OBJECTIVES:This study aimed to investigate the associations of biological age (BA) acceleration and genetic risk with the incidence of abdominal aortic aneurysm (AAA), and to evaluate the extent to which BA acceleration mediates the impact of a healthy lifestyle on AAA risk. DESIGN:A large prospective cohort study. SETTING AND PARTICIPANTS:This study included 279,944 participants from the UK Biobank. METHODS:Two validated measures of BA, Klemera-Doubal Method Biological Age (KDM-BA) and PhenoAge, were estimated using clinical biomarkers. BA acceleration was calculated as the residual from regressing BA on chronological age. A polygenic risk score (PRS) was constructed based on AAA-associated genetic variants, and a healthy lifestyle score was derived from key behavioral factors. Cox proportional hazards models were used to assess the independent and joint associations of BA acceleration, PRS, and lifestyle score with AAA risk. Interaction and mediation analyses were also conducted. RESULTS:Among the 279,944 participants, 1305 developed AAA over a mean follow-up of 15.5 years. Acceleration in both KDM-BA (HR, 1.89; 95% CI, 1.49-2.41) and PhenoAge (HR, 2.65; 95% CI, 2.21-3.17) was significantly positively associated with an increased risk of AAA. Significant interaction and joint effects were observed between genetic risk and BA acceleration. Compared with individuals with low genetic risk and low BA acceleration, those with both high PRS and high BA acceleration, particularly PhenoAge acceleration, had the highest risk of AAA (HR, 7.14; 95% CI, 5.64-8.46). Furthermore, a higher healthy lifestyle score was inversely associated with AAA risk, with approximately 7% of this association mediated through reduced BA acceleration. CONCLUSIONS:Both BA acceleration and genetic predisposition were significant risk factors for AAA, highlighting their potential utility in guiding precision prevention strategies and targeted interventions.

OBJECTIVE:Acute type A aortic dissection during pregnancy with situs inversus totalis is exceptionally rare. METHODS:We report a 27-year-old woman at 24 weeks of gestation who underwent emergency ascending aortic and total arch replacement with frozen elephant trunk implantation. RESULTS:Fetal demise occurred on postoperative day 1, but the mother recovered without neurological deficit and remained well at 10-year follow-up. CONCLUSIONS:This case demonstrates the feasibility of complex arch repair in mirror-image anatomy and highlights the importance of individualized operative planning and multidisciplinary maternal-fetal management in experienced aortic centres.

IntroductionDisrupted rest-activity rhythm (RAR), an accelerometer-derived measure of the strength and temporal organization of daily behavioral rhythms, has been linked to multiple adverse health outcomes. Given that the development of abdominal aortic aneurysm (AAA) involves chronic inflammation, extracellular matrix degradation, and vascular smooth muscle cell dysfunction, attenuated rest-activity rhythms (RAR) may be associated with AAA risk. However, prospective evidence on this association remains limited.MethodsThe primary analysis included 78,282 UK Biobank participants who completed accelerometer monitoring between 2013 and 2015. Thirteen parametric and nonparametric RAR parameters were derived. Cox proportional hazards models estimated associations between RAR parameters and AAA incidence, as well as potential interactions and joint effects with other risk factors. Causal mediation analysis examined the mediating role of inflammatory markers. An XGBoost-based survival model evaluated variable importance, and SHapley Additive exPlanations (SHAP) interpreted feature contributions.ResultsDuring a mean follow-up of 10.1 years, 229 AAA cases were recorded. Lower RAR parameters, particularly relative amplitude (RA), M10, amplitude, and mesor, were significantly associated with higher AAA risk [lowest vs. highest tertile HRs: RA 1.49 (95% CI 1.03–2.15); M10 1.51 (1.05–2.18); amplitude 1.58 (1.09–2.30); mesor 1.46 (1.04–2.14)]. Although no significant interactions were observed, individuals with weaker RAR combined with current smoking or high polygenic risk had markedly increased AAA risk. Mediation analysis indicated that neutrophil and monocyte counts explained about 5–6% of the RAR-AAA association. In the XGBoost model, beyond age, male sex, and PRS as dominant predictors, mesor, RA, and M10 emerged as meaningful contributors to AAA risk prediction.ConclusionAccelerometer-derived RAR parameters are strongly associated with the risk of developing AAA. Integrating RAR measures with genetic and traditional risk factors may improve risk stratification and provide novel insights for preventive strategies against AAA.

