Development and validation of a risk assessment tool for gastric cancer in a general Japanese population.

BACKGROUND: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. METHODS: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the validation cohort. RESULTS: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort. CONCLUSIONS: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual's risk of future gastric cancer.

The long-term association between physical activity and risk of dementia in the community: the Hisayama Study.

We investigated the long-term influence of physical activity on the risk of dementia in an elderly Japanese population. A total of 803 community-dwelling elderly Japanese individuals without dementia aged ≥65 years were followed prospectively for 17 years. Physically active status was defined as engaging in exercise at least one or more times per week during leisure time, and participants were divided into an active group and an inactive group by the presence or absence of such physical activity. The risk estimates of physical activity on the development of all-cause dementia and its subtypes were computed using a Cox proportional hazards model. During the follow-up, 291 participants developed all-cause dementia. Of these, 165 had Alzheimer's disease (AD), 93 had vascular dementia (VaD), and 47 had other dementia. Compared with the inactive group, the active group showed significantly lower crude incidence of AD (21.8 vs. 14.2 per 1000 person-years, p = 0.01), but no significant differences were observed for all-cause dementia (35.6 vs. 30.5, p = 0.17), VaD (11.3 vs. 9.8, p = 049), and other dementia (4.6 vs. 7.1, p = 0.15). After adjusting for potential confounders, the relationship between physical activity and risk of AD remained significant (adjusted hazard ratio 0.59, 95% confidence interval 0.41-0.84, p = 0.003). Our findings suggest that physical activity reduces the long-term risk of dementia, especially AD, in the general Japanese population.

Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study.

BACKGROUND: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. METHODS: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. RESULTS: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001). CONCLUSIONS: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.

Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study.

BACKGROUND: It is not clear which glucose measure is more useful in the assessment of atherosclerosis. We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), fasting plasma glucose (FPG), and 2-hour postload glucose (PG) with carotid intima-media thickness (IMT) in community-dwelling Japanese subjects. METHODS: A total of 2702 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test and measurements of HbA1c, GA, 1,5-AG, and carotid IMT by ultrasonography in 2007-2008. Carotid wall thickening was defined as a maximum IMT of >1.0 mm. The crude and multivariable-adjusted linear and logistic regression models were used to analyze cross-sectional associations between levels of glycemic measures and carotid IMT. RESULTS: The crude average of the maximum IMT increased significantly with rising quartiles of HbA1c, GA, FPG, and 2-hour PG levels in subjects with and without glucose intolerance (GI), while no clear association was observed for 1,5-AG. After adjustment for other confounding factors, positive trends for HbA1c, GA, and FPG (all p for trend < 0.05), but not 2-hour PG (p = 0.07) remained robust in subjects with GI, but no such associations were found in those without GI. When estimating multivariable-adjusted ß values for the associations of 1 SD change in glycemic measures with the maximum IMT in subjects with GI, the magnitude of the influence of HbA1c (ß = 0.021), GA (ß = 0.024), and FPG (ß = 0.024) was larger than that of 2-hour PG (ß = 0.014) and 1,5-AG (ß = 0.003). The multivariable-adjusted odds ratios for the presence of carotid wall thickening increased significantly with elevating HbA1c, GA, and FPG levels only in subjects with GI (all p for trend < 0.001). Among subjects with GI, the area under the receiver operating characteristic curve significantly increased by adding HbA1c (p = 0.04) or GA (p = 0.04), but not 1,5-AG, FPG, or 2-hour PG, to the model including other cardiovascular risk factors. CONCLUSIONS: In community-dwelling Japanese subjects with GI, elevated HbA1c, GA, and FPG levels were significantly associated with increased carotid IMT, and HbA1c and GA provided superior discrimination for carotid wall thickening compared to 1,5-AG, FPG, and 2-hour PG, suggesting that HbA1c and GA are useful for assessing carotid atherosclerosis.

[Helicobacter pylori infection and Hyperglycemia/Diabetes are associated with an increased risk of Gastric Cancer].

