Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Mushroom intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study (CIRCS).

It is uncertain whether dietary intake of mushrooms rich in dietary fibre and several antioxidants is associated with a lower risk of dementia. We sought to examine prospectively the association between mushroom intake and the risk of disabling dementia. We performed a prospective study involving 3750 people aged 40 to 64 years residing in three communities who participated in an annual cardiovascular risk survey from 1985 to 1999. Cases of incident disabling dementia were surveyed from 1999 to 2020. We calculated the hazard ratios (HR) and 95 % CI for incident total dementia according to mushroom intake among participants with or without a history of stroke. During a mean 16·0 years' follow-up in 3739 eligible participants, 670 people developed disabling dementia. For women, mushroom intake was inversely associated with the risk of total dementia and the association was confined to dementia without a history of stroke. The multivariable HR (95 % CI) for total dementia in women were 0·81 (0·62, 1·06) for mushroom intake of 0·1-14·9 g/d and 0·56 (0·42, 0·75) for mushroom intake above 15·0 g/d (Pfor trend = 0·003) compared with no intake. The corresponding HR (95 % CI) for dementia without a history of stroke were 0·66 (0·47, 0·93) and 0·55 (0·38, 0·79) (Pfor trend = 0·01). In men, no associations were observed between mushroom intake and the risk of disabling dementia. Among Japanese women, dietary mushroom intake was associated with a lower risk of disabling dementia.

Serum folate and risk of disabling dementia: a community-based nested case-control study.

PURPOSE: The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia). METHODS: We performed a nested case-control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. RESULTS: After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51-0.99), 0.76 (0.54-1.06), 0.70 (0.49-1.00), and 0.62 (0.43-0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke. CONCLUSION: In this nested case-control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals.

ASO Author Reflections: Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Values in Patients with Pancreatic Cancer: Focusing on the Usefulness in Patients with Normal CA19-9.

Pancreatic cancer (PC) is one of the most aggressive cancer types, and carbohydrate antigen (CA) 19-9 has been the most useful biomarker for its surveillance and prognosis prediction. However, CA19-9 may not be sufficiently prognostic in some patients, such as Lewis antigen-negative phenotype (Le[a-b-]) patients who secrete little or no CA19-9. Duke pancreatic monoclonal antigen type 2 (DUPAN-2) has been proposed as a complementary marker to CA19-9 in PC patients, but its utility in Le(a-b-) patients has only been reported in a limited number of cases. In a retrospective analysis of 224 PC patients who underwent surgery, the present study investigated the utility of DUPAN-2 in combination with CA19-9. The study subjects were divided into three groups based on their CA19-9 and DUPAN-2 levels. The normal CA19-9/high DUPAN-2 group had significantly larger tumors and a higher frequency of microscopic vascular invasion, perineural invasion, and recurrence than the normal CA19-9/normal DUPAN-2 group. Both the disease-free survival and disease-specific survival (DSS) of patients in the normal CA19-9/high DUPAN-2 group were significantly shorter than those in the normal CA19-9/normal DUPAN-2 group, and comparable with those in the high CA19-9 group. The results suggest that DUPAN-2 may be useful as a complementary biomarker to CA19-9 in PC, especially in patients who have normal CA19-9 levels. However, since this was a single-center, retrospective study, multicenter studies are needed to confirm the findings and determine the optimal cut-off value for patients with normal CA19-9 levels.

Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Levels in Patients with Pancreatic Cancer.

BACKGROUND: This study aimed to evaluate the clinical implication of Duke pancreatic monoclonal antigen type 2 (DUPAN-2) for patients with pancreatic cancer (PC), especially those with normal carbohydrate antigen (CA) 19-9 levels. METHODS: The study reviewed 224 patients who underwent surgery for PC from January 2003 through December 2019 at the Shizuoka Cancer Center. The patients were divided into three groups according to the following CA19-9 and DUPAN-2 levels: normal CA19-9/normal DUPAN-2, normal CA19-9/high DUPAN-2, and high CA19-9. The prognostic utility of the DUPAN-2 levels in the normal CA19-9 patients was investigated. RESULTS: Elevated serum levels of DUPAN-2 were observed in 29 (25.2%) of the normal CA19-9 patients. The cutoff value for serum DUPAN-2 level was set at 250 U/ml. Both disease-free survival and disease-specific survival (DSS) in the normal CA19-9/high DUPAN-2 group were significantly shorter than in the normal CA19-9/normal DUPAN-2 group and comparable with those in the high CA19-9 group. In the normal CA19-9 group, DUPAN-2 was identified as an independent prognostic factor for DSS. The patients with normal CA19-9/high DUPAN-2 had higher pathologic malignancy than the patients with normal CA19-9/normal DUPAN-2, which was comparable with that in the patients with high CA19-9. CONCLUSION: In PC, DUPAN-2 may be useful as a biomarker complementary with CA19-9. The combination of these two markers may aid in the preoperative prediction of prognosis for patients with PC.