BACKGROUND:Abdominal aortic aneurysm (AAA) is typically asymptomatic until rupture, and established risk factors do not fully explain its occurrence. Whether social isolation, loneliness, polygenic susceptibility, and systemic inflammation jointly influence AAA risk remains unclear. METHODS:We included 356,181 White British participants from the UK Biobank free of AAA at baseline. Social isolation and loneliness indices were derived from questionnaires. A genome-wide polygenic risk score (PRS) for AAA was constructed using PRS-CS and grouped into tertiles. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were calculated from baseline blood counts. Incident AAA was identified through linked hospital, primary care, mortality, and self-report records. Cox models estimated hazard ratios (HRs), and mediation analyses quantified the proportion of the social isolation-AAA association explained by inflammatory indices. RESULTS:Over 15.6 years of follow-up, 1727 AAA events occurred. A social isolation index ≥2 was associated with higher AAA risk (HR 1.23; 95% CI 1.05-1.46), and each 1-SD increase corresponded to ~11% higher risk; loneliness was not associated with AAA. Although statistical interactions were non-significant, individuals with both high PRS and high social isolation had fourfold higher risk than those with low PRS and no isolation. SIRI, but not SII, was independently associated with AAA (HR 1.24; 95% CI 1.06-1.46) and mediated ~5% of the association. CONCLUSIONS:Social isolation, particularly in genetically susceptible individuals, identifies a population at substantially elevated AAA risk, partly via systemic immune-inflammatory activation, and may represent a modifiable target for prevention.

Background Preoperative coagulation dysfunction is a common complication among patients with acute type A aortic dissection (ATAAD). However, evidence regarding its association with prolonged mechanical ventilation (PMV) following emergency surgery remains limited. Methods Clinical data from 793 patients with ATAAD were retrospectively collected. Patients were stratified into two groups according to preoperative coagulation function indicators. Logistic regression and nomogram analyses were conducted to assess the relationship between coagulopathy and PMV in patients with ATAAD. Results Patients with coagulation dysfunction demonstrated a longer awakening time [9.0 (5.50, 14.0) h versus 7.50 (4.0, 13.0) h, P = 0.015], a higher incidence of PMV [243 (35.5%) versus 28 (25.7%), P = 0.044], a higher incidence of postoperative acute kidney injury (AKI) [382 (55.8%) versus 39 (35.8%), P < 0.001], and a greater requirement for continuous renal replacement therapy (CRRT) [60 (8.8%) versus 3 (2.8%), P = 0.031]. Multivariable logistic regression analysis indicated that PMV was significantly associated with age, duration of surgery, duration of cardiopulmonary bypass (CPB), preoperative lactic acid, creatinine, and fibrin degradation products (FDPs). Subgroup analysis further demonstrated that patients with preoperative FDP levels >15.27 μg/mL experienced poorer early postoperative outcomes. Conclusion Preoperative coagulopathy was associated with PMV in patients with ATAAD. These findings underscore the clinical relevance of coagulation dysfunction in preoperative risk stratification for ATAAD.

