Introduction: Spironolactone (SPL) is a steroidal mineralocorticoid receptor antagonist (MRA) that binds non-specifically to sex hormone receptors. Given the role of sex hormones in sleep regulation, SPL may pose a theoretical risk of insomnia through off-target activity. Recently introduced, esaxerenone (ESAX) is a non-steroidal MRA with high mineralocorticoid receptor selectivity, attracting attention for its potentially favorable safety profile. Methods: This study was conducted to compare the risk of insomnia between SPL and ESAX. Individuals with a history of hypertension who newly initiated either agent were enrolled from the DeSC database. Inverse probability of treatment weighting was used to assess differences in insomnia incidence between treatment groups. Results: We analyzed 5,091 individuals without a history of insomnia: 1,910 received SPL and 3,181 received ESAX. The median age was 72 (interquartile range [IQR], 67-79) years, 55% of participants were male, and the median estimated glomerular filtration rate was 66.3 (IQR, 56.1-76.2) mL/min/1.73 m2. Over a median follow-up of 512 (IQR, 240-848) days, 356 insomnia events were observed. Weighted Cox regression analysis indicated a significantly higher risk of incident insomnia among SPL users than ESAX users (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.32-2.10). In sex-stratified analyses, the HRs were 1.79 (95% CI, 1.30-2.47) for men and 1.59 (95% CI, 1.15-2.20) for women. Conclusions: Using a nationwide claims database, we demonstrated that, compared with ESAX, SPL use was associated with a greater likelihood of developing insomnia.

Background: Chronic kidney disease is associated with an increased incidence of stent thrombosis (ST) following drug-eluting stent (DES) implantation, but the clinical outcomes after DES-ST in hemodialysis (HD) patients compared with non-HD patients have not been fully elucidated. Methods and Results: From the REAL-ST registry, we evaluated 655 patients with DES-ST, divided into 2 groups: HD group (n=59) and non-HD group (n=596). The primary endpoint was the cumulative 3-year incidence of all-cause death after the index ST event. Late ST was more prevalent in the HD group, whereas early and very late ST were common in the non-HD group. Following the index ST event, the HD group showed significantly higher 3-year incidences of all-cause death (48.2% vs. 22.9%, P=0.0005), cardiac death (33.4% vs.15.8%, P=0.003) and target lesion revascularization (TLR: 36.2% vs. 17.5%, P=0.0002) compared with the non-HD group. The cumulative 3-year incidence of recurrent ST did not differ significantly between groups (7.3% vs. 5.9%, P=0.88). After multivariable adjustment, HD remained significantly associated with an increased risk of all-cause death (adjusted hazard ratio [aHR], 1.95; 95% confidence interval [CI], 1.25-3.04; P=0.003), cardiac death (aHR, 1.75; 95% CI, 1.02-2.99; P=0.04) and TLR (aHR, 2.63; 95% CI, 1.52-4.57; P<0.001). Conclusions: Compared with non-HD patients, HD patients experienced worse clinical outcomes following their index DES-ST event.

Abstract Background Aortic stenosis (AS) is a progressive valvular disease associated with poor prognosis once symptoms develop, yet routine echocardiographic screening is impractical. While artificial intelligence (AI)-based electrocardiogram (ECG) models have shown promise for AS detection, it remains unclear whether they primarily reflect conventional left ventricular hypertrophy (LVH) voltage criteria or capture additional ECG features. Methods and Results We developed a deep learning model using 244,816 ECGs from 51,713 patients across six academic institutions in Japan (CLIDAS database). AS labels were derived from inpatient Diagnosis Procedure Combination (DPC) codes. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.849 (95% confidence interval 0.832–0.865) in the independent test cohort, with consistent performance across institutions, sex, and age. At a threshold of 0.1, sensitivity was 79.1%, specificity was 73.9%, and negative predictive value (NPV) was 98.0%. Conventional LVH voltage criteria (Sokolow–Lyon AUC 0.706; Cornell AUC 0.692) showed lower performance, and adding them to the AI model conferred no incremental benefit (AUC 0.849 vs. 0.847). Gradient-weighted class activation mapping (Grad-CAM) revealed predominant attention around QRS complexes in limb leads, beyond regions typically assessed in LVH evaluation. Conclusions This multicenter AI-ECG model demonstrated strong discrimination for AS and captured ECG features beyond conventional LVH voltage criteria. The high NPV supports its use as a rule-out pre-screening tool.

