BACKGROUND:Thyroid hormones support endothelial repair, whereas bedtime snacking is linked to a higher risk of chronic kidney disease (CKD). Since endothelial dysfunction is a core feature of CKD, bedtime snacking could potentially contribute to subclinical hypothyroidism (SCH) by elevating the demand for endothelial repair. This study aimed to explore the association between bedtime snacking and SCH. METHOD:In this cross-sectional study, 1,478 Japanese individuals aged 40-69 years with normal thyroid function were enrolled; normal thyroid function was defined as free triiodothyronine (T3) and free thyroxine (T4) levels within the reference ranges and the absence of thyroid-related medication use. Individuals with elevated serum concentrations of TSH (>4.01 µIU/mL) were defined as having SCH. Bedtime snacking was determined in the basis of participants' affirmation to the question "Do you consume a night meal or snack after dinner, within two hours of bedtime, three or more times per week? (Yes, No)". RESULTS:In the study population, 263 individuals reported a bedtime snacking habit, whereas SCH was identified in 81 individuals. A statistically significant association was found between bedtime snacking and SCH. The sex- and age-adjusted odds ratios (OR) and 95% confidence intervals (CI) were 1.77 (1.05, 2.99). This association remained significant after additional adjustment for skipping breakfast and late dinner; 1.83 (1.07, 3.11), and further adjustment for free T4, atherosclerosis, hypertension, diabetes, CKD, and thyroid cysts; 1.93 (1.11, 3.35), respectively. CONCLUSION:Bedtime snacking is positively associated with SCH, potentially due to an increased physiological demand for endothelial repair. This finding is not only an efficient tool for diagnosing the early stages of endothelial and thyroid dysfunction, but also for clarifying the mechanism underlying the regulation of thyroid hormones related to endothelial health.

Quizartinib is a FMS-like tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia (AML). We aimed to evaluate quizartinib resistance mechanisms, in addition to efficacy and safety outcomes, in patients with relapsed or refractory FLT3-ITD-positive AML. This multicenter, single-arm study in Japan (jRCTs071200015) enrolled 18 patients between May 2020 and December 2022. Of these, 15 patients received oral quizartinib (up to 53 mg once daily) for up to 12 cycles of 28 days each, then were followed for 12 months. The primary endpoint was to evaluate the type and rate of quizartinib resistance mutations; secondary endpoints included composite complete remission (CRc) rate, overall response rate (ORR), hematopoietic stem cell transplantation (HSCT) rate, relapse-free survival (RFS), overall survival (OS), and adverse events (AEs). Among seven evaluable patients, acquired mutations were detected in four patients (NF1 [R2616X], CSF3R [Q754X], NRAS [G13R], and FLT3 [D835Y] in one patient each), while loss of FLT3-ITD was observed in two patients. In efficacy analyses (n = 15), CRc rate was 66.7% (95% confidence interval [CI], 38.4-88.2), ORR was 73.3% (44.9-92.2), and median OS was 13.6 months (5.4-not evaluable). Three patients (20.0%) received HSCT directly after quizartinib; in these patients, median RFS was 8.5 months (95% CI, 6.2-not evaluable). Grade ≥ 3 non-hematologic AEs and grade 1 QT prolongation were each reported in three patients (20.0%). These data offer additional information on potential resistance mechanisms in patients with relapsed or refractory FLT3-ITD-positive AML. Trial Registration: Japan Registry of Clinical Trials (jRCTs071200015).

In our previous study, the absence of thyroid cysts was identified as an indicator of thyroid functional strain associated with thyroid peroxidase antibody (TPO-Ab) positivity. In individuals under this continuous functional load, higher levels of thyroid-stimulating hormone are required to maintain serum thyroid hormone concentrations within the normal range, potentially leading to subclinical hypothyroidism (SCH). However, no study has examined whether the association between TPO-Ab positivity and SCH differs according to thyroid cyst status. We conducted a cross-sectional study of 1432 euthyroid Japanese participants whose free triiodothyronine (T3) and free thyroxine levels were within normal ranges. Thyroid cysts were defined as cystic lesions with a maximum diameter ≥ 2.0 mm and no solid components. Among the study population, 964 participants had no thyroid cysts, 267 were TPO-Ab positive, and 80 had SCH. A significant positive association between TPO-Ab positivity and SCH was observed only in participants without thyroid cysts. After adjustment for potential confounders—including sex, age, free T3, body mass index, atherosclerosis, and hypertension—the adjusted odds ratios (95

