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Study objective: To examine first-time depression, anxiety, stress disorders or psychotropic drug prescriptions within one year after incident heart failure (HF). Design: Nationwide Epidemiological registry study. Setting: National patient registries. Participants: Patients in Denmark with a first-time HF diagnosis during 2005–2015. Interventions: None. Main outcome measures: Incidences of depression, anxiety, stress disorders or first-time prescription of a psychotropic drug were determined. Results: A total of 94,712 HF patients and 473,560 matched controls were included (median age 74.0 [64.0–81.0] years, 60.8 % males). At one year after incident HF, 11.9 % met the primary composite endpoint (depression, anxiety, or stress disorders or prescription of related psychotropic drugs), with 8.6 % outpatients and 13.3 % in-patients, versus 2.4 % of the controls. Starting psychotropic medication accounted for most of the composite endpoint events, as 11.6 % of the HF patients started antidepressants, anxiolytics, hypnotics, or sedative drugs (2.4 % among controls), while 0.6 % received a registered diagnosis of depression, anxiety, or stress disorder (<0.1 % among controls). The relative risk of psychotropic drug prescriptions in HF patients versus controls (standardized to the age, sex, and selected comorbidity distributions of all included subjects) was 3.85 [95 % CI 3.73–3.98]. The corresponding relative risk for one of the psychiatric diagnoses was 12.90 [95 % CI 10.60–15.19]. Conclusion: A substantial part of patients with newly diagnose heart failure started treatment with psychotropic drugs whereas only a small fraction was registered with depression, anxiety, or stress disorders within one-year follow-up. The incidences were significantly higher than in the background population.

Study objective: To examine first-time depression, anxiety, stress disorders or psychotropic drug prescriptions within one year after incident heart failure (HF). Design: Nationwide Epidemiological registry study. Setting: National patient registries. Participants: Patients in Denmark with a first-time HF diagnosis during 2005–2015. Interventions: None. Main outcome measures: Incidences of depression, anxiety, stress disorders or first-time prescription of a psychotropic drug were determined. Results: A total of 94,712 HF patients and 473,560 matched controls were included (median age 74.0 [64.0–81.0] years, 60.8 % males). At one year after incident HF, 11.9 % met the primary composite endpoint (depression, anxiety, or stress disorders or prescription of related psychotropic drugs), with 8.6 % outpatients and 13.3 % in-patients, versus 2.4 % of the controls. Starting psychotropic medication accounted for most of the composite endpoint events, as 11.6 % of the HF patients started antidepressants, anxiolytics, hypnotics, or sedative drugs (2.4 % among controls), while 0.6 % received a registered diagnosis of depression, anxiety, or stress disorder (<0.1 % among controls). The relative risk of psychotropic drug prescriptions in HF patients versus controls (standardized to the age, sex, and selected comorbidity distributions of all included subjects) was 3.85 [95 % CI 3.73–3.98]. The corresponding relative risk for one of the psychiatric diagnoses was 12.90 [95 % CI 10.60–15.19]. Conclusion: A substantial part of patients with newly diagnose heart failure started treatment with psychotropic drugs whereas only a small fraction was registered with depression, anxiety, or stress disorders within one-year follow-up. The incidences were significantly higher than in the background population.

OBJECTIVE: It remains disputed how much the risk of Staphylococcus aureus bacteraemia (SAB) is increased in patients with rheumatoid arthritis (RA), and the extent to which orthopaedic implants explain the risk. We assessed SAB incidence rates (IRs) and incidence rate ratios (IRRs), comparing RA patients with a general population cohort (GPC) and individuals with versus without orthopaedic implants.METHOD: Danish residents aged ≥ 18 years without prior RA or SAB (=GPC) were followed up for RA and microbiologically verified SAB events (1996-2017). IRRs were calculated by age- and sex-stratified Poisson regression adjusted for age, comorbidities, calendar year, and socioeconomic status.RESULTS: The GPC comprised 5 398 690 individuals. We identified 33 567 incident RA patients (=RA cohort) (median follow-up 7.3 years, IQR 3.6-12.3). We observed 25 023 SAB events (n = 224 in the RA cohort). IRs per 100 000 person-years were 81.0 (RA cohort) and 29.9 (GPC). IRs increased with age. Adjusted IRRs in 18-59-year-old RA patients were 2.6 (95% confidence interval 1.8-3.7) for women and 1.8 (1.1-3.1) for men, compared with same sex and age group GPC. IRRs declined with age. Compared with the GPC without implants, IRRs for RA patients with implants ranged from 1.9 (1.3-2.8) (women ≥ 70 years) to 5.3 (2.2-12.8) (18-59-year-old men).CONCLUSION: In this nationwide registry-based cohort study RA was a risk factor for SAB, and orthopaedic implants further increased the risk. Clinicians should be aware of potential SAB in patients with RA and orthopaedic implants.