Modifying Effect of Outdoor Recreational Activity on the Association Between Anger Expression and Cardiovascular Disease Risk: The Circulatory Risk in Communities Study.

OBJECTIVE: Outdoor recreational activity (ORA) has been suggested as a practical strategy for anger management to moderate the risk of cardiovascular disease (CVD). However, there is a lack of evidence pertaining to this topic. Our aim was to examine whether ORA modified the association between anger expression and the risk of CVD. METHODS: A community-based cohort study was conducted among 1877 Japanese individuals aged 40 to 79 years at baseline in 1997. The anger expression was measured using the Spielberger Anger Expression Scale. Stratified into low and high ORA (0 and ≥1 of the four behaviors), a Cox proportional hazards model was used to assess the anger expression-related risk of incident CVD (ischemic heart disease and stroke). RESULTS: We identified 76 incident CVDs during a median follow-up of 18.8 years. Among participants with low ORA, anger expression was associated with an increased risk of CVD, whereas no association was identified among those with high ORA. The standardized hazard ratios were 1.53 (95% confidence interval, 1.23-1.91) and 0.77 (0.51-1.15) among those with low and high ORA, respectively ( p for interaction = .004). Similar associations were observed regarding the risk of total and ischemic stroke, and ischemic CVD. CONCLUSIONS: We found an elevated risk of CVD associated with anger expression among participants with low ORA but not among those with high ORA, suggesting that ORA use may mitigate the association between anger expression and CVD risk.

Longitudinal trajectories of smoking status using 25 year annually-updated data and all-cause mortality followed over 30 years: A community-based prospective cohort study.

We aimed to evaluate the long-term risk of smoking for all-cause mortality according to smoking status trajectories using 25-year annually-repeated input, traced by group-based trajectory modeling with an extension to account for non-random participant attrition or truncation due to death. We examined 2682 men and 4317 women aged 40 to 59 years who participated in annual health checks for the community-based prospective cohort study, 1975-1984 enrollment in Japan. The main outcome measure was all-cause mortality (follow-up period: median 30.2 years in men and 32.2 years in women). We traced annual smoking trajectories, stratified by sex and smoking status at baseline. For smokers at baseline, we identified five trajectories in both sexes, with different patterns of smoking cessation (e.g., early quitters and lifelong smokers). We calculated HRs and 95% CI of all-cause mortality using Cox proportional hazards regression modeling adjusted for age, body mass index, alcohol intake, blood pressure category, dyslipidemia and glucose category. Compared with one-time-point-based smokers, trajectory-based lifelong smokers had an increased risk of all-cause mortality; HRs were 1.31 (95% CI, 1.18-1.46) in men and 1.26 (95% CI, 0.91-1.73) in women. Among community residents aged 40 to 59 years, 25-year-trajectory-based lifelong smokers had an approximately 30% increased risk for all-cause mortality compared to one-time-point-based smokers. Risk of all-cause mortality among smokers with earlier cessation varied materially. It is necessary to consider the trajectories of smoking status to clarify the long-term excess risk of smoking.