BACKGROUND:In late 2015, an automatic influenza alert system was developed in Goto City, Nagasaki Prefecture, Japan using drug-dispensing data to enable earlier provider response to increased case counts. However, changes in incidence after implementation of this system remain unassessed. METHODS:An analytical observational study was conducted on influenza surveillance data during 2007-2019. The outcome was the annual cumulative influenza incidence per sentinel site in Nagasaki Prefecture before and after alert system implementation in Goto City in the 2015-2016 season. To evaluate the effect of the system in Goto City, a Poisson generalized linear mixed model was applied. The model included variables for location (Goto City versus other districts in Nagasaki Prefecture), timing (before or after the implementation), and an interaction term between location and timing. RESULTS:Before 2015, the median annual cumulative incidence was 149 cases (interquartile range: 61-320) in Goto City and 284 (162-474) in other districts. Following implementation, annual incidence was 163 (102-274) in Goto and 302 (197-503) elsewhere. The effect of timing variable (before versus after implementation) on annual incidence significantly differed for Goto City sites versus other sites in Nagasaki Prefecture (p for interaction < 0.001). CONCLUSIONS:Although annual influenza incidence trended upwards, the increase in Goto City was significantly less than in other districts of Nagasaki Prefecture following alert system implementation. This study suggests the potential effect of a real-time surveillance strategy for settings with comprehensive, computerized dispensing data.

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are among the most clinically relevant molecular abnormalities in acute myeloid leukemia (AML); however, the therapeutic significance of rare non-canonical FLT3 mutations involving the juxtamembrane domain (JMD) remains poorly defined. We report a 34-year-old woman with acute monocytic leukemia harboring a rare FLT3-JMD missense mutation (V579A) who experienced early relapse following standard induction and consolidation chemotherapy. Targeted next-generation sequencing revealed the presence of FLT3 V579A along with a concurrent truncating ARID1A mutation. Salvage therapy with the type I FLT3 inhibitor gilteritinib induced rapid hematologic remission within three weeks, allowing successful bridging to haploidentical allogeneic hematopoietic stem cell transplantation. Three months after transplantation, the patient relapsed, and genomic analysis demonstrated loss of the FLT3-mutated clone with the emergence and expansion of TP53-mutated independent clones, indicating clonal evolution and an apparent shift away from FLT3-dependent disease biology. This case suggests that AML harboring rare FLT3-JMD point mutations may exhibit transient dependence on FLT3 signaling and may respond to FLT3 inhibition despite the absence of canonical FLT3 alterations. These findings highlight the potential value of extended molecular profiling and longitudinal genomic assessment to identify potential therapeutic targets and mechanisms of resistance in relapsed AML.

OBJECTIVE:This study aimed to determine how dental deposits are associated with periodontal conditions and the number of teeth in Goto Islands' residents. BACKGROUND:Previous studies have shown that dental deposits increase the risk of developing periodontal diseases. However, the relationships between dental deposits and the periodontal/dentitional conditions in a super-aging society remain unclear. MATERIALS AND METHODS:A cross-sectional study involving 671 participants (age: 65.0 ± 12.0 years) was conducted using data from the Nagasaki Islands Study (NaIS). Participants underwent a routine medical examination. Information on oral hygiene and smoking status was collected from a self-administered questionnaire. Dental examinations were conducted to determine the number of teeth, probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP) ratio, calculus index (CI) score, and debris index (DI) score. Saliva samples were collected from the participants to determine the levels of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans by real-time polymerase chain reaction. Multivariable logistic regression analyses were performed to evaluate the relationships between dental deposits and periodontal/dentitional conditions. RESULTS:Multivariable logistic regression analyses show that greater DI score was significantly associated with higher BOP ratio (OR = 2.51, 95% CI: 1.75-3.61), greater CAL (OR = 1.51, 95% CI: 1.02-2.23), and fewer teeth (OR = 1.70, 95% CI: 1.04-2.76). Greater CI score was significantly associated with a higher BOP ratio (OR = 2.18, 95% CI: 1.47-3.23), deeper PPD (OR = 2.04, 95% CI: 1.22-3.50), and more teeth (OR = 0.13, 95% CI: 0.08-0.23). CONCLUSIONS:Debris and calculus deposition were associated with more severe periodontal conditions, but calculus deposition was strongly associated with more teeth. The association between calculus deposition and more teeth may be an emerging trend in super-aging societies, and future longitudinal studies are warranted to elucidate the changing relationship between calculus and number of teeth.

