Circulation最新文献

{"title":"Declining Trend of Sudden Cardiac Death in Younger Individuals: A 20-Year Nationwide Study.","authors":"Carl Johann Hansen, Jesper Svane, Peder Emil Warming, Thomas Hadberg Lynge, Rodrigue Garcia, Carolina Malta Hansen, Christian Torp-Pedersen, Jytte Banner, Bo Gregers Winkel, Jacob Tfelt-Hansen","doi":"10.1161/CIRCULATIONAHA.124.069431","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069431","url":null,"abstract":"<p><strong>Background: </strong>Declining cardiovascular mortality rates have been well-documented, yet temporal trends of sudden cardiac death (SCD) in young individuals remain unclear. We provide contemporary nationwide estimates of the temporal trends of SCD in young individuals (1-35 years of age) from 2000 through 2019 and correlate these trends to changes in out-of-hospital cardiac arrest (OHCA) patterns, rates of inherited cardiac diseases, and implantations of implantable cardioverter defibrillators (ICD).</p><p><strong>Methods: </strong>All individuals between 1 and 35 years of age living in Denmark from 2000 through 2019 were included, with annual re-evaluation of the at-risk population in regard to age. Adjudication of SCD cases relied on multiple sources, including death certificates, medical files, and autopsy reports. Information on OHCA, diagnostic rates, and ICD implantations were captured from nationwide administrative registries. Annual incidence rates of SCD were calculated, and temporal trends in SCD incidence were computed as percentage change annualized. Trends in OHCA survival and characteristics, diagnostic rates of inherited cardiac diseases, and ICD implantations were assessed.</p><p><strong>Results: </strong>During the 20-year study period (47.5 million person-years), 1057 SCDs were identified (median age, 29 years; 69% male). The overall incidence of SCD was 2.2 per 100 000 person-years and declined by 3.31% (95% CI, 2.42-4.20) annually, corresponding to a 49% (95% CI, 38.7-57.6) reduction during the study. Rates of witnessed SCD declined markedly (percentage change annualized -7.03% [95% CI, -8.57 to -5.48]), but we observed no changes in the rate of unwitnessed SCD (percentage change annualized -0.09% [95% CI, -1.48 to 1.31]). Therefore, the proportion of unwitnessed SCD increased by 79% (<i>P</i><0.001). Survival after OHCA in young individuals (1 to 35 years of age) increased from 3.9% to 28%, mainly because of increased bystander cardiopulmonary resuscitation and defibrillation rates. Diagnostic rates of inherited cardiac diseases increased 10-fold (incidence rate ratio, 10.4 [95% CI, 8.46-12.90]) and the ICD implantation rate increased 2-fold (incidence rate ratio, 1.97 [95% CI, 1.51-2.60]).</p><p><strong>Conclusions: </strong>SCD incidence rates in young individuals declined by 49% over the past 2 decades. The decline was paralleled by improved survival of OHCA, higher diagnostic rates of inherited cardiac diseases, and higher ICD implantation rates. However, rates of unwitnessed SCD were unchanged, which calls for new perspectives in preventive strategies.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis.","authors":"Brendon L Neuen, Robert A Fletcher, Lauren Heath, Adam Perkovic, Muthiah Vaduganathan, Sunil V Badve, Katherine R Tuttle, Richard Pratley, Hertzel C Gerstein, Vlado Perkovic, Hiddo J L Heerspink","doi":"10.1161/CIRCULATIONAHA.124.071689","DOIUrl":"10.1161/CIRCULATIONAHA.124.071689","url":null,"abstract":"<p><strong>Background: </strong>GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter 2) inhibitors both improve cardiovascular and kidney outcomes in people with type 2 diabetes. We conducted a systematic review and meta-analysis to assess the effects of GLP-1 receptor agonists on clinical outcomes with and without SGLT2 inhibitors.</p><p><strong>Methods: </strong>We searched MEDLINE and Embase databases from inception until July 12, 2024, for randomized, double-blind, placebo-controlled outcome trials of GLP-1 receptor agonists in type 2 diabetes that reported treatment effects by baseline use of SGLT2 inhibitors, with findings supplemented by unpublished data. We estimated treatment effects by baseline SGLT2 inhibitor use using inverse variance-weighted meta-analysis. The main cardiovascular outcomes were major adverse cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure. Kidney outcomes included a composite of ≥50% reduction in estimated glomerular filtration rate, kidney failure or death caused by kidney failure, and annualized rate of decline in estimated glomerular filtration rate (estimated glomerular filtration rate slope). Serious adverse events and severe hypoglycemia were also evaluated. This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024565765).