Publications by authors named "Yoichiro Hirakawa"

122 Publications

Development of a risk prediction model for incident hypertension in Japanese individuals: the Hisayama Study.

Hypertens Res 2021 May 31. Epub 2021 May 31.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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 χ 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.
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http://dx.doi.org/10.1038/s41440-021-00673-7DOI Listing
May 2021

Comparison of the contributions of impaired beta cell function and insulin resistance to the development of type 2 diabetes in a Japanese community: the Hisayama Study.

Diabetologia 2021 Apr 28. Epub 2021 Apr 28.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aims/hypothesis: Our aim was to compare the contributions of impaired beta cell function (IBF) and insulin resistance with the development of type 2 diabetes in a Japanese community.

Methods: A total of 2094 residents aged 40-79 years without diabetes underwent a health examination including a 75 g OGTT in 2007. Participants were divided into four groups according to the presence or absence of IBF (insulinogenic index/HOMA-IR ≤28.5) and insulin resistance (HOMA-IR ≥1.61) and were followed up for 7 years (2007-2014). Cox's proportional hazards model was used to estimate HRs and 95% CIs for type 2 diabetes. The population attributable fractions (PAFs) due to IBF, insulin resistance, and their combination were calculated.

Results: At baseline, the prevalence of isolated IBF, isolated insulin resistance, and both IBF and insulin resistance were 5.4%, 24.1% and 9.5%, respectively. During the follow-up period, 272 participants developed type 2 diabetes. The multivariable-adjusted HRs (95% CI) and PAFs (95% CI) for type 2 diabetes were 6.3 (4.3, 9.2) and 13.3% (8.7, 17.7) in the participants with isolated IBF, 1.9 (1.3, 2.7) and 10.5% (4.0, 16.6) in those with isolated insulin resistance, and 8.0 (5.7, 11.4) and 29.3% (23.0, 35.1) in those with both IBF and insulin resistance, respectively, compared with the participants without either.

Conclusions/interpretation: The present study suggests that the combination of IBF and insulin resistance makes the main contribution to the development of type 2 diabetes in Japanese communities.
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http://dx.doi.org/10.1007/s00125-021-05459-7DOI Listing
April 2021

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study.

Environ Health Prev Med 2021 Apr 12;26(1):47. Epub 2021 Apr 12.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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 [R] = 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.
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http://dx.doi.org/10.1186/s12199-021-00970-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042718PMC
April 2021

Midlife and late-life diabetes and sarcopenia in a general older Japanese population: The Hisayama Study.

J Diabetes Investig 2021 Mar 20. Epub 2021 Mar 20.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aims/introduction: To investigate the association between midlife or late-life diabetes and the development of sarcopenia in an older Japanese population.

Materials And Methods: A total of 824 Japanese residents aged 65 to 84 years without sarcopenia were followed up from 2012 to 2017. Sarcopenia was determined following the Asian Working Group for Sarcopenia definition. The time of diabetes diagnosis was classified as midlife or late-life diabetes by the age at first diagnosis of diabetes (< 65 or ≥ 65 years) based on annual health checkups data over the past 24 years. The duration of diabetes was categorized into three groups of < 10, 10-15, and > 15 years. The odds ratios of incident sarcopenia according to the diabetic status were estimated using a logistic regression analysis.

Results: During follow-up, 47 subjects developed sarcopenia. The multivariable-adjusted odds ratio for incident sarcopenia was significantly greater in subjects with diabetes at baseline than in those without it (odds ratio 2.51, 95% confidence interval 1.26-5.00). Subjects with midlife diabetes had a significantly greater risk of incident sarcopenia, whereas no significant association between late-life diabetes and incident sarcopenia was observed. With a longer duration of diabetes, the risk of incident sarcopenia increased significantly (P for trend = 0.002).

Conclusions: The present study suggests that midlife diabetes and a longer duration of diabetes are significant risk factors for incident sarcopenia in the older population. Preventing diabetes in midlife may reduce the risk of the development of sarcopenia in later life.
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http://dx.doi.org/10.1111/jdi.13550DOI Listing
March 2021

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Diabetes Care 2021 May 3;44(5):1133-1142. Epub 2021 Mar 3.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research Design And Methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

Results: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

Conclusions: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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http://dx.doi.org/10.2337/dc20-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132316PMC
May 2021

Risk Prediction Model for Incident Atrial Fibrillation in a General Japanese Population - The Hisayama Study.

