Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-ß. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-ß is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Potential Protective Effects of Equol (Soy Isoflavone Metabolite) on Coronary Heart Diseases-From Molecular Mechanisms to Studies in Humans.

Equol, a soy isoflavone-derived metabolite of the gut microbiome, may be the key cardioprotective component of soy isoflavones. Systematic reviews have reported that soy isoflavones have no to very small effects on traditional cardiovascular disease risk factors. However, the potential mechanistic mode of action of equol on non-traditional cardiovascular risk factors has not been systematically reviewed. We searched the PubMed through to July 2021 by using terms for equol and each of the following markers: inflammation, oxidation, endothelial function, vasodilation, atherosclerosis, arterial stiffness, and coronary heart disease. Of the 231 records identified, 69 articles met the inclusion criteria and were summarized. Our review suggests that equol is more lipophilic, bioavailable, and generally more potent compared to soy isoflavones. Cell culture, animal, and human studies show that equol possesses antioxidative, anti-inflammatory, and vasodilatory properties and improves arterial stiffness and atherosclerosis. Many of these actions are mediated through the estrogen receptor ß. Overall, equol may have a greater cardioprotective benefit than soy isoflavones. Clinical studies of equol are warranted because equol is available as a dietary supplement.

Ambient fine particulate matter exposure and incident mild cognitive impairment and dementia.

BACKGROUND/OBJECTIVE: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between estimated ambient fine particulate matter (PM2.5 ) and risk of incident MCI and dementia in a post-industrial region known for historically poor air quality. SETTING/PARTICIPANTS: Adults aged 65+ years in a population-based cohort (n = 1572). MEASUREMENTS: Census tract level PM2.5 from Environmental Protection Agency (EPA) air quality monitors; Clinical Dementia Rating (CDR)®. DESIGN: We estimated ambient PM2.5 exposure (µg/m3 , single-year and 5-year averages) by geocoding participants' residential addresses to census tracts with daily EPA PM2.5 measurements from 2002 to 2014. Using Bayesian spatial regression modeling adjusted for age, sex, education, smoking history, and household income, we examined the association between estimated PM2.5 exposure and risk of incident MCI (CDR = 0.5) and incident dementia (CDR ≥ 1.0). RESULTS: Modeling estimated single-year exposure, each 1 µg/m3 higher ambient PM2.5 was associated with 67% higher adjusted risk of incident dementia (hazard ratio [HR] = 1.669, 95% credible interval [CI]: 1.298, 2.136) and 75% higher adjusted risk of incident MCI (HR = 1.746, 95% CI: 1.518, 2.032). Estimates were higher when modeling 5-year ambient PM2.5 exposure for incident dementia (HR = 2.082, 95% CI: 1.528, 3.015) and incident MCI (HR = 3.419, 95% CI: 2.806, 4.164). CONCLUSIONS: Higher estimated ambient PM2.5 was associated with higher risk of incident MCI and dementia, particularly when considering longer-term exposure, and independent of demographic characteristics and smoking history. Targeting poor air quality may be a reasonable population-wide intervention to reduce the risk of cognitive impairment in older adults, particularly in regions exceeding current recommendations for safe exposure to PM2.5 .

Physical activity levels in American and Japanese men from the ERA-JUMP Study and associations with metabolic syndrome.