Gastrointestinal bleeding is a clinically important complication after emergency surgery for acute type A aortic dissection. Dedicated postoperative risk-stratification tools for this high-risk population remain limited. We aimed to develop and internally validate an early postoperative prediction model for gastrointestinal bleeding after acute type A aortic dissection repair and to compare logistic regression with commonly used machine-learning classifiers. We conducted a single-centre retrospective cohort study of 1,345 consecutive patients who underwent emergency acute type A aortic dissection repair between 5 December 2017 and 4 August 2022. Comprehensive clinical data, laboratory findings, imaging results, operative variables, transfusion data, and postoperative outcomes were collected. The cohort was divided into training and validation sets at a 70:30 ratio using stratified sampling. Candidate predictors were screened using least absolute shrinkage and selection operator logistic regression, and a clinically interpretable five-variable logistic regression model was developed. Model performance was assessed by discrimination, calibration, decision-curve analysis, repeated-split analysis, temporal validation, and comparison with tuned machine-learning classifiers. Overall, 108 patients (8.0

Background: While emergency surgery for acute type A aortic dissection (TAAD) is lifesaving, real-world delays occur. Current risk stratification lacks objective imaging criteria. We aimed to develop a computed tomography angiography (CTA)-based model to predict imminent rupture risk in TAAD. Methods: This retrospective study included 121 consecutive patients with TAAD, diagnosed at Beijing Anzhen Hospital between January 2024 and March 2025. Patients were classified into acute rupture (n=46, 38%) and non-acute (n=75, 62%) groups. The primary endpoint was acute rupture-related death within 14 days of symptom onset, rigorously defined by CTA evidence and/or clinical findings. Clinical and imaging variables were screened using univariable logistic regression, followed by least absolute shrinkage and selection operator (LASSO) regression. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, bootstrap validation, calibration, and decision curve analysis (DCA). Results: The overall acute rupture rate was 38% (46/121). The median age of the cohort was 56 years; 72% were men. Univariable analysis showed that rupture patients had higher inflammatory and ischemic marker levels and were more likely to present with circumferential dissection, aortic sinus entry tear, pericardial effusion, entry tear diameter >20 mm, and ascending aorta diameter >50 mm (all P<0.05). LASSO regression identified aortic sinus entry tear [odds ratio (OR) =23.60; 95% confidence interval (CI): 2.27-245.58; P=0.008] and circumferential aortic dissection (OR =8.27; 95% CI: 1.06-64.65; P=0.044) as independent predictors. The combined ROC curve yielded an area under the curve (AUC) of 0.872 (95% CI: 0.803-0.941) with good calibration and net clinical benefit on DCA. Conclusions: We developed and validated a parsimonious CTA-based prediction model with robust performance for identifying TAAD patients at the highest risk of acute rupture. This tool may aid in urgent triage and reinforce the imperative for expedited surgical intervention when these high-risk imaging features are present.

Background Thoracic endovascular aortic repair (TEVAR) is a primary treatment for complicated type B aortic dissection (TBAD). However, some patients eventually require open thoracoabdominal aortic replacement (TAAR). Comparative outcomes data for TAAR with vs without prior TEVAR remain limited. Methods In this single-centre retrospective study of 198 patients undergoing TAAR for TBAD, we compared outcomes between those with (n = 60) vs without (n = 138) prior TEVAR. The primary endpoint was a composite of in-hospital death, spinal cord injury, or stroke. Results The composite endpoint was significantly higher in the prior-TEVAR group (25.0% vs 7.3%, P < 0.001). In-hospital mortality was similar (11.7% vs 5.1%, P = 0.173), whereas spinal cord injury (10.0% vs 2.2%, P = 0.040) and cerebral hemorrhage (6.7% vs 0%, P = 0.012) were higher with prior TEVAR. Prior TEVAR independently predicted this composite outcome (odds ratio 3.72, P = 0.006). Patients with prior TEVAR had higher rates of reintubation (8.3% vs 1.5%, P = 0.046), and dialysis-requiring acute kidney injury also trended higher in this group (23.3% vs 12.3%, P = 0.050).Prior TEVAR was an independent predictor for late reintervention (hazard ratio 2.74, P = 0.030). Conclusions Prior TEVAR was associated with increased perioperative morbidity and late reintervention risk in patients undergoing TAAR for TBAD. This association underscores the need for enhanced perioperative management and long-term follow-up in this high-risk cohort.

