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Background: Sparse information regarding the long-term risk of acute myocardial infarction (MI) following a transient ischemic attack (TIA) emphasizes further research to guide preventive strategies and risk stratification in patients with a TIA., Methods: We conducted a nationwide cohort study to investigate the 5-year risk of MI and all-cause mortality in patients with a first-time TIA. Patients with a first-time TIA were identified in the Danish Stroke Registry (2013-2020), matched on age, sex, and calendar year (1:4) with the general population and (1:1) with patients with first-time ischemic stroke. The 5-year risks of MI and all-cause mortality were estimated by the Aalen-Johansen and Kaplan-Meier estimators. The groups were compared using Cox regression, while adjusting for cardiovascular comorbidities., Results: We identified 21 743 patients with TIA, 86 972 matched individuals from the general population, and 21 743 matched control patients with ischemic stroke. Median age was 70 (25th to 75th percentile, 60-78) years; 52% were male. Comorbidity burden was the lowest in general population controls, intermediate in patients with TIA, and the highest in patients with ischemic stroke. The 5-year risk of MI was 2.0% in patients with TIA, 1.5% in the general population ( P <0.001), and 2.2% in the ischemic stroke population ( P <0.001). After adjustment, these differences in MI rate were similar (TIA versus general population; hazard ratio, 0.99 [95% CI, 0.98-1.02] and TIA versus ischemic stroke; hazard ratio, 0.99 [95% CI, 0.96-1.01]). The 5-year risk of mortality was 17.0% in patients with TIA compared with 14.0% in the general population ( P <0.001) and 27.0% in ischemic stroke population ( P <0.001). The differences in mortality persisted following adjustments for patients with TIA versus general population (hazard ratio, 1.25 [95% CI, 1.19-1.31]) and for patients with TIA versus ischemic stroke (hazard ratio, 0.43 [95% CI, 0.41-0.46])., Conclusions: Patients with first-time TIA had a low 5-year incidence of MI, which was not significantly different from that of the general population and patients with first-time ischemic stroke after adjustments for comorbidities. However, patients with TIA had a 25% higher all-cause mortality rate than the general population, which was not readily explained by MI risk. Hence, the findings do not endorse the need to raise further awareness regarding MI in patients with TIA., Competing Interests: Dr Kristensen reports advisory board honoraria from Bayer and AstraZeneca. Dr Johnsen reports consultant work for Bristol Myers Squibb and Pfizer and institutional grants from Bristol Myers Squibb, Pfizer, and Novo Nordisk. Dr Kruuse reports compensation from the Novo Nordisk Foundation and from Bayer Healthcare. Dr Torp-Pedersen reports grants for studies from Bayer and Novo Nordisk. Dr Køber reports speaker honoraria from Novo Nordisk, Novartis, AstraZeneca, Boehring, and Bayer. Dr Fosbøl reports grants from Novo Nordisk Fonden. Dr Sørensen reports compensation from Novo Nordisk for data and safety monitoring services. None of the disclosures mentioned are related to this study. The other authors report no conflicts.

Background: Despite improved survival, hospitalization is still common among patients with heart failure (HF)., Objective: This study aimed to examine temporal trends in infection-related hospitalization among HF patients and compare it to temporal trends in the risk of HF hospitalization and death., Methods: Using Danish nationwide registers, we included all patients aged 18 to 100 years, with HF diagnosed between January 1, 1997 and December 31, 2017, resulting in a total population of 147.737 patients. The outcomes of interest were primarily infection-related hospitalization and HF hospitalization and secondarily all-cause mortality. The Aalen Johansen's estimator was used to estimate 5-year absolute risks for the primary outcomes. Additionally, cox analysis was used for adjusted analyses., Results: The population had a median age of 74 [64, 82] years and 57.6 % were males. Patients with HF had a higher risk of infection over time 16.4 % (95% CI 16.0-16.8) in 1997 to 2001 vs 24.5% (95% CI 24.0-24.9) in 2012 to 2017. In contrast, they had a lower risk of HF hospitalization 26.5% (95% CI 26.1-27.0) in 1997 to 2001 vs 23.2% (95% CI 22.8-23.7) in 2012 to 2017. The risk of infection stratified by infection type showed similar trends for all infection types and marked the risk of pneumonia infection as the most significant in all subintervals., Conclusion: In the period from 1997 to 2017, we observed patients with HF had an increased risk of infection-related hospitalization, driven by pneumonia infections. In contrast, the risk of HF hospitalization decreased over time., Competing Interests: Conflict of interest None reported., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To assess the level of adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment using real-world data and to investigate the sociodemographic and clinical factors associated with discontinuation of GLP-1RAs., Methods: First-time users of GLP-1RAs with type 2 diabetes mellitus (T2DM), aged ≥18 years, in the period 2007 to 2020, were identified using Danish registries, allowing all participants a minimum of 18 months' follow-up. Adherence to GLP-1RA therapy (medication possession ratio >0.80) and discontinuation of GLP-1RA therapy was estimated at 6- and 12-month follow-ups. Multivariable cause-specific Cox regression was used to identify sociodemographic and clinical factors associated with risk of discontinuation., Results: In total, 44 343 first-time users of GLP-1RAs with T2DM were identified (mean age 58.6 years, 42.7% female, median duration of T2DM 6.8 years, median glycated haemoglobin level 65 mmol/mol). The absolute risk of discontinuing GLP-1RA treatment within 6 months was 14.2% (95% confidence interval [CI] 13.9-14.6) and 21.2% (95% CI 20.8-21.5) within 12 months. At 6 months, 50.4% were adherent to GLP-1RA therapy and at 12 months, 48.6% remained adherent. In the multivariable model, younger (<40 years) and older age (>75 years), higher Charlson Comorbidity Index score, lower household income, high school and longer university degree as educational attainment level, and longer diabetes duration were associated with a higher risk of discontinuing GLP-1RA treatment., Conclusion: Approximately one in five patients discontinued GLP-1RA therapy within the first 12 months and only half were adherent. Overall, lower socioeconomic status and higher comorbidity burden were associated with higher risk of discontinuing GLP-1RA treatment., (© 2024 John Wiley & Sons Ltd.)

