Pub Date : 2025-12-10DOI: 10.1001/jamacardio.2025.4491
Paul M Ridker,Florian M M Baeres,Anders Hveplund,Mads M D Engelmann,G Kees Hovingh,A Michael Lincoff,Nikolaus Marx,Ann Marie Navar,Naveed Sattar,Katherine Tuttle,Vlado Perkovic
ImportanceCardiovascular inflammation is a major determinant of atherosclerotic disease, and inhibition of the central signaling cytokine, interleukin 6 (IL-6), is a promising target for intervention. Patients with chronic kidney disease (CKD) commonly have plasma elevations of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hsCRP) and IL-6, and are at high risk for life-threatening atherosclerotic events as well as loss of kidney function and might therefore benefit from IL-6 inhibition.ObservationsThe Ziltivekimab Cardiovascular Outcomes Trial (ZEUS; NCT05021835) will determine the safety and efficacy of IL-6 inhibition with ziltivekimab among patients with atherosclerotic cardiovascular disease (ASCVD), CKD, and systemic inflammation. ZEUS is a multinational, double-blind, placebo-controlled, event-driven, randomized clinical trial inclusive of 6376 participants with ASCVD, CKD, and an hsCRP level greater than or equal to 2 mg/L who were randomized in a 1:1 fashion to receive either ziltivekimab, 15 mg, administered subcutaneously every month or matching placebo. At randomization, mean age was 69.5 years, 27.5% were female, 92.0% had hypertension, 65.7% had diabetes, and 41.3% had heart failure. At baseline, the mean estimated glomerular filtration rate (eGFR) was 44.5 mL/min/1.73 m2, mean low-density lipoprotein cholesterol level was 77.7 mg/dL, median hsCRP level was 4.5 mg/L, and median IL-6 level was 4.9 pg/mL. At enrollment, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were being used by 36.8% and 11.3% of the cohort, respectively. The primary outcome is 3-point major adverse cardiovascular events. Secondary cardiovascular outcomes include (1) an expanded major adverse cardiovascular event outcome including hospitalization for unstable angina requiring urgent coronary revascularization, (2) hospitalizations for heart failure or urgent heart failure visits or cardiovascular death, and (3) all-cause mortality. The secondary kidney outcome is a composite of greater than 40% decline in eGFR, eGFR less than 15 mL/min/1.73 m2, dialysis, kidney transplant, death from kidney disease, or cardiovascular death.Conclusions and RelevanceThe ZEUS randomized clinical trial will formally test the hypothesis that IL-6 inhibition with ziltivekimab will lower incident cardiovascular event rates and potentially slow kidney decline among participants with known ASCVD, CKD, and elevated hsCRP. If successful, the ZEUS trial would provide a fully novel approach for prevention of myocardial infarction, stroke, cardiovascular death, and kidney function decline among high-risk patients with CKD.
{"title":"Rationale, Design, and Baseline Clinical Characteristics of the Ziltivekimab Cardiovascular Outcomes Trial: Interleukin-6 Inhibition and Atherosclerotic Event Rate Reduction.","authors":"Paul M Ridker,Florian M M Baeres,Anders Hveplund,Mads M D Engelmann,G Kees Hovingh,A Michael Lincoff,Nikolaus Marx,Ann Marie Navar,Naveed Sattar,Katherine Tuttle,Vlado Perkovic","doi":"10.1001/jamacardio.2025.4491","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4491","url":null,"abstract":"ImportanceCardiovascular inflammation is a major determinant of atherosclerotic disease, and inhibition of the central signaling cytokine, interleukin 6 (IL-6), is a promising target for intervention. Patients with chronic kidney disease (CKD) commonly have plasma elevations of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hsCRP) and IL-6, and are at high risk for life-threatening atherosclerotic events as well as loss of kidney function and might therefore benefit from IL-6 inhibition.ObservationsThe Ziltivekimab Cardiovascular Outcomes Trial (ZEUS; NCT05021835) will determine the safety and efficacy of IL-6 inhibition with ziltivekimab among patients with atherosclerotic cardiovascular disease (ASCVD), CKD, and systemic inflammation. ZEUS is a multinational, double-blind, placebo-controlled, event-driven, randomized clinical trial inclusive of 6376 participants with ASCVD, CKD, and an hsCRP level greater than or equal to 2 mg/L who were randomized in a 1:1 fashion to receive either ziltivekimab, 15 mg, administered subcutaneously every month or matching placebo. At randomization, mean age was 69.5 years, 27.5% were female, 92.0% had hypertension, 65.7% had diabetes, and 41.3% had heart failure. At baseline, the mean estimated glomerular filtration rate (eGFR) was 44.5 mL/min/1.73 m2, mean low-density lipoprotein cholesterol level was 77.7 mg/dL, median hsCRP level was 4.5 mg/L, and median IL-6 level was 4.9 pg/mL. At enrollment, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were being used by 36.8% and 11.3% of the cohort, respectively. The primary outcome is 3-point major adverse cardiovascular events. Secondary