Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

Non-alcoholic beverages intake and risk of CVD among Japanese men and women: the Japan Public Health Center study.

The association between the intake of non-alcoholic beverages and CVD in Asians is uncertain. The intake of non-alcoholic beverages was estimated in 77 407 participants of the Japan Public Health Centre-based cohort study aged 45-74 years. The Cox regression calculated the hazard ratios (HR) and 95 % CI for incident CVD according to sex-specific quintiles of intake of non-alcoholic beverages. A total of 4578 incident CVD (3751 strokes and 827 CHD) were diagnosed during a 13·6-year median follow-up. The risks of stroke and total CVD were lower for the highest v. lowest intake quintiles of non-alcoholic beverages in men and women: the multivariable HRs (95 % CIs) were 0·82 (0·71, 0·93, Ptrend = 0·005) and 0·86 (0·76, 0·97, Ptrend = 0·02), respectively, in men and were 0·73 (0·63, 0·86, Ptrend = 0·003) and 0·75 (0·65, 0·87, Ptrend = 0·005), respectively, in women. The reduced risk was evident for both ischaemic and haemorrhagic strokes and was mainly attributable to green tea consumption. The intake of non-alcoholic beverages from coffee and other beverages was not associated with the risk of CVD in both men and women. Also, there was no association between the intake of non-alcoholic beverages and the risk of CHD in either sex. In conclusion, the risks of stroke and total CVD were lower with a higher intake of non-alcoholic beverages in Japanese men and women.

Consumption of flavonoid-rich fruits, flavonoids from fruits and stroke risk: a prospective cohort study.

We sought to examine the prospective associations of specific fruit consumption, in particular flavonoid-rich fruit (FRF) consumption, with the risk of stroke and subtypes of stroke in a Japanese population. A study followed a total of 39 843 men and 47 334 women aged 44-76 years, and free of CVD, diabetes and cancer at baseline since 1995 and 1998 to the end of 2009 and 2012, respectively. Data on total and specific FRF consumption for each participant were obtained using a self-administrated FFQ. The hazard ratios (HR) of stroke in relation to total and specific FRF consumption were estimated through Cox proportional hazards regression models. During a median follow-up of 13·1 years, 4091 incident stroke cases (2557 cerebral infarctions and 1516 haemorrhagic strokes) were documented. After adjustment for age, BMI, study area, lifestyles, dietary factors and other risk factors, it was found that total FRF consumption was associated with a significantly lower risk of stroke in women (HR = 0·70; 95 % CI 0·58, 0·84), while the association in men was not significant (HR = 0·93; 95 % CI 0·79, 1·09). As for specific FRF, consumptions of citrus fruits, strawberries and grapes were found associated with a lower stroke risk in women. Higher consumptions of FRF, in particular citrus fruits, strawberries and grapes, were associated with a lower risk of developing stroke in Japanese women.

Salt taste perception and blood pressure levels in population-based samples: the Circulatory Risk in Communities Study (CIRCS).

To examine the associations of salt perception with salt intake and blood pressure levels in general populations, we performed a cross-sectional study in two communities where salt intake level is different, Akita and Osaka in Japan. Taste perception (detection for certain taste and recognition for salt taste) was determined using a Na-impregnated test strip for 1024 Akita and 1199 Osaka adults aged 30-74 years. The proportions of detection for 0·1 % salt were 61, 62, 79, and 79 % in Akita men, Osaka men, Akita women and Osaka women, respectively. The corresponding proportions of not recognising of 1·6 % salt taste (>1·6 %) were 34, 30, 16 and 21 %. Detection threshold was higher in Akita than in Osaka for women aged 60-74 years, and recognition threshold was lower in Akita than in Osaka for women aged 30-59 and 60-74 years. The high detection (≥0·4 %) and recognition (>1·6 %) thresholds of salt taste were associated with higher salt intake scores for Akita men aged 30-59 years, whose detection and recognition thresholds tended be positively associated with systolic and diastolic blood pressures (SBP and DBP) after adjustment for potential confounders. Among Akita elderly men, detection threshold tended to be positively associated with SBP and DBP, while among Akita middle-aged women, recognition threshold was associated with SBP. In conclusion, the high thresholds of salt perception were inversely associated with salt intake for Akita middle-aged men and with blood pressure levels for Akita middle-aged and elderly men and middle-aged women.

