Journal of the American Heart Association最新文献

{"title":"Statin Use Among Women and Men Following Coronary Artery Bypass Surgery.","authors":"Sigrid Sandner, Alexandra Kaider, Julia Riebandt, Alissa Florian, Selma Rizvanovic, C Noel Bairey Merz, Jennifer S Lawton, Mary Charlson, Monika M Safford, Thomas Bergmair, Andreas Zuckermann, Mario Gaudino","doi":"10.1161/JAHA.124.039011","DOIUrl":"10.1161/JAHA.124.039011","url":null,"abstract":"<p><strong>Background: </strong>Limited data exist on sex differences in guideline-recommended statin therapy for secondary prevention after coronary artery bypass surgery (CABG). We examined sex differences in statin use after CABG and the association between sex-specific statin use and mortality.</p><p><strong>Methods and results: </strong>Data from the Austrian national cardiac surgery registry and federal social insurance claims database for patients who underwent CABG between 2013 and 2021 were used. Multivariable logistic regression models were calculated to obtain women-to-men odds ratios for filling any statin and high-intensity statin prescriptions. Cox proportional hazards models were used to evaluate the association between statin use and mortality. A total of 15 448 patients (19% women) were included. During the 5 years after CABG, statin use decreased from 95.7% to 85.9% in men and 95.2% to 84.3% in women (P for trend <0.0001; <i>P</i>_int=0.48), high-intensity statin use decreased from 69.4% to 57.2% in men and 67.8% to 54.3% in women (P for trend <0.0001; <i>P</i>_int=0.59). The adjusted odds ratio for filling any statin prescription comparing women with men was 1.03 (95% CI, 0.92-1.16) and for filling a high-intensity statin prescription was 1.12 (95% CI, 1.02-1.23). Statin use was associated with a significantly lower mortality risk in both sexes (any statin: hazard ratio [HR], 0.56 [95% CI, 0.46-0.68]; <i>P</i><0.0001, <i>P</i>_int=0.22; high-intensity statin: HR, 0.52 [95% CI, 0.42-0.63]; <i>P</i><0.0001, <i>P</i>_int=0.48).</p><p><strong>Conclusions: </strong>Women were as likely as men to fill a statin prescription after CABG and more likely to fill a high-intensity prescription. Statin use was associated with a similar mortality risk reduction among women and men.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e039011"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712148","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":"Decreased Extracellular Vesicle Vasorin in Severe Preeclampsia Plasma Mediates Endothelial Dysfunction.","authors":"Saravanakumar Murugesan, Dylan R Addis, Hanna Hussey, Mark F Powell, Lakshmi Saravanakumar, Adam B Sturdivant, Rachel G Sinkey, Michelle D Tubinis, Zachary R Massey, Chelsi Patton, James A Mobley, Alan N Tita, Tamas Jilling, Dan E Berkowitz","doi":"10.1161/JAHA.124.037242","DOIUrl":"10.1161/JAHA.124.037242","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a serious pregnancy complication affecting 5% to 8% of pregnancies globally. preeclampsia is a leading cause of maternal and neonatal morbidity and death. Despite its prevalence, the underlying mechanisms of preeclampsia remain unclear. This study investigated the role of vasorin in preeclampsia pathogenesis by examining its levels in extracellular vesicles (EVs) and effects on vascular function.</p><p><strong>Methods and results: </strong>We conducted unbiased proteomics on urine-derived EVs from women with severe preeclampsia and normotensive pregnancies, identifying differentially abundant proteins. Vasorin expression levels were measured in urinary EVs, plasma EVs, and placental tissue. EVs were generated from human and murine placental explants. Vascular functions were assessed using murine aortic rings and human aortic endothelial cells. Vasorin expression was manipulated in human aortic endothelial cells via overexpression and knockdown followed by RNA sequencing. One hundred twenty proteins showed ≥±1.5-fold regulation (<i>P</i><0.05) between severe preeclampsia and NTP. Vasorin levels decreased in severe preeclampsia in urinary EVs, plasma EVs, and placental tissue. Vasorin levels increased with gestational age in murine pregnancy and were diminished in a murine model of preeclampsia. Severe preeclampsia and murine preeclampsia EVs impaired human aortic endothelial cell migration and inhibited murine aortic ring vasorelaxation. Vasorin overexpression counteracted these effects. RNA sequencing showed that vasorin manipulation in human aortic endothelial cells differentially regulated hundreds of genes linked to vasculogenesis, proliferation, migration, and apoptosis.