Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: fibrinogen levels <2 g/L were significantly associated with increased mortality, whereas levels >4 g/L were significantly associated with reduced mortality. Notably, fibrinogen was undetectable in aortic samples from control individuals without AD but accumulated in the aortic media of both AD patients and model mice. Importantly, fibrinogen accumulation was more pronounced in mice with advanced but unruptured AD, suggesting its role in maintaining vascular stability. AAV8-mediated fibrinogen knockdown significantly exacerbated AD, whereas exogenous supplementation with fibrinogen alleviated AD in mice, as evidenced by changes in the survival rate, aortic dilation, AD incidence, elastic fiber degradation, and collagen accumulation. Mechanistically, fibrinogen inhibited Bmal1 signaling, preventing detrimental vascular smooth muscle cell (VSMC) phenotypic transformation and contractility impairment. Finally, exogenous supplementation with the optimal dose of fibrinogen mitigates the progression of AD in mice. This study identified fibrinogen as a key regulator of VSMC contractility and aortic structural integrity, highlighting its potential as a novel therapeutic target to delay AD progression and extend the window for elective surgery.

This study reports a congenital heart disease, characterized by ventricular wall thinning and septal defects, caused by a heterozygous missense mutation (R755 W) in the glycolytic gene PFKP (platelet isoform of phosphofructokinase-1). The pathogenic mechanism involves the PFKP mutation impairing enzyme activity, which inhibits cardiomyocyte proliferation and leads to the thinning of the compact myocardium. In the mouse model, we found that administering the downstream metabolite, fructose-1,6-bisphosphate, reversed the myocardial hypoplasia in fetal mice, providing proof-of-concept for in utero intervention. Clinically, we successfully prevented the transmission of the disease using preimplantation genetic testing, resulting in the birth of a healthy infant.

BACKGROUND:Rheumatic mitral valve disease remains a major global health challenge. Determining optimal surgical approaches is critical. This study aimed to identify key repairability factors and compare midterm outcomes of mitral repair versus replacement. METHODS:This retrospective cohort study consecutively enrolled rheumatic mitral valve surgery patients from two centres, excluding those with missing imaging or clinical data. CT angiography and echocardiogram was used to quantitatively assess factors affecting repairability. Inverse probability weighting was applied to balance baseline characteristics between groups, and mid-term outcomes were compared. Independent risk factors for prognosis were also explored. RESULTS:Among 972 patients, 621 (63.9%) successfully underwent mitral valve repair. Body mass index, diabetes, left atrial diameter, posterior leaflet calcification, anterior leaflet clear zone calcification and annular calcification were identified as independent factors affecting repairability. At a median follow-up of 3.51 years (IQR 1.62-5.14), the repair group demonstrated more favourable outcomes, with significantly reduced mortality and stroke rates compared with the replacement group, while maintaining comparable reoperation rates. Prior percutaneous mitral commissurotomy did not reduce valve repairability (OR=0.588, 95% CI 0.342 to 1.010; p=0.054) but emerged as an independent predictor of reoperation following repair (OR=7.496, 95% CI 1.325 to 42.404; p=0.023). CONCLUSIONS:In well-selected patients, rheumatic mitral valve repair was associated with lower mortality and stroke rates compared with replacement, with comparable reoperation rates. However, patients with a history of percutaneous mitral commissurotomy have a higher risk of reoperation after repair and should be carefully evaluated. TRIAL REGISTRATION NUMBER:ChiCTR2200067151.

