Takaaki Kondo

Perceived mental stress and mortality from cardiovascular disease among Japanese men and women : the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study)

Background—Perceived mental stress has been associated with risk of coronary heart disease (CHD) in white men, but no prospective data are available for other ethnic groups. Methods and Results—From 1988 to 1990, a total of 73 424 Japanese (30 180 men and 43 244 women), aged 40 to 79 years, without a history of stroke, CHD, or cancer completed a lifestyle questionnaire including perception of mental stress under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study). Systematic surveillance was completed until the end of 1997, with a 580 378 person-year follow-up, and the underlying causes of death were determined according to the International Classification of Diseases, 10th revision. For women, there were 316 with total stroke, 113 with CHD, and 643 with total cardiovascular disease (CVD); for men, there were 341, 168, and 778, respectively. Women who reported high stress had a 2-fold higher age-adjusted risk of mortality from total stroke and CHD and 1.5-fold higher risk of total CVD compared with those who reported low stress. Further adjustment for known cardiovascular risk factors and selected psychological variables did not alter the associations materially. The multivariate relative risk for women who perceived high stress versus low stress was 2.24 (95% CI 1.52 to 3.31, P <0.001) for total stroke, 2.28 (95% CI 1.17 to 4.43, P =0.02) for CHD, and 1.64 (95% CI 1.25 to 2.16, P <0.001) for total CVD. For men, these relations were generally weaker but suggestive of myocardial infarction. Conclusions—Perceived mental stress was associated with increased mortality from stroke for women and with CHD for men and women.

The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state.

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we exa-mined the association of circulating CRP in healthy reference range (≤1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS).DESIGN: Cross-sectional study of circulating CRP in adult men.SUBJECTS: A total of 3692 Japanese men aged 34–69 y.MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI).RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (≥0.06 mg/dl) and moderately (≥0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed.CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

Eating fast leads to obesity: findings based on self-administered questionnaires among middle-aged Japanese men and women.

BACKGROUND Few epidemiologic studies have examined the association between the rate of eating and obesity. In this study, we cross-sectionally examined the association of the self-reported rate of eating with current Body Mass Index (BMI), and BMI-change from 20 years of age to the current age. METHODS Subjects were 3737 male (mean age ± standard deviation and mean BMI ± standard deviation: 48.2 ± 7.1 years and 23.3 ± 2.7 kg/m2) and 1005 female (46.3 ± 7.0 years and 21.8 ± 2.8 kg/m2) Japanese civil servants. We measured self-reported categorical rate of eating, current BMI, BMI at age 20, and BMI-change from age 20. Energy intake was assessed over a 1-month period with a brief-type diet history questionnaire. RESULTS The multiple regression analysis in which the current BMI was regressed by categorical rate of eating, energy intake, age, and lifestyle factors showed that current BMI steadily increased by -0.99, -0.67, 0.81, and 1.47 kg/m2 along with the progress of categorical rate of eating from the ‘medium’ group to ‘very slow’, ‘relatively slow’, ‘relatively fast’, and ‘very fast’ groups, respectively, in men. In women, the corresponding values were -1.06, -0.35, 0.50, and 1.34 kg/m2. When the BMI increment from age 20 to current age was regressed in the same manner, the increment was -0.63, -0.34, 0.57, and 1.05 kg/m2 in men and -0.71, -0.32, 0.34, and 1.14 kg/m2 in women, respectively. Additionally, both BMI at age 20 and current height were positively associated with rate of eating. CONCLUSIONS Our results among middle-aged men and women suggest that eating fast would lead to obesity.

Fruit, vegetable and bean intake and mortality from cardiovascular disease among Japanese men and women: the JACC Study.