cardiovascular outcomes include (1) an expanded major adverse cardiovascular event outcome including hospitalization for unstable angina requiring urgent coronary revascularization, (2) hospitalizations for heart failure or urgent heart failure visits or cardiovascular death, and (3) all-cause mortality. The secondary kidney outcome is a composite of greater than 40% decline in eGFR, eGFR less than 15 mL/min/1.73 m2, dialysis, kidney transplant, death from kidney disease, or cardiovascular death.Conclusions and RelevanceThe ZEUS randomized clinical trial will formally test the hypothesis that IL-6 inhibition with ziltivekimab will lower incident cardiovascular event rates and potentially slow kidney decline among participants with known ASCVD, CKD, and elevated hsCRP. If successful, the ZEUS trial would provide a fully novel approach for prevention of myocardial infarction, stroke, cardiovascular death, and kidney function decline among high-risk patients with CKD.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"1 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710956","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}
Importance For patients presenting with symptomatic prosthetic valve thrombosis (PVT) after mechanical heart valve replacement, thrombolytic therapy with alteplase is accepted as a first-line therapeutic alternative. The utility of tenecteplase compared with conventional regimens remains unstudied, to the authors’ knowledge, in this patient population. Objective To assess the relative safety and efficacy of tenecteplase compared with standard infusions of alteplase in patients with PVT. Design, Setting and Participants This was an open-label, parallel-group, non-inferiority randomized clinical trial among consecutive adult patients presenting with obstructive PVT of a mechanical prosthetic valve over the study period from October 2022 to August 2024 to a single tertiary care center in India. Interventions Patients received thrombolytic therapy with a low-dose slow infusion alteplase or weight-based bolus doses of tenecteplase. Main Outcomes and Measures The primary outcomes were to determine the rates of complete thrombolytic success and the incidence of major complications. Results A total of 83 patients (mean [SD] age, 39.6 [12.4] years, 42 male [50.6%]) were randomized to receive alteplase (n = 43) or tenecteplase (n = 40). The rates of the primary efficacy end point (complete thrombolytic success) were significantly higher (risk ratio, 1.18; 95% CI, 1.03-1.39; P = .02 for noninferiority) in the tenecteplase group (39 patients [97.5%]) compared with the alteplase group (35 patients [81.5%]). Additionally, patients treated with tenecteplase had higher rates of complete success with the first administered dose and a shorter duration of hospital stay (median [IQR], 4.1 [3.2-5.1] days vs 6.5 [4.3-9.2] days; P < .001). The rates of major and minor adverse events were similar. Conclusions and Relevance Tenecteplase may be a safe and effective alternative to alteplase in patients presenting with obstructive PVT. Patients treated with tenecteplase in our study had higher rates of complete thrombolytic success and a shorter duration of hospital stay. Furthermore, the relative ease of drug administration with tenecteplase may translate to greater clinical benefit in a real-world setting. Trial Registration Clinical Trials Registry of India: CTRI/2022/10/046127
{"title":"Tenecteplase vs Alteplase in Mechanical Prosthetic Heart Valve Thrombosis","authors":"Gautam Sharma, Krishna Prasad Akkineni, Nayani Makkar, Asmita Shukla, Partha Haldar, Devagourou Velayoudam, Kamal Kamal, Sanjeev Kumar, Nitish Naik, Ambuj Roy, Sandeep Singh, Sandeep Seth, Rohit Bhatia","doi":"10.1001/jamacardio.2025.4369","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4369","url":null,"abstract":"Importance For patients presenting with symptomatic prosthetic valve thrombosis (PVT) after mechanical heart valve replacement, thrombolytic therapy with alteplase is accepted as a first-line therapeutic alternative. The utility of tenecteplase compared with conventional regimens remains unstudied, to the authors’ knowledge, in this patient population. Objective To assess the relative safety and efficacy of tenecteplase compared with standard infusions of alteplase in patients with PVT. Design, Setting and Participants This was an open-label, parallel-group, non-inferiority randomized clinical trial among consecutive adult patients presenting with obstructive PVT of a mechanical prosthetic valve over the study period from October 2022 to August 2024 to a single tertiary care center in India. Interventions Patients received thrombolytic therapy with a low-dose slow infusion alteplase or weight-based bolus doses of tenecteplase. Main Outcomes and Measures The primary outcomes were to determine the rates of complete thrombolytic success and the incidence of major complications. Results A total of 83 patients (mean [SD] age, 