Circ J 2021 Feb 23. Epub 2021 Feb 23.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

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.
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http://dx.doi.org/10.1253/circj.CJ-20-0794DOI Listing
February 2021

Serum High-Sensitivity C-Reactive Protein Levels and the Development of Atrial Fibrillation in a General Japanese Population - The Hisayama Study.

Circ J 2021 Feb 18. Epub 2021 Feb 18.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

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.
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http://dx.doi.org/10.1253/circj.CJ-20-0751DOI Listing
February 2021

Development and Validation of a Risk Prediction Model for Atherosclerotic Cardiovascular Disease in Japanese Adults: The Hisayama Study.

J Atheroscler Thromb 2021 Jan 22. Epub 2021 Jan 22.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

Aim: To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults.

Methods: 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.

Results: 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: P=0.29 for the multivariable model, 0.52 for the simplified score).

Conclusion: 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.
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http://dx.doi.org/10.5551/jat.61960DOI Listing
January 2021

High Serum Folate Concentrations Are Associated with Decreased Risk of Mortality among Japanese Adults.

J Nutr 2021 03;151(3):657-665

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1093/jn/nxaa382DOI Listing
March 2021

An adult patient with permanent neonatal diabetes successfully discontinued insulin therapy after initiating sitagliptin added to sulphonylurea.

Diabetes Obes Metab 2021 May 4;23(5):1213-1214. Epub 2021 Feb 4.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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http://dx.doi.org/10.1111/dom.14318DOI Listing
May 2021

Changes in Body Weight and Concurrent Changes in Cardiovascular Risk Profiles in Community Residents in Japan: the Hisayama Study.

J Atheroscler Thromb 2021 Jan 17. Epub 2021 Jan 17.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

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/m. 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.
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http://dx.doi.org/10.5551/jat.59394DOI Listing
January 2021

Influence of the Accumulation of Unhealthy Eating Habits on Obesity in a General Japanese Population: The Hisayama Study.

Nutrients 2020 Oct 16;12(10). Epub 2020 Oct 16.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

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/m 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 ( 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.
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http://dx.doi.org/10.3390/nu12103160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602721PMC
October 2020

Association between serum glycated albumin and risk of cardiovascular disease in a Japanese community: The Hisayama Study.

Atherosclerosis 2020 10 29;311:52-59. Epub 2020 Aug 29.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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 A levels (hemoglobin A <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 A levels, in a general Japanese population.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.08.016DOI Listing
October 2020

Dietary fiber intake and risk of type 2 diabetes in a general Japanese population: The Hisayama Study.

J Diabetes Investig 2021 Apr 1;12(4):527-536. Epub 2020 Sep 1.

Department of Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1111/jdi.13377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015811PMC
April 2021

30-minute postload plasma glucose levels during an oral glucose tolerance test predict the risk of future type 2 diabetes: the Hisayama Study.

BMJ Open Diabetes Res Care 2020 07;8(1)

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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.
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http://dx.doi.org/10.1136/bmjdrc-2019-001156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368480PMC
July 2020

Lifetime cumulative incidence of dementia in a community-dwelling elderly population in Japan.

Neurology 2020 08 7;95(5):e508-e518. Epub 2020 Jul 7.

From the Departments of Epidemiology and Public Health (D.Y., J.H., T.H., Y.F., E.O., T.N.), Neuropsychiatry (T.O., S.K.), Center for Cohort Studies (M.S., S.S.), and Medicine and Clinical Science (Y.H., T.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1212/WNL.0000000000009917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455343PMC
August 2020

Serum N-terminal pro-B-type natriuretic peptide as a predictor for future development of atrial fibrillation in a general population: the Hisayama Study.

Int J Cardiol 2020 Dec 24;320:90-96. Epub 2020 Jun 24.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

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.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.018DOI Listing
December 2020

Prevalence and Mortality of Sarcopenia in a Community-dwelling Older Japanese Population: The Hisayama Study.

J Epidemiol 2021 May 17;31(5):320-327. Epub 2020 Oct 17.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

Background: The prevalence of sarcopenia defined using the Asian Working Group for Sarcopenia (AWGS) criteria in Asian communities has not been fully addressed. Moreover, few studies have addressed the influence of sarcopenia on mortality.

Methods: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined using the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model.

Results: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (P = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both P for trend <0.001). Subjects with sarcopenia were more likely to exercise less regularly, to intake less total energy, and to exhibit a disability in activity of daily living than those without. The multivariable-adjusted hazard ratio for all-cause mortality was 2.20 (95% confidence interval, 1.25-3.85) in subjects with sarcopenia, compared to those without.

