Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hypertension Research  

Sleep-related breathing disorder (SRBD) causes hypertension, and obesity has been highly associated with SRBD, which has become a serious health problem in young and middle-aged Japanese males. However, the relation between SRBD and hypertension considering the effects of obesity remains unknown. In this cross-sectional study, we examined the relationship between SRBD and hypertension, with consideration for the effects of obesity, in Japanese occupational population. Using 3% oxygen desaturation index (3%ODI) obtained by simplified polysomnography (PSG), participants were classified into low (0 ≤ 3%ODI < 5), medium (5 ≤ 3%ODI < 15), and high (15 ≤ 3%ODI) 3%ODI groups. We excluded employees who had not undergone medical examination with simplified PSG in the same year from 2012 to 2018. Logistic regression analysis was performed to calculate odds ratios for having hypertension according to 3%ODI levels. In total, 2532 employees were included. Among them, 25% and 4% were categorized into the medium and high 3%ODI groups, respectively. The odds ratio for hypertension increased significantly with higher 3%ODI levels after adjustment for age, sex, alcohol drinking status and smoking status (p for trend < 0.0001). However, further adjustment for obesity status (body mass index ≥ 25 kg/m2) attenuated the associations. When we performed the stratified analysis by obesity status, the odds ratio for hypertension increased significantly with higher 3%ODI only for non-obese individuals, with significant interaction (p for interaction = 0.014). Higher 3%ODI was significantly associated with higher prevalence of hypertension especially in non-obese participants, suggesting the importance of vigilance for the presence of SRBD even in non-obese individuals. We investigated the association between SRBD and hypertension considering the effects of obesity, which would suggest the need to keep in mind the presence of SRBD even in non-obese individuals.

DOI： 10.1038/s41440-024-01612-y

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Language：English   Publisher：(一社)日本疫学会  

＜Highlight＞●本研究は、血清リポ多糖結合蛋白(LBP)値とメタボリックシンドローム(MetS)発症との関連を検討した最初の前向きコホート研究である。●血清LBP値の上昇に伴いメタボリックシンドロームおよびその構成要素の発症リスクは上昇した。●媒介解析において、HOMA-IRと血清高感度CRPは血清LBPとMetS発症との関連に、部分的に介在していた。●血清LBP値とメタボリックシンドロームの発症リスクの関連はインスリン抵抗性と慢性炎症を介した機序が示唆された。(著者抄録)

Language：English   Publisher：Journal of Cardiology Cases  

UNLABELLED: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that commonly originates from the right or noncoronary sinuses and rarely from the left sinus. SVA is usually diagnosed in the setting of clinical sequelae of a rupture. We herein report a case of an unruptured left SVA presenting as acute myocardial infarction. A 54-year-old woman with a history of radical operation for patent ductus arteriosus in childhood was transferred to our hospital. An electrocardiogram indicated extensive myocardial ischemia with ST elevation. Urgent coronary angiography was performed but was unable to identify the left coronary artery. Subsequent aortography and computed tomography revealed a large SVA originating from the left sinus and compressing the left coronary artery. The patient died after approximately one month of intensive care, including mechanical circulatory support and coronary artery bypass grafting. Autopsy confirmed that the left main coronary trunk was stretched and compressed by the SVA and revealed unexpected atherosclerosis in the left anterior descending artery. Although a left SVA is an extremely rare anomaly, it occasionally provokes fatal myocardial infarction. Since an SVA might hinder performing percutaneous coronary intervention, cardiac surgery should be considered when myocardial ischemia is recognized. LEARNING OBJECTIVE: We herein report a case of an unruptured left sinus of Valsalva aneurysm (SVA) with acute myocardial infarction. Urgent percutaneous coronary intervention (PCI) was unsuccessful, as the left coronary artery was compressed by the SVA. The patient died after intensive care, including coronary artery bypass grafting (CABG). SVA, especially from the left sinus, is extremely rare but occasionally provokes myocardial infarction by compressing the coronary arteries. Because SVA might hinder PCI, CABG should be considered when myocardial ischemia is recognized.

DOI： 10.1016/j.jccase.2023.10.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：European Journal of Preventive Cardiology  

AIMS: Several prospective studies have reported that higher visit-to-visit blood pressure variability (BPV) is associated with atrial fibrillation (AF). However, no studies have investigated the association between day-to-day BPV assessed by home blood pressure measurement and the development of AF. METHODS: A total of 2,827 community-dwelling Japanese aged ≥40 years without prior AF were followed up for 10 years (2007-2017). Day-to-day home BPV (defined as coefficients of variation [CoV] of home systolic blood pressure [SBP] for 28 days) were categorized into 4 groups according to the quartiles: Q1, ≤4.64%; Q2, 4.65%-5.70%; Q3, 5.71%-7.01%; Q4, ≥7.02%. The hazard ratios for developing AF were estimated using a Cox proportional hazards model. RESULTS: During the follow-up period, 134 participants developed new-onset AF. The crude incidence rates of AF increased significantly with higher CoV levels of home SBP: 2.1, 4.7, 5.3, and 8.8 per 1000 person-years in the first, second, third, and fourth quartiles, respectively (P for trend <0.01). After adjusting for potential confounders, increased CoV levels of home SBP were associated significantly with a higher risk of AF (P for trend =0.02). The participants in the highest quartile of CoV had a 2.18-fold (95% confidence intervals: 1.18-4.04) increased risk of developing AF compared to those in the lowest quartile. CONCLUSIONS: The present findings suggest that increased day-to-day home BPV levels are associated with a higher risk of the development of AF in a general Japanese population.

DOI： 10.1093/eurjpc/zwae035

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Language：English   Publisher：(一社)日本心臓病学会  

症例は54歳女性で、突然の胸痛のため救急医療部へ搬送された。動脈管開存症の既往があった。搬送時の血圧は73/50mmHg、心拍数は122bpmであった。心電図は洞性頻脈で左軸偏位を認め、I、aVR、aVL、V3～V6誘導でST上昇、II、III、aVF誘導でST低下を認めた。胸部X線検査で肺水腫を認めた。臨床検査で心筋トロポニンTは0.159ng/mL、クレアチニンキナーゼ(CK)-MBは36.7U/Lであった。緊急冠動脈造影で左冠動脈は描出されなかった。大動脈造影を施行した。その結果、左冠動脈洞が瘤化しており、瘤径は5cmであった。右および無冠動脈洞に異常はなかった。左バルサルバ洞動脈瘤と診断し、大動脈内バルーンパンピングと体外式膜型人工肺(VA-ECMO)を導入した。CT血管造影で左冠動脈主幹部は左冠動脈洞瘤により圧排されていた。3日後に完全房室ブロックが出現し、心原性ショックに陥った。心拍動下冠動脈バイパス術を施行した。5日後にImpella CPの併用を開始したが、左室壁運動は回復せず、26日後に出血性脳梗塞のため死亡した。剖検で左回旋枝にアテロームプラークによる狭窄病変が検出された。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：New England Journal of Medicine  

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

DOI： 10.1056/NEJMoa2206916

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5551/jat.ER61960

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Language：English   Publisher：Journal of Dental Research  

Ectopic enrichment of oral microbes in the gut is a notable alteration in gut microbial balance. These microbes are likely delivered from the oral cavity with saliva and food; however, evidence of oral–gut microbial transmission is insufficient and needs further investigation. In this observational study, we examined 144 pairs of saliva and stool samples collected from community-dwelling adults to verify the oral–gut microbial link and identify the relevant influencing factors on the increased abundance of oral microbes within the gut. The bacterial composition of each sample was determined using PacBio single-molecule long-read sequencing of the full-length 16S ribosomal RNA gene and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of salivary and gut microbiota were distinctly different, at least 1 ASV was shared between salivary and gut microbiota in 72.9% of subjects. Shared ASVs accounted for 0.0% to 63.1% (median 0.14%) of the gut microbiota in each subject and frequently included abundant Streptococcus salivarius and Streptococcus parasanguinis. Their total relative abundance in the gut was significantly higher in older subjects or those with dental plaque accumulation. The gut microbiota with ≥5% of shared ASVs displayed a higher abundance of Streptococcus, Lactobacillus, and Klebsiella and a lower abundance of Faecalibacterium, Blautia, Megamonas, and Parabacteroides. Our study presents evidence for the translocation of oral bacteria to the gut in community-dwelling adults and suggests that aging and dental plaque accumulation contribute to an increased abundance of oral microbes in the gut, which might be relevant to the compositional shift in the gut commensals.

DOI： 10.1177/00220345231160747

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Clinical Endocrinology and Metabolism  

CONTEXT: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) concentrations are known to be an indicator of chronic liver injury and fibrosis. OBJECTIVE: This study aimed to investigate the association between serum M2BPGi concentrations and the development of type 2 diabetes in a Japanese community. METHODS: A total of 2143 community-dwelling Japanese individuals aged 40-79 years without diabetes at baseline were followed up for 7 years. Serum M2BPGi concentrations were divided into quintiles: Q1, ≤0.37 cutoff index (COI); Q2, 0.38-0.49 COI; Q3, 0.50-0.62 COI; Q4, 0.62-0.80 COI; and Q5, ≥0.81 COI. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for the development of type 2 diabetes. RESULTS: During the follow-up period, 219 individuals developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes significantly increased with elevating serum M2BPGi levels (P for trend < .01). This association remained significant after adjustment for potential confounders (P for trend = .04). This significant association attenuated to a nonsignificant level after additionally adjusting for serum high-sensitivity C-reactive protein or homeostasis model assessment of insulin resistance. CONCLUSION: The present study demonstrated that higher serum M2BPGi concentrations were significantly associated with higher risk of diabetes in a Japanese community. Moreover, inflammation and insulin resistance were suggested to contribute to the excess risk of diabetes in individuals with higher serum M2BPGi levels. These findings shed light on the importance of inflammation and insulin resistance when considering the pathogenesis of diabetes.

DOI： 10.1210/clinem/dgad011

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Language：English   Publisher：(一社)日本動脈硬化学会  

日本の集団ベース研究である久山町研究のデータを用いて、集団レベルでの血清エイコサペンタエン酸(EPA)/アラキドン酸(AA)比、血清EPA濃度、血清AA濃度の10年間の変化を評価した。2002～2003年と2012～2013年に久山町研究に参加した40歳以上でEPA薬を服用していない地域住民(2002～2003年は3194名、2012～2013年は3220名)のデータを解析した。血清EPA/AA比は10年間で低下し、2002年と2012年の幾何平均値はそれぞれ0.40、0.32であった。血清EPA濃度は軽度に上昇し、2002年と2012年の幾何平均値はそれぞれ59.0μg/mL、65.1μg/mLであった。血清AA濃度は大きく上昇し、2002年と2012年の幾何平均値はそれぞれ147.6μg/mL、199.9μg/mLであった。年齢群別の解析では、血清EPA/AA比は80歳以上を除いて有意に低下し、若年群ほど低下が大きかった。血清EPA濃度は50～59歳で有意に低下し、70歳以上で有意に上昇した。血清AA濃度はすべての年齢群で有意に上昇した。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kidney Medicine  

RATIONALE & OBJECTIVE: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. STUDY DESIGN: Population-based cross-sectional study. SETTING & PARTICIPANTS: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. EXPOSURES: UACR and eGFR levels. OUTCOMES: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). ANALYTICAL APPROACH: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. RESULTS: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and <0.001, respectively). Lower eGFR levels were significantly associated with lower TBV/ICV, but not clearly associated with WMLV/ICV. In addition, higher UACR levels, but not lower eGFR, were significantly associated with lower temporal cortex volume-to-TBV ratio and lower hippocampal volume-to-TBV ratio. LIMITATIONS: Cross-sectional study, misclassification of UACR or eGFR levels, generalizability to other ethnicities and younger populations, and residual confounding factors. CONCLUSIONS: The present study demonstrated that higher UACR was associated with brain atrophy, especially in the temporal cortex and hippocampus, and with increased WMLV. These findings suggest that chronic kidney disease is involved in the progression of morphologic brain changes associated with cognitive impairment.

DOI： 10.1016/j.xkme.2022.100593

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Several prospective Western studies have reported an inverse association of vegetable and fruit intake with dementia risk. However, there is limited epidemiologic evidence in Asians. This study investigated the association of intakes of vegetables, fruits, and their nutrients on the risk of incident dementia and its subtypes in a Japanese community.

Methods

A total of 1071 participants (452 men and 619 women) aged ≥60 years without dementia at baseline were prospectively followed up for 24 years. Intakes of vegetables, fruits, and nutrients were evaluated using a 70-item semiquantitative food frequency questionnaire at baseline and were categorized into quartiles separately by gender. The outcome measure was the development of dementia and its subtypes—namely, Alzheimer’s disease (AD) and vascular dementia (VaD). The risk estimates of incident dementia were computed using a Cox proportional hazards model.