Although mortality rates owing to gastric cancer have gradually decreased, the morbidity rates are still high in Japan. Helicobacter pylori(H. pylori)infection is an important risk factor for gastric cancer, although most individuals with an H. pylori infection do not develop this malignancy. Therefore, it is speculated that other risk factors including lifestyle contribute to the enhanced risk of gastric cancer posed by H. pylori infection. It is also noteworthy that the prevalence of prediabetes and diabetes has dramatically increased in Japan, and cancer is now considered a possible complication of the latter. However, there have been very few epidemiological studies evaluating the relationship between diabetes and gastric cancer in Japan. The Hisayama Study, which is a prospective cohort study conducted in a Japanese community, demonstrated that the incidence of gastric cancer significantly increased with elevated fasting plasma glucose levels. A modest increase in hemoglobin A1c levels was also a significant risk factor for gastric cancer even after adjusting for other risk factors, including H. pylori infection. Moreover, among subjects who had both a high hemoglobin A1c level and H. pylori infection, the risk of gastric cancer increased synergistically. These findings suggest that even prediabetic hyperglycemia is a significant risk factor for gastric cancer in the general Japanese population. Early identification of hyperglycemia and an appropriate behavioral and therapeutic approach may help prevent gastric cancer in Japan where there is a high incidence of both this malignancy and diabetes.

Secular trends in cardiovascular disease and its risk factors in Japanese: half-century data from the Hisayama Study (1961-2009).

BACKGROUND: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. METHODS AND RESULTS: We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. CONCLUSIONS: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: the Hisayama Study.

BACKGROUND: There has been controversy over the diagnostic thresholds of hemoglobin A1c (HbA1c) for diabetes. In addition, no study has examined the thresholds of glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) for diagnosing diabetes using the presence of diabetic retinopathy (DR). We examined the optimal thresholds of various glycemic measures for diagnosing diabetes based on the prevalence of DR in community-dwelling Japanese subjects. METHODS: A total of 2,681 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test, measurement of HbA1c, GA, and 1,5-AG, and an ophthalmic examination in 2007-2008. The associations of glycemic measures with DR status were examined cross-sectionally. DR was assessed by an examination of the fundus photograph of each eye and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. We divided the values of glycemic measures into ten groups on the basis of deciles. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold of each glycemic measure for detecting the presence of DR. RESULTS: Of the subjects, 52 had DR. The prevalence of DR increased steeply above the ninth decile for fasting plasma glucose (FPG) (6.2-6.8 mmol/l), for 2-hour postload glucose (PG) (9.2-12.4 mmol/l), for HbA1c (5.9-6.2% [41-44 mmol/mol]), and for GA (16.2-17.5%), and below the second decile for 1,5-AG (9.6-13.5 µg/mL). The ROC curve analysis showed that the optimal thresholds for DR were 6.5 mmol/l for FPG, 11.5 mmol/l for 2-hour PG, 6.1% (43 mmol/mol) for HbA1c, 17.0% for GA, and 12.1 µg/mL for 1,5-AG. The area under the ROC curve (AUC) for 2-hour PG (0.947) was significantly larger than that for FPG (0.908), GA (0.906), and 1,5-AG (0.881), and was marginally significantly higher than that for HbA1c (0.919). The AUCs for FPG, HbA1c, GA, and 1,5-AG were not significantly different. CONCLUSIONS: Our findings suggest that the FPG and HbA1c thresholds for diagnosing diabetes in the Japanese population are lower than the current diagnostic criterion, while the 2-hour PG threshold is comparable with the diagnostic criterion. 2-hour PG had the highest discriminative ability, whereas FPG, HbA1c, GA, and 1,5-AG were similar in their ability.

Trends in the incidence and survival of intracerebral hemorrhage by its location in a Japanese community.

BACKGROUND: No previous population-based studies have examined secular trends in the incidence of intracerebral hemorrhage (ICH) by its location. METHODS AND RESULTS: We established 3 cohorts consisting of residents of Hisayama, Japan, aged ≥40 years without a history of stroke or myocardial infarction in 1961 (the first cohort, n=1,618), in 1974 (the second cohort, n=2,038), and in 1988 (the third cohort, n=2,637). Each cohort was followed for 13 years. The age- and sex-adjusted incidence of ICH significantly declined from the first to the second cohort and showed no further change in the third cohort. With regard to the ICH location, the incidence of putaminal hemorrhage decreased steadily, mainly in subjects aged 60-69 years, whereas the incidence of thalamic hemorrhage increased, especially in those aged ≥70 years. Both hypertension and alcohol intake were strong risk factors for ICH in the first cohort, but their influence declined with time. Blood pressure levels in hypertensive subjects decreased significantly, and the proportion of current drinkers decreased slightly over the study period. CONCLUSIONS: Our findings suggest that the ICH incidence steeply declined from the 1960s to the 1970s in Japan as a result of the reduced influence of hypertension and alcohol intake, but that this decline has leveled off since then, probably because of the increased incidence of thalamic hemorrhage in the elderly in recent years.

