Trends in the prevalence of dementia in Japan.

There is a paucity of data regarding trends in dementia and its subtype prevalence in Japan. Our aims in the current paper are to: (1) summarize epidemiological studies of dementia in Japan including relevant details of study protocol and diagnostic criteria, (2) compare the age-specific prevalence of all-cause dementia among studies, and (3) assess the trends in Alzheimer's disease (AD) versus vascular dementia (VaD) over time. We reviewed diagnostic criteria, all-cause dementia prevalence, and the AD/VaD ratio from 8 large population studies of dementia in Japan. Compared with the Okinawa 1992 study, studies conducted in 1994, 1998, 2005, and 2008 had a higher prevalence of all-cause dementia using Poisson regression models, after controlling for age and sex. In contrast to the US and some European countries, all-cause dementia prevalence is increasing in Japan. The prevalence of AD as opposed to VaD seems to be increasing over time, but large variability in diagnostic criteria, possible regional variability, and differences in prevalence of subtypes of dementia between men and women make it difficult to draw a conclusion about this trend at the national level. Further studies, for example, comparing the population attributable risk of vascular diseases to the prevalence and incidence of dementia could help to clarify the regional variations in etiological subtypes.

QT interval prolongation and the risks of stroke and coronary heart disease in a general Japanese population: the Hisayama study.

Uncertainty remains regarding the value of heart-rate-corrected QT interval (QTc) prolongation on electrocardiogram for predicting cardiovascular disease (CVD), particularly among Asian populations. The objective of the present analysis was to analyze the association of QTc prolongation with the development of CVD in a general Japanese population. During the follow-up period, 303 CVD events were observed. Among men, the age-adjusted incidence rates of CVD rose with prolonged QTc levels: 10.9, 12.1, 14.1 and 37.8 per 1000 person-years for subgroups defined by QTc levels of <400, 400-419, 420-439 and > or =440 ms, respectively (P=0.0007 for trend). The risk of CVD in the highest group was 3.09-fold (95% confidence interval, 1.82-5.25) higher than that in the lowest group even after controlling for other confounding factors: age, hypertension, heart rate, electrocardiogram abnormalities, diabetes, impaired glucose tolerance, impaired fasting glycemia, body mass index, total and high-density lipoprotein cholesterols, alcohol intake, smoking habit and regular exercise. Similar associations were observed for the outcomes of stroke and coronary heart disease. Among women, in contrast, no clear associations were found between QTc levels and the risk of CVD events. In conclusion, prolonged QTc levels were associated with the development of CVD among general Japanese men. Measurement of QTc intervals is likely to provide additional information for the detection of individuals at high risk of future CVD events.

Circulating resistin is increased with decreasing renal function in a general Japanese population: the Hisayama Study.

BACKGROUND: The purpose of this study is to investigate the relationship between serum resistin levels and chronic kidney disease (CKD). METHODS: A total of 3192 community-dwelling subjects (1377 men, 1815 women), aged ≥40 years and without renal failure, were divided into four groups according to quartiles of serum resistin concentrations: ≤7.1, 7.2-9.9, 10.0-14.7 and ≥14.8 ng/mL. The associations of resistin levels with renal function status were examined cross-sectionally. The estimated glomerular filtration rate (eGFR) was calculated using the equation from the Modification of Diet in Renal Disease Study, and CKD was defined as an eGFR of <60 mL/min/1.73 m(2). RESULTS: The age- and sex-adjusted mean values of eGFR decreased significantly with elevating quartiles of resistin (P for trend <0.001). The age- and sex-adjusted odds ratios (ORs) for the presence of CKD increased progressively with higher quartiles of resistin. This trend remained robust even after controlling for age, sex, body mass index, diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), triglycerides, high-density lipoprotein and total cholesterol, hypertension, current smoking, current drinking, and regular exercise [second quartile: OR 1.44, 95% confidence interval (CI) 1.05-1.99; third quartile: OR 2.15, 95% CI 1.58-2.92; fourth quartile: OR 2.32, 95% CI 1.71-3.16; P for trend <0.001]. In stratified analyses, high resistin level (≥7.2 ng/mL) was a significant relevant factor in CKD, independent of HOMA-IR or hs-CRP level. Conclusion. Our findings suggest that elevated resistin level is significantly associated with the likelihood of CKD in the general Japanese population.