Results

During the long-term follow-up period, 464 subjects developed dementia, of whom 286 had AD and 144 had VaD. Higher vegetable intake was associated gradually with lower risk of developing dementia and AD (both P-trend &lt; 0.05), but not VaD, after adjusting for confounders. Subjects allocated the highest quartile of vegetable intake had 27 and 31% lower risk of dementia and AD, respectively, than those with the lowest quartile. The risk of dementia decreased significantly with higher intakes of vitamin A, riboflavin, vitamin C, magnesium, calcium, and potassium (all P-trend &lt; 0.05). Subjects with higher total dietary fiber intake tended to be at decreased risk for total dementia (P-trend = 0.07). Meanwhile, there were no significant associations between fruit intake and the risk of dementia and its subtypes.

Conclusion

Higher intakes of vegetables and their constituent nutrients were associated with a lower risk of dementia in Japanese older adults. A diet rich in vegetables may be beneficial in reducing the dementia risk in Asians.

DOI： 10.1186/s12877-022-02939-2

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Other Link： https://link.springer.com/article/10.1186/s12877-022-02939-2/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

<p><b>Background:</b> The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population.</p><p><b>Methods:</b> 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002–2003 were followed up by repeated examination in 2007–2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1–4: 2.20–9.56, 9.57–10.78, 10.79–12.18, and 12.19–24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model.</p><p><b>Results:</b> At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1–4: 1.00 [reference], 2.92 [1.59–5.37], 3.48 [1.91–6.35], and 3.86 [2.12–7.03], respectively; <i>P</i> for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (<i>P</i> for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (<i>P</i> for trend = 0.07).</p><p><b>Conclusion:</b> In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.</p>

DOI： 10.2188/jea.JE20220232

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Language：English   Publisher：(一社)日本動脈硬化学会  

一般日本人集団の前向き追跡データを用いて、再発性脳卒中の5年リスクにみられる傾向を半世紀にわたり検討した。福岡県久山町の住民を対象に、1961年から続けられている久山町研究のデータを利用した。1961年(154名)、1974年(144名)、1988年(172名)、2002年(146名)を起点とする四つのコホートを設定し、脳卒中発症患者を起点から10年間追跡したデータを用いて再発性脳卒中リスクを調査した。全種類の脳卒中および虚血性脳卒中を発症した後の再発性脳卒中リスクは、一番目(1961年)のコホートから三番目のコホートにかけて有意に低下していたが、三番目から四番目のコホートでは明瞭な変化は示されなかった。出血性脳卒中後の同リスクは主として一番目から二番目のコホートにかけて低下しており、二番目から四番目まででは明らかな低下はみられなかった。こうした傾向は年齢・性別で調整しても実質的に不変であった。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of the American Heart Association  

Background Several longitudinal studies have reported that higher visit-to-visit blood pressure variability is associated with greater risk for developing chronic kidney disease. However, no population-based studies have investigated the association between day-to-day home blood pressure variability and incident chronic kidney disease. Methods and Results A total of 2342 Japanese community-dwelling residents aged ≥40 years without chronic kidney disease at baseline were followed up by annual health examinations for 10 years. Home blood pressure was measured 3 times every morning for 28 days. Day-to-day coefficients of variation of home systolic blood pressure levels were categorized into quintiles. Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m2 or the presence of proteinuria. The hazard ratios for developing chronic kidney disease were estimated with a Cox proportional hazards model. During the follow-up period, 772 participants developed chronic kidney disease. Increased coefficients of variation of home systolic blood pressure were associated significantly with higher risk of chronic kidney disease after adjusting for confounders (P for trend <0.001): Individuals in the highest quintile of coefficients of variation had a 1.50-fold (95% CI, 1.17-1.94) greater risk of developing chronic kidney disease than those in the lowest quintile. The combination of higher coefficients of variation and higher mean value of home systolic blood pressure was associated with the multivariable-adjusted risk of developing chronic kidney disease. Conclusions These findings suggest that increased day-to-day blood pressure variability is a significant risk factor for developing chronic kidney disease in a general Japanese population.

DOI： 10.1161/JAHA.122.027173

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

<p> <b>Aim:</b> Circulating omega-3 and omega-6 polyunsaturated fatty acids may to contribute to cardiovascular health at the population level. Over a decade, we investigated changes in the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio, and in serum concentrations of the individual fatty acids, in a Japanese community.</p><p> <b>Methods:</b> Community surveys took place in 2002–2003 and 2012–2013 in a rural area of Japan. The community surveys included 3,194 and 3,220 community dwellers aged ≥ 40 years who did not take EPA medication in 2002–2003 and 2012–2013, respectively. Fatty acid fractionations in serum were measured using a gas chromatography method. Changes in the serum EPA/AA ratio over time were examined using linear mixed models.</p><p><b>Results:</b> Overall, the average serum EPA/AA ratio decreased over the 10 years. A decreasing trend in the serum EPA/AA ratio occurred in all age groups except participants aged ≥ 80 years, with larger decreases in the younger age groups. A similar decline in serum EPA/AA ratio occurred in participants with and those without lipid-lowering therapy. Serum EPA concentrations were slightly increased in the whole population but remained stable or even decreased in participants aged 40–69. In contrast, the average serum AA concentrations increased in all age groups.</p><p><b>Conclusion:</b> In a Japanese community, the serum EPA/AA ratio decreased over 10 years at the population level, especially in middle-aged participants.</p>

DOI： 10.5551/jat.63727

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Diabetes Investigation  

AIMS/INTRODUCTION: We aimed to investigate the association of active commuting (cycling or walking to work), as well as the association of the individual commuting modes, with the risk of diabetes in a prospective cohort of community-dwelling adults in Japan. MATERIAL AND METHODS: A total of 1,270 residents aged 40-79 years were followed up for a median of 14 years. Active commuting was defined as either cycling or walking to work. A Cox proportional hazards model was used to examine the association of active commuting with the risk of diabetes. Associations for different forms of active commuting (cycling, walking and mixed modes of cycling or walking with non-active components) were also examined. RESULTS: During the follow-up period, 191 participants developed diabetes. Active commuting was associated with a lower risk of diabetes than non-active commuting after adjustment for potential confounders (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.31-0.92). With regard to the commuting modes, the risk of diabetes was significantly lower in individuals who commuted by cycling alone (HR 0.46, 95% CI 0.22-0.98), and tended to be lower in individuals who commuted by walking alone (HR 0.14, 95% CI 0.02-1.02) compared with that in individuals with non-active commuting. Meanwhile, no significant associations were observed for the mixed mode of walking and non-active commuting (HR 1.69, 95% CI 0.77-3.71). CONCLUSIONS: Active commuting, particularly that consisting exclusively of cycling or walking, was associated with a reduced risk of diabetes. Our findings support a public health policy that promotes the choice of active commuting for the prevention of diabetes.

DOI： 10.1111/jdi.13844

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Journal of Respiratory and Critical Care Medicine  

RATIONALE: Several Western studies have reported that participants with preserved ratio impaired spirometry (PRISm) have higher risks of airflow limitation (AFL) and death. However, evidence in East Asian populations is limited. OBJECTIVES: To investigate the relation between PRISm and the risks of death and incident AFL in a Japanese population. METHODS: A total of 3,032 community-dwelling Japanese participants aged ≥40 years were followed up for a median of 5.3 years by annual spirometry examinations. Participants were classified into lung function categories at baseline as follows: normal spirometry (forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ≥0.70 and FEV1 ≥80% predicted), PRISm (≥0.70 and <80%), AFL Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 (<0.70 and ≥80%), and AFL GOLD 2-4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using a Cox proportional hazard model. MEASUREMENTS AND MAIN RESULTS: During the follow-up period, 131 participants died, 22 of whom died from cardiovascular disease, and 218 participants developed AFL. When examining the prognosis of each baseline pulmonary function category, participants with PRISm had higher risks of all-cause death (HR 2.20 [95%CI: 1.35 to 3.59]) and cardiovascular death (HR 4.07 [1.07 to 15.42]) than those with normal spirometry after adjusting for confounders. Moreover, the multivariable-adjusted risk of incident AFL was greater in participants with PRISm than in those with normal spirometry (HR 2.48 [1.83 to 3.36]). CONCLUSIONS: PRISm was associated with higher risks of all-cause and cardiovascular death and a greater risk of the development of AFL in a Japanese community. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1164/rccm.202110-2302OC

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Language：English   Publisher：(一社)日本動脈硬化学会  

心血管疾患の既往がない成人被験者2454名(男性1026名、女性1428名、平均58.2±11.1歳)を対象に、Cox比例ハザードモデルを用いてアテローム動脈硬化性心血管疾患(ASCVD)発症のリスク予測モデルを開発し、妥当性を検証した。対象は久山町研究に参加した40歳から84歳までの一般住民で、ASCVDは冠状動脈性心疾患またはアテローム血栓性脳梗塞と定義した。平均追跡期間は24年で、ASCVDは270名で初発した。発生率は1000人あたり5.8人年であった。リスク予測モデルの予測因子として年齢、性別、収縮期血圧、糖尿病、血中HDLコレステロール、LDLコレステロール、蛋白尿、喫煙習慣、定期的な運動を選択した。上記の変数を組み込んで10年後のASCVD発症予測モデルを構築し、簡便なリスクスコアを作成した。C統計量により妥当性を評価したところ、ASCVD発症リスク予測モデル(0.786)と簡便なリスクスコア(0.789)のいずれも優れた識別能を呈した。またGreenwood-Nam-D' Agostino検定で良好なキャリブレーションが確認された(それぞれP=0.29とP=0.52)。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

<p> <b>Aim:</b> Secular trends in the risk of recurrent stroke have been reported in several epidemiological studies worldwide, but this issue has not been investigated in general Japanese populations. We examined the trends in the 5-year risk of recurrent stroke over a half century using community-based prospective data in Japan.</p><p><b>Methods:</b> We established 4 cohort studies in 1961, 1974, 1988, and 2002. To examine the risk of recurrent stroke, participants who developed stroke during a 10-year follow-up period in each cohort were followed-up for 5 years from the date of first onset. A total of 154 (first sub-cohort: 1961-1971), 144 (second sub-cohort: 1974-1984), 172 (third sub-cohort: 1988-1998), and 146 (fourth sub-cohort: 2002-2012) participants from each cohort were enrolled in the present study. The 5-year cumulative risk of recurrent stroke was compared among the sub-cohorts using the Kaplan-Meier method and the age- and sex-adjusted Cox proportional hazards model.</p><p><b>Results:</b> The risks of recurrent stroke after any stroke and ischemic stroke decreased significantly from the first to the third sub-cohort, but they did not clearly change from the third to the fourth sub-cohort. The risk of recurrent stroke after hemorrhagic stroke decreased mainly from the first to the second sub-cohort and there was no apparent decrease from the second to the fourth sub-cohort. These trends were substantially unchanged after adjusting for age and sex.</p><p><b>Conclusions:</b> In the Japanese community, the risk of recurrent stroke decreased mainly from the 1960s to 1990s, but there was no apparent decrease in recent years.</p>

DOI： 10.5551/jat.63344

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Information regarding the influence of serum uric acid (SUA) levels on pathological changes in the kidney is limited. In this study, we examined the association between SUA levels and pathological findings of nephrosclerosis in population-based autopsy samples. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of 923 deceased individuals in a Japanese community underwent autopsy examinations between 1974 and 1994. Of these, 547 individuals with available kidney tissues and health examination data within a median of 3 years before death were eligible for the present study. SUA levels were categorized into quintiles (Q1, 107–237; Q2, 238–279; Q3, 280–326; Q4, 327–380; Q5, 381–755 μmol/L). Advanced degrees of glomerular sclerosis, kidney arteriolar hyalinosis, and kidney arteriosclerosis were defined as the 90th percentile or more of a glomerular sclerosis index and an arteriolar hyalinosis index, and the 10th percentile or less of a wall-lumen ratio, respectively. A logistic regression model was used to evaluate odds ratios (ORs) and their 95% confidence intervals (CIs) of SUA levels on each kidney lesion. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Higher SUA levels were significantly associated with higher values of the age- and sex-adjusted glomerular sclerosis index and lower values of the wall-lumen ratio (both &lt;i&gt;p&lt;/i&gt; for trend &amp;#x3c;0.01). Individuals in the Q5 group had a significantly greater likelihood of advanced glomerular sclerosis (OR 7.19, 95% CI 2.42–21.38) and advanced kidney arteriosclerosis (OR 5.28, 95% CI 1.77–15.80) than individuals in the Q1 group after adjusting for potential covariates. There was no evidence of significant associations of SUA levels with either the arteriolar hyalinosis index or the presence of advanced arteriolar hyalinosis. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Elevated SUA levels were significantly associated with advanced glomerular sclerosis and advanced kidney arteriosclerosis, but not with advanced arteriolar hyalinosis in community-based autopsy samples of Japanese.

