Publications by authors named "Gunnar Gislason"

627 Publications

Bleeding risk following systemic fluconazole or topical azoles in patients with atrial fibrillation on apixaban, rivaroxaban or dabigatran.

Am J Med 2021 Nov 30. Epub 2021 Nov 30.

Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark.

Background Bleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations. Methods Using nationwide, Danish registers we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban or dabigatran from 2012-2018. We investigated associations between bleeding incidents, and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). Results We included 32,340 (36%), 32,409 (36%) and 24,940 (28%) patients initiated on apixaban, rivaroxaban and dabigatran, respectively. Patients on apixaban were older (median age: 77 [IQR 70-84]) compared with rivaroxaban users (median age: 75 [IQR 68-82]) and patients on dabigatran (median age: 73 [IQR 66-80]). Apixaban users had a significantly increased risk of bleeding following exposure to systemic fluconazole: OR of 3.5 (95% CI 1.4-10.6). No increased risk was found with among rivaroxaban and dabigatran users: ORs of 0.9 (95% CI 0.2-3.0) and 1.7 (95% CI 0.5-5.6), respectively. Bleeding risk pertaining to topical azole exposure among apixaban, rivaroxaban and dabigatran users, no association was found with corresponding ORs of 0.8 (95% CI 0.5-1.3), 1.3 (95% CI 0.9-2.1) and 1.2 (95% CI 0.8-1.8) Conclusion In patients with atrial fibrillation on either apixaban, rivaroxaban or dabigatran, an association between an elevated bleeding risk and use of systemic fluconazole was found among patients on apixaban. We found no increased risk of bleeding following co-exposure to topical azoles.
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http://dx.doi.org/10.1016/j.amjmed.2021.11.008DOI Listing
November 2021

Contacts With the Health Care System Before Out-of-Hospital Cardiac Arrest.

J Am Heart Assoc 2021 Dec 2:e021827. Epub 2021 Dec 2.

Department of Cardiology Nordsjaellands Hospital Hillerød Denmark.

Background It remains challenging to identify patients at risk of out-of-hospital cardiac arrest (OHCA). We aimed to examine health care contacts in patients before OHCA compared with the general population that did not experience an OHCA. Methods and Results Patients with OHCA with a presumed cardiac cause were identified from the Danish Cardiac Arrest Registry (2001-2014) and their health care contacts (general practitioner [GP]/hospital) were examined up to 1 year before OHCA. In a case-control study (1:9), OHCA contacts were compared with an age- and sex-matched background population. Separately, patients with OHCA were examined by the contact type (GP/hospital/both/no contact) within 2 weeks before OHCA. We included 28 955 patients with OHCA. The weekly percentages of patient contacts with GP the year before OHCA were constant (25%) until 1 week before OHCA when they markedly increased (42%). Weekly percentages of patient contacts with hospitals the year before OHCA gradually increased during the last 6 months (3.5%-6.6%), peaking at the second week (6.8%) before OHCA; mostly attributable to cardiovascular diseases (21%). In comparison, there were fewer weekly contacts among controls with 13% for GP and 2% for hospital contacts (<0.001). Within 2 weeks before OHCA, 57.8% of patients with OHCA had a health care contact, and these patients had more contacts with GP (odds ratio [OR], 3.17; 95% CI, 3.09-3.26) and hospital (OR, 2.32; 95% CI, 2.21-2.43) compared with controls. Conclusions The health care contacts of patients with OHCA nearly doubled leading up to the OHCA event, with more than half of patients having health care contacts within 2 weeks before arrest. This could have implications for future preventive strategies.
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http://dx.doi.org/10.1161/JAHA.121.021827DOI Listing
December 2021

Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40,000-cases across two countries.

Br J Clin Pharmacol 2021 Nov 26. Epub 2021 Nov 26.

Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Aim: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA-risk of opioids in the community.

Methods: We conducted two population-based case-control studies separately in the Netherlands (2009-2018) and Denmark (2001-2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to five non-OHCA-controls according to age, sex and OHCA-date. Conditional logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results: We included 5,473 OHCA-cases matched with 21,866 non-OHCA-controls in the Netherlands, and 35,017 OHCA-cases matched with 175,085 non-OHCA-controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA-risk in both regions (the Netherlands: OR 2.1 [95%-CI 1.8-2.5]; Denmark: OR 1.8 [95%-CI 1.5-2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95%-CI 1.5-2.1]; Denmark: OR 1.6 [95%-CI 1.5-1.7]) or without (the Netherlands: OR 3.4 [95%-CI: 2.4-4.8], P-interaction<0.0001; Denmark: OR 2.3 [95%-CI: 2.0-2.5], P-interaction<0.0001).

Conclusion: Use of opioids is associated with increased OHCA-risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids.
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http://dx.doi.org/10.1111/bcp.15157DOI Listing
November 2021

Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality.

Respir Care 2021 Nov 23. Epub 2021 Nov 23.

Cardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality.

Methods: In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0-24 per subject.

Results: Among 215 enrolled subjects, 168 with LUS data and no current signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome ( 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, < .001) and procalcitonin levels (0.35 μg/L vs 0.13, = .033) and higher supplemental oxygen requirements (median 4 L/min vs 2, = .001). However, LUS findings and score did not differ significantly between subjects with the composite outcome and those without, and were not associated with outcomes in unadjusted and adjusted logistic regression analyses.