39.6 [12.4] years, 42 male [50.6%]) were randomized to receive alteplase (n = 43) or tenecteplase (n = 40). The rates of the primary efficacy end point (complete thrombolytic success) were significantly higher (risk ratio, 1.18; 95% CI, 1.03-1.39; <jats:italic>P</jats:italic> = .02 for noninferiority) in the tenecteplase group (39 patients [97.5%]) compared with the alteplase group (35 patients [81.5%]). Additionally, patients treated with tenecteplase had higher rates of complete success with the first administered dose and a shorter duration of hospital stay (median [IQR], 4.1 [3.2-5.1] days vs 6.5 [4.3-9.2] days; <jats:italic>P</jats:italic> &amp;lt; .001). The rates of major and minor adverse events were similar. Conclusions and Relevance Tenecteplase may be a safe and effective alternative to alteplase in patients presenting with obstructive PVT. Patients treated with tenecteplase in our study had higher rates of complete thrombolytic success and a shorter duration of hospital stay. Furthermore, the relative ease of drug administration with tenecteplase may translate to greater clinical benefit in a real-world setting. Trial Registration Clinical Trials Registry of India: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NzMzMDU=&amp;amp;Enc=&amp;amp;userName=CTRI/2022/10/046127\">CTRI/2022/10/046127</jats:ext-link>","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"1 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145658247","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 : 2025-12-01DOI: 10.1001/jamacardio.2025.3939
Sanjay Rajagopalan, Robert D Brook, Salil Deo
{"title":"Heart Failure and Nonoptimal Temperatures.","authors":"Sanjay Rajagopalan, Robert D Brook, Salil Deo","doi":"10.1001/jamacardio.2025.3939","DOIUrl":"10.1001/jamacardio.2025.3939","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":"1237-1239"},"PeriodicalIF":14.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345170","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 : 2025-12-01DOI: 10.1001/jamacardio.2025.4082
Benjamin D Gallagher
{"title":"Concerns About Diagnosing Hypertension in the Emergency Department.","authors":"Benjamin D Gallagher","doi":"10.1001/jamacardio.2025.4082","DOIUrl":"10.1001/jamacardio.2025.4082","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":"1326"},"PeriodicalIF":14.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444837","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 : 2025-11-26DOI: 10.1001/jamacardio.2025.4345
Sanjay Kaul
{"title":"T-TEER for Severe Tricuspid Regurgitation in the TRILUMINATE Pivotal Trial.","authors":"Sanjay Kaul","doi":"10.1001/jamacardio.2025.4345","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4345","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"147 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599641","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 : 2025-11-26DOI: 10.1001/jamacardio.2025.4337
Benjamin Salter,Gilbert H L Tang,Rebecca T Hahn,Anuradha Lala,David H Adams,Anita Asgar,Michael A Borger,Neil P Fam,Edwin C Ho,Sahil Khera,Annapoorna S Kini,Azeem Latib,Alex P W Lee,Stamatios Lerakis,Phillipp Lurz,Lucy M Safi,Paul Sorajja,Ralph Stephan von Bardeleben,Fabien Praz,Patrick T O'Gara,Henry M K Wong,Randolph H L Wong,Syed Zaid,Kent C Y So
ImportanceUntreated severe tricuspid regurgitation carries a poor prognosis. We aim to provide a contemporary review of the anatomy, clinical manifestations, and diagnostic and management strategies, including medical, surgical and transcatheter options. By synthesizing current knowledge, this review seeks to equip clinicians with the insights necessary to navigate the complexities of TR treatment.ObservationsTricuspid regurgitation is predominantly secondary to annular dilation and leaflet tethering but can also be associated with cardiac implantable electronic device leads and primary leaflet pathologies. Isolated tricuspid valve surgery is infrequently performed, especially in high surgical risk patients, prompting the emergence of transcatheter treatment options. These advancements are complemented by significant strides in multimodality imaging, including three-dimensional echocardiography, computed tomography, and magnetic resonance imaging, which enhance diagnostic accuracy and procedural planning.Conclusions and RelevanceThe effective management of tricuspid regurgitation necessitates a multidisciplinary approach, integrating input from interventional cardiology, cardiac surgery, heart failure cardiology, imaging, and electrophysiology. Surgical and transcatheter interventions such as tricuspid transcatheter-edge-to-edge repair and transcatheter tricuspid valve replacement have demonstrated favorable early clinical and functional outcomes, but ongoing research is necessary to refine patient selection and improve treatment decision-making. Individualizing treatment plans to optimize health outcomes and quality of life for patients with tricuspid regurgitation is paramount.