Background Fluid retention is a known but underappreciated side-effect of non-steroidal anti-inflammatory drug (NSAID) use. As type 2 diabetes mellitus (T2DM) has been linked to both subclinical cardiomyopathy and a decline in kidney function, short-term NSAID use could lead to subsequently development of heart failure (HF) due to aberrations in fluid balances. Purpose We investigated associations between short-term NSAID use and the risk of HF in a nationwide cohort of patients with T2DM. Methods Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998–2018. Follow-up began 120 days after first-time T2DM diagnosis among patients without prior heart failure or a rheumatological diagnosis indicating long-term NSAID use. To describe use of NSAID among patients with T2DM, we reported proportions of patients claiming at least 1, 2, 3 or 4 prescriptions of NSAID within one year of start of follow-up. We investigated associations between use of NSAIDs (celecoxib, diclofenac, ibuprofen and naproxen) and new-onset HF hospitalizations using a case-crossover design with 28-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). The case-crossover design uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding. Sensitivity analyses using exposure windows of 14 and 42 days were performed as well. Results A total of 334,950 patients with T2DM was included (47.7% female, median age of 61 [interquartile range 50–70]). Celecoxib and naproxen were rarely used; on the contrary, prescriptions of diclofenac and ibuprofen were claimed at least once within one year from the beginning of follow-up by 4.9% and 15.5% of patients, respectively–0.9% and 2.7% claimed at least four prescriptions (Figure 1). The risk of new-onset HF hospitalization was increased

Background Treatment with medical cannabis for chronic pain is in popular demand, and a rising number of countries allow physicians to prescribe medical cannabis for pain management. However, data on drug-safety is scarce. Studies have showed a risk of cardiovascular side effects following use of recreational cannabis warranting further investigations into the safety of prescribing medical cannabis. Purpose We investigated risk of new-onset arrhythmias (tachy- or bradyarrhythmia and conduction disorders), acute coronary syndrome (ACS) and heart failure (HF) following use of prescribed medical cannabis compared with no use in a nationwide cohort of patients with chronic pain. Methods Using nationwide Danish registers, a cohort of patients with chronic pain and without prior history of arrhythmias, ACS, HF or prescribed medical cannabis (cannabinoid, cannabidiol or dronabinol) use were followed from 2018–2021. Any patient from the cohort initiating first-time treatment with medical cannabis was identified and matched 1:10 to corresponding controls within the cohort using incidence density sampling. Matching parameters were age group, sex, and chronic pain diagnosis. Follow-up was initiated at the date of the first claimed prescription of medical cannabis or the corresponding date among controls. We reported 180-day standardized absolute risks (AR) with 95% confidence intervals (CI) and risk ratios (RR) from fitted multivariable logistic regression models comparing patients exposed to medical cannabis with patients not exposed. Separate analyses for each chronic pain group were conducted as well. Results Among 1.6 million patients with chronic pain, 4,562 patients claimed at least one prescription of medical cannabis (exposed) and were each matched to 10 controls (non-exposed). Exposed and non-exposed patients were identical in relation to matching parameters; however, exposed patients were slightly more comorbid, and a larger