DOI： 10.1159/000521426

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Language：English   Publisher：(一社)日本動脈硬化学会  

体重変化が、モデルから予測される心血管疾患(CVD)の包括的リスクと個々の心血管リスクの変化に及ぼす影響について検討した。久山町研究の縦断データを用いて、2002年と2007年の健康診断に参加した40～74歳の地域住民2140名を対象に解析を行った。BMI 25kg/m2以上を肥満とし、2002年と2007年のBMIにより、「安定肥満」(両年とも肥満)、「肥満から非肥満」、「非肥満から肥満」、「安定非肥満」(両年とも肥満)に分類した。CVDの推定累積リスクおよびCVDリスク因子の2002年から2007年にかけての変化を群間比較した。2140名を解析対象とした。CVDの推定リスクは、2007年にかけて全ての群で増加した。CVDの推定リスクの増加は、「肥満から非肥満」群で最も小さく、「非肥満から肥満」群で最も大きかった。「肥満から非肥満」群は「安定肥満」群よりもウエスト周囲長、血圧、空腹時血糖値、血清HDLコレステロール値、血清トリグリセリド値、肝酵素の望ましい変化量が大きかった。全変数について、「非肥満から肥満」群と「安定非肥満」群では逆の傾向が認められた。以上から、肥満者での減量および非肥満者での過剰な体重増加の回避と、CVD包括的リスクおよび個々のCVDリスク要因に望ましい関連が認められた。

Language：Japanese  

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Aim: To evaluate the longitudinal association between yogurt product intake and oral health in a population-based study. Materials and Methods: This study included 1967 Japanese residents aged 40–79 years who underwent dental examinations in 2012. Among them, 1469 participants were followed up in 2017 for the incidence of tooth loss, which was defined as two or more teeth lost over 5 years. The intake of yogurt products, defined as yogurt and lactic acid beverages, was estimated using a semi-quantitative food frequency questionnaire. The composition of the salivary microbiota was evaluated. Results: The Poisson regression model showed that a higher intake of yogurt products was negatively associated with the incidence of tooth loss (p for trend =.020), adjusted for potential confounding factors. Mediation analysis confirmed that periodontal condition partly mediated the effect of yogurt product intake on tooth loss, while dental caries experience did not. Additionally, we confirmed the association of a high intake of yogurt products with a low percentage of the salivary microbiota pattern, which was associated with poor oral health. Conclusion: These findings suggest that the intake of yogurt products is associated with a lower risk of tooth loss resulting from periodontal disease, probably via modulation of the oral microbiome composition.

DOI： 10.1111/jcpe.13593

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Language：Japanese  

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The identification of individuals at high risk of developing hypertension can be of great value to improve the efficiency of primary prevention strategies for hypertension. The objective of this study was to develop a risk prediction model for incident hypertension based on prospective longitudinal data from a general Japanese population. A total of 982 subjects aged 40-59 years without hypertension at baseline were followed up for 10 years (2002-12) for the incidence of hypertension. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive agents. The risk prediction model was developed using a Cox proportional hazards model. A simple risk scoring system was also established based on the developed model. During the follow-up period (median 10 years, interquartile range 5-10 years), 302 subjects (120 men and 182 women) developed new-onset hypertension. The risk prediction model for hypertension consisted of age, sex, SBP, DBP, use of glucose-lowering agents, body mass index (BMI), parental history of hypertension, moderate-to-high alcohol intake, and the interaction between age and BMI. The developed model demonstrated good discrimination (Harrell's C statistic=0.812 [95% confidence interval, 0.791-0.834]; optimism-corrected C statistic based on 200 bootstrap samples=0.804) and calibration (Greenwood-Nam-D'Agostino χ2 statistic=12.2). This risk prediction model is a useful guide for estimating an individual's absolute risk for hypertension and could facilitate the management of Japanese individuals at high risk of developing hypertension in the future.

DOI： 10.1038/s41440-021-00673-7

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BACKGROUND: natriuretic peptide is associated with myocardial fibrosis in animal models and among patients with heart disease. However, it remains unclear whether serum N-terminal pro-B-type peptide (NT-proBNP) levels are associated with histopathologically proven myocardial fibrosis among individuals without apparent heart disease. This study aimed to evaluate the association between serum NT-proBNP levels and the histopathologically estimated myocardial fibrotic area in autopsied samples from a community. METHODS: we selected 63 cases without apparent heart disease with available data of serum NT-proBNP concentrations within six years before death (average age: 82 years; male: 52%) from autopsied cases in a community, and evaluated the percentage areas of myocardial fibrosis in four cardiac segments from each case (i.e. 252 cardiac segments in total). The association between serum NT-proBNP levels and the percentage area of myocardial fibrosis was estimated using a linear mixed model for repeated measures. RESULTS: serum NT-proBNP levels were positively correlated with myocardial fibrotic area [Pearson's correlation coefficient: r = 0.49 (95% confidence interval: 0.28-0.66), p <0.001]. Serum NT-proBNP levels were significantly associated with the percentage areas of myocardial fibrosis after adjusting for potential confounding factors. There was no evidence of heterogeneity in the association between the subgroups with and without reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2). CONCLUSIONS: the present study demonstrated that elevated serum NT-proBNP levels were associated with the histopathologically measured myocardial fibrotic area in autopsied cases from a community. These findings may help clarify the association between elevated serum NT-proBNP levels and myocardial fibrosis and their influence on prognosis.

DOI： 10.1016/j.jjcc.2021.03.014

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The risk prediction of incident atrial fibrillation (AF) is useful to prevent AF and its complications. The aim of this study is to develop a new risk prediction model for incident AF using the prospective longitudinal data from a general Japanese population.Methods and Results:A total of 2,442 community-dwelling AF-free residents aged ≥40 years were followed up from 1988 to 2012 (46,422 person-years). The development of AF was confirmed by a standard 12-lead electrocardiogram at repeated health examinations and by medical records at clinics or hospitals. The risk prediction model for incident AF was developed using a Cox proportional hazards model. During the follow up, 230 AF events were confirmed. Age, sex, systolic blood pressure, waist circumference, estimated glomerular filtration rate, abnormal cardiac murmur, high R-wave amplitude, and arrhythmia other than AF were selected for inclusion in the model. This model showed good discrimination (Harrell's c statistics: 0.785) and calibration (Greenwood-Nam-D'Agostino test: P=0.87) for AF risk at 10 years. CONCLUSIONS: The new risk prediction model showed good performance on the individual risk assessment of the future onset of AF in a general Japanese population. As this model included commonly used clinical parameters, it may be useful for determining the requirements for the careful evaluation of AF, such as frequent electrocardiogram examinations in clinical settings, and subsequent reductions in the risk of AF-related complications.

DOI： 10.1253/circj.CJ-20-0794

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BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in the elderly, and causes complications such as cardioembolic stroke. Serum high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, has been reported to be a risk factor for developing AF in Western countries. However, few community-based studies have examined this issue in general Asian populations.Methods and Results:A total of 2,510 community-dwelling Japanese participants aged ≥40 years without a history of AF were divided into 4 groups according to the sex-specific quartiles of serum hs-CRP concentrations (Q1, lowest and Q4, highest) and followed up for 24 years. The hazard ratios and their 95% confidence intervals for the development of AF were estimated using a Cox proportional hazards model. During the follow up, 234 subjects developed AF. The risk of AF increased significantly with elevating serum hs-CRP levels after adjustment for potential confounding factors (hazard ratio [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.26 [0.83-1.92]; Q3, 1.77 [1.18-2.66]; and Q4, 1.89 [1.24-2.86]; P for trend <0.001). CONCLUSIONS: The study findings suggest that elevated serum hs-CRP levels are an independent risk factor for the development of AF in a general Japanese population.

DOI： 10.1253/circj.CJ-20-0751

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Introduction: Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels have been associated with the progression of kidney impairment among patients with chronic kidney disease (CKD), but only a few studies have investigated the association between serum NT-proBNP levels and incident CKD in general populations. Methods: A total of 2486 Japanese community-dwelling residents ≥40 years of age without CKD at baseline were followed up by repeated annual health examinations for 10 years. Participants were divided into 4 groups according to serum NT-proBNP levels. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 or the presence of proteinuria. Cox proportional hazards models were used to estimate hazard ratios (HRs) for risk of CKD. Linear mixed models were used to compare changes in eGFR. Results: During the follow-up period, 800 participants developed CKD. The multivariable-adjusted HRs (95% confidence intervals [CIs]) for developing CKD were 1.00 (reference), 1.32 (1.11-1.57), 1.40 (1.10-1.78), and 1.94 (1.38-2.73) for serum NT-proBNP levels of <55, 55-124, 125-299, and ≥300 pg/ml, respectively (P for trend <0.001). The decline of eGFR during the follow-up was significantly more rapid among participants with higher serum NT-proBNP levels (P for trend <0.001). Adding serum NT-proBNP to the model composed of known risk factors for CKD improved the predictive ability for developing CKD. Conclusions: Higher serum NT-proBNP levels were associated with greater risks of developing CKD and greater decline in eGFR. Serum NT-proBNP could be a useful biomarker for assessing the future risk of CKD in a general Japanese population.

DOI： 10.1016/j.ekir.2021.01.006

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BACKGROUND: Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population. METHODS: A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model. RESULTS: The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R2] = 0.72): urinary concentrations of 20, 27, and 43 pg/mL were equivalent to serum concentrations of 55, 125, and 300 pg/mL, respectively. During the follow-up period, 170 subjects developed CVD. The age- and sex-adjusted risk of CVD increased significantly with higher urinary NT-proBNP levels (P for trend < 0.001). This association remained significant after adjustment for traditional cardiovascular risk factors (P for trend = 0.009). The multivariable-adjusted risk of developing CVD almost doubled in subjects with urinary NT-proBNP of ≥ 43 pg/mL as compared to those with urinary NT-proBNP of ≤ 19 pg/mL (HR 2.07, 95% CI 1.20-3.56). CONCLUSIONS: The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.

DOI： 10.1186/s12199-021-00970-0

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OBJECTIVE: The purpose of the present study was to investigate the effects of serum triglyceride levels on the risk of new-onset hypertension in Japanese. METHODS: Five thousand nine hundred and thirty-three Japanese workers without hypertension at baseline, who participated in medical check-ups from 2006 to 2018, were followed retrospectively. The participants were divided into quartiles of casual serum triglyceride levels and were followed from the first to last visit of the study period. The outcome was development of hypertension. Risk estimates were computed using Cox's proportional hazards model. RESULTS: During the follow-up period (average: 6.7 years), 946 individuals developed hypertension. The crude incidence rates of hypertension (per 1000 person-years) increased with rising serum triglyceride levels: 10.1 for quartile 1 (<0.76 mmol/l), 19.6 for quartile 2 (0.76-1.17 mmol/l), 26.0 for quartile 3 (1.18-1.84 mmol/l), and 36.5 for quartile 4 (>1.84 mmol/l) (P < 0.0001 for trend). These associations remained significant even after adjustment for other risk factors: the multivariable-adjusted hazard ratio was 1.29 (1.01-1.66) for the second quartile, 1.27 (0.99-1.63) for the third quartile, and 1.39 (1.09-1.77) for the highest quartile compared with the lowest. There were comparable effects of serum triglyceride levels for incidence of hypertension between subgroups defined by sex, obesity, and diabetes (all P > 0.1 for interaction), whereas stronger associations were observed for participants under 40 years of age than for those aged 40 or above (P = 0.002 for interaction). CONCLUSION: Serum triglyceride levels were significantly associated with development of hypertension in a Japanese worksite population.

DOI： 10.1097/HJH.0000000000002693

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BACKGROUND: Folate and vitamin B-12 are essential nutrients for normal cell growth and replication, but the association of serum folate and vitamin B-12 concentrations with mortality risk remains uncertain. OBJECTIVE: This study was performed to investigate the associations of serum folate and vitamin B-12 concentrations with mortality risk and test whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism modifies these associations. METHODS: A total of 3050 Japanese community residents aged ≥40 y were prospectively followed-up for mortality between 2002 and 2012. Cox proportional hazards models and restricted cubic splines were used to estimate HRs and 95% CIs of mortality. RESULTS: During a median follow-up period of 10.2 y, 336 participants died. Higher serum folate concentrations were associated with lower risks of all-cause mortality [multivariable-adjusted HR: 0.73; 95% CI: 0.56, 0.96 for the second tertile (8.8-12.2 nmol/L; median 10.4 nmol/L) and HR: 0.61; 95% CI: 0.46, 0.80 for the third tertile (≥12.5 nmol/L; median 15.6 nmol/L) serum folate concentrations compared with the first tertile (≤8.6 nmol/L; median 7.0 nmol/L)]. This association remained significant in all sensitivity analyses. Spline analyses showed a steady decline in all-cause mortality risk with increasing serum folate concentrations up to 20-25 nmol/L. This association persisted regardless of the MTHFR C677T genotypes. For serum vitamin B-12, the multivariable-adjusted HR of 1.32 (95% CI: 0.97, 1.79) of all-cause mortality was marginally significantly greater in the first tertile compared with the second tertile. This association was attenuated and nonsignificant after the exclusion of participants with a history of cardiovascular disease or cancer, or participants aged ≥85 y at baseline, or deaths in the first 3 y of follow-up. CONCLUSIONS: Serum folate concentrations were inversely associated with the risk of all-cause mortality in Japanese adults. Serum vitamin B-12 concentrations were not consistently associated with all-cause mortality risk after accounting for reverse-causation bias.