Aims: Chronic kidney disease (CKD) is a well-established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 have been systematically excluded from clinical trials. This study investigated the incidence of HF and kidney outcomes in HF patients with and without advanced CKD, that is, eGFR < 30., Methods: From nationwide registries, HF patients were identified from 2014 to 2018 and categorized into three groups according to baseline eGFR (eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30). The incidence of primary outcomes (all-cause mortality, HF hospitalization, end-stage kidney disease and sustained 50% eGFR decline) was estimated using cumulative incidence functions., Results: Of the 21 959 HF patients included, the median age was 73.9 years, and 30% of patients had an eGFR between 30 and 60 and 7% had an eGFR < 30. The 4 year incidence of all-cause mortality was highest for patients with eGFR < 30 (28.3% for patients with eGFR ≥ 60, 51.6% for patients with 60 > eGFR ≥ 30 and 72.2% for patients with eGFR < 30). The 4 year incidence of HF hospitalization was comparable between the groups (25.8%, 29.8% and 26.1% for patients with eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30, respectively). For patients with eGFR < 30, kidney outcomes were four times more often the first event than patients with eGFR > 30 (4 year incidence of kidney outcome as the first event was 5.0% for eGFR ≥ 60, 4.8% for 60 > eGFR ≥ 30 and 20.1% for eGFR < 30)., Conclusions: Patients with advanced CKD had a higher incidence of mortality and poorer kidney outcomes than those without advanced CKD, but a similar incidence of HF hospitalizations., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: To investigate return to work and workforce detachment in ischemic stroke, including the association with age and level of education., Methods: Patients in the workforce aged 18 to 60 with first-time ischemic stroke between 1997 and 2017 were identified in Danish registers and followed for 5 years. The cumulative incidence of return to work and subsequent workforce detachment was computed overall and stratified according to age group and education level. Cox regression analysis was used for multivariate analysis., Results: A total of 28,325 patients were included (median age 52.3 (interquartile range (IQR) 46.1 to 56.6) and 64.3% male). After 1 year, 62.0% were in the workforce, highest in age group 18 to 30 (80.0%) and lowest in patients aged 51 to 60 (58.5%). One-year cumulative incidence of return to work overall was 73.4% (20,475), highest in the young age group (87.0%, 76.7%, 74.5%, and 71.3% for age group 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high education (80.3%, 72.1%, and 71.3% for long higher, basic or vocational education, respectively). One-year cumulative incidence of subsequent workforce detachment was 25.6% (5248), lowest in young age (22.4%, 23.1%, 24.1%, and 27.2% for age groups 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high level of education (13.0%, 28.4%, and 27.2% for long higher, basic, and vocational education, respectively). During the full follow-up, 10,855 (53.0%) left the workforce again., Conclusions: A high proportion of patients returned to work within 1 year, but more than half left the workforce again. Young age and long education were associated with a higher incidence of return to work and lower subsequent workforce detachment., Competing Interests: C.T.P. has received grants for studies from Novo Nordisk and Bayer without relation to the current study. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Atrial fibrillation (AF) is a common arrhythmia associated with reduced quality of life that can lead to serious complications such as stroke and heart failure. Ablation is a safe and effective treatment for AF but is not offered equally to all patients. The aim of this study is to identify demographic groups more or less likely to undergo AF ablation., Methods and Results: All patients with newly diagnosed AF between 2010 and 2018 were identified in the Danish nationwide registries. The association between gender, age, level of education and attachment to the job market, and the likelihood of receiving AF ablation was investigated using multivariable Cox proportional hazard analysis. Cumulative incidence was calculated using the Aalen-Johansen estimator. A total of 176 248 patients were included. Men were more likely to receive ablation than women (7% vs. 3%). Patients aged 25-44 and 45-64 were most likely to receive ablation, while only 0.7% of patients aged 80 or above received ablation. The rate of ablation significantly decreased with decreasing level of education. Full-time employed patients were most likely to receive ablation, followed by self-employed, unemployed, on sick leave, undergoing education, and early retired patients. Retired patients were the least likely to receive ablation (3%)., Conclusion: This study found that women, older patients, patients with lower levels of education, and patients on social benefits are less likely to receive AF ablation. These findings suggest that there are significant social and economic disparities in AF ablation treatment in Denmark., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Catheter ablation (CA) is a well-established treatment option for atrial fibrillation (AF), where sedation and analgesia are pivotal for patient comfort and lesion formation. The impact of anaesthesia type on AF recurrence rates remains uncertain. This study aimed to examine AF recurrence rates depending on conscious sedation (CS) vs. general anaesthesia (GA) during CA., Methods and Results: Utilizing nationwide data from the Danish healthcare registries, we conducted this cohort study involving adults (≥18 years) undergoing first-time CA for AF between 2010 and 2018. Patients were categorized by anaesthesia type (CS or GA), with the primary endpoint being AF recurrence, defined by a composite endpoint of either antiarrhythmic drug (AAD) prescriptions, AF-related hospital admissions, electrical cardioversions, or AF re-ablation. The impact of anaesthesia type was evaluated using multivariable Cox proportional hazards analysis. The study cohort comprised 7957 (6421 CS and 1536 GA) patients. Persistent AF, hypertension, and heart failure, as well as use of AAD, were more prevalent in the GA group. Cumulative incidences of recurrent AF were higher in the CS group at 1 (46% vs. 37%) and at 5 (68% vs. 63%) years. Multivariate analysis revealed CS as significantly associated with increased risk of AF recurrence at 5-year follow-up [hazard ratio 1.26 (95% confidence interval 1.15-1.38)], consistent across paroxysmal and persistent AF subtypes., Conclusion: This nationwide cohort study suggests a higher risk of AF recurrence with CS during CA compared to GA. These results advocate for considering GA as the preferred anaesthesia type for improved CA outcomes., Competing Interests: Conflict of interest: L.D.R.-V., J.T., C.R.Z., C.M., R.H., A.J., R.H.W., G.G.: none. M.H.R.: Speaker honoraria from Boston Scientific and CardioFocus. J.H.: Speaker fees and consultant honoraria from Boston Scientific and Biosense Webster. M.L.H.: Received research grants from Biosense Webster and Medtronic., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Limited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021., Methods: Using nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry., Results: From 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77-84], 60.3% female) were included. From 2000 to 2003 to 2015-2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%)., Conclusions: From 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly., Competing Interests: Declaration of competing interest ML reports research grants from Karen Elise Jensen Fonden, Danish Heart Foundation, Bayer, and BMS; speaker fees from BMS/Pfizer, Bayer, Astra Zeneca, MSD, and Merck; and advisory board positions with BMS/Pfizer, Bayer, and Mundipharma. NN reports speaker fees from Astra Zeneca and Bayer. SKN, AH, JES, MHJ, GG, and PM report no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF., Methods and Results: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29-2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69-9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40-9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75-10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90-19.49]., Conclusion: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Aims: The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. The aim of this study was to determine the incidence of AF and stroke in HCM patients and identify the risk factors., Methods and Results: Using Danish national registries, all HCM patients from 2005 to 2018 were included. The association between HCM, incident AF, and stroke was investigated using multivariable Cox proportional hazards analysis. Cumulative incidences were calculated using the Aalen-Johansen estimator. Among the 3367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. Atrial fibrillation incidence was equal between sexes and increased for patients with ischaemic heart disease [IHD; hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.08-1.63], hypertension (HT) (HR 1.36, 95% CI 1.14-1.67), and obstructive HCM (HR 1.27, 95% CI 1.05-1.52). Seven per cent developed stroke, with no difference detected stratifying for the presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OACs), stroke was less likely (HR 0.4, 95% CI 0.18-0.86, P = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis., Conclusion: Obstructive HCM, HT, and IHD were associated with increased risk of AF. Prevalent AF alone was not predictive of stroke; however, AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 Aim: There are a paucity of studies investigating workforce affiliation in connection with first-time implantable cardioverter defibrillator (ICD)-implantation. This study explored workforce affiliation and risk markers associated with not returning to work in patients with ICDs., Methods: Using the nationwide Danish registers, patients with a first-time ICD-implantation between 2007 and 2017 and of working age (30-65 years) were identified. Descriptive statistic and logistic regression models were used to describe workforce affiliation and to estimate risk markers associated with not returning to work, respectively. All analyses were stratified by indication for implantation (primary and secondary prevention)., Results: Of the 4659 ICD-patients of working age, 3300 patients (71%) were members of the workforce (employed, on sick leave or unemployed) (primary: 1428 (43%); secondary:1872 (57%)). At baseline, 842 primary and 1477 secondary prevention ICD-patients were employed. Of those employed at baseline, 81% primary and 75% secondary prevention ICD-patients returned to work within 1 year, whereof more than 80% remained employed the following year. Among patients receiving sick leave benefits at baseline, 25% were employed after 1 year. Risk markers of not returning to work were 'younger age' in primary prevention ICD-patients, while 'female sex', left ventricular ejection fraction 'LVEF ≤40', 'lower income', and '≥3 comorbidities' were risk markers in secondary prevention ICD-patients. Lower educational level was a risk marker in both patient groups., Conclusion: High return-to-work proportions following ICD-implantation, with a subsequent high level of employment maintenance were found. Several significant risk markers of not returning to work were identified including 'lower educational level' that posed a risk in both patient groups., Trial Registration Number: Capital Region of Denmark, P-2019-051., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Trends in patient selection and use of pharmacotherapy prior to catheter ablation (CA) for supraventricular tachycardia (SVT) are not well described. This study examined temporal trends in patients undergoing first-time CA for regular SVT, including atrioventricular nodal re-entry tachycardia (AVNRT), accessory pathways (APs), and ectopic atrial tachycardia (EAT) on a nationwide scale in Denmark in the period 2001-2018., Methods and Results: Using Danish Nationwide registers, 9959 patients treated with first-time CA for SVT between 2001 and 2018 were identified, of which 6023 (61%) received CA for AVNRT, 2829 (28%) for AP, and 1107 (11%) for EAT. Median age was 55, 42, and 55 in the AVNRT, APs, and EAT group, respectively. The number of patients receiving CA increased from 1195 between 2001 and 2003 to 1914 between 2016 and 2018. The percentage of patients with a CHA 2 DS 2 -VASc score ≥ 2 increased in all patient groups. The number of patients who underwent CA with no prior use of antiarrhythmic- or rate limiting medicine increased significantly, though prior use of beta-blockers increased for AVNRT patients. Use of verapamil decreased in all three SVT groups (P < 0.05). Use of amiodarone and class 1C antiarrhythmics remained low, with the highest usage among EAT patients., Conclusion: Between 2001 and 2018, CA was increasingly performed in patients with SVT, primarily AVNRT- and EAT patients. The burden of comorbidities increased. Patients undergoing CA without prior antiarrhythmic- or rate-limiting drug therapy increased significantly. Use of beta-blockers increased and remained the most widely used drug., (© 2023. The Author(s).)