RATIONALE & OBJECTIVE:Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a broad range of extrarenal complications, yet epidemiologic data on its association with aortic dissection (AD) or aortic aneurysm (AA) remain limited. In the present study, we assessed whether ADPKD is associated with an increased risk of developing these aortic conditions. STUDY DESIGN:Observational cohort study. SETTING & PARTICIPANTS:2,568,283 individuals without a history of AD or AA, enrolled between April 2014 and August 2023 in a nationwide Japanese epidemiological database provided by DeSC Healthcare of Tokyo, Japan. EXPOSURE:Presence of ADPKD based on the International Classification of Diseases, Tenth Revision codes. OUTCOME:Incidence of AD or AA. ANALYTICAL APPROACH:Cause-specific hazards models were used to estimate associations (hazard ratios), adjusting for potential confounders. RESULTS:The median age was 68 years (IQR, 61-77), and 1,123,131 individuals (44%) were male. ADPKD was diagnosed in 1,102 individuals (0.04%) within the cohort. During a median follow-up of 1,043 days (IQR: 556-1,600), there were 15,019 occurrences of AD or AA. Multivariable cause-specific hazards models demonstrated that individuals with ADPKD had a significantly increased risk of developing these aortic diseases (HR, 1.76 [95% CI, 1.13-2.73]). When analyzed separately, the HRs were 2.53 (95% CI, 1.13-5.66) for AD and 1.56 (95% CI, 0.94-2.60) for AA. The association of ADPKD with incident AD or AA was more pronounced in individuals with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2. LIMITATIONS:Potential residual confounding, possible detection bias, and lack of data on ADPKD-causing genetic variant. CONCLUSIONS:Our analysis of a large-scale epidemiological dataset indicated an elevated risk of AD or AA occurrence in individuals with ADPKD. These findings may inform the clinical management of this condition. PLAIN-LANGUAGE SUMMARY:Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition that can impair kidney function and affect other organs. Previous studies have suggested that aortic dissection (AD) or aortic aneurysm (AA) may be among its complications, but the evidence has remained inconclusive. We used a nationwide dataset of more than 2.5 million individuals to examine whether individuals with ADPKD are at increased risk of developing AD or AA. Our analyses showed a significant association between ADPKD and these serious aortic disorders. These findings highlight the importance of multidisciplinary efforts to promote prevention, timely recognition, and early intervention for AD or AA in individuals with ADPKD.

Background:While international guidelines recommend 5-10% body weight reduction, evidence characterizing the dose-response relationship between specific weight loss amounts and metabolic syndrome (MetS) resolution in real-world populations is limited. Methods and Results:In this retrospective study, we analyzed a large-scale health check-up database provided by DeSC Healthcare (Tokyo, Japan). We identified 37,256 individuals with baseline MetS eligible for the Specific Health Guidance (SHG) program (2014-2023). Logistic regression assessed the association between 1-year weight changes and subsequent MetS status. Weight loss was significantly linked to MetS resolution. Compared with weight maintenance, a weight loss of 2.0-2.9 kg showed an adjusted odds ratio (OR) of 0.45 (95% confidence interval [CI] 0.41-0.49), and a loss of ≥3.0 kg showed an OR of 0.19 (95% CI 0.18-0.21). These associations were consistent across age and sex subgroups. Secondary analyses confirmed significant improvements in waist circumference, blood pressure, lipid profiles, and HbA1c. Conclusions:Weight loss over 1 year is significantly associated with MetS resolution among SHG-eligible individuals. These findings support the validity of weight loss recommendations in the fourth phase of the SHG program and offer empirical data for future health guidance design.