Impact of Perceived Social Support on the Association Between Anger Expression and the Risk of Stroke: The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: Anger has been suggested as a risk factor for stroke. Perceived social support (PSS) may relieve anger, thus reducing the risk of stroke; however, evidence supporting this is limited. We aimed to examine whether PSS modifies the risk of stroke associated with anger expression. METHODS: A cohort study was conducted among 1,806 community residents aged 40-74 years who received a cardiovascular risk survey, including anger expression, in 1997. A Cox proportional hazards model was applied to the participants with low and high PSS to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the risks of total stroke and its subtypes based on total anger expression after adjusting for known stroke risk factors. RESULTS: The median follow-up duration was 18.8 years, with 51 incident strokes. Among the participants with low PSS, anger expression had a positive association with the total stroke risk: The multivariable HR per standard deviation increment of total anger expression was 1.43 (95% CI, 1.13-1.82). In contrast, no association was identified among those with high PSS. The corresponding HR was 0.83 (95% CI, 0.49-1.40), with a significant interaction between low and high PSS (P = 0.037). Similar associations regarding the risk of ischemic stroke were found. CONCLUSION: We found an increased risk of stroke associated with anger expression among the participants with low PSS, but not among those with high PSS. Our results suggest that PSS might mitigate the risk of stroke associated with anger.

Profile of Nagasaki Islands Study (NaIS): A Population-Based Prospective Cohort Study on Multi-disease.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow-up with them for vital status (death), migration, and occurrence of diseases such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1) -associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014-2016, secondary surveys during 2017-2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed-up; and 3,594 and 3,364 residents (aged 27-96 and 28-98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Association between periodontitis and chronic kidney disease by functional atherosclerosis status among older Japanese individuals: A cross-sectional study.

AIM: This study aimed to clarify the influence of functional atherosclerosis on the association between periodontitis and chronic kidney disease (CKD). MATERIALS AND METHODS: A cross-sectional study of 998 older Japanese individuals aged 60-99 years who participated in an oral health check-up was conducted. Early and advanced periodontitis were defined as periodontal pocket depth of 4.0-5.9 mm and ≥6.0 mm, respectively. Functional atherosclerosis was defined as cardio-ankle vascular index ≥9.0. RESULTS: Of the 998 study participants, 238 (23.8%) had CKD. No significant associations between periodontitis and CKD were observed in participants without functional atherosclerosis. After adjusting for known cardiovascular risk factors, the odds ratio (OR) (95% confidence interval [CI]) was 1.31 (0.81-2.11) for early periodontitis and 0.74 (0.41-1.34) for advanced periodontitis. Significant positive associations were observed for participants with functional atherosclerosis; the adjusted ORs (95% CIs) were 1.76 (1.04-3.01) for early periodontitis and 1.95 (1.05-3.63) for advanced periodontitis. CONCLUSIONS: A significant positive association between periodontitis and CKD was established for older participants with functional atherosclerosis. No significant associations were observed for those without functional atherosclerosis. These results can help clarify the influence of periodontitis on systemic circulation.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

Relationships of habitual daily alcohol consumption with all-day and time-specific average glucose levels among non-diabetic population samples.

BACKGROUND: Alcohol consumption is a prevalent behavior that is bi-directionally related to the risk of type 2 diabetes. However, the effect of daily alcohol consumption on glucose levels in real-world situations in the general population has not been well elucidated. This study aimed to clarify the relationship between alcohol consumption and all-day and time-specific glucose levels among non-diabetic individuals. METHODS: We investigated 913 non-diabetic males and females, aged 40-69 years, during 2018-2020 from four communities across Japan. The daily alcohol consumption was assessed using a self-report questionnaire. All-day and time-specific average glucose levels were estimated from the interstitial glucose concentrations measured using the Flash glucose monitoring system for a median duration of 13 days. Furthermore, we investigated the association between all-day and time-specific average glucose levels and habitual daily alcohol consumption levels, using never drinkers as the reference, and performed multiple linear regression analyses after adjusting for age, community, and other diabetes risk factors for males and females separately. RESULTS: All-day average glucose levels did not vary according to alcohol consumption categories in both males and females. However, for males, the average glucose levels between 5:00 and 11:00 h and between 11:00 and 17:00 h were higher in moderate and heavy drinkers than in never drinkers, with the difference values of 4.6 and 4.7 mg/dL for moderate drinkers, and 5.7 and 6.8 mg/dL for heavy drinkers. Conversely, the average glucose levels between 17:00 and 24:00 h were lower in male moderate and heavy drinkers and female current drinkers than in never drinkers; the difference values of mean glucose levels were -5.8 for moderate drinkers, and -6.1 mg/dL for heavy drinkers in males and -2.7 mg/dL for female current drinkers. CONCLUSIONS: Alcohol consumption was associated with glucose levels in a time-dependent biphasic pattern.

Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score.

BACKGROUND: Surgical resection is the only potentially curative therapy for gallbladder carcinoma (GBC). However, the postoperative recurrence rate is high (approximately 50%), and recurrence occasionally develops early after surgery. PATIENTS AND METHODS: A total of 139 patients who underwent macroscopically curative resection for GBC between 2002 and 2018 were retrospectively reviewed. Early recurrence (ER) was defined as recurrence within 6 months after surgery. Univariate and multivariate logistic regression analysis was performed using preoperative factors that may influence early recurrence, namely patient background factors, tumor markers, imaging findings, and body composition parameters obtained preoperatively, to create a predictive score for ER. RESULTS: The median follow-up period was 21.9 months (range, 6.2-195.7 months). Postoperative recurrence was observed in 55 (39.6%) patients, of whom 14 (25.5%) developed ER. The median overall survival after surgery was 104.7 months for the non-ER group and 15.7 months for the ER group. On multivariate analysis, high carbohydrate antigen 19-9, low muscle attenuation, high visceral fat attenuation, liver invasion, and other organ invasion on preoperative computed tomography were identified as independent risk factors for ER. A preoperatively predictive scoring system for ER was constructed by weighting the above five factors. The nomogram showed an area under the curve of 0.881, indicating good predictive potential for ER. CONCLUSIONS: ER in resected GBC indicates a very poor prognosis. The present preoperative scoring system can sufficiently predict ER and may be helpful in determining the optimal treatment strategies.

Prognostic Impact of Indicators of Systemic Inflammation and the Nutritional Status of Patients with Resected Carcinoma of the Ampulla of Vater: A Single-Center Retrospective Study.

BACKGROUND: Several indicators of systemic inflammation and nutritional status were recently shown to serve as novel prognostic factors for certain cancers. Here, we aimed to investigate the prognostic impact of preoperative indicators of systemic inflammation and nutritional status associated with the survival of patients with resected ampulla of Vater carcinoma (AC). METHODS: We retrospectively analyzed the records of 91 patients who underwent pancreatoduodenectomy (PD) for AC from January 2002 through December 2018. Indices for systemic inflammation and nutritional status (Systemic immune-inflammation index [SII], Prognostic nutritional index [PNI], modified Glasgow prognostic score [mGPS], and Controlling nutritional status score [CONUT]) were determined using preoperative blood tests. Clinicopathological factors and these indices were analyzed to identify predictors of overall survival (OS). RESULTS: The median preoperative SII and PNI values were 456.7 and 47.5, respectively, and their optimal cut-off values were 670.0 and 50.0, respectively. Univariate analysis revealed that high SII, low PNI, mGPS ≥ 1, and malnutrition, assessed using the CONUT, were significant predictors of shorter OS. Multivariate analysis revealed that high SII (HR = 2.71, p = 0.023) and malnutrition assessed using the CONUT (hazard ratio = 3.98, p = 0.006) were independent predictors of shorter OS. CONCLUSION: SII and the CONUT predicted the survival of patients with AC after radical resection. These indicators are easily calculated using preoperative blood tests and may contribute to the development of improved strategies to treat AC.

Influence of height on endothelial maintenance activity: a narrative review.

Recent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.

Associations between handgrip strength and hypertension in relation to circulating CD34-positive cell levels among Japanese older men: a cross-sectional study.

BACKGROUND: A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension. METHODS: A cross-sectional study was conducted with 257 Japanese men aged 60-69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/µL) as the cutoff. RESULTS: Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37)). CONCLUSION: The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.

Association between height-related polymorphism rs17081935 and reduced handgrip strength in relation to status of atherosclerosis: a cross-sectional study.