ABSTRACT Objective The clinical efficacy and early outcomes of total arch replacement with frozen elephant trunk (TAR+FET) in elderly patients presenting with acute type A aortic dissection (ATAAD) remain incompletely characterized. This study aimed to comprehensively evaluate early clinical outcomes and perioperative risk profiles in elderly patients undergoing TAR+FET for ATAAD, thereby addressing gaps in the literature and providing evidence to guide surgical decision‐making in this high‐risk population. Methods A multicenter retrospective analysis was conducted involving 1634 patients who underwent TAR+FET for ATAAD between 2015 and 2023 across seven cardiovascular centers. Patients were categorized into elderly (≥ 60 years, n = 258) and non‐elderly (< 60 years, n = 1376) groups. Baseline characteristics, operative details, and early outcomes were compared between groups before propensity score matching (PSM). A 1:2 PSM established a balanced cohort of 699 patients (elderly, n = 245; non‐elderly, n = 454), in which postoperative complications and survival were compared. To evaluate the independent prognostic impact of age, multivariable Cox proportional hazards models with incremental covariate adjustments were applied. Results Before PSM, elderly patients had higher prevalences of coronary artery disease, diabetes, and hyperlipidemia, with significantly longer intensive care unit (ICU) stay, prolonged ventilation time, and lower 30‐day survival compared with non‐elderly patients. After PSM, baseline covariates were well balanced; however, elderly patients continued to demonstrate worse perioperative outcomes, including longer ICU stay (68 [35–162] vs. 47 [28–113] h, p = 0.001), prolonged ventilation time (49 [21–111] vs. 38 [18–86] h, p < 0.001), and higher incidences of reintubation, tracheostomy, respiratory failure, acute kidney injury (AKI), and dialysis (all p < 0.010). Kaplan–Meier analysis revealed significantly lower 30‐day survival in the elderly group (86.5% vs. 93.6%, p = 0.002). Multivariable Cox regression identified age ≥ 60 years as an independent predictor of mortality (hazard ratio = 2.286, 95% confidence interval: 1.361–3.840, p = 0.002). Within the elderly subgroup, non‐survivors were older, had longer operative and cardiopulmonary bypass times, and experienced substantially higher rates of severe postoperative complications—particularly neurological injury, dialysis‐requiring AKI, arrhythmia, and respiratory failure—than survivors. Conclusion Even after adjustment for baseline characteristics, elderly patients undergoing TAR+FET have higher risks of perioperative complications and early mortality than non‐elderly patients. This unfavorable prognosis likely reflects reduced physiological reserve rather than surgical factors alone. Future strategies should emphasize individualized procedure selection and organ‐protective perioperative management to improve outcomes in this population.

Background:Cognitive impairment is common in patients with end-stage heart failure and may adversely affect self-management, treatment adherence, and clinical outcomes after left ventricular assist device (LVAD) implantation. Although LVAD support can improve systemic and cerebral perfusion, postoperative cognitive trajectories remain heterogeneous, and the factors associated with failure to improve are not well defined, particularly in Asian populations. This study aimed to characterize changes in cognitive function after LVAD implantation and to identify clinical, laboratory, echocardiographic, and neuroimaging determinants of cognitive non-improvement. Methods:This single-center retrospective cohort study included 56 patients who underwent LVAD implantation and completed the Montreal Cognitive Assessment (MoCA) before surgery and approximately 1 year after surgery. Demographic and clinical characteristics, laboratory parameters, including bilirubin, echocardiographic indices, including right ventricular fractional area change (RV FAC) and valvular status, and head computed tomography (CT) findings were analyzed. Changes in MoCA scores were assessed using a paired t-test. Univariable and multivariable logistic regression analyses were performed to identify factors associated with postoperative cognitive non-improvement. Results:Before LVAD implantation, 39 of 56 patients (69.6%) had a MoCA score <26, indicating a high prevalence of baseline cognitive impairment. Alcohol use was more frequent among patients with cognitive impairment. At approximately 1 year after implantation, 43 of 56 patients (76.8%) showed improved MoCA scores, and the overall MoCA score increased significantly from baseline (P<0.05). In univariable analysis, ischemic cardiomyopathy, lower RV FAC, higher bilirubin levels, incident ischemic lesions on head CT, and new-onset ≥mild aortic regurgitation were associated with cognitive non-improvement. In multivariable analysis, elevated bilirubin and new-onset ≥mild aortic regurgitation remained independently associated with cognitive non-improvement. Conclusions:Most patients with end-stage heart failure experienced significant cognitive improvement within 1 year after LVAD implantation, whereas approximately one quarter did not. Elevated bilirubin and new-onset ≥mild aortic regurgitation may help identify patients at increased risk of limited cognitive recovery and may support closer postoperative surveillance and earlier targeted intervention.

