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Background and Aims: Coronary computed tomography angiography (CCTA) can guide downstream preventive treatment and improve patient prognosis, but its use in relation to education level remains unexplored., Methods: This nationwide register-based cohort study assessed all residents in Denmark between 2008 and 2018 without coronary artery disease (CAD) and 50-80 years of age (n = 1 469 724). Residents were divided according to four levels of education: low, lower-mid, higher-mid, and high. Outcomes were CCTA, functional testing, invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE)., Results: Individuals with the lowest education level underwent CCTA (absolute risk [AR] 3.95% individuals aged ≥50-59, AR 3.62% individuals aged ≥60-69, and AR 2.19% individuals aged ≥70-80) less often than individuals of lower-mid (AR 4.16%, AR 3.90%, and AR 2.41%), higher-mid (AR 4.38%, AR 4.30%, and AR 2.45%) and highest education level (AR 3.98%, AR 4.37%, and AR 2.30%). Similar differences were observed for functional testing. Conversely, use of ICA, and risks of revascularization and MACCE were more common among individuals of lowest education level. Among patients examined with CCTA (n = 50 234), patients of lowest education level less often underwent functional testing and more likely initiated preventive medication, underwent ICA, revascularization, and experienced MACCE., Conclusion: Despite tax-financed healthcare in Denmark, individuals of lowest education level were less likely to undergo CCTA and functional testing than persons of higher education level. Invasive coronary angiography utilization, revascularization, and MACCE risks were higher for individuals of lowest education level. Among CCTA-examined patients, patients of lowest education level were more likely to initiate preventive medication and had the highest risks of revascularization and MACCE when compared to higher education level groups. These findings suggest that the preventive potential of CCTA is underutilized in individuals of lower education level, a proxy for socioeconomic status. Socioeconomic differences in CAD assessment, care, and outcomes are likely even larger without tax-financed healthcare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned., Design and Methods: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024., Conclusion: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS)., Methods and Results: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%)., Conclusion: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—advisory board: AstraZeneca, Janssen-Cilag, and Novo Nordisk; grant support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number CPD5Y-2022004-HF); and speaker honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, and Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics; speaker engagements with Novartis and Roche Diagnostics; and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. C.B. discloses the following relationships—speaker honorarium: Bayer. T.B.-S. discloses the following relationships—steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial; advisory board: Sanofi Pasteur, Amgen, and GSK; speaker honorarium: Novartis, Sanofi Pasteur, and GSK; and research grants: GE Healthcare and Sanofi Pasteur. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. C.P.M. is supported by a grant from the National Institutes of Health (K23HL167659) and has received consulting fees/honorarium from Roche Diagnostics and Abbott Laboratories. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott and Shockwave. D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. The other authors report no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Aspirin is considered mandatory after myocardial infarction (MI). However, its long-term efficacy has been questioned. This study investigated the effectiveness of long-term aspirin after MI., Methods: Patients ≥ 40 years with MI from 2004-2017 who were adherent to aspirin one year after MI were included from Danish nationwide registries. At 2, 4, 6, and 8 years after MI, continued adherence to aspirin was evaluated. Absolute and relative risks of MI, stroke, or death at 2 years from each timepoint were calculated using multivariable logistic regression analysis with average treatment effect modeling standardized for age, sex, and comorbidities. Subgroup analyses were stratified by sex and age > and ≤ 65 years., Results: Among 40 114 individuals included, the risk of the composite endpoint was significantly higher for nonadherent patients at all timepoints. The absolute risk was highest at 2-4 years after MI for both adherent (8.34%, 95% confidence interval [CI]: 8.05-8.64%) and nonadherent patients (10.72%, 95% CI: 9.78-11.66%). The relative risk associated with nonadherence decreased from 4 years after index-MI and onwards: 1.41 (95% CI: 1.27-1.55) at 4-6 years and 1.21 (95% CI: 1.06-1.36) at 8-10 years (Ptrend = 0.056). Aspirin nonadherence in women and individuals > 65 years was not associated with increased risk. Pinteraction at each of the timepoints: Age-<0.001, <0.001, 0.002, 0.51; Sex - 0.25, 0.02, 0.02, 0.82., Conclusion: Nonadherence to long-term aspirin was associated with increased risk of MI, stroke, or death, but not in women or individuals > 65 years. The risk decreased from 4 years after MI with near statistical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The efficacy and safety of ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation (AF) on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) have not been established., Methods and Results: This was a nationwide cohort study of patients on OAC for AF who underwent PCI for MI from 2011 through 2019 and were prescribed a P2Y 12 inhibitor at discharge. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of death from any cause, stroke, recurrent MI, or repeat revascularization. The primary safety outcome was cerebral, gastrointestinal, or urogenital bleeding requiring hospitalization. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modelling. Outcomes were standardized for the individual components of the CHA 2 DS 2 -VASc and HAS-BLED scores as well as type of OAC, aspirin, and proton pump inhibitor use. We included 2259 patients of whom 1918 (84.9%) were prescribed clopidogrel and 341 (15.1%) ticagrelor or prasugrel. The standardized risk of MACE was significantly lower in the ticagrelor or prasugrel group compared with the clopidogrel group (standardized absolute risk, 16.3% vs. 19.4%; relative risk, 0.84, 95% confidence interval, 0.70-0.98; P = 0.02), while the risk of bleeding did not differ (standardized absolute risk, 5.5% vs. 5.1%; relative risk, 1.07, 95% confidence interval, 0.73-1.41; P = 0.69)., Conclusion: In patients with AF on OAC who underwent PCI for MI, treatment with ticagrelor or prasugrel vs. clopidogrel was associated with reduced ischaemic risk, without a concomitantly increased bleeding risk., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Aspirin therapy for primary prevention of cardiovascular disease (CVD) is controversial, and guideline recommendations have changed throughout the last decades. We report temporal trends in primary prevention aspirin use among persons with and without diabetes and describe characteristics of incident aspirin users., Methods and Results: Using Danish nationwide registries, we identified incident and prevalent aspirin users in a population of subjects ≥40 years without CVD eligible for primary preventive aspirin therapy from 2000 through 2020. Temporal trends in aspirin users with and without diabetes were assessed, as were CVD risk factors among incident users. A total of 522 680 individuals started aspirin therapy during the study period. The number of incident users peaked in 2002 (39 803 individuals, 1.78% of the eligible population) and was the lowest in 2019 (11 898 individuals, 0.49%), with similar trends for subjects with and without diabetes. The percentage of incident users with no CVD risk factors [diabetes, hypertension, hypercholesterolemia, or chronic obstructive pulmonary disease (a proxy for smoking)] decreased from 53.9% in 2000 to 30.9% in 2020. The temporal trends in prevalent aspirin users followed a unimodal curve, peaked at 7.7% in 2008, and was 3.3% in 2020. For subjects with diabetes, the peak was observed in 2009 at 38.5% decreasing to 17.1% in 2020., Conclusion: Aspirin therapy for primary prevention of CVD has decreased over the last two decades. However, the drug remained used in individuals with and without diabetes, and a large proportion of individuals started on aspirin therapy had no CVD risk factors., Competing Interests: Conflict of interest: M.P. discloses the following relationships not related to the content of the manuscript—Advisory Board: AstraZeneca, Janssen-Cilag; Grant Support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number: CPD5Y-2022004-HF); Speaker Honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen-Cilag., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome are unknown., Methods and Results: Individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity troponin-T (hsTnT) measurements 1-7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0-30 and 31-365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by <20%, > 20 to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modeling. Of the 28 902 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31-365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0-30 days: 4.3%, 31-365 days: 7.2%). In this group, mortality was significantly higher in those with a > 20 to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations (0-30 days: 0.1%, 31-365 days: 0.9%) and did not depend on relative or absolute changes between measurements., Conclusions: Individuals with suspected acute coronary syndrome and two consecutively elevated hsTnT concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—Advisory Board: AstraZeneca, Janssen-Cilag; Grant Support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number: CPD5Y-2022004-HF); Speaker Honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, speaker engagements with AstraZeneca, Novartis, and Roche Diagnostics, and participates on clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. C.B. discloses the following relationships—speaker honorarium: Bayer. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. T.B.-S. discloses the following relationships—Steering Committee member of the Amgen financed GALACTIC-HF trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘NUDGE-FLU’ trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘DANFLU-1’ trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘DANFLU-2’ trial, Steering Committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial, Advisory Board: Sanofi Pasteur, Amgen and GSK, speaker honorarium: Novartis, Sanofi Pasteur and GSK, Research grants: GE Healthcare and Sanofi Pasteur. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott, Shockwave. D.L.B. discloses the following relationships—advisory board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. The other authors report no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19-97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in ∼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUC ROC ), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (<50 versus ≥ 50 years) were performed. BMI, WHR, EFM, and total-cholesterol were independently associated with MACE (P ≤ 0.003) and resulted in significantly positive NRI when added to age, sex, smoking status, and systolic blood pressure. Only total-cholesterol increased discrimination ability (AUC ROC difference; P < 0.001). In subjects < 50 years, the prediction model with total-cholesterol was superior to the model including BMI, but not superior to models containing WHR or EFM, while in those ≥ 50 years, the model with total-cholesterol was superior to all models containing anthropometric variables, whether assessed individually or combined. We found a potential role for replacing total-cholesterol with anthropometric measures for MACE-prediction among individuals < 50 years when laboratory measurements are unavailable, but not among those ≥ 50 years., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VS has received honoraria from Novo Nordisk and Sanofi for consultations. He also has ongoing research collaboration with Bayer Ltd. (All unrelated to the present study). SSg has received speakers and consultant honoraria from Actelion Ltd. MHO has from 2013-2018 received a part time clinical research grant from the Novo Nordic Foundation. MP has the followings relationships – Advisory Board and Speaking Honoraria: AstraZeneca; Speaking Honoraria: Bayer, Boehringer Ingelheim., (© 2022 The Author(s).)