</p><p><strong>Conclusions: </strong>The data suggest that vasorin, delivered to the endothelium via EVs, regulates vascular function and that the loss of EV vasorin may be one of the mechanistic drivers of preeclampsia.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037242"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674841","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":"Polygenic Risk and Cardiovascular Event Risk in Patients With Atrial Fibrillation With Low to Intermediate Stroke Risk.","authors":"Juntae Kim, Dongmin Kim, Daehoon Kim, Byoung-Eun Park, Tae Soo Kang, Seong-Hoon Lim, Su Yeon Lee, Young Hak Chung, Myung-Yong Lee, Pil-Sung Yang, Boyoung Joung","doi":"10.1161/JAHA.124.037727","DOIUrl":"10.1161/JAHA.124.037727","url":null,"abstract":"<p><strong>Background: </strong>The clinical utility of the polygenic risk score in predicting cardiovascular events in patients with atrial fibrillation (AF) has not yet been established. This study aimed to determine whether the polygenic risk score for AF might be useful in the risk stratification of AF-related cardiovascular events.</p><p><strong>Methods and results: </strong>This study included 9597 oral anticoagulation-naive patients with AF with a CHA₂DS₂-VA (congestive heart failure; hypertension; age ≥75 years; diabetes; prior stroke or transient ischemic attack or thromboembolism; vascular disease; and age 65-74 years) score of 0 or 1 from the UK Biobank. Patients were stratified according to polygenic risk score tertiles and observed for the occurrence of ischemic stroke or systemic embolism, myocardial infarction, and heart failure hospitalization. The risks of incident events associated with the polygenic risk score were investigated using inverse probability of treatment weighting. Of 9597 individuals, 3800 (39.6%) were women and the mean±SD age was 65.3±6.4 years. During a median follow-up of 4.6 years (interquartile range, 1.7-7.9 years), the incidence rates of ischemic stroke or systemic embolism, myocardial infarction, and heart failure hospitalization were 0.83, 0.42, and 0.61 per 100 person-years, respectively. Compared with low genetic risk, high genetic risk was associated with a hazard ratio of 1.38 (95% CI, 1.08-1.76; <i>P</i>=0.011) for ischemic stroke or systemic embolism, 1.15 (95% CI, 0.82-1.61; <i>P</i>=0.422) for myocardial infarction, and 1.02 (95% CI, 0.78-1.34; <i>P</i>=0.895) for heart failure hospitalization.</p><p><strong>Conclusions: </strong>In patients with AF with low-intermediate stroke risk, genetic risk for AF is associated with increased risk of stroke or systemic embolism.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037727"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674926","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":"Methylated Arginine Metabolites as Biomarkers for Clinical Status and Response to Type 5 Phosphodiesterase Inhibition in Patients With Fontan Circulation.","authors":"Ari Cedars, Cedric Manlhiot, Bhargava Kumar Chinni, Alexander R Opotowsky, Kristian Becker, Anne Le, Pratik Khare, Jong Love Ko, Allen Everett, Shelby Kutty, Mark W Russell, R Mark Payne, Andrew M Atz, Brian W McCrindle, Rahul H Rathod, Matthew Lewis, David Goldberg, Kevin Hill, Michelle Ploutz, Jon Detterich, Kurt Schumacher, Robert Whitehill, Daniel J Penny, Mark Cartoski, Rachel Sullivan, Matthew Files, Ruchira Garg, Jonathan Wagner, Roni Jacobsen, Todd Nowlen, Scott Fletcher, Jennifer Conway, Gi Boem Kim, Fred Wu, Victor Zak","doi":"10.1161/JAHA.124.038061","DOIUrl":"10.1161/JAHA.124.038061","url":null,"abstract":"<p><strong>Background: </strong>There is significant interest in NO pathway modulators, specifically type 5 phosphodiesterase inhibitors (PDE5is), to treat patients with a Fontan circulation. Trials, however, have had mixed results. The relationship between the NO pathway and clinical status in patients with Fontan circulation is a significant knowledge gap.