Background:Hybrid aortic repair (HAR) has emerged as a less invasive alternative to conventional open arch repair for selected patients with aortic arch disease, but its comparative safety and mid-term effectiveness remain uncertain. This study aimed to compare the clinical outcomes of HAR and the frozen elephant trunk (FET) procedure for the treatment of aortic arch disease. Methods:We conducted a retrospective analysis of 785 patients with aortic arch disease treated at Beijing Anzhen Hospital between January 2015 and February 2023. Among these patients, 406 underwent HAR, which consisted of supra-aortic debranching combined with thoracic endovascular aortic repair (TEVAR), and 379 received the FET procedure. Inverse probability of treatment weighting (IPTW) was used to eliminate baseline differences between the two groups, ensuring comparability of outcomes. The primary endpoints of the study were postoperative mortality, while the secondary endpoints included reintervention, perioperative stroke, paraplegia, and dialysis. Results:Before IPTW adjustment, there was a significant difference in age between the two groups. Specifically, the patients in the HAR group were significantly older than those in the FET group [57.0 (49.0, 66.0) vs. 49.0 (40.0, 56.0) years, P<0.001]. The rates of diabetes (9.6% vs. 5.5%, P=0.045) and hyperlipidemia (21.7% vs. 9.0%, P<0.001) were also significantly higher in the HAR group than in the FET group. However, after adjusting for baseline differences using IPTW, none remained statistically significant. The pre-IPTW baseline data showed that, compared with the FET group, the HAR group had a significantly shorter operative time [5.5 (4.5, 6.5) vs. 6.5 (6.0, 7.0) minutes, P=0.02], lower blood loss [400.0 (150.0, 800.0) vs. 800.0 (600.0, 1,000.0) mL, P<0.001], and faster postoperative recovery [165.0 (75.0, 268.7) vs. 225.0 (145.0, 300.0) hours, P<0.001]. After IPTW adjustment, the HAR group continued to demonstrate significantly lower blood loss [500.0 (200.0, 900.0) vs. 800.0 (600.0, 1,000.0) mL, P=0.03]. No significant difference was observed between the two groups in terms of in-hospital mortality. The mid-term survival analysis revealed a higher mortality rate in the HAR group (8.6% vs. 3.9%, P=0.04); however, after IPTW adjustment, this difference was no longer statistically significant (P=0.18). Conclusions:This study found that, compared with the FET group, the HAR group demonstrated comparable postoperative mortality and reintervention rates, along with a shorter operative time, reduced blood loss, and a lower incidence of specific pulmonary complications, supporting its use in high-risk patients. However, HAR may increase the risk of neurological complications. Therefore, strict patient selection, careful anatomical assessment, and technical optimization are required to ensure long-term safety and efficacy.

Background:Three-vessel coronary artery disease (3V-CAD) often requires revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The SYNTAX score is widely used for anatomical risk stratification, but whether magnetocardiography (MCG) provides incremental information beyond anatomical assessment remains uncertain. Objectives:To evaluate, in an exploratory pilot analysis, whether MCG-derived parameters add information beyond the SYNTAX score for modeling clinician-selected revascularization category in 3V-CAD and to examine the noncausal association between model-treatment concordance and major adverse cardiovascular and cerebrovascular events (MACCEs). Methods:Prospective cohort data were analyzed retrospectively. Candidate MCG parameters were screened using Pearson correlation, random forest analysis, and stepwise logistic regression, and selected variables were combined with the SYNTAX score. Model discrimination, calibration, bootstrap internal validation, and LASSO penalized logistic regression sensitivity analysis were assessed. Model-treatment concordance was explored using Kaplan-Meier analysis and multivariable Cox regression. Results:Among 544 patients, 543 complete cases were available for model evaluation, including 42 CABG events. In the overall cohort, the combined MCG-SYNTAX model did not materially improve discrimination compared with the SYNTAX-only model (AUC, 0.853 vs. 0.847; p = 0.628). Discrimination was also similar in the low-risk subgroup (SYNTAX < 22; AUC, 0.824 vs. 0.848; p = 0.540). In the intermediate-high-risk subgroup (SYNTAX ≥ 22), the combined model had a numerically higher apparent AUC, but this finding was considered hypothesis-generating. Bootstrap internal validation did not support a maintained incremental value of the combined model (optimism-corrected AUC, 0.834 vs. 0.848 for the SYNTAX-only model). In LASSO sensitivity analysis using all appended MCG-derived candidate variables, only the SYNTAX score was retained. The exploratory follow-up analysis showed an unadjusted difference in MACCE-free survival between concordance groups, but this association was not retained after multivariable adjustment and was not interpreted causally. Conclusions:In this single-center pilot modeling study, selected MCG parameters showed limited and unstable incremental value beyond the SYNTAX score for modeling clinician-selected revascularization category in 3V-CAD. These findings do not support clinical implementation at this stage and require external validation. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2200066942.

