Evidence supporting multidisciplinary interventions for frailty in elderly cardiovascular inpatients remains limited. In this completed multicentre, single-blinded, randomised controlled trial (ChiCTR1900022623), 333 frail inpatients aged ≥ 70 years with cardiovascular diseases were randomly assigned to RENAP (Rehabilitation exercises, patient Education, Nutritional guidance, Acupoint massage, and Polypharmacy management) programme (n = 166) or usual care (n = 167). The trial was supported by grants from the Beijing Municipal Science and Technology Commission and the Chinese Academy of Medical Sciences. The primary outcomes were changes from baseline to 12 months in Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) scores at one year. RENAP significantly improved FFP score [t(993) = −4.79; P < 0.001; adjusted mean difference −0.79; 95% CI: −1.11 to −0.46] and SPPB score [t(993) = 4.06; P < 0.001; adjusted mean difference 2.02; 95% CI: 1.04 to 2.99]. No treatment-related serious adverse events were observed during the study. These findings suggest that a hospital-initiated multidisciplinary programme may improve frailty and physical function in frail elderly adults with cardiovascular diseases. The single-city setting and loss to follow-up may limit generalisability and warrant confirmation in broader healthcare settings. A hospital-initiated multidisciplinary program was associated with improved frailty and physical function and lower readmission risk in frail elderly patients with cardiovascular diseases, although larger studies are needed to confirm these.

Importance:Left ventricular structural assessment is fundamental in heart failure (HF). However, the independent prognostic value of left ventricular size beyond its association with ejection fraction remains poorly defined in real-world, large-scale populations. Objective:To investigate the association between left ventricular dimension and mortality risk within a large, nationwide cohort with HF. Design, Setting, and Participants:This was a nationwide cohort study using data from the Chinese Cardiovascular Association Database-Heart Failure Center Registry. Patients were enrolled from January 1, 2018, to May 31, 2022. The multicenter study involved 723 centers across 31 provincial-level administrative regions in mainland China. The study included patients hospitalized with HF. Patients were categorized into groups with a small, normal, or large left ventricle (LV) according to American Society of Echocardiography criteria for LV end-diastolic diameter (LVEDD). Data analysis was conducted from March to June 2025. Exposure:LVEDD measured by echocardiography. Main Outcomes and Measures:The primary and secondary end points were all-cause mortality and cardiovascular mortality, respectively. Results:A total of 273 921 patients (median [IQR] age, 71.0 [62.0-79.0] years; 161 589 male [59.0%]) hospitalized with HF were included in this study. A significant U-shaped association was found between LVEDD and both all-cause and cardiovascular mortality (P for nonlinearity <.001). Both a small LV (adjusted HR [aHR], 1.32; 95% CI, 1.28-1.37; P < .001) and a large LV (aHR, 1.38; 95% CI, 1.35-1.40; P < .001) were independently associated with elevated all-cause mortality. Sex-specific optimal LVEDD thresholds were identified (47 mm for male patients, 43 mm for female patients), with each 1-mm deviation associated with a significant increase in mortality risk. These findings were consistent across prespecified subgroups and were further corroborated by analysis of LVEDD indexed to body surface area and by extensive sensitivity analyses, including competing risk models and complete-case analyses. Conclusions and Relevance:This large-scale study established that a U-shaped association exists between LVEDD and mortality in HF, suggesting that both abnormally small and abnormally large ventricles signify high risk, likely through distinct mechanisms. These findings support the integration of LV size assessment into routine risk stratification to guide personalized management.

The triglyceride-glucose index (TyG) and atherogenic index of plasma (AIP) are emerging metabolic biomarkers associated with cardiovascular diseases. However, their combination prognostic value in patients with critical chronic heart failure (CHF) remains unclear. This study aimed to evaluate the combined predictive effect of these two biomarkers and clarify their interactive patterns in this association. 1,238 patients were recruited via the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with a median age of 71 years. Multivariable Cox regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve were employed to explore associations between TyG, AIP, and mortality. Mediation analysis was applied to assess their bidirectional mediation effects. Additionally, we developed a machine learning-driven prediction model, which was further utilized to evaluate the two indicators’ incremental predictive value. 1,238 patients were included, with 478 (38.61