</p><p><strong>Methods and results: </strong>We performed targeted metabolomic analysis using liquid chromatography coupled to mass spectrometry to quantify plasma NO pathway metabolite concentrations from 2 well-characterized populations of patients with Fontan circulation: the Boston Adult Congenital Heart Disease Biobank and Fontan Udenafil Exercise Longitudinal studies. We investigated associations between NO metabolite concentrations and clinical outcomes, exercise capacity, and response to PDE5is. Increased plasma concentration of asymmetric dimethyl arginine (ADMA), an inhibitor of NO production, was associated with risk for hospitalization or death. Increased ADMA and symmetric dimethyl arginine (another inhibitor of NO production) concentrations were associated with decreased baseline exercise capacity among patients with Fontan circulation with <90% predicted peak oxygen uptake, and change in ADMA and symmetric dimethyl arginine concentrations were predictive of change in exercise capacity over time. Treatment with the PDE5i udenafil uncoupled this association. Finally, baseline ADMA and symmetric dimethyl arginine concentrations predicted response to PDE5is among patients with subnormal peak oxygen uptake.</p><p><strong>Conclusions: </strong>Plasma concentrations of metabolites that inhibit NO flux are associated with negative clinical outcomes and worse exercise capacity. Moreover, metabolite shifts over time associated with increased NO flux are associated with improved exercise capacity. In patients with a Fontan circulation, the NO pathway modulators ADMA and symmetric dimethyl arginine may be useful as biomarkers of clinical status and predictive of response to PDE5is.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038061"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711937","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":"Nonprescription Magnesium Supplement Use and Risk of Heart Failure in Patients With Diabetes: A Target Trial Emulation.","authors":"Yan Cheng, Andrew R Zullo, Ying Yin, Yijun Shao, Simin Liu, Qing Zeng-Treitler, Wen-Chih Wu","doi":"10.1161/JAHA.124.038870","DOIUrl":"10.1161/JAHA.124.038870","url":null,"abstract":"<p><strong>Background: </strong>Both diabetes and low magnesium-containing food intake may increase the risk of heart failure (HF). However, the effect of nonprescription magnesium supplements on the risk of HF or major adverse cardiac events in patients with diabetes is unknown.</p><p><strong>Methods and results: </strong>Using a target-trial-emulation approach, we assembled a national cohort of 94 239 veterans ≥40 years with diabetes, without prior HF or magnesium use, who received ambulatory care in the US veterans-health care system documented by electronic clinic notes between January 1, 2006 and December 31, 2020. A natural language processing approach was used to detect self-reported magnesium-supplement use from clinic notes, n=17 619 were identified as users versus n=76 620 as nonusers. Using inverse probability treatment weighting, we constructed a cohort balanced in 88 baseline characteristics between users and nonusers. The primary outcome was incident HF. Secondary outcomes were major adverse cardiac events (myocardial infarction, stroke, HF hospitalization, or death). Hazard ratios (HRs) associated with magnesium-supplement use and outcomes were estimated in the inverse probability treatment weighting weighted cohort using Cox regression. The inverse probability treatment weighting weighted cohort had a mean age of 67.4±10.3 years; 18.4% were Black, and 5.1% were women. The mean duration of magnesium-supplement use was 3.5±3.1 (interquartile range, 1.1-5.1) years. Incident HF occurred in 8.0% of users and 9.7% of nonusers of magnesium supplements (HR, 0.94 [95% CI, 0.89-0.99]). Magnesium-supplement use was also associated with a reduced risk of major adverse cardiac events (HR, 0.94 [95% CI, 0.90-0.97]).</p><p><strong>Conclusions: </strong>Long-term nonprescription magnesium supplement use was associated with a lower risk of incident HF and major adverse cardiac events in patients with diabetes. These findings should be replicated in randomized controlled trials.