BACKGROUND:Traditional surgical video recording requires professional personnel to manually adjust the camera capturing position, which leads to low recording efficiency and interference with the surgical process. METHOD:To address these issues, this study proposes an automatic surgical video capture scheme based on an intelligent surgical video capture robot system. The method utilises the YOLO v5 algorithm and a 3D camera to identify and localise the surgical field area. Additionally, Convex Hull Edge Line Search (CHELS) algorithm is constructed to rapidly solve the optimal capturing position while avoiding obstacles. Finally, Position-Based Visual Servoing (PBVS) is applied to control the camera for precise capture of the surgical field. RESULT:The detection model for the surgical field achieved an mAP@0.5 of 0.962, and the average solution time of the CHELS is 0.1469s. CONCLUSION:Automatic surgical video capture schemes can efficiently enable the intelligent and automatic recording of surgical videos.

Additional exploration is required to determine how to treat patients with moderate aortic regurgitation (AR) in rheumatic mitral valve (MV) surgery. This study compared clinical outcomes in patients undergoing non-surgical treatment (NT) of aortic valve (AV), aortic valvuloplasty (AVP), and aortic valve replacement (AVR). This multicenter, retrospective observational cohort study included 338 moderate AR patients undergoing rheumatic MV surgery from January 2015 to January 2024. We followed up with patients for a median of 43.4 months. Furthermore, more-than-mild aortic valve dysfunction (AVD) in the follow-up period was our primary outcome. Our secondary outcomes were all-cause mortality and cardiac valve reoperation before discharge and during follow-up. We classified patients into three groups, namely, NT (n = 128), AVP (n = 91), and AVR (n = 119) groups, respectively. Moreover, 33.0%, 30.1%, and 3.9% of patients achieved our primary outcome, while 4.2%, 5.6%, and 9.6% of them attained our secondary outcomes in the three groups, respectively. We observed that fewer patients from the AVR group had achieved the primary outcome than those in the NT [adjusted relative risk (RR), 0.41; 95% confidence interval (CI), 0.21-0.68; p = 0.002] and AVP groups (adjusted RR, 0.14; 95% CI, 0.04-0.43; p = 0.002), respectively. The secondary outcomes did not significantly differ among the three groups. Without increasing surgical risks, the concurrent AVR significantly improves AV status in moderate AR patients undergoing rheumatic MV surgery throughout follow-up. None or mild AVD was observed in many patients from the NT group during the follow-up, thereby warranting the delay of surgery for AV.

Aims Type A aortic dissection (TAAD) is a life-threatening cardiovascular emergency for which no effective pharmacological therapy currently exists. Elevated bradykinin (BK) has been identified as an independent predictor of poor postoperative outcomes in TAAD patients. However, whether and how elevated BK contributes to TAAD pathogenesis remains unknown. Here, we aimed to delineate the mechanistic role of BK and its receptors in TAAD pathogenesis. Materials and methods BK levels were measured in plasma and aortic tissues from TAAD patients and matched controls. In a β-aminopropionitrile (BAPN)-induced TAAD mouse model, selective blockade of the bradykinin B2 receptor (B2R) with icatibant was evaluated. The underlying mechanisms were further investigated in human umbilical vein endothelial cells (HUVECs) by assessing intracellular superoxide and nitric oxide (NO) levels. Key findings BK levels were significantly elevated in TAAD patients and mice compared with controls. In the BAPN-induced model, icatibant significantly attenuated disease progression, reducing both TAAD incidence and mortality independently of blood pressure. Mechanistically, excessive BK activated endothelial B2R, which elevated intracellular superoxide levels, suppressed NO production, and ultimately resulted in endothelial damage and TAAD; icatibant reversed these changes by restoring P-VASP levels and NO bioavailability. Significance Our findings demonstrate that BK-driven B2R activation induces endothelial dysfunction and TAAD. Targeting this pathway with icatibant mitigates disease progression, nominating B2R inhibition as a viable pharmacological strategy against TAAD.