Background: Unstable angina (UA) is a component of acute coronary syndrome that is only occasionally included in primary composite endpoints in clinical cardiovascular trials. The aim of this paper is to elucidate the potential benefits and disadvantages of including UA in such contexts., Summary: UA comprises <10% of patients with acute coronary syndromes in contemporary settings. Based on the pathophysiological similarities, it is ideal as a part of a composite endpoint along with myocardial infarction (MI). By adding UA as a component of a primary composite endpoint, the number of events and feasibility of the trial should increase, thus decreasing its size and cost. Furthermore, UA has both economic and quality of life implications on a societal and an individual level. However, there are important challenges associated with the use of UA as an endpoint. With the introduction of high-sensitivity troponins, the number of individuals diagnosed with UA has decreased to rather low levels, with a reciprocal increase in the number of MI. In addition, UA is particularly challenging to define given the subjective assessment of the index symptoms, rendering a high risk of bias. To minimize bias, strict criteria are warranted, and events should be adjudicated by a blinded endpoint adjudication committee., Key Messages: UA should only be chosen as a component of a primary composite endpoint in cardiovascular trials after thoroughly evaluating the pros and cons. If it is chosen to include UA, appropriate precautions should be taken to minimize possible bias., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

[Figure: see text].

Aims: To determine whether a strategy of intensive blood pressure control reduces the risk of heart failure (HF) events consistently across the spectrum of kidney function and albuminuria., Methods and Results: SPRINT was a randomized clinical trial in which 9361 individuals ≥50 years, at high risk for or with cardiovascular disease, a systolic blood pressure of 130-180 mmHg, but without diabetes, were randomized to intensive (target <120 mmHg) vs. standard (target <140 mmHg) blood pressure control. We assessed whether estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) modified the effects of the blood pressure control strategy in reducing HF events (either hospitalization or emergency department visits) and the composite of HF events or cardiovascular death, using Cox proportional hazards regression and restricted cubic splines. Of the 9361 individuals included in SPRINT, eGFR and UACR were available for 9324 (99.6%) and 8913 (95.2%) subjects, respectively, including 2650 (28.4%) with eGFR <60 mL/min/1.73 m 2 and 248 (2.8%) with UACR >300 mg/g. During a median follow-up of 3.2 years (range 0-4.8 years), 160 (1.8%) participants had HF events and 233 (2.6%) had HF events or cardiovascular death. Risks of HF events or cardiovascular death increased from 0.42 (0.34-0.53) per 100 patient-years in patients with eGFR ≥60 mL/min/1.73 m 2 and UACR <30 mg/g to 4.55 (3.00-6.91) per 100 patient-years in patients with eGFR <60 mL/min/1.73 m 2 and UACR >300 mg/g. A similar gradient was observed for HF events alone. Both eGFR and UACR were independently, non-linearly associated with HF hospitalization and HF hospitalization or cardiovascular death (test for overall trend, P < 0.001). While the effects of intensive blood pressure control on HF event risk appeared to attenuate at lower eGFR and higher UACR, there was no significant interaction between eGFR or UACR and blood pressure control strategy (continuous and categorical interaction P > 0.05)., Conclusion: In SPRINT, eGFR and albuminuria were strong and additive determinants in forecasting HF risk. The effect of intensive blood pressure control in decreasing HF risk did not significantly vary across the spectrum of kidney function or albuminuria. Multidisciplinary pathways, incorporating blood pressure control, are needed for at-risk patients with chronic kidney disease to attenuate HF risk., Trial Registration: ClinicalTrials.gov Identifier NCT01206062., (© 2020 European Society of Cardiology.)

