Risk Classification for Metabolic Syndrome and the Incidence of Cardiovascular Disease in Japan With Low Prevalence of Obesity: A Pooled Analysis of 10 Prospective Cohort Studies.

Background It is uncertain whether risk classification under the nationwide program on screening and lifestyle modification for metabolic syndrome captures well high-risk individuals who could benefit from lifestyle interventions. We examined the validity of risk classification by linking the incidence of cardiovascular disease (CVD). Methods and Results Individual-level data of 29 288 Japanese individuals aged 40 to 74 years without a history of CVD from 10 prospective cohort studies were used. Metabolic syndrome was defined as the presence of high abdominal obesity and/or overweight plus risk factors such as high blood pressure, high triglyceride or low high-density lipoprotein cholesterol levels, and high blood glucose levels. The risk categories for lifestyle intervention were information supply only, motivation-support intervention, and intensive support intervention. Sex- and age-specific hazard ratios and population attributable fractions of CVD, which were also further adjusted to consider non-high density lipoprotein cholesterol levels, were estimated with reference to nonobese/overweight individuals, using Cox proportional hazard regression. Since the reference category included those with risk factors, we set a supernormal group (nonobese/overweight with no risk factor) as another reference. We documented 1023 incident CVD cases (565 men and 458 women). The adjusted CVD risk was 60% to 70% higher in men and women aged 40 to 64 years receiving an intensive support intervention, and 30% higher in women aged 65 to 74 years receiving a motivation-support intervention, compared with nonobese/overweight individuals. The population attributable fractions in men and women aged 40 to 64 years receiving an intensive support intervention were 17.7% and 6.6%, respectively, while that in women aged 65 to 74 years receiving a motivation-support intervention was 9.4%. Compared with the supernormal group, nonobese/overweight individuals with risk factors had similar hazard ratios and population attributable fractions as individuals with metabolic syndrome. Conclusions Similar CVD excess and attributable risks among individuals with metabolic syndrome components in the absence and presence of obesity/overweight imply the need for lifestyle modification in both high-risk groups.

Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).

BACKGROUND: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. METHODS: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. RESULTS: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease. CONCLUSIONS: The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

Parenting style during childhood is associated with the development of chronic pain and a patient's need for psychosomatic treatment in adulthood: A case-control study.

The aim of this study is to investigate the relation between parenting style and chronic pain and the patients' need for psychosomatic treatment in adulthood.We compared 4 combinations of 2 parenting style subscales, high and low care and overprotection, among the following 4 age- and sex-matched groups: community-dwelling subjects without chronic pain (n = 100), community-dwelling subjects with chronic pain (n = 100), outpatients with chronic pain (n = 50), and inpatients with chronic pain (n = 50). Parenting style was assessed for both the mother and father by use of the Parental Bonding Instrument questionnaire. The parenting style associated with the worst outcome was defined as both low care and high overprotection, as reported in previous studies.The frequency of reported adverse parenting style was significantly higher among chronic pain patients than community-dwelling subjects without chronic pain (all P < .05). The odds ratios for an adverse parenting style significantly increased through the categories after adjusting for demographic factors and the pain visual analog scale (P for trend <.01).These findings suggest that parental low care and high overprotection during childhood contribute to the future risk of chronic pain and the patients' need for psychosomatic treatment in adulthood.

Characteristics of the Salivary Microbiota in Patients With Various Digestive Tract Cancers.