This systematic review compared the efficacies of percutaneous mitral balloon commissurotomy (PMBC), mitral valvuloplasty (MVP), and mitral valve replacement (MVR) in patients with rheumatic mitral valve disease. Data from 15,271 patients across 23 cohort studies and randomized controlled trials were analyzed. Based on the results of the network meta-analysis, MVP demonstrated a lower early mortality rate [odds ratio (OR), 0.71; 95% confidence interval (CI): 0.54–0.92], follow-up mortality rate (OR: 0.84; 95% CI: 0.72-0.99), and complication rate (OR: 0.75; 95% CI: 0.64-0.88) compared to MVR. The follow-up reoperation rate in the MVP group was significantly lower than that in the PMBC group (OR: 0.49; 95% CI: 0.30–0.80). The optimal surgical strategy should be tailored to achieve better prognoses.

Background:Acute type A aortic dissection (ATAAD) is a high-risk disease complicated by organ malperfusion (OMP), which impairs surgical outcomes. This study explored computed tomography angiography (CTA) characteristics of OMP in ATAAD patients and identified imaging biomarkers for postoperative adverse complications (AC). Methods:A retrospective analysis included 432 ATAAD patients who underwent total arch replacement with frozen elephant trunk procedure (2016-2020), excluding those without preoperative aortic CTA. CTA assessed dissection features, branch vessel involvement, and tear severity. Analyses used Kaplan-Meier (KM) curves, Cox regression, logistic regression, and restricted cubic spline (RCS). Results:Preoperative OMP was present in 155 (35.9%) patients. The Pre-OMP group had higher false lumen arc length (FLAL) ratios at multiple aortic levels, higher postoperative AC (38.7% vs. 24.5%, p = 0.002) and 30-day mortality (17.4% vs. 6.5%, p < 0.001) than the non-Pre-OMP group. KM analysis showed postoperative AC, rather than preoperative OMP, was the critical determinant of survival at follow-up (p < 0.001 vs. p = 0.069), but this effect does not persist in patients surviving beyond 1 year. Multivariable logistic regression identified ascending aorta level (AAL) FLAL ratio as an independent predictor of postoperative AC (OR: 1.335, 95%CI: 1.079-1.651, p = 0.008); RCS confirmed nonlinearity, with AC risk rising significantly when AAL FLAL ratio >0.849. Conclusions:CTA of ATAAD patients with OMP mainly shows more severe central aortic tear characteristics. Postoperative AC is a critical determinant of survival at follow-up. The AAL FLAL ratio (>0.849) can serve as a reliable predictive biomarker for postoperative AC, aiding preoperative risk stratification and individualized surgical management in ATAAD.

Purpose: Machine learning-based coronary computed tomography fractional flow reserve (CT-FFR) holds great potential for assessing coronary ischemic status. The current literature lacks a comprehensive description of the routine implementation of CT-FFR in real world. To investigate the clinical characteristics and acceptance of CT-FFR in clinical decision-making among Chinese patients and subsequently assess the diagnostic accuracy of invasive coronary angiography as the reference. Materials and Methods: In this retrospective single-center study, 4564 patients were included. In the first part, we conducted a baseline analysis of patients and their epicardial coronary arteries. Then, we analyzed hospitalization and revascularization in the context of application of CT-FFR, using logistic regression and Sankey diagrams. Finally, we performed a diagnostic analysis of 2718 vessels in 906 patients. Results: The baseline analysis included a total of 4564 patients. A statistically significant distinction was observed in the traditional risk factors for coronary heart disease between 2 groups with CT-FFR 0.8 cutoff values. Logistic regression analysis and Sankey plots revealed a association between CT-FFR ≤0.8 and subsequent hospitalization. Finally, a diagnostic analysis was performed on 2718 vessels, and the optimal diagnostic model efficacy was achieved by using a CT-FFR cutoff value of 0.8 in conjunction with stenosis ≥70% for CCTA. Conclusions: Our study provides evidence that machine learning-based CT-FFR values exhibit a probably positive correlation with individuals presenting high-risk factors for coronary artery disease. Furthermore, we observed a influence of CT-FFR on the clinical decisions made by physicians. The integration of CT-FFR and CCTA has the potential to enhance diagnostic efficacy.