Conclusions: Pathologic findings on LUS were common a median of 3 d after admission in this cohort of non-ICU hospitalized subjects with COVID-19 and did not differ among subjects who experienced the composite outcome of incident ARDS, ICU admission, and all-cause mortality compared to subjects who did not. These findings should be confirmed in future investigations. The study is registered at Clinicaltrials.gov (NCT04377035).
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http://dx.doi.org/10.4187/respcare.09108DOI Listing
November 2021

Glycated haemoglobin (HbA1c) levels among 3,295 hospitalised COVID-19 patients with and without diabetes and risk of severe infection, admission to an intensive care unit, and all-cause mortality.

Diabetes Obes Metab 2021 Nov 14. Epub 2021 Nov 14.

Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark.

Aims: Diabetes and hyperglycaemia have been associated with a more severe disease course in COVID-19 patients. However, less is known regarding the risk of adverse outcomes across the spectrum of glycated haemoglobin(HbA1c) levels among COVID-19 patients with and without diabetes.

Materials And Methods: Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit(ICU)admission, or all-cause mortality. The study population comprised patients hospitalised with COVID-19(3 March-31 December 2020)with a positive PCR-test and an available HbA1c≤6 months before the first positive PCR-test. All patients had at least 30 days of follow-up. Among patients with diabetes,HbA1c was categorised as<48, 48-53, 54-58, 59-64(reference),and>64mmol/mol. Among patients without diabetes,HbA1c was stratified into<31, 31-36(reference), 37-41,and 42-47mmol/mol. 30-day standardised absolute risks and standardised absolute risk differences are reported.

Results: We identified 3,295 hospitalised COVID-19 patients with an available HbA1c(56.2% males and median age 73.9 years),of whom 35.8% had diabetes. The median HbA1c was 54mmol/mol and 37mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardised absolute risk difference of the composite outcome was higher with HbA1c<48mmol/mol(12.0%[3.3-20.8%]) and HbA1c>64mmol/mol(15.1%[6.2-24.0%]), compared with HbA1c 59-64mmol/mol(reference). Among patients without diabetes, the standardised absolute risk difference of the composite outcome was greater with HbA1c<31mmol/mol(8.5%[0.5-16.5%]) and HbA1c 42-47mmol/mol(6.7%[1.3-12.1%]), compared with HbA1c 31-36mmol/mol(reference).

Conclusions: Patients with COVID-19 and HbA1c<48mmol/mol or HbA1c>64mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dom.14604DOI Listing
November 2021

Incidence of Infective Endocarditis Among Patients With Tetralogy of Fallot.

J Am Heart Assoc 2021 Nov 3;10(22):e022445. Epub 2021 Nov 3.

Department of Cardiology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.

Background Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple invasive procedures, including pulmonary valve replacement (PVR). Data on the long-term risk of IE are sparse. Methods and Results In this observational cohort study, all patients with ToF born from 1977 to 2018 were identified using Danish nationwide registries and followed from date of birth until occurrence of first-time IE, emigration, death, or end of study (December 31, 2018). The comparative risk of IE among patients with ToF versus age- and sex-matched controls from the background population was assessed. Because of rules on anonymity, exact numbers cannot be reported if the number of patients is <4. A total of 1164 patients with ToF were identified and matched with 4656 controls. Among patients with ToF, 851 (73.1%) underwent early surgical intracardiac repair and 276 (23.7%) underwent PVR during follow-up. During a median follow-up of 20.3 years, 41 (3.5%) patients with ToF (comprising 24 [8.7%] with PVR and 17 [1.9%] without PVR) and <4 (<0.8%) controls were admitted with IE. The incidence rates of IE per 10 000 person-years were 22.4 (95% CI, 16.5-30.4) and 0.1 (95% CI, 0.01-0.7) among patients and controls, respectively. Moreover, PVR was associated with a further increased incidence of IE among patients with ToF (incidence rates per 10 000 person-years with and without PVR were 46.7 [95% CI, 25.1-86.6] and 2.8 [95% CI 2.0-4.0], respectively). Conclusions Patients with ToF are associated with a substantially higher incidence of IE than the background population. In particular, PVR was associated with an increased incidence of IE. With an increasing life expectancy of these patients, intensified awareness, preventive measures, and surveillance of this patient group are decisive.
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http://dx.doi.org/10.1161/JAHA.121.022445DOI Listing
November 2021

Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study.

J Am Heart Assoc 2021 Nov 30;10(22):e021286. Epub 2021 Oct 30.

Department of Cardiology, Herlev and Gentofte University Hospital Copenhagen Denmark.

Background It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first-degree family members with HF or dilated cardiomyopathy (DCM). Methods and Results Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre-existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first-degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5-year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8-10.7] versus 5.6% [95% CI, 5.0-6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13-1.64]). (HF 8.4% [95% CI, 7.0-9.8] versus 4.5% [95% CI, 4.1-5.0]); (adjusted HR, 1.49 [95% CI, 1.22-1.82]). However, familial HF/DCM was not significantly associated with an increased 5-year risk and rate of death (0.8% [95% CI, 0.4-1.2] versus 1.1% [95% CI, 0.8-1.3]); (adjusted HR, 0.80 [95% CI, 0.46-1.39]). Conclusions In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first-degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5-year incidence of HF compared with those without.
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http://dx.doi.org/10.1161/JAHA.120.021286DOI Listing
November 2021

Lifetime Risk of Heart Failure and Trends in Incidence Rates Among Individuals With Type 2 Diabetes Between 1995 and 2018.

