BACKGROUND:Left atrial appendage thrombus (LAAT) in non-valvular atrial fibrillation (AF) usually precludes catheter ablation and complicates left atrial appendage occlusion. Patients with persistent LAAT despite anticoagulation and heart failure have limited rhythm-control options. OBJECTIVE:To describe the feasibility and safety of combined occlusion and ablation therapy for LAAT (COAT), a same-session "thrombus-sealing first" strategy, in selected patients with persistent AF, heart failure, and persistent LAAT despite therapeutic oral anticoagulation. METHODS:This single-center retrospective proof-of-concept cohort included 5 patients who underwent COAT between January 2022 and April 2026. Left atrial appendage occlusion was performed first using a no-touch thrombus-trapping technique. Catheter ablation was performed after device release, confirmation of device stability and sealing, and absence of neurological abnormality. Follow-up included imaging and rhythm surveillance with electrocardiography and Holter monitoring. RESULTS:All 5 procedures were completed successfully, with first-attempt device deployment and pulmonary vein isolation in all patients. Sinus rhythm was restored in all patients. No periprocedural stroke, transient ischemic attack, systemic embolism, major bleeding, pericardial tamponade/effusion, device embolization, or death occurred. At a median imaging follow-up of 58 days, transesophageal echocardiography (TEE) confirmed complete LAA sealing without device-related thrombus in 4 patients; 1 patient declined TEE and cardiac computed tomography angiography. The 4 patients with TEE follow-up were transitioned from anticoagulation to lifelong single antiplatelet therapy. No thromboembolic or major bleeding events occurred. 4 patients remained arrhythmia-free. CONCLUSION:In this small, selected proof-of-concept cohort, COAT appeared feasible and was not associated with observed major complications. Larger prospective studies are required.

Recent research has indicated that cardiac lymphatic vessels (CLVs) serve as a direct drainage route into the mediastinal lymph nodes for inflammation resolution. However, the role of CLVs in coxsackievirus B3-induced acute viral myocarditis (AVMC) remains unknown. In this study, we found that AVMC in mice promoted pathological cardiac lymphangiogenesis while impairing CLV-mediated drainage, leading to heart inflammation and dysfunction. Overexpression of apelin in cardiomyocytes improved CLV integrity and promoted effective lymph drainage to decrease inflammatory responses and enhance cardiac function. In vitro studies revealed that apelin stabilizes lymphatic endothelial cadherin and zonula occludens 1 to enhance lymphatic function via the AKT signaling pathway. Moreover, pre-existing lymphatic defects induced by blocking vascular endothelial growth factor receptor 3 partially diminished the benefits of cardiomyocyte-derived apelin overexpression in AVMC. Taken together, these data indicate that functional CLVs restored by cardiomyocyte-derived apelin facilitate inflammation resolution and improve heart dysfunction in AVMC. Thus, CLV-based therapeutic strategies may serve as a novel approach for alleviating AVMC heart damage.

BackgroundThe optimal catheter ablation strategy for non-paroxysmal atrial fibrillation (non-PAF) is controversial. We examined the safety, feasibility, and efficacy of a new treatment strategy for non-PAF, defined as the Pulmonary vein isolation (PVI); left roof linear (RL), Mitral Isthmus linear (MIL), and left anterior SEptal linear (ASL) ablation; and leftatrial appendage (LAA) Device occlusion (PROMISED) procedure. MethodsOne-hundred forty-two patients with non-PAF underwent PVI + RL + ASL ablation with/without MIL ablation, combined with LAA occlusion (LAAO). The primary end point was atrial arrhythmia recurrence after a 3-month blanking period. ResultsEighty-two patients underwent the PROMISED procedure (MIL group) and 60 patients underwent PVI + RL + ASL ablation with LAAO without MIL ablation (Non-MIL group). The baseline characteristics were similar between the two groups. No serious procedure-related complications occurred during the procedure. Twelve months after a single procedure, atrial arrhythmia recurrence was observed in 17/82 patients (20.7%) in the MIL group versus 31/60 patients (51.7%) in the Non-MIL group (hazard ratio [HR]: 0.327 and 95% confidence interval [CI]: 0.181-0.592; p < 0.001). No peridevice leak > 5 mm was observed during the 12-month follow-up. Overall, 85.2% of the patients discontinued oral anticoagulant therapy within 6 months after the procedure. One patient experienced stroke in the MIL group 10 months after the procedure and one experienced stroke in the Non-MIL group 2 months after the procedure. ConclusionIn patients with non-PAF, the MIL group, which underwent the PROMISED procedure, was associated with a lower observed 12-month atrial arrhythmia recurrence rate without an apparent increase in complications.