Background: Although kidney insufficiency has been shown to be associated with increased risk of myocardial injury, benefit of coronary angiography (CAG) and revascularization remains uncertain, with implications on management strategies and outcomes. We aimed to compare rates of CAG and revascularization and subsequent risk of cardiovascular and kidney outcomes in hospitalized patients with myocardial injury and kidney dysfunction., Methods: Retrospective cohort study encompassing hospitalized patients with myocardial injury i.e. elevated troponin I or T and an eGFR ≤60 ml/min/1.73 m 2 identified between 2011 and 2021 in Danish national registers. 30-day odds for CAG were computed across granular eGFR-categories based on multiple logistic regression. Standardized one-year risks of cardiovascular and kidney outcomes including mortality were determined based on hazards obtained in multiple Cox regression., Results: A total of 52,798 patients with myocardial injury were identified. CAG was performed in 14.3 % (n = 7549). 30-day odds ratios for CAG were 0.64 [0.60-0.68], 0.38 [0.34-0.42], 0.18 [0.14-0.22], and 0.35 [0.30-0.40] in patients with eGFR 31-45 ml/min/1.73 m 2 , eGFR 15-30 ml/min/1.73 m 2 for eGFR<15 ml/min/1.73 m 2 and chronic dialysis, respectively (eGFR 46-60 ml/min/1.73 m 2 as reference). Median follow-up was 4.1 years. One-year mortality risk differences associated with CAG and revascularization (no CAG as reference) were -7.8 [-7.0; -8.7] and -9.1 [-8.4; -9.9] for eGFR 46-60 ml/min/1.73 m 2 ; -7.0 [-5.7;-8-3] and -8.0 [-6.6; -9.5] for eGFR 31-45 ml/min/1.73 m 2 ; -5.4 [-3.0; -7.2] and -5.2 [-2.2; -8.3] for eGFR 15-30 ml/min/1.73 m 2 ; -8.8 [-3.1; -13.7] and -5.4 [3.1; -13.4] for eGFR<15 ml/min/1.73 m 2 ; and -4.9 [-0.1; -9.7] and -4.2 [1.5; -9.2] for chronic dialysis, respectively., Conclusion: Probability of CAG following myocardial injury declined with progressive kidney dysfunction. Overall, CAG was associated with lower mortality irrespective of kidney function and subsequent revascularization., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To identify the absolute risk, causes, and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE)., Methods and Results: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease [1-year AR: 9.5% (95% CI: 9.3%-9.8%)], followed by cardiovascular disease [1-year AR: 6.3% (95% CI: 5.9%-6.5%)], cancer [1-year AR: 6.0% (95% CI: 5.8%-6.4%)], venous thromboembolism [1-year AR: 5.2% (95% CI: 5.0%-5.2%)], and symptom diagnoses [1-year AR: 5.2% (95% CI: 5.0%-5.4%)]. Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization., Conclusion: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function., Methods: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding., Results: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2., Conclusions: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background We describe calendar time trends of patients with simple congenital heart disease. Methods and Results Using the nationwide Danish registries, we identified individuals diagnosed with isolated ventricular septal defect, atrial septal defect, patent ductus arteriosus, or pulmonary stenosis during 1977 to 2015, who were alive at 5 years of age. We reported incidence per 1 000 000 person-years with 95% CIs, 1-year invasive cardiac procedure probability and age at time of diagnosis stratified by diagnosis age (children ≤18 years, adults >18 years), and 1-year all-cause mortality stratified by diagnosis age groups (5-30, 30-60, 60+ years). We identified 15 900 individuals with simple congenital heart disease (ventricular septal defect, 35.2%; atrial septal defect, 35.0%; patent ductus arteriosus, 25.2%; pulmonary stenosis, 4.6%), of which 75.7% were children. From 1977 to 1986 and 2007 to 2015, the incidence rates increased for atrial septal defect in adults (8.8 [95% CI, 7.1-10.5] to 31.8 [95% CI, 29.2-34.5]) and in children (26.6 [95% CI, 20.9-32.3] to 150.8 [95% CI, 126.5-175.0]). An increase was only observed in children for ventricular septal defect (72.1 [95% CI, 60.3-83.9] to 115.4 [95% CI, 109.1-121.6]), patent ductus arteriosus (49.2 [95% CI, 39.8-58.5] to 102.2 [95% CI, 86.7-117.6]) and pulmonary stenosis (5.7 [95% CI, 3.0-8.3] to 21.5 [95% CI, 17.2-25.7]) while the incidence rates remained unchanged for adults. From 1977-1986 to 2007-2015, 1-year mortality decreased for all age groups (>60 years, 30.1%-9.6%; 30-60 years, 9.5%-1.0%; 5-30 years, 1.9%-0.0%), and 1-year procedure probability decreased for children (13.8%-6.6%) but increased for adults (13.3%-29.6%) were observed. Conclusions Increasing incidence and treatment and decreasing mortality among individuals with simple congenital heart disease point toward an aging and growing population. Broader screening methods for asymptomatic congenital heart disease are needed to initiate timely treatment and follow-up.