J Am Heart Assoc 2021 11 29;10(21):e021230. Epub 2021 Oct 29.

Department of Medicine Section of Cardiovascular Medicine Boston Medical CenterBoston University School of Medicine Boston MA.

Background There are limited data on the lifetime risk of heart failure (HF) in people with type 2 diabetes and how incidence has changed over time. We estimated the cumulative incidence and incidence rates of HF among Danish adults with type 2 diabetes between 1995 and 2018 using nationwide data. Methods and Results In total, 398 422 patients (49% women) with type 2 diabetes were identified. During follow-up, 36 400 (9%) were diagnosed with HF and 121 459 (30%) were censored due to death. Using the Aalen-Johansen estimators, accounting for the risk of death, the estimated residual lifetime risk of HF at age 50 years was calculated as 24% (95% CI 22%-27%) in women and 27% (25%-28%) in men. During the observational period, the proportion of patients treated with statins, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and metformin increased from <30% to >60%. Similarly, the annual incidence rates of HF decreased significantly, with declines being greater in older versus younger individuals (5% versus 2% in age >50 versus ≤50 years, respectively; <0.0001) and in women versus men (5% versus 4%, =0.02), but similar in patients with and without IHD (4% versus 4%, =0.53). Conclusions The current lifetime risk of HF in type 2 diabetes approximates 1 in 4 for men and women. Paralleled by an increase in use of evidence-based pharmacotherapy over the past decades, the risk of developing HF has declined across several subgroups and regardless of underlying IHD, suggesting that optimal diabetes treatment can mitigate HF risk.
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http://dx.doi.org/10.1161/JAHA.121.021230DOI Listing
November 2021

Increased 5-year risk of stroke, atrial fibrillation, acute coronary syndrome, and heart failure in out-of-hospital cardiac arrest survivors compared with population controls: A nationwide registry-based study.

Resuscitation 2021 Oct 22;169:53-59. Epub 2021 Oct 22.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Aim: Long-term risks of stroke, atrial fibrillation, or flutter (AF), acute coronary syndrome (ACS), and heart failure (HF) among survivors of out-of-hospital cardiac arrest (OHCA) are unknown. We aimed to examine 5-year risks of these outcomes among 30-day survivors of OHCA.

Methods: Thirty-day survivors of OHCA without a prior (or within 30 days after cardiac arrest) history of stroke, AF, ACS, or HF and population controls without a prior history of these conditions were identified using Danish nationwide registries. Five-year risks of stroke, AF, ACS, and HF standardized to the distributions of age, sex, and comorbidities among OHCA survivors and controls were obtained using multivariable regression.

Results: Of 4,362 30-day OHCA-survivors, 1,051 were stroke-, AF-, ACS-, and HF-naïve and matched with controls using age, sex, and time of OHCA event. Absolute five-year risks for OHCA survivors vs. controls were for stroke: 6.3% [95% confidence interval (CI) 4.1-8.5] vs. 2.0% [1.6-2.5], AF: 7.9% [5.7-10.2] vs. 2.6% [2.1-3.1], ACS: 5.0% [3.2-6.8] vs. 1.5% [1.1-1.9], and HF: 12.7% [10.1-15.4] vs. 1.2% [0.9-1.6], respectively. Corresponding relative risks were 3.18 [95% CI 1.76-4.61] for stroke, 3.03 [1.93-4.14] for AF, 3.23 [1.69-4.77] for ACS, and 10.40 [6.57-14.13] for HF.

Conclusion: When compared with population controls, OHCA survivors had significantly increased five-year risks of incident stroke, AF, ACS, and HF.
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http://dx.doi.org/10.1016/j.resuscitation.2021.10.024DOI Listing
October 2021

Prediabetes Defined by First Measured HbA Predicts Higher Cardiovascular Risk Compared With HbA in the Diabetes Range: A Cohort Study of Nationwide Registries.

Diabetes Care 2021 Oct 21. Epub 2021 Oct 21.

Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark.

Objective: To assess the risk of major adverse cardiovascular events (MACE), all-cause mortality, and initiation of medical treatment in subjects with prediabetes according to first-time measured HbA.

Research Design And Methods: Through registry databases, we identified 326,305 Danish patients with a first HbA between 40 and 51 mmol/mol (5.8-6.8%) from 2011 to 2017. After exclusion of patients with prior disease, 84,678 patients were followed 12 months after first HbA measurement. Cox regression models were used to estimate hazard ratios (HRs) of MACE and standardized absolute risks. Cumulative incidences were used to analyze initiation of glucose-lowering, antihypertensive, cholesterol-lowering, and antithrombotic medication.