The salivary microbiota is constantly swallowed and delivered to the digestive tract. These bacteria may be associated with gastrointestinal diseases. This case-control study examined the salivary microbiota in patients with digestive tract cancer (DTC) and evaluated their differential distribution based on the cancer sites. We collected saliva samples from 59 patients with cancer in any part of the digestive tract (tongue/pharynx, esophagus, stomach, and large intestine) and from 118 age- and sex-matched control subjects. There was no significant difference in periodontal status between DTC patients and control subjects (P = 0.72). We examined the bacterial diversity and composition in saliva by 16S ribosomal RNA gene sequencing. Salivary bacterial diversity in DTC patients was significantly higher than that in control subjects [number of operational taxonomic units (OTUs), P = 0.02; Shannon index, P < 0.01; Chao1, P = 0.04]. Eleven differentially abundant OTUs in DTC patients were identified using the linear discriminant analysis effect size (LEfSe) method. Based on the cancer sites, the diversity of salivary bacteria was especially higher in tongue/pharyngeal or esophageal cancer patients than in control subjects. Among the 11 differentially abundant OTUs in DTC patients, an OTU corresponding to Porphyromonas gingivalis was more abundant in the saliva of all groups of DTC patients compared to that in control subjects, and an OTU corresponding to Corynebacterium species was more abundant in all groups other than gastric cancer patients (P < 0.01). In addition, the relative abundances of OTUs corresponding to Fusobacterium nucleatum, Streptococcus parasanguinis II, and Neisseria species were significantly higher in tongue/pharyngeal cancer patients compared to their abundances in control subjects (P < 0.01). The relative abundance of an OTU corresponding to the Neisseria species was also significantly higher in gastric cancer patients and that of an OTU corresponding to Actinomyces odontolyticus was significantly higher in colorectal cancer patients (P < 0.01). These results suggest that the salivary microbiota might be associated with various digestive tract cancers.

Dairy consumption and risk of functional disability in an elderly Japanese population: the Hisayama Study.

BACKGROUND: Little is known about the association between dairy intake and risk of functional disability in the elderly. OBJECTIVES: We examined the influence of dairy intake on the development of declining functional capacity and activities of daily living (ADL) in a prospective cohort study of an elderly population. METHODS: A total of 859 community-dwelling Japanese residents, aged ≥65 y without functional disability, were followed up for 7 y. Functional capacity impairment was defined as a Tokyo Metropolitan Institute of Gerontology Index of Competence score of ≤12, and ADL disability was defined as a Barthel Index score of ≤95. Dairy intake was evaluated using a 150-item semiquantitative food frequency questionnaire, grouped into quartiles. The RR of dairy intake on incident functional disability was computed using a Poisson regression model. RESULTS: The multivariable-adjusted RR of impaired functional capacity decreased significantly with increasing dairy intake levels (RR [95% CI]: quartile 1, 1.00 [reference]; quartile 2, 0.85 [0.71, 1.02]; quartile 3, 0.81 [0.68, 0.98]; and quartile 4, 0.74 [0.61, 0.90]; P-trend = 0.001). Regarding the three subscales of functional capacity, the inverse association between dairy intake and risk for impairment of intellectual activity and social role remained significant (P-trend = 0.0009 and 0.02, respectively), but such an association was not observed for instrumental ADL. The multivariable-adjusted risk of ADL disability also decreased weakly but significantly with elevating dairy intake (P-trend = 0.04). A similar association was seen for severity of functional disability (P-trend = 0.002). However, the magnitude of these associations was attenuated after further adjustment for protein intake. CONCLUSION: Our findings suggest that higher dairy intake is associated with a lower risk of functional disability and its progression in the elderly, probably via an increase in protein intake.

Associations of Overweight, Obesity, and Underweight With High Serum Total Cholesterol Level Over 30 Years Among the Japanese Elderly: NIPPON DATA 80, 90, and 2010.

BACKGROUND: The trend of association between overweight and high serum total cholesterol (TC) among the elderly is unclear. In addition, there is little evidence of risk of underweight for high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data. METHODS: Data of the National Survey on Circulatory Disorders and National Health and Nutrition Survey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was defined as 220 mg/dL and above. For participants aged ≥50 years, sex-specific odds ratios (ORs) of overweight or underweight compared with normal body mass index participants for high TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia. RESULTS: A total of 5,734, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980, 1990, 2000, and 2010, respectively. Although overweight was positively and significantly associated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83-3.24 and 0.92; 95% CI, 0.66-1.27 among men and 1.43; 95% CI, 1.18-1.72 and 1.08; 95% CI, 0.81-1.44 among women, respectively). While underweight was inversely and significantly associated with high TC in 1980, the association also gradually weakened among women (ORs in 1980 and 2010 were 0.28; 95% CI, 0.12-0.60 and 0.37; 95% CI, 0.10-1.28 among men and 0.39; 95% CI, 0.26-0.57 and 0.96; 95% CI, 0.58-1.57 among women, respectively). CONCLUSIONS: These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.

