Pub Date : 2024-09-09DOI: 10.1161/circulationaha.124.068237
Alain Cribier,Hélène Eltchaninoff
{"title":"Transcatheter Aortic Valve Implantation: Two Decades of a Revolutionary and Ongoing Odyssey.","authors":"Alain Cribier,Hélène Eltchaninoff","doi":"10.1161/circulationaha.124.068237","DOIUrl":"https://doi.org/10.1161/circulationaha.124.068237","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165889","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}
Pub Date : 2024-09-09DOI: 10.1161/circulationaha.124.068928
Sabina A Murphy,Andrea Bellavia
{"title":"Noninferiority Clinical Trials: Overview for the Clinical Cardiologist.","authors":"Sabina A Murphy,Andrea Bellavia","doi":"10.1161/circulationaha.124.068928","DOIUrl":"https://doi.org/10.1161/circulationaha.124.068928","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165888","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}
Pub Date : 2024-09-05DOI: 10.1161/CIRCULATIONAHA.124.070694
Regina Royan, Brian Stamm, Timmy Lin, Janette Baird, Christopher Becker, Rebecca Karb, Tina Burton, Dawn Kleindorfer, Shyam Prabhakaran, Tracy E Madsen
Background: Disparities in time to hospital presentation and prehospital stroke care may be important drivers in inequities in acute stroke treatment rates, functional outcomes, and mortality. It is unknown how patient-level factors, such as race and ethnicity and county-level socioeconomic status, affect these aspects of prehospital stroke care.
Methods: Cross-sectional study of patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage in the Get With the Guidelines-Stroke registry, presenting from July 2015 to December 2019, with symptom onset <24 hours. Multivariable logistic regression and quantile regression were used to investigate the outcomes of interest: emergency medical services (EMS) transport (versus private vehicle), EMS prehospital notification (versus no prehospital notification), and stroke symptom onset to time of arrival at the emergency department. Prespecified covariates included patient-level, hospital-level, and county-level characteristics.
Results: The inclusion criteria was met by the 606 369 patients. Of the patients, 51.2% were men and 69.9% White, with a median National Institutes of Health Stroke Severity of 4 (IQR, 2-10), and median social deprivation index (SDI) of 51 (IQR, 27-75). Median symptom onset to arrival time was 176 minutes (IQR, 64-565). Black race was significantly associated with prolonged symptom onset to emergency department arrival time (+28.21 minutes [95% CI, 25.59-30.84]), and decreased odds of EMS prehospital notification (OR, 0.80 [95% CI, 0.78-0.82]). SDI was not associated with differences in EMS use but was associated with lower odds of EMS prehospital notification (upper SDI tercile versus lowest, OR, 0.79 [95% CI, 0.78-0.81]). SDI was also significantly associated with stroke symptom onset to emergency department arrival time (upper SDI tercile versus lowest +2.56 minutes [95% CI, 0.58-4.53]).
Conclusions: In this national cross-sectional study, Black race was associated with prolonged onset to time of arrival intervals and significantly decreased odds of EMS prehospital notification, despite similar use of EMS transport. Greater county-level deprivation was also associated with reduced odds of EMS prehospital notification and slightly prolonged stroke symptom onset to emergency department arrival time. Efforts to reduce place-based disparities in stroke care must address significant inequities in prehospital care of acute stroke and continue to address health inequities associated with race and ethnicity.