We aimed to specify the characteristics of group A Streptococcus M1 (n = 23) or non-M1 (n = 282) isolates from adult (n = 176) and pediatric (n = 129) populations in central Japan, October 2024-April 2025. Of the speA-possessing fourteen non-M1 isolates, there were seven emm3.93 isolates from six non-invasive samples of pediatric patients and one invasive specimen of an adult patient. We found the distribution of M1 clones containing M1global (n = 1)/M113snps (n = 4)/M1UK (n = 18)-lineages in central Japan of Tokyo/Chiba/Tochigi/Saitama/Kanagawa. The M1 clones were from twenty-one non-invasive samples of pediatric/adult patients and two invasive specimens of adult patients. Additionally, we determined the sic nucleotide alleles and observed the M1global/M113snps/M1UK sic clustering. Of the CovS amino acid (AA) mutations among M1, there was an insertion of transposase (ISAs1-like IS1548 transposase, 377 AA) into CovS histidine kinase-like ATPase domain (following AA position 458) of one invasive M1UK isolate. Our observations suggest that CovS AA mutations of invasive isolates with M1UK should be specified within its four functional domains to evaluate their hypervirulent properties.

Abstract Background In adult patients with Philadelphia chromosome–negative B-cell acute lymphoblastic leukemia (Ph– B-ALL), treatment strategies must balance long-term survival with the mitigation of therapy-related toxicity. The introduction of the bispecific T-cell engager blinatumomab (Blina) has emerged as a promising approach, particularly for measurable residual disease (MRD)-positive patients. However, the optimal timing of Blina administration and its role in modulating chemotherapy intensity remain to be fully elucidated. We conducted a comparative analysis of two prospective clinical trials: ALL/MRD2019, which added Blina only for patients with post-intensive chemotherapy MRD positivity, and ALL/MRD2023, which implemented upfront Blina in all patients following early consolidation with reduced-intensity chemotherapy. Methods Both protocols consisted of induction therapy (Treatment A) followed by consolidation using cytarabine (Treatment B) and methotrexate (Treatment C). MRD was evaluated by allele-specific oligonucleotide quantitative PCR targeting rearranged TCR and IG genes. In the ALL/MRD2019 protocol, patients who were MRD-negative after Treatment C-1 received additional cycles of A, B, and C, followed by maintenance. MRD-positive patients received one additional A course, omitted additional B and C, and received 4 cycles of Blina. In the ALL/MRD2023 protocol, all patients received 4 cycles of Blina after Treatment C-1, regardless of MRD status. In both protocols, patients with MRD positivity after C-1 or with relapse during therapy were recommended for allogeneic stem cell transplantation if feasible; non-transplant candidates received 2 years of maintenance. ALL/MRD2023 omitted Treatment B-2 and C-2 (thus reducing chemotherapy intensity) but increased intrathecal prophylaxis from 7 to 12 doses. As both studies are ongoing, the primary endpoints of this interim analysis were 2-year overall survival (OS) and leukemia-free survival (LFS). Results As of June 2025, 137 patients had been enrolled in the ALL/MRD2023 study and 121 in the ALL/MRD2019 study (total 258 patients). The MRD negativity rate after induction (Treatment A-1) was 53.3% in ALL/MRD2023 vs 45.5% in ALL/MRD2019 (p=0.21). In the ALL/MRD2019 cohort, 26.4% were MRD-positive after Treatment C-1 and received Blina accordingly. The 2-year OS and LFS were 98.9% (95%CI: 92.5 to 99.8) and 85.6% (95%CI: 71.9 to 92.9) in ALL/MRD2023, compared to 89.6% (95%CI: 82.0 to 94.1) and 74.1% (95%CI: 64.7 to 81.3) in ALL/MRD2019, respectively (OS: p=0.07, LFS: p=0.69). Age-stratified analyses showed consistently superior 2-year OS and LFS in ALL/MRD2023 across all age groups (16–35, 36–55, 56–65 years), with OS: 100% (95%CI: not reached to not reached) vs 91.4% (95%CI: 78.7 to 96.7), 97.3% (95%CI: 82.3 to 99.6) vs 88.5% (95%CI: 72.2 to 85.5), and 100% (95%CI: not reached to not reached) vs 87.5% (95%CI: 65.8 to 95.9); and LFS: 87.3% (95%CI: 71.9 to 94.6) vs 71.3% (95%CI: 56.3 to 81.9), 90.9% (95%CI: 77.4 to 96.5) vs 73.6% (95%CI: 55.4 to 85.3), and 93.3% (95%CI: 61.3 to 99.0) vs 80.3% (95%CI: 58.8 to 91.4), respectively. Among MRD-negative patients after Treatment C-1, 2-year OS and LFS were 98.6% (95%CI: 90.4 to 99.8) and 92.0% (95%CI: 82.7 to 96.4) in ALL/MRD2023 vs 91.1% (95%CI: 82.3 to 95.7) and 76.8% (95%CI: 65.6 to 84.7) in ALL/MRD2019 (OS: p=0.13, LFS: p=0.57). Among MRD-positive patients after Treatment C-1, ALL/MRD2023 showed 2-year OS and LFS of 100% (95%CI: not reached to not reached) and 72.2% (95%CI: 41.6 to 88.6) compared to ALL/MRD2019 [85.3% (95%CI: 65.4 to 19.9) and 67.2% (95%CI: 65.4 to 94.2)] (OS: p=0.22, LFS: p=0.93). Conclusion Although the follow-up period remains relatively short and statistical significance has not yet been demonstrated, preliminary data suggest that the ALL/MRD2023 protocol with upfront blinatumomab administration and reduced-intensity chemotherapy may offer improved OS and LFS compared to the conventional intensive chemotherapy approach of ALL/MRD2019. Given the numerically superior outcomes observed across multiple age groups and MRD strata, the ALL/MRD2023 regimen represents a promising treatment strategy that warrants further validation through longer follow-up and mature outcome analyses. These findings support the potential of upfront Blina to enhance survival while minimizing chemotherapy-related toxicity in adult Ph– B-ALL.