The effect of metabolic syndrome defined by various criteria on the development of ischemic stroke subtypes in a general Japanese population.

OBJECTIVE: We evaluated the impact of metabolic syndrome (MetS) defined by various criteria on the occurrence of ischemic stroke subtypes in a general Japanese population. METHODS: A total of 2452 residents of a Japanese community, Hisayama, aged 40 years or older, were followed up for 14 years. To define MetS, we used the original Japanese criteria, the modified Japanese criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program's Adult Treatment Panel III (NCEP) criteria, and the modified NCEP criteria. We substituted a waist circumference of > or = 90 cm in men and > or = 80 cm in women for the values of > or = 85 cm and > or = 90 cm, respectively, in the modified Japanese criteria and for > 102 cm and > 88cm, respectively, in the modified NCEP criteria. RESULTS: Only MetS defined by the modified Japanese criteria showed a significant association with the development of lacunar infarction, and its hazard ratios (HRs) for the development of atherothrombotic and cardioembolic infarction were significant and greater than those of MetS defined by the other criteria: adjusted HRs for lacunar, atherothrombotic and cardioembolic infarction were 1.94 (95% confidence interval (CI), 1.13-3.32; P=0.02), 2.55 (95% CI, 1.25-5.18; P=0.01) and 3.94 (95% CI, 1.89-8.22, P<0.001), respectively, after adjustment for confounding factors. CONCLUSION: Our findings suggest that MetS defined by the Japanese criteria with the modification of a waist circumference of > or = 90 cm in men and > or = 80 cm in women is a better predictor of each ischemic stroke subtype in the Japanese population.

Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study.

BACKGROUND: Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD) was investigated in a general Japanese population. METHODS: A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women) were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. RESULTS: Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002) or ischemic stroke (p < 0.001), especially in those with lacunar and atherothrombotic infarction, but not elevated in subjects with hemorrhagic stroke or coronary heart disease. When analyzed by quintile of serum resistin concentration, the age- and sex-adjusted odds ratio (OR) for having CVD and ischemic stroke increased with quintile of serum resistin (p for trends, 0.02 for CVD, < 0.001 for ischemic stroke), while such associations were not observed for hemorrhagic stroke or coronary heart disease. Compared to the first quintile, the age- and sex-adjusted OR of ischemic stroke was greater in the third (OR = 3.54; 95% confidence interval [CI], 1.17-10.67; p = 0.02), fourth (OR = 4.48; 95% CI, 1.53-13.09; p = 0.006), and fifth quintiles (OR = 4.70; 95% CI, 1.62-13.61; p = 0.004). These associations remained substantially unchanged even after adjustment for other confounding factors including high-sensitivity C-reactive protein. In the stratified analysis, the combination of high serum resistin and either diabetes or hypertension markedly increased the risk of ischemic stroke. CONCLUSION: Elevated serum resistin concentration appears to be an independent risk factor for ischemic stroke, especially lacunar and atherothrombotic infarction in the general Japanese population. The combination of high resistin and the presence of either diabetes or hypertension increased the risk of ischemic stroke.

Development and validation of a cardiovascular risk prediction model for Japanese: the Hisayama study.

The objective of this paper is to develop a new risk prediction model of cardiovascular disease and to validate its performance in a general population of Japanese. The Hisayama study is a population-based prospective cohort study. A total of 2634 participants aged 40 years or older were followed up for 14 years for incident cardiovascular disease (stroke and coronary heart disease (myocardial infarction, coronary revascularization and sudden cardiac death)). We used data among a random two-thirds (the derivation cohort, n=1756) to develop a new risk prediction model that was then tested to compare observed and predicted outcomes in the remaining one-third (the validation cohort, n=878). A multivariable cardiovascular risk prediction model was developed that incorporated age, sex, systolic blood pressure, diabetes, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and smoking. We assessed the performance of the model for predicting individual cardiovascular event among the validation cohort. The risk prediction model demonstrated good discrimination (c-statistic=0.81; 95% confidence interval, 0.77 to 0.86) and calibration (Hosmer-Lemeshow chi(2)-statistic=6.46; P=0.60). A simple risk score sheet based on the cardiovascular risk prediction model was also presented. We developed and validated a new cardiovascular risk prediction model in a general population of Japanese. The risk prediction model would provide a useful guide to estimate absolute risk of cardiovascular disease and to treat individual risk factors.