Conclusions: Approximately 7% of older subjects had sarcopenia in a community-dwelling older Japanese population. Moreover, subjects with sarcopenia had an increased mortality risk. Our findings suggest that a public health strategy for sarcopenia is needed to extend healthy life expectancy.
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http://dx.doi.org/10.2188/jea.JE20190289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021883PMC
May 2021

Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese - The Hisayama Study.

Circ J 2020 05 9;84(6):935-942. Epub 2020 Apr 9.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

Background: Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality.Methods and Results:In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin : creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV : ICV) ratio, and the association of the combination of UACR and the WMHV : ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV : ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; P=0.01). In contrast, there was no clear association between eGFR and the WMHV : ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV : ICV ratio (<0.257% [median]), subjects with albuminuria and a larger WMHV : ICV ratio (≥0.257%) had higher probabilities of cognitive decline at baseline and all-cause death during the follow-up.

Conclusions: This study suggests that subjects with albuminuria have a greater risk of WMH enlargement and that the combination of albuminuria and WMH enlargement increases the risk of cognitive decline and all-cause mortality in an elderly Japanese population.
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http://dx.doi.org/10.1253/circj.CJ-19-1069DOI Listing
May 2020

Serum homocysteine and risk of dementia in Japan.

J Neurol Neurosurg Psychiatry 2020 05 31;91(5):540-546. Epub 2020 Mar 31.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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.
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http://dx.doi.org/10.1136/jnnp-2019-322366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231445PMC
May 2020

Association of glucose tolerance status with pancreatic β- and α-cell mass in community-based autopsy samples of Japanese individuals: The Hisayama Study.

J Diabetes Investig 2020 Sep 10;11(5):1197-1206. Epub 2020 Mar 10.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aims/introduction: Changes in histologically quantified β- and α-cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β- and α-cell mass according to the glucose tolerance status.

Materials And Methods: Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75-g oral glucose tolerance test within 5 years before death were selected from 643 community-based autopsy samples collected from 2002 to 2016. Fractional β-cell area (BCA) and α-cell area were quantified with Image Pro Plus software. Associations of BCA and α-cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman's correlation coefficients between glycemic markers and β-cell function were estimated.

Results: The mean values of BCA decreased significantly with worsening glucose tolerance status (mean ± standard error 1.85 ± 0.10% in normal glucose tolerance, 1.59 ± 0.11% in prediabetes and 1.17 ± 0.11% in type 2 diabetes mellitus, P for trend < 0.001), whereas there was no significant association between α-cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2-h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (all P < 0.01).

Conclusions: β-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining β-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus.
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http://dx.doi.org/10.1111/jdi.13232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477504PMC
September 2020

Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort: The Hisayama Study.

Stroke 2020 03 31;51(3):759-765. Epub 2020 Jan 31.

Department of Epidemiology and Public Health (J.H., D.Y., Y.F., T.N.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background and Purpose- Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods- A total of 3038 subjects aged ≥40 years were followed up for 10 years (2002-2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results- During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels ( for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16-5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors ( for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04-2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions- A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.
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http://dx.doi.org/10.1161/STROKEAHA.119.027520DOI Listing
March 2020

Elevated serum glycated albumin and glycated albumin : hemoglobin A ratio were associated with hippocampal atrophy in a general elderly population of Japanese: The Hisayama Study.

J Diabetes Investig 2020 Jul 1;11(4):971-979. Epub 2020 Mar 1.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aims/introduction: To investigate the association of alternative glycemic measures - namely, serum glycated albumin (GA), hemoglobin A (HbA ) and the GA : HbA ratio - with global brain and hippocampal atrophy in a general elderly Japanese population.

Materials And Methods: A total of 1,278 Japanese individuals aged ≥65 years in a community participated in brain magnetic resonance imaging scanning and screening examination of health status in 2012. We measured total brain volume (TBV), hippocampal volume (HV) and intracranial volume (ICV) using the data from the magnetic resonance imaging examination. The association of each glycemic measure with the ratios of TBV : ICV (an indicator of global brain atrophy) and HV : ICV (an indicator of hippocampal atrophy) was examined by analysis of covariance.

Results: The mean values of the TBV : ICV and HV : ICV ratios decreased significantly with elevating serum GA levels and GA : HbA ratio levels (all P for trend < 0.05), but not with higher HbA levels, after adjusting for age, sex, low education, systolic blood pressure, antihypertensive medication, diabetes mellitus, serum total cholesterol, electrocardiogram abnormalities, body mass index, smoking habits, alcohol drinking habits and regular exercise. These significant associations were still observed in the sensitivity analysis after excluding individuals with mild cognitive impairment and dementia. In addition, increased serum GA levels and the GA : HbA ratio levels, but not HbA , were closely associated with lower mean values of the TBV : ICV and HV : ICV ratios, irrespective of the presence or absence of diabetes mellitus.