Background In addition to lifestyle intervention, guidelines recommend initiation of antidiabetic (AD) treatment within 3 months of diagnosing type 2 diabetes (T2D). Yet, patients with an initial HbA1c level between 48 and 57 mmol/mol may await effects of lifestyle intervention up to 6 months. Omitting initial AD treatment and any lifestyle-induced remission, may affect initiation of statins and renin-angiotensin system inhibitors (RASi) and, thus, cardiovascular risk. Purpose To examine whether omission of initial AD treatment is associated with an increased 5-year risk of first-time major cardiovascular event (MACE: myocardial infarction/stroke/all-cause death) compared with well-controlled patients on AD. Further, whether lower initial use of statins and RASi could explain this excess risk of MACE. Methods We used Danish registers to identify patients with a first-measured HbA1c of 48–57 mmol/mol between 2014 and 2020. We included patients aged 40–80 years without prior atherosclerotic disease that were alive the following 180 days (the index date). At date of index, we divided patients into four groups according to AD treatment and achieved HbA1c (mmol/mol): well-controlled (HbA1c ≤47) on AD; poorly controlled (HbA1c ≥48) on AD; remission (HbA1c ≤47) not on AD; poorly controlled (HbA1c ≥48) not on AD. Based on a Cox-regression model and imputations of treatment values of statins and RASi from two logistic regression models, we examined to what extent the observed standardised 5-year risk of MACE within each group could be reduced if each group had the same probability of treatment initiation with statin and RASi as well-controlled patients on AD. Results We included 14,206 patients (median age 59 [IQR 51–68] years; 52.0% men) with the following distribution according to AD group: well-controlled on AD: 22.3%; poorly controlled on AD: 14.7%; remission not on AD: 38.3%; poorly controlled not on AD: 24.6%. Patients not on

Objective To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population. Method In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored. Results The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1–35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8–35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5–0.6%) in 2018: 0.8% (95% CI 0.7–0.8%) for women and 0.3% (95% CI 0.3–0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018. Conclusion The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator.

Objectives: This study aimed to explore return to work after COVID-19 and how disease severity affects this. Study design: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. Methods: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. Results: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. Conclusion: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Objectives: This study aimed to explore return to work after COVID-19 and how disease severity affects this. Study design: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. Methods: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. Results: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. Conclusion: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Introduction The 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is diagnostic cutoff for myocardial infarction (MI). Several factors are known to lead to an increase in cTn including sex, kidney function, left ventricular function and various comorbidities. Similarly, studies have shown that cTn concentration of patients increase with age. However, the impact of age on the concentration of cTn in healthy individuals is unclear as several studies of healthy populations showed little to no impact of age. Purpose To determine the effect of age on the URL of cTn for the Danish population. Methods We invited active and retired blood donors with the aim of including 250 participants of each sex in each of four age groups, <50, 50–60, 60–70 and >70 years, for a total of about 2000 participants. cTn levels were measured by 4 cTn assays (Siemens Atellica and Vista cTnI, Roche cTnT and Abbott Alinity cTnI). The age specific URL were calculated using the non-parametric method. Quantile regression for the 99th percentile was adjusted for sex and creatinine concentration. Results A total of 2287 participants were sampled in the study, of which 4 (0.2%) were excluded due to a history of heart disease and 7 (0.3%) were excluded due to insufficient plasma for screening biomarkers. The median age was 58.6 (IQR 48.2–69.7), and 52.6% were female. Figure 1 shows the distribution of cTn concentrations in age intervals. There was a significant increase in cTn with age for all assays (all p<0.001). After adjusting for sex and creatinine concentration, increasing age was only significantly associated with cTnT (0.40 ng/L increase per year, p=0.03). Figure 2 panel A shows the age specific URL for each assay, where we observed a significant difference for cTnT with the URL increasing from 15.8 ng/L (90% CI 12.4–33.9 ng/L) for participants <50 years to 37.6 ng/L (90% CI 34.6–41.5 ng/L) for participants >70 years.

