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Abstract Background This study investigated whether intraoperative blood salvage was associated with coagulation disorder diagnosed by conventional coagulation tests and thromboelastography (TEG) after cardiopulmonary bypass (CPB). Study design and methods This was a prospective, observational study. Ninety-two patients who underwent cardiovascular surgery with CPB were enrolled. We evaluated coagulation function in patients with or without cell salvage blood transfusion at the following time points: before CPB, just after protamine administration, and 1 h after protamine administration. We evaluated platelet count, fibrinogen concentration, and TEG parameters. Patients were considered to have coagulation disorder if one or more of the following criteria were present: (1) residual heparin, (2) low platelet count, (3) low fibrinogen level, (4) low clotting factor level, and (5) hyperfibrinolysis. Results Fifty-three of 92 patients (57.6%) received intraoperative cell salvage. Coagulation disorder was observed in 56 of 92 patients (60.9%) after CPB. There was no significant difference between patients with or without intraoperative blood salvage in terms of the incidence of coagulation disorder (p = 0.542) or the total volume of blood from the drain after CPB (p = 0.437). Intraoperative blood salvage was not associated with coagulation disorder diagnosed by either TEG or conventional coagulation tests (odds ratio 1.329, 95% confidence interval: 0.549–3.213, p = 0.547). There were no significant interactions between patients with or without intraoperative blood salvage regarding coagulation parameters derived from TEG. Conclusions The incidence of coagulation disorder and the total blood volume from the drain after CPB did not differ significantly between patients with or without intraoperative blood salvage.

Abstract Aims Cognitive impairment and functional status are both important determinants of poor outcomes in heart failure (HF). However, little is known about how functional status impacts the changes in cognitive status during the disease course. This study aimed to describe the cognitive transitions in patients with HF and assess the relationship of these transitions to functional status, which was assessed by the dependency of activities of daily living (ADL). Methods and results This retrospective cohort study included 1764 patients with an International Classification of Diseases‐10 code of HF (≥65 years, mean age 82.3 ± 7.9 years, 39% male) from a long‐term care and medical insurance database from Nobeoka city, a rural city of south‐western Japan. Cognitive status at baseline and 6, 12, 18, and 24 month time points was collected, and participants were stratified based on ADL status at baseline. Generalized estimating equations and multi‐state modelling were used to examine associations between ADL dependency and cognitive changes/mortality. Transition probabilities were estimated using multi‐state modelling. At baseline, there were 1279 (73%) and 485 (27%) patients with independent and dependent ADL, respectively. In overall patients, 1656 (93.9%) patients had normal/mild cognitive status and 108 (6%) patients had a moderate/severe cognitive status at baseline. The majority [104 (96%) patients] of patients with moderate/severe cognitive status at baseline had dependent ADL. In patients with moderate/severe cognitive status, the number of patients with dependent ADL always outnumbered that of the independent ADL throughout the follow‐up. Multi‐state modelling estimated that patients with dependent ADL and normal/mild cognitive status at baseline had 47% probability of maintaining the same cognitive status at 24 months, while the probability of maintaining the same cognitive status was 86% for those with independent ADL. Patients with normal/mild cognitive status in the dependent ADL group at baseline had a higher risk of experiencing a transition to moderate/severe cognitive status at any time point during 24 months compared with those with independent ADL [hazard ratio 5.24 (95% confidence interval 3.47–7.90)]. Conclusions In older patients with HF, the prevalence of cognitive impairment was always higher for those with reduced functional status. Despite having a normal/mild cognitive status at baseline, patients with dependent ADL are at high risk of experiencing cognitive decline over 24 months with substantially less chance of maintaining their cognitive status. ADL dependency was an important risk factor of cognitive decline in patients with HF.