Conclusions: The present study suggests that higher serum GA and higher GA : HbA ratio are significantly associated with global brain and hippocampal atrophy.
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http://dx.doi.org/10.1111/jdi.13220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378434PMC
July 2020

Serum uric acid levels and cardiovascular mortality in a general Japanese population: the Hisayama Study.

Hypertens Res 2020 06 17;43(6):560-568. Epub 2020 Jan 17.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1038/s41440-019-0390-8DOI Listing
June 2020

Small Dense Low-Density Lipoprotein Cholesterol and the Risk of Coronary Heart Disease in a Japanese Community.

J Atheroscler Thromb 2020 Jul 11;27(7):669-682. Epub 2019 Nov 11.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

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.
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http://dx.doi.org/10.5551/jat.51961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406411PMC
July 2020

Serum elaidic acid concentration and risk of dementia: The Hisayama Study.

Neurology 2019 11 23;93(22):e2053-e2064. Epub 2019 Oct 23.

From the Departments of Epidemiology and Public Health (T.H., T.O., J.H., D.Y., M.Shibata, Y.H., S.S., T.N.), Neuropsychiatry (T.O., S.K.), Medicine and Clinical Science (J.H., Y.H., S.S., T.K.), and Psychosomatic Medicine (M.Shibata), and Center for Cohort Studies (J.H., M.Shibata, S.S., T.K., T.N.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; Divisions of Epidemiology (M.Shinohara), Evidence-Based Laboratory Medicine (R.T., Y.I.), and Cardiovascular Medicine (T.I., K.-I.H.), and Integrated Center for Mass Spectrometry (M.Shinohara., Y.I.), Kobe University Graduate School of Medicine, Hyogo; and Department of Health Promotion (K.U.), School of Health and Nutrition Sciences, Nakamura-Gakuen University, Fukuoka, Japan.

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 ( for trend = 0.003) and AD ( 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 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.
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http://dx.doi.org/10.1212/WNL.0000000000008464DOI Listing
November 2019

NT-proBNP and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study.

J Am Heart Assoc 2019 09 24;8(17):e011652. Epub 2019 Aug 24.

Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Fukuoka Japan.

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.
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http://dx.doi.org/10.1161/JAHA.118.011652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755853PMC
September 2019

Ratios of serum eicosapentaenoic acid to arachidonic acid and docosahexaenoic acid to arachidonic acid were inversely associated with serum resistin levels: The Hisayama Study.

J Diabetes Investig 2020 Mar 15;11(2):482-489. Epub 2019 Sep 15.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aims/introduction: Resistin is an adipocyte-derived polypeptide that leads to the progression of insulin resistance and subsequent atherosclerosis. Some studies have reported an association between self-reported intake of n-3 polyunsaturated fatty acids (PUFAs) and serum resistin levels. However, no studies have investigated the association between the ratio of serum levels of n-3 to serum n-6 PUFAs and the serum resistin concentration in the general population.

Materials And Methods: We carried out a cross-sectional study of 3,200 community-dwelling Japanese individuals aged ≥40 years in 2002-2003. The ratios of serum eicosapentaenoic acid or docosahexaenoic acid to arachidonic acid (AA) were categorized into quartiles. The associations of serum eicosapentaenoic acid/AA and docosahexaenoic acid/AA with the serum resistin concentration were assessed using linear regression models with adjustment for potential confounding factors.

Results: The geometric mean of serum resistin was 10.3 ng/mL. The age- and sex-adjusted geometric mean of serum resistin decreased significantly with increased levels of serum eicosapentaenoic acid/AA (quartile 1: 11.3 ng/mL; quartile 2: 10.6 ng/mL; quartile 3: 10.3 ng/mL; quartile 4: 9.3 ng/mL; P for trend <0.001). A similar association was observed for serum docosahexaenoic acid/AA (quartile 1: 11.1 ng/mL; quartile 2: 10.6 ng/mL; quartile 3: 10.1 ng/mL; quartile 4: 9.7 ng/mL; P for trend <0.001). An adjustment for potential confounding factors did not change these associations.

Conclusions: Higher ratios of serum n-3 to n-6 PUFAs were associated with lower serum resistin levels. Consumption of a large amount of n-3 PUFAs might have desirable effects on resistin-mediated diseases.
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http://dx.doi.org/10.1111/jdi.13129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078098PMC
March 2020