BACKGROUND AND AIMS:Heart failure (HF) imposes a growing public health and macroeconomic burden in low- and middle-income countries (LMICs), yet its long-term economic impact remains unquantified. China, characterized by rapid ageing and escalating cardiovascular risks, provides a critical setting to model HF economic implications. METHODS:Using data from the Global Burden of Disease Study 2021, China Cardiovascular Association Registry, and national insurance databases, HF macroeconomic burden (2025-35) was projected via a health-augmented macroeconomic model. Three interventions were evaluated: B-type natriuretic peptide (BNP) screening (adults ≥40 years), intensive blood pressure (BP) control (hypertensive patients), and guideline-directed medical therapy (GDMT) optimization for HF with reduced ejection fraction. Costs are reported in 2017 international dollars (INT$). RESULTS:By 2035, HF cases in China will reach 22.7 million [95% uncertainty interval (UI): 9.5-36.9 million], with an age-standardized prevalence of 760.65/100 000 (95% UI: 283.2-1340.8/100 000). The cumulative economic burden (2025-35) is INT$1001.1 billion (95% UI: 733.4-1365.6 billion), representing 0.26% of gross domestic product (95% UI: 0.19%-0.34%), driven by labour force attrition (72.1%; 95% UI: 64.4%-74.8%). Interventions reduced the total burden by 12.5% (95% UI: 10.4%-14.5%): BNP screening (25% coverage) saved INT$78.5 billion (95% UI: 62.8-94.1 billion; 8.10% reduction; cost-benefit ratio 0.49), Intensive BP control saved INT$27.5 billion (95% UI: 25.1-29.9 billion; 2.74% reduction; ratio 0.22), GDMT optimization saved INT$17.0 billion (95% UI: 12.8-22.4 billion; 1.70% reduction; ratio 0.48). CONCLUSIONS:HF imposes a substantial and increasing macroeconomic burden in China, largely through workforce productivity losses. Scalable, cost-effective strategies, including primary care-based BNP screening, subsidized hypertension control, and enhanced GDMT adherence, are essential to curb economic losses. These findings inform policy priorities for China and other LMICs confronting demographic transitions.

Background For patients with a high risk of sudden cardiac death, despite the benefits of an implantable cardioverter defibrillator (ICD), some patients are still at high risk of death.Aim The purpose of this study was to develop and validate a nomogram predicting all-cause mortality for patients with an ICD.Methods We retrospectively analysed the data of multicentre ICD registration study from 2010 to 2014 in China. A total of 617 ICD patients formed a development cohort. The physical activity monitored by ICD and clinical data was collected. Univariate and multivariate Cox regression analyses were used to screen mortality predictors and construct the nomogram. The performance of the nomogram was evaluated by the consistency index (C-index) and the calibration curve. Additionally, extensive subgroup and sensitivity analyses were conducted to evaluate the model’s robustness. A total of 196 ICD patients formed a validation cohort.Results In the development cohort, physical activity, diabetes and left ventricular end-diastolic diameter were selected as independent prognostic factors. The nomogram was constructed by these three factors. The C-index of the nomogram was 0.80 (95% CI 0.75 to 0.84). The calibration curve showed that the predicted survival probability of the nomogram was in good agreement with the actual survival probability. In the validation cohort, the C-index of the nomogram was 0.74 (95% CI 0.64 to 0.84), and the calibration curve still maintained good consistency. Crucially, the nomogram maintained stable and excellent discriminative capacity across primary and secondary prevention subgroups, as well as for predicting specific cardiac and sudden cardiac death.Conclusions Our study develops and validates a nomogram predicting all-cause mortality for patients with an ICD by integrating the physical activity monitored by ICD and clinical data. The nomogram performs well and can provide personalised death risk assessment for ICD patients.Trial registration number ChiCTR-ONRC-13003695.

SGLT2 inhibitors (SGLT2is) improve outcomes in patients with heart failure (HF), but their effects may depend on background medical therapy. The Heart Failure Collaboratory score, which incorporates medication type and dose, may modify the benefit of SGLT2is. To evaluate the association between the scoring system and the mortality benefit of SGLT2 inhibitors in patients with heart failure. This retrospective multicenter cohort study used real-world data from the Chinese Cardiovascular Association Database–HF Center (HFC) Registry. 52 hospitals were selected with 26 HFCs and 26 NHFCs. Patients with a diagnosis of HF and one-year follow-up from July 1, 2022, to March 31, 2023, were included. The primary outcome was one-year all-cause mortality. Cox regression and multivariable fractional polynomial interaction (MFPI) models were used to assess the effect of SGLT2is on mortality risk across Heart Failure Collaboratory scores. A total of 4,077 patients (median age 70.0 years; 60.1

