Publications by authors named "Christian Torp-Pedersen"

929 Publications

Seroprevalence of SARS-CoV-2 antibodies and reduced risk of reinfection through six months: a Danish observational cohort study of 44,000 healthcare workers.

Clin Microbiol Infect 2021 Sep 17. Epub 2021 Sep 17.

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address:

Objectives: Antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor against COVID-19. We examined longitudinal changes in seroprevalence in healthcare workers (HCW) in Copenhagen and the protective effect of antibodies against SARS-CoV-2.

Methods: In this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCW three times over six months. HCW-characteristics were obtained by questionnaires. ClinicalTrials.gov, NCT04346186.

Results: From April to October 2020 we screened 44,698 HCW of which 2,811 were seropositive at least once. The seroprevalence increased from 4.0% (1,501/37,452) to 7.4% (2,022/27,457) during the period (p<0.001) and was significantly higher than in non-HCW. Frontline HCW had a significantly increased risk of seropositivity compared to non-frontline HCW with risk ratios (RR) at the three rounds of 1.49 (95% CI 1.34-1.65, p<0.001), 1.52 (1.39-1.68, p<0.001) and 1.50 (1.38-1.64, p<0.001). The seroprevalence was 1.42- to 2.25-fold higher (p<0.001) in HCW from dedicated COVID-19 wards compared to other frontline HCW. Seropositive HCW had a RR of 0.35 (0.15-0.85, p=0.012) of reinfection during the following six months and 2,115 (95%) out of 2,248 of those who were seropositive during rounds one or two remained seropositive after four to six months. The 133 of 2,248 (5.0%) participants who seroreverted were slightly older and reported fewer symptoms than other seropositive participants.

Conclusions: HCW remained at increased risk of infection with SARS-CoV-2 during the six months period. Seropositivity against SARS-CoV-2 persisted for at least six months in the vast majority of HCW and was associated with a significantly lower risk of reinfection.
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http://dx.doi.org/10.1016/j.cmi.2021.09.005DOI Listing
September 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 Sep 17: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

Systolic Blood Pressure and Outcome in Patients Admitted With Acute Heart Failure: An Analysis of Individual Patient Data From 4 Randomized Clinical Trials.

J Am Heart Assoc 2021 Sep 13:e022288. Epub 2021 Sep 13.

Department of Cardiology Bispebjerg Hospital University of Copenhagen Copenhagen Denmark.

BACKGROUND In acute heart failure (AHF), systolic blood pressure (SBP) is an important clinical variable. This study assessed the association between SBP and short-term and long-term outcomes in a large cohort of patients with AHF. METHODS AND RESULTS This is an analysis of 4 randomized controlled trials investigating serelaxin versus placebo in patients admitted with AHF and SBPs from 125 to 180 mm Hg. Outcomes were 180-day all-cause mortality and a composite end point of all-cause mortality, worsening heart failure, or hospital readmission for heart failure the first 14 days. Left ventricular ejection fraction (LVEF) was examined as LVEF<40% and LVEF≥40%. Multivariable Cox regression models were adjusted for known confounders of outcomes in AHF. A total of 10 533 patients with a mean age of 73 (±12) years and a mean SBP of 145 (±7) mm Hg were included. LVEF was assessed in 9863 patients (93%); 4737 patients (45%) had LVEF<40%. Increasing SBP was inversely associated with 180-day mortality (adjusted hazard ratio [HR], 0.93; 95% CI, 0.89-0.98; =0.008 per 10 mm Hg increase) and with the composite end point (HR, 0.90; 95% CI, 0.85-0.94; <0.001 per 10 mm Hg increase). A significant interaction with LVEF was observed, revealing that SBP was not associated with mortality in patients with LVEF≥40% (HR, 0.98; 95% CI, 0.91-1.04; per 10 mm Hg increase), but was strongly associated with increased mortality in LVEF<40% (HR, 0.84; 95% CI, 0.77-0.92; per 10 mm Hg increase). CONCLUSIONS Elevated SBP is associated with favorable short-term and long-term outcomes in patients with AHF. In our predefined subgroup analysis, we found that baseline SBP was not associated with mortality in LVEF≥40%, but was strongly associated with mortality in patients with LVEF<40%.
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http://dx.doi.org/10.1161/JAHA.121.022288DOI Listing
September 2021

Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark.