Results: The 12-months risk of MACE and all-cause mortality increased gradually with increasing HbA until 47 mmol/mol (6.5%). In comparisons of subjects with HbA 40-41 mmol/mol (5.8-5.9%), subjects with HbA 46-47 mmol/mol (6.4-6.5%) had a 0.79% (95% CI 0.33-1.24) higher standardized absolute risk and an HR of 2.21 (95% CI 1.67-2.92) of MACE. Patients with HbA 48-49 mmol/mol (6.5-6.6%) had a 0.09% (95% CI -0.35 - 0.52) lower absolute risk and an HR of 1.33 (95% CI 0.87-2.05) of MACE. Initiation of medication was significantly lower among patients with HbA of 46-47 mmol/mol (6.4-6.5%) than among patients with HbA of 48-49 mmol/mol (6.5-6.6%).

Conclusions: In the Danish population screened for diabetes with HbA, the highest risk of MACE and all-cause mortality was found in subjects with HbA just below the diagnostic threshold for diabetes. Our results highlight the need for increased focus on the treatment of cardiovascular risk factors for subjects with prediabetes.
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http://dx.doi.org/10.2337/dc21-1062DOI Listing
October 2021

Electrical cardioversion of atrial fibrillation and the risk of brady-arrhythmic events.

Am Heart J 2021 Oct 16;244:42-49. Epub 2021 Oct 16.

Department of Cardiology, Herlev-Gentofte University Hospital, University of Copenhagen, Hellerup, Denmark.

Background: Electrical cardioversion (ECV) is a common procedure for terminating atrial fibrillation (AF). ECV is associated with brady-arrhythmic events, however, the age-specific risks of clinically significant brady-arrhythmic events are unknown.

Methods: Using Danish nationwide registers, we identified patients with AF at their first non-emergent ECV between 2005 and 2018 and estimated their 30-day risk of brady-arrhythmic events. Moreover, factors associated with increased risks of brady-arrhythmias were identified. Absolute risks were estimated using logistic regression models fitted with natural splines as well as standardization (G-formula).

Results: We identified 20,725 eligible patients with a median age of 66 years (IQR 60-72) and most males (73%). The 30-day risks of brady-arrhythmic events after ECV were highly dependent on age with estimated risks ranging from 0.5% (95% CI 0.2-1.7) and 1.2% (95% CI 0.99-1.5) to 2.7% (95% CI 2.1-3.3) and 5.1% (95% CI 2.6-9.7) in patients aged 40, 65, 80, and 90 years, respectively. Factors associated with brady-arrhythmias were generally related to cardiovascular disease (eg, ischemic heart disease, heart failure, valvular AF) or a history of syncope. We found no indications that pre-treatment with anti-arrhythmic drugs conferred increased risks of brady-arrhythmic events (standardized absolute risk difference -0.25% [95% CI -0.67 to 0.17]).

Conclusions: ECV conferred clinically relevant 30-day risks of brady-arrhythmic events, especially in older patients. Anti-arrhythmic drug treatment was not found to increase the risk of brady-arrhythmias. Given the widespread use of ECV, these data should provide insights regarding the potential risks of brady-arrhythmic events.
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http://dx.doi.org/10.1016/j.ahj.2021.10.182DOI Listing
October 2021

Importance of diagnostic setting in determining mortality in patients with new-onset heart failure: temporal trends in Denmark 1997-2017.

Eur Heart J Qual Care Clin Outcomes 2021 Oct 8. Epub 2021 Oct 8.

Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark.

Aim: To investigate temporal trends in in-patient versus out-patient diagnosis of new-onset heart failure (HF) and the subsequent risk of death and hospitalization.

Methods And Results: Using nationwide registers, 192,581 patients with a first diagnosis of HF (1997-2017) were included. We computed incidences of HF, age-standardized mortality rates, and absolute risks (AR) of death and hospitalization (accounting for competing risk of death) to understand the importance of the diagnosis setting in relation to subsequent mortality and hospitalization. The overall incidence of HF was approximately the same (170/100,000 persons) every year during 1997-2017. However, in 1997, 77% of all first diagnoses of HF were made during a hospitalization, whereas the proportion was 39% in 2017. As in-patient diagnoses decreased, out-patient diagnoses increased from 23% to 61%. Out-patients had lower mortality and hospitalization rates than in-patients throughout the study period, although the 1-year age-standardized mortality rate decreased for each of in-patients (24 to 14/100-person) and out-patients (11 to 7/100-person). 1-year and 5-year AR of death decreased by 11.1% and 17.0%, respectively, for all HF patients, while the risk of hospitalization for HF did not decrease significantly (1.13% and 0.96%, respectively).

Conclusions: Between 1997 and 2017, HF changed from being primarily diagnosed during hospitalization to being mostly diagnosed in the outpatient setting. Out-patients had much lower mortality rates than in-patients throughout the study period. Despite a significant decrease in mortality risk for all HF patients, neither in-patients nor out-patients experienced a reduction in the risk of a HF hospitalization.
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http://dx.doi.org/10.1093/ehjqcco/qcab073DOI Listing
October 2021

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015.

Drug Saf 2021 Nov 5;44(11):1231-1242. Epub 2021 Oct 5.

National Institute of Public Health, University of Southern Denmark, Studiestræde 6, 1455, Copenhagen, Denmark.

Introduction: A small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure.

Objective: The aim was to study the association between DL exposure and incidence of first seizure.

Methods: A new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001-2015 was conducted. DL exposure was defined as days' supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure.

Results: A total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0-5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34-1.59). The aIRR ranged from 1.85 (95% CI 1.65-2.08) in children aged 0-5 years to 1.01 in adults aged 20 years or more (95% CI 0.85-1.19).