To examine the association of plant-based food intakes with CVD and total mortality among Japanese. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, 25 206 men and 34 279 women aged 40-79 years, whose fruit, vegetable and bean intakes were assessed by questionnaire at baseline in 1988-90, were followed for 13 years. Deaths from total stroke, stroke subtypes, CHD and total CVD, according to the International Classification for Diseases 10th Revision, were registered. During 756 054 person-years of follow-up, there were 559 deaths from total stroke, 258 from CHD, 1207 from total CVD and 4514 from total mortality for men, and for women, 494, 194, 1036 and 3092, respectively. Fruit intake was inversely associated with mortality from total stroke (the multivariable hazard ratio (HR (95 % CI)) in the highest v. lowest quartiles = 0.67 (0.55, 0.81)), total CVD (HR = 0.75 (0.66, 0.85)) and total mortality (HR = 0.86 (0.80, 0.92)). Vegetable intake was inversely associated with total CVD (HR = 0.88 (0.78, 0.99)). Bean intake was inversely associated with other CVD (HR = 0.79 (0.64, 0.98)), total CVD (HR = 0.84 (0.74, 0.95)) and total mortality (HR = 0.90 (0.84, 0.96)). Further adjustment for other plant-based foods did not alter the association of fruit intake with mortality from total stroke, total CVD and total mortality, but attenuated the associations of vegetables and beans with mortality risk. In conclusion, intakes of plant-based foods, particularly fruit intake, were associated with reduced mortality from CVD and all causes among Japanese men and women.

The accuracy of long-term recall of past body weight in Japanese adult men

OBJECTIVE: To examine the influences of recall period, current body weight, weight gain and loss, and weight variability on the accuracy of long-term recall of past weight.DESIGN AND SUBJECTS: Comparison of recalled weights around 25 y old with weights measured at age 25y in health checkup records among 2453 Japanese men (age: 34–61 y).MEASUREMENTS: Deviations between reported and measured weights were examined as to the three indexes: actual error (reported−measured), percent error (actual error/measured×100), and absolute value of the percent error. Weight variability was defined as (1) the coefficient of variation of weight (CV) and (2) the root mean square error around the slope of weight on age (RMSE).RESULTS: Recalled weight strongly correlated with measured weight (r=0.849). Correlation coefficients decreased as age or the elapsed time since age 25y increased. Recalled weight (mean=58.3 kg) was slightly greater than measured weight at age 25y (mean=57.0 kg, mean actual error=1.28 kg). Subjects with a current body mass index (BMI) of less than 28.6 kg/m2 overestimated their past weights, whereas those with BM1 of 28.6 kg/m2 or over underestimated it. Subjects with weight loss since age 25y underestimated their past weights, whereas those with stable weight or gain overestimated it. There were monotonic increases in the three indexes of deviation across the CV quartile categories. Concerning the effect RMSE, a similar trend was observed.CONCLUSION: These results indicate that past body weights over a long period seem to be recalled with good accuracy. However, it should be kept in mind when using recalled weight in an epidemiologic study that accuracy of recall is influenced by age or elapsed time, current BMI, weight gain and loss, and weight variability.

Genetic factors involved in the development of Helicobacter pylori-related gastric cancer

Developmental process to gastric cancer by Helicobacter pylori infection consists of three steps: (1) H. pylori infection; (2) gastric atrophy development; and (3) carcinogenesis. In each step, genetic traits may influence the process, interacting with lifestyle. In the step of H. pylori infection, two lines of genetic polymorphisms were assumed: one influencing gastric acid inhibition interacting with smoking, and the other concerning innate immune response attenuation. The former includes functional polymorphisms of IL‐1B (C‐31T or tightly linked T‐511C), and TNF‐A (T‐1031C and C‐857T), and the latter possibly includes NQO1 C609T. In the step to gastric atrophy, polymorphisms pertaining to the signal transduction from cytotoxin‐associated gene A (PTPN11 A/G at intron 3) and to T‐cell responses (IL‐2 T‐330G and IL‐13 C‐1111T) were hypothesized. There are a limited number of epidemiological genotype studies on the final step of literal carcinogenesis, potentially interacting with smoking, a low vegetable and fruit intake, and salty foods, the well‐documented risk factors. In past case‐control studies on the associations between genotype and gastric cancer risk, the cases consisted of H. pylori‐related and unrelated gastric cancer patients and the controls consisted of individuals including the uninfected (H. pylori unexposed and exposed) and the infected with and without gastric atrophy. Accordingly, it was not clear whether the observed risk was for H. pylori‐related or ‐unrelated gastric cancer, nor which step was involved in the observed associations even when nearly all cases were H. pylori‐related. In order to elucidate the genetic traits of H. pylori‐related gastric cancer, stepwise evaluation will be required. (Cancer Sci 2006; 97: 1129–1138)

Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan.