BACKGROUND:Association between serum albumin levels and bleeding events in patients with venous thromboembolism was unclear. METHODS:In this Japanese multi-center registry, we enrolled 993 consecutive patients diagnosed with acute venous thromboembolism and treated with anticoagulants between 2015 and 2024, where 732 patients were finally analysed. The primary outcome was 180-day bleeding events, defined as moderate or severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. The effect of serum albumin level on the outcome was determined using a multivariate Cox proportional hazard regression model adjusted for conventional bleeding risk scoring systems. RESULTS:The mean age was 68.6 ± 14.5 years, and 37.2% were men. In total, 38.4% had concomitant active cancer, 6% had a previous history of venous thromboembolism, and 90% were treated with direct oral anticoagulants. The primary outcome occurred in 36 patients (5%), and serum albumin level was significantly lower in the event group than in the event-free group (2.9 ± 0.7 g/dL versus. 3.2 ± 0.7 g/dL, P = 0.014). In multivariate Cox proportional risk analysis, serum albumin level was independently associated with the outcome (adjusted hazard ratio 1.77, per 1 g/dL decrease; 95% confidence interval, 1.12-2.75; P = 0.013). This was consistent in patients with active cancer (adjusted hazard ratio 2.15, per 1 g/dL decrease; 95% confidence interval, 1.29-3.57; P = 0.003), but not in patients without it. CONCLUSIONS:Decreased serum albumin levels were associated with 180-day bleeding events in patients with venous thromboembolism treated with anticoagulants, especially in those with concomitant active cancer.

BackgroundSocioeconomic disparities adversely affect heart failure (HF) outcomes; however, the extent to which public assistance (PA) mitigates these differences remains uncertain.Methods and resultsWe retrospectively analyzed 596 patients who were discharged alive after hospitalization for acute HF between January and December 2015. The patients were classified according to their PA status. The primary outcome was a composite of all-cause death and HF rehospitalization. Secondary outcomes included individual components. Kaplan–Meier curves were used to compare unadjusted event rates, while Cox proportional hazards models adjusted for 25 clinical and sociodemographic covariates were used to evaluate associations in the full cohort. To confirm model robustness, 1:1 propensity score matching (PSM) was performed (n = 82 pairs) and sensitivity analyses were conducted in the matched cohort. The mean medical follow-up duration was 3.5 years. In the entire cohort, the primary outcome occurred in 69.6% of patients. During follow-up, the cumulative incidence of the primary outcome did not differ significantly between the PA and non-PA groups (log-rank test, p = 0.45). In the multivariable analysis, PA was not associated with a higher risk of the primary outcome (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.78–1.40; p = 0.68). Similar results were observed after PSM (HR, 0.87; 95% CI, 0.61–1.24; p = 0.46).ConclusionPA was not associated with worse long-term outcomes after hospitalization for acute HF, suggesting that comprehensive public insurance coverage may help reduce socioeconomic disparities in HF care.