Background: Metabolic syndrome (MetS) is a global health problem. Physical activity (PA) is a known modifiable risk factor for MetS and individual MetS components. However, the role of PA could differ between sub-populations due to differences in the variability of PA and other MetS risk factors. To examine these differences, multi-country studies with standardized outcome measurement methods across cohorts are needed. Methods: Cross-sectional PA levels (total and domain specific) in healthy middle-aged (44-56 years) men in the Risk Factor Assessment among Japanese and U.S. Men in the Post-World War II Birth Cohort (ERA-JUMP) Study (n = 730; American: n = 417; Japanese: n = 313; from population-representative samples in Pittsburgh, Pennsylvania, USA, and Kusatsu, Shiga, Japan) were compared. The relationships between PA levels and MetS (overall and specific components) in/across the American and Japanese sub-cohorts (adjusting for age, smoking, and alcohol consumption) were also assessed using the same instruments (pedometer and validated questionnaire) to measure PA in both cohorts. Results: A total of 510 individuals provided complete data on PA (American: n = 265; Japanese: n = 245). The American cohort had significantly lower mean ± SD steps/day (7878 ± 3399 steps/day) vs. the Japanese cohort (9055 ± 3797 steps/day) (p < 0.001) but had significantly higher self-reported moderate-vigorous leisure PA (American: 15.9 (7.4-30.3) metabolic task equivalent hours per week (MET-h/week) vs. Japanese: 4.0 (0-11.3) MET-h/week, p < 0.0001). In both sub-cohorts, each 1000 steps/day increase was associated with lower odds of having MetS (American: OR = 0.90, 95%CI: 0.83-0.98; Japanese: OR = 0.87, 95%CI: 0.79-0.95) and the individual MetS component of high waist circumference (American: OR = 0.86, 95%CI: 0.79-0.94; Japanese: OR = 0.87, 95%CI: 0.80-0.95). In the American cohort only, higher self-reported leisure PA (Met-h/week) was associated with lower odds of MetS and high waist circumference (OR = 0.98, 95%CI: 0.97-0.99 for MetS and waist circumference, respectively). Conclusion: Higher total step counts/day had an important protective effect on MetS prevalence in both the Japanese and American cohorts, despite differences in PA levels and other MetS risk factors. The effect of steps/day (across all intensity levels) was much greater than domain-specific moderate-vigorous PA captured by questionnaire, suggesting the need for measurement tools that can best capture total movement when examining the effects of PA on MetS development.

The association of home and accurately measured office blood pressure with coronary artery calcification among general Japanese men.

OBJECTIVE: We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men. METHODS: We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors. RESULTS: The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813). CONCLUSION: The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

Explaining the decline in coronary heart disease mortality rates in Japan: Contributions of changes in risk factors and evidence-based treatments between 1980 and 2012.

BACKGROUND: We aimed to quantify contributions of changes in risks and uptake of evidence-based treatment to coronary heart disease (CHD) mortality trends in Japan between 1980 and 2012. METHODS: We conducted a modelling study for the general population of Japan aged 35 to 84 years using the validated IMPACT model incorporating data sources like Vital Statistics. The main outcome was difference in the number of observed and expected CHD deaths in 2012. RESULTS: From 1980 to 2012, age-adjusted CHD mortality rates in Japan fell by 61%, resulting in 75,700 fewer CHD deaths in 2012 than if the age and sex-specific mortality rates had remained unchanged. Approximately 56% (95% uncertainty interval [UI]: 54-59%) of the CHD mortality decrease, corresponding to 42,300 (40,900-44,700) fewer CHD deaths, was attributable to medical and surgical treatments. Approximately 35% (28-41%) of the mortality fall corresponding to 26,300 (21,200-31,000) fewer CHD deaths, was attributable to risk factor changes in the population, 24% (20-29%) corresponding to 18,400 (15,100-21,900) fewer and 11% (8-14%) corresponding to 8400 (60,500-10,600) fewer from decreased systolic blood pressure (8.87 mm Hg) and smoking prevalence (14.0%). However, increased levels of cholesterol (0.28 mmol/L), body mass index (BMI) (0.68 kg/m2), and diabetes prevalence (1.6%) attenuated the decrease in mortality by 2% (1-3%), 3% (2-3%), and 4% (1-6%), respectively. CONCLUSIONS: Japan should continue their control policies for blood pressure and tobacco, and build a strategy to control BMI, diabetes, and cholesterol levels to prevent further CHD deaths.

International Comparison of Abdominal Fat Distribution Among Four Populations: The ERA-JUMP Study.