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40–79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow‐up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate‐adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46–1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long‐chain n‐3 fatty acids; the RR were 0.56 (95% CI 0.33–0.94) and 0.50 (0.30–0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trend P = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08‐fold increase in risk (95% CI 1.05–4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long‐chain n‐3 fatty acids that are abundant in fish. (Cancer Sci 2005; 96: 590 – 599)

Relationships of Age at Menarche and Menopause, and Reproductive Year with Mortality from Cardiovascular Disease in Japanese Postmenopausal Women: The JACC Study

BACKGROUND Early menopause is associated with increased risk of coronary heart disease in Caucasian women. However, this association has not been examined in Asian women. METHODS We conducted a 10-year cohort study of 37,965 Japanese post-menopausal women aged 40-79 years in the Japan Collaborative Cohort (JACC) Study. Causes of death were determined based on the International Classification of Disease. RESULTS There were 487 mortality of stroke and 178 mortality of coronary heart disease. Late menarche or early menopause, or shorter duration of reproductive period was not associated with risk of mortality from coronary heart disease. However, compared with women with age at menarche ≤13 years, those with age at menarche ≥17 years tended to have increased risk of mortality from stroke: the multivariable hazard ratio was 1.32 (95% confidence interval [CI]: 0.93-1.87, p = 0.10). Compared with women with age at menopause of ≥49 years, those with age at menopause of <49 years tended to have increased risk of coronary heart disease among women aged 40-64 years; the multivariable hazard ratio was 1.85 (95% CI: 0.92-3.73, p = 0.08). CONCLUSIONS The possible association between early menopause and coronary heart disease among middle-aged women was consistent with the result of observational studies for Caucasian women, and can be explained by a protective effect of endogenous estrogen on the development of atherosclerosis.

Prospective study of screening for stomach cancer in Japan

Although screening for stomach cancer is a widespread community service in Japan, the benefits of the screening program remain unclear. Our study investigated prospectively the relation between participation in stomach‐cancer screening during the past 12 months and subsequent deaths. Data was derived from the Japan Collaborative Cohort Study, in which 480 stomach‐cancer deaths were identified during an 8‐year follow‐up period. Cox proportional hazard regression was used to estimate the relative risk of death from stomach cancer and that from other causes while adjusting for potential confounding factors. In men, screening participation was associated significantly with a reduced risk of death from stomach cancer (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.41–0.70). The extent of the risk reduction was greater than potential health selection (for deaths other than stomach, RR = 0.71). The adjustment for potential confounding variables, however, attenuated the difference in risk of death (stomach cancer, RR = 0.65; other causes, RR = 0.71). In women, the magnitude of the association between screening participation and death from stomach cancer (RR = 0.74; 95% CI = 0.52–1.07) was equal to that for deaths from non‐stomach cancers (RR = 0.74). Subgroup analysis showed that women with a parental history of stomach cancer had a reduced risk of death from stomach cancer associated with screening (RR = 0.32; 95% CI = 0.12–0.87). The present results underline the potential for selection bias in observational studies, and thus it remains an open question whether screening for stomach cancer is effective.

Leptin Is Associated with an Increased Female Colorectal Cancer Risk: A Nested Case-Control Study in Japan

Objective: To elucidate whether leptin is involved in the etiology of female colorectal cancer. Methods: A case-control study nested in the Japan Collaborative Cohort Study. We compared serum leptin levels in 58 cases of female colorectal cancer with those in 145 controls matched for study area and age. Data were analyzed using a conditional logistic regression model with adjustments for known risk factors for the development of colorectal cancer. Quintile cutoff points were determined on the distribution of leptin levels in cases and controls combined. Results: Serum geometric mean levels of leptin were 6.88 ng/ml in cases and 6.00 ng/ml in controls. The odds ratios of female colorectal cancer risk were 1.40 (95% confidence interval, CI: 0.41–4.78) for the category of the second and third quintiles combined, and 4.84 (CI: 1.29–18.1) for the category of the fourth and fifth quintiles combined relative to the first quintile after adjustment for body mass index (BMI), life-style factors, reproductive factors, and hormonal variables including insulin-like growth factor and its binding protein. Conclusion: Our results suggest that leptin most likely increases the risk of female colorectal cancer substantially independent of BMI.