Background:The cumulative impact of multidomain adverse exposures on abdominal aortic aneurysm (AAA) risk and the underlying metabolic pathways remain insufficiently understood. Methods:We analyzed 304,482 UK Biobank participants free of aortic aneurysm at baseline. Twenty-six exposures were grouped into five domains to derive domain specific and overall exposure scores. Associations with incident AAA were assessed using Cox models. To explore potential metabolic pathways, we applied a two stage NMR metabolomics framework combining multivariable linear regression, metabolite specific Cox models, and a 10-fold cross validated elastic net Cox model to generate a metabolite score. Mediation analyses and XGBoost models were also performed. Results:During a mean follow up of 14.9 years, 1,671 participants developed AAA. A higher overall exposure score was associated with an increased risk of incident AAA (per SD increase: HR, 1.08; 95% CI, 1.07-1.11). Among domain specific scores, the socioeconomic, social psychology, and lifestyle scores were independently associated with AAA, whereas the environmental pollution and living environment scores were not. Current smoking showed the strongest association among individual exposures (HR, 7.95; 95% CI, 6.81-9.27). Overall exposure burden was associated with broad metabolomic perturbations, and a 13-metabolite score was significantly associated with AAA (per SD increase: HR, 1.38; 95% CI, 1.35-1.41), mediating 5.78% of this association. Adding exposure and metabolite scores improved prediction beyond clinical factors alone. Conclusions:Greater multidomain adverse exposure burden was associated with higher incident AAA risk, partly through metabolic signatures related to inflammation and lipoprotein metabolism, and may provide incremental value for AAA risk stratification.

BACKGROUND:Uric acid (UA) is a routinely measured biomarker linked to cardiovascular and metabolic disorders, but its role in the development of aortic aneurysm (AA) and aortic dissection (AD) remains unclear. This study aimed to evaluate the association between UA levels and incident AA/AD. METHODS:We included 468,223 participants without baseline AA/AD from the UK Biobank prospective cohort. Baseline UA was measured and categorized by quartiles. The primary outcome was incident AA/AD. Cox proportional hazards models and restricted cubic spline (RCS) analyses were employed. Subgroup analyses were performed by age, sex, smoking status, blood pressure status, and history of coronary artery or cerebrovascular disease. RESULTS:During a median follow-up of 15.1 years, 4,504 AA/AD events were recorded. At baseline, elevated UA levels were significantly associated with decreased estimated glomerular filtration rate and increased C-reactive protein levels. AA/AD incidence increased across UA quartiles. In fully adjusted models, hazard ratios (HRs) for AA/AD were 1.00 (reference), 1.03 (95% CI 0.92-1.15), 1.04 (95% CI 0.92-1.16), and 1.17 (95% CI 1.04-1.31) from lowest to highest UA quartile. RCS analyses indicated a linear association between UA and AA/AD risk. The association was significant for AA (Q4 vs Q1: HR 1.15, 95% CI 1.02-1.31), but not for AD (Q4 vs Q1: HR 1.30, 95% CI 0.90-1.86). Subgroup analyses showed stronger associations in participants younger than 60 years, previous smokers, and those without prior coronary artery or cerebrovascular disease. Notably, the association remained statistically significant even in participants with clinically normal blood pressure. CONCLUSIONS:Elevated UA levels are independently associated with a higher risk of AA/AD, particularly AA. This association persists independently of hypertension and may be linked to inflammatory mechanisms and renal dysfunction. These findings support the role of UA as a potential biomarker for risk assessment and prevention of AA, especially in high-risk populations.