Objective: Out-of-hospital cardiac arrest (OHCA) occurrence has been shown to exhibit a circadian rhythm, following the circadian rhythm of acute myocardial infarction (AMI) occurrence. Diabetes mellitus (DM) is associated with changes in circadian rhythm. We aimed to compare the temporal variation of OHCA occurrence over the day and week between OHCA patients with DM and those without.Methods: In two population-based OHCA registries (Amsterdam Resuscitation Studies [ARREST] 2010-2016, n = 4163, and Danish Cardiac Arrest Registry [DANCAR], 2010-2014, n = 12,734), adults (≥18y) with presumed cardiac cause of OHCA and available medical history were included. Single and double cosinor analysis was performed to model circadian variation of OHCA occurrence. Stratified analysis of circadian variation was performed in patients with AMI as immediate cause of OHCA.Results: DM patients (22.8% in ARREST, 24.2% in DANCAR) were older and more frequently had cardiovascular risk factors or previous cardiovascular disease. Both cohorts showed 24 h-rhythmicity, with significant amplitudes in single and double cosinor functions (P-range < 0.001). In both registries, a morning peak (10:00-11:00) and an evening peak (20:00-21:00) was observed in both DM and non-DM patients. No septadian variation was observed in either DM or non-DM patients (P-range 0.13-84).Conclusions: In these two population-based OHCA registries, we observed a similar circadian rhythm of OHCA occurrence in DM and non-DM patients.

Background: Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. Objectives: To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. Methods: Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996–2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). Results: The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16–9.16%) vs 4.58% (3.79–5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94–12.71%) vs 7.07% (6.09–8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12–3.27%) vs 0.64% (0.40–0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64–39.21%) vs 16.57% (15.10–18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01–2.47]). Conclusion: Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.

Objective: Out-of-hospital cardiac arrest (OHCA) occurrence has been shown to exhibit a circadian rhythm, following the circadian rhythm of acute myocardial infarction (AMI) occurrence. Diabetes mellitus (DM) is associated with changes in circadian rhythm. We aimed to compare the temporal variation of OHCA occurrence over the day and week between OHCA patients with DM and those without.Methods: In two population-based OHCA registries (Amsterdam Resuscitation Studies [ARREST] 2010-2016, n = 4163, and Danish Cardiac Arrest Registry [DANCAR], 2010-2014, n = 12,734), adults (≥18y) with presumed cardiac cause of OHCA and available medical history were included. Single and double cosinor analysis was performed to model circadian variation of OHCA occurrence. Stratified analysis of circadian variation was performed in patients with AMI as immediate cause of OHCA.Results: DM patients (22.8% in ARREST, 24.2% in DANCAR) were older and more frequently had cardiovascular risk factors or previous cardiovascular disease. Both cohorts showed 24 h-rhythmicity, with significant amplitudes in single and double cosinor functions (P-range < 0.001). In both registries, a morning peak (10:00-11:00) and an evening peak (20:00-21:00) was observed in both DM and non-DM patients. No septadian variation was observed in either DM or non-DM patients (P-range 0.13-84).Conclusions: In these two population-based OHCA registries, we observed a similar circadian rhythm of OHCA occurrence in DM and non-DM patients.

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.

Background: Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. Objectives: To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. Methods: Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996–2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). Results: The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16–9.16%) vs 4.58% (3.79–5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94–12.71%) vs 7.07% (6.09–8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12–3.27%) vs 0.64% (0.40–0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64–39.21%) vs 16.57% (15.10–18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01–2.47]). Conclusion: Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.

Background The significance of chronic kidney disease on susceptibility to COVID-19 and subsequent outcomes remains unaddressed. Objective To investigate the association of estimated glomerular filtration rate (eGFR) on risk of contracting COVID-19 and subsequent adverse outcomes. Methods Rates of hospital-diagnosed COVID-19 were compared across strata of eGFR based on conditional logistic regression using a nested case–control framework with 1:4 matching of patients diagnosed with COVID-19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID-19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G-computation of results to determine 60-day risk standardized to the distribution of risk factors in the sample. Results Estimated glomerular filtration rate was inversely associated with rate of hospital-diagnosed COVID-19: eGFR 61–90 mL/min/1.73m2 HR 1.13 (95% CI 1.03–1.25), P = 0.011; eGFR 46–60 mL/min/1.73m2 HR 1.26 (95% CI 1.06–1.50), P = 0.008; eGFR 31–45 mL/min/1.73m2 HR 1.68 (95% CI 1.34–2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50–4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60-day risk of death or severe COVID-19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7–15.0); eGFR 90–61 mL/min/1.73m2 16.1% (95% CI 14.5–17.7); eGFR 46–60 mL/min/1.73m2 17.8% (95% CI 14.7–21.2); eGFR 31–45 mL/min/1.73m2 22.6% (95% CI 18.2–26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1–29.1). Conclusions Renal insufficiency was associated with progressive increase in both rate of hospital-diagnosed COVID-19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID-19.

Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown. We used Danish population-based registers to systematically investigate whether the 41 most used individual antihypertensive drugs were associated with an altered risk of incident depression. Analyses of diuretics were included for comparisons. Participants were included in the study in January 2005 and followed until December 2015. Two different outcome measures were included: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants. Continued use of classes of angiotensin agents, calcium antagonists, and β-blockers was associated with significantly decreased rates of depression, whereas diuretic use was not. Individual drugs associated with decreased depression included 2 of 16 angiotensin agents: enalapril and ramipril; 3 of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations; and 4 of 15 β-blockers: propranolol, atenolol, bisoprolol, and carvedilol. No drug was associated with an increased risk of depression. In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents. This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.

Contains fulltext : 220353.pdf (Publisher’s version ) (Closed access), The field of observational studies or "real world studies" is in rapid development with many new techniques introduced and increased understanding of traditional methods. For this reason the current paper provides an overview of current methods with focus on new techniques. Some highlights can be emphasized: We provide an overview of sources of data for observational studies. There is an overview of sources of bias and confounding. Next There is an overview of causal inference techniques that are increasingly used. The most commonly used techniques for statistical modelling are reviewed with focus on the important distinction of risk versus prediction. The final section provides examples of common problems with reporting observational data.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Contains fulltext : 220353.pdf (Publisher’s version ) (Closed access), The field of observational studies or "real world studies" is in rapid development with many new techniques introduced and increased understanding of traditional methods. For this reason the current paper provides an overview of current methods with focus on new techniques. Some highlights can be emphasized: We provide an overview of sources of data for observational studies. There is an overview of sources of bias and confounding. Next There is an overview of causal inference techniques that are increasingly used. The most commonly used techniques for statistical modelling are reviewed with focus on the important distinction of risk versus prediction. The final section provides examples of common problems with reporting observational data.

Contains fulltext : 220353.pdf (Publisher’s version ) (Closed access), The field of observational studies or "real world studies" is in rapid development with many new techniques introduced and increased understanding of traditional methods. For this reason the current paper provides an overview of current methods with focus on new techniques. Some highlights can be emphasized: We provide an overview of sources of data for observational studies. There is an overview of sources of bias and confounding. Next There is an overview of causal inference techniques that are increasingly used. The most commonly used techniques for statistical modelling are reviewed with focus on the important distinction of risk versus prediction. The final section provides examples of common problems with reporting observational data.

Aims: The hospitalization of patients with MI has decreased during global lockdown due to the COVID-19 pandemic. Whether this decrease is associated with more severe MI, e.g. MI-CS, is unknown. We aimed to examine the association of Corona virus disease (COVID-19) pandemic and incidence of acute myocardial infarction with cardiogenic shock (MI-CS). Methods: On March 11, 2020, the Danish government announced national lock-down. Using Danish nationwide registries, we identified patients hospitalized with MI-CS. Incidence rates (IR) and incidence rate ratios (IRR) were used to compare MI-CS before and after March 11 in 2015–2019 and in 2020. Results: We identified 11,769 patients with MI of whom 696 (5.9%) had cardiogenic shock in 2015–2019. In 2020, 2132 MI patients were identified of whom 119 had cardiogenic shock (5.6%). The IR per 100,000 person years before March 11 in 2015–2019 was 9.2 (95% CI: 8.3–10.2) and after 8.9 (95% CI: 8.0–9.9). In 2020, the IR was 7.5 (95% CI: 5.8–9.7) before March 11 and 7.7 (95% CI: 6.0–9.9) after. The IRRs comparing the 2020-period with the 2015–2019 period before and after March 11 (lockdown) were 0.81 (95% CI: 0.59–1.12) and 0.87 (95% CI: 0.57–1.32), respectively. The IRR comparing the 2020-period during and before lockdown was 1.02 (95% CI: 0.74–1.41). No difference in 7-day mortality or in-hospital management was observed between study periods. Conclusion: We could not identify a significant association of the national lockdown on the incidence of MI-CS, along with similar in-hospital management and mortality in patients with MI-CS.