Triglyceride-glucose (TyG) is a vital marker for assessing cardiovascular risk and insulin resistance (IR) in individuals with Type 2 diabetes mellitus (T2DM) or metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the prognostic significance of TyG, especially in patients manifesting both conditions, is insufficiently characterized. In this study, the association between TyG and the occurrence of major adverse cardiovascular events (MACEs) in patients concurrently diagnosed with T2DM and MASLD was examined. In this retrospective cohort study, 1021 patients diagnosed with both T2DM and MASLD at Wenzhou Hospital from 2019 to 2022 were encompassed. To explore the non-linear association between TyG and outcomes, such as all-cause mortality (ACM) or MACEs, a cox proportional hazards model was employed. Additionally, subgroups were analyzed to assess the consistency across different demographic and clinical subgroups. Furthermore, mediation analyses were conducted to investigate the potential mediating effects of body roundness index (BRI) and estimated glomerular filtration rate (eGFR). Parallel supportive analysis was performed on a cohort of 1343 individuals from NHANES 1999–2018. Over a median follow-up of 53.4 months, 62 instances of ACM and 101 MACEs were documented. Cox proportional hazards regression analysis revealed that an elevated TyG was significantly associated with an increased risk of mortality (HR = 1.85, 95

Pulse pressure has been commonly used to assess atherosclerosis and cardiovascular outcomes with the defects of fluctuation. However, the pulse pressure index (PPI), a feasible alternative with the advantage of lower fluctuations, has not been sufficiently researched. This study included 10,796 participants over 65 years from the National Health and Nutrition Examination Survey 1999–2018. Cox proportional hazards models, restricted cubic splines and subgroup analysis were used to investigate the association between PPI in the elderly and all-cause and cardiovascular mortality. Subsequently, a prediction model for identifying coronary heart disease (CHD) in elderly individuals was developed using three machine learning algorithms. The impact of each feature on CHD was visualized in the optimal model after comparing the performances of the models. This study discovered that the highest levels of PPI were associated with a 28

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett’s esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction ( P < 4.8 × 10 −5 ), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.

Pericardial-esophageal fistula is a rare complication after radiofrequency ablation for atrial fibrillation. A 52-year-old man developed pneumopericardium, which was revealed by echocardiogram and computed tomography, after a combined ablation and left atrial appendage occlusion procedure for atrial fibrillation. He was diagnosed with a pericardial-esophageal fistula and underwent surgical pericardial and mediastinal drainage tube placement. However, the patient developed constrictive pericarditis 2 months after the first surgery and subsequently underwent pericardiolysis. A month after the second surgery, the patient's condition was significantly improved and he was allowed home.