J Clin Med 2021 Aug 27;10(17). Epub 2021 Aug 27.

Department of Rheumatology, Aalborg University Hospital, 9000 Aalborg, Denmark.

Background: Patients with systemic lupus erythematosus (SLE) have an increased risk of infections due to impaired immune functions, disease activity, and treatment. This study investigated the impact of having SLE on the incidence of hospitalisation with COVID-19 infection.

Methods: This was a nationwide cohort study from Denmark between 1 March 2020 to 2 February 2021, based on the linkage of several nationwide registers. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with SLE compared with the general population in Cox-regression models. Among SLE patients, the hazard ratio (HR) for hospitalisation was analysed as nested case-control study.

Results: Sixteen of the 2533 SLE patients were hospitalised with COVID-19 infection. The age-sex adjusted rate per 1000 person years was 6.16 (95% CI 3.76-10.08) in SLE patients, and the corresponding hazard ratio was 2.54 (95% CI 1.55-4.16) compared with the matched general population group after adjustment for comorbidities. Among SLE patients, hydroxychloroquine treatment was associated with a HR for hospitalisation of 0.61 (95% CI 0.19-1.88), and 1.06 (95% CI 0.3-3.72) for glucocorticoid treatment.

Conclusion: Patients with SLE were at increased risk of hospitalisation with COVID-19.
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http://dx.doi.org/10.3390/jcm10173842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432052PMC
August 2021

The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction.

Int J Cardiol 2021 Sep 6. Epub 2021 Sep 6.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Sciences, Cardiology, Lund University, Skane University Hospital, Lund, Sweden. Electronic address:

Aims: Peripheral artery disease (PAD) constitute a high-risk with adverse clinical outcomes. We aimed to investigate the cardiovascular outcomes following myocardial infarction (MI).

Methods And Results: This nationwide, Danish register-based follow-up study includes all patients experiencing an MI between 2000 and 2017. Patients with and without PAD were compared. Multivariable logistic regression was used to derive relative risks of 1-year major adverse cardiovascular events (MACE; all-cause mortality, reinfarction, stroke or heart failure). Individual components, cardiovascular mortality, and bleeding, standardized to age, sex and comorbidity distributions of all patients were assessed. MI patients with PAD (n = 5083, 2.9%) were older and more comorbid compared to patients without PAD (n = 174,673). After standardization, PAD was associated with higher 1-year relative risks of MACE (RR 1.21 [95% CI 1.17;1.25]), all-cause (RR 1.29 [95% CI 1.24;1.35]) and cardiovascular mortality (RR 1.3 [95% CI 1.24;1.36]), reinfarction (RR 1.17 [95% CI 1.11;1.22]), stroke (RR 1.12 [95% CI 0.92;1.32]), heart failure (RR 1.22 [95% CI 1.12;1.32]), and bleeding episodes (RR 1.25 [95% CI 1.04,1.46]). Similar results were seen in 30-day survivors after adjustment for antithrombotic post-discharge medication for MACE (RR 1.25 [95% CI 1.20,1.31]), all-cause mortality (RR 1.47 [95% CI 1.37,1.57], cardiovascular mortality (RR 1.49 [95% CI 1.37,1.61]), reinfarction (RR 1.17 [95% CI 1.08,1.12]) and heart failure (RR 1.22 [95% CI 1.12,1.32]).

Conclusion: Comparing to patients without PAD, patients with PAD had increased 1-year relative risk of MACE, all-cause mortality, reinfarction, stroke, heart failure, cardiovascular mortality and bleeding following MI. The low prevalence of PAD is suggestive of considerable under-diagnosing.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.053DOI Listing
September 2021

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

Nefrologia 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

The genomics of heart failure: design and rationale of the HERMES consortium.

ESC Heart Fail 2021 Sep 3. Epub 2021 Sep 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods And Results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 under an additive genetic model.

Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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http://dx.doi.org/10.1002/ehf2.13517DOI Listing
September 2021

Incidence of ischaemic stroke and mortality in patients with acute coronary syndrome and first-time detected atrial fibrillation: a nationwide study.

Eur Heart J 2021 09 3. Epub 2021 Sep 3.

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

Aims: The aim of this study was to examine contemporary data on the 1-year prognosis of patients surviving acute coronary syndrome (ACS) and concomitant first-time detected atrial fibrillation (AF).

Methods And Results: Using Danish nationwide registries, we identified all patients surviving a first-time admission with ACS from 2000 to 2018 and grouped them into (i) those without AF prior to or during ACS; (ii) those with a history of AF; and (iii) those with first-time detected AF during admission with ACS. With 1 year of follow-up, rates of ischaemic stroke, death, and bleeding were compared between study groups using multivariable adjusted Cox proportional hazards analysis. We included 161 266 ACS survivors: 135 878 (84.2%) without AF, 18 961 (11.8%) with history of AF, and 6427 (4.0%) with first-time detected AF at admission with ACS. Compared to those without AF, the adjusted 1-year rates of outcomes were as follows: ischaemic stroke [hazard ratio (HR) 1.38 (95% CI 1.22-1.56) for patients with history of AF and HR 1.67 (95% CI 1.38-2.01) for patients with first-time detected AF]; mortality [HR 1.25 (95% CI 1.21-1.31) for patients with history of AF and HR 1.52 (95% CI 1.43-1.62) for patients with first-time detected AF]; and bleeding [HR 1.22 (95% CI 1.14-1.30) for patients with history of AF and HR 1.28 (95% CI 1.15-1.43) for patients with first-time detected AF].

Conclusion: In patients with ACS, first-time detected AF appeared to be at least as strongly associated with the 1-year rates of ischaemic stroke, mortality, and bleeding as compared with patients with a history of AF.
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http://dx.doi.org/10.1093/eurheartj/ehab575DOI Listing
September 2021

Risk of Stroke, Myocardial Infarction, and Death Among Patients With Retinal Artery Occlusion and the Effect of Antithrombotic Treatment.

Transl Vis Sci Technol 2021 Sep;10(11)

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

Purpose: To evaluate the risk of future stroke, myocardial infarction (MI), and death of patients with retinal artery occlusion (RAO) and the effect of various antithrombotic treatments as secondary prevention.

Methods: This cohort study was based on nationwide health registries and included the entire Danish population from 2000 to 2018. All patients with RAO were identified and their adjusted risks of stroke, MI, or death in time periods since RAO were compared with those of the Danish population. Furthermore, antithrombotic treatment of patients with RAO was determined by prescription claims, and the association with the risk of stroke, MI, or death was assessed using multivariate Poisson regression models and expressed as rate ratios (RR) with 95% confidence intervals (95% CIs).

Results: After inclusion, 6628 individuals experienced a first-time RAO, of whom 391 had a stroke, 66 had a MI, and 402 died within the first year after RAO. RAO was associated with an increased risk of stroke, MI, or death which persisted for more than 1 year for all three outcomes but was highest on days 3 to 14 after RAO for stroke, with an adjusted RR of 50.71 (95% CI, 41.55-61.87), and on days 14 to 90 after RAO for MI and death, with adjusted RRs of 1.98 (95% CI, 1.25-3.15) and 1.64 (95% CI, 1.28-189), respectively. Overall, antithrombotic treatment was not associated with any protective effect the first year.

Conclusions: Patients with RAO had an increased risk of stroke, MI, or death. No protective effect of antithrombotic treatment was shown.

Translational Relevance: These findings are relevant to the management of patients with RAO.
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http://dx.doi.org/10.1167/tvst.10.11.2DOI Listing
September 2021

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

J Stroke Cerebrovasc Dis 2021 Aug 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
August 2021

Race Differences in Interventions and Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010 to 2014.

J Am Heart Assoc 2021 Sep 25;10(17):e019082. Epub 2021 Aug 25.

Duke Clinical Research Institute Durham NC.