Impact of blood pressure levels on different types of stroke: the Hisayama study.

OBJECTIVE: Clinical uncertainty remains whether the blood pressure classification and risk stratifications recommended by the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009) are useful in predicting the risks of stroke and its subtypes in the general Japanese population. METHODS: A total of 1621 stroke-free residents of a Japanese community aged at least 40 years were followed up for 32 years. Outcomes were total and cause-specific stroke (lacunar infarction, atherothrombotic infarction, cardioembolic infarction, cerebral haemorrhage and subarachnoid haemorrhage). Incidence was calculated by the pooling of repeated observations method. RESULTS: The age-adjusted incidence of total stroke rose progressively with higher blood pressure levels in both sexes (both P for trend <0.0001). A similar pattern was observed for lacunar infarction in both sexes and for cerebral haemorrhage in men: the differences were significant between optimal blood pressure and grades 1-3 hypertension (all P < 0.05). The age-adjusted incidence of atherothrombotic infarction in either sex and that of cardioembolic infarction and subarachnoid haemorrhage in women significantly increased in grade 3 hypertension (all P < 0.05). These associations remained substantially unchanged even after adjustment for other risk factors. In regard to risk stratification, the age-adjusted incidence of stroke significantly increased with the level of risk in both sexes. CONCLUSION: Our findings suggest that the blood pressure classification and risk stratifications recommended by the JSH 2009 guidelines are useful in predicting the risk of stroke in a general Japanese population, but the magnitude and patterns of the impact of blood pressure categories are different among stroke subtypes.

Proposed criteria for metabolic syndrome in Japanese based on prospective evidence: the Hisayama study.

BACKGROUND AND PURPOSE: The current criteria of metabolic syndrome (MetS) are not based on evidence derived from prospective studies on cardiovascular disease (CVD). METHODS: In a 14-year follow-up study of 2452 community-dwelling Japanese individuals aged >or=40 years, we examined which of the MetS criteria are most predictive for the development of CVD. During the follow-up, 246 first-ever CVD events occurred. RESULTS: An optimal cutoff point of waist circumference for predicting CVD was 90 cm in men (age-adjusted hazard ratio=1.81; 95% CI, 1.19 to 2.74; P=0.005) and 80 cm in women (age-adjusted hazard ratio=1.46; 95% CI, 0.99 to 2.16; P=0.05). A comparison of MetS criteria showed that the modified Japanese criteria using this cutoff point instead of the original definition were the strongest predictor of CVD events in both sexes (men: age-adjusted hazard ratio=2.58; 95% CI, 1.65 to 4.02; P<0.001; women: age-adjusted hazard ratio=2.39; 95% CI, 1.65 to 3.48; P<0.001). These observations remained robust even after adjustment for other confounding factors. According to this criteria set, only in the presence of central obesity, the hazard ratios for future CVD increased significantly as the number of MetS components increased, and a significant relationship was identified from 2 or more MetS components compared with individuals who had no MetS component. CONCLUSIONS: Our findings suggest that the optimal cutoff point of waist circumference is 90 cm in men and 80 cm in women and that the modified Japanese criteria of MetS with this cutoff point as an essential component better predict CVD in the general Japanese population.

Seroprevalence of herpes simplex virus 1 and 2 in a population-based cohort in Japan.

BACKGROUND: There have been few population-based studies of the seroprevalence and correlates of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Japan. METHODS: We enrolled a total of 1244 adults, aged 18-59 years, from a population-based cohort in southern Japan, and tested their serum samples using an ELISA kit containing HSV type-specific antigens to glycoproteins G1 and G2. RESULTS: The seroprevalence of HSV-1 and HSV-2 was 55.4% and 7.4% in men and 63.3% and 9.3% in women, respectively. Overall, 4 percent of the participants (2.3% of men and 5.0% of women) were co-infected with HSV-1 and HSV-2. The seroprevalences of both HSV-1 and HSV-2 increased with age in both sexes, and were always higher among women than among men in each age bracket. The prevalence of HSV-2 infection among HSV-1 infected individuals was lower than that among uninfected individuals, both in men and women. Male current drinkers, and male and female current smokers, were more likely to be infected with HSV-1 and HSV-2, as compared to never drinkers and never smokers, respectively. CONCLUSION: It is hoped that the estimates produced in this study will help in understanding the burden of these infections in Japan.