Backgrounds Venous drainage is a critical aspect of peripheral cardiopulmonary bypass (CPB) management in minimally invasive cardiac surgery (MICS), particularly for superior vena cava (SVC) drainage. The most commonly used method for SVC drainage currently is percutaneous cannulation via the internal jugular vein. However, this method still faces challenges in drainage efficiency, cosmetic outcomes, and puncture-related complications. This study aimed to compare the safety, effectiveness, and cosmetic outcomes of direct SVC cannulation (SVCC) and percutaneous internal jugular vein (PIJV) for SVC drainage in MICS. Methods A retrospective analysis was conducted of patients who underwent MICS with CPB at the Cardiovascular Surgery Department of the First Affiliated Hospital of Jinan University and Guangdong General Hospital between January 2012 and August 2023. In this study, 499 patients underwent SVCC, and 572 patients received PIJV for SVC drainage. Results In the SVCC group, one central venous catheter was mistakenly fixed with a purse-string suture (0.2%). In the PIJV group, complications included neck hematoma in 11 cases (1.9%), puncture site infection in 3 cases (0.5%), and catheter failure in 1 case (0.2%). Significant differences were noted in central venous pressure (CVP) during aortic cross-clamping (p < 0.001), duration of mechanical ventilation (p = 0.049), pleural drainage volume (p = 0.001) and lactate levels at Intensive Care Unit (ICU) admission (p < 0.001) between the two groups. Additionally, lactate levels were significantly different only in the subgroup of patients weighing > 50 kg. Patients with a CVP <= 0 mmHg during aortic cross-clamping exhibited lower lactate levels on ICU admission than those with CVP > 0 mmHg. Conclusion SVCC in MICS provides an easy and safe method with minimal complications, improved venous drainage, and better cosmetic results than the PIJV method.

Background:Chronic inflammation and genetic susceptibility are important factors in abdominal aortic aneurysm (AAA) pathogenesis, yet evidence regarding the impact of dietary inflammation on AAA risk remains limited. This study aimed to investigate the association between dietary inflammatory potential, genetic susceptibility, and systemic inflammation in relation to AAA incidence. Methods:In this prospective cohort study, 142,862 participants from the UK Biobank were followed over an average of 13.8 years. Dietary inflammatory potential was assessed using the Energy-Adjusted Dietary Inflammatory Index (E-DII), while genetic susceptibility was quantified using polygenic risk scores (PRS) derived via PRS-CS methodology. Systemic inflammation indices, including the Systemic Immune-Inflammation Index and the Systemic Inflammation Response Index (SIRI), as well as nutritional and immunological status assessed by the Prognostic Nutritional Index and the Controlling Nutritional Status score, were also examined. In addition, the mediating roles of systemic inflammation indices were evaluated. Results:Higher E-DII scores were significantly associated with increased AAA risk (HR: 1.36, 95% CI: 1.09-1.71). Individuals with high PRS and high E-DII exhibited a markedly elevated AAA risk compared to those with low PRS and low E-DII (HR: 3.04, 95% CI: 2.21-4.79). SIRI mediated 9.16% (95% CI: 4.81%-17.90%) of the association between dietary inflammation and AAA. Conclusion:This study demonstrates that both dietary inflammatory potential and genetic susceptibility are associated with increased AAA risk, highlighting SIRI as a critical mediator. These findings suggest the potential utility of integrating dietary strategies, genetic screening, and inflammatory biomarkers into targeted AAA prevention programs.

