Lifestyle interventions can substantially improve obesity and cardiometabolic risks. However, evidence of long-term benefits of national intervention is sparse. We aimed to evaluate the long-term effectiveness of a nationwide program for abdominal obesity. A retrospective cohort study was performed using a longitudinal nationwide individual data in subjects aged 40–74 years who underwent checkups in fiscal year (FY) 2008. Lifestyle interventions were provided via interview in subjects with abdominal obesity and at least one cardiometabolic risk factor. Subjects who attended the lifestyle intervention (participants) were compared to those who did not attend (non-participants). Outcomes were waist circumferences (WC) and body mass index (BMI) reduction, reversal of metabolic syndrome (MetS), and changes in cardiometabolic risks. We used a three-step process with robust analytic approaches to account for selection bias that included traditional multivariate analysis, propensity-score matching and instrumental variable (IV) analyses. Of 19,969,722 subjects, 4,370,042 were eligible for analyses; 111,779 participants and 907,909 non-participants. A higher percentage of participants had ≥5% reductions in obesity profiles at year 3, compared to non-participants (WC, 21.4% vs 16.1%; BMI, 17.6% vs 13.6%; p<0.001 each). Participants also had higher reversal for MetS (adjusted odds ratio 1.31; 95% confidence interval: 1.29–1.33; p<0.001). Greater reductions in cardiometabolic risks were observed in participants. Those results were confirmed in analyses using a propensity score-matched cohort (n = 75,777, each) and IV analyses. Limitations of this work include the use of non-randomized national data in Japan to assess the effectiveness of the nationwide preventive program. In the nationwide lifestyle intervention for abdominal obesity, the at-risk population achieved significant reductions in WC, BMI, and cardiometabolic risks in 3 years. This study provides evidence that the nationwide program effectively achieved long-term improvement in abdominal obesity and cardiometabolic risks.

Few recent large-scale studies have evaluated the risks and benefits of continuing oral anticoagulant (OAC) therapy after catheter ablation (CA) for atrial fibrillation (AF). This study evaluated the status of continuation of OAC therapy and the association between continuation of OAC therapy and thromboembolic and bleeding events according to the CHADS₂ score. This retrospective study included data from the Japanese nationwide administrative claims database of patients who underwent CA for AF between April 2014 and March 2021. Patients without AF recurrence assessed by administrative data of the treatment modalities were divided into two groups according to continuation of OAC therapy 6 months after the index CA. The primary outcomes were thromboembolism and major bleeding after a landmark period of 6 months. After inverse probability of treatment weighting analysis, the association between OAC continuation and outcomes was determined according to the CHADS₂ score. Among 231 374 patients included, 69.7%, 21.6%, and 8.7% had CHADS₂ scores of ≤1, 2, and ≥3, respectively. Of these, 71% continued OAC therapy at 6 months. The OAC continuation rate was higher in the high CHADS₂ score group than that in the low CHADS₂ score group. Among all patients, 2451 patients (0.55 per 100 person-years) had thromboembolism and 2367 (0.53 per 100 person-years) had major bleeding. In the CHADS₂ score ≤1 group, the hazard ratio of the continued OAC group was 0.86 [95% confidence interval (CI): 0.74–1.01, P = .06] for thromboembolism and was 1.51 (95% CI: 1.27–1.80, P < .001) for major bleeding. In the CHADS₂ score ≥3 group, the hazard ratio of the continued OAC group was 0.61 (95% CI: 0.46–0.82, P = .001) for thromboembolism and was 1.05 (95% CI: 0.71–1.56, P = 0.81) for major bleeding. This observational study suggests that the benefits and risks of continuing OAC therapy after CA for AF differ based on the patient’s CHADS₂ score. The risk of major bleeding due to OAC continuation seems to outweigh the risk reduction of thromboembolism in patients with lower thromboembolic risk. Status of the continuation of OAC therapy and the association between the continuation of OAC therapy and thromboembolic and bleeding events according to the CHADS₂ score. AF, atrial fibrillation; CA, catheter ablation; HR, hazard ratio; OAC, oral anticoagulant.

Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia–reperfusion injury. Using lipophilic extract from the injured kidney, we identified β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death–triggered, sustained inflammation after acute kidney injury.