Serum Albumin and Risks of Stroke and Its Subtypes　- The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: Few studies have investigated the association between serum albumin levels and the risk of stroke subtypes among the general Japanese population.Methods and Results:In this study, 5,071 men and 7,969 women aged 40-74 years, initially free from stroke, coronary artery disease, and kidney and hepatic failure, and residing in 4 Japanese communities completed a baseline risk factor survey between 1985 and 1994. During the 24-year follow-up, 528 men and 553 women experienced stroke. In the entire study cohort, multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) of total stroke, ischemic stroke, and intracerebral hemorrhage for the lowest vs. highest quartiles of serum albumin were 1.45 (1.18-1.77), 1.52 (1.17-1.97), and 1.57 (1.04-2.37), respectively. In men, multivariable HRs (95% CIs) for total stroke, ischemic stroke, and intracerebral hemorrhage in the lowest vs. highest serum albumin quartile were 1.44 (1.07-1.92), 1.48 (1.03-2.11) and 1.71 (0.92-3.18), respectively, whereas in women they were 1.50 (1.13-1.99), 1.63 (1.11-2.39), and 1.56 (0.89-2.74), respectively. Similar inverse associations were observed for each of the ischemic stroke subtypes, but not for subarachnoid hemorrhage. CONCLUSIONS: Low serum albumin levels were associated with an increased risk of total stroke, ischemic stroke, ischemic stroke subtypes, and intracerebral hemorrhage.

Gene Suppression of the Chloride Channel 2 Suppressed TGF-ß1-Induced Proliferation, Collagen Synthesis, and Collagen Gel Contraction Mediated by Conjunctival Fibroblasts.

BACKGROUND: Excessive scarring of filtering blebs is the main cause of surgical failure in glaucoma. Previous studies have highlighted the role of chloride channels (ClCs) in scar formation, whereas the role of ClCs in scarring of filtering blebs has not been studied. OBJECTIVES: The objective of this study was to investigate the effects of the chloride channel 2 (ClC-2) on scar formation of filtering blebs after glaucoma filtering surgery. METHODS: ClC-2 siRNA-transfected human conjunctival fibroblasts (HConFs) were cultured in type 1 collagen gels in the presence of transforming growth factor (TGF)-ß1. Collagen gel contraction was evaluated based on the gel area. 3D-cultured HConFs were treated with the ClC blocker NPPB in the presence of TGF-ß1, and cell proliferation collagen synthesis and contractility were measured. The expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in HConFs were assessed by Western blotting and qPCR. RESULTS: TGF-ß1 induced cell proliferation, cell cycle progression, collagen synthesis, and collagen gel contraction in HConFs. TGF-ß1 increased MMP-2 and MMP-9 levels but inhibited the expression of TIMPs. NPPB and ClC-2 siRNA transfection inhibited TGF-ß2-induced cell proliferation, cell cycle progression, collagen synthesis, and collagen gel contraction, mediated by HConFs. TGF-ß2-induced increases in MMP-2 and MMP-9 were also inhibited by NPPB and ClC-2 siRNA transfection, but TIMP expression was increased by NPPB and ClC-2 siRNA transfection. CONCLUSIONS: These findings demonstrate that ClC-2 ClCs modulate TGF-ß1-induced cell proliferation, collagen synthesis, and collagen gel contraction of HConFs by attenuating MMP-2 and MMP-9 production and by stimulating TIMP1 production. NPPB may therefore prove to be of clinical value for the inhibition of scar formation of filtering blebs.

Determinants of alcohol consumption and marijuana use among young adults in the Republic of Palau.

