Language：Japanese  

Language：Japanese  

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

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&#37;) 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&#37; 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)  

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&#37; 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

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

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)  

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

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

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&#37; 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: 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&#37; 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&#37; 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&#37; 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&#37; 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

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

AIM: We investigated the influence of weight change on concurrent changes in predicted cardiovascular disease (CVD) risk and individual CVD risk factors over time. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

DOI： 10.5551/jat.59394

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&#37; 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)  

OBJECTIVES: To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. METHOD: A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales-namely, social and emotional loneliness-by using the 6-Item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. RESULTS: During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95&#37; confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08-2.40) and 1.65 (1.07-2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. DISCUSSION: The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.

DOI： 10.1093/geronb/gbaa196

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

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 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&#37; 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&#37;), the multivariable-adjusted HRs (95&#37; CI) of the highest quartile (≥15.7&#37;) 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&#37;). 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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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&#37;. 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&#37; (95&#37; confidence interval, 49&#37;-60&#37;). Women had an approximately 1.5 times greater lifetime risk of dementia than men (65&#37; [57&#37;-72&#37;] vs 41&#37; [33&#37;-49&#37;]). The lifetime risks of developing AD and VaD were 42&#37; (35&#37;-50&#37;) and 16&#37; (12&#37;-21&#37;) in women vs 20&#37; (7&#37;-34&#37;) and 18&#37; (13&#37;-23&#37;) in men, respectively. CONCLUSION: Lifetime risk of all dementia for Japanese elderly was substantial at approximately 50&#37; or higher. This study suggests that the lifetime burden attributable to dementia in contemporary Japanese communities is immense.

DOI： 10.1212/WNL.0000000000009917

Language：Japanese  

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&#37; 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&#37; 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

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BACKGROUND: The association between decline in handgrip strength from midlife to late life and dementia is unclear. METHODS: Japanese community-dwellers without dementia aged 60 to 79 years (ie, individuals in late life; mean age, 68 years) were followed for 24 years (1988-2012) (n = 1,055); 835 of them had participated in a health examination in 1973-1974 (mean age, 53 years), and these earlier data were used for the midlife analysis. Using a Cox proportional hazards model, we estimated the risk conferred by a decline in handgrip strength over a 15-year period (1973-74 to 1988) from midlife to late life on the development of total dementia, Alzheimer's disease (AD), and vascular dementia (VaD) over the late-life follow-up period from 1988 to 2012. RESULTS: During the follow-up, 368 subjects experienced total dementia. The age- and sex-adjusted incidence of total dementia increased significantly with greater decline in handgrip strength (increased or unchanged handgrip strength [≥+0&#37;] 25.1, mildly decreased [-14 to -1&#37;] 28.4, and severely decreased [≤-15&#37;] 38.9 per 1,000 person-years). A greater decline in handgrip strength was significantly associated with higher risk of total dementia after adjusting for potential confounding factors; subjects with severely decreased handgrip strength had 1.51-fold (95&#37; confidence interval, 1.14-1.99, P < 0.01) increased risk of total dementia compared to those with increased or unchanged handgrip strength. Similar significant findings were observed for AD, but not for VaD. CONCLUSIONS: Our findings suggest that a greater decline in handgrip strength from midlife to late life is an important indicator for late-life onset of dementia.

DOI： 10.2188/jea.JE20180137

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&#37; 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&#37; CI, 0.60-1.78]; quartile 3: HR, 1.52 [95&#37; CI, 0.92-2.51]; and quartile 4: HR, 1.90 [95&#37; 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：Japanese  

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  

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&#37; 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&#37; confidence interval=1.45-3.55, P<0.001 for all-cause dementia; hazard ratio=2.79, 95&#37; confidence interval=1.04-7.51, P=0.03 for VaD; hazard ratio=2.22, 95&#37; 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)  

DOI： 10.18632/oncotarget.22993

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&#37; 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&#37;, and 6.1&#37;, respectively. Among the 135 severe OSA subjects, 105 (77.8&#37;) 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, HbA1c, 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

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&#37;) 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&#37;). 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-and-go test compared with those without OH. During the follow-up period, 22 patients (34.4&#37;) had a poor prognosis, of which 8 (36.4&#37;) 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)  

Many studies have demonstrated that increased carotid intima-media thickness (IMT) is related to future cardiovascular events and is influenced by cardiovascular risk factors such as sex, hypertension, diabetes, and hypercholesterolemia. Although aging is a well-known risk factor for an increase in carotid IMT, few studies have investigated which factors influence carotid IMT in the very elderly. In the present study, we investigated the relationship of pulse pressure (PP), blood pressure (BP), and its variability (six consecutive visits) with carotid IMT among 240 high-risk elderly in whom risk factors were managed clinically (average age was 79 ± 5 years). In the simple correlation, mean systolic BP (SBP) had a positive correlation with IMT and max IMT (P = .012 and P = .045), as did PP (P = .018 and P = .004), but did not diastolic BP or standard deviation of BP and coefficient of variation of BP. In multiple regression analyses, mean SBP and mean PP were each determinants of both IMT and max IMT, when each parameter was added separately to the regression model. We concluded that high SBP and wide PP still have an influence on increased carotid IMT in the very elderly Japanese patients.

DOI： 10.3109/10641963.2013.780072

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我が国では、認知症患者の急増が医療・社会問題となっている。近年の国内外の疫学調査において、血圧変動と認知機能低下および認知症発症との関係が報告されている。福岡県糟屋郡久山町における認知症コホート研究(久山町研究)の成績では、家庭血圧の日間変動の増大に伴い、血管性認知症およびアルツハイマー型認知症の発症リスクが有意に上昇した。認知症予防において、血圧値のみならず血圧変動にも留意した高血圧管理が重要であると言えよう。(著者抄録)

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地域高齢者における中年期から老年期までの握力変化と認知症発症の関連 久山町研究

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地域高齢者における中年期から老年期の握力低下と認知症発症の関連 久山町研究

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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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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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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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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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降圧薬内服下における血漿レニン活性(PRA)、血清アルドステロン濃度(PAC)の測定が原発性アルドステロン症(PA)のスクリーニングに及ぼす影響を検討した。高血圧内科に紹介され、初診時にPRA、PACを測定していた患者321名(男156名、女165名、平均年齢56.1±15.5歳)を対象として、内服降圧薬の種類別にPRA、PAC、PAC/PRA比(ARR)を比較した。その結果、RA系抑制薬はPAC、ARRを過小評価、β遮断薬はPRAを抑制しARRを過大評価することが示唆されたが、PA診断の特異度への影響は少ないと考えられた。PAのスクリーニングの感度を上げるためには、二次性を除外すべき対象者は降圧薬開始前にホルモン測定を行うことを心掛け、すでに降圧薬内服中の患者には内服下でスクリーニングを行い、臨床上PAが疑われるRA系抑制薬内服者がPAC、ARR低値を示した場合には、薬剤調整後に再検することが望ましいと考えられた。

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