Conclusion: This study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.
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http://dx.doi.org/10.1007/s40264-021-01106-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553702PMC
November 2021

Association between vitamin K intake and mortality in the Danish Diet, Cancer, and Health cohort.

Eur J Epidemiol 2021 Oct 30;36(10):1005-1014. Epub 2021 Sep 30.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.

Reported associations between vitamin K and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52-60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87-192 µg/d) intake of vitamin K was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.
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http://dx.doi.org/10.1007/s10654-021-00806-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542554PMC
October 2021

Temporal trends in utilization of transcatheter aortic valve replacement and patient characteristics: A nationwide study.

Am Heart J 2022 Jan 26;243:140-146. Epub 2021 Sep 26.

Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark.

Aim: To investigate trends in the utilization of transcatheter aortic valve replacement (TAVR) and changes in the characteristics of patients undergoing first-time TAVR.

Methods: Using Danish nationwide registers, we included all patients undergoing TAVR between 2008 and 2020. To compare patient characteristics, the study population was stratified according to calendar year of procedure: 2008-2010, 2011-2013, 2014-2016, and 2017-2020.

Results: We identified 6,097 patients undergoing TAVR with year-by-year increases in TAVR penetration rate. Over time, the age of the patients remained stable (2008-2010: median age 82 year [interquartile range (IQR): 77-86] vs 2017-2020: median age 81 years [IQR: 77-85]). Moreover, there was an increase in male patients (2008-2010: 49.9% vs 2017-2020: 57.4%) and patients with diabetes (2008-2010: 14.2% vs 2017-2020: 19.2%). Conversely, a history of stroke (2008-2010: 15.8% vs 2017-2020: 13.1%), previous myocardial infarction (2008-2010: 22.4% vs 2017-2020: 10.0%), heart failure (2008-2010: 40.5% vs 2017-2020: 25.2%), and peripheral artery disease (2008-2010: 14.8% vs 2017-2020: 10.4) decreased among patients.

Conclusions: TAVR utilization increased markedly in the years 2008-2020. Patients undergoing TAVR had less comorbidity over time while age remained stable. Thus, despite expanding to patients at lower surgical risk, TAVR is still offered mainly to older patients.
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http://dx.doi.org/10.1016/j.ahj.2021.09.010DOI Listing
January 2022

Importance of Risk Assessment in Timing of Invasive Coronary Evaluation and Treatment of Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome: Insights From the VERDICT Trial.

J Am Heart Assoc 2021 10 29;10(19):e022333. Epub 2021 Sep 29.

Department of Cardiology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) (=0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.
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http://dx.doi.org/10.1161/JAHA.121.022333DOI Listing
October 2021

Long-Term Mortality Associated With Use of Carvedilol Versus Metoprolol in Heart Failure Patients With and Without Type 2 Diabetes: A Danish Nationwide Cohort Study.

J Am Heart Assoc 2021 09 17;10(18):e021310. Epub 2021 Sep 17.

Department of Cardiology Herlev and Gentofte Hospital Copenhagen University Hellerup Denmark.

Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well-balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazard ratio (HR) 0.97 (0.90-1.05) in patients with T2D versus 1.00 (0.95-1.05) for those without T2D, for difference =0.99. Rates of new-onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75-0.91), <0.0001. Conclusions In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long-term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new-onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.
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http://dx.doi.org/10.1161/JAHA.121.021310DOI Listing
September 2021

Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study.

Eur J Heart Fail 2021 Sep 12. Epub 2021 Sep 12.

Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

Aims: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19.

Methods And Results: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls.

Conclusion: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.
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http://dx.doi.org/10.1002/ejhf.2347DOI Listing
September 2021

Acute kidney injury and risk of cardiovascular outcomes: A nationwide cohort study.

Nefrologia (Engl Ed) 2021 Sep 3. Epub 2021 Sep 3.

Department of Nephrology, Rigshospitalet, Denmark.

Background: Acute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI.

Methods: In a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age <50 years, estimated glomerular filtration rate (eGFR) <15ml/min/1.73m, renal transplantation, index-admission due to cardiovascular disease or death during index-admission. The primary outcome was cardiovascular risk within one year from discharge, which was a composite of the secondary outcomes ischemic heart disease, heart failure or stroke. To estimate risks, we applied multiple logistic regression fitted by inverse probability of censoring weighting and stratified estimations by eGFR and age. We adjusted for proteinuria in the subcohort with measurements available.

Results: Among 565,056 hospital admissions, 39,569 (7.0%) cases of AKI were present. In total, 18,642 patients sustained a cardiovascular outcome. AKI was significantly associated with cardiovascular outcome with an adjusted OR [CI] of 1.33 [1.16-1.53], 1.43 [1.33-1.54], 1.23 [1.14-1.34], 1.38 [1.18-1.62] for eGFR ≥90, 60-89, 30-59 and 15-29ml/min/1.73m, respectively. When omitting the outcome heart failure, these results were 1.24 [1.06-1.45], 1.22 [1.11-1.33], 1.05 [0.95-1.16], 1.25 [1.02-1.54]. Results did not change substantially in strata of age groups, in AKI stages and in the subcohort adjusted for proteinuria.