BACKGROUND: This study aimed to describe the status of alcohol consumption and drug use among young adults as well as their determinants. METHODS: We conducted a cross-sectional study of 356 young adults (aged 18 to 24 years) living in Palau in 2013. The prevalence of self-reported alcohol and marijuana usage were compared within and between sexes, age groups, ethnicities, and education levels. RESULTS: The proportion of current drinking was higher in people aged 21-24 than in those aged 18-20 (73.2% vs. 60.9%, p = 0.09 in men and 48.3% vs. 30.0%, p = 0.02 in women), while that of marijuana use did not differ between the age groups. The proportions of current drinking and marijuana use were higher in Palauan than in other ethnicities (current drinking: 70.6% vs. 40.6%, p = 0.005 in men and 38.8% vs. 16.6%, p = 0.04 in women; lifetime marijuana use: 80.0% vs. 52.9%, p = 0.02 in men and 56.1% vs. 30.6%, p = 0.09 in women). The proportion of frequent (3 times or more) marijuana users was higher for the lower educated than for the higher educated (62.5% vs. 32.1%, p < 0.001 in men and 33.9% vs. 24.4%, p = 0.12 in women). CONCLUSIONS: Sex, age, ethnicity, and education were significant determinants of alcohol and marijuana use.

Consumption of flavonoid-rich fruits and risk of CHD: a prospective cohort study.

Although the association between fruit consumption and CHD risk has been well studied, few studies have focused on flavonoid-rich fruits (FRF), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87 177 men and women aged 44-75 years who were free of CVD and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a FFQ. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13·2 years, we identified 1156 incident CHD cases. After full adjustment for covariates including demographics, lifestyles and dietary factors, the HR were 0·93 (95 % CI 0·77, 1·11), 0·91 (95 % CI 0·75, 1·11), 0·84 (95 % CI 0·67, 1·04) and 0·78 (95 % CI 0·62, 0·99) for the second, third, fourth and fifth quintiles compared with the lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRF, in particular, citrus fruits, may be associated with a lower risk of developing CHD.

Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling.

AIMS: Oxidative damage plays a vital role in the pathogenesis of age-related macular degeneration (AMD). Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, possesses several pharmacological functions, such as anti-inflammatory and antioxidative properties. However, the effects and mechanism of EX4 on oxidative stress in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H2O2) remain unclear. The present study aimed to investigate the protective mechanism of EX4 on human RPE cells subjected to oxidative stress. METHODS: Human RPE ARPE-19 cells were treated with H2O2 to induce oxidative damage. Cell viability was determined by Cell Counting Kit-8 and lactate dehydrogenase assay. Levels of intracellular reactive oxygen species (ROS), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were measured using commercial kits. The expression of nuclear factor erythroid 2-related factor-2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1) was measured using reverse transcription quantitative polymerase chain reaction assay and western blot, respectively. RESULTS: H2O2 significantly induced oxidative stress to reduce viability of RPE cells and increased intracellular ROS generation. EX4 significantly ameliorated H2O2-induced oxidative damage by reducing intracellular ROS generation, decreasing MDA concentration, and increasing antioxidant enzymes activities (SOD and GSH). In addition, EX4 markedly increased expression of NRF2, HO-1, and NQO-1 and significantly improved protein expression of NRF2 and HO-1 in H2O2-treated ARPE-19 cells, caused by increased nuclear NRF2 protein expression. NRF2 knockdown by targeted siRNA alleviated EX4-mediated HO-1 expression and significantly nullified EX4-mediated RPE cell protection against H2O2. CONCLUSIONS: EX4 attenuated oxidative damage induced by H2O2 in ARPE-19 cells through the activation of the NRF2 signaling pathway. The findings suggested that EX4 may be a potential therapeutic agent for the treatment of AMD.

Sleep duration and risk of breast cancer: The JACC Study.