BACKGROUND: Abdominal fat distribution varies across groups with different races or environments. Whether environmental factors, apart from racial differences, affect abdominal fat distribution is unknown. METHODS: We compared the abdominal fat distribution of four groups; different races with similar environments (Caucasians vs. Japanese Americans), different environments with an identical race (Japanese Americans vs. Japanese), and similar races with similar environments (Japanese vs. Koreans). A population-based sample of 1212 men aged 40-49 were analyzed: 307 Caucasians and 300 Japanese Americans in the United States, 310 Japanese in Japan, and 295 Koreans in Korea. We compared the proportion of visceral adipose tissue area to total abdominal adipose tissue area (VAT%) and other factors that can affect abdominal fat distribution (smoking, alcohol use, physical activity levels, and metabolic factors). RESULTS: VAT% was significantly higher in Japanese and Koreans than in Japanese Americans and Caucasians (50.0, 48.5, 43.2, 41.0%, respectively, P < 0.001). Even after adjustment for possible confounders, the significant VAT% difference remained in comparing groups with identical race but different environments (i.e., Japanese vs. Japanese Americans). In contrast, comparing groups with different races but similar environments (i.e., Caucasians vs. Japanese Americans), VAT% was not significantly different. Comparing groups with similar races and similar environments (i.e., Japanese vs. Koreans), VAT% did not significantly differ. CONCLUSIONS: Environmental differences, apart from racial differences, affect the difference in abdominal fat distribution across different groups in middle-aged men.

Association of Coronary Artery Calcification with Estimated Coronary Heart Disease Risk from Prediction Models in a Community-Based Sample of Japanese Men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

AIM: The clinical significance of coronary artery calcification (CAC) is not fully determined in general East Asian populations where background coronary heart disease (CHD) is less common than in USA/Western countries. We cross-sectionally assessed the association between CAC and estimated CHD risk as well as each major risk factor in general Japanese men. METHODS: Participants were 996 randomly selected Japanese men aged 40-79 y, free of stroke, myocardial infarction, or revascularization. We examined an independent relationship between each risk factor used in prediction models and CAC score ≥100 by logistic regression. We then divided the participants into quintiles of estimated CHD risk per prediction model to calculate odds ratio of having CAC score ≥100. Receiver operating characteristic curve and c-index were used to examine discriminative ability of prevalent CAC for each prediction model. RESULTS: Age, smoking status, and systolic blood pressure were significantly associated with CAC score ≥100 in the multivariable analysis. The odds of having CAC score ≥100 were higher for those in higher quintiles in all prediction models (p-values for trend across quintiles ＜0.0001 for all models). All prediction models showed fair and similar discriminative abilities to detect CAC score ≥100, with similar c-statistics (around 0.70). CONCLUSIONS: In a community-based sample of Japanese men free of CHD and stroke, CAC score ≥100 was significantly associated with higher estimated CHD risk by prediction models. This finding supports the potential utility of CAC as a biomarker for CHD in a general Japanese male population.

Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) for small colorectal polyps has lower incidence of adverse events, especially delayed postpolypectomy bleeding (DPPB). However, few data are available on comparisons of the incidence of DPPB of CSP and hot polypectomy (HP). The aim of this study was to evaluate the incidence of DPPB after CSP and compare it with that of HP. A propensity score model was used as a secondary analysis. PATIENTS AND METHODS: This was a retrospective cohort study conducted in a single municipal hospital. We identified 539 patients with colorectal polyps from 2 mm to 11 mm in size who underwent CSP (804 polyps in 330 patients) or HP (530 polyps in 209 patients) between July 2013 and June 2015. RESULTS: There were no cases of DPPB in the CSP group. Conversely, DPPB occurred in 4 patients (1.9 %) after HP, resulting in a significant difference between the CSP and HP groups (0.008 % vs 0 %, P  = 0.02). Propensity score-matching analysis created 402 matched pairs, yielding a significantly higher DPPB rate in the HP group than CSP group (0.02 % vs 0 %, P  = 0.04). However, significantly more patients in the CSP group had unclear horizontal margins that precluded assessment (83 vs 38 cases, P  < 0.001). The retrieval failure rate was significantly higher in the CSP group than in the HP group (3 % vs 0.7 %, P  = 0.01). CONCLUSIONS: DPPB was less frequent with CSP than HP, as selected by the propensity score-matching model. Our findings indicate that CSP is recommended polypectomy in daily clinical setting. However, special care should be taken during polyp retrieval and horizontal margin assessment, and these issues could be taken into account in follow-up after CSP.

Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men.

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score ≥10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 512·7 (interquartile range (IQR) 194·1, 1170·0), 9·1 (IQR 0·10, 33·1) and 0·0 (IQR 0·0, 1·0) nm, respectively. Prevalence of CAC and equol-producers was 9·6 and 16·0 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 0·10 (95 % CI 0·01, 0·90, P<0·04). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

Progression of coronary artery calcium in Japanese American men and white men in the ERA JUMP study.

BACKGROUND: Progression of coronary artery calcium (CAC) is associated with increased risk of coronary heart disease (CHD) and is reported to be greater in whites than blacks, Hispanics, and Chinese in the US. Our objective was to compare progression of CAC between Japanese Americans and whites. METHODS: Population-based sample of 303 Japanese American men and 310 white men aged 40-49years, free of clinical cardiovascular disease at baseline, were examined for CAC at baseline (2004-2007) and follow-up (2008-2013). Progression of CAC was defined as change in coronary calcium scores (CCS) in participants with baseline CCS>0 and incident CAC in participants with baseline CCS=0. Multiple linear regression and relative risk regression were used to compare change in CCS scores and incident CAC between the two races, respectively. RESULTS: Japanese American men had significantly greater annual change in CCS than white men (median [interquartile range]: 11.3 Agatston units [1.4, 24.9] vs 2.5 [-0.22, 14.5]) in the unadjusted analyses. After adjusting for cardiovascular risk factors and follow-up time, change in CCS (beta±CI) and incidence rate ratio of CAC was similar in Japanese American men and white men: -0.12 (-0.34, 0.15) and (0.87 [95% CI: 0.20, 3.9]), respectively. CONCLUSIONS: In contrast to previously reported greater progression of CAC in whites than other races, we found a similar progression of CAC in Japanese American men as white men. Our study identifies Japanese American men as a target group for prevention of CHD. Large prospective studies are warranted to confirm these findings.

Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification.

BACKGROUND: Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C). OBJECTIVES: Whether LDL-P is associated with subclinical atherosclerosis, independent of LDL-C, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis. METHODS: We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined. RESULTS: LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made. CONCLUSIONS: In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P.

Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men.

BACKGROUND: Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia. METHODS AND RESULTS: In a population-based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross-sectional associations of smoking status, cumulative pack-years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima-media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle-brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16-2.79]; CIMT >1.0 mm, 1.88 [1.02-3.47]; AoAC >0, 4.29 [2.30-7.97]; and ankle-brachial index <1.1, 1.78 [1.16-2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13-3.34]; and AoAC >0, 2.55 [1.45-4.49]). Dose-response relationships of pack-years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle-brachial index, were observed among both current and former smokers, and even a small amount of pack-years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices. CONCLUSIONS: Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

A Significant Positive Association of Vitamin D Deficiency with Coronary Artery Calcification among Middle-aged Men: For the ERA JUMP Study.

OBJECTIVE: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults. METHODS: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men). Liquid chromatography-tandem mass spectrometry was utilized to measure serum vitamin D. CAC was examined by electron beam computed tomography using standardized protocols and read centrally at the University of Pittsburgh using Agatston's methods. To investigate an association between vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) and CAC (defined as Agatston score ≥ 10), we utilized multivariable logistic regression models. RESULTS: Prevalence of CAC and vitamin D deficiency was 27.2% and 10.3%, respectively. Participants with CAC were significantly older, had significantly higher body mass index (BMI), and had higher rates of smoking. Those with CAC were 3.31 times likely to be vitamin D deficient, after adjusting for traditional cardiovascular risk factors (odds ratio [OR] = 3.31, 95% confidence interval [CI], 1.12-9.77). CONCLUSIONS: In this population-based study of healthy middle-aged men, vitamin D deficiency had a significant positive association with the presence of CAC.

Gastric atrophy and xanthelasma are markers for predicting the development of early gastric cancer.