Objective Abstaining from alcohol improves the outcome of alcohol-related cirrhosis. This study evaluated the effect of alcohol abstinence on the outcomes of patients with alcohol-related cirrhosis recruited from a Methods This single-center retrospective study recruited 116 patients with alcohol-related cirrhosis who were admitted to our department between April 2014 and October 2022. Taking the day of discharge as day 0, the patients were divided into two groups based on their subsequent behavior (abstinence/non-abstinence from alcohol). The study analysis included 98 patients after excluding 13 who died during hospitalization and 5 for whom follow-up at our hospital ended after discharge. We evaluated differences in the patient survival between the abstaining and drinking groups. Results The abstaining and drinking groups comprised 57 and 41 patients, respectively. We excluded from the analysis 10 and 6 patients with viable hepatocellular carcinoma in the abstaining and drinking groups, respectively. The findings revealed that the survival rate plateaued in the abstaining group from the third year onward, whereas the survival rate in the drinking group gradually decreased with time. Conclusion Our findings suggest that at least two years of alcohol abstinence is required to sustain the survival of patients with alcohol-related cirrhosis. The data collected by our hospital retrospectively demonstrated the importance of abstinence on a timescale of years of sustained abstinence.

Background and Aim:Acute-on-chronic liver failure (ACLF) carries high short-term mortality, but real-world evidence under the Japanese ACLF criteria remains limited. We assessed incidence, clinical profile, outcomes, and prognostic factors at a tertiary center in urban Japan. Methods:We retrospectively reviewed 363 consecutive hospitalizations of patients with cirrhosis (2014-2022) at a tertiary care center in Japan. ACLF per Japanese criteria was categorized as confirmed (meeting both PT INR/PT activity and bilirubin thresholds) or extended (meeting either biochemical criterion alone). We pre-specified a parsimonious Cox model with age (per 10 years) and MELD-Na (per 5 points); the primary outcome was time to all-cause death within 90 days (administrative censoring at day 90). Results:ACLF occurred in 40/363 (11.0%) patients (confirmed n = 10, extended n = 30). Frequent precipitants were infection, gastrointestinal bleeding, and alcohol use, often in combination. The 90-day mortality by Kaplan-Meier was 30.5%. Age (per 10 years) was associated with higher 90-day mortality (HR, 2.29; 95% CI 1.31-4.00; p < 0.01), as was Model for End-Stage Liver Disease including sodium (MELD-Na) (per 5 points) (HR, 1.74; 95% CI 1.16-2.63; p < 0.01). Conclusions:In this Japanese single center cohort, ACLF (per national criteria) was not rare and carried substantial short-term mortality. Age and MELD-Na were dominant prognostic factors, underscoring early trigger control (notably infection, gastrointestinal bleeding, and alcohol cessation) and timely risk stratification in routine care.