PURPOSE: The evidence on beneficial or adverse effects of sleep duration on risk of breast cancer remains controversial and limited, especially in Asia. METHODS: A prospective study of 34,350 women aged 40-79 years in whom sleep duration, and menstrual and reproductive histories were determined by a self-administered questionnaire. The follow-up period was from 1988 to 2009, and hazard ratios (HRs) with 95% confidence intervals (CIs) of breast cancer incidence were calculated for shorter sleep duration in reference to sleep duration of ≥ 8 h/day by Cox proportional hazard models. RESULTS: During 19.2-year median follow-up (236 cases), we found a significant inverse association between sleep duration and risk of breast cancer, especially among postmenopausal women and women with low parity (nulliparous and women with < 3 children); the multivariable HRs (95% CIs) among postmenopausal women who reported 7 h/day and ≤ 6 h/day of sleep in reference to ≥ 8 h/day were 1.49 (0.81-2.76) and 1.98 (1.08-3.70) (P for trend = 0.028), respectively, and the corresponding values among women with low parity were 1.50 (0.96-2.35) and 1.76 (1.01-2.79) (P for trend = 0.018). CONCLUSIONS: Short sleep duration was associated with increased risk of incident breast cancer, especially among postmenopausal women and women with low parity.

Prevalence and Correlates of Dyslipidemia Among Men and Women in Palau: Findings of the Palau STEPS Survey 2011-2013.

BACKGROUND: Epidemiological evidence of dyslipidemia in Pacific Island countries is limited despite the knowledge that non-communicable diseases have a high burden in the region. We aimed to examine the prevalence and correlates of dyslipidemia among residents of Palau. METHODS: The Palau STEPwise approach to Surveillance (STEPS), which was conducted from 2011 through 2013, comprised three parts: behavioral risk factors; physical measurements; and biochemical tests, covering areas such as blood lipids. We used STEPS-generated data to perform a cross-sectional study of 2,184 randomly selected Palau residents, comprising Palauans and non-Palauans aged 25-64 years. RESULTS: The age-adjusted mean BMI was 29.3 kg/m2 in men and 29.9 kg/m2 in women; age-adjusted mean triglycerides value was 182 mg/dL in men and 166 mg/dL in women; and age-adjusted mean cholesterol was 178 mg/dL in men and 183 mg/dL in women. The prevalence of overweight/obesity (BMI ≥25 kg/m2) was 75% in men and 76% in women, and those of hypertriglyceridemia (triglycerides ≥150 mg/dL) and hypercholesterolemia (total cholesterol ≥200 mg/dL) were 48% in men and 41% in women and 18% in men and 23% in women, respectively. Mean values of total cholesterol were 177 mg/dL in Palauan men and 182 mg/dL in non-Palauan men. Mean values of triglycerides were 171 mg/dL in Palauan women and 150 mg/dL in non-Palauan women. Women living in rural areas showed a higher mean value of total cholesterol than those in urban areas. CONCLUSION: We found a high mean BMI and high prevalence of overweight/obesity and hypertriglyceridemia, but low mean total cholesterol and a low prevalence of hypercholesterolemia in Palau. Lipid profiles varied by age, ethnicity, and living area.

The Circulatory Risk in Communities Study (CIRCS): A Long-Term Epidemiological Study for Lifestyle-Related Disease Among Japanese Men and Women Living in Communities.

The Circulatory Risk in Communities Study (CIRCS) is an ongoing community-based epidemiological study of lifestyle-related disease involving dynamic prospective cohorts of approximately 12,000 adults from five communities of Japan: Ikawa, Ishizawa and Kita-Utetsu (Akita Prefecture), Minami-Takayasu (Osaka Prefecture), Noichi (Kochi Prefecture), and Kyowa (Ibaraki Prefecture). One of the most notable features of CIRCS is that it is not only an observational cohort study to identify risk factors for cardiovascular diseases (CVD), such as stroke, coronary heart disease, and sudden cardiac death, but it also involves prevention programs for CVD. Using basic, clinical, epidemiological, and statistical techniques, CIRCS has clarified characteristics of CVD and the related risk factors to develop specific methodologies towards CVD prevention in Japanese middle-aged or older adults for more than half a century.