</p><p><strong>Results: </strong>We identified 3 trials with 1743 of 17 072 (10.2%) participants with type 2 diabetes receiving an SGLT2 inhibitor at baseline. GLP-1 receptor agonists reduced the risk of major adverse cardiovascular events by 21% (hazard ratio [HR], 0.79 [95% CI, 0.71-0.87]), with consistent effects in those receiving and not receiving SGLT2 inhibitors at baseline (HR, 0.77 [95% CI, 0.54-1.09] and HR, 0.79 [95% CI, 0.71-0.87], respectively; <i>P</i>-heterogeneity=0.78). The effect on hospitalization for heart failure was similarly consistent regardless of SGLT2 inhibitor use (HR, 0.58 [95% CI, 0.36-0.93] and HR, 0.73 [95% CI, 0.63-0.85]; <i>P</i>-heterogeneity=0.26). Effects on the composite kidney outcome (risk ratio, 0.79 [95% CI, 0.66-0.95]) and estimated glomerular filtration rate slope (0.78 mL/min/1.73 m²/y [95% CI, 0.57-0.98]) also did not vary according to SGLT2 inhibitor use (<i>P</i>-heterogeneity=0.53 and 0.94, respectively). Serious adverse effects and severe hypoglycemia were also similar regardless of SGLT2 inhibitor use (<i>P</i>-heterogeneity=0.29 and 0.50, respectively).</p><p><strong>Conclusions: </strong>In people with type 2 diabetes, the cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of SGLT2 inhibitor use.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1781-1790"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.","authors":"William F McIntyre, Alexander P Benz, Jeff S Healey, Stuart J Connolly, Mu Yang, Shun Fu Lee, Thalia S Field, Marco Alings, J Benezet-Mazuecos, Giuseppe Boriani, J Cosedis Nielsen, Michael R Gold, Francesco Pergolini, Taya V Glotzer, Christopher B Granger, Renato D Lopes","doi":"10.1161/CIRCULATIONAHA.124.069903","DOIUrl":"10.1161/CIRCULATIONAHA.124.069903","url":null,"abstract":"<p><strong>Background: </strong>In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population.</p><p><strong>Methods: </strong>We performed a retrospective cohort study in ARTESiA. Using Cox regression adjusted for CHA₂DS₂-VASc score and treatment allocation (apixaban or aspirin), we assessed frequency of SCAF episodes and duration of the longest SCAF episode in the 6 months before randomization as predictors of stroke risk and of apixaban treatment effect.</p><p><strong>Results: </strong>Among 3986 patients with complete baseline SCAF data, 703 (17.6%) had no SCAF episode ≥6 minutes in the 6 months before enrollment. Among 3283 patients (82.4%) with ≥1 episode of SCAF ≥6 minutes in the 6 months before enrollment, 2542 (77.4%) had up to 5 episodes, and 741 (22.6%) had ≥6 episodes. The longest episode lasted <1 hour in 1030 patients (31.4%), 1 to <6 hours in 1421 patients (43.3%), and >6 hours in 832 patients (25.3%). Higher baseline SCAF frequency was not associated with increased risk of stroke or systemic embolism: 1.1% for 1 to 5 episodes versus 1.2%/patient-year for ≥6 episodes (adjusted hazard ratio, 0.89 [95% CI, 0.59-1.34]). In an exploratory analysis, patients with previous SCAF but no episode ≥6 minutes in the 6 months before enrollment had a lower risk of stroke or systemic embolism than patients with at least one episode during that period (0.5% versus 1.1%/patient-year; adjusted hazard ratio, 0.48 [95% CI, 0.27-0.85]). The frequency of SCAF did not modify the reduction in stroke or systemic embolism with apixaban (<i>P</i>_interaction=0.1). The duration of the longest SCAF episode in the 6 months before enrollment was not associated with the risk of stroke or systemic embolism during follow-up (<1 hour: 1.0%/patient-year [reference]; 1-6 hours: 1.2%/patient-year [adjusted hazard ratio, 1.27 (95% CI, 0.85-1.90)]; >6 hours: 1.0%/patient-year [adjusted hazard ratio, 1.02 (95% CI, 0.63-1.66)]). SCAF duration did not modify the reduction in stroke or systemic embolism with apixaban (<i>P</i>_trend=0.1).</p><p><strong>Conclusions: </strong>In ARTESiA, baseline SCAF frequency and longest episode duration were not associated with risk of stroke or systemic embolism and did not modify the effect of apixaban on reduction of stroke or systemic embolism.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT01938248.