Background: Research regarding out-of-hospital cardiac arrest (OHCA) survival of diabetes patients is sparse and it remains unknown whether initiatives to increase OHCA survival benefit diabetes and non-diabetes patients equally. We therefore examined overall and temporal survival in diabetes and non-diabetes patients following OHCA., Methods: Adult presumed cardiac-caused OHCAs were identified from the Danish Cardiac Arrest Registry (2001-2014). Associations between diabetes and return of spontaneous circulation upon hospital arrival and 30-day survival were estimated with logistic regression adjusted for patient- and OHCA-related characteristics., Results: In total, 28,955 OHCAs were included of which 4276 (14.8%) had diabetes. Compared with non-diabetes patients, diabetes patients had more comorbidities, same prevalence of bystander-witnessed arrests (51.7% vs. 52.7%) and bystander cardiopulmonary resuscitation (43.2% vs. 42.0%), more arrests in residential locations (77.3% vs. 73.0%) and were less likely to have shockable heart rhythm (23.5% vs. 27.9%). Temporal increases in return of spontaneous circulation and 30-day survival were seen for both groups (return of spontaneous circulation: 8.8% in 2001 to 22.3% in 2014 (diabetes patients) vs. 7.8% in 2001 to 25.7% in 2014 (non-diabetes patients); and 30-day survival: 2.8% in 2001 to 9.7% in 2014 vs. 3.5% to 14.8% in 2014, respectively). In adjusted models, diabetes was associated with decreased odds of return of spontaneous circulation (odds ratio 0.74 (95% confidence interval 0.66-0.82)) and 30-day survival (odds ratio 0.56 (95% confidence interval 0.48-0.65)) (interaction with calendar year p =0.434 and p =0.243, respectively)., Conclusion: No significant difference in temporal survival was found between the two groups. However, diabetes was associated with lower odds of return of spontaneous circulation and 30-day survival.