It is unclear whether 12-lead ECG employing standard criteria for left ventricular hypertrophy (LVH) provides similar information with respect to long-term cardiovascular risk as echocardiography. The authors performed a retrospective cohort study of 1376 individuals without cardiovascular disease, who underwent ECG (LVH defined using the Sokolow-Lyon voltage combination (>35 mm) or the Cornell voltage-duration product (>2440 mm × ms)) and echocardiography (LVH defined as LV mass index (LVMI) >95 g/m 2 for women and >115 g/m 2 for men). The prognostic ability of LVH was assessed in Cox regression models adjusted for age, sex, smoking, systolic blood pressure, total cholesterol, antihypertensive medication, and fasting glucose. The primary end point was the composite of coronary events, heart failure, stroke, or death. The main secondary end point was heart failure or cardiovascular death. Median age was 67 (range 56-79) years, 68% were male. Eleven percent had ECG-defined LVH, 17% had echocardiographic LVH. Over median 8.5 years, 29% experienced a primary event. Event rates were 29%/35% for persons without/with ECG-defined LVH and 27%/39% for those without/with echocardiographic LVH. The Sokolow-Lyon combination, Cornell product, and ECG-defined LVH did not significantly predict the primary end point (P ≥ .05), but ECG-defined LVH predicted heart failure or cardiovascular death (adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.13-3.08); P = .02). Conversely, LVMI was a significant, independent predictor of the primary end point (adjusted HR, 1.87, 95% CI, 1.13-3.10; P = .01), as was echocardiographic LVH (adjusted HR, 1.27, 95% CI, 1.01-1.61; P = .04). Echocardiographic LVH may be a better predictor of long-term cardiovascular risk than ECG-defined LVH in middle-aged and older individuals., (© 2020 Wiley Periodicals LLC.)

Background: Treatment with beta-blockers is currently recommended after myocardial infarction (MI). The evidence relies on trials conducted decades ago before implementation of revascularization and contemporary medical therapy or in trials enrolling patients with heart failure or reduced left ventricular ejection fraction (LVEF ≤ 40%). Accordingly, the impact of beta-blockers on mortality and morbidity following acute MI in patients without reduced LVEF or heart failure is unclear., Methods/design: The Danish trial of beta-blocker treatment after myocardial infarction without reduced ejection fraction (DANBLOCK) is a prospective, randomized, controlled, open-label, non-blinded endpoint clinical trial designed to evaluate the efficacy of beta-blocker treatment in post-MI patients in the absence of reduced LVEF or heart failure. We will randomize 3570 patients will be randomized within 14 days of index MI to beta-blocker or control for a minimum of 2 years. The primary endpoint is a composite of all-cause mortality, recurrent MI, acute decompensated heart failure, unstable angina pectoris, or stroke. The primary composite endpoint will be assessed through locally reported and adjudicated endpoints supplemented by linkage to the Danish national registers. A number of secondary endpoints will be investigated including patient reported outcomes and cardiovascular mortality. Data from similar ongoing trials in Norway and Sweden will be pooled to perform an individual patient data meta-analysis., Discussion: DANBLOCK is a randomized clinical trial investigating the effect of long-term beta-blocker therapy after myocardial infarction in patients without heart failure and reduced LVEF. Results from the trial will add important scientific evidence to inform future clinical guidelines., Trial Registration: Clinicaltrials.gov, NCT03778554. Registered on 19 December 2018. European Clinical Trials Database, 2018-002699-42, registered on 28 September 2018.

Massive, submassive, and nonmassive pulmonary embolism relate to the hemodynamic state, while saddle pulmonary embolus is a purely radiologic term. Patients with saddle embolus often present with hemodynamic compromise. However, treatment depends on the clinical presentation, and stable patients with a saddle pulmonary embolus can respond well to conventional anticoagulation., Competing Interests: None declared.

Infarction of the anterior myocardial wall results in anterior ST-elevation. However, ST-deviation may also appear inferiorly and may aid in localizing the culprit lesion., Competing Interests: None declared.