DOI： 10.1093/jn/nxaa382

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Abstract

Introduction

We aimed to develop a risk prediction model for incident dementia using predictors that are available in primary‐care settings.

Methods

A total of 795 subjects aged 65 years or over were prospectively followed‐up from 1988 to 2012. A Cox proportional‐hazards regression was used to develop a multivariable prediction model. The developed model was translated into a simplified scoring system based on the beta‐coefficient. The discrimination of the model was assessed by Harrell's C statistic, and the calibration was assessed by a calibration plot.

Results

During the follow‐up period, 364 subjects developed dementia. In the multivariable model, age, female sex, low education, leanness, hypertension, diabetes, history of stroke, current smoking, and sedentariness were selected as predictors. The developed model and simplified score showed good discrimination and calibration.

Discussion

The developed risk prediction model is feasible and practically useful in primary‐care settings to identify individuals at high risk for future dementia.

DOI： 10.1002/dad2.12221

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

<p><b>Aim:</b>To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. </p><p><b>Methods:</b> A total of 2,454 participants aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell’s C statistics, a calibration plot with the Greenwood-Nam-D’Agostino test, and a bootstrap validation procedure. </p><p><b>Results:</b> During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell’s C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D’Agostino test: <i>P</i>=0.29 for the multivariable model, 0.52 for the simplified score). </p><p><b>Conclusion:</b> We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients. </p>

DOI： 10.5551/jat.61960

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

<p><b>Aim:</b> We investigated the influence of weight change on concurrent changes in predicted cardiovascular disease (CVD) risk and individual CVD risk factors over time. </p><p><b>Methods:</b> A total of 2,140 community-dwellers aged 40–74 years participated in both 2002 and 2007 health examinations. Obesity was defined as body mass index ≥ 25 kg/m². Weight trajectories were classified as: “stable obese” (obese at both examinations), “obese to nonobese” (obese in 2002 but nonobese in 2007), “nonobese to obese” (nonobese in 2002 but obese in 2007), or “stable nonobese” (nonobese at both examinations). We compared changes in the model-predicted risk for CVD and individual CVD risk factors across weight-change categories. </p><p><b>Results:</b> The predicted risk for CVD increased during 5 years in all groups; the increment in the predicted risk for CVD was smallest in the obese to nonobese participants and steepest in the nonobese to obese subjects. Compared with the stable obese participants, the obese to nonobese participants had greater favorable changes in waist circumferences, blood pressure, fasting plasma glucose, serum high-density lipoprotein cholesterol, serum triglycerides, and liver enzymes. For all these parameters, opposite trends were observed when comparing the nonobese to obese participants with the stable nonobese group. </p><p><b>Conclusions:</b> We demonstrated the favorable association of losing weight in obese people and avoiding excessive weight gain in nonobese people with global risk of future CVD and individual CVD risk factors in a real-world setting. The findings could improve behavioral lifestyle interventions that provide information on the health consequences of weight change at health checkups. </p>

DOI： 10.5551/jat.59394

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Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: We aimed to investigate the association of serum glycated albumin (GA) levels with the risk of cardiovascular disease (CVD) and its subtypes, including coronary heart disease (CHD) and stroke, in a general Japanese population. METHODS: A total of 2965 Japanese community-dwellers aged ≥40 years were followed prospectively for a median of 10.2 years (2002-2012). Serum GA was measured by the enzymatic method and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum GA levels on CVD risk. RESULTS: During the follow-up, 213 subjects developed CVD; 95 had CHD, and 133 had stroke. The cumulative incidence of CVD, CHD, and stroke increased significantly with increasing serum GA levels (all p for trend <0.02). Compared with the lowest serum GA quartile (<13.6%), the multivariable-adjusted HRs (95% CI) of the highest quartile (≥15.7%) were 2.33 (1.46-3.68) for CVD, 2.23 (1.11-4.50) for CHD, and 2.47 (1.38-4.40) for stroke. In addition, a subgroup analysis showed that CVD risk increased significantly with increasing levels of serum GA in both subjects with and without diabetes mellitus. The increasing trend of CVD risk for higher serum GA levels was also observed in subjects with low hemoglobin A1c levels (hemoglobin A1c <5.46%). CONCLUSIONS: Our findings suggest that higher serum GA levels are significantly associated with the development of CVD and its subtypes, even among subjects without diabetes or those with normal hemoglobin A1c levels, in a general Japanese population.

DOI： 10.1016/j.atherosclerosis.2020.08.016

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Few studies have examined the association between the accumulation of unhealthy eating habits and the likelihood of obesity or central obesity in a general Japanese population. We examined this association in a sample of 1906 community-dwelling Japanese subjects (age: 40-74 years) who participated in a health check-up in 2014. A face-to-face questionnaire interview was conducted to collect information about three unhealthy eating habits, i.e., snacking, eating quickly, and eating late-evening meals. Obesity was defined as body mass index ≥25 kg/m2 and central obesity was defined as waist circumference ≥90 cm in men and ≥80 cm in women. The odds ratios (OR) were estimated by using a logistic regression analysis. Subjects with any one of the three eating habits had a significantly higher likelihood of obesity than those without that habit after adjusting for confounding factors. The multivariable-adjusted OR for obesity increased linearly with an increase in the number of accumulated unhealthy eating habits (p for trend < 0.001). Similar associations were observed for central obesity. Our findings suggest that modifying each unhealthy eating habit and avoiding an accumulation of multiple unhealthy eating habits might be important to reduce the likelihood of obesity.

DOI： 10.3390/nu12103160

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although many studies have been conducted on the relationship between masticatory performance and nutrient ingestion in the elderly, few large-scale studies have been carried out using relatively young individuals. OBJECTIVES: The objective of this study was to clarify the association between the masticatory performance evaluated by the gummy-jelly test, not by visual examination, and nutrient ingestion state based on the brief self-administered diet history questionnaire (BDHQ). METHODS: This was a cross-sectional survey of 540 male workers. Somatometry, blood pressure measurement, blood test and medical interview were performed as a periodic health check-up. In the dental check-up, an oral examination, gummy-jelly test (glucosensor) and survey of ingested food and nutrients using BDHQ were performed. The participants were classified into two groups with low and normal values of masticatory performance. Participants with a score on the gummy-jelly test below 150 mg/dL or 150 mg/dL or higher were included in the low and normal groups, respectively. RESULTS: Two hundred and forty-eight participants (45.8%) had low masticatory performance, and 292 (53.2%) had normal masticatory performance. The intakes of some minerals and vitamins, such as calcium, vitamin D, vitamin B2 , small fish with bones and non-oily fish, were significantly lower in the low masticatory group than in the normal group. In contrast, the intake of sugar for coffee and tea and that of chicken were significantly higher in the low masticatory group than in the normal group. CONCLUSION: This study suggested that low masticatory performance can affect nutrient intake, which may cause non-communicable diseases.

DOI： 10.1111/joor.13039

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AIMS/INTRODUCTION: The investigation of the influence of dietary fiber intake on the incidence of type 2 diabetes in a general Japanese population. MATERIALS AND METHODS: A total of 1,892 individuals aged 40-79 years without diabetes at baseline were prospectively followed up for 14 years. The glucose tolerance status of participants was defined by a 75-g oral glucose tolerance test with the 1998 World Health Organization criteria. Dietary fiber intake was estimated by a semiquantitative food frequency questionnaire and divided to quintile levels separately by sex. A Cox proportional hazards model was applied for computing the hazard ratios and their 95% confidence intervals for the incidence of diabetes. RESULTS: During the follow-up period, 280 participants had developed diabetes. The age-adjusted cumulative diabetes incidence decreased significantly with higher total dietary fiber intake (P-for trend = 0.01). Participants in the highest quintile of total dietary fiber intake had a 0.53-fold (95% confidence interval 0.31-0.90) lower risk of developing diabetes than those in the lowest quintile after for the adjustment with potential confounding factors. Total dietary fiber intake showed a moderate positive correlation to the intake of soybean and soybean products, green vegetables, and other vegetables. Similar associations with diabetes and food sources were observed for both of the soluble and insoluble dietary fiber intake. CONCLUSIONS: The present study showed that higher dietary fiber intake was associated with a lower risk of type 2 diabetes in a general Japanese population. The intake of high dietary fiber foods might be useful for diabetes prevention.

DOI： 10.1111/jdi.13377

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Despite the clinical usefulness of self-measured home blood pressure (BP), reports on the characteristics of home BP have not been sufficient and have varied due to the measurement conditions in each study. We constructed a database on self-measured home BP, which included five Japanese general populations as subdivided aggregate data that were clustered and meta-analyzed according to sex, age category, and antihypertensive drug treatment at baseline (treated and untreated). The self-measured home BPs were collected after a few minutes of rest in a sitting position: (1) the morning home BP was measured within 1 h of waking, after urination, before breakfast, and before taking antihypertensive medication (if any); and (2) the evening home BP was measured just before going to bed. The pulse rate was simultaneously measured. Eligible data from 2000 onward were obtained. The morning BP was significantly higher in treated participants than in untreated people of the same age category, and the BP difference was more marked in women. Among untreated residents, home systolic/diastolic BPs measured in the morning were higher than those measured in the evening; the differences were 5.7/5.0 mmHg in women (ranges across the cohorts, 5.3-6.8/4.7-5.4 mmHg) and 7.3/7.7 mmHg in men (ranges, 6.4-8.5/7.0-8.7 mmHg). In contrast, the home pulse rate in women and men was 2.4 (range, 1.5-3.7) and 5.6 (range, 4.6-6.6) beats per minute, respectively, higher in the evening than in the morning. We demonstrated the current status of home BP and home pulse rate in relation to sex, age, and antihypertensive treatment status in the Japanese general population. The approach by which fine-clustered aggregate statistics were collected and integrated could address practical issues raised in epidemiological research settings.

DOI： 10.1038/s41440-020-0530-1

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: To estimate the lifetime cumulative incidence of dementia and its subtypes from a community-dwelling elderly population in Japan. METHODS: A total of 1,193 community-dwelling Japanese individuals without dementia, aged 60 years or older, were followed up prospectively for 17 years. The cumulative incidence of dementia was estimated based on a death- and dementia-free survival function and the hazard functions of dementia at each year, which were computed by using a Weibull proportional hazards model. The lifetime risk of dementia was defined as the cumulative incidence of dementia at the point in time when the survival probability of the population was estimated to be less than 0.5%. RESULTS: During the follow-up, 350 participants experienced some type of dementia; among them, 191 participants developed Alzheimer disease (AD) and 117 developed vascular dementia (VaD). The lifetime risk of dementia was 55% (95% confidence interval, 49%-60%). Women had an approximately 1.5 times greater lifetime risk of dementia than men (65% [57%-72%] vs 41% [33%-49%]). The lifetime risks of developing AD and VaD were 42% (35%-50%) and 16% (12%-21%) in women vs 20% (7%-34%) and 18% (13%-23%) in men, respectively. CONCLUSION: Lifetime risk of all dementia for Japanese elderly was substantial at approximately 50% or higher. This study suggests that the lifetime burden attributable to dementia in contemporary Japanese communities is immense.