Background: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. Objectives: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. Methods: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51–74 and >74 years). Results: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64–11.3), 51–74 years (23.3; 22.9–23.7), >74 years (58.5; 57.9–59.0); hazard ratios 245.18 (141.45–424.76), 45.85 (42.77–49.15) and 24.5 (23.64–25.68) for those ≤50, 51–74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). Conclusions: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.

Aims: The hospitalization of patients with MI has decreased during global lockdown due to the COVID-19 pandemic. Whether this decrease is associated with more severe MI, e.g. MI-CS, is unknown. We aimed to examine the association of Corona virus disease (COVID-19) pandemic and incidence of acute myocardial infarction with cardiogenic shock (MI-CS). Methods: On March 11, 2020, the Danish government announced national lock-down. Using Danish nationwide registries, we identified patients hospitalized with MI-CS. Incidence rates (IR) and incidence rate ratios (IRR) were used to compare MI-CS before and after March 11 in 2015–2019 and in 2020. Results: We identified 11,769 patients with MI of whom 696 (5.9%) had cardiogenic shock in 2015–2019. In 2020, 2132 MI patients were identified of whom 119 had cardiogenic shock (5.6%). The IR per 100,000 person years before March 11 in 2015–2019 was 9.2 (95% CI: 8.3–10.2) and after 8.9 (95% CI: 8.0–9.9). In 2020, the IR was 7.5 (95% CI: 5.8–9.7) before March 11 and 7.7 (95% CI: 6.0–9.9) after. The IRRs comparing the 2020-period with the 2015–2019 period before and after March 11 (lockdown) were 0.81 (95% CI: 0.59–1.12) and 0.87 (95% CI: 0.57–1.32), respectively. The IRR comparing the 2020-period during and before lockdown was 1.02 (95% CI: 0.74–1.41). No difference in 7-day mortality or in-hospital management was observed between study periods. Conclusion: We could not identify a significant association of the national lockdown on the incidence of MI-CS, along with similar in-hospital management and mortality in patients with MI-CS.

Introduction Drugs that influence cardiac electrophysiological properties by impacting on cardiac ion channels have been associated with an increased risk of out-of-hospital cardiac arrest (OHCA) due to ventricular tachycardia/ventricular fibrillation (VT/VF). It is unknown whether dihydropyridines, which block L-type calcium channels, are associated with increased risk of OHCA. Purpose To determine whether the widely used dihydropyridines nifedipine and amlodipine are associated with increased OHCA risk. Methods We performed a multi-country case-control study using data from the Dutch Amsterdam Resuscitation Studies registry (ARREST, 2005-2011) and the Danish Cardiac Arrest Registry (DANCAR, 2001-2014). Both registries are community-based registries of all-cause OHCA and are part of the ESCAPE-NET consortium that studies OHCA across Europe. Cases were cardiac-caused OHCA patients with VT/VF, and controls (up to 5 per case) were non-OHCA individuals matched on age, sex and index (OHCA) date. Dutch controls were sampled from PHARMO Database Network and Danish controls from the general (Danish) population. We compared current use on the index date of the study drugs (prescription within 90 days before OHCA) to no use of any dihydropyridine, using conditional logistic regression analysis with adjustment for well-known risk factors of OHCA. Results We studied 2,503 cases and 10,543 controls in ARREST (median age 67.0 years, interquartile range [IQR] 57.0-77.0 years; 77.4% male), and 22,208 cases and 111,040 controls in DANCAR (median age 74 years, IQR 64-82 years; 62.9% male). In both registries, current use of high-dose nifedipine (≥60mg/day), but not low-dose nifedipine (

ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants a

Contains fulltext : 215442.pdf (publisher's version ) (Open Access), OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major blee

Contains fulltext : 215442.pdf (publisher's version ) (Open Access), OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major blee

Contains fulltext : 215442.pdf (publisher's version ) (Open Access), OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major blee