White-coat and masked hypertension are associated with carotid atherosclerosis in a general population: the Hisayama study.

BACKGROUND AND PURPOSE: On the basis of combined measurements of clinic blood pressure (CBP) and home blood pressure (HBP), blood pressure status can be divided into normotension, white-coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Despite the clear impact of MHT and SHT on clinical and subclinical arterial disease, uncertainty about the influence of WCHT remains. The objective of this study was to investigate the associations of WCHT, MHT, and SHT with carotid atherosclerosis in a general population. METHODS: This is a cross-sectional survey of 2915 community-dwelling Japanese aged ≥ 40 years. Normotension was defined as CBP<140/90 and HBP<135/85 mm Hg; WCHT, CBP ≥ 140/90 and HBP<135/85 mm Hg; MHT, CBP<140/90 and HBP ≥ 135/85 mm Hg; and SHT, CBP ≥ 140/90 and HBP ≥ 135/85 mm Hg. Mean intima-media thickness of carotid arteries was measured using a computer-automated system, and carotid stenosis was defined as diameter stenosis ≥ 30%. RESULTS: There were 1374 subjects (47.1%) with normotension, 200 (6.9%) with WCHT, 639 (21.9%) with MHT, and 702 (24.1%) with SHT. The geometric average of mean intima-media thickness was significantly higher among subjects with WCHT (0.73 mm), MHT (0.77 mm), and SHT (0.77 mm) than those with normotension (0.67 mm; all P<0.001 versus normotension). Compared with normotension, all types of hypertension were also associated with increased likelihood of carotid stenosis (age- and sex-adjusted odds ratio, 2.36 [95% confidence interval, 1.27-4.37] for WCHT, 1.95 [1.25-3.03] for MHT, and 3.02 [2.01-4.54] for SHT). These associations remained significant even after adjustment for other cardiovascular risk factors. CONCLUSIONS: WCHT, as well as MHT, and SHT were associated with carotid atherosclerosis in a general Japanese population.

Temporal trends in sudden unexpected death in a general population: the Hisayama study.

BACKGROUND: Studies addressing the temporal trends in the prevalence of sudden unexpected death (SUD) and its underlying causes in the general population are limited. METHODS: Among a total of 1934 residents aged ≥20 years of the town of Hisayama, Japan, who died of endogenous causes of death and underwent autopsy examination (autopsy rate 78.5%) from 1962 to 2009, 204 were determined to be cases of SUD within 24 hours. RESULTS: The trend in the age- and sex-adjusted prevalence of SUD among all autopsy subjects was stable over four 12-year periods (13.1% in 1962-1973, 13.4% in 1974-1985, 15.0% in 1986-1997, and 14.6% in 1998-2009; P for trend = .80). Regarding causes of death, the prevalence of SUD from stroke significantly declined with time (8.0%, 5.0%, 2.3%, and 2.1%, respectively; P for trend < .001), whereas significant increments were observed in the prevalence of SUD from heart disease (4.0%, 6.2%, 8.6%, and 9.7%; P for trend = .02) and from aortic aneurysm and dissection (0.2%, 1.2%, 2.9%, and 2.8%; P for trend = .01). In particular, the prevalence of ischemic heart disease increased 3-fold from 2.1% in 1962-1973 to 6.6% in 1998-2009 (P = .04). Reflecting the increment of ischemic heart disease, SUD within 1 hour increased significantly from 2.5% to 7.6% during this period (P = .01). CONCLUSIONS: The trend in the prevalence of SUD was stable across a half century in a general Japanese population. Despite the decrement in the prevalence of SUD from stroke, that from heart disease, especially ischemic heart disease, increased significantly with time.