DOI： 10.1212/WNL.0000000000009917

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: To investigate the associations of 30 min postload plasma glucose (30 mPG) levels during an oral glucose tolerance test (OGTT) with the risk of future diabetes in a general Japanese population. RESEARCH DESIGN AND METHODS: A total of 2957 Japanese community-dwelling residents without diabetes, aged 40-79 years, participated in the examinations in 2007 and 2008 (participation rate, 77.1%). Among them, 2162 subjects who received 75 g OGTT in a fasting state with measurements of plasma glucose level at 0, 30, and 120 min were followed up for 7 years (2007-2014). Cox's proportional hazards model was used to estimate HRs and their 95% CIs of each index for the development of type 2 diabetes using continuous variables and quartiles with adjustment for traditional risk factors. The influence of 30 mPG on the predictive ability was estimated with Harrell's C-statistics, integrated discrimination improvement (IDI), and the continuous net reclassification index (cNRI). RESULTS: During follow-up, 275 subjects experienced type 2 diabetes. Elevated 30 mPG levels were significantly associated with increased risk of developing diabetes (p<0.01 for trend): the multivariable-adjusted HR was 8.41 (95% CI 4.97 to 14.24) for the highest versus the lowest quartile, and 2.26 (2.04 to 2.52) per 1 SD increase. This association was attenuated but remained significant after further adjustment for fasting and 2-hour postload plasma glucose levels. Incorporation of 30 mPG into the model including traditional risk factors with fasting and 2-hour postload plasma glucose levels for diabetes improved the predictive ability of type 2 diabetes (improvement in Harrell's C-statistics values: from 0.828 to 0.839, p<0.01; IDI: 0.016, p<0.01; cNRI: 0.103, p=0.37). CONCLUSIONS: Elevated 30 mPG levels were associated with increased risk of diabetes, and inclusion of 30 mPG levels significantly improved the predictive ability for future diabetes, suggesting that 30 mPG may be useful for identifying high-risk populations for type 2 diabetes.

DOI： 10.1136/bmjdrc-2019-001156

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

AIMS: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese community. METHODS: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years. The participants were divided into the quartiles of serum sdLDL cholesterol levels. The risk estimates were computed using a Cox proportional hazards model. RESULTS: During the follow-up period, 79 subjects developed CHD. Subjects in the highest quartile had a 5.41- fold (95% confidence interval, 2.12-13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders. In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of ＜32.9 mg/dL and serum LDL cholesterol of ＜120.1 mg/dL (median). When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p=0.02), and the net reclassification improvement was also significant (0.40; p＜0.001). CONCLUSIONS: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.

DOI： 10.5551/jat.51961

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Biomarkers for predicting future development of atrial fibrillation (AF) have not been fully established in general populations. The aim of this study was to assess the predictive ability of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) for the development of AF. METHODS AND RESULTS: A total of 3126 community-dwelling Japanese subjects aged ≥ 40 years without a history of AF in 2002 were followed up for a median of 10.2 years. Serum NT-proBNP levels at baseline were divided into four categories (≤ 54, 55-124, 125-299, and ≥ 300 pg/mL) according to the current guidelines and prior reports. The hazard ratios for the development of AF were estimated using a Cox proportional hazards model. During the follow-up period, 153 subjects developed new-onset AF. The age- and sex-adjusted cumulative incidence of AF increased significantly with higher serum NT-proBNP levels (p < 0.001 for trend). The association remained significant after adjustment for known risk factors for AF and cardiovascular disease (hazard ratio [95% confidence interval]: ≤ 54 pg/mL: 1.00 [reference]; 55-124 pg/mL: 1.72 [1.00-2.97]; 125-299 pg/mL: 3.95 [2.23-6.98]; ≥ 300 pg/mL: 8.51 [4.48-16.17]; p < 0.001 for trend). Furthermore, incorporation of serum NT-proBNP levels into the model consisting of known risk factors for AF and cardiovascular disease significantly improved the predictive ability for developing AF (Harrell's c-statistics: 0.828 to 0.844, p = 0.01; continuous net reclassification improvement: 0.41, p < 0.001; integrated discrimination improvement: 0.031, p < 0.001). CONCLUSIONS: Serum NT-proBNP levels can be a risk biomarker for predicting future development of AF in a general Japanese population.

DOI： 10.1016/j.ijcard.2020.06.018

Language：English   Publishing type：Research paper (scientific journal)  

Studies on the association between serum uric acid levels and the risk of cardiovascular disease have yielded inconsistent results. We investigated the association of serum uric acid levels with cardiovascular disease mortality in a Japanese community. A total of 2633 community-dwelling Japanese people aged ≥40 years without a history of cardiovascular disease were followed up for 19 years. Serum uric acid levels were categorized into quintiles (Q1, lowest; Q5, highest). The hazard ratios for mortality from cardiovascular disease, stroke, and coronary heart disease were computed using a Cox proportional hazards model. During the follow-up, 235 subjects died from cardiovascular disease (including 84 from stroke and 53 from coronary heart disease). Risks for cardiovascular disease mortality were higher in both the Q1 and Q5 groups than in the Q3 group after adjustment for confounding factors (Q1, hazard ratio 1.50 [95% confidence interval 0.94-2.39]; Q2, 1.06 [0.66-1.72]; Q3, 1.00 [reference]; Q4, 1.44 [0.93-2.23]; and Q5, 1.89 [1.23-2.91]). A similar U-shaped association was observed for stroke mortality (Q1, 3.26 [1.29-8.25]; Q2, 2.21 [0.85-5.73]; Q3, 1.00 [reference]; Q4, 2.65 [1.07-6.58]; and Q5, 3.77 [1.54-9.24]), while coronary heart disease mortality was increased only in the Q5 group (Q1, 1.27 [0.46-3.50]; Q2, 0.85 [0.29-2.48]; Q3, 1.00 [reference]; Q4, 1.57 [0.63-3.92]; and Q5, 2.53 [1.03-6.18]). Elevated serum uric acid was suggested to be a significant risk factor for stroke or coronary heart disease mortality in a Japanese community. Conversely, the excess risk of stroke mortality in individuals with lower serum uric acid levels may indicate a possible cerebroprotective role of uric acid.

DOI： 10.1038/s41440-019-0390-8

Language：English   Publishing type：Research paper (scientific journal)  

Objective To examine the association between serum total homocysteine levels (tHcy) and dementia risk. Methods A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia. Results During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 μmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 μmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 μmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07). Conclusion High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.

DOI： 10.1136/jnnp-2019-322366

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: To examine the association between serum total homocysteine levels (tHcy) and dementia risk. METHODS: A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia. RESULTS: During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07). CONCLUSION: High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.

DOI： 10.1136/jnnp-2019-322366

Language：English   Publishing type：Research paper (scientific journal)  

AIM: The present study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in subjects at high cardiovascular risk. METHODS: A total of 3,080 participants without prior cardiovascular disease (CVD), aged ≥ 40 years, were followed up for a median of 8.3 years, which were divided into two groups, those with serum sdLDL cholesterol levels of ＜35 mg/dL or ≥ 35 mg/dL. Then, subjects were stratified by the status of diabetes, CVD-related comorbidities (defined as the presence of diabetes, chronic kidney disease, or peripheral artery disease), and the CVD risk assessment according to the Japan Atherosclerosis Society Guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using a Cox proportional hazards model. RESULTS: During the follow-up, 79 subjects developed CHD. The risk for incident CHD was higher in subjects with serum sdLDL cholesterol of ≥ 35 mg/dL than those with sdLDL cholesterol of ＜35 mg/dL (HR 2.09, 95%CI 1.26-3.45) after adjusting for traditional risk factors. In the subgroup analyses, the multivariable-adjusted HR for incident CHD increased significantly in those with serum sdLDL cholesterol of ≥ 35 mg/dL among subjects with diabetes (HR 2.76, 95%CI 1.09-7.01), subjects with CVD-related comorbidities (HR 2.60, 95%CI 1.21-5.58), and high-risk category defined as the presence of CVD-related comorbidities or a Suita score of ≥ 56 points (HR 1.93, 95%CI 1.02-3.65). CONCLUSIONS: Elevated serum sdLDL cholesterol was associated with the development of CHD even in subjects at high cardiovascular risk.

DOI： 10.5551/jat.55350

Language：English   Publishing type：Research paper (scientific journal)  

Studies on the association between serum uric acid levels and the risk of cardiovascular disease have yielded inconsistent results. We investigated the association of serum uric acid levels with cardiovascular disease mortality in a Japanese community. A total of 2633 community-dwelling Japanese people aged ≥40 years without a history of cardiovascular disease were followed up for 19 years. Serum uric acid levels were categorized into quintiles (Q1, lowest; Q5, highest). The hazard ratios for mortality from cardiovascular disease, stroke, and coronary heart disease were computed using a Cox proportional hazards model. During the follow-up, 235 subjects died from cardiovascular disease (including 84 from stroke and 53 from coronary heart disease). Risks for cardiovascular disease mortality were higher in both the Q1 and Q5 groups than in the Q3 group after adjustment for confounding factors (Q1, hazard ratio 1.50 [95% confidence interval 0.94–2.39]; Q2, 1.06 [0.66–1.72]; Q3, 1.00 [reference]; Q4, 1.44 [0.93–2.23]; and Q5, 1.89 [1.23–2.91]). A similar U-shaped association was observed for stroke mortality (Q1, 3.26 [1.29–8.25]; Q2, 2.21 [0.85–5.73]; Q3, 1.00 [reference]; Q4, 2.65 [1.07–6.58]; and Q5, 3.77 [1.54–9.24]), while coronary heart disease mortality was increased only in the Q5 group (Q1, 1.27 [0.46–3.50]; Q2, 0.85 [0.29–2.48]; Q3, 1.00 [reference]; Q4, 1.57 [0.63–3.92]; and Q5, 2.53 [1.03–6.18]). Elevated serum uric acid was suggested to be a significant risk factor for stroke or coronary heart disease mortality in a Japanese community. Conversely, the excess risk of stroke mortality in individuals with lower serum uric acid levels may indicate a possible cerebroprotective role of uric acid.

DOI： 10.1038/s41440-019-0390-8

Language：English   Publishing type：Research paper (scientific journal)  

Background: Despite a steady world-wide decline over recent decades, rates of smoking remain high in developed countries. In Japan, 30% of men and 10% of women are smokers. Based on these rates, 18.8 million (14.06 million men and 4.74 million women) in Japan are smokers. The rate of success for smoking cessation has recently improved due to the widespread availability of drug therapy; however, the success rate for quitting smoking one year after beginning therapy is only around 50%. Previous studies have demonstrated that exercise can relieve mental stress during continuous abstinence from smoking and curb smoking resumption. To date, no large-scale, randomized controlled trials have examined the effects of exercise on smoking cessation. The present study aims to determine the effects of exercise instruction on continuous abstinence from smoking after completion of smoking cessation therapy. Methods: This is a multicenter, prospective, parallel-group, randomized controlled trial in Japan. We will enroll 300 individuals visiting a smoking cessation clinic (over 3 months) who have abstained from smoking in the second month after their initial visit as potential participants. Participants will not habitually exercise and will need to consent to participate. Participants will be randomly assigned to the exercise intervention group or control group. The intervention group will receive instruction on exercises that can be incorporated into their daily lives. The control group will be followed during the standard smoking cessation support program. The primary endpoint will be the continuous abstinence rate, and secondary endpoints will be weight, blood pressure, exhaled carbon monoxide concentration, psychological state, and blood test results. These indices will be compared between the intervention and control groups, with follow-up periods of 9 months in both groups. Discussion: By examining the effects of exercise instruction after completion of 12-week smoking cessation therapy, this study should yield quality information that can be used to develop protocols to improve the continuous abstinence rate and inhibit weight gain after smoking cessation therapy. Trial registration: UMIN Clinical Trials Registry, UMIN000014615. Registered on 1 October 2014.

DOI： 10.1186/s13063-019-3820-7

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Despite a steady world-wide decline over recent decades, rates of smoking remain high in developed countries. In Japan, 30% of men and 10% of women are smokers. Based on these rates, 18.8 million (14.06 million men and 4.74 million women) in Japan are smokers. The rate of success for smoking cessation has recently improved due to the widespread availability of drug therapy; however, the success rate for quitting smoking one year after beginning therapy is only around 50%. Previous studies have demonstrated that exercise can relieve mental stress during continuous abstinence from smoking and curb smoking resumption. To date, no large-scale, randomized controlled trials have examined the effects of exercise on smoking cessation. The present study aims to determine the effects of exercise instruction on continuous abstinence from smoking after completion of smoking cessation therapy. METHODS: This is a multicenter, prospective, parallel-group, randomized controlled trial in Japan. We will enroll 300 individuals visiting a smoking cessation clinic (over 3 months) who have abstained from smoking in the second month after their initial visit as potential participants. Participants will not habitually exercise and will need to consent to participate. Participants will be randomly assigned to the exercise intervention group or control group. The intervention group will receive instruction on exercises that can be incorporated into their daily lives. The control group will be followed during the standard smoking cessation support program. The primary endpoint will be the continuous abstinence rate, and secondary endpoints will be weight, blood pressure, exhaled carbon monoxide concentration, psychological state, and blood test results. These indices will be compared between the intervention and control groups, with follow-up periods of 9 months in both groups. DISCUSSION: By examining the effects of exercise instruction after completion of 12-week smoking cessation therapy, this study should yield quality information that can be used to develop protocols to improve the continuous abstinence rate and inhibit weight gain after smoking cessation therapy. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000014615. Registered on 1 October 2014.