Abstract Introduction Postoperative delirium is a common complication after cardiovascular surgery. A meta-analysis revealed that postoperative delirium was associated with cognitive decline and dementia, which may affect long-term mortality. However, few studies have reported the association between postoperative delirium after cardiovascular surgery and long-term postoperative mortality. Therefore, we investigated the effect of postoperative delirium on 5-year survival rates of patients who underwent cardiovascular surgery. Methods We retrospectively reviewed the records of patients who underwent cardiovascular surgery with cardiopulmonary bypass from January 2016 to December 2019. Postoperative delirium was defined as an Intensive Care Delirium Screening score ≥ 3, which might include subclinical delirium. Cox proportional hazards modeling was performed to assess the association between postoperative delirium and mortality. Postoperative mortality in patients with and without delirium was assessed using the Kaplan–Meier method and compared using the log-rank test. Results Postoperative delirium was observed in 562 (31.9%) of 1731 patients. There were more elderly patients, more emergent surgery procedures, longer operative time, and larger transfusion volume in the postoperative delirium group. Cox regression analyses showed that delirium (hazard ratio (HR), 1.501; 95% confidence interval (CI), 1.053–2.140; p = 0.025) and emergent surgery (HR, 3.380; 95% CI, 2.231–5.122; p

Introduction Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population.Methods and analysis This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse.Ethics and dissemination The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals.Trial registration number jRCTs041220126.

Abstract Aims With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super‐aged society. Methods and results The KUNIUMI registry chronic cohort is a community‐based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P 75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long‐standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P

Background Differences in the clinical course of heritable thoracic aortic disease based on the disease‐causing gene have not been fully evaluated. To clarify the clinical relevance of causative genes in heritable thoracic aortic disease, we assessed the clinical course of patients categorized based on genetic diagnosis. Methods and Results We investigated cardiovascular events and mortality in 518 genetically diagnosed patients in 4 groups: Group 1, FBN1 (n=344); Group 2, TGFBR1, TGFBR2, SMAD3, or TGFB2 (n=74); Group 3, COL3A1 (n=60); and Group 4, ACTA2 or MYH11 (n=40). The median age at the first cardiovascular event ranged from 30.0 to 35.5 years (P=0.36). Patients with gene variants related to transforming growth factor‐β signaling had a significantly higher rate of subsequent events than those with FBN1 variants (adjusted hazard ratio, 2.33 [95% CI, 1.60–3.38]; P

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

This study aimed to investigate whether n−3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n−3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults (n = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n−3 fatty acids to placebo. The primary result was a nonsignificant benefit of this supplementation for the prioritized primary CVD outcome (reciprocal win ratio [95% confidence interval]: 0.90 [0.78–1.04]), similar to the 0.92 (0.80–1.06) hazard ratio in our original time-to-first event analysis without outcome prioritization. Its benefits came from reducing MI (0.71 [0.57–0.88]) but not stroke (1.01 [0.80 to 1.28]) components. For the primary CVD outcome, participants with low fish consumption at baseline benefited (0.79 [0.65–0.96]) more than those with high consumption (1.05 [0.85–1.30]). These results are consistent with, but slightly stronger than, those without outcome prioritization.

Abstract Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation. Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.

Background We investigated the impact of the ring finger protein 213 p.R4810K variant, a founder variant for moyamoya disease in East Asians, on endovascular therapy outcomes in patients with acute anterior‐circulation large‐vessel occlusion stroke in comparison with noncarriers. Methods Of the consecutive patients with ischemic stroke admitted to our institute from 2011 to 2021, patients who underwent endovascular therapy for acute occlusion of the intracranial internal carotid artery or M1 segment of the middle cerebral artery were included. Outcomes were instant reocclusion, final modified Thrombolysis in Cerebral Infarction reperfusion ≥2b, and early reocclusion. Instant reocclusion was defined as the occurrence of reocclusion during the procedure, and early reocclusion was defined as reocclusion detected on magnetic resonance angiography within 2 weeks after the confirmation of successful reperfusion. Results Of the 277 patients analyzed (128 women; median age, 76 years), 10 patients (3.6%) carried the ring finger protein 213 p.R4810K variant. Variant carriers were younger (P=0.01) and more frequently had intracranial atherosclerotic disease‐related large‐vessel occlusion as a cause of acute large‐vessel occlusion (P