The C-reactive protein–triglyceride glucose index (CTI) has emerged as a promising composite biomarker for cardiovascular disease (CVD) risk. However, whether incorporating obesity-related metrics such as waist circumference (WC), body mass index (BMI), or waist-to-height ratio (WHtR) into CTI to form modified indices such as CTI-WC, CTI-BMI, and CTI-WHtR improves predictive performance remains uncertain. The performance of these modified indices requires validation in large-scale prospective cohorts stratified by glycemic status. This study used data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, involving 7,579 participants aged ≥ 45 years. Multivariate Cox regression and restricted cubic splines (RCSs) analyses were used to assess the associations of the CTI and its modified indices with CVD risk. To compare the predictive performance, time-dependent Harrell’s C-indices, integrated discrimination improvement and net reclassification index were utilized. Weighted quantile sum (WQS) regression was used to evaluate component contributions. During a mean follow-up of 8.28 years, 1,871 (24.69

Heart failure (HF) is a major endpoint of cardiovascular disease (CVD) and a growing global public health challenge. This study assessed the global burden of CVD-related HF from 1990 to 2021 and projected trends to 2050. Utilizing data from the Global Burden of Disease (GBD) 2021 study, we analyzed years lived with disability (YLD) and prevalence for CVD-related HF, stratified by sex, age, socio-demographic index (SDI), region, and specific CVD etiology. In 2021, CVD-related HF affected approximately 45.56 million individuals globally, causing 4.32 million YLD. The global age-standardized prevalence and YLD rates were 548.81 and 52.00 per 100,000 population, respectively, with higher rates in males. Hypertensive and ischemic heart disease were predominant causes, except in the under-20 age group where cardiomyopathy/myocarditis and rheumatic heart disease prevailed. From 1990 to 2021, global age-standardized prevalence and YLD rates increased, with the sharpest rise in the 20–54 age group, males and middle to high–middle SDI countries. Age-standardized prevalence and YLD rates declined for rheumatic heart disease, stroke, and non-rheumatic valvular heart disease-related HF, whereas most other etiologies exhibited upward trends, most notably atrial fibrillation/flutter and endocarditis. There were significant disparities in various CVD-related HF across sex, age, SDI country, and region in 2021 and from 1990 to 2021. By 2050, projections indicate that CVD-related HF will increase to varying degrees across sex, age, and specific CVD types. The global burden of CVD-related HF is substantial, escalating, and characterized by significant disparities across sex, age, SDI country, region, and CVD type. Urgent and targeted public health strategies are essential to mitigate this rising burden.

Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome that poses challenges for therapeutic development and contributes to suboptimal patient outcomes. The phenotypic classification of patients with HFpEF to guide etiology-specific therapeutic strategies represents a rational approach to address the current dilemma. However, the clinical outcomes of HFpEF under different etiological classifications remain poorly understood. Here, we assessed the clinical outcomes of HFpEF patients across different etiological phenotypes, based on a novel classification system comprising five categories: vascular-related, cardiomyopathy-related, right heart/pulmonary-related, valvular/rhythm-related, and extracardiac disease-related HFpEF. Data from the Chinese Cardiovascular Association Database-Heart Failure Center Registry (2017-2021) were analyzed, including 51,466 hospitalized HFpEF patients with 1-year follow-up. Significant differences in baseline characteristics and clinical outcomes were observed among phenotypes. Patients with right heart/pulmonary-related, valvular/rhythm-related, and extracardiac disease-related HFpEF showed a higher incidence of adverse outcomes. Specifically, the right heart/pulmonary-related and valvular/rhythm-related phenotypes were associated with increased heart failure rehospitalization, while extracardiac disease-related HFpEF was linked to higher cardiovascular mortality. Prognostic risk factors also varied across phenotypes. In conclusion, 1-year outcomes exhibit significant variations across HFpEF phenotypic subgroups. Future studies should explore whether phenotype-specific personalized treatment strategies can improve clinical outcomes, especially in high-risk phenotypes.

