Published papers

保健師活動におけるICT(Information and Communication Technology)活用の推進へ向け、本邦の地方自治体における保健師活動へのICT活用の促進要因と阻害要因を整理することを目的に、医学中央雑誌Web版を用いて、情報通信技術に関する国および地方公共団体の責務について定めた法律である高度情報通信ネットワーク社会形成基本法が制定された2000年から2023年3月の文献を対象に検索を行い、得られた9件を分析した。その結果、保健師活動におけるICT活用の促進要因として、保健師個人の要因では「業務の効率化」「住民の健康管理・健康増進」が、保健師が所属する組織の要因では「目的が明確化できていること」「必要性が認識されていること」「ICT専門職を含めた連携体制」に加え「国や制度によるデジタル推進の流れ」が挙げられた。ここから、保健師活動におけるICT活用の推進へ向け、組織内での合意形成とともに、事務職やICT専門職等との連携・協力体制構築の必要性が示された。ICT活用の阻害要因では、保健師個人の要因である「ICTへの無関心さ」「苦手意識」「ネガティブな認識」「ICTの活用状況やスキルの差」などが、保健師が所属する組織の要因として「職場のICT環境の不十分さ」「予算・マンパワーの課題」などが挙げられていたほか、電子記録システム自体の整備や標準化も課題として挙げられていた。

Aim: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75–31.50) for men and 4.44 (95% CI 1.14–17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

Introduction: Seasonal influenza vaccination for the elderly is highly recommended during the COVID-19 pandemic. In Japan, the amount of subsidy for influenza differs among municipalities. Thus, we investigated the amount of and variation in subsidy for influenza vaccination for the elderly in 2020. Methods: This was an ecological study of 1,922 municipalities in Japan. The amount of subsidy for influenza vaccines for the elderly in each municipality was surveyed through websites or via telephone. Geographic and financial data for municipalities and prefectures were obtained from the open data. The amount of co-payment for the influenza vaccine and the geographical and financial status of each municipality were compared, according to the aging rate. Univariate logistic regression analysis was performed to explore factors related to the free influenza vaccine. Results: Municipalities with higher aging rates tended to have higher median co-payments for vaccines in 2020. (0 yen vs 1000 yen, p < 0.001) In addition, they tended to have worse financial conditions and lower per capita incomes. A similar trend was observed in the analysis by prefecture, i.e., a higher influenza mortality rate in prefectures with a higher aging rate. Despite having lower incomes, municipalities and prefectures with higher aging populations had higher mortality rates from influenza and higher co-payments for influenza vaccination. Conclusions: In Japan, there is a disparity among elderly people; areas with an aging population have higher co-payments for influenza vaccines despite lower incomes, suggesting that the government needs to implement corrective measures to reduce this disparity.

Aims: P-wave terminal force in lead V1 (PTFV1) is an electrocardiogram marker of increased left atrial pressure and may be a noninvasive and early detectable marker for future cardiovascular events in the general population compared to serum B-type natriuretic peptide (BNP) concentration. The clinical significance of PTFV1 in the contemporary general population is an area of unmet need. We aimed to demonstrate the correlation between PTFV1 and BNP concentrations in a contemporary representative Japanese population. Methods: Among 2,898 adult men and women from 300 randomly selected districts throughout Japan (NIPPON DATA2010), we analyzed 2,556 participants without cardiovascular disease (stroke, myocardial infarction, and atrial fibrillation). Elevated BNP was defined as a value of ≥ 20 pg/mL based on the definition from the Japanese Circulation Society guidelines. Results: In total, 125 (4.9%) participants had PTFV1. Participants with PTFV1 were older with a higher prevalence of hypertension, major electrocardiographic findings, and elevated BNP concentrations (13.5 [6.9, 22.8] versus 7.8 [4.4, 14.5] pg/mL; P＜0.001). After adjustment for confounders, PTFV1 was correlated with elevated BNP (odds ratio, 1.66; 95% confidence interval, 1.05–2.62; P= 0.030). This correlation was consistent among various subgroups and was particularly evident in those aged ＜65 years or those without a history of hypertension. Conclusions: In the contemporary general population cohort, PTFV1 was independently related to high BNP concentration. PTFV1 may be an alternative marker to BNP in identifying individuals at a higher risk of future cardiovascular events in the East Asian population.