Background: Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs., Methods: We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE, and cardiac device., Results: Among 6506 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men) the IE prevalence was 7.1% (95% CI, 6.5-7.8). The lowest IE prevalence was found with Streptococcus pneumoniae ( S pneumoniae ) 1.2% (0.8-1.6) and Spyogenes 1.9% (0.9-3.3). An intermediary IE prevalence was found with Sanginosus 4.8% (3.0-7.3), Ssalivarius 5.8% (2.9-10.1), and Sagalactiae 9.1% (6.6-12.1). The highest IE prevalence was found with Smitis/oralis 19.4% (15.6-23.5), Sgallolyticus (formerly Sbovis ) 30.2% (24.3-36.7), Ssanguinis 34.6% (26.6-43.3), Sgordonii 44.2% (34.0-54.8), and Smutans 47.9% (33.3-62.8). In multivariable analysis using S pneumoniae as reference, all species except S pyogenes were associated with significantly higher IE risk, with the highest risk found with S gallolyticus odds ratio (OR) 31.0 (18.8-51.1), S mitis/oralis OR 31.6 (19.8-50.5), S sanguinis OR 59.1 (32.6-107), S gordonii OR 80.8 (43.9-149), and S mutans OR 81.3 (37.6-176)., Conclusions: The prevalence of IE in streptococcal BSIs is species dependent with S mutans, S gordonii, S sanguinis, S gallolyticus , and S mitis/oralis having the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.

Background Mortality is increased following a hospitalization for decompensated heart failure (HF), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for HF. Methods and Results From nationwide administrative registers, we identified all Danish patients who were diagnosed with HF from 2001 to 2016 and received angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β blocker within 120 days. Subsequent follow-up tracked progressive events of diuretic intensification and HF hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1-year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened HF controls and absolute 1-year mortality risks were calculated using Kaplan-Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow-up. One-year mortality was 18.0% after an intensification event, 22.6% after HF hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1-year death after an intensification event was 1.75 (95% CI, 1.66-1.85), and it was 2.28 (95% CI, 2.16-2.41) after HF hospitalization. Conclusions In a nationwide cohort of patients with HF, outpatient intensification events were associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.

Aims: To determine whether beta-blockers, aspirin, and statins are underutilized after first-time myocardial infarction (MI) in patients with chronic obstructive pulmonary disease (COPD) compared with patients without COPD. Further, to determine temporal trends and risk factors for non-use., Methods and Results: Using Danish nationwide registers, we performed a cross-sectional study investigating the utilization of beta-blockers, aspirin, and statins after hospitalization for first-time MI among patients with and without COPD from 1995 to 2015. Risk factors for non-use were examined in multivariable logistic regression models. During 21 years of study, 140 278 patients were included, hereof 13 496 (9.6%) with COPD. Patients with COPD were less likely to use beta-blockers (53.2% vs. 76.2%, P < 0.001), aspirin (73.9% vs. 78.8%, P < 0.001), and statins (53.5% vs. 61.9%, P < 0.001). Medication usage increased during the study period but in multivariable analyses, COPD remained a significant predictor for non-use: odds ratio (95% confidence interval) for non-use of beta-blockers 1.86 (1.76-1.97); aspirin 1.24 (1.16-1.32); statins 1.50 (1.41-1.59). Analyses stratified by ST-segment elevation myocardial infarction (STEMI) and non-STEMI showed similar undertreatment of COPD patients. Risk factors for non-use of beta-blockers in COPD included increasing age, female sex, and increasing severity of COPD (frequent exacerbations, use of multiple inhaled medications, and low lung function). Similar findings were demonstrated for aspirin and statins., Conclusion: Beta-blockers, and to a lesser extent aspirin and statins, were systematically underutilized by patients with COPD following hospitalization for MI despite an overall increase in the utilization over time. Increasing severity of COPD was a risk factor for non-use of the medications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: The aim of the study was to investigate the associated risk of stroke after discharge of infective endocarditis (IE) in patients with stroke during IE admission compared with patients without stroke during IE admission., Methods: Using Danish nationwide registries, we identified nonsurgically treated patients with IE discharged alive in the period from 1996 to 2016. The study population was grouped into (1) patients with stroke during IE admission and (2) patients without stroke during IE admission. Multivariable adjusted Cox proportional-hazard analysis was used to compare the associated risk of stroke between groups., Results: We identified 4,284 patients with IE, of whom 239 (5.6%) had a stroke during IE admission. We identified differentials in the associated risk of stroke during follow-up between groups (P = .006 for interaction with time). The associated risk of stroke was higher in patients with stroke during IE admission with a 1-year follow-up, HR = 3.21 (95% CI 1.66-6.20), compared with patients without stroke during IE admission. From 1 to 5 years of follow-up, we identified no difference in the associated risk of stroke between groups, HR = 0.91 (95% CI 0.33-2.50)., Conclusions: Patients with nonsurgically treated IE with a stroke during IE admission were at significant higher associated risk of subsequent stroke within the first year of follow-up as compared with patients without a stroke during IE admission. This risk difference was not evident beyond 1 year of discharge. These findings underline the need for identification of causes and mechanisms of recurrent strokes after IE to develop preventive means., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Cancer may influence the risk of thromboembolism and bleeding associated with the CHA 2 DS 2 -VASc score. We examined the risk of thromboembolism and bleeding associated with the CHA 2 DS 2 -VASc score in atrial fibrillation patients with and without recent cancer. Methods and results Using nationwide registers all patients diagnosed with atrial fibrillation from 2000 to 2015 and not on oral anticoagulation or heparin therapy were included and followed for 2 years. Recent cancer was defined by a cancer diagnosis 5 years or fewer earlier. Risks of thromboembolism and bleeding were estimated in cumulative incidence curves and Cox regression models. We included 122,053 patients with incident atrial fibrillation, 12,014 (10%) had recent cancer. The 2-year cumulative incidence of thromboembolism and bleeding in patients with versus without recent cancer was 1.7% (95% confidence interval (CI) 0.5-2.8) and 4.3% (95% CI 2.4-6.2) versus 1.2% (95% CI 0.9-1.5) and 1.7% (95% CI 1.4-2.0) for CHA 2 DS 2 -VASc score 0; 3.2% (95%CI 2.2-4.3) and 4.4% (95%CI 3.2-5.6) versus 1.8% (95%CI 1.6-2.1) and 3.0% (95% CI 2.7-3.3) for CHA 2 DS 2 -VASc score 1; and 7.1% (95% CI 6.6-7.7) and 6.8% (95% CI 6.3-7.2) versus 10.9% (95% CI 10.7-11.1) and 6.2% (95% CI 6.1-6.4) for CHA 2 DS 2 -VASc score 2 or greater. Although the CHA 2 DS 2 -VASc score was associated with thromboembolism and bleeding in both patients with and without cancer, the association differed between the groups for thromboembolism (test for interaction, p < 0.001) and bleeding (test for interaction, p < 0.001). Conclusion The association of the CHA 2 DS 2 -VASc score and risk of thromboembolism and bleeding differed between atrial fibrillation patients with and without recent cancer. Therefore, the CHA 2 DS 2 -VASc score should be used with caution in patients with recent cancer.