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038870"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711940","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":"Accelerated Vascular Aging as a Possible Mechanism of Troponin I Release in the Absence of Clinically Manifested Myocardial Injury.","authors":"G A Alanis, P Boutouyrie, M Abouqateb, R M Bruno, M Andrieu, B Vedie, D Geromin, N Danchin, S Laurent, X Jouven, J P Empana","doi":"10.1161/JAHA.124.037718","DOIUrl":"10.1161/JAHA.124.037718","url":null,"abstract":"<p><strong>Background: </strong>We examined the association between clusters of vascular aging manifestations and ultrasensitivity cardiac troponin I in individuals without cardiovascular disease.</p><p><strong>Methods and results: </strong>A cross-sectional analysis was conducted using baseline data from PPS-3 (Paris Prospective Study III), a French cohort of 10 157 participants. Cardiac troponin I was measured with an ultrasensitive immunoassay with a limit of detection of 0.013 pg/mL. Vascular aging manifestations were assessed via echotracking of the right common carotid artery to measure structural and functional parameters. Hierarchical clustering was used to identify clusters of vascular aging. Multinomial regression assessed the association between vascular aging clusters and cardiac troponin I quintiles. The study included 8722 cardiovascular disease-free participants (mean±SD age, 59.5±6.3 years; 39% women). Three vascular aging clusters were identified. Cluster 1 (n=4158; 47.4%) was characterized as healthy vascular aging with the lowest arteriosclerosis and atherosclerosis indices; cluster 2 (n=2237; 25.5%) was characterized by the highest arteriosclerosis indices, including increased pulse wave velocity, β index, and Young elastic modulus and lowest distensibility coefficient; and cluster 3 (n=2377; 27.0%) was characterized by the highest atherosclerosis indices, including more frequent plaque prevalence and greater intima-media thickness. Compared with healthy vascular aging, arteriosclerosis and atherosclerosis clusters showed a graded positive association with cardiac troponin I quintiles, independent of traditional risk factors. The adjusted odds ratio for belonging to the highest quintile (quintile 5 versus quintile 1) was 1.55 (95% CI, 1.31-1.92) for arteriosclerosis and 2.66 (95% CI, 2.18-3.23) for atherosclerosis clusters.</p><p><strong>Conclusions: </strong>Vascular aging manifestations of arteriosclerosis and atherosclerosis may partly explain the release of troponin I into the bloodstream in adults without clinical cardiovascular disease.</p><p><strong>Registration: </strong>URL: https://clinicaltrials.gov; Unique identifier: NCT00741728.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037718"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722525","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":"Understanding Reasons for Oral Anticoagulation Nonprescription in Atrial Fibrillation Using Large Language Models.","authors":"Sulaiman Somani, Dale Daniel Kim, Eduardo Perez-Guerrero, Summer Ngo, Tina Seto, Sadeer Al-Kindi, Tina Hernandez-Boussard, Fatima Rodriguez","doi":"10.1161/JAHA.124.040419","DOIUrl":"10.1161/JAHA.124.040419","url":null,"abstract":"<p><strong>Background: </strong>Rates of oral anticoagulation (OAC) nonprescription in atrial fibrillation approach 50%. Understanding reasons for OAC nonprescription may reduce gaps in guideline-recommended care. We aimed to identify reasons for OAC nonprescription from clinical notes using large language models.</p><p><strong>Methods: </strong>We identified all patients and associated clinical notes in our health care system with a clinician-billed visit for atrial fibrillation without another indication for OAC and stratified them on the basis of active OAC prescriptions. Three annotators labeled reasons for OAC nonprescription in clinical notes on 10% of all patients (\"annotation set\"). We engineered prompts for a generative large language model (Generative Pre-trained Transformer 4) and trained a discriminative large language model (ClinicalBERT) to identify reasons for OAC nonprescription and selected the best-performing model to predict reasons for the remaining 90% of patients (\"inference set\").