Introduction: We hypothesized that hybrid artificial nerves might overcome the limitations of a nerve conduit by isolating nerve fascicles from autologous nerves. Nerve sacrifice during harvest, a drawback of conventional autologous nerve transplantation, may be reduced by the hot dog method. The hot dog method (based on the morphology of hybrid artificial nerves) adds nerve conduits to autologous nerve fascicles. Methods: Forty-eight rats with a 10-mm sciatic nerve defect were divided into six groups (n = 8 per group) according to the neural reconstruction method: autologous nerve transplantation, the hot dog method, nerve conduit, nerve fascicle transplantation, sham control, and nerve fascicle isolation were classified as Groups I, II, III, IV, V, and VI, respectively. The sciatic nerve function was assessed in these groups, a histological evaluation was performed, and statistical analyses were conducted based on these data. Results: Group III (nerve conduit) and Group IV (nerve fascicle transplantation) showed the lowest functional and axonal regenerative effects, followed by Group II (hot dog method) and Group I (autologous nerve transplantation). Group VI (nerve fascicle isolation) tended to achieve better recovery in motor function and axonal regeneration than Group I (autologous nerve transplantation). Conclusions: The hot dog method is simple, safe, and easy to execute. This method can serve as a new neural reconstruction method that uses artificial nerves.

Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.

The aim of this study was to investigate the effect of the COVID-19 pandemic on regular clinic visits among people with diabetes and to elucidate the factors related to visit patterns among these patients during the pandemic. This was a longitudinal study using anonymized insurance claims data from the Joint Health Insurance Society in Tokyo from October 2017 to September 2020. First, we identified patients with diabetes who were fully enrolled in the health plan from fiscal year 2017 until September 2020 and who were regularly receiving glucose-lowering medications (every 1-3 months) from October 2017 to September 2018. We divided follow-up into the pre-pandemic period (October 2018 to March 2020) and the pandemic period (April 2020 to September 2020). A multilevel logistic regression model was used to determine the risks of delayed clinic visits/medication prescriptions (i.e., >3 months after a previous visit/prescription) during the pandemic period. We identified 1118 study participants. The number of delayed clinic visits/medication prescriptions during the pre-pandemic and pandemic periods was 188/3354 (5.6%) and 125/1118 (11.2%), respectively. There was a significant increase in delayed clinic visits during the pandemic (adjusted odds ratio 3.68 (95% confidence interval 2.24 to 6.04, P <.001), even after controlling for confounding factors. We also found a significant interaction between sex and delayed visits; women had significantly fewer clinic visits during the COVID-19 pandemic than men. We clarified the relationship of the COVID-19 pandemic with delays in regular clinic visits and medication prescriptions among people with diabetes. The response to the COVID-19 pandemic differed between men and women.

Background: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. Methods: The participants were 1193 female residents aged 40–60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. Results: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. Conclusion: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

Background: The current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors. Methods: This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP © HR ² 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables. Results: Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone. Conclusions: High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.

Fatty liver has been suggested to be associated with the development of hypertension. However, whether this association is related to glycemia has not been elucidated. Therefore, we investigated whether the fatty liver index (FLI) predicts the development of hypertension among individuals with and without dysglycemia in a general Japanese population. A total of 3114 participants (1036 males and 2078 females) without hypertension who underwent a Specific Health Checkup in the fiscal year 2013 were followed up until 2018. The participants were divided into six groups based on FLI tertiles (low, moderate, or high) and whether they had dysglycemia. We estimated the hazard ratios (HRs) of each group by sex using the Cox proportional hazard model. Models were adjusted for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking, and alcohol consumption and further adjusted for systolic blood pressure (SBP). During the mean follow-up period of 2.8 years, 160 of the 3114 participants developed hypertension. Using the low FLI group with normoglycemia as a reference, the HR for incident hypertension was increased in the high FLI group with and without dysglycemia in both sexes after adjusting for confounders, except SBP (HR [95% confidence interval]: male: 1.52 (1.06–2.17) in normoglycemia and 2.05 (1.43–2.92) in dysglycemia, and female: 1.86 (1.43–2.42) in normoglycemia and 2.98 (2.19–4.07) in dysglycemia). Furthermore, in females, this association was observed after adjusting for SBP. We concluded that FLI was independently associated with an increased risk of incident hypertension in individuals with and without dysglycemia. [Figure not available: see fulltext.].