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.

LDL cholesterol and the development of stroke subtypes and coronary heart disease in a general Japanese population: the Hisayama study.

BACKGROUND AND PURPOSE: Although the relation between serum LDL cholesterol level and coronary heart disease (CHD) is well established, its relation with stroke subtypes is less clear. METHODS: A total of 2351 inhabitants age >or=40 years in a Japanese community were followed up for 19 years. RESULTS: During follow-up, 271 subjects developed stroke and 144 developed CHD. Whereas the age- and sex-adjusted incidences of CHD significantly increased with increasing LDL cholesterol levels (P for trend <0.001), the associations between LDL cholesterol level and the incidences of ischemic or hemorrhagic stroke were not significant. The age- and sex-adjusted incidences of atherothrombotic infarctions (ATIs) and lacunar infarctions (LIs) significantly increased with increasing LDL cholesterol level (P for trend=0.03 for ATIs and=0.02 for LIs), but no such association was observed for cardioembolic infarction. After multivariate adjustment, the positive associations of LDL cholesterol level with the risks of ATI and CHD remained significant (P for trend=0.02 for ATIs and=0.03 for CHD), whereas the association with LIs was not significant. The risk of ATI significantly increased in the fourth quartile of LDL cholesterol compared with the first quartile (multivariate-adjusted hazard ratio=2.84; 95% CI, 1.17 to 6.93). The multivariate-adjusted risks for developing nonembolic infarction (ATIs and LIs) and CHD were significantly elevated in the groups with elevated LDL cholesterol values with and without the metabolic syndrome. CONCLUSIONS: Our findings suggest that an elevated LDL cholesterol level is a significant risk factor for developing ATI as well as CHD, and these associations are independent of the metabolic syndrome.

Secular trends in the incidence of and risk factors for ischemic stroke and its subtypes in Japanese population.

BACKGROUND: The study of long-term trends in the incidence of and risk factors for ischemic stroke subtypes could offer insights into primary and secondary prevention. METHODS AND RESULTS: We established 3 cohorts of residents >/=40 years of age in 1961, 1974, and 1988 in the Japanese community of Hisayama. Morphological examinations by autopsy or brain imaging were performed on most of the ischemic stroke cases developed in these cohorts. When 13-year follow-up data were compared, the age-adjusted incidence of ischemic stroke and lacunar infarction declined significantly from the first to the third cohort for both sexes, whereas the incidences of atherothrombotic and cardioembolic infarction did not change during this period. Hypertension was a powerful risk factor for the development of ischemic stroke, and improvement of hypertension control would have largely influenced this declining trend: The age- and sex-adjusted hazard ratio of hypertension decreased from 3.25 (95% CI 2.17 to 4.86) in the first cohort to 1.83 (1.29 to 2.58) in the third cohort. A rapid increase in the prevalence of metabolic disorders may have offset the impact of improvements in hypertension control and resulted in a slowdown of the decline in the incidence of ischemic stroke in the cohorts in the present study; however, hypertension still makes a large contribution to the development of ischemic stroke. CONCLUSIONS: These findings suggest that in the Japanese population, the incidence of ischemic stroke has declined significantly over the past 40 years, probably owing to better management of hypertension. There is a need for greater primary prevention efforts in the treatment of hypertension and metabolic disorders.

Arterial stiffness and QT interval prolongation in a general population: the Hisayama study.