Summary: Galactose (Gal)-deficient IgA1 (Gd-IgA1) is involved in IgA nephropathy (IgAN) pathogenesis. To reflect racial differences in clinical characteristics, we assessed disease- and race-specific heterogeneity in the O-glycosylation of the IgA1 hinge region (HR). We determined serum Gd-IgA1 levels in Caucasians (healthy controls [HCs], n = 31; IgAN patients, n = 63) and Asians (HCs, n = 20; IgAN patients, n = 60) and analyzed profiles of serum IgA1 HR O-glycoforms. Elevated serum Gd-IgA1 levels and reduced number of Gal residues per HR were observed in Caucasians. Reduced number of N-acetylgalactosamine (GalNAc) residues per HR and elevated relative abundance of IgA1 with three HR O-glycans were common features in IgAN patients; these features were associated with elevated blood pressure and reduced renal function. We speculate that the mechanisms underlying the reduced GalNAc content in IgA1 HR may be relevant to IgAN pathogenesis.

Abstract Aims Optimal pharmacological treatment for chronic heart failure has been established. However, treatments that can improve the prognosis of acute heart failure (AHF) are controversial. Although intravenous diuretics may be one optimal treatment option, little evidence has shown the effect of early administration of diuretics on clinical outcomes in patients with AHF. The aim of this study was to evaluate the association between door‐to‐furosemide (D2F) time, improved oxygenation, and in‐hospital mortality in patients hospitalized for AHF. Methods and results We screened 494 patients hospitalized for AHF in Miyazaki Prefectural Nobeoka Hospital. AHF patients who were treated with intravenous furosemide within 24 h of arrival at the hospital were included in this study. D2F time was defined as the time from patient arrival at the hospital to the first intravenous dose of furosemide. The early administration group was defined as those with D2F time ≤60 min, whereas the non‐early group was defined as those with D2F time >60 min. The primary outcome was the rate of improved oxygenation at Day 1. The secondary outcomes were in‐hospital mortality and cardiac death. There were 219 patients treated with the first intravenous dose of furosemide within 24 h analysed after the exclusion of 275 patients. The median D2F time was 55 min (interquartile range: 30–120 min) in the final cohort. The early administration group included 121 patients (55.3%). The rate of improved oxygenation was higher in the early group than the non‐early group [median 16.7% (interquartile range: 0.0–40.0) vs. 0.0% (0.0–20.6), respectively, P

In the context of climate change, heatstroke is expected to become an increasingly relevant public health concern. Here, the authors develop and validate prediction models for the number of all heatstroke cases in different cities in Japan.

Abstract Background The present study aimed to investigate associations between long-term renal function, whether IgG4-related tubulointerstitial nephritis (TIN) was diagnosed by renal biopsy at initial examination, chronic kidney disease (CKD) stage, and histological stage in patients with IgG4-related TIN. Methods This study used a retrospective cohort design including almost all patients who underwent renal biopsy at Fujita Health University Hospital and Nagoya University or its affiliated hospitals in Aichi between April 2003 and March 2015 (n = 6977 renal biopsies). The primary outcome was longitudinal changes in eGFR. Main exposures were whether IgG4-related TIN was diagnosed by renal biopsy at the initial examination, CKD stage, and its histological stage. Linear mixed models were performed to examine associations. Results Of the 6977 samples, there were 24 patients (with 201 records due to repeated measures) with IgG4-related TIN (20 men, mean age, 68.7 ± 9.7 years). They were followed up 6.6 ± 2.8 years after the renal biopsy and underwent glucocorticoid treatment. We found significant increase in eGFR from the baseline to 2 and 6 months after treatment initiation, which was maintained until 60 months. Patients initially diagnosed with IgG4-related TIN had higher eGFR from the baseline (at the start of treatment) to 60 months than those who were not. Compared with patients with CKD stage 3, patients with CKD stages 4 and 5 had lower eGFR at the baseline and other time points. Patients with histological stage B had comparatively lower eGFR at each point than stage A patients. Those mean differences of eGFR were stable from the baseline to 60 months. Conclusions After the treatment initiation, renal function rapidly improved and maintained for a long period, even with advanced CKD stage. We showed importance of early diagnosis of IgG4-related TIN in maintaining eGFR.