Background: The association between Patient-Rated Elbow Evaluation: Japanese version (PREE-J) and Japanese Orthopaedic Association-Japan Elbow Society Elbow Function score (JOA-JES score) is unclear. This study evaluated the association between PREE-J and JOA-JES scores. Methods: The patients with elbow disorders were divided into two groups: Group A (conservative treatment, n = 97) and Group B (surgical treatment, n = 156). The patients were also divided into four disease subgroups according to the JOA-JES classification (rheumatoid arthritis, trauma, sports, and epicondylitis groups), and the association between PREE-J and JOA-JES scores in each disease category was examined. In group B, associations between PREE-J and JOA-JES scores were examined pre-and postoperatively. Results: In group A, there were significant associations between PREE-J and JOA-JES scores. In group B, a strong association between preoperative PREE-J and JOA-JES scores was observed in all disease categories. There was also a significant association between postoperative PREE-J and JOA-JES scores. Additionally, group B showed significant postoperative improvements in PREE-J and JOA-JES scores. Conclusions: The PREE-J score correlates well with the JOA-JES score and reflects treatment response before and after treatment.

Objectives: This study developed and psychometrically validated a new instrument – the Digital Health Competency Scale for Public Health Nurses (hereafter, DHCP) – to assess digital health competencies among public health nurses working in administrative agencies. Methods: DHCP was developed based on a literature review and expert interviews with four public health nurses (PHNs) and three researchers. A cross-sectional national survey was conducted with 1810 PHNs from stratified, randomly selected municipalities across Japan. Exploratory factor analysis (EFA) was used to identify the initial structure of DHCP, followed by confirmatory factor analysis (CFA) to assess construct validity. Internal consistency was calculated using Cronbach's alpha and criterion-related validity was examined by correlating DHCP scores with the eHealth Literacy Scale (eHEALS). Results: In total, 521 valid responses were obtained. The EFA applied an initial version of the scale with 28 items. The analysis identified a 12-item scale with a three-factor structure (motivation for digitalization, ethical-social assessment, and technical skills). The CFA supported the three-factor structure for DHCP, demonstrating a good model fit (GFI = 0.949, AGFI = 0.922, CFI = 0.960, RMSEA = 0.067). The Cronbach's alpha for the scale was 0.869. The total DHCP score was positively correlated with eHEALS (r = 0.444, 95 % confidence interval 0.372–0.511, p < 0.001), supporting criterion-related validity. Conclusions: DHCP is a novel instrument with good psychometric properties for assessing digital health competencies among PHNs. It has the potential to support digitalization efforts within municipal public health services.

Aims: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness. Methods: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35–74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: “Category I (Low risk),” “Category II (Middle risk),” and “Category III (High risk).” Results: The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61–5.43) and 7.33 (4.03–13.3) for males and 3.99 (2.55–6.24) and 3.34 (2.16–5.16) for females, respectively. Conclusions: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

Aim: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual’s lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. Methods: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2–3 hypertension groups, we defined “normal BP” as systolic/diastolic BP ＜130/＜80 mmHg and “high BP” as 130–139/80–89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. Results: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%–10.28%/3.83%–7.25%) in men/women with grade 2–3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. Conclusions: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments.

Survival analysis is a set of methods for statistical inference concerning the time until the occurrence of an event. One of the main objectives of survival analysis is to evaluate the effects of different covariates on event time. Although the proportional hazards model is widely used in survival analysis, it assumes that the ratio of the hazard functions is constant over time. This assumption is likely to be violated in practice, leading to erroneous inferences and inappropriate conclusions. The accelerated failure time model is an alternative to the proportional hazards model that does not require such a strong assumption. Moreover, it is sometimes plausible to consider the existence of cured patients or long-term survivors. The survival regression models in such contexts are referred to as cure models. In this study, we consider the accelerated failure time cure model with frailty for uncured patients. Frailty is a latent random variable representing patients’ characteristics that cannot be described by observed covariates. This enables us to flexibly account for individual heterogeneities. Our proposed model assumes a shifted gamma distribution for frailty to represent uncured patients’ heterogeneities. We construct an estimation algorithm for the proposed model, and evaluate its performance via numerical simulations. Furthermore, as an application of the proposed model, we use a real dataset, Specific Health Checkups, concerning the onset of hypertension. Results from a model comparison suggest that the proposed model is superior to existing alternatives.