Few population studies have addressed the association of QT interval prolongation with clinical or subclinical arterial disease. The primary objective here was to examine the relationship between the pulse wave velocity (PWV) and the heart rate-corrected QT interval duration (QTc). This is a cross-sectional study, based on a survey of a general population of Japanese. We examined 2,666 community-dwelling individuals without history of cardiovascular disease, aged 40 or over. The PWV was measured between the brachial and ankle regions (baPWV). QTc was estimated using Bazett's equation. The age-adjusted mean values of QTc increased progressively with rising baPWV levels for either sex: for men, 397, 401, 403, and 406 ms for quartile groups defined by baPWV values of less than 1,369, 1,370 to 1,560, 1,561 to 1,840, and 1,841 or greater cm/s, respectively (p < 0.0001 for trend); for women, 406, 410, 414, and 417 ms for quartile groups defined by baPWV of less than 1,269, 1,270 to 1,493, 1,494 to 1,821, and 1,822 or greater cm/s, respectively (p < 0.0001 for trend). When male and female subjects were combined, this positive relationship between baPWV and QTc remained significant, even after controlling for age, sex, hypertension, ECG abnormalities, dyslipidemia, diabetes, obesity, serum calcium and potassium, alcohol intake, and smoking habits (p < 0.0001 for trend). In conclusion, baPWV is independently associated with QT interval prolongation.

Population-based prospective study of the combined influence of cigarette smoking and Helicobacter pylori infection on gastric cancer incidence: the Hisayama Study.

The authors assessed the separate and joint influences of cigarette smoking and Helicobacter pylori infection on the development of gastric cancer in a population-based prospective study. A total of 1,071 Japanese men aged > or =40 years were followed up prospectively for 14 years (1998-2002). Compared with that for current nonsmokers, the multivariate-adjusted hazard ratios of gastric cancer for smokers of 1-9, 10-19, and > or =20 cigarettes per day were 1.36 (95% confidence interval (CI): 0.50, 3.71), 1.93 (95% CI: 1.01, 3.67), and 1.88 (95% CI: 1.02, 3.43), respectively. The risk of gastric cancer increased steeply for subjects who had both a smoking habit and H. pylori infection compared with those who did not have both risk factors (hazard ratio = 11.41, 95% CI: 1.54, 84.67). If causal, the estimated population attributable fraction of gastric cancer for cigarette smoking was approximately half that for H. pylori infection (28.4% vs. 56.2%). The overlap of the population attributable fractions for the 2 factors was 49.6%. Findings suggest that cigarette smoking and H. pylori infection are significant risk factors for gastric cancer in Japanese men, and the magnitude of their combined influence is considerable.

Fasting plasma glucose cutoff for diagnosis of diabetes in a Japanese population.

OBJECTIVE: We examined the relationship between fasting plasma glucose (FPG) and 2-h post-load glucose (PG) levels, and the optimal FPG cutoff level to correspond to a 2-h PG of 11.1 mmol/liter, the gold standard diagnostic criterion, in a general Japanese population. DESIGN: Cross-sectional study populations of 2421 subjects in 1988 and 2698 subjects in 2002, aged 40-79 yr and without antidiabetic medication, were tested with an oral glucose tolerance test. The relationship between FPG and 2-h PG was investigated by various regression models and a receiver operating characteristic curve. RESULTS: The best-fit model for the relationship between FPG and 2-h PG was a quadratic regression model. The FPG cutoff levels corresponding to the 2-h PG of 11.1 mmol/liter by this model were 6.2 mmol/liter in 1988 and 6.3 mmol/liter in 2002. In the combined populations, the FPG cutoff point was 6.3 mmol/liter; the sensitivity and specificity of this cutoff point for detecting a 2-h PG of 11.1 mmol/liter were 75.2 and 88.6%, respectively. The receiver operating characteristic curve analysis confirmed that the corresponding FPG point was 6.2 mmol/liter in both the 1988 and 2002 populations. In a stratified analysis, the FPG cutoff level increased with increasing body mass index levels; however, even in subjects with body mass index more than or equal to 30 kg/m2, the FPG cutoff level was lower than 7.0 mmol/liter. CONCLUSIONS: Our findings suggest that the FPG cutoff level corresponding to the 2-h PG of 11.1 mmol/liter in the general Japanese population is lower than the current diagnostic criterion.

Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: the Hisayama study.