{"title":"A Contemporary Look at the Landscape of Treatment of Tricuspid Regurgitation: A Review.","authors":"Benjamin Salter,Gilbert H L Tang,Rebecca T Hahn,Anuradha Lala,David H Adams,Anita Asgar,Michael A Borger,Neil P Fam,Edwin C Ho,Sahil Khera,Annapoorna S Kini,Azeem Latib,Alex P W Lee,Stamatios Lerakis,Phillipp Lurz,Lucy M Safi,Paul Sorajja,Ralph Stephan von Bardeleben,Fabien Praz,Patrick T O'Gara,Henry M K Wong,Randolph H L Wong,Syed Zaid,Kent C Y So","doi":"10.1001/jamacardio.2025.4337","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4337","url":null,"abstract":"ImportanceUntreated severe tricuspid regurgitation carries a poor prognosis. We aim to provide a contemporary review of the anatomy, clinical manifestations, and diagnostic and management strategies, including medical, surgical and transcatheter options. By synthesizing current knowledge, this review seeks to equip clinicians with the insights necessary to navigate the complexities of TR treatment.ObservationsTricuspid regurgitation is predominantly secondary to annular dilation and leaflet tethering but can also be associated with cardiac implantable electronic device leads and primary leaflet pathologies. Isolated tricuspid valve surgery is infrequently performed, especially in high surgical risk patients, prompting the emergence of transcatheter treatment options. These advancements are complemented by significant strides in multimodality imaging, including three-dimensional echocardiography, computed tomography, and magnetic resonance imaging, which enhance diagnostic accuracy and procedural planning.Conclusions and RelevanceThe effective management of tricuspid regurgitation necessitates a multidisciplinary approach, integrating input from interventional cardiology, cardiac surgery, heart failure cardiology, imaging, and electrophysiology. Surgical and transcatheter interventions such as tricuspid transcatheter-edge-to-edge repair and transcatheter tricuspid valve replacement have demonstrated favorable early clinical and functional outcomes, but ongoing research is necessary to refine patient selection and improve treatment decision-making. Individualizing treatment plans to optimize health outcomes and quality of life for patients with tricuspid regurgitation is paramount.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"24 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599642","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 : 2025-11-19DOI: 10.1001/jamacardio.2025.4283
Sadiya S Khan,Clyde W Yancy
{"title":"Detecting Atherosclerosis-From Autopsy to Angiography With Computed Tomography.","authors":"Sadiya S Khan,Clyde W Yancy","doi":"10.1001/jamacardio.2025.4283","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4283","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"1 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545131","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 : 2025-11-19DOI: 10.1001/jamacardio.2025.4271
Ángel Herraiz-Adillo,Hampus Eriksson,Viktor H Ahlqvist,Marcel Ballin,Patrik Wennberg,Bledar Daka,Cecilia Lenander,Daniel Berglind,Carl Johan Östgren,Oskar Lundgren,Karin Rådholm,Pontus Henriksson
ImportanceElevated blood pressure (BP) in adolescence has been linked to higher risk of cardiovascular disease mortality, as well as surrogate markers of atherosclerosis, such as carotid intima-media thickness and coronary artery calcification. However, these markers do not fully capture the complex spectrum of subclinical atherosclerotic cardiovascular disease.ObjectiveTo examine the association between systolic and diastolic BP in adolescence and atherosclerosis in middle age, measured by coronary computed tomography angiography (CCTA).Design, Setting, and ParticipantsThis population-based cohort study conducted in Sweden linked BP data from the Swedish Military Conscription Register (1972-1987) during adolescence to atherosclerosis data from the Swedish Cardiopulmonary Bioimage Study (2013-2018) during middle age. Data analyses were performed in May 