Abstract Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.

Abstract Objective An ecological study using secondary open data from Japanese government statistics was conducted. The study aimed to verify differences in three measures of healthy life expectancy (HLE); namely, disability-free life expectancy without activity limitation (DFLE-AL), life expectancy with self-perceived health (LE-SH), and disability-free life expectancy without care need (DFLE-CN). Results Each HLE from 47 prefectures in 2010, 2013, and 2016 was extended over time. There were strong Cronbach’s coefficient alpha (α) between DFLE-AL and LE-SH (Minimum α; 0.80, Maximum α; 0.90) as well as between LE and DFLE-CN (Minimum α; 0.92, Maximum α; 0.99) in both sexes in every data year. However, the other pairs had weaker associations. In regression analysis with each HLE as a dependent variable and aging rate, mortality, the proportion of unhealthy people as independent variables, the subjective unhealthy rate had significant standardized partial regression coefficients (β) in models with DFLE-AL and LE-SH as dependent variables (Minimum β; − 0.56, Maximum β; − 0.34). Therefore, DFLE-CN tended to differ from the other HLEs. The subjective unhealthy rate had a significant influence on DFLE-AL and LE-SH.

Introduction There are few studies on the association between serum uric acid (UA) level and mortality in incident dialysis patients. We aimed to clarify whether the serum UA level at dialysis initiation is associated with mortality during maintenance dialysis. Methods We enrolled 1486 incident dialysis patients who participated in a previous multicenter prospective cohort study in Japan. We classified the patients into the following five groups according to their serum UA levels at dialysis initiation: G1 with a serum UA level

Abstract Introduction : Few large, randomized trials have evaluated marine n‐3 supplements and cognition in healthy older adults. Methods : Healthy community‐dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.8] years) in VITAL (randomized trial of n‐3 fats [1 g/day, including 840 mg of eicosapentaenoic acid + docosahexaenoic acid] and vitamin D) were included: 3424 whose cognition was assessed by phone (VITAL‐Cog; eight neuropsychological tests; 2.8 years) and 794 evaluated in person (CTSC‐Cog; nine tests; 2.0 years). The primary outcome was a global score (average of test z‐scores) of change over two assessments. We used multivariable‐adjusted linear mixed models; substudy‐specific results were meta‐analyzed. Results : We observed no significant effect of n‐3 supplementation: the mean difference in annual rate of cognitive change for the n‐3 versus placebo group was –0.01 standard units (95% confidence interval [CI]: –0.02, 0.003) in VITAL‐Cog and –0.002 (95% CI: –0.04, 0.03) in CTSC‐Cog; the pooled difference was –0.01 (95% CI: –0.02, 0.003; P = .15). Discussion : Marine n‐3 supplementation (1 g/day) did not confer cognitive benefits over 2 to 3 years in community‐dwelling older adults.

