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Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Abstract Introduction Underwater endoscopic mucosal resection (uEMR) technique has gained popularity for removal of large non-pedunculated colorectal polyps (LNPCPs) due to high en-bloc resection rates and lower recurrence rates. However, there is no information regarding outcomes of uEMR for giant colorectal polyps. Therefore, we aimed to evaluate the outcomes of uEMR for giant colorectal polyps across multiple centers in North America. Methods We conducted a multicenter retrospective study of adults with giant colorectal polyps undergoing uEMR between January 2019 and November 2025. Giant colorectal polyps were defined as LNPCPs ≥40 mm. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were severe adverse events (SAEs) and predictors of technical success, recurrence, and SAEs. Results A total of 137 polyps, with mean polyp size 47.6 mm were included. Majority of the lesions were located in right colon (61%, n = 83) with the most common histopathology being high-grade dysplasia (HGD) (31.4%, n = 43). Technical success was achieved in 90.5% (n = 124) with en-bloc resection rate of 11.7% (n = 16). Polyp fibrosis (OR: 0.08) and HGD (OR: 0.15) were independent predictors of inability to achieve technical success. Of 92 (67.1%) patients with follow-up, recurrent polyp was present in 8.7% (n = 8). SAEs were noted in 9.5%, consisting of delayed bleeding (9.5%, n = 13), while no delayed perforation or post polypectomy syndrome was noted. Discussion Our study demonstrates that uEMR is technically feasible for the removal of giant colorectal polyps with an acceptable safety profile and recurrence rate.

Abstract Background Helicobacter pylori is a major global pathogen with recognized potential for waterborne transmission. Intermittent water supply affects over one billion worldwide and may promote H. pylori contamination of municipal sources. Whether water supply discontinuity contributes to population-level H. pylori burden has not been examined globally. Materials and Methods We conducted a cross-sectional ecological analysis of 79 countries with matched utility-level water infrastructure data and country-level H. pylori prevalence estimates from a published global meta-analysis. The primary exposure was continuity of water supply (hours/day). Secondary exposures included non-revenue water percentage (NRW %), pipe breaks per utility, and operating cost coverage ratio. Unadjusted and adjusted linear regression models with heteroscedasticity-consistent standard errors were estimated, controlling for basic sanitation coverage and log-transformed population density. A sensitivity analysis used a population-based measure of water availability on demand. Results Greater water supply continuity was independently associated with lower H. pylori prevalence in both unadjusted (β = −0.987, 95% CI −1.669 to −0.305, p = 0.005) and adjusted models (β = −1.125, 95% CI −1.876 to −0.375, p = 0.004). Higher NRW % and lower operating cost coverage were each associated with higher H. pylori prevalence after adjustment. Pipe breaks were not significant in regression models though the Spearman correlation was in the expected direction. Sensitivity analysis produced consistent findings. Conclusion IWS and broader water infrastructure deterioration are associated with higher H. pylori prevalence at the country level. These findings implicate water supply continuity as a potentially relevant environmental determinant of H. pylori transmission and suggest a role for water system investment within long-term gastric cancer prevention strategies.