Conclusion: Non-selected patients aged 50 years or above with AKI during admission had significantly higher one-year risk of cardiovascular event or death, especially, but not only due to heart failure, independent of age and eGFR.
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http://dx.doi.org/10.1016/j.nefro.2021.06.007DOI Listing
September 2021

Joint mapping of cardiovascular diseases: comparing the geographic patterns in incident acute myocardial infarction, stroke and atrial fibrillation, a Danish register-based cohort study 2014-15.

Int J Health Geogr 2021 08 30;20(1):41. Epub 2021 Aug 30.

National Institute of Public Health, University of Southern Denmark, Studiestræde 6, 1455, Copenhagen, Denmark.

Background: Disease mapping aims at identifying geographic patterns in disease. This may provide a better understanding of disease aetiology and risk factors as well as enable targeted prevention and allocation of resources. Joint mapping of multiple diseases may lead to improved insights since e.g. similarities and differences between geographic patterns may reflect shared and disease-specific determinants of disease. The objective of this study was to compare the geographic patterns in incident acute myocardial infarction (AMI), stroke and atrial fibrillation (AF) using the unique, population-based Danish register data.

Methods: Incident AMI, stroke and AF was modelled by a multivariate Poisson model including a disease-specific random effect of municipality modelled by a multivariate conditionally autoregressive (MCAR) structure. Analyses were adjusted for age, sex and income.

Results: The study included 3.5 million adults contributing 6.8 million person-years. In total, 18,349 incident cases of AMI, 28,006 incident cases of stroke, and 39,040 incident cases of AF occurred. Estimated municipality-specific standardized incidence rates ranged from 0.76 to 1.35 for AMI, from 0.79 to 1.38 for stroke, and from 0.85 to 1.24 for AF. In all diseases, geographic variation with clusters of high or low risk of disease after adjustment was seen. The geographic patterns displayed overall similarities between the diseases, with stroke and AF having the strongest resemblances. The most notable difference was observed in Copenhagen (high risk of stroke and AF, low risk of AMI). AF showed the least geographic variation.

Conclusion: Using multiple-disease mapping, this study adds to the results of previous studies by enabling joint evaluation and comparison of the geographic patterns in AMI, stroke and AF. The simultaneous mapping of diseases displayed similarities and differences in occurrence that are non-assessable in traditional single-disease mapping studies. In addition to reflecting the fact that AF is a strong risk factor for stroke, the results suggested that AMI, stroke and AF share some, but not all environmental risk factors after accounting for age, sex and income (indicator of lifestyle and health behaviour).
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http://dx.doi.org/10.1186/s12942-021-00294-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404297PMC
August 2021

Diabetes increases the risk of bone fractures in patients on kidney replacement therapy: A Danish national cohort study.

Bone 2021 12 28;153:116158. Epub 2021 Aug 28.

Department of Nephrology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.

Background: Patients treated with dialysis or living with a kidney transplant (kidney replacement therapy, KRT) have an increased risk of bone fracture. Patients with diabetes also have an increased risk of fracture. The aim of this study was to investigate whether the presence of diabetes in patients on KRT aggravates the risk of fracture.

Methods: Nationwide Danish registries were used in this retrospective cohort study. All prevalent adult patients on hemodialysis (HD) or peritoneal dialysis (PD) on 1st of January 2000 and all incident patients starting KRT (HD, PD, kidney transplanted (KTX)) until 31st of December 2011 were included in the KRT group. Adult persons not on KRT and without diabetes on 1st of January 2000 were used as a reference group. Patients were separated in groups with and without (+/-) diabetes. They were followed until first fracture, emigration, death, or end-of-study on 31st of December 2016.

Results: A total of 4,074,085 not on KRT +/- diabetes and 9053 patients on KRT +/- diabetes were included. Comparing the different groups with diabetes to the corresponding group without diabetes, the unadjusted HR (95% CI) for any first fracture were 1.2 (1.0-1.3) in the HD population, 1.4 (1.1-1.7) in the PD population, and 1.7 (1.4-2.2) in the KTX population. Further adjustments for age, sex, prior fractures, comorbidity and medication did not change these results significantly.

Conclusions: Diabetes increases the risk of fracture in patients on KRT.
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http://dx.doi.org/10.1016/j.bone.2021.116158DOI Listing
December 2021

Workforce Attachment after Ischemic Stroke - The Importance of Time to Thrombolytic Therapy.

J Stroke Cerebrovasc Dis 2021 Nov 24;30(11):106031. Epub 2021 Aug 24.

Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen 2100, Denmark.

Objectives: The ability to remain in employment addresses an important consequence of stroke beyond the usual clinical parameters. However, data on the association between time to intravenous thrombolysis and workforce attachment in patients with acute ischemic stroke are sparse.

Materials And Methods: In this nationwide cohort study, stroke patients of working age (18-60 years) treated with thrombolysis (2011-2016) who were part of the workforce prior to admission and alive at discharge were identified using the Danish Stroke Registry. The association between time to thrombolysis and workforce attachment one year later was examined with multivariable logistic regression.