Objective Although there are regional reports that the COVID-19 pandemic is associated with a reduction in acute myocardial infarction presentations and primary percutaneous coronary intervention (PCI) procedures, little is known about the impact of the COVID-19 pandemic on mechanical complications resulting from ST-segment elevation myocardial infarction (STEMI) and mortality.Methods This single-centre retrospective cohort study analysed presentations, incidence of mechanical complications, and mortality in patients with STEMI before and after a state of emergency was declared due to the COVID-19 pandemic by the Japanese government on 7 April 2020.Results We analysed 359 patients with STEMI hospitalised before the declaration and 63 patients hospitalised after the declaration. The proportion of patients with late presentation was significantly higher after the declaration than before (25.4% vs 14.2%, p=0.03). The incidence of late presentation was significantly higher during the COVID-19 pandemic than before (incidence rate ratio (IRR), 2.41; 95% CI, 1.37 to 4.05; p=0.001, even after adjusting for month (IRR, 2.61; 95% CI, 1.33 to 5.13; p

Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are associated with mtDNAcn or whether age, sex or race/ethnicity moderate associations. In this cross-sectional study, we selected 391 adults (183 non-Hispanic White, 110 Black and 98 Hispanic; mean = 67 years) from the VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) ancillary to the VITAL trial. We estimated associations between lifestyle and behavioral factors (PA, alcohol consumption, cigarette smoking and depression) and log-transformed mtDNAcn using multivariable linear regression models. MtDNAcn was not correlated with chronological age; women had ~17% higher mtDNAcn compared to men. There were no significant associations between PA measures (frequency, amount or intensity) or alcohol consumption with mtDNAcn. Cigarette smoking (per 5 pack-years) was significantly associated with mtDNAcn (percent difference = -2.9% (95% confidence interval (CI) = -5.4%, -0.4%)); a large contrast was observed among heavy vs. non-smokers (≥30 vs. 0 pack-years): percent difference = -28.5% (95% CI = -44.2%, -8.3%). The estimate of mtDNAcn was suggestively different for past vs. no depression history (percent difference = -15.1% 95% CI = -30.8%, 4.1%), but this difference was not statistically significant. The association between smoking and log-mtDNAcn varied by sex and race/ethnicity; it was stronger in men and Black participants. While chance findings cannot be excluded, results from this study support associations of smoking, but not chronological age, with mtDNAcn and suggest nuanced considerations of mtDNAcn as indicative of varying oxidative stress states vs. biological aging itself.

Background: White coat effect (WCE), the blood pressure (BP) difference between clinical and non-clinical settings, can lead to clinical problems such as misdiagnosis of hypertension. Etiology of WCE has been still unclear, especially from genetic aspects. The present article investigated association between genome-wide single nucleotide polymorphisms (SNPs) and WCE in patients with essential hypertension. Methods: The present cross-sectional analyses were based on 295 Japanese essential hypertensive outpatients aged ≧40 years enrolled in randomized control study, Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study, who were not taking antihypertensive medications before the randomization. Home and clinic BP were measured. WCE was defined by subtracting home BP from clinic BP. Genotyping was conducted with 500K DNA microarray chips. Association between genome-wide SNPs and WCE were analyzed. For replication (p

In-home monitoring systems have been used to detect cognitive decline in older adults by allowing continuous monitoring of routine activities. In this study, we investigated whether unobtrusive in-house power monitoring technologies could be used to predict cognitive impairment. A total of 94 older adults aged ≥65 years were enrolled in this study. Generalized linear mixed models with subject-specific random intercepts were used to evaluate differences in the usage time of home appliances between people with and without cognitive impairment. Three independent power monitoring parameters representing activity behavior were found to be associated with cognitive impairment. Representative values of mean differences between those with cognitive impairment relative to those without were −13.5 min for induction heating in the spring, −1.80 min for microwave oven in the winter, and −0.82 h for air conditioner in the winter. We developed two prediction models for cognitive impairment, one with power monitoring data and the other without, and found that the former had better predictive ability (accuracy, 0.82; sensitivity, 0.48; specificity, 0.96) compared to the latter (accuracy, 0.76; sensitivity, 0.30; specificity, 0.95). In summary, in-house power monitoring technologies can be used to detect cognitive impairment.