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1747-1755"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Complications and Their Association With Short- and Long-Term Outcomes in Patients With Multiple Myeloma and Lymphoma Undergoing Chimeric Antigen Receptor T-Cell Therapy.","authors":"Osnat Itzhaki Ben Zadok, Panagiotis Simitsis, Caron Jacobson, Omar Nadeem, Matthew J Frigault, Noopur Raje, Caitlyn Duffy, Patrick Costello, Jamie Dela Cruz, Andrew Looka, Anju Nohria","doi":"10.1161/CIRCULATIONAHA.124.070432","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070432","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 22","pages":"1815-1817"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technologic Advances in Cardiac Electrophysiology.","authors":"Jonathan P Piccini, Augustus Grant","doi":"10.1161/CIRCULATIONAHA.124.071542","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071542","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 22","pages":"1745-1746"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Role for the Intracellular Cell Death Mediator RIPK3 in Myocardial Infarction.","authors":"Dongze Qin, Radheshyam Modanwal, Richard N Kitsis","doi":"10.1161/CIRCULATIONAHA.124.072172","DOIUrl":"10.1161/CIRCULATIONAHA.124.072172","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 22","pages":"1812-1814"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Genetic Variants in <i>LDLR</i>, <i>APOB</i>, and <i>PCSK9</i> Are Associated With Aortic Stenosis.","authors":"Joel T Rämö, Sean J Jurgens, Shinwan Kany, Seung Hoan Choi, Xin Wang, Andrey N Smirnov, Samuel F Friedman, Mahnaz Maddah, Shaan Khurshid, Patrick T Ellinor, James P Pirruccello","doi":"10.1161/CIRCULATIONAHA.124.070982","DOIUrl":"10.1161/CIRCULATIONAHA.124.070982","url":null,"abstract":"<p><strong>Background: </strong>Despite a proposed causal role for LDL-C (low-density lipoprotein cholesterol) in aortic stenosis (AS), randomized controlled trials of lipid-lowering therapy failed to prevent severe AS. We aimed to assess the impact on AS and peak velocity across the aortic valve conferred by lifelong alterations in LDL-C levels mediated by protein-disrupting variants in 3 clinically significant genes for LDL (low-density lipoprotein) metabolism (<i>LDLR</i>, <i>APOB</i>, and <i>PCSK9</i>).</p><p><strong>Methods: </strong>We used sequencing data and electronic health records from UK Biobank (UKB) and All of Us and magnetic resonance imaging data from UKB. We identified predicted protein-disrupting variants with the Loss Of Function Transcript Effect Estimator (LOFTEE) and AlphaMissense algorithms and evaluated their associations with LDL-C and peak velocity across the aortic valve (UK Biobank), as well as diagnosed AS and aortic valve replacement (UK Biobank and All of Us).</p><p><strong>Results: </strong>We included 421 049 unrelated participants (5621 with AS) in UKB and 195 519 unrelated participants (1087 with AS) in All of Us. Carriers of protein-disrupting variants in <i>LDLR</i> had higher mean LDL-C (UKB: +42.6 mg/dL; <i>P</i>=4.4e-237) and greater risk of AS (meta-analysis: odds ratio, 3.52 [95% CI, 2.39-5.20]; <i>P</i>=2.3e-10) and aortic valve replacement (meta-analysis: odds ratio, 3.78 [95% CI, 2.26-6.32]; <i>P</i>=4.0e-7). Carriers of protein-disrupting variants in <i>APOB</i> or <i>PCSK9</i> had lower mean LDL-C (UKB: -32.3 mg/dL; <i>P</i><5e-324) and lower risk of AS (meta-analysis: odds ratio, 0.49 [95% CI, 0.31-0.75]; <i>P</i>=0.001) and aortic valve replacement (meta-analysis: odds ratio, 0.54 [95% CI, 0.30-0.97]; <i>P</i>=0.04). Among 57 371 UKB imaging substudy participants, peak velocities across the aortic valve were greater in carriers of protein-disrupting variants in <i>LDLR</i> (+12.2 cm/s; <i>P</i>=1.6e-5) and lower in carriers of protein-disrupting variants in <i>PCSK9</i> (-6.9 cm/s; <i>P</i>=0.022).</p><p><strong>Conclusions: </strong>Rare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively. Early and sustained lipid-lowering therapy may slow or prevent AS development.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1767-1780"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter by Zhang et al Regarding Article, \"Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era\".","authors":"Meng Zhang, Xudong Pan, Xiaoyan Zhu","doi":"10.1161/CIRCULATIONAHA.124.070129","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070129","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 22","pages":"e467"},"PeriodicalIF":35.