AIMS:At present, there is a lack of recent heart failure (HF) epidemiological data up to 2021. This study aims to assess the HF burden and its risk factors from 1990 to 2021 and project trends to 2050. METHODS AND RESULTS:We derived HF prevalence and years lived with disability (YLDs) from Global Burden of Disease Study 2021, performing subgroup analyses by sex, age, sociodemographic index (SDI), and regions. Health inequalities were measured using the Inequality Slope Index and Concentration Index. Additionally, we made a decomposition analysis of the HF burden and forecasted its impact by 2050. The global age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) of HF were 676.68 (95% UI: 598.68-776.84) and 64.7 (95% UI: 44.2-89.47) per 100 000 people and increased by 5.5% and 5.9% from 1990 to 2021, respectively. The ASPR and ASYR were higher in regions in the relatively higher SDI quintile, while the HF burden in regions in the lower SDI quintile is increasing. Ischaemic heart disease accounted for the highest ASPR of HF globally [244.02 (95% UI: 179.09-322.13)], followed by hypertensive heart disease [148.32 (95% UI: 117.32-186.28)]. The ASPR and ASYR of HF are projected to rise from 2022 to 2050, with males dominating. CONCLUSION:The escalating HF burden represents a critical public health challenge, necessitating immediate intervention. Policymakers must devise precise strategies aimed at curbing and preventing the HF burden.

To investigate the relationship between abdominal obesity and long-term prognosis in patients with a pacemaker. In the SUMMIT Study, patients were categorized by baseline waist circumference into obesity, normal, and lean groups. WC was measured at the midpoint between the last rib and hip bone after exhalation. Regular follow-ups were conducted, with all-cause mortality as the primary endpoint and cardiac death as the secondary endpoint. In total, 492 patients were included in the analysis. The average baseline waist circumference was 84.2 ± 12.7 cm, and abdominal obesity was observed in 37.6

Background: To examine the predictive value of the Timed Up and Go test (TUGT) for five-year mortality among older patients with cardiovascular disease (CVD). Methods: This prospective cohort study was conducted at the Beijing Hospital in China from September 2018 to April 2019, with a follow-up period of 5 years. Patients underwent the TUGT at baseline and were categorized into two groups based on the subsequent results: Group 1 (TUGT >15 s) and Group 2 (TUGT ≤15 s). The primary outcome of the study was all-cause mortality over five years. Results: The study included 491 older patients from the cardiology ward (average age 74.83 ± 6.38 years; 50.92% male). A total of 69 patients (14.05%) died over the five-year follow-up period. Patients in Group 1 were significantly older (78.36 ± 6.39 vs. 73.47 ± 5.83; p < 0.001) and exhibited higher prevalence rates of heart failure (HF) (21.17% vs. 11.86%; p = 0.009) and stroke or transient ischemic attack (TIA) (24.09% vs. 12.15%; p = 0.001) compared to those in Group 2. After adjusting for covariates, multivariate Cox regression analysis revealed that a TUGT >15 s in CVD patients was significantly associated with an elevated hazard ratio for five-year all-cause mortality (hazard ratio (HR): 2.029; 95% confidence interval (CI): 1.198–3.437; p = 0.004). Conclusions: The TUGT is independently associated with 5-year all-cause mortality among older patients with CVD, with a TUGT >15 s indicating a poorer prognosis. Clinical Trial Registration: ChiCTR1800017204; date of registration: 07/18/2018. URL: https://www.chictr.org.cn/showproj.html?proj=28931.

AIMS:Implementing optimal guideline-directed medical therapy is still challenging in patients with heart failure (HF). This prospective study assessed the benefits of large-scale, nationwide, multi-annual implementation of HF therapies in China. METHODS AND RESULTS:This longitudinal, pre-post comparison design included patients in hospitals accredited by the National Heart Failure Center Accreditation Program (HF-CAP). Patients were divided into four groups: 6-12 months before accreditation (Pre); >0 -≤12 months after accreditation (Y1); >12-≤24 months after accreditation (Y2), and >24 months after accreditation (Y2+). The primary endpoint was 1-year composite HF readmission and/or cardiovascular death. Secondary endpoints included 1-year HF readmission alone, 1-year cardiovascular death alone, and association between phone calls and/or visits and outcomes. Overall, 408 073 patients with HF from 646 centres were included. After HF-CAP accreditation, more patients with HF were treated following discharge. Compared with the Pre group, risk of meeting the primary endpoint decreased in Y1 and was incrementally lower in Y2 and Y2+: fully adjusted odds ratios (OR) and 95% confidence intervals (CIs) were 0.893 (0.871-0.916), 0.855 (0.830-0.880) and 0.720 (0.695-0.745), respectively (all p < 0.0001). Risk of HF readmission alone reduced from Y1 onwards (OR 0.865 [95% CI 0.841-0.891]). Risk of cardiovascular death reduced from Y2 onwards (OR 0.942 [95% CI 0.904-0.983]). Phone calls had little association with patient outcomes; however, face-to-face visits reduced risk of cardiovascular death (OR 0.624 [95% CI 0.597-0.651]). CONCLUSIONS:Guideline-directed medical therapy implementation and follow-up after HF hospitalization was achievable in ~400 000 patients and was associated with cardiovascular benefits 1-year post-initiation.