BACKGROUND:Cardiac lymphatic vessels are important channels for cardiac fluid circulation and immune regulation. In myocardial infarction and chronic heart failure, promoting cardiac lymphangiogenesis is beneficial in reducing cardiac edema and inflammation. However, the specific involvement of cardiac lymphangiogenesis in viral myocarditis (VMC) has not been studied. Despite the recognized participation of macrophages in lymphangiogenesis, the contribution of macrophages to cardiac lymphangiogenesis in VMC is still unclear. METHODS:The male Balb/c mice with VMC were grouped according to the time to explore changes in inflammation, cardiac function and lymphangiogenesis. Adeno-associated virus (AAV) was used to determine the effect of cardiac lymphangiogenesis in VMC. Macrophage depletion and VEGF-CC156S treatment were used to investigate the connection between macrophages and cardiac lymphangiogenesis. RESULTS:Cardiac inflammation and lymphatic vessel density were both upregulated, peaking on day 7 following CVB3 infection. After treatment with AAV-sVEGFR3, lymphangiogenesis was inhibited, leading to worsened cardiac dysfunction and aggravated inflammation. However, these effects were reversed by AAV-VEGF-C treatment. Furthermore, macrophages infiltrated the inflamed myocardium and secreted VEGF-C. In vitro, VEGF-C was upregulated when RAW264.7 cells were co-cultured with CVB3. Macrophage depletion in mice with VMC inhibited lymphangiogenesis, while supplementation with VEGF-CC156S depressed it. CONCLUSION:Collectively, these results indicate that activation of the VEGF-C/VEGFR3 axis exerts a protective effect in CVB3-induced VMC by resolving inflammation and alleviating cardiac dysfunction through increased lymphatic vasculature density, with macrophage-derived VEGF-C partially contributing to this effect.

Background:The clinical performance of left atrial appendage occlusion (LAAO) as a procedure and the long-term impact of its varied implantation configurations and anticoagulation regimens remain unclear. Objectives:This study sought to provide data in routine practice from a prospective multicenter registry. Methods:A total of 3,096 consecutive patients from 39 Chinese centers undergoing LAAO were enrolled between April 1, 2019, and October 31, 2020. Results:The baseline CHA2DS2-VASc and HAS-BLED scores were 4.0 ± 1.8 and 2.4 ± 1.2, respectively; mean age was 69 ± 9 years. One-year follow-up was completed in 3,013 (97.8%) patients. The ischemic endpoint of death, stroke, and systemic embolism occurred in 133 (4.51%) patients, and life-threatening, disabling, or major bleeding occurred in 71 (2.36%) patients. After inverse probability of treatment weighting, no significant association was found between anesthesia type (moderate sedation vs general anesthesia) or image guidance (transesophageal/intracardiac echocardiography vs fluoroscopy) and ischemic or bleeding events. In 1,295 (42.0%) cases, LAAO combined with catheter ablation was associated with a significantly lower rate of death, stroke, or systemic embolism than LAAO only (3.5% vs 5.2%, inverse probability of treatment weighting HR: 0.68; 95% CI: 0.47-0.99). The most common post-LAAO antithrombotic regimen was warfarin/direct oral anticoagulant monotherapy for 45 days, followed by single-/dual-antiplatelet therapy (38.1%). Conclusions:In Chinese centers, patients undergoing LAAO had low rates of ischemic and bleeding events at 1 year. Combining LAAO with catheter ablation was associated with a lower rate of ischemic events than LAAO only. (Registry to Evaluate Chinese Real-World Clinical Outcomes in Patients With Atrial Fibrillation Using the Watchman Left Atrial Appendage Closure Technology [RECORD]; NCT03917563).

BACKGROUND:The relationship between long-term outcomes and operator experience for left atrial appendage occlusion (LAAO) is still unknown. OBJECTIVES:This study sought to explore the association between operator LAAO experience and one-year clinical outcomes. METHODS:The RECORD study (Registry to Evaluate Chinese Real-World Clinical Outcomes in Patients With AF Using the WATCHMAN Left Atrial Appendage Closure Technology; NCT03917563) was a multicenter, prospective registry that included patients with the WATCHMAN LAAO device (Boston Scientific) in China from April 1, 2019, to October 31, 2020. The current analyses included patients with solely LAAO from the registry; those who had concomitant LAAO and ablation/other procedures were excluded. The primary outcome was a composite endpoint of death, stroke, systemic embolism, and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding at 1 year. RESULTS:A total of 1,547 LAAO patients and 111 operators were included. The mean CHA2DS2-VASc and HAS-BLED scores of patients were 4.0 ± 1.8 and 2.5 ± 1.1, respectively. The mean age of operators was 47.0 ± 7.2 years, 15 (13.5%) were female, and 52 (46.8%) were electrophysiologists. Utilizing maximally selected log-rank statistics, the thresholds to categorize an experienced operator were performing ≥32 LAAOs annually or ≥134 LAAOs in total. Performing ≥32 LAAOs annually is the better criterion than ≥134 LAAOs in total (absolute net reclassification index: 25.79%; P < 0.001). Compared with the ≥32 LAAO annually group, the <32 group was associated with a 1.8-fold (HRadjusted: 1.79; 95% CI: 1.16-2.78; P = 0.009) increase in the risk of the primary endpoint, and such risk in the <32 group can be reduced by ∼12% after performing each additional 5 cases (HRadjusted per 5 cases: 0.88; 95% CI: 0.78-0.99; P = 0.033). CONCLUSIONS:Performing ≥32 LAAOs annually could be a threshold to categorize an experienced operator. Before reaching this threshold, the risk of death, stroke, systemic embolism, and BARC-defined type 3 or 5 bleeding decreased by 12% after every 5 cases performed.