Haemoglobin A1c even within non-diabetic level is a predictor of cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: There is little information about predictive ability of haemoglobin A1c (HbA1c) for cardiovascular disease (CVD) in Asians. To investigate the discriminatory ability of HbA1c to identify subjects who are at greater risk of developing CVD in a prospective study of a defined community-dwelling Japanese population. METHODS: A total of 2,851 subjects aged 40-79 years were stratified into five groups (HbA1c levels with ≤ 5.0, 5.1-5.4, 5.5-6.4, and ≥ 6.5% and a group with antidiabetic medication) and followed up prospectively for 7 years (2002-2009). RESULTS: During the follow-up, 119 subjects developed CVD. The multivariable-adjusted risk of CVD was significantly increased in subjects with HbA1c levels of 5.5-6.4 and ≥ 6.5% and diabetic medication compared to HbA1c level with ≤ 5.0% (hazard ratio, 2.26 [95% confidence interval, 1.29-3.95] for the 5.5-6.4%; 4.43 [2.09-9.37] for the ≥ 6.5%; and 5.15 [2.65-10.0] for the antidiabetic medication group). With regard to CVD subtype, the positive associations between HbA1c levels and the risk of coronary heart disease (CHD) and ischaemic stroke were also significant, but no such associations were seen for haemorrhagic stroke. The C statistic for developing CVD was significantly increased by adding HbA1c values to the model including other risk factors (0.789 vs. 0762, p = 0.006), and the net reclassification improvement was 0.105 (p = 0.004). CONCLUSIONS: Our findings suggest that elevated HbA1c levels are an independent risk factor for CVD, especially CHD and ischaemic stroke, and that the addition of HbA1c to the model with traditional risk factors significantly improves the predictive ability of CVD.

White blood cell count and risk of gastric cancer incidence in a general Japanese population: the Hisayama study.

The authors examined the association between white blood cell (WBC) count and the development of gastric cancer in a 19-year follow-up study of 2,558 Japanese subjects aged ≥40 years (1988-2007). The subjects were stratified into 4 groups according to baseline WBC quartile (≤4.4, 4.5-5.2, 5.3-6.3, or ≥6.4 × 10(3) cells/µL). During follow-up, 128 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer increased linearly with higher WBC level: 1.7, 2.6, 3.9, and 5.4 per 1,000 person-years, respectively, for the 4 quartile groups (P for trend < 0.01). The risk of gastric cancer was 2.22-fold (95% confidence interval: 1.19, 4.14) higher in the highest WBC quartile group than in the lowest group after adjustment for confounding factors. With respect to Helicobacter pylori infection status, H. pylori-seropositive subjects in the highest WBC quartile group showed a significantly greater risk of gastric cancer than those in the lower 3 quartile groups, whereas such an association was not observed in H. pylori-seronegative subjects. There was no evidence of heterogeneity in the association (P for heterogeneity = 0.65). The study findings suggest that higher WBC levels are a risk factor for gastric cancer, especially in subjects with H. pylori infection.

N-terminal pro-brain natriuretic peptide and risk of cardiovascular events in a Japanese community: the Hisayama study.

OBJECTIVE: Few studies have examined the association between natriuretic peptides and the incidence of cardiovascular disease (CVD) in Asian populations. METHODS AND RESULTS: A total of 3104 community-dwelling Japanese individuals aged ≥40 years without history of CVD were followed up for 5 years. A total of 127 CVD events were identified. The age- and sex-adjusted incidence of CVD increased with increasing N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (<55, 55-124, 125-399, and ≥400 pg/mL) at baseline and was significantly higher even in subjects with a modest increase. This association remained robust even after adjustment for other potential risk factors (55-124 pg/mL: multivariate-adjusted hazard ratio=1.85 [95% CI 1.07-3.18], P=0.03; 125-399 pg/mL: 2.98 [95% CI 1.65-5.39], P<0.001; ≥400 pg/mL: 4.54 [95% CI 2.22-9.29], P<0.001). The multivariate-adjusted hazard ratios for the development of total CVD and its subtypes, coronary heart disease and stroke, were significantly increased by a 1 SD increment of the log NT-proBNP concentrations and were nearly equal among CVD subtypes. Similar findings were observed for stroke subtypes of ischemic stroke and intracerebral hemorrhage but not subarachnoid hemorrhage. The effects of the 1 SD increment in log NT-proBNP values were comparable in subjects with and without other cardiovascular risk factors, except for sex. The area under the receiver operating characteristic curve was significantly (P=0.006) increased by adding NT-proBNP values to the model including other potential risk factors. CONCLUSIONS: Elevated NT-proBNP levels were shown to be a significant risk factor for the development of CVD and its subtypes in a general Japanese population, independently of other cardiovascular risk factors.