DOI： 10.1186/s13063-019-3820-7

Language：English   Publishing type：Research paper (scientific journal)  

Background: Epidemiological studies have reported a link between serum LBP (lipopolysaccharide-binding protein) levels and lifestyle-related diseases. However, there have been no longitudinal studies investigating the association of serum LBP levels and the incidence of cardiovascular disease (CVD) in general populations. Methods and Results: A total of 2568 community-dwelling Japanese individuals 40 years and older without prior CVD were followed for 10 years (2002–2012). Serum LBP levels were divided into quartiles (quartile 1: 2.20–9.68 μg/mL; quartile 2: 9.69–10.93 μg/mL; quartile 3: 10.94–12.40 μg/mL; quartile 4: 12.41–24.34 μg/mL). The hazard ratios (HRs) and their 95% CIs for the incidence of CVD were computed using a Cox proportional hazards model. During the follow-up period, 180 individuals developed CVD. The age- and sex-adjusted cumulative incidence of CVD increased significantly with higher serum LBP levels (P for trend=0.005). Individuals with higher serum LBP levels had a significantly greater risk of the development of CVD after adjusting for conventional cardiovascular risk factors (quartile 1: HR, 1.00 [reference]; quartile 2: HR, 1.04 [95% CI, 0.60–1.78]; quartile 3: HR, 1.52 [95% CI, 0.92–2.51]; and quartile 4: HR, 1.90 [95% CI, 1.17–3.09]; P for trend=0.01). This association remained significant after additional adjustment for homeostasis model assessment of insulin resistance (P for trend=0.01). However, when additional adjustment was made for high-sensitivity C-reactive protein, the association was attenuated to the nonsignificant level (P for trend=0.08). Conclusions: The present findings suggest that higher serum LBP levels are associated with increased risk of the development of CVD in the general Japanese population. Low-grade endotoxemia may contribute to the pathogenesis of CVD through chronic systemic inflammation.

DOI： 10.1161/JAHA.119.013628

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The associations between trans fatty acids and dementia have been unclear. We investigated the prospective association between serum elaidic acid (trans 18:1 n-9) levels, as an objective biomarker for industrial trans fat, and incident dementia and its subtypes. METHODS: In total, 1,628 Japanese community residents aged 60 and older without dementia were followed prospectively from when they underwent a screening examination in 2002-2003 to November 2012 (median 10.3 years, interquartile range 7.2-10.4 years). Serum elaidic acid levels were measured using gas chromatography/mass spectrometry and divided into quartiles. The Cox proportional hazards model was used to estimate the hazard ratios for all-cause dementia, Alzheimer disease (AD), and vascular dementia by serum elaidic acid levels. RESULTS: During the follow-up, 377 participants developed some type of dementia (247 AD, 102 vascular dementia). Higher serum elaidic acid levels were significantly associated with greater risk of developing all-cause dementia (p for trend = 0.003) and AD (p for trend = 0.02) after adjustment for traditional risk factors. These associations remained significant after adjustment for dietary factors, including total energy intake and intakes of saturated and polyunsaturated fatty acids (both p for trend <0.05). No significant associations were found between serum elaidic acid levels and vascular dementia. CONCLUSIONS: The findings suggest that higher serum elaidic acid is a possible risk factor for the development of all-cause dementia and AD in later life. Public health policy to reduce industrially produced trans fatty acids may assist in the primary prevention of dementia.

DOI： 10.1212/WNL.0000000000008464

Language：English   Publishing type：Research paper (scientific journal)  

Background Epidemiological studies have reported a link between serum LBP (lipopolysaccharide-binding protein) levels and lifestyle-related diseases. However, there have been no longitudinal studies investigating the association of serum LBP levels and the incidence of cardiovascular disease (CVD) in general populations. Methods and Results A total of 2568 community-dwelling Japanese individuals 40 years and older without prior CVD were followed for 10 years (2002-2012). Serum LBP levels were divided into quartiles (quartile 1: 2.20-9.68 μg/mL; quartile 2: 9.69-10.93 μg/mL; quartile 3: 10.94-12.40 μg/mL; quartile 4: 12.41-24.34 μg/mL). The hazard ratios (HRs) and their 95% CIs for the incidence of CVD were computed using a Cox proportional hazards model. During the follow-up period, 180 individuals developed CVD. The age- and sex-adjusted cumulative incidence of CVD increased significantly with higher serum LBP levels (P for trend=0.005). Individuals with higher serum LBP levels had a significantly greater risk of the development of CVD after adjusting for conventional cardiovascular risk factors (quartile 1: HR, 1.00 [reference]; quartile 2: HR, 1.04 [95% CI, 0.60-1.78]; quartile 3: HR, 1.52 [95% CI, 0.92-2.51]; and quartile 4: HR, 1.90 [95% CI, 1.17-3.09]; P for trend=0.01). This association remained significant after additional adjustment for homeostasis model assessment of insulin resistance (P for trend=0.01). However, when additional adjustment was made for high-sensitivity C-reactive protein, the association was attenuated to the nonsignificant level (P for trend=0.08). Conclusions The present findings suggest that higher serum LBP levels are associated with increased risk of the development of CVD in the general Japanese population. Low-grade endotoxemia may contribute to the pathogenesis of CVD through chronic systemic inflammation.

DOI： 10.1161/JAHA.119.013628

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The associations between trans fatty acids and dementia have been unclear. We investigated the prospective association between serum elaidic acid (trans 18:1 n-9) levels, as an objective biomarker for industrial trans fat, and incident dementia and its subtypes. METHODS: In total, 1,628 Japanese community residents aged 60 and older without dementia were followed prospectively from when they underwent a screening examination in 2002-2003 to November 2012 (median 10.3 years, interquartile range 7.2-10.4 years). Serum elaidic acid levels were measured using gas chromatography/mass spectrometry and divided into quartiles. The Cox proportional hazards model was used to estimate the hazard ratios for all-cause dementia, Alzheimer disease (AD), and vascular dementia by serum elaidic acid levels. RESULTS: During the follow-up, 377 participants developed some type of dementia (247 AD, 102 vascular dementia). Higher serum elaidic acid levels were significantly associated with greater risk of developing all-cause dementia (p for trend = 0.003) and AD (p for trend = 0.02) after adjustment for traditional risk factors. These associations remained significant after adjustment for dietary factors, including total energy intake and intakes of saturated and polyunsaturated fatty acids (both p for trend <0.05). No significant associations were found between serum elaidic acid levels and vascular dementia. CONCLUSIONS: The findings suggest that higher serum elaidic acid is a possible risk factor for the development of all-cause dementia and AD in later life. Public health policy to reduce industrially produced trans fatty acids may assist in the primary prevention of dementia.

DOI： 10.1212/WNL.0000000000008464

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

We examined the association between serum concentrations of β-alanine, a metabolite of carnosine and anserine, and the risk of dementia in a general population of elderly Japanese persons. In 2007, 1,475 residents of Hisayama, Japan, aged 60-79 years and without dementia were divided into 4 groups according to quartiles of serum β-alanine concentrations (quartile 1, lowest; quartile 4, highest) and followed for a median of 5.3 years. During follow-up, 117 subjects developed all-cause dementia (Alzheimer in 77 cases and vascular dementia in 31). The risk of all-cause dementia decreased with increasing serum β-alanine levels after adjustment for potential confounding factors (quartile 2, hazard ratio (HR) = 0.73 (95% confidence interval (CI): 0.45, 1.18); quartile 3, HR = 0.50 (95% CI: 0.28, 0.89); quartile 4, HR = 0.50 (95% CI: 0.27, 0.92); P = 0.01 for trend). A similar inverse association was observed for Alzheimer disease (quartile 2, HR = 0.78 (95% CI: 0.44, 1.38); quartile 3, HR = 0.53 (95% CI: 0.26, 1.06); quartile 4, HR = 0.53 (95% CI: 0.25, 1.10); P = 0.04 for trend) but not for vascular dementia. We found that higher serum β-alanine levels were significantly associated with lower risks of all-cause dementia and Alzheimer disease. Because serum β-alanine levels reflect intakes of carnosine/anserine, higher intakes of carnosine/anserine might be beneficial for the prevention of dementia.

DOI： 10.1093/aje/kwz116

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Background Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels and dementia. Methods and Results A total of 1635 community-dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT-proBNP levels were divided into 4 categories (≤54, 55-124, 125-299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow-up period, 377 subjects developed all-cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age- and sex-adjusted incidence of all-cause dementia was 31.5 per 1000 person-years and increased significantly with higher serum NT-proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend <0.01). Subjects with serum NT-proBNP levels of ≥300 pg/mL had a significantly higher risk of all-cause dementia (hazard ratio=2.46, 95% CI 1.63-3.71) than those with serum NT-proBNP levels of ≤54 pg/mL after adjusting for confounders. Similar risks were observed for Alzheimer disease and vascular dementia. Incorporation of the serum NT-proBNP level into a model with known risk factors for dementia significantly improved the predictive ability for incident dementia (c-statistics 0.780-0.787, P=0.02; net reclassification improvement 0.189, P=0.001; integrated discrimination improvement 0.011, P=0.003). Conclusions Higher serum NT-proBNP levels were significantly associated with an increased risk of dementia. Serum NT-proBNP could be a novel biomarker for predicting future risk of dementia in the general elderly population.

DOI： 10.1161/JAHA.118.011652

Language：English   Publishing type：Research paper (scientific journal)  

Association Between Serum β-Alanine and Risk of Dementia.
We examined the association between serum concentrations of β-alanine, a metabolite of carnosine and anserine, and the risk of dementia in a general population of elderly Japanese persons. In 2007, 1,475 residents of Hisayama, Japan, aged 60-79 years and without dementia were divided into 4 groups according to quartiles of serum β-alanine concentrations (quartile 1, lowest; quartile 4, highest) and followed for a median of 5.3 years. During follow-up, 117 subjects developed all-cause dementia (Alzheimer in 77 cases and vascular dementia in 31). The risk of all-cause dementia decreased with increasing serum β-alanine levels after adjustment for potential confounding factors (quartile 2, hazard ratio (HR) = 0.73 (95% confidence interval (CI): 0.45, 1.18); quartile 3, HR = 0.50 (95% CI: 0.28, 0.89); quartile 4, HR = 0.50 (95% CI: 0.27, 0.92); P = 0.01 for trend). A similar inverse association was observed for Alzheimer disease (quartile 2, HR = 0.78 (95% CI: 0.44, 1.38); quartile 3, HR = 0.53 (95% CI: 0.26, 1.06); quartile 4, HR = 0.53 (95% CI: 0.25, 1.10); P = 0.04 for trend) but not for vascular dementia. We found that higher serum β-alanine levels were significantly associated with lower risks of all-cause dementia and Alzheimer disease. Because serum β-alanine levels reflect intakes of carnosine/anserine, higher intakes of carnosine/anserine might be beneficial for the prevention of dementia.

DOI： 10.1093/aje/kwz116

Language：English   Publishing type：Research paper (scientific journal)  

Background Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels and dementia. Methods and Results A total of 1635 community-dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT-proBNP levels were divided into 4 categories (≤54, 55-124, 125-299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow-up period, 377 subjects developed all-cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age- and sex-adjusted incidence of all-cause dementia was 31.5 per 1000 person-years and increased significantly with higher serum NT-proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend <0.01). Subjects with serum NT-proBNP levels of ≥300 pg/mL had a significantly higher risk of all-cause dementia (hazard ratio=2.46, 95% CI 1.63-3.71) than those with serum NT-proBNP levels of ≤54 pg/mL after adjusting for confounders. Similar risks were observed for Alzheimer disease and vascular dementia. Incorporation of the serum NT-proBNP level into a model with known risk factors for dementia significantly improved the predictive ability for incident dementia (c-statistics 0.780-0.787, P=0.02; net reclassification improvement 0.189, P=0.001; integrated discrimination improvement 0.011, P=0.003). Conclusions Higher serum NT-proBNP levels were significantly associated with an increased risk of dementia. Serum NT-proBNP could be a novel biomarker for predicting future risk of dementia in the general elderly population.

DOI： 10.1161/JAHA.118.011652

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS: A total of 2,253 community-dwelling Japanese individuals aged 40-79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87-2.10, 2.11-5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of l-theanine-rich green tea products containing 8 mg of l-theanine by 12 healthy volunteers. RESULTS: During follow-up, 282 subjects developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine (P for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariable-adjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49-0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was >5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h. CONCLUSIONS: Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of l-theanine consumption.

DOI： 10.2337/dc18-2655

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE This study investigated the association between serum ethylamine levels as an indicator of L-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS A total of 2,253 community-dwelling Japanese individuals aged 40-79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87-2.10, 2.11-5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of L-theanine-rich green tea products containing 8 mg of L-theanine by 12 healthy volunteers. RESULTS During follow-up, 282 subjects developed type 2 diabetes. The age- and sexadjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine (P for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariableadjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49-0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was >5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h. CONCLUSIONS Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of L-theanine consumption.