e16229 Background: Liver cancer is a leading cause of cancer-related mortality worldwide, with rising incidence linked to metabolic disorders. Conditions such as obesity, diabetes mellitus, and metabolic syndrome contribute substantially to non-viral liver carcinogenesis. However, long-term temporal trends and mortality disparities among adults with metabolic disorders in the United States remain incompletely characterized. Methods: Mortality data for liver cancer among adults with metabolic disorders were obtained from the centers for disease control and prevention (CDC) mortality database. Adults aged 25 years and older were included and age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Temporal trends were evaluated using joinpoint regression and average annual percent change (AAPC) with 95% confidence intervals. Results: From 1999–2023, AAMR for liver cancer in adults with metabolic disorders rose from 0.17 to 0.65 per 100,000 in the U.S., with an overall AAPC of 5.95% [95% CI 5.2–6.7]. Men had higher absolute mortality (0.25→0.93; AAPC 5.68%), while women showed a sharper recent rise (0.11→0.41; AAPC 7.08%), peaking at 11.86% annually after 2016. Hispanic/Latino (0.27→0.89; AAPC 6.73%) and Black populations (0.15→0.75; AAPC 6.15%) experienced steady increases, whereas White mortality accelerated post-2011 (AAPC 9.37%). Regionally, the West had highest rates, the South showed highest growth, and Northeast/Midwest had sharp recent increases. Rural mortality overtook urban by 2020 (0.50 vs. 0.48). Most deaths occurred in medical facilities (48.2%) or home (33.1%), with highest state rates in Hawaii (0.56), Texas (0.47), and Rhode Island (0.47). Conclusions: Mortality from liver cancer in adults with metabolic disorders rose sharply in the U.S. since 1999, with accelerating trends and marked disparities by sex, race/ethnicity, region, and urbanization. These findings highlight an urgent need for targeted metabolic risk reduction and equity-focused prevention strategies. Trends in Age-Adjusted Mortality Rates (AAMR) from 1999 to 2023 by demographic and geographic variables. Variable AAMR 1999 (per 100,000) AAMR 2023 (per 100,000) AAPC (95% CI) Overall 0.16 0.64 5.94* (5.22 – 6.67) Males 0.25 0.92 5.67* (4.82 – 6.5) Females 0.11 0.40 7.08* (5.79 – 8.38) White 0.16 0.63 6.12* (5.41 – 6.82) Black 0.15 0.75 6.15* (5.11 – 7.19) Hispanic or Latino 0.27 0.89 6.73* (5.98 – 7.48) Variable AAMR 1999 (per 100,000) AAMR 2020 (per 100,000) AAPC (95% CI) Urban 0.16 0.47 5.38* (4.43 – 6.33) Rural 0.19 0.50 5.73* (4.48 – 6.99) AAPC denotes the average annual percent change; * indicates p < 0.05.

Abstract Rationale Chronic thromboembolic disease (CTED), which is the result of persistent pulmonary vascular obstruction despite 3 months of anticoagulation, can present with significant functional limitations and exercise intolerance despite normal resting hemodynamics. These patients may experience functional impairment due to exercise-induced pulmonary hypertension, impaired stroke volume augmentation with exercise, ventilatory inefficiency, and/or preload insufficiency. Such exercise-induced pathophysiological abnormalities can significantly impair quality of life and contribute to poor long-term outcomes. Although balloon pulmonary angioplasty (BPA) has shown benefit in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its role in CTED patients with normal resting hemodynamics remains uncertain. This systematic review and meta-analysis evaluated the efficacy of BPA in this population. Methods A systematic search of PubMed, Cochrane, Embase, and Scopus was performed from inception through March 1, 2025. A total of 763 studies were screened, of which 42 full-text articles were assessed: six met the inclusion criteria (four retrospective, two prospective), comprising 98 patients. Results Across the included studies, baseline mean values were 20.81 +/- 3.62 mmHg for mean pulmonary arterial pressure (mPAP), 3.49 +/- 1.42 Wood units for pulmonary vascular resistance (PVR), and 405.72 +/- 108.40 m for the 6-minute walk distance (6MWD). Balloon Pulmonary Angioplasty (BPA) was consistently associated with significant improvements in hemodynamic and functional outcomes; BPA reduced mPAP by 3.40 mmHg and PVR by 0.90 WU, while increasing 6MWD by 31.90 m. These changes were also statistically robust across studies, with pooled standardized mean changes (SMC) of -0.88 for mPAP (95% CI, -1.10 to -0.67; P &lt; .05), -0.68 for PVR (95% CI, -0.87 to -0.49; P &lt; .05), and 0.29 for 6MWD (95% CI, 0.13 to 0.45; P &lt; .05). Study-level effect sizes for 6MWD ranged from 0.19 to 0.54 (Figure 1A). Functional improvements were further demonstrated by shifts in NYHA class distribution (Figure 1B). Conclusion BPA was associated with meaningful reductions in mPAP and PVR and significant improvements in functional capacity among patients with CTED. These results indicate that BPA could be an effective treatment for certain patients with CTED, though more research is necessary. This abstract is funded by: None