Background Atrial fibrillation (AF) is associated with diverse histological abnormalities, but their contributions to atrial dysfunction and functional recovery remain unclear. Methods In a discovery cohort of 375 patients with nonvalvular AF undergoing catheter ablation, atrial biopsy samples were quantitatively analyzed for fibrosis, intercellular space expansion, myofibrillar loss, myocardial nuclear density, and amyloid deposition. Left atrial reservoir strain (LASr) was assessed as a measure of atrial function during sinus rhythm (Group 1) or AF (Group 2) at the time of echocardiography. Functional recovery was defined as the change in LASr 12 months after ablation. Findings were validated in an independent cohort of 191 patients with AF. A subset of samples was additionally analyzed for DNA damage markers, poly(ADP‐ribose), and phosphorylated histone H2A.X. Results LASr improved significantly after ablation in Group 2 but not in Group 1. Multivariable analyses identified greater fibrosis, reduced myocardial nuclear density, and advanced amyloid deposition as significant determinants of impaired atrial function in both groups and of limited postablation functional recovery in Group 2 (all P<0.01). Amyloid deposition was also significantly associated with adverse clinical outcomes. Decision‐tree models incorporating LASr accurately identified advanced amyloid deposition in both cohorts (accuracy, 94%–96%). DNA damage markers were inversely associated with myocardial nuclear density and positively associated with cardiomyocyte hypertrophy. Conclusions Fibrosis, DNA damage–associated reduction in myocardial nuclear density, and advanced atrial amyloidosis are key determinants of atrial dysfunction and impaired postablation functional recovery in patients with AF. LASr enables noninvasive identification of advanced atrial amyloidosis.

Objective There are limited clinical data on whether low lean body mass is a risk factor for adverse kidney outcomes. We aimed to investigate the association between lean body mass, derived from a simple formula, and adverse kidney outcomes in men. Methods This cohort study utilized nationwide data from the DeSC database, encompassing a total of 468,597 men. The components for predicting lean body mass include age, height, body weight, waist circumference, and ethnicity. The primary outcome was a decrease in estimated glomerular filtration rate (eGFR) ≥ 40% from the baseline measurement. Results During a mean follow-up of 4.0 years, a decrease in eGFR of ≥ 40% was observed in 2,047 individuals. Individuals in tertile 1 of predicted lean body mass had a higher risk of a decrease in eGFR of ≥ 40% than those in tertile 3 (hazard ratio, 1.54; 95% confidence interval, 1.33-1.78). In cubic spline analysis, the hazard ratio was observed to decrease progressively with higher predicted lean body mass up to the median level, after which it plateaued. The significant association between lower predicted lean body mass and the risk of eGFR of ≥ 40% was generally consistent across subgroups stratified by baseline characteristics, including eGFR levels. Conclusion Men with lower predicted lean body mass had a higher risk of adverse kidney outcome. Our results suggest the clinical importance of lean body mass assessment for kidney disease risk stratification.

AIMS:Despite strong recommendations for medical consultation, the treatment status and low-density lipoprotein cholesterol (LDL-C) levels at 1-year follow-up of individuals with referral-level LDL-C identified in health checkups remain unclear. We evaluated the treatment status and 1-year LDL-C control among individuals identified in health checkups as requiring early medical consultation due to LDL-C levels of ≥ 180 mg/dL. METHODS:We conducted a nationwide cohort study including health checkup data for individuals aged 20-74 years. We identified 102,049 individuals (median age: 48 years; male: 66.8%) with uncontrolled LDL-C (≥ 180 mg/dL) at baseline, who had no prior lipid-lowering therapy. Poisson regression with robust error variance was used to assess factors associated with uncontrolled LDL-C at 1 year. RESULTS:Among individuals with LDL-C ≥ 180 mg/dL at baseline, 56,147 (55.0%) visited a medical institution within 3 months of the checkup, and 13,124 (12.9%) were prescribed lipid-lowering medications at 1 year. At 1 year follow-up, 49,260 (48.3%) still had LDL-C ≥ 180 mg/dL. Factors associated with persistent LDL-C ≥ 180 mg/dL at 1 year included obesity (RR: 1.07, [95% CI: 1.06-1.09]), 10 mg/dL increase in LDL-C at baseline (1.11 [1.10-1.11]), smoking (1.05 [1.04-1.07]), alcohol consumption (0.95 [0.94-0.97]), poor sleep quality (1.02 [1.01-1.03]), and skipping breakfast ≥ 3 times per week (1.07 [1.05-1.08]). CONCLUSIONS:Despite being classified as requiring early medical intervention, only half of individuals with LDL-C ≥ 180 mg/dL visited a physician within 3 months, and nearly half continued to have uncontrolled LDL-C at 1 year. Strategies to facilitate timely medical visits and appropriate lipid management in health checkup-identified cases are warranted.