{"title":"Disparities in Emergency Medical Services Use, Prehospital Notification, and Symptom Onset to Arrival in Patients With Acute Stroke.","authors":"Regina Royan, Brian Stamm, Timmy Lin, Janette Baird, Christopher Becker, Rebecca Karb, Tina Burton, Dawn Kleindorfer, Shyam Prabhakaran, Tracy E Madsen","doi":"10.1161/CIRCULATIONAHA.124.070694","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070694","url":null,"abstract":"<p><strong>Background: </strong>Disparities in time to hospital presentation and prehospital stroke care may be important drivers in inequities in acute stroke treatment rates, functional outcomes, and mortality. It is unknown how patient-level factors, such as race and ethnicity and county-level socioeconomic status, affect these aspects of prehospital stroke care.</p><p><strong>Methods: </strong>Cross-sectional study of patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage in the Get With the Guidelines-Stroke registry, presenting from July 2015 to December 2019, with symptom onset <24 hours. Multivariable logistic regression and quantile regression were used to investigate the outcomes of interest: emergency medical services (EMS) transport (versus private vehicle), EMS prehospital notification (versus no prehospital notification), and stroke symptom onset to time of arrival at the emergency department. Prespecified covariates included patient-level, hospital-level, and county-level characteristics.</p><p><strong>Results: </strong>The inclusion criteria was met by the 606 369 patients. Of the patients, 51.2% were men and 69.9% White, with a median National Institutes of Health Stroke Severity of 4 (IQR, 2-10), and median social deprivation index (SDI) of 51 (IQR, 27-75). Median symptom onset to arrival time was 176 minutes (IQR, 64-565). Black race was significantly associated with prolonged symptom onset to emergency department arrival time (+28.21 minutes [95% CI, 25.59-30.84]), and decreased odds of EMS prehospital notification (OR, 0.80 [95% CI, 0.78-0.82]). SDI was not associated with differences in EMS use but was associated with lower odds of EMS prehospital notification (upper SDI tercile versus lowest, OR, 0.79 [95% CI, 0.78-0.81]). SDI was also significantly associated with stroke symptom onset to emergency department arrival time (upper SDI tercile versus lowest +2.56 minutes [95% CI, 0.58-4.53]).</p><p><strong>Conclusions: </strong>In this national cross-sectional study, Black race was associated with prolonged onset to time of arrival intervals and significantly decreased odds of EMS prehospital notification, despite similar use of EMS transport. Greater county-level deprivation was also associated with reduced odds of EMS prehospital notification and slightly prolonged stroke symptom onset to emergency department arrival time. Efforts to reduce place-based disparities in stroke care must address significant inequities in prehospital care of acute stroke and continue to address health inequities associated with race and ethnicity.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132034","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}
Pub Date : 2024-09-04DOI: 10.1161/CIRCULATIONAHA.124.069903
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
Background: 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.
Methods: 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.
Results: 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 (Pinteraction=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 (Ptrend=0.1).
Conclusions: 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.
{"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":"https://doi.org/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 CHA<sub>2</sub>DS<sub>2</sub>-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><sub>interaction</sub>=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><sub>trend</sub>=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":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-04","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}
Background: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China.
Methods: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months.
Results: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up.
Conclusions: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham.
背景:肾脏去神经支配(RDN)可在高血压患者服药或不服药的情况下降低血压。这是中国首次对肾脏去神经支配疗法的安全性和有效性进行假对照试验:这项前瞻性、多中心、随机、患者和结果评估者盲法假对照试验研究了射频降压网对接受标准化三联降压治疗的高血压患者的疗效。符合条件的患者按 1:1 随机分配到使用多电极射频导管(Iberis;AngioCare,中国上海)或假手术进行 RDN 治疗。主要疗效指标是随机分组至6个月期间,经基线调整后的24小时卧床平均收缩压变化的组间差异:在217名随机患者中(平均年龄为45.3±10.2岁;21%为女性),107人随机接受了RDN治疗,110人随机接受了假对照治疗。6个月时,RDN组(-13.0±12.1 mm Hg)与假对照组(-3.0±13.0 mm Hg;基线调整后组间差异为-9.4 mm Hg [95% CI, -12.8 to -5.9];PPP=0.003)和-5.1 mm Hg([95% CI, -8.2 to -2.0];P=0.001)相比,24小时收缩压降低幅度更大。RDN 组中有一名患者发生了入路部位并发症(血肿),但并无后遗症。随访期间未发生其他与器械或手术相关的重大安全事件:在这项针对接受标准化三联药物治疗的中国未控制高血压患者的试验中,RDN 是安全的,与假药相比,RDN 可在 6 个月内降低非卧床血压和诊室血压:URL:https://clinicaltrials.gov;唯一标识符:NCT02901704。