Results: The study population comprised 1,329 patients (median age 51 years [25-75 percentile 45-56], 67.3% men). The median National Institutes of Health Stroke Scale score at presentation was 4 (25-75 percentile 2-8), and the median time from symptom-onset to initiation of thrombolysis was 140min (25-75 percentile 104-196min). The proportion of patients who were part of the workforce at one-year follow-up was 64.6%, 64.3%, 64.9%, and 60.0% in patients receiving thrombolysis within 90min, between 91-180min, between 181-270min, and after 270min, respectively. In adjusted analysis, time to thrombolysis between 91-180min, 181-270min, and >270min was not significantly associated with workforce attachment compared with thrombolysis received ≤90min of symptom-onset (ORs 0.89 [95%CI 0.60-1.31], 0.93 [0.66-1.31], and 0.80 [0.43-1.52], respectively).

Conclusions: In patients of working age admitted with stroke and treated with thrombolysis, two out of three were part of the workforce one year after discharge. There was no graded relationship between time to thrombolysis and the likelihood of workforce attachment.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106031DOI Listing
November 2021

DOAC discontinuation among patients with atrial fibrillation according to gender and cohabitation status; A Nationwide Cohort Study.

Eur Heart J Cardiovasc Pharmacother 2021 Aug 20. Epub 2021 Aug 20.

Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, 2900 Hellerup, Denmark.

Aims: The aim of this study was to evaluate the risk of discontinuing treatment with direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF) according to cohabitation status and gender.

Methods And Results: Using the Danish national registers, we identified 32,364 patients with AF aged 40-90 years in treatment with DOAC. The study period was from 2013 to 2017, and patients were followed for two years, or until death, outcome, or emigration. The main outcome was discontinuation of DOAC-treatment for at least 30 days.The absolute two-year risk of DOAC discontinuation was highest among men living alone (35.7%, 95% Confidence interval (CI): 37.3% to 34.1%). Men living alone had a 4.6% (95% CI: 6.4% to 2.8%) higher absolute risk of discontinuation and a 12% (HR 1.12, 95% CI: 1.04 to 1.20) higher relative risk of discontinuation compared to men living with a partner. Female patients living alone likewise had a higher absolute risk of DOAC discontinuation (2.6%, 95% CI: 4.4% to 0.09%) compared to female patients living with a partner, yet no statistically significant difference in relative risk. In an analysis evaluating gender, we found male gender to be associated with a significantly higher relative risk of DOAC-discontinuation (HR: 1.33, 95% CI: 1.26 to 1.40) compared to female gender (p-value for interaction with cohabitant status, P = 0.5996).

Conclusion: In this nationwide population study, male gender and living alone was associated with a higher risk of DOAC discontinuation among patients with AF.
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http://dx.doi.org/10.1093/ehjcvp/pvab065DOI Listing
August 2021

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants.

Heart 2021 Aug 13. Epub 2021 Aug 13.

Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.

Objective: Gastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.

Methods: This is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012-2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case-control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.

Results: 98 376 patients on NOACs (median age: 75 years (IQR: 68-82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).

Conclusions: Concomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.
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http://dx.doi.org/10.1136/heartjnl-2021-319503DOI Listing
August 2021

Out-of-hospital cardiac arrest and differential risk of cardiac and non-cardiac QT-prolonging drugs in 37 000 cases.

Br J Clin Pharmacol 2021 Aug 9. Epub 2021 Aug 9.

Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Aims: Drugs that prolong the QT interval, either by design (cardiac QT-prolonging drugs: anti-arrhythmics) or as off-target effect (non-cardiac QT-prolonging drugs), may increase the risk of ventricular arrhythmias and out-of-hospital cardiac arrest (OHCA). Risk mitigation measures were instituted, in particular, surrounding prescription of cardiac QT-prolonging drugs. We studied OHCA risk of both drug types in current clinical practice.

Methods: Using data from large population-based OHCA registries in the Netherlands and Denmark, we conducted two independent case-control studies. OHCA cases with presumed cardiac causes were matched on age/sex/index date with up to five non-OHCA controls. We calculated odds ratios (ORs) for the association of cardiac or non-cardiac QT-prolonging drugs with OHCA risk using conditional logistic regression analyses.

Results: We identified 2503 OHCA cases and 10 543 non-OHCA controls in the Netherlands, and 35 017 OHCA cases and 175 085 non-OHCA controls in Denmark. Compared to no use of QT-prolonging drugs, use of non-cardiac QT-prolonging drugs (Netherlands: cases: 3.0%, controls: 1.9%; Denmark: cases: 14.9%, controls: 7.5%) was associated with increased OHCA risk (Netherlands: OR 1.37 [95% CI: 1.03-1.81]; Denmark: OR 1.63 [95% CI: 1.57-1.70]). The association between cardiac QT-prolonging drugs (Netherlands: cases: 4.0%, controls: 2.5%; Denmark: cases: 2.1%, controls: 0.9%) and OHCA was weaker (Netherlands: OR 1.17 [95% CI: 0.92-1.50]; Denmark: OR 1.21 [95% CI: 1.09-1.33]), although users of cardiac QT-prolonging drugs had more medication use and comorbidities associated with OHCA risk than users of non-cardiac QT-prolonging drugs.

Conclusion: In clinical practice, cardiac QT-prolonging drugs confer lower OHCA risk than non-cardiac QT-prolonging drugs, although users of the former have higher a priori risk. This is likely due to risk mitigation measures surrounding prescription of cardiac QT-prolonging drugs.
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http://dx.doi.org/10.1111/bcp.15030DOI Listing
August 2021

Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study.