Rationale: Parkin (an E3 ubiquitin protein ligase) is an important regulator of mitophagy. However, the role of Parkin in viral myocarditis (VMC) remains unclear. Methods: Coxsackievirus B3 (CVB3) infection was induced in mice to create VMC. Cardiac function and inflammatory response were evaluated by echocardiography, histological assessment, and molecular analyses. AAV9 (adeno-associated virus 9), transmission electron microscopy (TEM) and western blotting were used to investigate the mechanisms by which Parkin regulates mitophagy and cardiac inflammation. Results: Our data indicated that Parkin- and BNIP3 (BCL2 interacting protein 3 like)-mediated mitophagy was activated in VMC mice and neonatal rat cardiac myocytes (NRCMs) infected with CVB3, which blocked autophagic flux by inhibiting autophagosome-lysosome fusion. Parkin silencing aggravated mortality and accelerated the development of cardiac dysfunction in CVB3-treated mice. While silencing of Parkin did not significantly increase inflammatory response through activating NF-κB pathway and production of inflammatory cytokines post-VMC, the mitophagy activity were reduced, which stimulated the accumulation of damaged mitochondria. Moreover, Parkin silencing exacerbated VMC-induced apoptosis. We consistently found that Parkin knockdown disrupted mitophagy activity and inflammatory response in NRCMs. Conclusion: This study elucidated the important role of Parkin in maintaining cardiac function and inflammatory response by regulating mitophagy activity and the NF-κB pathway during acute VMC. Although the functional impact of mitophagy remains unclear, our findings suggest that Parkin silencing may accelerate VMC development.

BackgroundInsulin resistance (IR) is closely correlated with a deficiency or decrease of testosterone levels in males. Cardiometabolic index (CMI) is correlated with various diseases correlated with IR. The primary objective of this study is to explore the correlation between CMI and testosterone levels in male adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES) during the period from 2013 to 2020 were analyzed through a cross-sectional design. CMI was calculated by multiplying waist-to-height ratio (WHtR) with the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C).ResultsA total of 5012 subjects were included in the final analysis. After controlling confounding variables, multiple linear regression analysis indicated an independent negative correlation between CMI and testosterone levels (β= -6.40, 95% CI: -8.95, -3.86, P<0.001) through the. In addition, a negative non-linear correlation was also found between CMI and testosterone (P<0.05), with CMI’s inflection point as 0.73. Subgroup analyses indicated a more significant negative correlation among those with normal weight and the elderly (p< 0.05 for all interactions). The area under the ROC curve (AUC) of CMI (AUC =0.724, 95% CI: 0.709–0.740) was the largest compared with those of TG/HDL and WHtR.ConclusionElevated CMI is significantly and negatively correlated with testosterone in male adults.