Aims: To compare the hazard of all-cause, chronic obstructive pulmonary disease (COPD) and heart failure (HF) hospitalization in carvedilol vs. metoprolol/bisoprolol/nebivolol users with COPD and concurrent HF from 2009 to 2012, and to evaluate the use and persistence in treatment of these β-blockers, their impact on the risk of COPD-related hospitalization, and the factors important for their selection., Methods and Results: Cox and logistic regression were used for both unadjusted and adjusted analyses. Carvedilol users had a higher hazard of being hospitalized for HF compared with metoprolol/bisoprolol/nebivolol users in both the unadjusted [hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.65-1.83] and adjusted (HR 1.61; 95% CI 1.52-1.70) analyses. No significant differences were found for all-cause and COPD hospitalization between the two groups. Carvedilol users had a significant lower restricted mean persistence time than metoprolol/bisoprolol/nebivolol users. Patients exposed to carvedilol had an odds ratio (OR) of 1.38 (95% CI 1.23-1.56) for being hospitalized due to COPD within 60 days after redeeming the first carvedilol prescription, which was similar to that observed in metoprolol/bisoprolol/nebivolol users (OR 1.37; 95% CI 1.27-1.48). Patients with concurrent chronic kidney disease had a higher probability of receiving carvedilol (OR 1.16; 95% CI 1.04-1.29)., Conclusion: Carvedilol prescription carried an increased hazard of HF hospitalization and lower restricted mean persistence time among patients with COPD and concurrent HF. Additionally, we found a widespread phenomenon of carvedilol prescription at variance with the European Society of Cardiology guidelines and potential for improving the proportion of patients treated with β-blockers., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk of first-time ischemic stroke and myocardial infarction (MI) are poorly understood., Methods: All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause-specific Cox regression and g-formula methods to analyze long-term use., Results: Amongst 214 998 individuals, during a median follow-up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08-1.19) and MI (HR 1.31, CI 1.23-1.39) after adjusting for age, sex, comorbidities and concomitant medication. High-dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21-1.42) and MI (HR 1.43, CI 1.30-1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84-1.24) or MI (HR 1.15, CI 0.92-1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%) greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI within a 6-month period., Conclusion: Use of PPIs was associated with increased risks of first-time ischemic stroke and MI, particularly amongst long-term users and at high doses., (© 2017 The Association for the Publication of the Journal of Internal Medicine.)

Objectives: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation., Background: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease., Methods: The study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission., Results: The composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use was not associated with an altered risk of composite outcome (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.91 to 1.05), but it was associated with an increased risk of myocardial infarction (HR: 1.34; 95% CI: 1.08 to 1.67), whereas no differences were observed in all-cause mortality and stroke. An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result., Conclusions: No association was detected between low-dose aspirin use and the composite outcome of all-cause mortality, admission for myocardial infarction, and admission for stroke in patients with HF with no history of atrial fibrillation. Aspirin use was associated with an increased risk of readmission for HF., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: Long-term prognostic impact of coronary artery disease (CAD) severity in stable post-myocardial infarction (MI) patients is not well known. We examined the impact of CAD severity and co-morbidity on the long-term (1 year and beyond) risk of cardiovascular events post-MI., Methods and Results: From nationwide administrative and clinical registers, we identified 55 747 MI patients, during 2004-2010, who had not experienced subsequent MI, stroke, or death within 7 days post-discharge. The risk for primary composite endpoint (MI, stroke, or cardiovascular death) was estimated for the first 365 days after MI (index MI) and from day 366 to study completion (stable post-MI population), corresponding to a mean follow-up of 3.6 (2.2) years. Risk was assessed using cumulative incidence, multivariable adjusted logistic regression and Cox proportional-hazards models. The 1-year cumulative incidence for primary endpoint was 20.0% [95% confidence interval (CI), (19.6-20.3)]. Correspondingly, the 4-year cumulative incidence for primary endpoint was 21.0% (95% CI, 20.6-21.4) in patients without events on the first year. In multivariable models with no significant stenosis as reference, CAD severity was the most important risk factor for cardiovascular events the first 365 days [left main stenosis (LMS): odds ratio and 95% CI, 4.37, 3.69-5.17; 3-vessel disease (VD), 4.18, 3.66-4.77; 2-VD, 3.23, 2.81-3.72; 1-VD, 2.12,-1.85-2.43] and remained from day 366 to study completion [LMS: hazard ratio and 95% CI, 1.91, 1.64-2.22; 3-VD, 1.85,1.65-2.07; 2-VD, 1.55, 1.38-1.74; 1-VD, 1.30, 1.16-1.45]., Conclusion: Despite contemporary treatment at baseline, stable post-MI patients' 4-year outcome was similar to 1-year outcome after MI, and CAD severity remained a critical risk factor the first year and thereafter., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Dual anti-platelet treatment with clopidogrel and aspirin is indicated for most patients after myocardial infarction. We examined the risk/benefit relationship of dual anti-platelet treatment according to age in a nationwide cohort of 30,532 myocardial infarction patients without revascularization., Methods: Patients admitted with first-time myocardial infarction in 2002-2010, not undergoing revascularization, were identified from nationwide Danish registers. Dual anti-platelet treatment use was assessed by claimed prescriptions. Stratified into age groups, risk of bleeding, all-cause mortality and a combined endpoint of cardiovascular death, recurrent myocardial infarction and ischaemic stroke was analysed by Cox proportional-hazard models and tested in a propensity-score matched population., Results: A total of 21,302 users and 9230 non-users of dual anti-platelet treatment were included (mean age 67.02 (±13.8) years and 64.7% males). Use of dual anti-platelet treatment decreased with age: 80% (<60 years), 76% (60-69 years), 66% (70-79 years) and 52% (>79 years). We found a reduced risk of cardiovascular death, recurrent myocardial infarction and ischaemic stroke in users <60 years (Hazard ratio (HR) =0.69; 95% confidence interval (CI) 0.59-0.80), 60-69 years (HR=0.64; 95% CI 0.56-0.73), 70-79 years (HR=0.80; 95% CI 0.72-0.89) and >79 years (HR=0.92; 95% CI 0.84-1.01, NS). Risk of bleeding increased with dual anti-platelet treatment use in patients aged <60 years (HR=1.63; 95% CI 1.17-2.26), 60-69 years (HR=1.22; 95% CI 0.97-1.59, NS), 70-79 years (HR=1.42; 95% CI 1.17-1.72) and >79 years (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found in the propensity-matched population., Conclusion: Dual anti-platelet treatment use was less likely among elderly patients although similar effects regarding both risk and benefit were found in all age groups. Increased focus on initiating dual anti-platelet treatment in elderly, non-invasively treated myocardial infarction patients is warranted.