BackgroundThe difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) is closely associated with various adverse outcomes. This study aims to comprehensively evaluate the association between eGFRdiff, all-cause mortality, and the risk of multiple cardiovascular-related diseases.MethodsThis study analyzed data from 297,140 participants in the UK Biobank to assess the association between eGFRdiff, mortality, and the incidence of multiple cardiovascular-related diseases. eGFRdiff was classified into three groups: negative (< −15 mL/min/1.73 m2), intermediate (−15 to 15 mL/min/1.73 m2), and positive (≥ 15 mL/min/1.73 m2). Cox proportional hazards regression models were used to evaluate this association, while various sensitivity analyses were performed to assess its robustness.ResultsDuring a mean follow-up of 13.1 years, the positive eGFRdiff group exhibited significantly lower mortality, cardiovascular disease (CVD) incidence, and the occurrence of CVD-related conditions. In the fully adjusted model, participants in the negative eGFRdiff group had a hazard ratio of 1.44 (95% confidence interval [CI], 1.40–1.49) for all-cause mortality, 1.49 (95% CI, 1.41–1.59) for CVD incidence, and 1.25 (95% CI, 1.22–1.27) for CVD mortality. The risk of all 10 CVD-related conditions was also significantly higher in the negative group, whereas the positive group exhibited significantly lower risks. For every 10 mL/min/1.73 m2 increase in eGFRdiff, the incidence of various diseases decreased by approximately 10–19%.ConclusioneGFRdiff is significantly associated with increased risks of mortality, CVD incidence, and multiple CVD-related conditions. These findings underscore the critical need for developing targeted prevention strategies, particularly for populations with reduced eGFRdiff.

Stanford type A aortic dissection (TAAD) is a life-threatening disease. This study explored the role of LIM domain binding 3 (LDB3) in TAAD progression. Four datasets from the Gene Expression Omnibus were analyzed to identify TAAD-related hub genes. LDB3 single nucleotide polymorphisms (SNPs) were assessed in the UK Biobank. Western blotting and immunofluorescence detected LDB3 expression in angiotensin II (Ang II) stimulated human aortic vascular smooth muscle cells (HA-VSMC), human samples, and a murine model. Bioinformatics identified tissue inhibitor of metalloproteinase-1 (TIMP1) and LDB3 as TAAD hub genes. TIMP1 was expressed in macrophages, mesenchymal cells, and smooth muscle cells, while LDB3 was mostly expressed in smooth muscle cells. Validation showed TIMP1 was upregulated and LDB3 downregulated in TAAD. Six LDB3 SNPs were associated with aortic aneurysm and dissection in the UK Biobank. In human and murine samples, LDB3 expression was reduced in diseased tissues and co-localized with smooth muscle. Ang II-stimulated HA-VSMC exhibited LDB3 reduction and altered intercellular connections. The aforementioned findings suggest that the newly identified gene LDB3 is crucial in the progression of TAAD.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent comorbidity strongly associated with cardiovascular diseases, particularly in patients with aortic dissection (AD). However, the long-term impact of severe OSA on survival and distal aortic remodeling after total arch replacement for acute type A aortic dissection (ATAAD) remains unclear. OBJECTIVES: This study aimed to elucidate the specific long-term prognostic impact of severe OSA in patients undergoing ATAAD repair. METHODS: A total of 86 prospectively collected patients who underwent acute type A aortic dissection repair at Beijing Anzhen Hospital between January 2018 and December 2018 were enrolled in the study. All these patients underwent total aortic arch replacement. All patients underwent sleep monitoring within 90 days postoperatively. The association between severe OSA and major adverse events (MAEs) was analyzed using a multivariable Cox proportional hazards model. Kaplan-Meier survival analysis was performed to assess long-term survival. RESULTS: Of these 86 patients, 22 (25.6%) exhibiting severe OSA and 64 (74.4%) not. Individuals with severe OSA had a notably higher rate of major adverse events (MAEs) compared to those without severe OSA (27.3% vs. 7.8%, P =0.047) and a significantly lower long-term survival rate (81.8% vs. 97.4%, P =0.003). After adjusting for potential confounding variables, severe OSA remained an independent predictor of MAEs (HR=3.7, 95% CI: 1.1–12.4, P =0.032). Imaging follow-ups indicated that patients with severe OSA experienced significantly higher stent-graft distal aortic expansion rates (1.8 mm/year vs. 0.4 mm/year, P =0.030), abdominal aortic expansion rates (2.2 mm/year vs. 0.7 mm/year, P <0.001), and false lumen expansion rates in the descending aorta (2.5 mm/year vs. 0.8 mm/year, P =0.003). Moreover, partial thrombosis of the false lumen was more frequently observed in patients with severe OSA (40.9% vs. 14.1%, P =0.028). Conversely, complete false lumen thrombosis (64.1% vs. 45.5%, P =0.028) and false lumen patency (21.9% vs. 13.6%, P =0.028) were more commonly observed in patients without severe OSA. CONCLUSIONS: Severe OSA is associated with an elevated risk of MAEs and is implicated in abnormal distal aortic expansion and false lumen thrombosis among patients undergoing ATAAD repair. These results highlight the importance role of identifying and managing severe OSA in the long-term postoperative care of patients with ATAAD.