This study aims to fill this gap by leveraging Global Burden of Disease 2021 (GBD 2021) data to conduct a comprehensive assessment of the disease burden attributable to high systolic blood pressure (SBP) in young adults. Data from the Global Health Data Exchange were utilized to estimate the disease burden attributable to high SBP in young adults, stratified by overall disease, sex, socio-demographic index (SDI) level, GBD region, nation, and specific disease. In 2021, the overall disease attributable to high SBP in young adults was substantial, with approximately 24,626,362 disability-adjusted life years (DALYs) and 477,992 deaths, and the DALYs and mortality rates were 623.68 and 12.11 per 100,000 populations, respectively. The DALYs and mortality rates of specific disease were highest for ischemic heart disease (IHD), followed by intracerebral hemorrhage (ICH), and hypertensive heart disease (HHD). From 1990 to 2021, the DALYs and mortality rates for overall disease attributable to high SBP in young adults showed no significant change.However, there were greater declines in HHD and ICH, while the majority of diseases exhibited an upward trend. The DALYs and mortality rates for overall disease attributable to high SBP in young adults showed no significant change in females but increased in males. The SDI regions like middle and low-middle SDI regions, GBD regions like Oceania and Caribbean, and countries like Lesotho and Zimbabwe presented the largest increases in the DALYs and mortality rates for overall disease attributable to high SBP in young adults. The trends for certain diseases attributable to high SBP in young adults, when analyzed by sex, SDI level, and region, diverge from the overall disease trends. This study highlights the significant overall disease burden attributable to high SBP in young adults. Despite an overall steady trend in the DALYs and mortality rates since 1990, significant disparities persist across overall diseases, sexes, SDI levels, regions, countries, and specific diseases. These disparities highlight the need for strategic interventions to reduce the health impact of high SBP in young adults.

Among very older patients with atrial fibrillation (AF), the frequency of inappropriate direct oral anticoagulant (DOAC) dosing, associated factors, and temporal trends in practice are unknown. This retrospective study included consecutive inpatients aged 80 years or older with a discharge diagnosis of atrial fibrillation who were prescribed DOACs at discharge from Beijing Hospital between January 2018 and August 2023. Patients were stratified into underdosed, overdosed, or recommended dosing groups. Logistic regression analysis was performed to identify risk factors associated with inappropriate dosing, and temporal trends were evaluated using the Cochran–Mantel–Haenszel test. Among 676 inpatients aged ≥ 80 years with AF (mean age 84.4 ± 3.5 years; 53.1