</p><p><strong>Results: </strong>A total of 35 737 patients were identified, of which 7712 (21.6%) did not have active OAC prescriptions. A total of 910 notes across 771 patients were annotated. Generative Pre-trained Transformer 4 outperformed ClinicalBERT (macro-F1 score across all reasons of 0.79, compared with 0.69 for ClinicalBERT). Using Generative Pre-trained Transformer 4 on the inference set, 61.1% of notes had documented reasons for OAC nonprescription, most commonly the alternative use of an antiplatelet agent (23.3%), therapeutic inertia (21.0%), and low burden of atrial fibrillation (17.1%).</p><p><strong>Conclusions: </strong>This is the first study using large language models to extract documented reasons for OAC nonprescription from clinical notes in patients with atrial fibrillation and reveals guideline-discordant practices and actionable insights for the development of health system interventions to reduce OAC nonprescription.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e040419"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722603","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":"Reliability and Validity of Self-Reported Risk Factors for Stroke and Dementia.","authors":"Reinier W P Tack, Jasper R Senff, Tamara N Kimball, Savvina Prapiadou, Benjamin Y Q Tan, Nirupama Yechoor, Jonathan Rosand, Sanjula D Singh, Christopher D Anderson","doi":"10.1161/JAHA.124.038730","DOIUrl":"10.1161/JAHA.124.038730","url":null,"abstract":"<p><strong>Background: </strong>Stroke and dementia are leading causes of mortality and can be prevented through risk factor management. Risk factor assessment requires laboratory or physical measurements. We aimed to determine whether self-reported risk factors serve as reliable proxies and predict stroke- and dementia-related mortality.</p><p><strong>Methods and results: </strong>We used cross-sectional data from the NHANES (National Health and Nutrition Examination Survey) from 1999 to 2018 linked to National Death Index records. We included participants with available data on self-reported and measured hypertension, hypercholesterolemia, diabetes, kidney disease, hearing impairment and overweight. Reliability was assessed using F1 scores, and used survey-weighted Cox-proportional hazards models evaluated associations with stroke- or dementia-related mortality. Reliability of self-reported risk factors was highest in overweight (F1 score 0.81, sensitivity 76%, specificity 77%) and diabetes (F1 score 0.71, sensitivity 77%, specificity 97%) and lowest for kidney disease (F1 score 0.25, sensitivity 16%, specificity 98%). Self-reported hypertension (hazard ratio [HR], 1.49 [95% CI, 1.14-1.94]) and diabetes (HR, 1.58 [95% CI, 1.18-2.12]) were associated with stroke-related mortality, comparable to measured risk factors. For dementia-related mortality, only measured hearing impairment (all dementia cases had hearing impairment at baseline) and both self-reported (HR, 0.50 [95% CI, 0.37-0.68]) and measured overweight (HR, 0.70 [95% CI, 0.52-0.93]) were associated.</p><p><strong>Conclusions: </strong>In conclusion, the reliability and validity of self-reported risk factors for stroke and dementia differ between risk factors. Although self-reported measures vary in their reliability, they perform equally as well as objective metrics for evaluating the risk of stroke- and dementia-related mortality.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038730"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674863","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":"Blockade of YAP Mechanoactivation Prevents Neointima Formation and Adverse Remodeling in Arterialized Vein Grafts.","authors":"Gloria Garoffolo, Thijs J Sluiter, Anita Thomas, Luca Piacentini, Matthijs S Ruiter, Alessia Schiavo, Massimo Salvi, Claudio Saccu, Stefano Zoli, Mattia Chiesa, Takumi Yokoyama, Marco Agrifoglio, Monica Soncini, Gianfranco B Fiore, Fabio Martelli, Gianluigi Condorelli, Paolo Madeddu, Filippo Molinari, Umberto Morbiducci, Paul H A Quax, Gaia Spinetti, Margreet R de Vries, Maurizio Pesce","doi":"10.1161/JAHA.124.037531","DOIUrl":"10.1161/JAHA.124.037531","url":null,"abstract":"<p><strong>Background: </strong>Bypass surgery using saphenous vein (SV) grafts is commonly performed to revascularize the ischemic heart and lower limbs. These interventions have limited success due to adverse remodeling caused by overproliferation of smooth muscle cells in the intima layer, leading to progressive bypass stenosis. We previously showed that cyclic strain deriving from exposure to coronary flow induces the expression of the matricellular protein thrombospondin-1 in the human SV, promoting activation of progenitor cells normally residing in the adventitia.