Background Following the implementation of the HeartRescue project, with interventions in the community, emergency medical services, and hospitals to improve care and outcomes for out-of-hospital cardiac arrests (OHCA) in North Carolina, improved bystander and first responder treatments as well as survival were observed. This study aimed to determine whether these improvements were consistent across Black versus White individuals. Methods and Results Using the Cardiac Arrest Registry to Enhance Survival (CARES), we identified OHCA from 16 counties in North Carolina (population 3 million) from 2010 to 2014. Temporal changes in interventions and outcomes were assessed using multilevel multivariable logistic regression, adjusted for patient and socioeconomic neighborhood-level factors. Of 7091 patients with OHCA, 36.5% were Black and 63.5% were White. Black patients were younger, more females, had more unwitnessed arrests and non-shockable rhythm (Black: 81.0%; White: 75.4%). From 2010 to 2014, the adjusted probabilities of bystander cardiopulmonary resuscitation (CPR) went from 38.5% to 51.2% in White, <0.001; and 36.9% to 45.6% in Black, =0.002, and first-responder defibrillation went from 13.2% to 17.2% in White, =0.002; and 14.7% to 17.3% in Black, =0.16. From 2010 to 2014, survival to discharge only increased in White (8.0% to 11.4%, =0.004; Black 8.9% to 9.5%, =0.60), though, in shockable patients the probability of survival to discharge went from 24.8% to 34.6% in White, =0.02; and 21.7% to 29.0% in Black, =0. 10. Conclusions After the HeartRescue program, bystander CPR and first-responder defibrillation increased in both patient groups; however, survival only increased significantly for White patients.
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http://dx.doi.org/10.1161/JAHA.120.019082DOI Listing
September 2021

Immediate psychological impact on citizen responders dispatched through a mobile application to out-of-hospital cardiac arrests.

Resusc Plus 2021 Sep 13;7:100155. Epub 2021 Aug 13.

Copenhagen Emergency Medical Services, University of Copenhagen, Denmark.

Background: Activating citizen responders may increase survival after out-of-hospital cardiac arrest (OHCA) but could induce significant psychological impact on the citizen responders. We examined psychological impact among citizen responders within the first days following resuscitation attempt.

Methods And Results: A mobile phone application to activate citizen responders to perform cardiopulmonary resuscitation (CPR) was implemented in the Capital Region of Denmark. All dispatched citizen responders (September 2017 to May 2019) received a survey 90 minutes after an alarm, including self-rating of perceived psychological impact on a scale of 1-4.Of 5,395 included citizen responders, most (88.6%) completed the survey within 24 hours.The majority reported no psychological impact (68.6%), whereas 24.7%, 5.5% and 1.2% reported low, moderate, or severe impact, respectively. Severe impact was more commonly reported in the following groups: No CPR training (3.8% vs 1.2%, p = 0.02), age < 30 years (2.0% vs 0.9%, p < 0.001), female sex (1.8% vs 0.7%, p < 0.001), provided CPR (2.7% vs 1.0%, p < 0.001), and arrived prior to the emergency medical services (EMS) (2.8% vs 0.7%, p < 0.001) compared to no to moderate impact.Chi square test, Mann-Whitney U test, Fischer's exact test and a logistic regression model were used to assess differences in psychological impact across groups.

Conclusion: Very few citizen responders reported severe psychological impact. Lack of prior CPR training, younger age, female sex, performing CPR and arrival prior to the EMS were associated with greater psychological impact. Though very few citizen responders reported severe impact, the possibility of professional debriefing should be considered in citizen responder programs.
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http://dx.doi.org/10.1016/j.resplu.2021.100155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371246PMC
September 2021

Reintervention rates following bioprosthetic surgical aortic valve replacement-a Danish Nationwide Cohort Study.

Eur J Cardiothorac Surg 2021 Aug 19. Epub 2021 Aug 19.

Department of Cardiology, Zealand University Hospital, Roskilde, Denmark.

Objectives: Updated European guidelines recommend annual echocardiographic evaluation after bioprosthetic surgical aortic valve replacement (bio-SAVR). Given the increased demand on health care resources, only clinically relevant controls can be prioritized. We therefore aimed to explore reintervention rates following bio-SAVR.