BACKGROUND: Aging is a process that increases oxidative stress. Increased oxidative stress leads to the development of atherosclerosis and mitochondrial dysfunction. Mitochondria contribute to energy production that might have a beneficial influence on maintaining muscle strength. Therefore, the height-related single nucleotide polymorphism (SNP) rs17081935, which is also reported to be associated with mitochondrial metabolism, might be associated with reduced muscle strength and this association might be affected by atherosclerosis status. To clarify those associations, a cross-sectional study of 1374 elderly Japanese individuals aged 60-89 years was conducted. METHODS: Logistic regression was used to clarify the association between rs17081935 and reduced handgrip strength. Since atherosclerosis might affect handgrip strength, participants were stratified by atherosclerosis status. Reduced handgrip strength was defined as being in the lowest quintile of handgrip strength (< 25.6 kg for men and < 16.1 kg for women). RESULTS: No significant associations were found between a minor allele of rs17081935 and reduced handgrip strength among elderly participants without atherosclerosis. A significant inverse association was observed among elderly participants with atherosclerosis. After adjusting for known cardiovascular risk factors and height, the adjusted odd ratio (OR) and 95% confidence interval (CI) for reduced handgrip strength and a minor allele of rs17081935 were 1.13 (0.86, 1.43) for elderly participants without atherosclerosis and 0.55 (0.36, 0.86) for those with atherosclerosis, respectively. CONCLUSION: A minor allele of the height-related SNP rs17081935 was significantly inversely associated with reduced handgrip strength among older individuals with atherosclerosis, but not among those without atherosclerosis.

Possible mechanisms underlying the association between human T-cell leukemia virus type 1 (HTLV-1) and hypertension in elderly Japanese population.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up. METHODS: Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway. RESULTS: HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]). CONCLUSION: Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.

Anger Expression and the Risk of Cardiovascular Disease Among Urban and Rural Japanese Residents: The Circulatory Risk in Communities Study.

OBJECTIVE: It has been suggested that urbanization, which has been expanding rapidly for the past several decades, increases the risk of cardiovascular disease (CVD) associated with psychological factors such as anger, but the evidence is limited. We examined the hypothesis that urbanicity modifies the association of anger expression with the risk of CVD. METHODS: A prospective study was conducted in 5936 residents of urban and rural communities aged 40 to 79 years who had completed an annual health checkup including a questionnaire on anger expression between 1995 and 1998. Associations of anger expression with the risk of CVDs were examined using Cox proportional hazards models, after adjusting for classical cardiovascular risk factors. RESULTS: During a median follow-up of 16.6 years, we identified 312 incident CVDs. The means (SDs) of anger expression were 24.7 (5.8) among urban residents and 24.6 (5.7) among rural participants (p = .87). Among urban residents, anger expression was positively associated with the risk of total CVD: the multivariable hazard ratio (95% confidence interval) was 1.27 (1.05-1.54). In contrast, no association was found among rural residents: the corresponding ratio (interval) was 0.96 (0.85-1.09), with a significant interaction between urban and rural residency with anger expression for incident CVD (p = .047). Similar associations were observed with the risk of CVD subtypes, including ischemic stroke and ischemic CVD. CONCLUSIONS: We found a positive association between anger expression and the risk of CVD among urban residents but not rural residents, suggesting that urbanicity enhances the anger-CVD association.

The role of mental disease on the association between multimorbidity and medical expenditure.

BACKGROUND: Multimorbidity is the presence of two or more chronic diseases and is associated with increased adverse outcomes, including hospitalization, mortality and frequency of use of medical institutions. OBJECTIVE: This study aimed to describe multimorbidity patterns, determine whether multimorbidity was associated with high medical expenditure, and determine whether mental diseases had an interaction effect on this association. METHODS: We conducted a claims data-based observational study. Data were obtained for 7526 individuals aged 0-75 years from a medical claims data set for Goto, Japan, over a 12-month period (2016-17). Annual medical expenditure was divided into quintiles; the fifth quintile represented high medical expenditure. Multimorbidity status was defined as the occurrence of two or more health conditions from 17 specified conditions. Odds ratios (OR) and 95% confidence intervals (CI) for high medical expenditure were calculated by number of comorbidities. RESULTS: In total, 5423 (72.1%) participants had multimorbidity. Multimorbidity was significantly associated with high medical expenditure, even after adjustment for age, sex and income category (OR: 10.36, 95% CI: 7.57-14.19; P < 0.001). Mental diseases had a significant interaction effect on the association between multimorbidity and high medical expenditure (P = 0.001). CONCLUSIONS: Multimorbidity is associated with high medical expenditure in Japan. Mental diseases may contribute to increased medical costs.