DOI： 10.2337/dc18-2655

Language：English   Publishing type：Research paper (scientific journal)  

Background and aims: Predicting cardiovascular events is of practical benefit for disease prevention. The aim of this study was to develop and evaluate an updated risk prediction model for cardiovascular diseases and its subtypes. Methods: A total of 2462 community residents aged 40–84 years were followed up for 24 years. A Cox proportional hazards regression model was used to develop risk prediction models for cardiovascular diseases, and separately for stroke and coronary heart diseases. The risk assessment ability of the developed model was evaluated, and a bootstrapping method was used for internal validation. The predicted risk was translated into a simplified scoring system. A decision curve analysis was used to evaluate clinical usefulness. Results: The multivariable model for cardiovascular diseases included age, sex, systolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking habits, and regular exercise as predictors. The models for stroke and coronary heart diseases incorporated both shared and unique variables. The developed models showed good discrimination with little evidence of overfitting (optimism-corrected Harrell's C statistics 0.726–0.777) and calibrations (Hosmer-Lemeshow test, p = 0.44–0.90). The decision curve analysis revealed that the predicted risk-based decision-making would have higher net benefit than either a CVD intervention strategy for all individuals or no individuals. Conclusions: The developed risk prediction models showed a good performance and satisfactory internal validity, which may help understand individual risk and setting personalized goals, and promote risk stratification in public health strategies for CVD prevention.

DOI： 10.1016/j.atherosclerosis.2018.10.014

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Predicting cardiovascular events is of practical benefit for disease prevention. The aim of this study was to develop and evaluate an updated risk prediction model for cardiovascular diseases and its subtypes. METHODS: A total of 2462 community residents aged 40-84 years were followed up for 24 years. A Cox proportional hazards regression model was used to develop risk prediction models for cardiovascular diseases, and separately for stroke and coronary heart diseases. The risk assessment ability of the developed model was evaluated, and a bootstrapping method was used for internal validation. The predicted risk was translated into a simplified scoring system. A decision curve analysis was used to evaluate clinical usefulness. RESULTS: The multivariable model for cardiovascular diseases included age, sex, systolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking habits, and regular exercise as predictors. The models for stroke and coronary heart diseases incorporated both shared and unique variables. The developed models showed good discrimination with little evidence of overfitting (optimism-corrected Harrell's C statistics 0.726-0.777) and calibrations (Hosmer-Lemeshow test, p = 0.44-0.90). The decision curve analysis revealed that the predicted risk-based decision-making would have higher net benefit than either a CVD intervention strategy for all individuals or no individuals. CONCLUSIONS: The developed risk prediction models showed a good performance and satisfactory internal validity, which may help understand individual risk and setting personalized goals, and promote risk stratification in public health strategies for CVD prevention.

DOI： 10.1016/j.atherosclerosis.2018.10.014

Language：English   Publishing type：Research paper (scientific journal)  

Blood pressure variability (BPV) has been shown to be associated with cardiovascular diseases. The effects on long-term BPV of obstructive sleep apnea (OSA) are not yet known. We evaluated a total of 1653 Japanese male workers (18–69 years) at a work site to diagnose OSA, and we divided them into three groups: non-OSA (apnea–hypopnea index (AHI): < 5, n = 1414), mild-to-moderate OSA (5 ≤ AHI < 30: n = 131) and severe OSA (AHI ≥ 30: n = 108). The standard deviation and coefficient of variation of the subjects’ BPV were calculated by using their annual blood pressure measurements at routine physical examinations from 2012 to 2015 (four measurements). The multivariable-adjusted BPV of systolic blood pressure (SBP) was significantly higher in the severe-OSA group compared to the non-OSA group. A multiple regression analysis also revealed that OSA was positively associated with BPV of SBP. We focused on the mild-to-moderate OSA group to evaluate the association of OSA treatment with BPV, because most of the severe-OSA subjects were being treated with continuous positive airway pressure or an oral appliance. The BPV of both systolic and diastolic blood pressure was significantly decreased in the treated subjects. These findings suggest that OSA is associated with increases in long-term BPV which was improved by the treatment of OSA in Japanese men of a work-site population.

DOI： 10.1038/s41440-018-0096-3

Language：English   Publishing type：Research paper (scientific journal)  

Blood pressure variability (BPV) has been shown to be associated with cardiovascular diseases. The effects on long-term BPV of obstructive sleep apnea (OSA) are not yet known. We evaluated a total of 1653 Japanese male workers (18-69 years) at a work site to diagnose OSA, and we divided them into three groups: non-OSA (apnea-hypopnea index (AHI): < 5, n = 1414), mild-to-moderate OSA (5 ≤ AHI < 30: n = 131) and severe OSA (AHI ≥ 30: n = 108). The standard deviation and coefficient of variation of the subjects' BPV were calculated by using their annual blood pressure measurements at routine physical examinations from 2012 to 2015 (four measurements). The multivariable-adjusted BPV of systolic blood pressure (SBP) was significantly higher in the severe-OSA group compared to the non-OSA group. A multiple regression analysis also revealed that OSA was positively associated with BPV of SBP. We focused on the mild-to-moderate OSA group to evaluate the association of OSA treatment with BPV, because most of the severe-OSA subjects were being treated with continuous positive airway pressure or an oral appliance. The BPV of both systolic and diastolic blood pressure was significantly decreased in the treated subjects. These findings suggest that OSA is associated with increases in long-term BPV which was improved by the treatment of OSA in Japanese men of a work-site population.

DOI： 10.1038/s41440-018-0096-3

Language：English   Publishing type：Research paper (scientific journal)  

It has been shown that obstructive sleep apnea (OSA) is related to hypertension and cardiovascular disease; however, the prevalence of OSA in general population and the impact of it on blood pressure especially in Japan has not been well determined. We have conducted a screening test for OSA from 2003 to 2011. In addition, a cross-sectional analysis was performed in 2012 to determine the association of OSA and cardiovascular risk factors in Japanese men (18–69 years of age; mean age, 44.4 ± 0.2). The study group consisted of 2208 male employees, and OSA was evaluated by using the 4% oxygen desaturation index and apnea-hypopnea index (AHI). The prevalence of mild-to-moderate (5≤AHI<30) and severe (AHI≥30) OSA in the studied subjects were 7.1%, and 6.1%, respectively. Among the 135 severe OSA subjects, 105 (77.8%) had been treated with continuous positive airway pressure. Both systolic and diastolic blood pressures (DBP) were significantly increased in the subjects with severe OSA compared with those without OSA. These associations in DBP remained observed after adjustment for age, body mass index (BMI), estimated glomerular filtration rate, HbA_1c, current alcohol intake, current smoking habits, and OSA treatment. DBP in severe OSA subjects were significantly increased in 1807 subjects who were not treated for hypertension or OSA. However, the levels of blood pressures were not decreased by OSA treatment. These results suggest that the prevalence of OSA is relatively high in middle-aged Japanese men and that blood pressures were elevated in the subjects with severe OSA.

DOI： 10.1080/10641963.2017.1324476

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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.

DOI： 10.1038/hr.2017.74

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1038/hr.2017.74

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1253/circj.CJ-16-1306

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1161/CIRCULATIONAHA.116.025667

Language：English   Publishing type：Research paper (scientific journal)  

The purpose of the present study was to investigate blood pressure (BP) control and salt intake in hypertensive outpatients treated at a general hospital and to examine the relationship between their lifestyles and amount of salt intake. Subjects comprised 429 hypertensive patients (206 males, 223 females, and average age of 71 ± 11 years). We estimated 24-hour salt excretion using spot urine samples and assessed lifestyle using a self-description questionnaire. Average clinic BP and the number of antihypertensive drugs were 132 ± 11/73 ± 8 mmHg and 1.8 ± 0.9, respectively. In all subjects, average estimated salt intake was 9.2 ± 2.8 g/day and the rate of achievement of the estimated salt intake of <6 g/day was 11.2%. In patients with chronic kidney disease or cardiovascular disease, these values were 8.6 ± 2.6 g/day and 15.5%, and 9.1 ± 3.3 g/day and 18.2%, respectively. Estimated salt intake was lower in patients living alone than in those with a family. In a multivariate analysis, estimated salt intake correlated positively with body mass index and negatively with age. Among patients with an excessive salt intake (≥10 g/day), 75.2% answered that they made an effort to reduce their salt intake. The amount of food and processed food consumption correlated with estimated salt intake. In conclusion, the rate of achievement of salt restriction was low in hypertensive patients treated at a general hospital. It may be important to provide data on actual salt intake and guide salt restriction in the individual management of hypertension.

DOI： 10.1080/10641963.2016.1200605

Language：English   Publishing type：Research paper (scientific journal)  

Salt restriction is important for the prevention and treatment of hypertension; however, salt consumption is still high in Japan. Improvements in dietary habits, including salt reduction in childhood, may contribute to the prevention of hypertension. The aim of the present study was to investigate the salt intake of school-aged children and the relationship between their diet diary and actual salt intake. The subjects comprised 580 schoolchildren (471 elementary school pupils and 109 junior high school pupils) who wanted to evaluate their salt intake in Kuji, a northeast coastal area in Japan. We estimated salt intake using spot urine samples and a formula. Lifestyle was assessed using a questionnaire. We also evaluated the salt intake and the lifestyles of 440 parents. The estimated salt intakes of elementary school pupils, junior high school pupils and their parents were 7.1±1.5, 7.6±1.5 and 8.0±1.7 g per day, respectively. The proportion of lower-grade children who achieved the recommended salt intake was low. In the multivariate analysis, the estimated salt intake of school-aged children correlated with their age, estimated salt intake of their parents and the menu priorities of the household. The estimated salt intake of the parents was associated with female gender, obesity, age and the habitual consumption of bread and noodles. In conclusion, the estimated salt intake of school-aged children positively correlated with the estimated salt intake of their parents, and the proportion of lower-grade children who achieved the recommended salt intake was low. Guidance on salt restriction for children and their parents may reduce the salt intake of school-aged children.

DOI： 10.1038/hr.2016.73

Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.2169/internalmedicine.55.4524

Language：English   Publishing type：Research paper (scientific journal)  

Salt restriction is important for the prevention and treatment of hypertension; however, salt consumption is still high in Japan. Improvements in dietary habits, including salt reduction in childhood, may contribute to the prevention of hypertension. The aim of the present study was to investigate the salt intake of school-aged children and the relationship between their diet diary and actual salt intake. The subjects comprised 580 schoolchildren (471 elementary school pupils and 109 junior high school pupils) who wanted to evaluate their salt intake in Kuji, a northeast coastal area in Japan. We estimated salt intake using spot urine samples and a formula. Lifestyle was assessed using a questionnaire. We also evaluated the salt intake and the lifestyles of 440 parents. The estimated salt intakes of elementary school pupils, junior high school pupils and their parents were 7.1±1.5, 7.6±1.5 and 8.0±1.7 g per day, respectively. The proportion of lower-grade children who achieved the recommended salt intake was low. In the multivariate analysis, the estimated salt intake of school-aged children correlated with their age, estimated salt intake of their parents and the menu priorities of the household. The estimated salt intake of the parents was associated with female gender, obesity, age and the habitual consumption of bread and noodles. In conclusion, the estimated salt intake of school-aged children positively correlated with the estimated salt intake of their parents, and the proportion of lower-grade children who achieved the recommended salt intake was low. Guidance on salt restriction for children and their parents may reduce the salt intake of school-aged children.

DOI： 10.1038/hr.2016.73

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The relationship between salt (sodium chloride) intake and pregnancy-induced hypertension (PIH) remains unclear. The aim of this study was therefore to investigate the current status of salt intake during pregnancy and identify effective predictors for PIH. METHODS AND RESULTS: Participants were 184 pregnant women who collected 24-h home urine as well as early morning urine samples. We investigated urinary salt excretion, home blood pressure (HBP) measurements for 7 consecutive days before the 20th and after the 30th gestational week, and the development of PIH. Urinary salt excretion according to early morning urine before the 20th gestational week was 8.6±1.7 g/day, and was significantly correlated with that measured from 24-h collected urine. Early morning urine estimated urinary salt excretion was slightly but significantly increased during pregnancy. HBP was 102±10/63±8 mmHg before the 20th gestational week and 104±12/64±10 mmHg after the 30th gestational week. On multiple regression analysis, serum uric acid and body mass index, but not urinary salt excretion, contributed to HBP both before the 20th and after the 30th gestational week. Fourteen participants (7.6%) developed PIH. On multivariate analysis, higher HBP and older age, but not urinary salt excretion, were significantly associated with PIH. CONCLUSIONS: Higher HBP and older age, but not urinary salt excretion, are predictors of PIH. (Circ J 2016; 80: 2165-2172).