Background Few previous studies used information on changes in fasting plasma glucose (FPG) assessed at multiple points in time in relationship to cardiovascular disease (CVD) incidence. The present study aimed to identify subgroups of FPG trajectories with assessing CVD incidence. Methods and Results The present study was based on the Suita study, a population‐based cohort study in Japan. The primary outcome was incidence of the first CVD events consisting of stroke and coronary heart diseases between 1989 and 2013. The main exposure was FPG assessed every 2 years. We used joint latent class mixed models to derive FPG trajectories over time while evaluating cumulative incidence of CVD, and categorized participants into several subgroups based on those trajectories and cumulative incidence. We observed 356 and 243 CVD events during the median follow‐up of 17.2 and 20.2 years among 3120 men and 3482 women, respectively. The joint latent mixed models found 3 subgroups in men and 2 subgroups in women. Of the 3 subgroups in men, 1 subgroup had FPG levels that increased sharply (96.5–205.0 mg/dL from aged 40 to 80 years) and higher CVD cumulative incidence. Of the 2 subgroups in women, 1 subgroup had FPG levels that increased sharply (97.7–190.5 mg/dL from aged 40 to 80 years) and tended to have slightly higher CVD incidence compared with the other subgroup. Conclusion It can be important to manage CVD risk factors especially for people whose FPG trajectories sharply increased to prevent CVD.

The objective of the present study was to establish the heritability of pain catastrophizing and its subdomains of helplessness, magnification, and rumination and to further explore the genetic and environmental sources that may contribute to pain catastrophizing as well as to its commonly reported psycho-affective correlates, including neuroticism, anxiety sensitivity, and fear of pain. N = 2,401 female twin individuals from the TwinsUK registry were subject to univariate and multivariate twin analyses. Well validated questionnaires including the Pain Catastrophizing Scale, the Pain Anxiety Symptom Scale, the Ten Item Personality Index, and the Anxiety Sensitivity Index were used to assess the study variables. Moderate estimates of heritability for pain catastrophizing (36%) and the three subdomains of helplessness (35%), rumination (27%), and magnification (36%) were detected. The high correlations observed between the three subdomains were explained mainly by overlapping genetic factors, with a single factor loading on all three phenotypes. High genetic correlations between pain catastrophizing and its psycho-affective correlates of fear of pain and anxiety sensitivity were found, while the genetic overlap between neuroticism and pain catastrophizing was low. Each measure of negative affect demonstrated relatively distinct environmental contributing factors, with very little overlap. This is the first study to show shared genetic factors in the observed association between pain catastrophizing and other measures of negative affect. Our findings provide deeper insight into the aetiology of pain catastrophizing and confirm that it is at least partially distinct from other measures of negative affect and personality that may influence the development and treatment of chronic pain conditions. Further research in males is warranted to check the comparability of the findings.

Brain atrophy is part of the aging process and accelerated by neurodegenerative diseases, so an understanding of the background heritability of brain volume is essential. The purpose of this study was to determine the heritability of brain volume in middle to advanced age East Asian adults, an age group less studied and an ethnicity not previously studied. 3T magnetic resonance images were obtained and volumetric analyses conducted for a total of 74 individuals, 20 monozygotic twin pairs (mean age 61y min 41y max 75y) and 17 dizygotic twin pairs (mean age 64y min 41y max 85y). Total brain volume and a further seven regions were assessed, including lobar volumes, lateral divisions, and separated grey and white matter. Additive genetics and unique environment (AE) models for global brain volumes including total brain (90%), grey matter (91%) and white matter (84%) and many lobar volumes demonstrated high heritability in our study population. Our results present the heritability of brain volume in middle to advanced age as possibly higher in East Asian adults.