Background Shift work is associated with various health problems, but its impact on aortic aneurysm (AA) is unclear. The role of lifestyle factors in this regard is also less clear. This study aimed to explore the combined effects of shift work and lifestyle on AA risk. Methods A total of 213971 employed or self‐employed participants from the UK Biobank were included in the study. Employment and lifestyle information was collected. Cox proportional hazards regression models were applied to assess the association between shift work and AA. Restricted cubic spline functions, mediation, interaction, and joint analyses were used to further explore the relationship between unhealthy lifestyle, shift work, and AA risk. Results Among 213 971 participants, 1035 developed AA during a mean follow‐up of 14.9 years. In fully adjusted models, shift work was associated with a significantly higher risk of AA (hazard ratio [HR], 1.24 [95% CI, 1.06–1.46]), with frequent shift workers showing an elevated risk (HR, 1.27 [95% CI, 1.03–1.57]). A dose‐dependent relationship was observed between the unhealthy lifestyle score and the risk of AA, with the risk of AA increasing as the unhealthy lifestyle score increased. The joint effect of shift work and unhealthy lifestyle showed a significant association, particularly among shift workers with 4 to 5 unhealthy lifestyle factors (HR, 2.26 [95% CI, 1.63–3.14]). Conclusions In this cohort study, we found that shift work was significantly associated with an increased risk of AA. Additionally, unhealthy lifestyles, particularly smoking, may play a crucial role in this association. These findings underscore the need for targeted prevention strategies, especially for shift workers with unhealthy lifestyle factors.

Terazosin (TZ), a well-known antagonist of the α1-adrenergic receptor (α1-AR), has demonstrated protective effects on vascular endothelial cells (ECs) and reduced vascular stiffness in clinical studies. Endothelial dysfunction and oxidative stress are central drivers of cardiometabolic diseases such as diabetes, where sustained ROS burden accelerates EC senescence and barrier failure. These findings suggest its potential role in combating vascular aging and atherosclerosis; however, the underlying mechanisms remain partially understood. In this study, we investigated whether TZ can prevent atherosclerosis in ApoE-/- mice fed a high-cholesterol diet and aimed to elucidate the mechanisms involved. Our results showed that TZ significantly reduced plaque size, EC senescence, vascular permeability, and reactive oxygen species (ROS) levels, effectively inhibiting atherosclerosis independently of α1-AR signaling. In cultured primary human umbilical vein ECs (HUVECs), TZ inhibited EC senescence via the Pgk1/Hsp90 pathway. It enhanced the interaction between Hsp90 and the antioxidant enzyme peroxiredoxin 1 (Prdx1), leading to lower ROS levels-a key driver of cellular senescence. These findings were confirmed in atherosclerotic ApoE-/- mice. Furthermore, senescent ECs exhibited increased levels of vascular endothelial growth factor A (VEGFA) and decreased levels of angiostatin, contributing to higher vascular permeability and exacerbating atherosclerosis. TZ effectively reversed these changes. Overall, our study demonstrates that TZ primarily alleviates EC senescence and atherosclerosis through the Pgk1/Hsp90/Prdx1 pathway, highlighting Pgk1 activation as a strategy that may also mitigate endothelial dysfunction and oxidative stress in broader cardiometabolic contexts (e.g., diabetes), suggesting that TZ is a promising senomorphic agent for treating vascular aging and atherosclerosis in clinical settings and that Pgk1-targeted interventions could have implications beyond atherosclerosis.