J Am Heart Assoc 2021 08 7;10(16):e020551. Epub 2021 Aug 7.

Institute for Nutrition Research School of Medical and Health Sciences Edith Cowan University Perth Australia.

Background Dietary vitamin K (K and K) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K and vitamin K were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K, the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K or K. The similar inverse associations with both vitamin K and K, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.
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http://dx.doi.org/10.1161/JAHA.120.020551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475061PMC
August 2021

Initiation of domiciliary care and nursing home admission following first hospitalization for heart failure, stroke, chronic obstructive pulmonary disease or cancer.

PLoS One 2021 4;16(8):e0255364. Epub 2021 Aug 4.

Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Patients with chronic diseases are at higher risk of requiring domiciliary and nursing home care, but how different chronic diseases compare in terms of risk is not known. We examined initiation of domiciliary care and nursing home admission among patients with heart failure (HF), stroke, COPD and cancer.

Methods: Patients with a first-time hospitalization for HF, stroke, COPD or cancer from 2008-2016 were identified. Patients were matched on age and sex and followed for five years.

Results: 111,144 patients, 27,786 with each disease, were identified. The median age was 69 years and two thirds of the patients were men. The 5-year risk of receiving domiciliary care was; HF 20.9%, stroke 25.2%, COPD 24.6% and cancer 19.3%. The corresponding adjusted hazard ratios (HRs), with HF patients used as reference, were: stroke 1.35[1.30-1.40]; COPD 1.29[1.25-1.34]; and cancer 1.19[1.14-1.23]. The five-year incidence of nursing home admission was 6.6% for stroke, and substantially lower in patients with HF(2.6%), COPD(2.6%) and cancer (1.5%). The adjusted HRs were (HF reference): stroke, 2.44 [2.23-2.68]; COPD 1.01 [0.91-1.13] and cancer 0.76 [0.67-0.86]. Living alone, older age, diabetes, chronic kidney disease, depression and dementia predicted a higher likelihood of both types of care.

Conclusions: In patients with HF, stroke, COPD or cancer 5-year risk of domiciliary care and nursing home admission, ranged from 19-25% and 1-7%, respectively. Patients with stroke had the highest rate of domiciliary care and were more than twice as likely to be admitted to a nursing home, compared to patients with the other conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255364PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336831PMC
November 2021

Layer-specific global longitudinal strain and the risk of heart failure and cardiovascular mortality in the general population: the Copenhagen City Heart Study.

Eur J Heart Fail 2021 Jul 29. Epub 2021 Jul 29.

Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark.

Aims: Layer-specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer-specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLS ), endomyocardial (GLS ), and epimyocardial (GLS ) GLS in the general population.

Methods And Results: A total of 4013 citizens were included in the present study. All 4013 had two-dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow-up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex-stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLS [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02-1.31, per 1% decrease] and GLS (HR 1.19, 95% CI 1.04-1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models.

Conclusions: In the general population, sex modifies the prognostic value of GLS resulting in GLS being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females.
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http://dx.doi.org/10.1002/ejhf.2315DOI Listing
July 2021

Trends in Use of Cardioprotective Medication in Peripheral Artery Disease: A Nationwide Study.

J Am Heart Assoc 2021 08 28;10(15):e020333. Epub 2021 Jul 28.

Department of Cardiology Bispebjerg-Frederiksberg University Hospital Copenhagen Denmark.

Background Guideline-based cardioprotective medical therapy is intended to reduce the burden of adverse cardiovascular and limb outcomes in patients with peripheral artery disease (PAD). However, contemporary data describing trends in use of medication remains limited. The present study, therefore, aims to investigate changes in use of cardioprotective medication in PAD. Methods and Results By using Danish national healthcare registries, we identified all patients with first-time diagnosis of PAD (1997-2016) and classified them into two groups: (1) PAD+ that includes all patients with PAD with a history of cardiovascular disease, ie, myocardial infarction, atrial fibrillation, and stroke (n=162 627); and (2) PAD (n=87 935) that comprise patients without a history of cardiovascular disease. We determined the use of medication in the first 12 months after the incident diagnosis of PAD and estimated age standardized 1-year mortality rates. Our results showed increase in use of cardioprotective medication throughout the study period in both groups. However, PAD+ had a higher use of medication (acetylsalicylic acid, 3.5%-48.4%; Clopidogrel, 0%-17.6%; vitamin K antagonists, 0.9%-7.8%; new oral anticoagulants, 0.0%-10.1%; Statins, 1.9%-58.1%; angiotensin-converting enzyme inhibitors, 1.2%-20.6%), compared with PAD (acetylsalicylic acid, 2.9%-54.4%; Clopidogrel, 0%-11.9%; vitamin K antagonists, 0.9%-2.4%; new oral anticoagulants, 0.0%-3.4%; Statins, 1.5%-56.9%; angiotensin-converting enzyme, 0.9%-17.2%), respectively. Furthermore, 1-year mortality rates in PAD declined with increased use of medications during study. Conclusions In this nationwide study, use of cardioprotective medication increased considerably with time, but compared to patients with other atherosclerotic diseases, there remains an underuse of guideline-based medical therapy in patients with PAD.
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http://dx.doi.org/10.1161/JAHA.120.020333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475709PMC
August 2021
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