Background: Although the COVID-19 pandemic altered hospitalization trends for acute cardiovascular diseases (CVD) in Japan, the effects of a concomitant COVID-19 diagnosis on mortality in this high-risk population remains unclear. We investigated the association between COVID-19 infection and 30-day mortality among patients hospitalized for acute CVD using a nationwide database. Methods and Results: This retrospective cohort study used data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database from January 2020 to March 2022. We included patients hospitalized for acute myocardial infarction, acute heart failure, aortic rupture, or venous thromboembolism. We compared patients with and without COVID-19, with 30-day mortality as the primary outcome. We used 1:1 propensity score matching to balance baseline patient and hospital characteristics. Of 395,671 eligible patients in the JROAD-DPC database, 41,794 (10.6%) had a concomitant COVID-19 diagnosis. In the matched cohort of 41,794 pairs, the risk of 30-day mortality was significantly higher patients for patients with than without COVID-19 (6.6% vs. 5.8%; odds ratio 1.14; 95% confidence interval 1.08-1.21; P<0.001). This increased risk was consistent across all major diagnostic subgroups (P for interaction >0.3). Conclusions: In this large nationwide study of patients hospitalized for acute CVD in Japan, concomitant COVID-19 infection was associated with a significant increase in 30-day mortality. These findings suggest that COVID-19 infection is associated with increased mortality in this vulnerable patient population.

There were few data on the clinical characteristics of ST-segment elevation myocardial infarction (STEMI) patients with late presentation (long symptom onset to door [hospital arrival] time). Among 719 consecutive patients with STEMI who underwent percutaneous coronary intervention (PCI) in the SAGA-ACS registry, we compared baseline characteristics and clinical outcomes between patients with early presentation (symptom onset to door time <2.3 hours) and late presentation (≥2.3 hours). The cut-off point of 2.3 hours was the median value for the present study population. The median onset to door time was 1.3 hours in the early presentation group, and 4.8 hours in the late presentation group. Door to balloon time was not different between the groups (62.0 minutes vs 60.5 minutes). Late night to early morning onset (OR, 2.03; 95% CI, 1.45 to 2.85), age ≥75 years (OR, 1.56; 95% CI, 1.09 to 2.22), and women (OR, 1.49; 95% CI, 1.03 to 2.16) were independently associated with the late presentation, while culprit lesions in right coronary artery (RCA) was inversely associated the late presentation (OR, 0.62; 95% CI, 0.46 to 0.85). During the median 2.7 years follow-up, the cumulative incidence of all-cause death was numerically, but not statistically, higher in the late presentation group than in the early presentation group (16.3% vs 11.6% at 3 years, HR, 1.42; 95% CI, 0.97 to 2.07; p = 0.07). In conclusion, among patients with STEMI who underwent PCI, late night to early morning onset, advanced age, women, and culprit lesions in non-RCA were strongly associated with the late presentation. Strategies for minimizing symptom onset to door time should be targeted especially in these patients.

Background:Atrial biopsy is technically challenging owing to the atria's thin walls and relatively thick endocardium. This study assessed the feasibility and safety of echocardiography-guided atrial biopsy in a consecutive cohort of 1,000 patients who underwent catheter ablation for atrial tachyarrhythmias or percutaneous left atrial (LA) appendage occlusion. Methods and Results:Atrial biopsy was performed at the limbus of the fossa ovalis through the femoral vein using a 5.5-Fr (n=233) or a 7.0-Fr (n=767) bioptome under intracardiac (n=963) or transesophageal (n=37) echocardiography guidance, alongside fluoroscopy. For histological analysis, 5 tissue samples were collected from the same site. Biopsy was successfully completed in 996 (99.6%) patients. Patients were divided based on histological depth into Group A (biopsy beyond the endocardium; n=885) and Group B (endocardial-only biopsy; n=111). Multivariable logistic regression identified larger LA volume, use of a 5.5-Fr bioptome, and amyloid deposition as independent predictors of Group B (P=0.009, P<0.001, and P=0.001, respectively). Moreover, biopsy-related complications were unrecorded. Conclusions:Echocardiography-guided atrial biopsy is a feasible and safe technique. However, atrial enlargement, smaller bioptome size, and amyloid deposition are associated with unsuccessful endocardial penetration and collection of myocardial tissue.