Optimal cutoff value of the serum pepsinogen level for prediction of gastric cancer incidence: the Hisayama Study.

BACKGROUND: Serum pepsinogen (sPG) levels have been established as a good marker of chronic atrophic gastritis and the sequential occurrence of gastric cancer. However, there have been few prospective investigations which investigated the predictive performance of sPG for future gastric cancer incidence. SUBJECTS AND METHODS: We prospectively followed-up a total of 2446 community-dwelling Japanese aged ≥ 40 years for 10 years and used the Youden's index to determine the cutoff values of the pepsinogen I level and pepsinogen I/II ratio to accurately discriminate gastric cancer events. Predictive performance of sPG was assessed by ROC curve. RESULTS: During the follow-up, 69 subjects developed gastric cancer. The most predictive sPG test criteria were determined to be a pepsinogen I level ≤ 59 ng/ml and pepsinogen I/II ratio ≤ 3.9. The sensitivity and specificity of these criteria to discriminate the actual occurrence of gastric cancer were 71.0% and 69.2%, respectively. The area under the ROC curve for gastric cancer occurrence increased significantly by adding the sPG test to the model that included the status of Helicobater pylori infection and other potential risk factors (from 0.742 to 0.809; p for difference in the area < 0.001). CONCLUSIONS: This study determined the optimal sPG test criteria for predicting gastric cancer occurrence over 10 years in a general Japanese population. These criteria would be effective to screen for individuals at high risk of this disease.

Dietary vitamin A intake and incidence of gastric cancer in a general Japanese population: the Hisayama Study.

BACKGROUND: The results of prospective studies examining the association between dietary vitamin A intake and the risk of gastric cancer have often been conflicting. The objective of this study was to investigate this issue in a general Japanese population. METHODS: A total of 2,467 community-dwelling Japanese subjects aged 40 years or older were followed up prospectively for 14 years. Dietary vitamin A intake was estimated using a semiquantitative food frequency method. RESULTS: During the follow-up period, gastric cancer developed in 93 subjects. The age- and sex-adjusted incidence of gastric cancer rose progressively with increasing levels of dietary vitamin A intake: at 2.2, 3.0, 3.8, and 4.5 per 1,000 person-years for quartile groups defined by dietary vitamin A intake levels of <639, 639-837, 838-1,061, and >1,061 µg retinol equivalents (RE)/day, respectively (P for trend <0.01). The risk of gastric cancer was significantly higher in the fourth quartile than in the first one even after multivariate adjustment [hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 0.70-3.09, P = 0.30 for the second quartile; HR = 1.85, 95% CI = 0.82-4.18, P = 0.14 for the third quartile; HR = 2.96, 95% CI = 1.12-7.80, P = 0.03 for the fourth quartile]. Comparable effects of vitamin A intake were observed irrespective of the location or histological type of gastric cancer. The HR for gastric cancer increased significantly only in subjects with a combination of high vitamin A intake (>1,061 µg RE/day) and Helicobacter pylori infection. CONCLUSIONS: Our findings suggest that dietary vitamin A intake is clearly associated with the risk of gastric cancer in the general Japanese population.

Prevalence and causes of functional disability in an elderly general population of Japanese: the Hisayama study.

BACKGROUND: There are limited data on the prevalence and causes of disability in the elderly general population in Japan. METHODS: In a population-based cross-sectional study of 1550 Japanese aged 65 years or older, we examined the prevalence of functional disability (defined as a Barthel Index score of ≤95) and its causes. RESULTS: A total of 311 of the participants had a disability (prevalence 20.1%). The prevalence of disability increased with age and doubled with every 5-year increment in age. Prevalence was higher in women than in men, especially among those aged 85 years or older. With respect to the cause of functional disability, dementia accounted for 23.5%, stroke for 24.7%, orthopedic disease for 12.9%, and other disease for 38.9% of cases in men; in women, the respective values were 35.8%, 9.3%, 31.0%, and 23.9%. Regarding age, dementia was the most frequent cause of disability in subjects aged 75 years or older, whereas stroke was most common in subjects aged 65 to 74 years. Approximately two-thirds of cases of total dependence were attributed to dementia in both sexes, whereas the main cause of slight or moderate/severe dependence was stroke in men and orthopedic disease in women. Among participants with total dependence, 94.8% resided in a hospital or health care facility. CONCLUSIONS: Our findings indicate that functional disability is common among Japanese elderly adults and that its major cause is stroke in men and dementia in women.