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.","authors":"Dorothea Kehr, Julia Ritterhoff, Manuel Glaser, Lukas Jarosch, Rafael E Salazar, Kristin Spaich, Karl Varadi, Jennifer Birkenstock, Michael Egger, Erhe Gao, Walter J Koch, Max Sauter, Marc Freichel, Hugo A Katus, Norbert Frey, Andreas Jungmann, Cornelius Busch, Paul J Mather, Arjang Ruhparwar, Martin Busch, Mirko Völkers, Rebecca C Wade, Patrick Most","doi":"10.1161/CIRCULATIONAHA.123.066961","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.123.066961","url":null,"abstract":"<p><strong>Background: </strong>The EF-hand Ca²⁺ sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca²⁺ ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.</p><p><strong>Methods: </strong>We applied an integrative translational research pipeline ranging from in silico computational molecular modeling and in vitro biochemical molecular assays as well as isolated rodent and human cardiomyocyte performance assessments to in vivo safety and efficacy studies in small and large animal cardiac disease models.</p><p><strong>Results: </strong>We characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardium in vitro and in vivo. This activity translates into improved contractile performance and survival in preclinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca²⁺ cycling and prevents β-adrenergic receptor-triggered Ca²⁺ imbalances by targeting SERCA2a and RyR2 activity. In line with the S100A1ct-mediated enhancement of SERCA2a activity, modeling suggests an interaction of the peptide with the transmembrane segments of the sarcoplasmic Ca²⁺ pump. Incorporation of a cardiomyocyte-targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potency in vitro and in vivo.</p><p><strong>Conclusions: </strong>S100A1ct is a promising lead for the development of novel peptide-based therapeutics against heart failure with reduced ejection fraction.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS.","authors":"Yuekai Ji, Michael J Zhang, Wendy Wang, Faye L Norby, Anne A Eaton, Riccardo M Inciardi, Alvaro Alonso, Sanaz Sedaghat, Peter Ganz, Jeremy Van't Hof, Scott D Solomon, Paulo H M Chaves, Susan R Heckbert, Amil M Shah, Lin Yee Chen","doi":"10.1161/CIRCULATIONAHA.124.070278","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070278","url":null,"abstract":"<p><strong>Background: </strong>Coagulation factor XI (FXI) inhibitors are a promising and novel class of anticoagulants, but a recent animal study found that FXI inhibition exacerbated diastolic dysfunction and heart failure (HF). In the ARIC study (Atherosclerosis Risk in Communities), we investigated whether plasma FXI level was associated with cardiovascular events and cardiac function.</p><p><strong>Methods: </strong>ARIC was our primary analytic cohort. We included 4471 participants (median age, 75 years; 57% female; 17% Black) who attended visit 5 (2011-2013) with Somalogic-quantified plasma FXI levels and echocardiographic cardiac function. Prevalent HF and atrial fibrillation (AF) cases were defined as having HF or AF diagnosed at or before each participant's visit 5 exam date. Incident HF and AF events were ascertained through 2021. Associations were assessed using Cox, logistic, and linear regression models. Primary prospective associations were also validated in the CHS (Cardiovascular Health Study) using an orthogonal FXI assay (enzyme-linked immunosorbent assay).</p><p><strong>Results: </strong>At ARIC visit 5, there were 665 and 419 participants with prevalent HF and AF, respectively. During a median follow-up of 9 years, there were 580 and 788 incident HF and AF events, respectively. Lower FXI level was associated prospectively with higher incidence of HF (hazard ratio [HR], 1.36 [for each 1-unit decrement of log₂-transformed FXI level] [95% CI, 1.01-1.83]) but not incident AF, and cross-sectionally with increased odds of AF (odds ratio [OR], 1.96 [95% CI, 1.23-3.07]) but not HF. In age-stratified analyses, decreased FXI was associated with higher incidence of HF in participants ≥75 years of age (HR, 1.57 [95% CI, 1.08-2.28]) but not <75 years of age (HR, 1.11 [95% CI, 0.68-1.79]). The inverse FXI-HF association was validated in CHS (HR, 1.18 [95% CI, 1.02-1.36]). At ARIC visit 5, lower FXI level was also associated with higher prevalence of diastolic dysfunction and worse E/A ratio, left atrial (LA) volume index, LA function, and left ventricular mass index, but not left ventricular ejection fraction or global longitudinal strain.</p><p><strong>Conclusions: </strong>Decreased FXI level is associated with greater incidence of HF, especially in older adults. It is also associated with prevalent AF, worse diastolic function, worse LA function, and greater LA size. More research is needed to assess potential unwanted effects of FXI inhibition on the risk of cardiovascular events and cardiac function.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}