2025.ExposureAdolescent BP was categorized according to the 2025 American College of Cardiology/American Heart Association (ACC/AHA) and the 2024 European Society of Cardiology (ESC) guidelines.Main Outcomes and MeasuresThe primary outcome was coronary atherosclerosis, evaluated via CCTA stenosis. The associations were analyzed using multinomial logistic regression, adjusted (marginal) prevalences, and restricted cubic splines.ResultsA total of 10 222 men with mean (SD) age of 18.3 (0.5) years at baseline and median (IQR) age of 57.8 (53.4-61.2) years at follow-up were included. At baseline, mean (SD) systolic BP (SBP) and diastolic BP (DBP) were 127.6 (10.7) mm Hg and 68.3 (9.5) mm Hg, respectively. After a median (IQR) follow-up of 39.5 (35.2-42.8) years, 4159 participants (45.7%) had 1% to 49% coronary stenosis and 784 (8.6%) had 50% or greater coronary stenosis. Elevated BP in adolescence was associated with coronary stenosis in a dose-response fashion. Adolescents with stage 2 hypertension had a higher risk of severe coronary stenosis (≥50%), with an odds ratio of 1.84 (95% CI, 1.40-2.42) and an adjusted prevalence of 10.1% (95% CI, 8.6%-11.5%) compared to those with normal BP (adjusted prevalence, 6.9%; 95% CI, 5.7%-8.1%). Elevated BP categories according to the 2025 ACC/AHA (120-129/<80 mm Hg) and the 2024 ESC (120-139/70-89 mm Hg) were associated with severe coronary atherosclerosis in middle age. The association was stronger for SBP than for DBP.Conclusions and RelevanceIn this population-based cohort study, higher BP levels in adolescence were associated with a dose-dependent higher risk for atherosclerosis in middle age, particularly for severe coronary atherosclerosis. Excess risks of atherosclerosis were even evident in the elevated BP range in adolescence as defined by the 2025 ACC/AHA and 2024 ESC BP guidelines.
{"title":"Blood Pressure in Adolescence and Atherosclerosis in Middle Age.","authors":"Ángel Herraiz-Adillo,Hampus Eriksson,Viktor H Ahlqvist,Marcel Ballin,Patrik Wennberg,Bledar Daka,Cecilia Lenander,Daniel Berglind,Carl Johan Östgren,Oskar Lundgren,Karin Rådholm,Pontus Henriksson","doi":"10.1001/jamacardio.2025.4271","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4271","url":null,"abstract":"ImportanceElevated blood pressure (BP) in adolescence has been linked to higher risk of cardiovascular disease mortality, as well as surrogate markers of atherosclerosis, such as carotid intima-media thickness and coronary artery calcification. However, these markers do not fully capture the complex spectrum of subclinical atherosclerotic cardiovascular disease.ObjectiveTo examine the association between systolic and diastolic BP in adolescence and atherosclerosis in middle age, measured by coronary computed tomography angiography (CCTA).Design, Setting, and ParticipantsThis population-based cohort study conducted in Sweden linked BP data from the Swedish Military Conscription Register (1972-1987) during adolescence to atherosclerosis data from the Swedish Cardiopulmonary Bioimage Study (2013-2018) during middle age. Data analyses were performed in May 2025.ExposureAdolescent BP was categorized according to the 2025 American College of Cardiology/American Heart Association (ACC/AHA) and the 2024 European Society of Cardiology (ESC) guidelines.Main Outcomes and MeasuresThe primary outcome was coronary atherosclerosis, evaluated via CCTA stenosis. The associations were analyzed using multinomial logistic regression, adjusted (marginal) prevalences, and restricted cubic splines.ResultsA total of 10 222 men with mean (SD) age of 18.3 (0.5) years at baseline and median (IQR) age of 57.8 (53.4-61.2) years at follow-up were included. At baseline, mean (SD) systolic BP (SBP) and diastolic BP (DBP) were 127.6 (10.7) mm Hg and 68.3 (9.5) mm Hg, respectively. After a median (IQR) follow-up of 39.5 (35.2-42.8) years, 4159 participants (45.7%) had 1% to 49% coronary stenosis and 784 (8.6%) had 50% or greater coronary stenosis. Elevated BP in adolescence was associated with