{"title":"Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.","authors":"Xiongjing Jiang, Felix Mahfoud, Wei Li, Hui Dong, Jing Yu, Shuhua Yu, Xiaoping Chen, Peijian Wang, Zhiqiang Li, Lucas Lauder, Zhifang Wang, Zheng Ji, Yifei Dong, Bing Han, Zhiming Zhu, Yulin Chen, Jianzhong Xu, Xingsheng Zhao, Weidong Fan, Wen Xie, Brad Hubbard, Xi Hu, Kazuomi Kario, Runlin Gao","doi":"10.1161/CIRCULATIONAHA.124.069215","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069215","url":null,"abstract":"<p><strong>Background: </strong>Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China.</p><p><strong>Methods: </strong>This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months.</p><p><strong>Results: </strong>Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; <i>P</i><0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; <i>P</i><0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; <i>P</i>=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; <i>P</i>=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up.</p><p><strong>Conclusions: </strong>In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham.</p><p><strong>Registration: </strong>URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125027","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}
Pub Date : 2024-09-03DOI: 10.1161/CIRCULATIONAHA.123.067970
Robin A P Weir
{"title":"Letter by Weir Regarding Article, \"Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity\".","authors":"Robin A P Weir","doi":"10.1161/CIRCULATIONAHA.123.067970","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.123.067970","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125031","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}
Pub Date : 2024-09-03Epub Date: 2024-08-01DOI: 10.1161/CIRCULATIONAHA.124.069414
Irene Martinez-Morata, Kathrin Schilling, Ronald A Glabonjat, Arce Domingo-Relloso, Melanie Mayer, Katlyn E McGraw, Marta Galvez Fernandez, Tiffany R Sanchez, Anne E Nigra, Joel D Kaufman, Dhananjay Vaidya, Miranda R Jones, Michael P Bancks, R Graham Barr, Daichi Shimbo, Wendy S Post, Linda Valeri, Steven Shea, Ana Navas-Acien
Background: Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (the Multi-Ethnic Study of Atherosclerosis).
Methods: We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as a mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net.
Results: During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the hazard ratios (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted hazard ratios (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality.
Conclusions: This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.
{"title":"Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA).","authors":"Irene Martinez-Morata, Kathrin Schilling, Ronald A Glabonjat, Arce Domingo-Relloso, Melanie Mayer, Katlyn E McGraw, Marta Galvez Fernandez, Tiffany R Sanchez, Anne E Nigra, Joel D Kaufman, Dhananjay Vaidya, Miranda R Jones, Michael P Bancks, R Graham Barr, Daichi Shimbo, Wendy S Post, Linda Valeri, Steven Shea, Ana Navas-Acien","doi":"10.1161/CIRCULATIONAHA.124.069414","DOIUrl":"10.1161/CIRCULATIONAHA.124.069414","url":null,"abstract":"<p><strong>Background: </strong>Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (the Multi-Ethnic Study of Atherosclerosis).</p><p><strong>Methods: </strong>We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as a mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net.</p><p><strong>Results: </strong>During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the hazard ratios (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted hazard ratios (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality.</p><p><strong>Conclusions: </strong>This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859209","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}
Pub Date : 2024-09-03Epub Date: 2024-06-17DOI: 10.1161/CIRCULATIONAHA.123.066628
Gregory A Wyant, Qinqin Jiang, Madhu Singh, Shariq Qayyum, Clara Levrero, Bradley A Maron, William G Kaelin
Background: HIF (hypoxia inducible factor) regulates many aspects of cardiac function. We and others previously showed that chronic HIF activation in the heart in mouse models phenocopies multiple features of ischemic cardiomyopathy in humans, including mitochondrial loss, lipid accumulation, and systolic cardiac dysfunction. In some settings, HIF also causes the loss of peroxisomes. How, mechanistically, HIF promotes cardiac dysfunction is an open question.
Methods: We used mice lacking cardiac pVHL (von Hippel-Lindau protein) to investigate how chronic HIF activation causes multiple features of ischemic cardiomyopathy, such as autophagy induction and lipid accumulation. We performed immunoblot assays, RNA sequencing, mitochondrial and peroxisomal autophagy flux measurements, and live cell imaging on isolated cardiomyocytes. We used CRISPR-Cas9 gene editing in mice to validate a novel mediator of cardiac dysfunction in the setting of chronic HIF activation.