Methods: From the nationwide Danish Register of Surgical Procedures, we identified all patients ≥40 years with isolated bio-SAVR ± concomitant coronary artery bypass graft surgery (CABG) during 2000-2016. In 90-day reintervention-free survivors, we assessed aortic valve reintervention rates (primary outcome) and all-cause mortality rates (secondary outcome) at 1, 3 and 5 years with total follow-up until 31 December 2017 and further estimated annual theoretical echocardiographic control visits.

Results: In 10 518 patients with bio-SAVR (+CABG 39.7%), we observed low reintervention rates at 1, 3 and 5 years, but with high rates of all-cause mortality; i.e. 5-year reintervention rate of 3.7/1000 person-years (≤1.5%) and 5-year mortality rate of 21.7/1000 person-years. Accounting for the competing risk of death, 5-year rates were inversely related to age group and remained relatively low across all age categories but increased gradually in the long term. A significant proportion of reinterventions were presumed due to infectious endocarditis (48% at 3 years, 37% at 5 years). With annual transthoracic echocardiography, the theoretical ratio of echocardiographies per reintervention in the first 5 years was 248, and 425 when endocarditis events were excluded.

Conclusion: Reintervention rates within the first 5 years following bio-SAVR were relatively rare, and with a substantial number due to endocarditis.
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http://dx.doi.org/10.1093/ejcts/ezab365DOI 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

Employment Status, Readmission and Mortality After Acute Exacerbation of COPD.

Int J Chron Obstruct Pulmon Dis 2021 5;16:2257-2265. Epub 2021 Aug 5.

Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark.

Introduction: The understanding of whether and to what extent employment status affects readmission and mortality is limited in patients with COPD.

Aim: To explore how employment status affects readmission and mortality after first admission to the hospital with acute exacerbation of COPD (AECOPD).

Methods: This study used Danish national registry-based data. All patients admitted for the first time to the hospital between 1999 and 2014 with a diagnosis of AECOPD, age 35-59, without a previous asthma diagnosis were included in the study. Employment status effect on 30-, 90-, and 365-day readmission and mortality was examined using logistic regression, adjusting for relevant confounders.

Results: A total of 11,850 COPD patients were included in the study of which 3563 (30%) were working, 1368 (12%) unemployed, 840 (7%) on sick leave, and 6079 (51%) receiving early retirement. Patients receiving early retirement had, compared to patients working, an adjusted increased likelihood of readmission at 30, 90, and 365 days (odds ratio (OR) 1.26 (CI (1.06-1.49)), 1.33 (CI (1.16-1.53)), and 1.48 (CI (1.33-1.66)), respectively). An increased likelihood was also seen in unemployed at 365 days follow-up (OR 1.44 (CI (1.22-1.68))). Early retirement was associated with an increased mortality at 30, 90, and 365 days (OR 1.39 (CI (1.07-1.80)) 1.37 (CI (1.09-1.79)) and 1.48 (CI (1.25-1.75)), respectively). An increased likelihood was also seen in patients receiving sick leave (OR 1.57 (CI (1.21-2.04))).

Conclusion: Patients with COPD who are not working at the time of first admission have a higher likelihood of readmission and mortality.
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http://dx.doi.org/10.2147/COPD.S319840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352575PMC
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 Aug 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
August 2021

Prediction of Residual Stroke Risk in Anticoagulated Patients with Atrial Fibrillation: mCARS.

J Clin Med 2021 Jul 29;10(15). Epub 2021 Jul 29.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK.

Our ability to evaluate residual stroke risk despite anticoagulation in atrial fibrillation (AF) is currently lacking. The Calculator of Absolute Stroke Risk (CARS) has been proposed to predict 1-year absolute stroke risk in non-anticoagulated patients. We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients from 'real-world' and 'clinical trial' cohorts. We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS were estimated for each patient. None of the patients were treated with non-vitamin K antagonist oral anticoagulants. The predicted residual stroke risk was compared to actual stroke risk. 3503 patients were included (2205 [62.9%] clinical trial and 1298 [37.1%] real-world). There was wide variation of CARS for each category of CHADS-VASc score in both cohorts. Average predicted residual stroke risk by mCARS (1.8 ± 1.8%) was identical to actual stroke risk (1.8% [95% CI, 1.3-2.4]) in the clinical trial, and broadly similar in the real-world (2.1 ± 1.9% vs. 2.4% [95% CI, 1.6-3.4]). AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598-0.758) and 0.712 [95% CI, 0.618-0.805], respectively. mCARS was able to refine stroke risk estimation for each point of the CHADS-VASc score in both cohorts. Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS, thereby allowing an assessment of the absolute risk reduction of treatment and facilitating a patient-centred approach in the management of AF. Such identification of patients with high residual stroke risk could help target more aggressive interventions and follow-up.
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http://dx.doi.org/10.3390/jcm10153357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348193PMC
July 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
August 2021