Association between vitamin B group supplementation with changes in % flow-mediated dilatation and plasma homocysteine levels: a randomized controlled trial.

There is limited evidence examining the association between B vitamin supplementation and improved endothelial function via lowering plasma homocysteine levels. This study investigated whether low-dose B vitamin supplementation improves endothelial dysfunction in Japanese adults with one or more components of metabolic syndrome. A randomized, controlled, crossover trial, without a washout period or blinding of subjects, was conducted from May-September, 2010. The subjects were 127 Japanese men and women aged 40-65 years who had at least one component of metabolic syndrome without medication. Participants took a supplement drink for two months but were divided into early intervention or later intervention groups. The flow-mediated dilatation, plasma homocysteine level, serum B-vitamins, and vitamin C levels were measured. A significant increase in serum B vitamins and vitamin C levels, and a reduction in plasma homocysteine levels were observed. The mean serum homocysteine level pre- and post-intervention was 9.8 and 8.2 µmol/L in the early intervention group and 10.8 and 7.4 µmol/L in the later intervention group (p<0.01). However, no significant changes in flow-mediated dilatation was found. Low-dose multivitamin supplementation including B vitamins is associated with a significant reduction in plasma homocysteine levels among patients with one or more components of metabolic syndrome. This study was registered at the University Hospital Medical Information Network (UMIN) centre, and has the identifier UMIN000004436.

Sleep Shortage Is Associated With Postherpetic Neuralgia Development Through Hyperesthesia and Acute Pain Intensity: A Community-Based Prospective Cohort Study.

OBJECTIVES: There have been no community-based studies investigating the association between sleep duration and postherpetic neuralgia (PHN) development. The aim of the current study was to examine the association of sleep with herpes zoster (HZ) incidence and PHN. METHODS: In total, 12,329 residents (ages 50 to 103 years) of Shozu County, Japan, participated in our study from December 2009 to November 2010 and were followed up for 3 years. At baseline, the participants completed self-administered health questionnaires, including those on usual sleep duration. Three dermatologists diagnosed HZ on the basis of clinical symptoms and virus identification testing by polymerase chain reaction and serological tests, and evaluated pain using a modified Zoster Brief Pain Inventory survey form via telephone. We used a Cox proportional hazard regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HZ and PHN. We also performed mediation analysis to examine whether hyperesthesia and acute pain intensity mediated the association between sleep shortage and chronic pain intensity. RESULTS: During follow-up, 400 cases of HZ were identified. Of these, 55 participants developed PHN. Sleep duration was not associated with HZ incidence. Sleep shortage increased the risk for PHN (HR 2.02 [95% CI: 1.06 to 3.85]). Hyperesthesia and acute pain intensity mediated the association between sleep shortage and chronic pain intensity (indirect/total effect ratio = 50% mediation). CONCLUSIONS: Sleep shortage was associated with increased risk for PHN, and hyperesthesia and acute pain intensity appeared to mediate this association. Sleep shortage may be a novel risk factor for PHN.

Relationship Between Dietary Vitamin D and Deaths From Stroke and Coronary Heart Disease: The Japan Collaborative Cohort Study.

BACKGROUND AND PURPOSE: There is growing evidence about the importance of vitamin D for cardiovascular health. Therefore, we examined the relationship between dietary vitamin D intake and risk of mortality from stroke and coronary heart disease in Japanese population. METHODS: A prospective study encompassing 58 646 healthy Japanese adults (23 099 men and 35 547 women) aged of 40 to 79 years in whom dietary vitamin D intake was determined via a self-administered food frequency questionnaire. The median follow-up period was 19.3 years (1989-2009). The hazard ratios and 95% confidence intervals of mortality were calculated using categories of vitamin D intake. RESULTS: During 965 970 person-years of follow-up, 1514 stroke and 702 coronary heart disease deaths were documented. Vitamin D intake was inversely associated with risk of mortality from total stroke especially intraparenchymal hemorrhage but not from coronary heart disease; the multivariable hazard ratios (95% confidence intervals) for the highest (≥440 IU/d) versus lowest (<110 IU/D) categories of vitamin D intake were 0.70 (0.54-0.91; P for trend=0.04) for total stroke and 0.66 (0.46-0.96; P for trend=0.04) for intraparenchymal hemorrhage. CONCLUSIONS: Dietary vitamin D intake seems to be inversely associated with mortality from stroke.