Background：Heart failure (HF) imposes a growing public health and macroeconomic burden in low- and middle-income countries (LMICs), yet its long-term economic implications remain unquantified. China, characterized by rapid population aging and escalating cardiovascular risks, provides a critical setting to model HF's economic impact. Methods: Using data from the Global Burden of Disease Study 2021, China Cardiovascular Association Registry, and national insurance databases, we quantified the macroeconomic burden of heart failure (2025-2035) through a health-augmented macroeconomic model. We evaluated three interventions: BNP screening (adults ≥40 years), intensive blood pressure control (hypertensive patients), and guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Costs are reported in 2017 international dollars (INT$). Findings：By 2035, HF cases in China are projected to reach 22.7 million (95% UI: 9.5-36.9 million), with an age-standardized prevalence of 760.65 per 100,000 (283.21-1,340.77). The cumulative economic burden (2025-2035) is estimated at INT$1,001.1 billion (733.4-1,346.6 billion), representing 0.256% (0.188%-0.344%) of annual GDP, driven by labor force attrition (72.1%; 64.4-74.8%) and direct medical costs (27.9%; 25.2-35.6%). Three interventions could reduce the total burden by 12.5%: BNP screening (25% coverage among adults ≥40 years) could save INT$78.5 billion (62.8-94.1 billion; 8.10% burden reduction; cost-benefit ratio = 0.49; 0.39-0.59);intensive blood pressure control (41.4% coverage among hypertensive patients) could reduce costs by INT$27.5 billion (25.1-29.9 billion; 2.74% reduction; ratio = 0.22; 0.20-0.24);and GDMT for incident HFrEF patients could yield savings of INT$17.0 billion (12.8-22.4 billion; 1.70% reduction; ratio = 0.48; 0.36-0.63). Interpretation：This study highlights HF's dual clinical and macroeconomic burden in China, advocating three scalable strategies: nationwide BNP screening in primary care, subsidized hypertension management, and GDMT optimization. These interventions might offer a blueprint for LMICs to mitigate HF-related economic losses amid demographic aging. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (No: 2023ZD0504600); Capital's Funds for Health Improvement and Research (2022-1-4052); the National High-Level Hospital Clinical Research Funding (BJYY-2023-070); the National Natural Science Foundation of China (No. 82170396); and the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-050). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of the Central Ethics Committee of Beijing Hospital gave ethical approval for this work (Approval No.: 2022BJYYEC-346-01). Ethics committee of the Central Ethics Committee of Beijing Hospital waived ethical approval for the use of de-identified national insurance databases (IRB No.: 2019BJYYEC-219-01). The Global Burden of Disease Study 2021 is a publicly available dataset requiring no additional ethics review. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to Hua Wang (wanghua2764@bjhmoh.cn)

BACKGROUND:Tyrosine kinase inhibitor (TKI) and rivaroxaban co-administration is common for patients with cancer and venous thromboembolism. However, the drug-drug interactions (DDIs) between epidermal growth factor receptor (EGFR) TKIs and rivaroxaban remain uncertain. METHODS:DDIs were investigated in vitro and in vivo. In vitro experiments were conducted using rat liver microsomes, and rivaroxaban metabolites were tested to identify the two TKIs that exhibit the most significant DDIs. The type of inhibition was investigated using Lineweaver-Burk plots. For in vivo experiments, eighteen rats were randomly divided into three groups and pretreated with CMC-Na together with avitinib or gefitinib, or with CMC-Na alone for 7 days. On day 8, rivaroxaban was orally administered to each group. Blood samples were collected at various time points, and plasma rivaroxaban was quantified. Molecular docking was performed to explore the mechanism of DDIs. RESULTS:Avitinib and gefitinib showed the most potent inhibitory effects among multiple EGFR TKIs and inhibited rivaroxaban metabolism in a mixed model of noncompetitive and uncompetitive inhibition. The area under the drug-time curve and maximum plasma concentration of rivaroxaban were significantly higher following avitinib and gefitinib pretreatment, while the apparent volume of distribution and clearance rates were significantly lower. Our molecular docking analysis revealed that these two drugs may inhibit rivaroxaban metabolism by overlapping with its binding site on CYP3A4 and CYP2D6. CONCLUSION:These findings confirm the presence of DDIs between EGFR TKIs and rivaroxaban. Avitinib and gefitinib significantly inhibit rivaroxaban metabolism, and their co-administration may aggravate the risk of bleeding.

Frailty is a multifactorial syndrome associated with adverse health outcomes. The metabolic underpinnings of frailty, particularly lipid metabolism, are not fully understood. Unlike isolated lipid fractions or inflammatory markers, atherogenic index of plasma (AIP) integrates atherogenic lipid profiles and systemic inflammation. However, its association with frailty has not been extensively studied. Six thousand four hundred participants from the National Health and Nutrition Examination Survey (NHANES) were enrolled. Frailty was calculated with the frailty index (FI), with scores ≥ 0.21 indicating frailty. Logistic regression adjusted for demographic, socioeconomic, and lifestyle factors evaluated the association between AIP and frailty. Restricted cubic splines (RCS) explored nonlinear associations, and subgroup analyses assessed interactions across age, sex, race, poverty income ratio, smoking status, drinking status, and marital status. This study demonstrated a strong dose–response relationship between AIP and frailty. After full adjustment, Individuals in quartile 3 and 4 showed higher odds of frailty than those in lowest quartile, with ORs (95