Background: Sacubitril/valsartan (Sac/Val) has been shown to reduce N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with acute heart failure (AHF), yet the therapeutic response may differ according to underlying cardiac phenotype. Hypothesis: We hypothesized that specific baseline echocardiographic parameters may modify the NT-proBNP-lowering effect of Sac/Val in this population. Aims: This study aimed to explore whether baseline echocardiographic markers could identify patients with AHF, who will experience greater reductions in NT-proBNP following Sac/Val therapy. Methods: This was a sub-analysis of the multicenter, physician-initiated, prospective, randomized, open-label PREMIER study (NCT05164653), in which the clinical effects of early initiation of Sac/Val, compared to the standard renin-angiotensin system inhibitor therapy (control), were evaluated in Japanese inpatients stabilized after hospitalization for AHF. Participants were stratified according to echocardiographic characteristics at baseline, including LVEDVI, LVESVI, LVMI, LVOT-VTI, E/e′, LAVI, and TRV. The proportional change in geometric mean NT-proBNP from baseline to 8 weeks was compared between the Sac/Val and control groups within each stratum. Results: Among 206 patients with echocardiographic data (median age, 76 years; 31% female; median left ventricular ejection fraction, 39%), 94 were assigned to the sacubitril/valsartan (Sac/Val) group and 112 to the control group. Overall, Sac/Val treatment led to a significantly greater reduction in NT-proBNP than control (group ratio 0.75; 95% CI, 0.60 to 0.93). Among the echocardiography-based subgroups, the treatment effect was more evident in subgroups with elevated LVMI (LVMI ≥123.7 g/m 2 ; group ratio, 0.56; 95% CI, 0.40 to 0.77) and reduced LVOT-VTI (LVOT-VTI <13 cm; group ratio, 0.59; 95% CI, 0.43 to 0.80), compared to each corresponding counterpart (P for interaction = 0.009 and 0.045, respectively) ( Figure ). In contrast, no significant between-group differences in the treatment effect were observed in subgroups stratified by other echocardiographic parameters (all P for interaction >0.1). Conclusions: Baseline LVMI and LVOT-VTI values may help identify the optimal patients who derive greater benefit from early initiation of Sac/Val therapy after an AHF episode, supporting a phenotype-guided approach to individualized treatment in this population.

BACKGROUND:Body compositions are closely related to stroke risk. Recently, lean mass index (LMI) has been demonstrated to be a precise indicator of cardiovascular disease (CVD) risk, and the newly proposed formula enabled the simple estimation of LMI without a computed tomography scan. However, little is known about its attribution to a risk of stroke. Using a large-scale epidemiological cohort, we sought to clarify the association of LMI with a subsequent risk of developing stroke. METHODS:This retrospective observational cohort study included 1,410,568 participants in Japan without a history of CVD or kidney replacement therapy from the DeSC Database between 2014 and 2022. The median age was 62 years (IQR, 48-67), and 642,343 participants (45.5 %) were men. Using age, sex, height, weight, and waist circumference, LMI was estimated, with a median of 14.9 (13.2-17.0). Participants were categorized into quintiles based on LMI. The primary endpoint was overall stroke, comprising ischemic and hemorrhagic stroke. RESULTS:During a mean follow-up period of 1372 ± 793 days, 35,210 stroke events were recorded. Cox regression analysis modeling a restricted cubic spline showed monotonously inverse correlation between LMI and stroke occurrence, with hazard ratios of 1.23 and 0.82 at the lowest and highest LMI quintile, respectively, compared to the middle quintile. This inverse association was consistent across ischemic and hemorrhagic strokes and observed in men and women. CONCLUSIONS:The high LMI was associated with a lower risk of developing stroke, suggesting the importance of maintaining adequate muscle mass from the perspective of stroke prevention.