Aortic disease is a series of life-threatening cardiovascular diseases, including aortic dissection (AD) and aortic aneurysm (AA). Rupture of the aorta is the main cause of death for AA and AD, the estimated global death rate related to AA and AD was 2.5-3.0 per 100,000 individuals. Type 2 diabetes mellitus (T2DM) had been known as an independent risk factor for diverse cardiovascular diseases, but it was said to be negatively associated with AA and AD. However, the causal relationship between T2DM and AA/AD remains unclear. Hypoglycemic drugs was also proven to be associated with lowering the risk of AA and prolonging the growth of AA, and the role of hypoglycemic drugs in the relationship between T2DM and AA/AD was not fully estimate. The current study aimed to clarify the causal relationship between T2DM and AA/AD. The potential indirect effect of hypoglycemic drugs was also estimated. We supposed that the protective effect from T2DM on AA/AD was mediated by hypoglycemic drugs. This study was a large prospective cohort study using data from the UK biobank. After exclusion of individuals considered type 1 diabetes mellitus and were diagnosed with AA/AD before their initial assessment visit, 496,410 individuals were enrolled. Then participants were divided into two groups based on prevalent T2DM at their initial assessment visit (22,713 in the T2DM group and 468,934 in the non-T2DM group). The endpoint was incidence of AA/AD, and the first date of diagnosis was collected. Multivariable Cox analysis was used to estimate hazard ratios (HR) and 95% confidence interval (CI) of T2DM on AA/AD by adjusting for confounders and mediators with 2 models: Model 1 adjusted for demographic characteristics and comobidities (hypertension and coronary artery disease); Model 2 further adjusted for hypoglycemic drugs based on Model 1. Furthermore, mediation analysis was conducted to further estimate the indirect effect that hypoglycemic drugs mediated and Bootstrap method was used to calculated the 95% CIs. During a median follow-up of 15.12 years, 4,763 cases of AA/AD occurred. After adjustment for Model 1, the total effect of T2DM on AA/AD is significant, but the direct effect was insignificant after adjustment for Model 2. Mediation analysis showed that usage of oral hypoglycemic drugs significantly mediated the protective effect of T2DM on AA/AD, especially on AA. The protective direct effect of T2DM on AA/AD is insignificant. The previously described protective role that T2DM played in AA/AD is predominantly mediated by oral hypoglycemic drugs. In the future, we plan to verify the effect of oral hypoglycemic drugs with cohort study and further estimate the effect of diverse drugs with drug target Mendelian randomization.Association between T2DM and AA/AD.Mediation analysis of hypoglycemic drugs

Context/Objectives:Metabolic syndrome (MetS) is associated with various diseases, yet its connection with aortic aneurysm (AA) is not well understood. The role of chronic inflammation as a mediator in this relationship also remains unclear. This study explores the combined effects of MetS and inflammation on AA risk. Methods:Data from 312,505 UK Biobank participants were analyzed to assess the relationship between MetS and AA. Cox proportional hazards regression models evaluated the association, while restricted cubic splines, mediation analyses, interaction assessments, and joint analyses explored the impact of inflammatory indicators, including the low-grade chronic inflammation (INFLA) score. Results:Over a mean follow-up of 14.6 years, 2,382 participants developed AA. MetS was associated with a higher AA risk (HR: 1.27; 95% CI: 1.16-1.39) in fully adjusted models. Each additional MetS component increased AA risk by 16%. Inflammatory markers, including the INFLA score, significantly mediated this relationship. Joint analyses revealed a stronger association in MetS patients with high INFLA scores (HR: 1.68; 95% CI: 1.45-1.95). Conclusion:MetS and its components notably elevate AA risk, with inflammation playing a key mediating role. These findings underscore the importance of targeted prevention strategies, particularly for MetS populations with high chronic inflammation.