BACKGROUND:The magnitude of cognitive change before and after incident heart failure (HF) is unclear. We investigated whether incident HF is associated with changes in cognitive function at the time of diagnosis and accelerated trajectory in cognitive decline in the subsequent years. METHODS:We used data from the Health and Retirement Study, a nationally representative survey of US adults aged 50 years or older. Participants underwent a cognitive assessment at baseline (wave 5, 2000), and at least 1 other time point (from wave 6 [2002] to wave 15 [2020]). The outcomes were change in global cognition, memory, and executive function. Outcomes were standardized into Z-scores, with higher scores indicating better cognitive performance. Linear mixed-effects models estimated changes in cognition at the time of HF (change in the intercept) and the rate of cognitive change over the years after HF (change in the slope), after adjusting for pre-HF cognitive trajectories and potential confounders. RESULTS:We included 12 850 adults (mean [SD] age, 66.1 [9.4] years; 61.8 % women). Over a median follow-up of 16 years (interquartile range: 8 to 20 years), 1457 participants had incident HF. The annual rate of cognitive decline before HF diagnosis among individuals with incident HF was similar to that of participants who remained HF-free throughout follow-up. However, incident HF was associated with subsequent decreases in global cognition (-0.073 SD [95 % CI -0.109 to -0.038]), memory (-0.070 SD [95 % CI -0.108 to -0.032]), and executive function (-0.054 SD [95 % CI -0.092 to -0.016]) around the time of the HF diagnosis. Moreover, individuals with incident HF vs those without HF demonstrated faster and long-term declines in global cognition (-0.011 SD/year [95 % CI -0.018 to -0.004]) and executive function (-0.008 SD/year [95 % CI -0.015 to -0.001]), but not in memory (-0.006 SD/year [95 % CI -0.013 to 0.001]) over the years after HF compared with pre-HF slopes. CONCLUSIONS:Incident HF was associated with subsequent decreases in cognitive function at the time of diagnosis and accelerated cognitive decline over the following years.

Abstract Inflammatory processes and glycemic dysregulation are recognized contributors to poor cerebrovascular and cardiovascular events. This study proposed a new composite indicator, the systemic glucose–inflammation index (SGI) and evaluated its capacity to predict postoperative cerebral infarction among individuals who underwent off‐pump coronary artery bypass grafting (OPCABG). Our cohort comprised 6549 patients undergoing elective OPCABG from January 2021 to October 2022 across eight medical centers in China. The primary outcome was in‐hospital postoperative cerebral infarction, with secondary outcomes including in‐hospital death and acute kidney injury (AKI) and postoperative myocardial infarction. We employed logistic regression modeling and restricted cubic spline (RCS) techniques to examine the relationship between SGI levels and endpoint events. The SGI was derived using the formula: [fasting blood glucose × platelet count]/admission white blood cell count. Stroke after OPCABG developed in 136 participants (2.08%). Patients in the uppermost SGI quartile had markedly elevated stroke rates compared to those in the lowest quartile (3.54% vs. 1.10%, p < 0.001). After multivariable adjustment, the SGI remained independently correlated with stroke risk (OR = 1.28, p < 0.001). RCS analysis showed that the association between the SGI and postoperative stroke was consistent with a linear relationship (p for nonlinearity = 0.076). The SGI is an independent prognostic marker for stroke following OPCABG. Incorporating the SGI into established risk evaluation frameworks may enhance predictive value.

Aortic aneurysm (AA) and aortic dissection (AD) are life-threatening cardiovascular diseases. AA includes thoracic (TAA) and abdominal (AAA) subtypes, while AD involves primary intimal tear. In the U.S., mortality trends, and demographic disparities remain unclear. This retrospective population-based study analyzed US AA/AD burden and disparities to guide targeted prevention and management. We extracted AA/AD mortality data (1999–2023; urban-rural 1999–2020) for adults aged ≥ 25 in the continental U.S. from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research, stratified by sex, age, race/ethnicity and region. We calculated crude and age-adjusted rates (CMR/AAMR), and estimated annual and average annual percentage change (APC/AAPC) via joinpoint regression. Two-tailed t-tests were used (p < 0.05). Between 1999 and 2023, there were 289,971 AA/AD-related deaths in the U.S., with AAMR declining (AAPC = -3.73