BackgroundChronic widespread muscoloskeletal pain (CWP) is prevalent in the general population and associated with high health care costs, so understanding the risk factors for chronic pain is important for both those affected and for society. In the present study we investigated the underlying etiological structure of CWP to understand better the association between the major clinical features of fatigue, depression and dihydroepiandrosterone sulphate (DHEAS) using a multivariate twin design.Methodology/principle findingsData were available in 463 UK female twin pairs including CWP status and information on depression, chronic fatigue and serum DHEAS levels. High to moderate heritabilities for all phenotypes were obtained (42.58% to 74.24%). The highest phenotypic correlation was observed between fatigue and CWP (r = 0.45), and the highest genetic correlation between CWP and fatigue (rg = 0.78). Structural equation modeling revealed the AE Cholesky model to provide the best model of the observed data. In this model, two additive genetic factors could be detected loading heavily on CWP-A2 explaining 40% of the variance and A3 20%. The factor loading heaviest on DHEAS showed only a small loading on the other phenotypes and none on fatigue at all. Furthermore, one distinct non-shared environmental factor loading specifically on CWP-but not on any of the other phenotypes-could be detected suggesting that the association between CWP and the other phenotypes is due only to genetic factors.Conclusions/significanceOur results suggest that CWP and its associated features share a genetic predisposition but that they are relatively distinct in their environmental determinants.

Depressive state has been reported to be significantly associated with higher-level functional capacity among community-dwelling elderly. However, few studies have investigated the associations among people with long-term care requirements. We aimed to investigate the associations between depressive state and higher-level functional capacity and obtain marginal odds ratios using propensity score analyses in people with long-term care requirements. We conducted a cross-sectional study based on participants aged ≥ 65 years (n = 545) who were community dwelling and used outpatient care services for long-term preventive care. We measured higher-level functional capacity, depressive state, and possible confounders. Then, we estimated the marginal odds ratios (i.e., the change in odds of impaired higher-level functional capacity if all versus no participants were exposed to depressive state) by logistic models using generalized linear models with the inverse probability of treatment weighting (IPTW) for propensity score and design-based standard errors. Depressive state was used as the exposure variable and higher-level functional capacity as the outcome variable. The all absolute standardized differences after the IPTW using the propensity scores were < 10% which indicated negligible differences in the mean or prevalence of the covariates between non-depressive state and depressive state. The marginal odds ratios were estimated by the logistic models with IPTW using the propensity scores. The marginal odds ratios were 2.17 (95%CI: 1.13-4.19) for men and 2.57 (95%CI: 1.26-5.26) for women. Prevention of depressive state may contribute to not only depressive state but also higher-level functional capacity.

Although researchers have recently demonstrated a relationship between oral health and arterial sclerosis, the genetic contribution to this relationship has been ignored even though genetic factors are expected to have some effect on various diseases. The aim of this study was to evaluate oral health as a significant risk factor related to arterial sclerosis after eliminating genetic confounding through study of older Japanese twins.Medical and dental surveys were conducted individually for 106 Japanese twin pairs over the age of 50 years. Maximal carotid intima-media thickness (IMT-Cmax) was measured as a surrogate marker of arterial sclerosis. IMT-Cmax > 1.0 mm was diagnosed as arterial sclerosis. All of the twins were examined for the number of remaining teeth, masticatory performance, and periodontal status. We evaluated each measurement related with IMT-Cmax and arterial sclerosis using generalized estimating equations analysis adjusted for potential risk factors. For non-smoking monozygotic twins, a regression analysis using a "between within" model was conducted to evaluate the relationship between IMT-Cmax and the number of teeth as the environmental factor controlling genetic and familial confounding.We examined 91 monozygotic and 15 dizygotic twin pairs (males: 42, females: 64) with a mean (± standard deviation) age of 67.4 ± 10.0 years. Out of all of the oral health-related measurements collected, only the number of teeth was significantly related to arterial sclerosis (odds ratio: 0.72, 95% confidence interval: 0.52-0.99 per five teeth). Regression analysis showed a significant association between the IMT-Cmax and the number of teeth as an environmental factor (p = 0.037).Analysis of monozygotic twins older than 50 years of age showed that having fewer teeth could be a significant environmental factor related to arterial sclerosis, even after controlling for genetic and familial confounding.