Aims: Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and prognostic significance of possible FH in patients with myocardial infarction (MI)., Methods and Results: By individual-level linkage of data from the Eastern Danish Heart Registry and national administrative registries, a study population of patients referred for coronary angiography due to MI was selected. The study population was divided into "unlikely FH" and "possible FH" based on the Dutch Lipid Clinic Network criteria, which included a plasma low-density lipoprotein cholesterol (LDL-C) and age for onset of cardiac disease. A score of ≥3 points was used as the cutpoint between the 2 groups. Among the study population of 13,174 MI patients, 1,281 (9.7%) had possible FH. These patients were younger (59.1 vs 65.7 years, P ≤ .0001), had similar levels of comorbidities, and were treated more aggressively with cholesterol-lowering drugs compared with patients with unlikely FH. During a median of 3.3 years of follow-up, the unadjusted and adjusted event rates of recurrent MI were higher in patients with possible FH compared with unlikely FH (16% vs 11%, adjusted hazard ratio 1.28, 95% CI 1.09-1.51, P = .003.). Differences in adjusted all-cause mortality were not statistically significant (17% vs 23%, adjusted hazard ratio 0.89 [0.74-1.04], P = .1)., Conclusion: We found that MI patients with possible FH have higher risk of recurrent MI but similar risk of mortality compared with unlikely FH patients. Further studies on secondary prevention are warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups., Methods: We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR., Results: A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97-1.56), 1.26 (95% CI, 1.14-1.40), 1.18 (95% CI, 1.07-1.31), 1.11 (95% CI, 0.87-1.42), 2.01 (95% CI, 1.14-3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and <15 mL/min per 1.73 m 2 , respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m 2 ; hazard ratios 0.57 (95% CI, 0.43-0.76), 0.57 (95% CI, 0.51-0.64), 0.48 (95% CI, 0.44-0.54), 0.60 (95% CI, 0.45-0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m 2 , respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR<15 mL/min per 1.73 m 2 ; hazard ratio 1.18 (95% CI, 0.58-2.40)., Conclusions: In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m 2 ., (© 2016 American Heart Association, Inc.)

Background: Dialysis-requiring acute kidney injury (AKI) is associated with substantial mortality and risk of end-stage renal disease (ESRD). Despite considerable growth in incidence of severe AKI, information pertaining to trends in outcomes remains limited. We evaluated time trends in one year risks of ESRD and death in patients with dialysis-requiring AKI over an eight year period in Denmark., Methods: In a retrospective nationwide study based on national registers, all adults requiring acute renal replacement therapy between 2005 and 2012 were identified. Patients with preceding ESRD were excluded. Through individual-level cross-referencing of administrative registries, information pertaining to comorbidity, preceding surgical interventions, and concurrent other organ failure and sepsis was ascertained. Comparisons of period-specific one year odds ratios for ESRD and death were calculated in a multiple logistic regression model., Results: A total of 13,819 patients with dialysis-requiring AKI were included in the study. Within one year, 1,017 (7.4%) patients were registered with ESRD, and 7,908 (57.2%) patients died. The one-year rate of ESRD decreased from 9.0% between 2005 and 2006 to 6.1% between 2011 and 2012. Simultaneously, the one-year mortality rate decreased from 58.2% between 2005 and 2006 to 57.5% between 2011 and 2012. Consequently, the adjusted odds ratios for the period 2011-2012 (with the period 2005-2006 as reference) were 0.75 (0.60-0.95, p = 0.015) and 0.87 (95% CI 0.78-0.97, p = 0.010) for ESRD and death, respectively., Conclusions: In a nationwide retrospective study on time trends in one year outcomes following dialysis-requiring AKI, risk of all-cause mortality and ESRD decreased over a period of 8 years.