Background and aim: Rivaroxaban is an emerging oral anticoagulant for postoperative anticoagulation after percutaneous left atrial appendage closure (LAAC). Because a once-daily dosing regimen of rivaroxaban causes fluctuations in the drug plasma concentration, we studied the feasibility and safety of twice-daily rivaroxaban as a postoperative anticoagulation regimen for patients with atrial fibrillation (AF) undergoing LAAC.Methods: This study involved patients with AF who underwent LAAC and took rivaroxaban postoperatively. A total of 326 patients who received a standard total dose (15 or 20 mg) of rivaroxaban based on their creatinine clearance rate were divided into the twice-daily (BID) rivaroxaban group (n = 208) and once-daily (QD) rivaroxaban group (n = 118) according to their anticoagulation strategy. Transesophageal echocardiography was recommended at 3–6 months postoperatively to check for device-related thrombosis (DRT). Clinical outcomes were evaluated during postoperative anticoagulation.Results: The median CHA2DS2-VASc score (4 [3, 5] vs. 4 [3, 5], p = 0.28) and HAS-BLED score (2 [2, 3] vs. 2 [2, 3], p = 0.48) were not significantly different between the groups. During the anticoagulation period (4.1 ± 0.7 vs. 4.1 ± 0.9 months, p = 0.58), 148 (71.2%) patients in the BID group and 75 (63.6%) in the QD group underwent follow-up transesophageal echocardiography. There were no statistically significant differences between the two groups in terms of DRT (1.4% vs. 2.7%, p = 0.60), minor bleeding (8.2% vs. 11.0%, p = 0.39), thromboembolic events (1.0% vs. 0.8%, p = 1.00), major bleeding (0.5% vs. 0.8%, p = 1.00), or death.Conclusion: A short course of twice-daily rivaroxaban following LAAC is a feasible alternative regimen with a low rate of major bleeding events, DRT, and thromboembolic events for patients with AF.

AIMS:A three-dimensional electroanatomic mapping system-guided transseptal puncture (3D-TSP), without fluoroscopy or echocardiography, has been only minimally reported. Indications for 3D-TSP remain unclear. Against this background, this study aims to establish a precise technique and create a workflow for validating and selecting eligible patients for fluoroless 3D-TSP. METHODS AND RESULTS:We developed a new methodology for 3D-TSP based on a unipolar electrogram derived from a transseptal needle tip (UEGM tip) in 102 patients (the derivation cohort) with intracardiac echocardiography (ICE) from March 2018 to February 2019. The apparent current of injury (COI) was recorded at the muscular limbus of the foramen ovalis (FO) on the UEGM tip (sinus rhythm: 2.57 ± 0.95 mV, atrial fibrillation: 1.92 ± 0.77 mV), which then disappeared or significantly reduced at the central FO. Changes in the COI, serving as a major criterion to establish a 3D-TSP workflow, proved to be the most valuable indicator for identifying the FO in 99% (101/102) of patients compared with three previous techniques (three minor criteria) of reduction in atrial unipolar or bipolar potential and FO protrusion. A total of 99.9% (1042/1043) patients in the validation cohort underwent successful 3D-TSP through the workflow from March 2019 to July 2023. Intracardiac echocardiography guidance was required for 6.6% (69/1042) of patients. All four criteria were met in 740 patients, resulting in a 100% pure fluoroless 3D-TSP success rate. CONCLUSION:In most patients, fluoroless 3D-TSP was successfully achieved using changes in the COI on the UEGM tip. Patients who met all four criteria were considered suitable for 3D-TSP, while those who met none required ICE guidance.

BackgroundPatients with non-valvular atrial fibrillation (NVAF) and previous stroke have a significantly higher risk of stroke recurrence. This study aimed to examine the safety and efficacy of the LAmbre left atrial appendage occlusion device in NVAF patients with a history of stroke.MethodsWe examined 103 consecutive NVAF patients in 11 Chinese medical centers who had a history of stroke or transient ischemic attacks (TIA) and underwent placement of the LAmbre device. Follow-up was conducted 1, 3, 6, and 12 months after the procedure. The primary endpoints were the incidence of new ischemic or hemorrhagic stroke, TIA, systemic embolism, or cardiac death. Secondary endpoints were serious perioperative or device-related complications and cerebral, gastrointestinal, or other bleeding events requiring transfusion of at least 2 units of packed red blood cells.ResultsMean patient age was 67.63 +/- 7.14 years; mean CHA2DS2-VASc score was 4.72 +/- 1.18 and mean HAS-BLED score was 1.90 +/- 1.00. LAmbre device placement was successful in 101 patients (98.05%). Mean follow-up was 12.2 months. Five patients (4.95%) developed a new pericardial effusion after the procedure; none required treatment. Eighty-six patients (85.15%) exhibited no peri-device leak (PDL). However, 13 (12.8%) had a small (0-3 mm) PDL and two (2.3%) had a moderate PDL (3-5 mm). One recurrent stroke occurred during follow-up (1.1%). No other complications occurred.ConclusionsThis multicenter study shows the safety and efficacy of LAmbre left atrial appendage occlusion for NVAF patients with a history of stroke or TIA.