BACKGROUND: The significance of gastric xanthelasma in relation to gastric cancer still remains unclear. We investigated whether gastric xanthelasma would be a useful marker for predicting the development of early gastric cancer. METHODS: A total of 1823 patients who underwent a medical health checkup were enrolled. We examined the relationship between gastric xanthelasma and various clinical features, and in an endoscopic follow-up study investigated whether the presence of gastric xanthelasma was predictive of the development of early gastric cancer. RESULTS: In the initial endoscopic examination, gastric xanthelasma was detected in 107 (5.9 %) of the 1823 patients. The presence of gastric xanthelasma was significantly associated with age ≥65 years, male gender, open-type atrophy, and the presence of diabetes mellitus (DM) (p < 0.0001, p < 0.0001, p < 0.0001, and p < 0.0001, respectively). During the endoscopic follow-up period, early gastric cancer was found in 29 (1.6 %) of the 1823 patients. Gastric cancer occurred in 15 (14.0 %) of 107 patients with gastric xanthelasma, whereas it occurred in 14 (0.8 %) of 1716 patients without (p < 0.0001). Multivariate analysis revealed that open-type atrophy and gastric xanthelasma were independently related to the development of gastric cancer (odds ratio 7.19 [2.50-20.83]; p = 0.0003 and 5.85 [2.67-12.82]; p < 0.0001, respectively). The presence of gastric xanthelasma was significantly predictive of gastric cancer development even in the selected high-risk groups with open-type atrophy or DM (p < 0.0001 or p < 0.0001, respectively). CONCLUSIONS: Gastric xanthelasma is a useful marker for predicting the development of gastric cancer.

A Case of Myelodysplastic Syndrome with Intestinal Behçet's Disease-Like Symptoms Treated by Prednisolone and Azacitidine.

BACKGROUND Intestinal Behçet's disease-like symptoms are rare complications of myelodysplastic syndrome and are often refractory to immunosuppressive therapies. We described a case of myelodysplastic syndrome complicated by Behçet's disease-like symptoms treated with prednisolone and azacitidine. CASE REPORT A 68-year-old Japanese woman was admitted to our hospital because of persistent high fever and lower abdominal pain. Oral ulcerations developed after admission, and multiple ulcers were found in her terminal ileum by endoscopic examination. She was diagnosed with myelodysplastic syndrome with trisomy 8 by bone marrow examination. Her symptoms diminished after administration of prednisolone, but relapsed afterwards. She began azacitidine therapy and her symptoms have been controlled for at least 10 months. CONCLUSIONS This case might suggest the possibility of azacitidine as a treatment option for myelodysplastic syndrome complicated by Behçet's disease-like symptoms.

Cadmium exposure and risk of pancreatic cancer: a meta-analysis of prospective cohort studies and case-control studies among individuals without occupational exposure history.

Pancreatic cancer is one of the most deadly types of cancer for both genders. Classified as a human carcinogen, cadmium has been related to diverse cancers. However, the association between cadmium exposure and the risk of pancreatic cancer is still unclear. We quantitatively reviewed the observational studies on the association of cadmium exposure with pancreatic cancer risk among individuals without occupational exposure history published through July 2014 in PubMed by using a fixed-effect model. Four prospective cohort studies (112,934 participants with 335 events) and two case-control studies (177 cases and 539 controls) were identified. The summarized relative risk (RR) with a 95% confidence interval (CI) was 2.05 (95% CI = 1.58-2.66), comparing the highest to the lowest category of cadmium exposure. This positive association persisted in men (RR = 1.78, 95% CI = 1.04-3.05) but not in women (RR = 1.02, 95% CI = 0.63-1.65). Further research is needed to provide more solid evidence on the association of cadmium exposure with pancreatic cancer risk and to elucidate the underlying biological mechanism of the potential gender difference.

Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study.

BACKGROUND: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries. METHODS: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys. RESULTS: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries. CONCLUSIONS: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese.

Associations between Inflammatory Markers and Subclinical Atherosclerosis in Middle-aged White, Japanese-American and Japanese Men: The ERA-JUMP Study.

AIM: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians. METHODS: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models. RESULTS: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all ＜0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC. CONCLUSIONS: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.