DOI： 10.1253/circj.CJ-16-0405

Language：English   Publishing type：Research paper (scientific journal)  

Objective The purpose of the present study was to assess the prevalence of orthostatic hypotension (OH) and elucidate its associations with the demographic characteristics and the prognosis in elderly subjects with dementia who visited a hospital for elderly daycare. Methods A total of 64 outpatients (44 females) with a mean age of 84±6 years who visited a hospital for daycare were enrolled in the study. The prevalence of OH and demographic characteristics were examined. Then, the subjects were followed up for 1 year. The blood pressure was measured in the supine position and immediately, 1, 3 and 5 minutes after standing. Poor outcome measures included death, hospitalization for any reason, and admission to a nursing home or geriatric facility. Results OH was present in 17 patients (26.6%). The presence of OH was associated with a higher supine systolic blood pressure. The increase in heart rate in the standing position was also reduced in subjects with OH compared with those without. The presence of OH was associated with faster time in the timed up-andgo test compared with those without OH. During the follow-up period, 22 patients (34.4%) had a poor prognosis, of which 8 (36.4%) had OH, which tended to be higher than those with a favorable prognosis. The event-free survival rate appeared to be lower in subjects with OH than in those without. Conclusion OH is relatively common in frail elderly patients with dementia, and it also appears to be associated with a poor prognosis.

DOI： 10.2169/internalmedicine.55.4524

Language：English   Publishing type：Research paper (scientific journal)  

Background: The relationship between salt (sodium chloride) intake and pregnancy-induced hypertension (PIH) remains unclear. The aim of this study was therefore to investigate the current status of salt intake during pregnancy and identify effective predictors for PIH. Methods and Results: Participants were 184 pregnant women who collected 24-h home urine as well as early morning urine samples. We investigated urinary salt excretion, home blood pressure (HBP) measurements for 7 consecutive days before the 20th and after the 30th gestational week, and the development of PIH. Urinary salt excretion according to early morning urine before the 20th gestational week was 8.6±1.7 g/day, and was significantly correlated with that measured from 24-h collected urine. Early morning urine estimated urinary salt excretion was slightly but significantly increased during pregnancy. HBP was 102±10/63±8 mmHg before the 20th gestational week and 104±12/64±10 mmHg after the 30th gestational week. On multiple regression analysis, serum uric acid and body mass index, but not urinary salt excretion, contributed to HBP both before the 20th and after the 30th gestational week. Fourteen participants (7.6%) developed PIH. On multivariate analysis, higher HBP and older age, but not urinary salt excretion, were significantly associated with PIH. Conclusions: Higher HBP and older age, but not urinary salt excretion, are predictors of PIH.

DOI： 10.1253/circj.CJ-16-0405

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Assessing an individual's salt intake is necessary for providing guidance with respect to salt restriction. However, the methods that exist for assessing salt intake have both merits and limitations. Therefore, the evaluation methods should be selected for their appropriateness to the patients and the environment of the medical facilities. The purpose of the present study was to investigate the validity of a brief self-administered diet-history questionnaire (BDHQ) by comparing the responses with 24-h urinary salt excretion. A total of 136 hypertensive outpatients (54 men and 82 women) were included in this study. All subjects were given the BDHQ and performed 24-h home urine collection. The energy-adjusted salt intake as assessed by the BDHQ was 12.3 (95% confidence interval: 11.8-12.9) g per day, and the urinary salt excretion evaluated by 24-h urinary collection was 9.0 (8.4-9.5) g per day. The energy-adjusted salt intake assessed by the BDHQ correlated significantly with the urinary salt excretion evaluated by 24-h urinary collection (r=0.34, P<0.001). In conclusion, the estimated salt intake evaluated by the BDHQ weakly, but significantly, correlated with 24-h urinary salt excretion. In clinical practice, it seems important to utilize both methods to assess an individual's salt intake in order to provide adequate guidance for salt restriction.

DOI： 10.1038/hr.2015.35

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DOI： 10.3109/10641963.2015.1057831

Language：English   Publishing type：Research paper (scientific journal)  

Assessing an individual's salt intake is necessary for providing guidance with respect to salt restriction. However, the methods that exist for assessing salt intake have both merits and limitations. Therefore, the evaluation methods should be selected for their appropriateness to the patients and the environment of the medical facilities. The purpose of the present study was to investigate the validity of a brief self-administered diet-history questionnaire (BDHQ) by comparing the responses with 24-h urinary salt excretion. A total of 136 hypertensive outpatients (54 men and 82 women) were included in this study. All subjects were given the BDHQ and performed 24-h home urine collection. The energy-adjusted salt intake as assessed by the BDHQ was 12.3 (95% confidence interval: 11.8-12.9) g per day, and the urinary salt excretion evaluated by 24-h urinary collection was 9.0 (8.4-9.5) g per day. The energy-adjusted salt intake assessed by the BDHQ correlated significantly with the urinary salt excretion evaluated by 24-h urinary collection (r=0.34, P<0.001). In conclusion, the estimated salt intake evaluated by the BDHQ weakly, but significantly, correlated with 24-h urinary salt excretion. In clinical practice, it seems important to utilize both methods to assess an individual's salt intake in order to provide adequate guidance for salt restriction.

DOI： 10.1038/hr.2015.35

Language：English   Publishing type：Research paper (scientific journal)  

Among the several methods used to assess salt intake, estimating 24 h urinary salt excretion by spot urine seems appropriate for clinical practice. In this study, we investigated variability in urinary salt excretion using spot urine in hypertensive outpatients. Participants included 200 hypertensive patients who underwent spot urinary salt excretion at least three times during the observation period. Mean urinary salt excretion and the coefficient of the variation were 8.62 ± 1.96 g/day and 19.0 ± 10.2%, respectively. In the analysis of participants who underwent assessment of urinary salt excretion at least eight times (n = 54), a significant reduction in mean urinary salt excretion was found at the 5th measurement. On the contrary, the coefficient of the variation of urinary salt excretion continued to increase until the 5th measurement, and became stable thereafter. Mean urinary salt excretion was positively correlated with mean clinic diastolic blood pressure (r = 0.27, p < 0.05). Clinic diastolic blood pressure in the high urinary salt excretion group (≥10 g/day) was significantly higher than that of the low group (76.2 ± 7.5 vs 73.4 ± 8.3 mmHg, p < 0.05). Mean urinary salt excretion in summer was significantly lower than that of the other seasons (7.75 ± 1.94 vs 9.09 ± 2.68 (spring), 8.72 ± 2.12 (autumn), 8.92 ± 2.17 (winter) g/day, p < 0.01). In conclusion, repeated measurements of urinary salt excretion using spot urine are required to assess daily salt intake of hypertensive patients.

DOI： 10.3109/10641963.2015.1057831

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Language：English   Publishing type：Research paper (scientific journal)  

Strict control of blood pressure is important to prevent cardiovascular disease, although it is sometimes difficult to decrease blood pressure to target levels. The aim of this study was to investigate the clinical characteristics of resistant hypertension evaluated by ambulatory blood pressure monitoring. One hundred in-hospital patients, whose 24-hour average blood pressure was higher than 130/80ommHg even after treatment with more than three antihypertensive drugs, were included in the present analysis. Circadian variation of blood pressure was evaluated by nocturnal fall in systolic blood pressure. Average blood pressures of all patients were high in both daytime and nighttime, 150.0/82.9 and 143.8/78.2ommHg, respectively. Twenty patients had been treated with hemodialysis or peritoneal dialysis. In 63 patients out of the other 80 patients (79%), estimated glomerular filtration rate (eGFR) was also decreased (<60omL/min/1.73oom²). The patients classified into dipper, non-dipper, riser and extreme-dipper were 20%, 43%, 34% and 3%, respectively. In addition, in 17 patients whose eGFR was preserved, 12 patients showed a non-dipper or riser pattern, suggesting that it was difficult to account for this altered circadian blood pressure variation only by renal dysfunction. These results show that a large number of the patients with resistant hypertension suffered from renal dysfunction, although it was difficult to explain altered circadian blood pressure variation based on renal dysfunction alone.

DOI： 10.3109/10641963.2013.846360

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DOI： 10.3109/10641963.2013.846360

Language：English   Publishing type：Research paper (scientific journal)  

Background: It has been reported that elevated levels of serum uric acid are related to hypertension and cardiovascular disease. Recent studies, however, have found little association between hyperuricemia and hypertension. Methods and Results: The association of serum uric acid with blood pressure was examined in 3,960 Japanese male workers (18-64 years of age; mean age, 42.3±0.2 years). Systolic blood pressure was significantly correlated with serum uric acid. Multiple regression analysis also showed that both systolic and diastolic blood pressures were independently associated with serum uric acid. When subjects were divided into 6 groups according to blood pressure on the basis of the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009), serum uric acid was elevated in a linear fashion as blood pressure increased. A similar relationship was found even in 3,608 subjects who were not taking anti-hypertensive or uric acid-lowering agents. In contrast, no relation was found between serum uric acid and blood pressure in 352 subjects taking anti-hypertensive medicine. Conclusions: Blood pressure is closely associated with serum uric acid. Serum uric acid might be associated with the increase in blood pressure, because there is no relation between serum uric acid and blood pressure in the subjects treated with anti-hypertensive medications.

DOI： 10.1253/circj.CJ-11-0592

Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.1253/circj.cj-11-0592

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To determine whether polymorphisms at codon 487 (*1, GAA=Glu; *2, AAA=Lys) of mitochondrial aldehyde dehydrogenase 2 (ALDH2) influence nitroglycerine (glyceryl trinitrate (GTN))-induced vasodilation, and whether GTN or isosorbide dinitrate (ISDN) is a more effective antianginal agent in each ALDH2 genotype. DESIGN: A randomised, open-label, crossover trial with 117 healthy Japanese (20-39 years) whose genotypes were determined (*1/*1, n=47; *1/*2, n=48; *2/*2, n=22) was performed at Kyushu University Hospital, Fukuoka, Japan. Participants were randomly assigned to treatment: sublingual spray of GTN (0.3 mg) or ISDN (1.25 mg). After ≥ 1 week, measurements were repeated using the other drug. The main outcome measures were the maximal rate of increase in the brachial artery diameter determined by ultrasonography, the time required to attain maximal dilation (T(max)) and the time required to attain 90% maximal dilation (T(0.9)). RESULTS: The maximal artery diameter increase in response to GTN or ISDN did not differ among genotypes. However, GTN T(max) was significantly longer for *2/*2 (299.7 s, 269.0-330.4) than *1/*1 (254.7 s, 238.6-273.4; p=0.0190). GTN T(0.9) was significantly longer in the *1/*2 (206.1 s, 191.7-219.3) and *2/*2 (231.4 s, 211.8-251.0) genotypes than *1/*1 (174.9 s, 161.5-188.3; p=0.0068, p<0.0001, respectively). In contrast, the time-course of ISDN-induced vasodilation did not differ among genotypes. GTN T(max) and T(0.9) among *1 allele carriers (*1/*1 and *1/*2) were significantly shorter than those of ISDN, whereas the time course of GTN and ISDN vasodilation did not differ among participants carrying *2/*2. CONCLUSIONS: The amplitude of GTN-induced vasodilation was not influenced by the ALDH2 genotype, but the response was significantly delayed in *2 allele carriers, especially *2/*2. GTN dilated the artery more quickly than ISDN in *1/*1 and *1/*2, but not in *2/*2. Trial registration number UMIN000001492 (UMIN-CTR database).

DOI： 10.1136/bmjopen-2011-000133

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地域住民における潜在的MAC感染症者有病率の検討 久山町研究

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地域一般住民における血清高感度CRPレベルと心房細動発症との関連 久山町研究

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日本人コミュニティーにおけるsmall dense LDLコレステロールと冠動脈心疾患発症 Hisayama Study(Small Dense Low-Density Lipoprotein Cholesterol and the Development of Coronary Heart Disease in a Japanese Community: The Hisayama Study)

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【ガイドラインに沿った高血圧診療】 高血圧の疫学

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【知っておきたい突然死の知識】 久山町研究からみた突然死の実態

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地域住民における血清尿酸値が心血管病死亡におよぼす影響 久山町研究

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一般住民における血清尿酸値と心血管病死亡との関連 久山町研究

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【認知症の予防と早期介入:その危険因子と防御因子】 高血圧と認知症予防

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剖検にて敗血症による死亡が判明した高齢者骨髄異形成症候群の1例

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これからの認知症治療を考える(基礎・臨床) 家庭血圧の日間変動と認知症発症との関連 久山町研究

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一般住民における臥位高血圧と心血管病発症の関連 久山町研究

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一般住民における起床時および就床前家庭血圧と内膜中膜複合体厚との関連 久山町研究