Results: We identify a previously unknown pathway by which cardiac HIF activation promotes the loss of mitochondria and peroxisomes. We found that DEPP1 (decidual protein induced by progesterone 1) is induced under hypoxia in a HIF-dependent manner and localizes inside mitochondria. DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes ex vivo. DEPP1 loss increases cardiomyocyte survival in the setting of chronic HIF activation ex vivo, and whole-body Depp1 loss decreases cardiac dysfunction in hearts with chronic HIF activation caused by VHL loss in vivo.
Conclusions: Our findings identify DEPP1 as a key component in the cardiac remodeling that occurs with chronic ischemia.
{"title":"Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy.","authors":"Gregory A Wyant, Qinqin Jiang, Madhu Singh, Shariq Qayyum, Clara Levrero, Bradley A Maron, William G Kaelin","doi":"10.1161/CIRCULATIONAHA.123.066628","DOIUrl":"10.1161/CIRCULATIONAHA.123.066628","url":null,"abstract":"<p><strong>Background: </strong>HIF (hypoxia inducible factor) regulates many aspects of cardiac function. We and others previously showed that chronic HIF activation in the heart in mouse models phenocopies multiple features of ischemic cardiomyopathy in humans, including mitochondrial loss, lipid accumulation, and systolic cardiac dysfunction. In some settings, HIF also causes the loss of peroxisomes. How, mechanistically, HIF promotes cardiac dysfunction is an open question.</p><p><strong>Methods: </strong>We used mice lacking cardiac pVHL (von Hippel-Lindau protein) to investigate how chronic HIF activation causes multiple features of ischemic cardiomyopathy, such as autophagy induction and lipid accumulation. We performed immunoblot assays, RNA sequencing, mitochondrial and peroxisomal autophagy flux measurements, and live cell imaging on isolated cardiomyocytes. We used CRISPR-Cas9 gene editing in mice to validate a novel mediator of cardiac dysfunction in the setting of chronic HIF activation.</p><p><strong>Results: </strong>We identify a previously unknown pathway by which cardiac HIF activation promotes the loss of mitochondria and peroxisomes. We found that DEPP1 (decidual protein induced by progesterone 1) is induced under hypoxia in a HIF-dependent manner and localizes inside mitochondria. DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes ex vivo. DEPP1 loss increases cardiomyocyte survival in the setting of chronic HIF activation ex vivo, and whole-body Depp1 loss decreases cardiac dysfunction in hearts with chronic HIF activation caused by <i>VHL</i> loss in vivo.</p><p><strong>Conclusions: </strong>Our findings identify DEPP1 as a key component in the cardiac remodeling that occurs with chronic ischemia.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330454","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}
Pub Date : 2024-09-03Epub Date: 2024-05-06DOI: 10.1161/CIRCULATIONAHA.122.059102
Feng Xiao, Ngoc Uyen Nhi Nguyen, Ping Wang, Shujuan Li, Ching-Cheng Hsu, Suwannee Thet, Wataru Kimura, Xiang Luo, Nicholas T Lam, Ivan Menendez-Montes, Waleed M Elhelaly, Alisson Campos Cardoso, Ana Helena Macedo Pereira, Rohit Singh, Sakthivel Sadayappan, Mohammed Kanchwala, Chao Xing, Feria A Ladha, J Travis Hinson, Roger J Hajjar, Joseph A Hill, Hesham A Sadek
Background: Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes.
Methods: Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo.
Results: We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in vitro and in vivo identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin.
Conclusions: These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.
{"title":"Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis.","authors":"Feng Xiao, Ngoc Uyen Nhi Nguyen, Ping Wang, Shujuan Li, Ching-Cheng Hsu, Suwannee Thet, Wataru Kimura, Xiang Luo, Nicholas T Lam, Ivan Menendez-Montes, Waleed M Elhelaly, Alisson Campos Cardoso, Ana Helena Macedo Pereira, Rohit Singh, Sakthivel Sadayappan, Mohammed Kanchwala, Chao Xing, Feria A Ladha, J Travis Hinson, Roger J Hajjar, Joseph A Hill, Hesham A Sadek","doi":"10.1161/CIRCULATIONAHA.122.059102","DOIUrl":"10.1161/CIRCULATIONAHA.122.059102","url":null,"abstract":"<p><strong>Background: </strong>Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes.</p><p><strong>Methods: </strong>Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo.</p><p><strong>Results: </strong>We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in vitro and in vivo identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin.</p><p><strong>Conclusions: </strong>These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847102","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}