To explore the validity of the criteria for dementia with Lewy bodies (DLB) revised in 2005, we examined community based consecutive autopsy cases. 10.3% of the non-demented subjects and 31.2% of the demented subjects showed the Lewy body pathology. Applying the revised pathological criteria to the 205 demented subjects, the types of LB pathology of 11 cases (5.4%) were brainstem-predominant, 24 cases (11.7%) were limbic type and 24 cases (11.7%) were diffuse neocortical type, although there were many subjects not to fit the criteria exactly. The prevalence of Lewy bodies (LBs) was almost same regardless of gender; however, the extent of the LB pathology among females was more severe than that in males. The likelihood of DLB being modified by concomitant Alzheimer's pathology was as follows: 27 cases (13.2%) showed low likelihood, 16 cases (7.8%) showed intermediate likelihood and 16 cases (7.8%) showed high likelihood. Since the numbers of clinical features of DLB were significantly higher in the pathological intermediate and high likelihood DLB groups than in the low likelihood DLB group or no LB group, both the intermediate and high likelihood groups of DLB should be considered as pathological DLB.

High-sensitivity C-reactive protein and coronary heart disease in a general population of Japanese: the Hisayama study.

OBJECTIVE: The purpose of this study was to investigate the effects of high-sensitivity C-reactive protein (hs-CRP) on the risks of coronary heart disease (CHD) in a general population of Japanese. METHODS AND RESULTS: The Hisayama study is a population-based prospective cohort study. A total of 2589 participants aged 40 years or older were followed up for 14 years. Outcomes are incident CHD (myocardial infarction, coronary revascularization, and sudden cardiac death). The median hs-CRP level was 0.43 mg/L at baseline. During the follow-up period, 129 coronary events were observed. Age- and sex-adjusted annual incidence rates of CHD rose progressively with higher hs-CRP levels: 1.6, 3.3, 4.5, and 7.4 per 1000 person-years for quartile groups defined by hs-CRP levels of <0.21, 0.21 to 0.43, 0.44 to 1.02, and >1.02 mg/L, respectively (P<0.0001 for trend). The risk of CHD in the highest quartile group was 2.98-fold (95% CI, 1.53 to 5.82) higher than that in the lowest group even after controlling for other cardiovascular risk factors. CONCLUSIONS: hs-CRP levels were clearly associated with future CHD events in a general population of Japanese. In Japanese populations, the hs-CRP cut-off point for high-risk of future development of CHD is likely to be >1.0 mg/L, which is much lower than that for Western populations.

Polymorphisms in the lymphotoxin alpha gene and the risk of ischemic stroke in the Japanese population. The Fukuoka Stroke Registry and the Hisayama Study.

BACKGROUND AND PURPOSE: Lymphotoxin alpha (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population. METHODS: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study. RESULTS: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke. CONCLUSIONS: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.

Impact of serum total cholesterol on the incidence of gastric cancer in a population-based prospective study: the Hisayama study.

The results of prospective studies that have examined the association between serum cholesterol levels and the incidence of gastric cancer remain controversial. To examine this issue in a general population, a total of 2,604 subjects aged 40 years or older were followed up prospectively for 14 years. During the follow-up period, gastric cancer developed in 97 subjects. The age- and sex-adjusted incidence of gastric cancer by quartiles of serum cholesterol level, namely, <4.06, 4.06-5.32, 5.33-6.04 and >or=6.05 mmol/L, were 3.9, 3.3, 3.1 and 2.1 per 1,000 person-years, respectively. The risk of gastric cancer increased with decreasing cholesterol level (age- and sex-adjusted hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.49; p = 0.04 for a decrease of 1 mmol/L in serum cholesterol level). This inverse association remained unchanged even after adjustment for other confounding factors, namely, Helicobacter pylori infection, atrophic gastritis, family history of malignant neoplasm, smoking habits, body mass index, hemoglobin A1c, white blood cell count and dietary factors (adjusted HR, 1.28; 95% CI, 1.03-1.58; p = 0.02). This association was significant for intestinal-type gastric cancers, but not for diffuse-type. As regards cancer stage, the inverse cholesterol-cancer association was marginally significant for early gastric cancer after multivariate-adjustment (adjusted HR, 1.25; 95% CI, 0.97-1.61; p = 0.09), but was not for advanced gastric cancer probably due to the small number of cases. In conclusion, our findings suggest that low serum cholesterol levels are an independent risk factor for developing gastric cancer, especially intestinal-type gastric cancer.