Serum Fatty Acid and Risk of Coronary Artery Disease　- Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: Few prospective studies have explored the association between fatty acids (FA) and risk of CAD. Understanding of the role of each individual serum FA as a coronary risk or protective factor is still limited. The aim was to investigate which serum FA are associated with the incidence of CAD in Japanese subjects. Methods and Results: A prospective nested case-control study of 40-85-year-old Japanese subjects was undertaken using frozen serum samples collected from 12,840 participants who participated in cardiovascular risk surveys from 1984 to 1998 for 1 community and 1989-1997 for 2 other communities. Three control subjects per case were matched by sex, age, community, year of serum storage and fasting status. By 2005 we had identified 152 incident cases of CAD. Mean n-3-polyunsaturated and saturated FA did not differ between cases and controls, while mean n-6-polyunsaturated FA was higher in controls compared with cases. The multivariable OR of CAD for the highest vs. lowest quartiles of miristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1), and linoleic acid (18:2) were 2.8 (95% CI: 1.5-5.2), 2.7 (95% CI: 1.4-5.5), 3.2 (95% CI: 1.7-6.1) and 0.4 (95% CI: 0.2-0.7), respectively. CONCLUSIONS: High serum miristic acid, palmitic acid and palmitoleic acid have an adverse effect, and high serum linoleic acid had a protective effect, on the risk of CAD.

Nonfasting Glucose and Incident Stroke and Its Types　- The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: The effect of postprandial glucose on the risk of cardiovascular disease has been emphasized, but it is controversial whether nonfasting glucose is related to incident stroke and its types.Methods and Results:We investigated the associations of nonfasting glucose with incident stroke and its types among 7,198 participants aged 40-74 years from the Circulatory Risk in Communities Study, enrolled in 1995-2000. We estimated multivariable hazard ratios (HR) using Cox proportional hazard models. Over a median follow-up of 14.1 years, 291 cases of total stroke (ischemic strokes: 191 including 109 lacunar infarctions) were identified. Nonfasting glucose concentration was associated with greater risk of incident total stroke, ischemic stroke and lacunar infarction when modeled categorically (for prediabetic type: 7.8-11.0 mmol/L vs. normal type: <7.8 mmol/L among all subjects, HR for lacunar infarction was 2.02, 95% confidence interval (CI): 1.19, 3.43) or continuously (per one standard deviation increment among all subjects, HR for lacunar infarction was 1.29, 95% CI: 1.15, 1.45). Diabetic type showed similar results. Population attributable fractions of nonfasting hyperglycemia were 13.2% for ischemic stroke and 17.4% for lacunar infarction. CONCLUSIONS: Nonfasting glucose concentration, either as a diagnosis of prediabetic and diabetic types or as a continuous variable, proved to be an independent predictor significantly attributed to incident total stroke, especially ischemic stroke and lacunar infarction, in the general population.

Water intake from foods and beverages and risk of mortality from CVD: the Japan Collaborative Cohort (JACC) Study.