We aimed to quantify contributions of changes in risks and uptake of evidence-based treatment to coronary heart disease (CHD) mortality trends in Japan between 1980 and 2012. We conducted a modelling study for the general population of Japan aged 35 to 84 years using the validated IMPACT model incorporating data sources like Vital Statistics. The main outcome was difference in the number of observed and expected CHD deaths in 2012. From 1980 to 2012, age-adjusted CHD mortality rates in Japan fell by 61%, resulting in 75,700 fewer CHD deaths in 2012 than if the age and sex-specific mortality rates had remained unchanged. Approximately 56% (95% uncertainty interval [UI]: 54-59%) of the CHD mortality decrease, corresponding to 42,300 (40,900-44,700) fewer CHD deaths, was attributable to medical and surgical treatments. Approximately 35% (28-41%) of the mortality fall corresponding to 26,300 (21,200-31,000) fewer CHD deaths, was attributable to risk factor changes in the population, 24% (20-29%) corresponding to 18,400 (15,100-21,900) fewer and 11% (8-14%) corresponding to 8400 (60,500-10,600) fewer from decreased systolic blood pressure (8.87 mm Hg) and smoking prevalence (14.0%). However, increased levels of cholesterol (0.28 mmol/L), body mass index (BMI) (0.68 kg/m2), and diabetes prevalence (1.6%) attenuated the decrease in mortality by 2% (1-3%), 3% (2-3%), and 4% (1-6%), respectively. Japan should continue their control policies for blood pressure and tobacco, and build a strategy to control BMI, diabetes, and cholesterol levels to prevent further CHD deaths.

Background: Patients with familial hypercholesterolemia who harbored both low‐density lipoprotein receptor ( LDLR ) and PCSK9 (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low‐density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both LDLR and PCSK9 gene variants. Methods and Results: A total of 232 unrelated patients with LDLR and/or PCSK9 gene variants were stratified as follows: patients with LDLR and PCSK9 ( LDLR/PCSK9 ) gene variants, patients with LDLR gene variant, and patients with PCSK9 gene variant. Clinical demographics and the occurrence of primary outcome (nonfatal myocardial infarction) were compared. The observation period of primary outcome started at the time of birth and ended at the time of the first cardiac event or the last visit. Patients with LDLR/PCSK9 gene variants were identified in 6% of study patients. They had higher levels of low‐density lipoprotein cholesterol ( P =0.04) than those with LDLR gene variants. On multivariate Cox regression model, they experienced a higher incidence of nonfatal myocardial infarction (hazard ratio, 4.62; 95% CI, 1.66–11.0; P =0.003 versus patients with LDLR gene variant). Of note, risk for nonfatal myocardial infarction was greatest in male patients with LDLR/PCSK9 gene variants compared with those with LDLR gene variant (86% versus 24%; P <0.001). Conclusions: Patients with LDLR/PCSK9 gene variants were high‐risk genotype associated with atherogenic lipid profiles and worse cardiovascular outcomes. These findings underscore the importance of genetic testing to identify patients with LDLR/PCSK9 gene variants, who require more stringent antiatherosclerotic management.

Background: Aging is one of the major concerns and determinants of the indications for catheter ablation (CA) for atrial fibrillation. This study aimed to assess the safety of CA in older patients with atrial fibrillation undergoing CA. Methods and Results: The JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases‐Diagnosis Procedure Combination) is a nationwide claims database using data from the Japanese Diagnosis Procedure Combination/Per Diem Payment System. Among 6 632 484 records found between April 2012 and March 2018 from 1058 hospitals, 135 299 patients with atrial fibrillation (aged 65±10 years, 38 952 women) who underwent CA in 456 hospitals were studied and divided into the following age groups: <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, 80 to 84, and ≥85 years. The overall in‐hospital complication rate was 3.4% (cardiac tamponade 1.2%), and in‐hospital mortality was 0.04%. Older patients had a higher prevalence of women, lower body mass index, and a higher burden of comorbidities such as hypertension, and all of those characteristics were predictors for complications in multivariate analysis. A multivariate adjusted odds ratio revealed that increased age was independently and significantly associated with overall complications (60–64 years, 1.19; 65–69 years, 1.29; 70–74 years, 1.57; 75–79 years, 1.63; 80–84 years, 1.90; and ≥85 years, 2.86; the reference was <60 years). Conclusions: The nationwide JROAD‐DPC database demonstrated that the frequency of complications following CA in patients with atrial fibrillation increased according to age.