coronary stenosis in a dose-response fashion. Adolescents with stage 2 hypertension had a higher risk of severe coronary stenosis (≥50%), with an odds ratio of 1.84 (95% CI, 1.40-2.42) and an adjusted prevalence of 10.1% (95% CI, 8.6%-11.5%) compared to those with normal BP (adjusted prevalence, 6.9%; 95% CI, 5.7%-8.1%). Elevated BP categories according to the 2025 ACC/AHA (120-129/<80 mm Hg) and the 2024 ESC (120-139/70-89 mm Hg) were associated with severe coronary atherosclerosis in middle age. The association was stronger for SBP than for DBP.Conclusions and RelevanceIn this population-based cohort study, higher BP levels in adolescence were associated with a dose-dependent higher risk for atherosclerosis in middle age, particularly for severe coronary atherosclerosis. Excess risks of atherosclerosis were even evident in the elevated BP range in adolescence as defined by the 2025 ACC/AHA and 2024 ESC BP guidelines.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"7 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545132","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 : 2025-11-12DOI: 10.1001/jamacardio.2025.4151
Deborah M Siegal,Christian Sticherling,Jeff S Healey,William F McIntyre,Lene S Christensen,Ratika Parkash,Thomas Vanassche,David Conen,Michael Gold,Christopher B Granger,Jens Cosedis Nielsen,Marc Carrier,Daniel M Wojdyla,Julia W Erath,Lena Rivard,Valentina Kutyifa,David J Wright,Renato D Lopes
ImportanceThe Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation (ARTESiA) randomized clinical trial showed that in patients with subclinical atrial fibrillation (SCAF) apixaban, compared with aspirin, reduced stroke/systemic embolism but increased major bleeding.ObjectivesTo characterize major bleeding events (site and severity) and identify factors associated with major bleeding.Design, Setting, and ParticipantsThis was a prespecified subanalysis of the ARTESiA population who received treatment. This was an international, double-blind, double-dummy randomized clinical trial. Included were patients with 1 or more episodes of SCAF lasting 6 minutes to 24 hours with stroke risk factors (CHA2DS2-VASc score ≥3) or prior stroke without other risk factors. Study data were analyzed from August to November 2024.InterventionsApixaban, 5 mg, twice daily (2.5 mg twice daily when indicated) or aspirin, 81 mg, once daily.Main Outcomes and MeasuresMajor bleeding adjudicated by a blinded committee according to International Society on Thrombosis and Hemostasis criteria.ResultsA total of 3961 patients (mean [SD] age, 76.8 [7.6] years; 2535 male [64%]) were included in this analysis. After a mean (SD) follow-up of 3.5 (1.8) years, 1 or more major bleeding episodes occurred in 133 patients, 86 of 1989 taking apixaban and 47 of 1972 taking aspirin (1.71 vs 0.94 per 100-patient-years; hazard ratio [HR], 1.80; 95% CI, 1.26-2.57). The rates of intracranial (0.33 vs 0.40 per 100 patient-years; HR, 0.82; 95% CI, 0.43-1.57) and fatal (0.10% vs 0.16% per 100 patient-years; HR, 0.63; 95% CI, 0.20-1.91) bleeding were similar in the apixaban and aspirin groups, whereas the rate of gastrointestinal bleeding was higher in the apixaban group (0.89% vs 0.40% per 100 patient-years; HR, 2.23; 95% CI, 1.32-3.78). Among 133 index major bleeding events, those that occurred with apixaban were less likely to occur at critical sites (27.9% [24 of 86] vs 46.8% [22 of 47]; P = .03) including intracranial (18.6% [16 of 86] vs 42.6% [20 of 47]; P = .003). Most major bleeding events were nonemergencies characterized by decreased hemoglobin greater than or equal to 2 g/dL. Factors associated with major bleeding included nonsteroidal anti-inflammatory drug (NSAID) use (HR, 10.25; 95% CI, 6.57-15.99), cancer (HR, 2.87; 95% CI, 1.49-5.53), randomization to apixaban (HR, 1.84; 95% CI, 1.29-2.63), and age (HR, 1.47; 95% CI, 1.28-1.67, per 5-year increase).Conclusions and RelevanceResults of this subanalysis of the ARTESiA randomized clinical trial found that although the rate of major gastrointestinal bleeding was higher in patients with SCAF who were treated with apixaban vs aspirin, rates of fatal and intracranial bleeding were not different. Most major bleeding events were nonemergencies characterized by a decrease in hemoglobin level greater than or equal to 2 g/dL. NSAID use, cancer, randomization to apixaban, and increasing age wer