Vaginal estrogen and association with dementia: A nationwide population-based study.

Alzheimers Dement 2021 Jul 28. Epub 2021 Jul 28.

Department of Gynaecology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Introduction: Use of systemic hormone therapy has been positively associated with development of dementia. Little is known about the dose-dependent effect of vaginal estradiol on dementia risk.

Methods: We assessed associations between cumulative dose of vaginal estradiol tablets and dementia in a case-control study nested in a nationwide Danish cohort of women aged 50 to 60 years at study initiation, who did not use systemic hormone therapy. Each case was age-matched to 10 female controls.

Results: A total of 4574 dementia cases were matched to 45,740 controls. Cumulative use of vaginal estradiol tablets was not associated with all-cause dementia; adjusted hazard ratio 1.02 (95% confidence interval [CI] 0.89-1.18) for low dose (< 750 mcg), 1.07 (0.94-1.21) for medium dose (750-2000 mcg), and 0.93 (0.84-1.03) for high dose (> 2000 mcg). Similarly, Alzheimer's disease (AD) only was not associated with vaginal estradiol.

Discussion: Exposure to vaginal estradiol tablets was not associated with all-cause dementia or AD only.
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http://dx.doi.org/10.1002/alz.12417DOI Listing
July 2021

Heart failure associated with imported malaria: a nationwide Danish cohort study.

ESC Heart Fail 2021 Jul 27. Epub 2021 Jul 27.

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

Aims: Despite adequate treatment, recent studies have hypothesized that malaria may affect long-term cardiovascular function. We aimed to investigate the long-term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark.

Methods: Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all-cause death (1 January 1994 to 1 January 2017). The population was age- and sex-matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion.

Results: We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow-up was 9.8 years (interquartile range 3.9-16.4 years). Event rates per 1000 person-years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all-cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21-2.09], P = 0.001), but not MI (HR: 1.00 [0.72-1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74-1.35], P = 0.98) or all-cause death (HR 1.11 [0.94-1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14-2.36], P = 0.008).

Conclusion: Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF.
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http://dx.doi.org/10.1002/ehf2.13441DOI Listing
July 2021

Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction.

Int J Cardiol 2021 Jul 24. Epub 2021 Jul 24.

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

Background: To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials.

Methods: All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models.

Results: In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35-0.70) and prasugrel (HR 0.48, 95% CI 0.33-0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011-2015 showed similar results.

Conclusions: Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.047DOI Listing
July 2021

Implications for cardiac arrest coverage using straight-line versus route distance to nearest automated external defibrillator.

Resuscitation 2021 Jul 22. Epub 2021 Jul 22.

Copenhagen Emergency Medical Services, University of Copenhagen, Denmark; Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Denmark.

Aim: Quantifying the ratio describing the difference between "true route" and "straight-line" distances from out-of-hospital cardiac arrests (OHCAs) to the closest accessible automated external defibrillator (AED) can help correct likely overestimations in AED coverage. Furthermore, we aimed to examine to what extent the closest AED based on true route distance differed from the closest AED using "straight-line".

Methods: OHCAs (1994-2016) and AEDs (2016) in Copenhagen, Denmark and in Toronto, Canada (2007-2015 and 2015, respectively) were identified. Three distances were calculated between OHCA and target AED: 1) the straight-line distance ("straight-line") to the closest AED, 2) the corresponding true route distance to the same AED ("true route"), and 3) the closest AED based only on true route distance ("shortest true route"). The ratio between "true route" and "straight-line" distance was calculated and differences in AED coverage (an OHCA ≤ 100 m of an accessible AED) were examined.