Background:Low sleep quality induces inflammation. Because anti-thyroid peroxidase antibody (TPO-Ab) is an autoantibody that induces inflammation in the thyroid, insufficient sleep may stimulate the production of TPO-Ab. However, the thyroid function is also associated with sleep. Therefore, to evaluate the association between TPO-Ab positivity and insufficient sleep, the target population should be limited to euthyroid individuals whose free triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) are within the normal ranges. Method:This cross-sectional study recruited 1324 euthyroid individuals who participated in annual health checkups. Insufficient sleep was assessed by using a questionnaire. Individuals with free T3, free T4, and TSH levels within the normal ranges were defined as euthyroid. Results:Among the study population, 406 had insufficient sleep, and 242 were TPO-Ab-positive. Insufficient sleep was associated with a higher likelihood of TPO-Ab positivity. Sex and age adjusted odd ratios (95 % confidence intervals, p) of TPO-Ab positive for insufficient sleep was 1.47 (1.08, 2.01, p = 0.014). These associations remained unchanged even after further adjustment for free T4 and TSH, status of body mass index, smoking status, drinking status, mental distress, and physical activity; 1.53 (1.11, 2.10, p = 0.009). Conclusion:Euthyroid individuals with insufficient sleep may be at risk of autoimmune thyroiditis. Although further investigations are necessary, sleep disorder therapy might reduce the risk of the incidence of autoimmune thyroiditis.

BACKGROUND:Epstein-Barr (EB) virus infection stimulates the production of vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis. Angiogenesis plays an important role in the development of atherosclerosis. Since serum anti-early antigen EB virus IgG (EBV EA-IgG) titer is a sign of active EB virus infection, EBV EA-IgG titer could be associated with atherosclerosis. The number of minor (T) alleles in VEGF polymorphism rs3025039 has been reported to be inversely associated with serum VEGF concentration, suggesting that rs3025039 might have a strong influence on the association between EBV EA-IgG titer and atherosclerosis. By focusing on the role of VEGF in the development of atherosclerosis, this study aimed to investigate the association between active EB virus infection and atherosclerosis. METHODS:A cross-sectional study of 2,661 older Japanese individuals aged 60-89 years who participated in annual health check-ups during 2017-2019 was conducted. Logistic regression was used to evaluate the association between EBV EA-IgG titer and atherosclerosis in relation to rs3025039 genotype. The influence of rs3025039 (T) allele carrier status on the association between EBV EA-IgG titer and atherosclerosis was also evaluated by using logistic regression. RESULTS:Among rs3025039 CC-homozygotes, with the lowest EBV EA-IgG titer tertile as the reference, the multivariable odds ratio (95% confidence interval) was 1.11 (0.82, 1.50) for the medium tertile and 1.07 (0.78, 1.47) for the high tertile. Among rs3025039 (T) allele carriers, the corresponding values were 1.44 (0.88, 2.36) and 1.88 (1.15, 3.05), respectively. There was a significant interaction between rs3025039 (T) allele carrier status and the association between EBV EA-IgG titer and atherosclerosis (adjusted p = 0.0497). CONCLUSION:EBV EA-IgG titer was significantly positively associated with atherosclerosis only among participants who are genetically less likely to have progressive angiogenesis. An angiogenesis-related genetic factor was revealed as a determinant of the association between EBV EA-IgG titer and atherosclerosis. These findings introduce a novel concept that could explain the association between viral infection and atherosclerosis.

Although both thyroid function and skipping breakfast influence circadian rhythms, no study has yet examined an association between subclinical hypothyroidism (SCH) and breakfast skipping in the middle-aged to elderly population. This cross-sectional study included 1,725 Japanese individuals aged 40-74 with normal free triiodothyronine and free thyroxine levels. Skipping breakfast more than three times a week is defined as having a habit of skipping breakfast. Logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between SCH and breakfast skipping. Analyses were stratified according to the thyroid cyst status, as the absence of thyroid cysts may indicate latent thyroid damage. Among the study population, 564 individuals had thyroid cysts, and 98 had SCH. In the overall analysis, a positive association was observed between SCH and skipping breakfast, though statistical significance was not reached (the potential confounder-adjusted OR: 1.47, 95% CI: 0.77-2.82). However, when analyses were restricted to individuals without thyroid cysts, the association became significant (adjusted OR: 2.26, 95% CI: 1.13-4.51). Skipping breakfast is significantly associated with SCH in individuals without thyroid cysts. While further research is warranted, these findings suggest that breakfast skipping may contribute to latent thyroid dysfunction.