Pooled Analysis of the Associations between Body Mass Index, Total Cholesterol, and Liver Cancer-related Mortality in Japan

Objective: We employed a large-scale pooled analysis to investigate the association of liver cancer-related mortality with being overweight/obese and total cholesterol (TC) levels, since limited and inconsistent data on these associations exist in Japan. Methods: A total of 59,332 participants (23,853 men and 35,479 women) from 12 cohorts without a history of cancer who were followed for a median of 14.3 years were analyzed. A sex-specific stratified Cox proportional hazards model adjusted for age and other potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for liver cancer-related mortality. Results: A total of 447 participants (266 men and 181 women) died of liver cancer within the follow-up period. Individuals classified as having a high BMI (≥25.0 kg/m2) and low TC levels (<160 mg/dL) had a significantly increased risk for liver cancer-related mortality (HR 7.05, 95% CI 4.41­11.26 in men; HR 8.07, 95% CI 4.76­13.67 in women) when compared with those in the intermediate BMI (18.5­24.9 kg/m2) and TC (160­219 mg/dL) categories. These associations remained after limiting the follow-up duration to >5 years. Conclusion: Being overweight/obese, combined with low TC levels, was strongly associated with liver cancer-related mortality in the EPOCH-JAPAN.

Prevalence of and risk factors for cerebral microbleeds in a general Japanese elderly community.

BACKGROUND: We investigated the prevalence of and risk factors for cerebral microbleeds (CMBs) in a cross-sectional study of a general population of Japanese elderly. METHODS: In 2012, brain MRI scanning at 1.5T and comprehensive health examination were conducted for 1281 residents aged 65 years or older. CMBs were defined as ovoid hypointensity lesions less than 10 mm in diameter on T2*-weighted images and classified into deep/infratentorial or lobar CMBs. Age- and sex-specific and overall prevalence of CMBs were estimated, and the associations of traditional cardiovascular risk factors and APOE polymorphism with the presence of CMBs were examined using a logistic regression analysis. RESULTS: The crude prevalences of total, deep/infratentorial, and lobar CMBs were 18.7% (n = 240), 13.5% (n = 173), and 9.6% (n = 123), respectively. The prevalence of total CMBs was 23.0% in men and 15.5% in women and increased with aging in both sexes (both p for trend <0.01). Hypertension was significantly associated with the presence of both deep/infratentorial and lobar CMBs. Lower serum total cholesterol was a significant risk factor for deep/infratentorial CMBs, but not for lobar CMBs, while APOE ε4 carriers had a significantly higher likelihood only of lobar CMBs compared with noncarriers. CONCLUSIONS: Our study suggests that approximately 1 of 5 Japanese elderly people have CMBs, and that risk factors for deep/infratentorial and lobar CMBs are different, indicating the distinct pathologic backgrounds of these lesions.

Prevalence and Risk Factors for Polypoidal Choroidal Vasculopathy in a General Japanese Population: The Hisayama Study.

PURPOSE: To estimate the prevalence and risk factors for polypoidal choroidal vasculopathy (PCV) in a general Japanese population. METHODS: This population-based, cross-sectional study was conducted in 2007 with subjects from the Hisayama Study. Of the 3,648 residents in Hisayama, Japan, 2,663 who were ≥ 50 years old were enrolled in this study. The characteristics of PCV were determined by fundus examination or based on indocyanine green and fluorescein angiographic findings. We evaluated the contributions of the risk factors for PCV. RESULTS: Among the 207 participants with age-related macular degeneration (AMD), 174 (6.5%) had early AMD, and 33 (1.2%) had late AMD, including 10 participants with PCV (0.4%). Male and smoking habit were significant risk factors for the development of PCV. CONCLUSIONS: The prevalence of PCV is higher among Japanese subjects than Caucasians in Western countries. Male gender and smoking habit were significant risk factors for PCV in a general Japanese population.