Results: The "straight-line" AED coverage of 100 m was 24.2% (n = 2008/8295) in Copenhagen and 6.9% (n = 964/13916) in Toronto. The corresponding "true route" distance reduced coverage to 9.5% (n = 786) and 3.8% (n = 529), respectively. The median ratio between "true route" and "straight-line" distance was 1.6 in Copenhagen and 1.4 in Toronto. In 26.1% (n = 2167) and 22.9% (n = 3181) of all Copenhagen and Toronto OHCAs respectively, the closest AED in "shortest true route" was different than the closest AED initially found by "straight-line".

Conclusions: Straight-line distance is not an accurate measure of distance and overestimates the actual AED coverage compared to a more realistic true route distance by a factor 1.4-1.6.
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http://dx.doi.org/10.1016/j.resuscitation.2021.07.014DOI Listing
July 2021

Long-term outcomes after out-of-hospital cardiac arrest in relation to socioeconomic status.

Resuscitation 2021 Jul 22. Epub 2021 Jul 22.

Department of Clinical Investigation, North Zealand Hospital, Hillerød, Denmark.

Aims: This study aimed to examine whether socioeconomic differences exist in long-term outcomes after out-of-hospital cardiac arrest (OHCA).

Methods: We included 2309 30-day OHCA survivors ≥ 30 years of age from the Danish Cardiac Arrest Registry, 2001-2014, divided in tertiles of household income (low, medium, high). Absolute probabilities were estimated using logistic regression for 1-year outcomes and cause-specific Cox regression for 5-year outcomes. Differences between income-groups were standardized with respect to age, sex, education and comorbidities.

Results: High-income compared to low-income patients had highest 1-year (96.4% vs. 84.2%) and 5-year (87.6% vs. 64.1%) survival, and lowest 1-year (11.3% vs. 7.4%) and 5-year (13.7% vs. 8.6%) risk of anoxic brain damage/nursing home admission. The corresponding standardized probability differences were 8.2% (95%CI 4.7-11.6%) and 13.9% (95%CI 8.2-19.7%) for 1- and 5-year survival, respectively; and -4.5% (95%CI -8.2 to -1.2%) and -5.1% (95%CI -9.3 to -0.9%) for 1- and 5-year risk of anoxic brain damage/nursing home admission, respectively. Among 831 patients < 66 years working prior to OHCA, 72.1% returned to work within 1 year and 80.8% within 5 years. High-income compared to low-income patients had the highest chance of 1-year (76.4% vs. 58.8%) and 5-year (85.3% vs. 70.6%) return to work with the corresponding absolute probability difference of 18.0% (95%CI 3.8-32.7%) for 1-year and 9.4% (95%CI -3.4 to 22.3%) for 5-year.

Conclusion: Patients of high socioeconomic status had higher probability of long-term survival and return to work, and lower risk of anoxic brain damage/nursing home admission after OHCA compared to patients of low socioeconomic status.
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http://dx.doi.org/10.1016/j.resuscitation.2021.07.015DOI Listing
July 2021

European Heart Journal quality standards.

Eur Heart J 2021 07;42(28):2729-2736

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

The aim of the European Heart Journal (EHJ) is to attract innovative, methodologically sound, and clinically relevant research manuscripts able to change clinical practice and/or substantially advance knowledge on cardiovascular diseases. As the reference journal in cardiovascular medicine, the EHJ is committed to publishing only the best cardiovascular science adhering to the highest ethical principles. EHJ uses highly rigorous peer-review, critical statistical review and the highest quality editorial process, to ensure the novelty, accuracy, quality, and relevance of all accepted manuscripts with the aim of inspiring the clinical practice of EHJ readers and reducing the global burden of cardiovascular diseases. This review article summarizes the quality standards pursued by the EHJ to fulfill its mission.
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http://dx.doi.org/10.1093/eurheartj/ehab324DOI Listing
July 2021

Nationwide cardiovascular disease admission rates during a second COVID-19 lockdown.