Background. Bone marrow infiltration of lymphoma cells is a candidate risk factor for infusion-related reactions (IRRs) in patients with CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). However, despite with the lack of sufficient data, the effect of bone marrow infiltration of B-NHL cells on the incidence rate of grade 2 or higher IRRs with the administration of rituximab has been retrospectively studied in this paper. Methods. Patients with CD20-positive B-NHL who received the rituximab induction therapy for the first time were enrolled in this study. To evaluate the bone marrow infiltration of B-NHL cells, May-Giemsa stain of bone marrow films and flow cytometry examination of bone marrow aspiration samples were performed. IRR grade was determined using the IRR criteria in the Common Terminology Criteria for Adverse Events version 4.0. Results. A total of 127 patients were eligible for this study. Grade 2 or higher IRRs were observed in 43 (34%) patients. In univariate analysis, use of glucocorticoid before rituximab infusion was a strong risk-avoiding factor for grade 2 or higher IRRs. Advanced stage of disease (Ann Arbor: stages III and IV) or bone marrow infiltration of B-NHL cells revealed the risk factors, regardless of glucocorticoid premedication. Using multivariate analysis, bone marrow infiltration was found to be an independent risk factor for patients without prior glucocorticoid use. Conclusion. Bone marrow infiltration of B-NHL cells is a risk factor for grade 2 or higher IRRs at the first rituximab induction therapy without glucocorticoid premedication.

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1-96.2] vs. 82.1 [95% CI, 79.1-85.0] in men and 95.8 [95% CI, 94.1-97.5] vs. 89.4 [95% CI, 87.8-90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8-97.2] vs. 81.6 [95% CI, 77.9-85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

Background: The application of metabolomics-based profiles in environmental epidemiological studies is a promising approach to refine the process of health risk assessment. We aimed to identify potential metabolomics-based profiles in urine and plasma for the detection of relatively low-level cadmium (Cd) exposure in large population-based studies. Method: We analyzed 123 urinary metabolites and 94 plasma metabolites detected in fasting urine and plasma samples collected from 1,412 men and 2,022 women involved in the Tsuruoka Metabolomics Cohort Study. Regression analysis was performed for urinary N-acetyl-beta-D-glucosaminidase (NAG), plasma, and urinary metabolites as dependent variables, and urinary Cd (U-Cd, quartile) as an independent variable. The multivariable regression model included age, gender, systolic blood pressure, smoking, rice intake, BMI, glycated hemoglobin, low-density lipoprotein cholesterol, alcohol consumption, physical activity, educational history, dietary energy intake, urinary Na/K ratio, and uric acid. Pathway-network analysis was carried out to visualize the metabolite networks linked to Cd exposure. Result: Urinary NAG was positively associated with U-Cd, but not at lower concentrations (Q2). Among urinary metabolites in the total population, 45 metabolites showed associations with U-Cd in the unadjusted and adjusted models after adjusting for the multiplicity of comparison with FDR. There were 12 urinary metabolites which showed consistent associations between Cd exposure from Q2 to Q4. Among plasma metabolites, six cations and one anion were positively associated with U-Cd, whereas alanine, creatinine, and isoleucine were negatively associated with U-Cd. Our results were robust by statistical adjustment of various confounders. Pathway-network analysis revealed metabolites and upstream regulator changes associated with mitochondria (ACACB, UCP2, and metabolites related to the TCA cycle). Conclusion: These results suggested that U-Cd was associated with metabolites related to upstream mitochondrial dysfunction in a dose-dependent manner. Our data will help develop environmental Cd exposure profiles for human populations.

Aims: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites.Methods: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted.Results: NAFLD was positively associated with CAVI (coefficients [95% Confidence intervals (CI)]=0.23 [0.09–0.37]; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI.Conclusions: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.