes (yes or no), smoking status (never, former, or current [1 to 19, 20 to 29, or 30 cigarettes/d]), alcohol intake (never, former, or current [1 to 22, 23 to 45, 46 to 68, or 69 g/d]), sex-specific quintiles of magnesium intake, hours of walking (<0.5, 0.5, 0.6 to 0.9, and 1.0 h/d), and hours of participation in sports (<1, 1 to 2, 3 to 4, and 5 h/wk). Sex-specific quintiles of BMI and magnesium intake were used because of different distributions between the sexes. We adjusted for magnesium intake because previous cohort studies indicated an inverse association between magnesium intake and risk for diabetes (13, 14). We conducted a test for trend by treating median values of each category of beverage or caffeine intake as continuous variables. We examined the association between caffeine intake and the risk for diabetes stratified by age group (40 to 54 years and 55 to 65 years), sex, family history of diabetes (yes or no), current smoking status (yes or no), current alcohol intake (yes or no), magnesium intake (below and above the sex-specific median), BMI (<25.0 kg/m2 and 25.0 kg/m2), hours of walking (<0.5 and 0.5 h/d), and hours of participation in sports (<5 and 5 h/wk). The interactions with these stratified variables were tested by using cross-product terms of caffeine intake and the stratified variables. All analyses were conducted by using the SAS statistical package, version 8.2 (SAS Institute Inc., Cary, North Carolina). P values for statistical tests were 2-tailed, and 95% CIs were estimated. Role of the

Is early natural menopause a biologic marker of health and aging

The relation between age at natural menopause and all-cause mortality was investigated in a sample of 5,287 White women, ages 55 to 100 years, naturally-postmenopausal, Seventh-day Adventists who had completed mailed questionnaires in 1976. The age-adjusted odds ratio of death during 1976-82 in women with natural menopause before age 40 was 1.95 (95% confidence interval = 1.24, 3.07), compared to the reference group of women reporting natural menopause at ages 50 to 54. Corresponding odds ratios of death were 1.39 (95% CI = 1.06, 1.81) for natural menopause at ages 40 to 44, and 1.03 (95% CI = 0.84, 1.25) for natural menopause at ages 45 to 49. Among 3,166 White, 55- to 100-year-old, surgically-postmenopausal, Adventist women, there was no relation between age at surgical menopause and mortality. Logistic regression analyses indicated that findings from this study were apparently not due to confounding by smoking, over- or underweight, reproductive history, or replacement estrogen use.

Carotid Intima-Media Thickness and Plaque Characteristics as a Risk Factor for Stroke in Japanese Elderly Men

Background and Purpose— Few cohort studies have examined the association of carotid intima-media thickness (IMT) and plaque characteristics with the risk of stroke in apparently healthy persons. We examined the relationship of carotid IMT and the surface, morphology, and calcification of carotid plaques with the incidence of stroke among Japanese men. Methods— Carotid IMT and plaque were evaluated bilaterally with ultrasonography in 1289 men aged 60 to 74 years without a previous stroke or coronary heart disease. In this cohort, the subsequent incidence of stroke was investigated. Results— During the 4.5-year follow-up, 34 strokes occurred. The multivariate-adjusted relative risk (95% CI) for the highest versus lowest quartiles of maximum IMT of the common carotid artery (CCA; ≥1.07 versus ≤0.77 mm) was 3.0 (1.1 to 8.3) for stroke. The combination of CCA and internal carotid artery (ICA) wall thickness was a better predictor of the risk of stroke than was CCA wall thickness alone. Men with a plaque, defined as a focal wall thickness of ≥1.5 mm, in the ICA had a 3-fold higher risk of stroke than those without a plaque, and the plaque surface irregularity further increased the stroke risk. A significant excess risk of stroke was confined to men with an uncalcified plaque. Conclusions— Increased IMT of the CCA and an uncalcified plaque in the ICA, as assessed by ultrasonography, are risk factors for stroke in elderly Japanese men.

Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modified by a Japanese coefficient

BackgroundThe number of patients with end-stage renal disease (ESRD) in Japan has continuously increased in the past three decades. In 2005, 36 063 patients whose average age was 66 years entered a new dialysis program. This large number of ESRD patients could be just the tip of the iceberg of an increasing number of patients with chronic kidney disease (CKD). However, to date, a nationwide epidemiological study has not been conducted yet to survey the CKD population.MethodsData for 527 594 (male, 211 034; female, 316 560) participants were obtained from the general adult population aged over 20 years who received annual health check programs in 2000–2004, from seven different prefectures in Japan: Hokkaido, Fukushima, Ibaraki, Tokyo, Osaka, Fukuoka, and Okinawa prefectures. The glomerular filtration rate (GFR) for each participant was estimated from the serum creatinine values, using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation modified by the Japanese coefficient.ResultsThe prevalences of CKD stage 3 in the study population, stratified by age groups of 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, and 80–89 years, were 1.4%, 3.6%, 10.8%, 15.9%, 31.8%, 44.0%, and 59.1%, respectively, predicting 19.1 million patients with stage 3 CKD in the Japanese general adult population of 103.2 million in 2004. CKD stage 4 + 5 was predicted in 200 000 patients in the Japanese general adult population. Comorbidity of hypertension, diabetes, and proteinuria increased as the estimated GFR (eGFR) decreased. The prevalence of concurrent CKD was significantly higher in hypertensive and diabetic populations than in the study population overall when CKD was defined as being present with an eGFR of less than 40 ml/min per 1.73 m2 instead of less than 60 ml/min per 1.73 m2.ConclusionsAbout 20% of the Japanese adult population (i.e., approximately 19 million people) are predicted to have stage 3 to 5 CKD, as defined by a GFR of less than 60 ml/min per 1.73 m2.