</p><p><strong>Methods: </strong>We analyzed the data of an RNA-sequencing profiling of human SV progenitors subjected to uniaxial strain we previously performed by. Experiments in cell culture, ex vivo, and in vivo vein arterialization models were performed to substantiate findings with particular reference to the role of mechanically activated transcription factors. Validation was performed in vitro and in ex vivo/in vivo models of vein graft disease.</p><p><strong>Results: </strong>Results of bioinformatic assessment of the RNA-sequencing data indicated Yes-associated protein (YAP) as a possible mechanically regulated effector in pathologic evolution of SV progenitors. Inhibition of YAP by verteprofin-a drug that abolishes the interaction of YAP with Tea Domain DNA-binding proteins-reduced the expression of pathologic markers in vitro and reduced intima hyperplasia in vivo.</p><p><strong>Conclusions: </strong>Our results reveal that desensitizing the SV-resident cells to mechanoactivation of YAP is feasible to reduce the graft disease progression.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037531"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674894","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":"Body Mass Index, Comorbidities, and Ambulatory Care Visits: The REGARDS Study.","authors":"Emily B Levitan, Aowen Zhu, Vera Bittner, Todd M Brown, Michael E Farkouh, Mariam Girguis, Lei Huang, Elizabeth A Jackson, Suzanne E Judd, Shannon Rhodes, Monika M Safford, Jennifer L Strande, Min-Jung Wang, Mark Woodward, D Leann Long","doi":"10.1161/JAHA.124.037034","DOIUrl":"10.1161/JAHA.124.037034","url":null,"abstract":"<p><strong>Background: </strong>Individuals with obesity have more ambulatory care usage than individuals with normal weight and overweight. There is limited information on whether this is consistent across provider specialties and whether comorbidities explain the associations.</p><p><strong>Methods and results: </strong>Among REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study participants with Medicare fee-for-service coverage (n=9648), we identified ambulatory visits over 5 years. We used marginalized zero-inflated Poisson models to calculate ratios of means by body mass index (BMI), adjusted for demographics and health behaviors, and inverse odds weighting to evaluate mediation by diabetes, hypertension, dyslipidemia, stroke, coronary heart disease, atrial fibrillation, heart failure, chronic kidney disease, depressive symptoms, cancer, arthritis, and sleep apnea. The mean age of participants was 71.7±7.3 years, 35.1% were Black individuals and 64.9% White individuals, and 51.1% were women. Participants had a mean of 37.8 total, 16.0 primary care, 3.4 cardiology, 1.9 orthopedics, 0.9 pulmonology, and 0.4 endocrinology visits. Compared with individuals with BMI 18.5 to <25 kg/m² (n=2613), participants with BMI ≥35 kg/m² (n=1259) had 23% (95% CI, 21%-24%) more ambulatory visits. Participants with BMI ≥35 kg/m² had 26% more primary care, 20% more cardiology, 74% more orthopedics, 62% more pulmonology, and 85% more endocrinology visits. Comorbidities partly explained associations with overall, primary care, and orthopedics visits (39%, 38%, and 15%, respectively) and largely explained associations with cardiology, pulmonology, and endocrinology visits.</p><p><strong>Conclusions: </strong>Understanding which specialty visits are associated with higher BMI can help with workforce planning and allocation of resources.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037034"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674897","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}