BACKGROUND:Staying active in daily life is believed to help maintain individuals' oral motor function and prevent oral frailty, a potential risk factor for general health. However, there is limited epidemiological evidence of this association. This study focused on vocalising frequency as an indicator of activeness in daily life. METHODS:We conducted a home-visit survey targeting residents aged ≥ 65 years in a rural community in the Goto Islands, Japan. Among 563 participants, those with missing data for the main outcome or vocalising (n = 84) were excluded. Tongue pressure was measured thrice; we used maximum tongue pressure as a marker of tongue motor function. Frequency of conversation, laughter and other vocalising opportunities (e.g., singing or Buddhist chanting) was measured. The multivariate-adjusted regression models were used to calculate parameter estimates (B) for tongue pressure according to the frequency of vocalisation. RESULTS:Among the 479 participants, the proportion of individuals who answered 'every day' was 77% for conversation, 48% for laughter and 47% for other vocalising opportunities. Participants engaging every day in other vocalising opportunities recorded higher maximum tongue pressure (B = 2.26; p = 0.03) than those who did not at all. Sex did not affect this association (p interaction = 0.72). Conversation and laughter every day overlapped with the everyday category of other vocalising opportunities, but they were not associated with tongue pressure. CONCLUSION:Engaging every day in vocalising opportunities other than conversation or laughter was independently associated with a higher maximum tongue pressure in older adults than those who vocalised less often.

Background:Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment landscape for relapsed or refractory non-Hodgkin lymphoma, achieving a 5-year overall survival rate of 40-50%. However, relapse remains a major challenge, especially due to CD19-negative clones. Epcoritamab, a bispecific antibody targeting CD20 and CD3, offers a potential solution for post-CAR-T relapse; however, clinical data in this setting remain limited, particularly in Japan. The case:A 68-year-old woman with CD5-positive diffuse large B-cell lymphoma (DLBCL) relapsed multiple times following various treatments, including CAR-T therapy. Genetic profiling revealed a MYD88/CD79B-mutated (MCD) subtype with CD19-negative clones resistant to CAR-T cells. Given her high tumor burden, she received debulking therapy followed by epcoritamab treatment. Despite concerns about tumor lysis syndrome, cytokine release syndrome, and neurotoxicity, no significant adverse events occurred. The patient achieved a complete remission, demonstrating the efficacy and safety of this approach. Conclusion:This case highlights the potential of epcoritamab combined with debulking therapy for treating CAR-T-refractory CD19-negative DLBCL. This is the first validated case in Japan showing that epcoritamab is a viable and safe treatment option for post-CAR-T relapse, addressing a critical unmet need in the current therapeutic landscape.

Few epidemiological studies have explored the longitudinal relationship between atherosclerosis and periodontitis. The aim of this study was to investigate the longitudinal relationship between atherosclerosis and the progression of periodontitis in community-dwelling individuals in Japan. Progression of periodontitis was defined as the presence of the teeth demonstrating a longitudinal loss of proximal attachment ≥ 3 mm during the study period. Oral examinations and subclinical atherosclerosis assessments were performed. The surrogate markers of early-stage atherosclerosis were increased carotid intima-media thickness (cIMT), low ankle-brachial index (ABI), and cardio-ankle vascular index (CAVI). The study included 222 Japanese adults. While CAVI increased significantly in both groups, the prevalence of CAVI ≥ 8 was significantly increased in only the progression group during the study period. Logistic regression analysis indicated that the progression of periodontitis was significantly associated with cIMT. Additionally, CAVI positively correlated with changes in probing pocket depth, while ABI negatively correlated with changes in clinical attachment loss. These results suggest that participants with high cIMT, high CAVI and low ABI had a high risk of periodontitis progression after adjusting for risk factors. In conclusion, subclinical markers of early-stage atherosclerosis are significantly associated with a greater risk of periodontitis progression in community-dwelling Japanese participants.