Importance: Syncope may have serious consequences for traffic safety. Current clinical guideline recommendations on driving following syncope are primarily based on expert consensus., Objective: To identify whether there is excess risk of motor vehicle crashes among patients with syncope compared with the general population., Design, Setting, and Participants: Danish nationwide cohort study from January 1, 2008, to December 31, 2012. Through individual-level linkage of nationwide administrative registers, all Danish residents 18 years or older were identified. Of 4 265 301 eligible Danish residents, we identified 41 039 individuals with a first-time diagnosis of syncope from emergency department or hospital., Main Outcomes and Measures: Rate of motor vehicle crashes (including nonfatal and fatal crashes), based on multivariate Poisson regression models, using the total Danish population as reference., Results: The 41 039 patients with syncope had a median age of 66 years (interquartile range [IQR], 47-78 years); 51.0% were women; and 34.8% had cardiovascular disease. Through a median follow-up of 2.0 years (IQR, 0.8-3.3 years), 1791 patients with syncope (4.4%) had a motor vehicle crash, 78.1% of which led to injury (n = 1398) and 0.3% to death (n = 6). The crude incidence rate of motor vehicle crashes was almost doubled among patients with syncope (20.6 per 1000 person-years; 95% CI, 19.7-21.6) compared with the general population (12.1; 95% CI, 12.0-12.1), with a rate ratio (RR) of 1.83 (95% CI, 1.74-1.91) after adjustment for age, sex, socioeconomic position, and relevant comorbidities and pharmacotherapy. Men had a relatively higher rate of motor vehicle crashes (RR, 1.91; 95% CI, 1.79-2.03) than women (RR, 1.74; 95% CI, 1.63-1.87). The excess risk of motor vehicle crashes persisted throughout the follow-up period. The 5-year crash risk following syncope was 8.2% (95% CI, 7.5%-8.8%) among the population aged 18 to 69 years compared with 5.1% (95% CI, 4.7%-5.4%) in the general population., Conclusions and Relevance: Prior hospitalization for syncope was associated with increased risk of motor vehicle crashes throughout the follow-up period. This study suggests that syncope should be considered as one of several factors in a broad assessment of fitness to drive.

Background: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments., Methods: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen., Results: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke and 1.47 (95% CI: 1.18-1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95% CI: 0.59-0.81) and 0.72 (95% CI: 0.55-0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95% CI: 10.2-12.2), 7.7 (95% CI: 7.3-8.3), and 8.0 (95% CI: 6.9-8.7) for ischemic stroke, respectively; while, the risks for bleeding were 3.4 (95% CI: 2.8-3.9), 2.4 (95% CI: 2.1-2.7), and 2.4 (95% CI: 1.9-2.9), respectively., Conclusion: Clopidogrel and the combination of acetylsalicylic acid and dipyridamole were associated with similar risks for recurrent ischemic stroke and bleeding; whereas acetylsalicylic acid was associated with higher risks for both ischemic stroke and bleeding. The latter finding may partially be explained by selection bias.

Background: Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors., Methods and Results: In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001-2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18-65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1-3, 46-59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1-3, 1-19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001-2005 versus 78.1% in 2006-2011; P=0.002). In multivariable Cox regression analysis, factors associated with return to work with ≥6 months of sustainable employment were as follows: (1) arrest during 2006-2011 versus 2001-2005, hazard ratio (HR), 1.38 (95% CI, 1.05-1.82); (2) male sex, HR, 1.48 (95% CI, 1.06-2.07); (3) age of 18 to 49 versus 50 to 65 years, HR, 1.32 (95% CI, 1.02-1.68); (4) bystander-witnessed arrest, HR, 1.79 (95% CI, 1.17-2.76); and (5) bystander cardiopulmonary resuscitation, HR, 1.38 (95% CI, 1.02-1.87)., Conclusions: Of 30-day survivors employed before arrest, 76.6% returned to work. The percentage of survivors returning to work increased significantly, along with improved survival during 2001-2011, suggesting an increase in the proportion of survivors with preserved function over time., (© 2015 American Heart Association, Inc.)

Background: Patients with psoriasis have increased prevalence of coronary risk factors and limited recent results have suggested that these risk factors are undertreated in patients with psoriasis. This may contribute to the increased risk of cardiovascular diseases observed in patients with psoriasis., Objective: To examine the pharmacological treatment of coronary risk factors in patients with severe psoriasis treated with biologic agents in a real-world setting., Methods and Findings: Medical history of patients with severe psoriasis treated with biologic agents in the time period 2007-09 was retrieved from a Danish nationwide registry (DERMBIO). Individual-level linkage of nationwide administrative registries of hospitalizations, concomitant medications, and socioeconomic status was performed to gain insights into the use of pharmacological treatment. A total of 693 patients (mean age 46.1 ± 12.7 years, 65.7% male) with severe psoriasis treated with biologic agents were identified. Hypertension, hypercholesterolemia, and diabetes mellitus were identified in 16.6%, 9.2%, and 6.7% of cases, respectively. Patients with severe psoriasis were significantly less likely to receive cardiovascular pharmacotherapy compared to age, sex, and coronary risk factor matched controls. In psoriatic patients with hypertension 27.7% received no antihypertensive pharmacotherapy. Patients with dyslipidemia received cholesterol-lowering medications in 55.8% of cases and patients with diabetes mellitus received angiotensin converting enzyme inhibitors/angiotensin II receptor blockers and cholesterol-lowering medications in 42.1% and 23.7% of cases, respectively. Similar results were found for the subset of patients with >1 coronary risk factor and for high risk patients with established atherosclerotic disease., Conclusion: This nationwide study of patients with severe psoriasis demonstrated substantial undertreatment of coronary risk factors. Increased focus on identifying cardiovascular risk factors and initiation of preventive cardiovascular pharmacotherapy in patients with psoriasis is warranted.

Background: Sulfonylureas have been linked to an increased cardiovascular risk by inhibition of myocardial preconditioning. Whether individual sulfonylureas affect outcomes in diabetic patients after emergent percutaneous coronary intervention for myocardial infarction is unknown., Methods: All Danish patients receiving glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006 who underwent emergent percutaneous coronary intervention were identified from national registers. Multivariable Cox proportional hazards models were used to analyze the risk of cardiovascular mortality and morbidity associated with sulfonylureas., Results: A total of 926 patients were included and 163 (17.6%) patients died during the first year of which 155 (16.7%) were cardiovascular deaths. The most common treatment was sulfonylureas which were received by 271 (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard regression analyses adjusted for age, sex, calendar year, comorbidity and concomitant pharmacotherapy showed an increased risk of cardiovascular mortality (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p=0.012), cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI 1.21-6.00; p=0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47; p=0.027), respectively, with glyburide compared to metformin., Conclusions: Glyburide is associated with increased cardiovascular mortality and morbidity in patients with diabetes mellitus undergoing emergent percutaneous coronary intervention after myocardial infarction. Early reperfusion therapy is the mainstay in modern treatment of myocardial infarction and the time may have come to discard glyburide in favour of sulfonylureas that do not appear to confer increased cardiovascular risk., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)