Am Heart J 2021 Jul 15;241:35-37. Epub 2021 Jul 15.

The Danish Heart Foundation, Copenhagen, Denmark.

Societal lockdowns during the first wave of the coronavirus disease 2019 pandemic were associated with decreased admission rates for acute cardiovascular conditions worldwide. In this nationwide Danish study of the first five weeks of a second pandemic lockdown, incidence of new-onset heart failure and atrial fibrillation remained stable, but there was a significant drop in new-onset ischemic heart disease and ischemic stroke during the fourth week of lockdown, which normalized promptly. The observed drops were lower compared to the first Danish lockdown in March 2020; thus, our data suggest that declines in acute cardiovascular disease admission rates during future lockdowns are avoidable.
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http://dx.doi.org/10.1016/j.ahj.2021.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280375PMC
July 2021

Proposal for the use of echocardiography in bloodstream infections due to different streptococcal species.

BMC Infect Dis 2021 Jul 16;21(1):689. Epub 2021 Jul 16.

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

Background: Infective endocarditis (IE) is diagnosed in 7-8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs.

Methods: In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3-10%, high-risk 10-30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3-10%), or "wait & see" (IE < 3%).

Results: We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to "wait & see" strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence.

Conclusion: In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography.
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http://dx.doi.org/10.1186/s12879-021-06391-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285817PMC
July 2021

Risk of Physical Injury for Dispatched Citizen Responders to Out-of-Hospital Cardiac Arrest.

J Am Heart Assoc 2021 Jul 14;10(14):e021626. Epub 2021 Jul 14.

Copenhagen Emergency Medical Services Copenhagen University Hospital Copenhagen Denmark.

Background Citizen responder programs are implemented worldwide to dispatch volunteer citizens to participate in out-of-hospital cardiac arrest resuscitation. However, the risk of injuries in relation to activation is largely unknown. We aimed to assess the risk of physical injury for dispatched citizen responders. Methods and Results Since September 2017, citizen responders have been activated through a smartphone application when located close to a suspected cardiac arrest in the Capital Region of Denmark. A survey was sent to all activated citizen responders, including a specific question about risk of acquiring an injury during activation. We included all surveys from September 1, 2017, to May 15, 2020. From May 15, 2019, to May 15, 2020, we followed up on all survey nonresponders by phone call, e-mail, or text messages to examine if nonresponders were at higher risk of severe or fatal injuries. In 1665 suspected out-of-hospital cardiac arrests, 9574 citizen responders were dispatched and 76.6% (7334) answered the question regarding physical injury. No injury was reported by 99.3% (7281) of the responders. Being at risk of physical injury was reported by 0.3% (24), whereas 0.4% (26) reported an injury (25 minor injuries and 1 severe injury [ankle fracture]). When following up on nonresponders (2472), we reached 99.1% (2449). No one reported acquired injuries, and only 1 reported being at risk of injury. Conclusions We found low risk of physical injury reported by volunteer citizen responders dispatched to out-of-hospital cardiac arrest. Risk of injury should be considered and monitored as a safety measure in citizen responder programs.
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http://dx.doi.org/10.1161/JAHA.121.021626DOI Listing
July 2021

Pharmacoepidemiological methods for computing the duration of pharmacological prescriptions using secondary data sources.

Eur J Clin Pharmacol 2021 Jul 10. Epub 2021 Jul 10.

Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, 2100, København Ø, Denmark.

Purpose: In pharmacoepidemiology, correctly defining the exposure period of pharmacological treatment is a challenging step when information on the time in treatment is missing or incomplete.

Methods: In this review, we describe several methods for defining exposure to pharmacological treatments using secondary data sources that lack such information.

Results And Conclusion: Several methods for assessing the duration of redeemed prescriptions and combining them into temporal sequences are available. We present a set of considerations to make researchers aware of the potentials and pitfalls of these methods that may aid in minimizing biases in research using these methods. Additionally, we highlight that, to date, there is no one-size-fits-all solution. Thus, the choice of method should be based on their area of applicability combined with a careful mapping to the research scenario under investigation.
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http://dx.doi.org/10.1007/s00228-021-03188-9DOI Listing
July 2021
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