Smoking cessation improves mortality in Japanese men: the Hisayama study.

BACKGROUND: Although the smoking rate among Japanese men has been the highest in developed countries, the epidemiological evidence about whether smoking cessation can extend their lifespan is not well established. METHODS: A total of 1083 Japanese men aged ≥40 years were classified by their smoking status and followed up prospectively for 18 years (1988-2006). RESULTS: Current smoking was a significant risk factor for all-cause death: the multivariate-adjusted HRs of all-cause death for current smokers of 1-19, 20-39 and ≥40 cigarettes per day were 1.61 (95% CI 1.16 to 2.22), 1.56 (95% CI 1.08 to 2.23) and 3.15 (95% CI 1.59 to 6.24), respectively. Former smokers did not have an increased risk of all-cause death compared with never smokers. The excess risk of all-cause death for current smokers tended to decrease within 5 years after smoking cessation, eventually reaching a level almost equivalent to that of never smokers. The risk of cancer death decreased by 53% in subjects who had quit smoking for ≥10 years, while the risk of cardiovascular death decreased by 56% in subjects with the cessation period of <10 years. CONCLUSIONS: Our findings suggest that even a modest smoking habit significantly increases the risk of death among Japanese men, and the risk of death diminishes soon after cessation of smoking. These results imply the importance of smoking cessation to extend life in Japanese men.

Combined effects of smoking and hypercholesterolemia on the risk of stroke and coronary heart disease in Japanese: the Hisayama study.

BACKGROUND: Cigarette smoking is an established risk factor for stroke and coronary heart disease (CHD) in Western countries. However, it is uncertain whether or not smoking raises the risk of stroke in Japanese. We examined the influence of smoking on the development of stroke and CHD and the effects of interactions between smoking and hypercholesterolemia on these outcomes in a general Japanese population. METHODS: A total of 2,421 community-dwelling Japanese individuals, aged 40-79 years, with no history of cardiovascular disease, were followed up for 14 years. RESULTS: During the follow-up, 194 total stroke and 112 CHD events occurred. Compared with never smokers, the multivariate-adjusted hazard ratios for the occurrence of total stroke were 1.53 (95% confidence interval = 0.90-2.61) in former smokers, 1.90 (1.18-3.06) in current light smokers (<20 cigarettes/day) and 2.01 (1.11-3.65) in current heavy smokers (≥ 20 cigarettes/day). The multivariate-adjusted hazard ratios for the development of CHD were 1.10 (0.56-2.15), 1.88 (1.02-3.47) and 2.31 (1.17-4.57), respectively. In regard to stroke subtypes, current smoking was an independently significant risk factor for ischemic stroke and subarachnoid hemorrhage. Furthermore, the combination of smoking and hypercholesterolemia synergistically increased the risks of total stroke and CHD (all p for interaction <0.05). CONCLUSION: Our findings suggest that smoking raises the risks of ischemic stroke, subarachnoid hemorrhage and CHD occurrence in the Japanese population, and that this effect is strengthened by hypercholesterolemia.

Hyperglycemia increases risk of gastric cancer posed by Helicobacter pylori infection: a population-based cohort study.

BACKGROUND & AIMS: Although diabetes mellitus and hyperglycemia are considered to be possible risk factors for various types of malignancy, the epidemiologic evidence concerning gastric cancer is scarce. The aim of this study was to evaluate the impact of hemoglobin A1c (HbA1c) levels on gastric cancer occurrence and their interaction with Helicobacter pylori infection. METHODS: A total of 2603 Japanese subjects aged>or=40 years were stratified into 4 groups according to baseline HbA1c levels (or=7.0%) and followed up prospectively for 14 years. RESULTS: During the follow-up, 97 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer significantly increased in the 6.0%-6.9% (5.1 per 1000 person-years; P<.05) and >or=7.0% groups (5.5 per 1000 person-years; P<.05) compared with the 5.0%-5.9% group (2.5 per 1000 person-years), whereas it was slightly but not significantly high in the or=7.0% group). Among subjects who had both high HbA1c levels (>or=6.0%) and Helicobacter pylori infection, the risk of gastric cancer was dramatically elevated (interaction term, P=.004). CONCLUSIONS: Our findings suggest that casual hyperglycemia is a risk factor for gastric cancer and is a possible cofactor increasing the risk posed by Helicobacter pylori infection.