Abstract Rationale Chronic thromboembolic disease (CTED) is characterized by persistent pulmonary vascular obstruction due to unresolved thromboemboli despite at least three months of anticoagulation. Although resting hemodynamics often remain normal, affected patients frequently develop functional limitation due to exercise-induced pulmonary hypertension, ventilatory inefficiency, limited stroke volume augmentation, or preload insufficiency. Such exercise-induced pathophysiological dysregulation can significantly impair quality of life and contribute to poor long-term outcomes. Pulmonary endarterectomy (PEA) is an established treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH), offering significant improvements in hemodynamics and survival. Its role in CTED, however, remains unclear. While CTED has traditionally been managed with anticoagulation and supportive therapy, emerging evidence suggests PEA may provide symptomatic and functional benefit in selected CTED patients. Given the ongoing uncertainty regarding the role of PEA in CTED, we performed a systematic review and meta-analysis to define its safety profile and clinical efficacy in this patient subset. Methods A systematic search of PubMed, Cochrane, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar was conducted from database inception to March 1, 2025. Of 2,244 records screened, 34 full-text articles were assessed, and seven met the inclusion criteria. Results Across the included studies, the pooled baseline mean values were 20.48 ± 3.03 mm Hg for mean pulmonary arterial pressure (mPAP), 2.83 ± 1.11 Wood units for pulmonary vascular resistance (PVR), and 397 ± 100.08 m for the 6-minute walk distance (6MWD). Pulmonary Endarterectomy (PEA) was consistently associated with significant improvements in hemodynamic and functional outcomes; PEA reduced mPAP by 3.58 mmHg (pooled Standardized Mean Change (SMC)=-1.03; 95% CI, -1.23 to -0.83; P &lt; .05), PVR by 0.86 Woods units (pooled SMC=-0.86; 95% CI, -1.05 to -0.67; P &lt; .05), while, conversely, increased 6MWD by 37.49 m (pooled SMC, 0.49; 95% CI, 0.32 to 0.67; P &lt; .05). Study-level effect sizes for 6MWD ranged from 0.21 to 1.47 (Figure 1A). This clinical improvement is further reflected in the enhancement of the NYHA functional class, as illustrated in Figure 1B. Conclusion PEA was associated with significant reductions in mPAP and PVR, as well as a considerable improvement in functional capacity in patients with CTED, with robust results across multiple tests for bias, influence, and sensitivity analyses. These findings support PEA as a viable therapeutic option for selected patients with CTED, although further research is warranted. This abstract is funded by: None

Objective To comprehensively examine hypertension- and heart failure–related mortality rates in the United States to develop a targeted approach to health policy development. Methods We analyzed death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database, focusing on mortality caused by hypertensive heart failure in adults aged ≥25 years from 2006 to 2020. Age-adjusted mortality rates per 1,000,000 and annual percent changes were calculated and categorized by year, sex, race, urban status, age group, and census region. Results A total of 268,545 deaths occurred due to hypertensive heart failure between 2006 and 2020. The overall age-adjusted mortality rates increased from 60.5 in 2006 to 134.9 in 2020. Males had higher age-adjusted mortality rates than women (76.6 vs. 73.8). Older-aged people exhibited significantly higher age-adjusted mortality rates than young and middle-aged adults. Age-adjusted mortality rates were highest in non-Hispanic Blacks/African Americans and lowest in non-Hispanic Asians/Pacific Islanders (126.8–43.6). Furthermore, age-adjusted mortality rates were highest in individuals from nonmetropolitan areas and the Western region. Conclusion Following a period of decline, the age-adjusted mortality rates increased until 2020. The highest age-adjusted mortality rates were observed in non-Hispanic Blacks and nonmetropolitan areas. An urgent restructuring of healthcare policy is needed to reduce heart failure-associated mortality.

Abstract Objectives Minimally invasive cardiac surgery (MICS) offers significant advantages over conventional sternotomy, including reduced trauma and faster recovery. Preoperative planning is crucial, with computed tomography (CT) emerging as an essential imaging tool. This systematic review aims to evaluate CT’s role in MICS planning, focusing on imaging protocols, surgical guidance, and patient outcomes. Methods This study included studies published between January 2003 and January 2025 that examined the role of CT imaging in planning minimally invasive valvular heart surgery. A comprehensive search was conducted in Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Excerpta Medica Database (EMBASE) using predefined keywords and medical subject headings (MeSH) terms related to CT imaging, angiography, minimally invasive surgery, robotic surgery, aortic valve surgery, and mitral valve surgery. Results Initial search found 378 studies, and 17 studies were included in the review. The studies highlight CT’s value in assessing surgical feasibility, vascular access, and risk stratification. CT aids in selecting arterial cannulation sites, guiding aortic occlusion strategies, and optimizing port placement. It also identifies contraindications, such as extensive atherosclerosis and anatomical abnormalities, that may necessitate sternotomy. Conclusions Current evidence underscores CT’s critical role in optimizing MICS planning and enhancing patient safety.

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.