Aims:Cardiovascular-kidney-metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association. Methods and results:We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80-1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1-3 differed between the sexes: HR by Stage 1, 1.12 (1.04-1.21) vs. 1.12 (1.07-1.16); by Stage 2, 1.78 (1.69-1.88) vs. 1.43 (1.39-1.48); by Stage 3, 1.99 (1.89-2.10) vs. 1.82 (1.76-1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively. Conclusion:In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex.

Aims:Cancer survivors are at increased cardiovascular risk due to shared risk factors and treatment-related toxicity. The recently proposed cardiovascular-kidney-metabolic (CKM) syndrome framework provides a novel approach for cardiometabolic risk stratification, but its prognostic value in cancer patients remains unclear. In this study, we aimed to evaluate the association between CKM stages and cardiovascular outcomes in cancer patients using a large-scale nationwide dataset. Methods and results:We conducted a retrospective cohort study of 76 111 cancer patients without prior CVD from the DeSC database (2014-2023). Participants were classified into CKM stages (0-3) at baseline, with Stage 4 defined as the composite outcome of myocardial infarction, heart failure, atrial fibrillation, stroke, or peripheral artery disease. Multivariable Cox proportional hazards models were used to assess the risk of progression to Stage 4. Over a median follow-up of 2.6 years, advancing CKM stages were associated with a graded increase in cardiovascular disease (CVD) risk. Compared to Stage 0-1 (reference), adjusted hazard ratios for Stage 4 were 1.23 (95% confidence interval: 1.13-1.33) for Stage 2 and 1.47 (1.36-1.60) for Stage 3. Sensitivity analyses confirmed consistent associations across different groups stratified by age, sex, chemotherapy history, and cancer types. Furthermore, sensitivity analyses using alternative risk prediction models or expanded CVD definitions yielded similar results. Conclusion:The CKM staging system effectively stratifies cardiovascular risk in cancer patients, with higher stages predicting significantly worse outcomes. These findings advocate for integrating CKM assessment into onco-cardiologic practice to guide early intervention and improve patient outcomes.

Enhancement of self-care ability is essential for patients with heart failure (HF), and executive function plays a critical role. We investigated the clinical influence of a home-based remote care program using telemonitoring and telecoaching on executive function in patients with HF and assessed the relationship between executive functional status and clinical outcomes. This prospective study enrolled outpatients with HF, and they received home-based remote care program with telemonitoring and telecoaching using self-measured physical data. Executive function was assessed using the Trail Making Test Part B (TMT-B). The incidences of HF hospitalization and all-cause death were also compared according to baseline executive function status based on TMT-B test performance. Forty-one participants were enrolled in this study (mean age: 64.8 ± 13.8 years; male 68.3%; New York Heart Association [NYHA] class II/III: 78.0/22.0%). Twelve months after the initiation of the program, TMT-B significantly improved (p = 0.039), accompanied by an obvious amelioration of HF symptoms as assessed by the NYHA class (p = 0.027). During a median follow-up of 20.5 months, the incidence of HF hospitalization was significantly higher in patients with executive dysfunction than in those without (hazard ratio: 4.97, 95% confidence interval: 1.15-21.4, p = 0.031). This was unchanged even in a subcohort without cognitive dysfunction, as assessed using the Mini-Mental State Examination. Telemonitoring and telecoaching at home may be effective in improving executive function in patients with HF. Further studies are needed to assess whether supportive care assisting executive functioning improves clinical outcomes in patients with HF.