BACKGROUND:The MemoLefort is a new plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF). This study compares the safety and efficacy of MemoLefort and the well-established Watchman occluder for LAAC. METHODS:Between January 2021 and September 2022, a cohort of 189 consecutive patients who underwent LAAC with MemoLefort or Watchman at The Second Affiliated Hospital of Wenzhou Medical University were included. Patients with MemoLefort or Watchman devices were compared in terms of the primary safety endpoints encompassing major periprocedural complications and major bleeding events at follow-up, the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, and the combined hazard endpoint, a composite of all the above-mentioned hazards. RESULTS:Of the MemoLefort group (n = 83) and Watchman group (n = 106), the mean age, CHA2DS2-VASc score, and HAS-BLED score were 67.6 ± 9.2 vs. 69.0 ± 10.6 years, 3.9 ± 1.9 vs. 3.8 ± 1.9, and 1.6 ± 1.0 vs. 1.7 ± 1.2, respectively. After a median follow-up duration of 198 (99-329) vs. 334 (171-497) days, the primary endpoints of efficacy [2/49, 4.1% (MemoLefort) vs. 2/97, 2.1% (Watchman); hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.20-11.08; P = 0.68] and safety (1/49, 2.0% vs. 5/97, 5.2%; HR, 0.26; 95% CI, 0.05-1.31; P = 0.19), as well as the combined hazard endpoint (3/49, 61% vs. 6/97, 6.2%; HR, 0.70; 95% CI, 0.18-2.58; P = 0.59) were similar between groups. CONCLUSIONS:In the short term, LAAC with MemoLefort provided similar efficacy, safety, and net clinical benefit in comparison to Watchman devices.

Objectives: To investigate excessive dietary salt intake as an independent risk factor of cognitive impairment and dementia in older adults.Design: Prospective, population-based cohort study.Settings and Participants: Two thousand forty-one community residents aged >= 60 years were recruited between April 2007 and August 2009 from the Shandong area of China. Measurements: Participants were classified into low, mild, moderate, and high salt intake groups according to urinary sodium measurements for 7 consecutive days. Global cognitive function was assessed at baseline and biennially thereafter using the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Dementia Rating Scale (DRS), and Informant Questionnaire on Cognitive Decline in the Elderly. Demographics and apolipoprotein E (APOE) genotype were also obtained for each participant. Participants were monitored for 11.4 +/- 2.0 years.Results: During follow-up, MMSE, MoCA, and DRS scores decreased progressively faster with increasing salt intake (Padjustment < 0.05 among all intake groups). In total, 319 participants (13.74 per 1000 personyears) developed cognitive impairment. Compared with the low salt intake group, cognitive impairment risk was increased by 75% in the mild group (Padjustment = 0.027), 180% in the moderate group (Padjustment < 0.001), and 330% in the high group (Padjustment < 0.001) after adjustment for age, education, mean, and variability in visit-to-visit systolic and diastolic blood pressure, and APOE genotype. The hazard ratio for cognitive impairment increased by 1.59 (95% CI 1.40-1.79) with each 1-SD increment in salt intake after confounder adjustment (Padjustment < 0.001).Conclusions and Implications: Excessive dietary salt impairs cognitive function and increases cognitive impairment risk in older adults independently of known risk factors, including hypertension and APOE genotype.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).