Secular trends in the incidence, risk factors, and prognosis of transient ischemic attack in Japan: The Hisayama Study.

BACKGROUND AND AIMS: We aimed to investigate secular trends in the incidence, risk factors, and prognosis of transient ischemic attack (TIA) in a general Japanese population. METHODS: Two cohorts consisting of stroke-free Japanese individuals aged ≥40 years in 1961 (n = 1621) and 1988 (n = 2646) were followed up for 24 years. The associations of potential risk factors with the development of TIA were estimated by a Cox proportional hazards model. The influence of TIA on the risk of total stroke over the subsequent 10 years was compared between the sub-cohorts of subjects with TIA and age- and sex-matched control subjects from each cohort. RESULTS: During follow-up, 28 subjects in the 1961 cohort and 34 in the 1988 cohort experienced TIA. The age-standardized incidence of TIA was significantly lower in the 1988 cohort than the 1961 cohort (0.66 vs. 1.01 per 1000 person-years, p = 0.02). While elevated systolic blood pressure was significantly associated with the risk of TIA in both cohorts, glucose intolerance and higher serum cholesterol levels were associated with TIA risk only in the 1988 cohort. The subjects experiencing TIA had approximately 7-8-fold higher risks for the 10-year incidence of total and ischemic strokes compared with the corresponding control subjects without TIA both in the 1961 and 1988 sub-cohorts, and the relative risks were not significantly different between sub-cohorts. CONCLUSIONS: Our results suggest that the incidence of TIA decreased during the past half century, probably due to the spread of antihypertensive treatments in the general Japanese population.

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community-Dwelling Japanese Elderly: The Hisayama Study.

BACKGROUND: Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). METHODS AND RESULTS: A total of 1562 community-dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all-cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin-creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow-up, 358 subjects developed all-cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable-adjusted risks of all-cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78-1.60], 1.65 [1.18-2.30], and 1.56 [1.11-2.19] for UACR of ≤6.9, 7.0-12.7, 12.8-29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77-1.86], 1.75 [1.16-2.64], and 1.58 [1.03-2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46-2.29], 1.94 [0.96-3.95], and 2.19 [1.09-4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of <60 mL/min per 1.73 m2 had 3.3-fold greater risk of VaD than those with UACR <12.8 mg/g and eGFR of ≥60 mL/min per 1.73 m2. CONCLUSIONS: Albuminuria is a significant risk factor for the development of both AD and VaD in community-dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD.

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.

Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation.

Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid ß (Aß) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aß pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App NL-G-F/NL-G-F and 3xTg-AD-H mouse models. Genes commonly altered in App NL-G-F/NL-G-F and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App NL-G-F/NL-G-F cortex as Aß amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App NL-G-F/NL-G-F cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aß amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.

White-coat and masked hypertension are associated with albuminuria in a general population: the Hisayama Study.

Epidemiological and clinical studies have investigated the influence of hypertension on chronic kidney disease (CKD), but limited data are available for the associations of white-coat hypertension (WCHT), masked hypertension (MHT) and sustained hypertension (SHT) with kidney dysfunction in general populations. We examined the associations of these types of hypertension with CKD (albuminuria and reduction in estimated glomerular filtration rate (eGFR)) in a cross-sectional survey of 2974 community-dwelling Japanese aged ⩾40 years. The types of hypertension were defined based on combined measurements of clinic and home blood pressures. Albuminuria was determined as urinary albumin-creatinine ratio (UACR) levels ⩾30.0 mg g-1. The eGFR was calculated using the Japanese equation. The age- and sex-adjusted geometric mean of the UACR values was significantly higher in the subjects with WCHT (20.2 mg g-1), MHT (19.6 mg g-1) and SHT (31.6 mg g-1) than in those with normotension (NT) (12.5 mg g-1) (all P<0.001). Compared with NT, all types of hypertension were significantly associated with an increased likelihood of albuminuria (the age- and sex-adjusted prevalence of albuminuria; NT 14.1%, WCHT 26.3%, MHT 26.4% and SHT 43.3%; all P<0.001). These associations remained significant even after adjustment for other risk factors. However, the age- and sex-adjusted mean of eGFR and the prevalence of low eGFR (<60 ml min-1 per 1.73 m2) did not differ between NT and the three hypertension types. The associations of the types of hypertension with the likelihood of CKD were similar to those for albuminuria. Our findings suggest that WCHT, MHT and SHT are associated with albuminuria in the general Japanese population.

Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study.

BACKGROUND: Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia. METHODS: A total of 1674 community-dwelling Japanese elderly without dementia, ≥60 years of age, were followed up for 5 years (2007-2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model. RESULTS: During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age- and sex-adjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend <0.05). These associations remained unchanged after adjustment for potential confounding factors, including home SBP. Compared with subjects in the first quartile of CoV levels of home SBP, the risks of the development of all-cause dementia, VaD, and AD were significantly higher in those in the fourth quartile (hazard ratio=2.27, 95% confidence interval=1.45-3.55, P<0.001 for all-cause dementia; hazard ratio=2.79, 95% confidence interval=1.04-7.51, P=0.03 for VaD; hazard ratio=2.22, 95% confidence interval=1.31-3.75, P<0.001 for AD). Similar associations were observed for CoV levels of home diastolic blood pressure. Meanwhile, home SBP levels were significantly associated with the risk of VaD but not with the risks of all-cause dementia and AD. There was no interaction between home SBP levels and CoV levels of home SBP on the risk of each subtype of dementia. CONCLUSIONS: Our findings suggest that increased day-to-day blood pressure variability is, independently of average home blood pressure, a significant risk factor for the development of all-cause dementia, VaD, and AD in the general elderly Japanese population.

The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study.

BACKGROUND: Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations. METHODS: A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002-2012). The levels of the serum EPA:AA ratio were categorized into quartiles (<0.29, 0.29-0.41, 0.42-0.60, and >0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations. RESULTS: During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend<0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15-3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend<0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend>0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers. CONCLUSIONS: These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.

Alternative Measures of Hyperglycemia and Risk of Alzheimer's Disease in the Community: The Hisayama Study.

Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.

Morning and Evening Blood Pressures Are Associated With Intima-Media Thickness in a General Population　- The Hisayama Study.

BACKGROUND: The association of morning and evening home blood pressures (HBPs) with carotid atherosclerosis has been uncertain in general populations, so we aimed to investigate it in a general Japanese population.Methods and Results:We performed a cross-sectional survey of 2,856 community-dwelling individuals aged ≥40 years to examine the association of morning and evening HBPs with carotid mean intima-media thickness (IMT). The age- and sex-adjusted geometric averages of carotid mean IMT increased significantly with increasing morning HBP (optimal: 0.67 mm; normal: 0.69 mm; high normal: 0.72 mm; grade 1 hypertension: 0.74 mm; and grade 2+3 hypertension: 0.76 mm) and with increasing evening HBP (0.68 mm, 0.71 mm, 0.73 mm, 0.76 mm, and 0.78 mm, respectively) (both P for trend <0.001). These associations remained significant even after adjusting for potential confounding factors. Likewise, both isolated morning hypertension (morning HBP ≥135/85 mmHg and evening HBP <135/85 mmHg) and isolated evening hypertension (evening HBP ≥135/85 mmHg and morning HBP <135/85 mmHg) as well as sustained hypertension (both morning and evening HBP ≥135/85 mmHg) were significantly associated with thicker mean IMT. CONCLUSIONS: Our findings suggested that both morning and evening HBPs were significantly associated with carotid atherosclerosis in this general Japanese population.