{"title":"Major Bleeding With Apixaban vs Aspirin: A Subanalysis of the ARTESiA Randomized Clinical Trial.","authors":"Deborah M Siegal,Christian Sticherling,Jeff S Healey,William F McIntyre,Lene S Christensen,Ratika Parkash,Thomas Vanassche,David Conen,Michael Gold,Christopher B Granger,Jens Cosedis Nielsen,Marc Carrier,Daniel M Wojdyla,Julia W Erath,Lena Rivard,Valentina Kutyifa,David J Wright,Renato D Lopes","doi":"10.1001/jamacardio.2025.4151","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.4151","url":null,"abstract":"ImportanceThe Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation (ARTESiA) randomized clinical trial showed that in patients with subclinical atrial fibrillation (SCAF) apixaban, compared with aspirin, reduced stroke/systemic embolism but increased major bleeding.ObjectivesTo characterize major bleeding events (site and severity) and identify factors associated with major bleeding.Design, Setting, and ParticipantsThis was a prespecified subanalysis of the ARTESiA population who received treatment. This was an international, double-blind, double-dummy randomized clinical trial. Included were patients with 1 or more episodes of SCAF lasting 6 minutes to 24 hours with stroke risk factors (CHA2DS2-VASc score ≥3) or prior stroke without other risk factors. Study data were analyzed from August to November 2024.InterventionsApixaban, 5 mg, twice daily (2.5 mg twice daily when indicated) or aspirin, 81 mg, once daily.Main Outcomes and MeasuresMajor bleeding adjudicated by a blinded committee according to International Society on Thrombosis and Hemostasis criteria.ResultsA total of 3961 patients (mean [SD] age, 76.8 [7.6] years; 2535 male [64%]) were included in this analysis. After a mean (SD) follow-up of 3.5 (1.8) years, 1 or more major bleeding episodes occurred in 133 patients, 86 of 1989 taking apixaban and 47 of 1972 taking aspirin (1.71 vs 0.94 per 100-patient-years; hazard ratio [HR], 1.80; 95% CI, 1.26-2.57). The rates of intracranial (0.33 vs 0.40 per 100 patient-years; HR, 0.82; 95% CI, 0.43-1.57) and fatal (0.10% vs 0.16% per 100 patient-years; HR, 0.63; 95% CI, 0.20-1.91) bleeding were similar in the apixaban and aspirin groups, whereas the rate of gastrointestinal bleeding was higher in the apixaban group (0.89% vs 0.40% per 100 patient-years; HR, 2.23; 95% CI, 1.32-3.78). Among 133 index major bleeding events, those that occurred with apixaban were less likely to occur at critical sites (27.9% [24 of 86] vs 46.8% [22 of 47]; P = .03) including intracranial (18.6% [16 of 86] vs 42.6% [20 of 47]; P = .003). Most major bleeding events were nonemergencies characterized by decreased hemoglobin greater than or equal to 2 g/dL. Factors associated with major bleeding included nonsteroidal anti-inflammatory drug (NSAID) use (HR, 10.25; 95% CI, 6.57-15.99), cancer (HR, 2.87; 95% CI, 1.49-5.53), randomization to apixaban (HR, 1.84; 95% CI, 1.29-2.63), and age (HR, 1.47; 95% CI, 1.28-1.67, per 5-year increase).Conclusions and RelevanceResults of this subanalysis of the ARTESiA randomized clinical trial found that although the rate of major gastrointestinal bleeding was higher in patients with SCAF who were treated with apixaban vs aspirin, rates of fatal and intracranial bleeding were not different. Most major bleeding events were nonemergencies characterized by a decrease in hemoglobin level greater than or equal to 2 g/dL. NSAID use, cancer, randomization to apixaban, and increasing age wer","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"19 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491718","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}
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