OBJECTIVE: To examine the association of water intake with risk of mortality from CVD. DESIGN: Prospective cohort study.Setting/SubjectsA total of 22 939 men and 35 362 women aged 40-79 years enrolled in the Japan Collaborative Cohort (JACC) Study with available data regarding water intake from foods and beverages. The underlying causes of death were determined based on the International Classification of Diseases. RESULTS: During the median 19·1 years of follow-up, 1637 men and 1707 women died from CVD. There was an inverse trend between high water intake and risk of CVD in both sexes. Compared with participants in the lowest quintile of water intake, the multivariable-adjusted hazard ratios (95 % CI) for mortality from total CVD in the highest quintile of water intake were 0·88 (0·72, 1·07; P for trend=0·03) in men and 0·79 (0·66, 0·95; P for trend=0·10) in women. Those for CHD were 0·81 (0·54, 1·21; P for trend=0·06) in men and 0·60 (0·39, 0·93; P for trend=0·20) in women. Reduced risk of mortality from ischaemic stroke was also observed among women in the highest water intake quintile: 0·70 (0·47, 0·99; P for trend=0·19). There was no association between water intake and mortality from haemorrhagic stroke in either sex. CONCLUSIONS: Higher intake of fluids from foods and beverages was associated with reduced risk of cardiovascular mortality in both sexes and reduced risk of ischaemic stroke in women in Japan.

Impact of Hypertension and Subclinical Organ Damage on the Incidence of Cardiovascular Disease Among Japanese Residents at the Population and Individual Levels　- The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: In Japan, a community-based screening program for cardiovascular disease (CVD) has been effective in preventing stroke and coronary artery disease (CAD). The present study aimed to clarify which risk factors assessed at the screening examinations affect the incidence of CVD and the magnitude of the association after the late 1990 s.Methods and Results:We conducted a 12.5-year prospective study of 10,612 Japanese residents aged 40-74 years between 1995 and 2000, initially free of CVD and who underwent the screening examinations. During the follow-up, 364 cases of stroke and 137 cases of CAD were identified. The population attributable fraction of stroke was the largest for hypertension (HT; 46%), while the relative risk of stroke was the highest for atrial fibrillation (multivariable hazard ratio, 4.9; 95% confidence interval, 2.9-8.3). The population attributable fraction of CAD was relatively large for HT, current smoking, and high non-high-density lipoprotein cholesterol (20-29%). A dose-response relationship was found between the incidence of these cardiovascular events and the number of comorbid hypertensive subclinical organ damage markers: funduscopic changes, ST-T changes on ECG at rest, proteinuria and low estimated glomerular filtration rate. CONCLUSIONS: HT and hypertensive subclinical organ damage are significantly associated with incident stroke and CAD at the population level, suggesting that management of HT and assessment of subclinical organ damage in hypertensive subjects at a screening program are still beneficial for community-based CVD prevention.

Disparity in metabolic risk factors of non-communicable diseases between Palauans and Filipinos living in Palau.

Non-communicable diseases have been recognized as a serious threat to public health in Palau. To tackle the problem, different strategies might be necessary for populations with different ethnic backgrounds. This study aims to find the differences in the prevalence of metabolic risk factors of non-communicable diseases between Palauans and Filipinos living in Palau, and examine possible determinants of the differences. We selected data of 2,032 participants, including native Palauans and Filipinos, from the Palau STEPS Survey 2011-2013 for this study. Logistic regression models were used to inspect the association of each metabolic risk factor with ethnicity by calculating odds ratios adjusted for potential confounding factors. Palauans had higher age-standardized prevalence of overweight or obesity (84% vs. 45%), hypertension (50% vs. 38%) and diabetes (19% vs. 13%) than Filipinos. However, after adjusting for BMI and various lifestyle related factors, there are no statistical significant differences in the prevalence of hypertension and diabetes between these two ethnic groups. Palauan men were less likely to have elevated total cholesterol, especially after adjusting for BMI (odds ratio=0.55, 95% confidence interval: 0.33-0.91), while Palauan women were more likely to have elevated triglycerides than their Filipino counterparts (odds ratio=1.45, 95% confidence interval: 1.02-2.06). Our findings suggested that Palauans' higher BMI distribution might be able to explain their higher prevalence of hypertension and partially explain their higher diabetes prevalence. Palauans were not consistently more likely to have all metabolic risk factors, namely dyslipidemia were less likely to be observed in Palauan men.