Publications by authors named "Lars Frost"

89 Publications

Newly diagnosed atrial fibrillation and hospital utilization in heart failure: a nationwide cohort study.

ESC Heart Fail 2021 Dec 2;8(6):4808-4819. Epub 2021 Nov 2.

Diagnostic Centre, University Clinic for Development of Innovative Patient Pathways, Silkeborg Regional Hospital, Falkevej 3, Silkeborg, 8600, Denmark.

Aims: Atrial fibrillation (AF) constitutes a major burden to health services, but the importance of incident AF in patients with heart failure (HF) is unclear. We examined the associations between incident AF and hospital utilization in patients with HF.

Methods And Results: In a nationwide matched-cohort study of HF patients, we identified patients diagnosed with incident AF between 2008 and 2018 in the Danish Heart Failure Registry (N = 4463), and we compared them to matched referents without AF (N = 17 802). Incident AF was associated with a multivariable-adjusted 4.8-fold increase (95% CI 4.1-5.6) and 4.3-fold increase (95% CI 3.9-4.8) in the cumulative incidence of inpatient and outpatient contacts within 30 days, respectively. At 1 year, the cumulative incidence ratios were 1.8 (95% CI 1.7-1.9) and 1.4 (95% CI 1.4-1.5). Incident AF was also associated with increases in the total numbers of inpatient and outpatient hospital contacts within 30 days (multivariable-adjusted rate ratio 1.4, 95% CI 1.4-1.5, and 1.6, 95% CI 1.6-1.7, respectively). At 1 year, the ratios were 2.2 (95% CI 2.1-2.3) and 2.0 (95% CI 1.9-2.1). The multivariable-adjusted proportion of bed-day use among HF patients with incident AF was 10.9-fold (95% CI 9.3-12.9) higher at 30 days and 5.3-fold (95% CI 4.3-6.4) higher at 1 year compared with AF-free referents.

Conclusions: Incident AF in HF is associated with earlier hospital contact, more hospital contacts, and more hospital bed-days. More evidence on interventions that may prevent the risk and subsequent burden of AF in HF is urgently needed.
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http://dx.doi.org/10.1002/ehf2.13668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712819PMC
December 2021

Trends in the incidence and mortality of intracerebral hemorrhage, and the associated risk factors, in Denmark from 2004 to 2017.

Eur J Neurol 2022 Jan 28;29(1):168-177. Epub 2021 Sep 28.

Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Background And Purpose: The distribution of the major modifiable risk factors for intracerebral hemorrhage (ICH) changes rapidly. These changes call for contemporary data from large-scale population-based studies. The aim of the present study was to examine trends in incidence, risk factors, and mortality in ICH patients from 2004 to 2017.

Methods: In a population-based cohort study, we calculated age- and sex-standardized incidence rates (SIRs), incidence rates (IRs) stratified by age and sex per 100,000 person-years, and trends in risk profiles. We estimated absolute mortality risk, and the Cox proportional hazards regression multivariable-adjusted hazard ratios for 30-day and 1-year mortality.

Results: We included 16,902 patients (53% men; median age 75 years) from 2004 to 2017. The SIR of ICH decreased from 33 (95% confidence interval [CI] 32-34) in 2004/2005 to 28 (95% CI 27-29) in 2016/2017. Among patients aged ≥70 years, the IR decreased from 137 (95% CI 130-144) in 2004/2005 to 112 (95% CI 106-117) in 2016/2017. The IR in patients aged <70 years was unchanged. From 2004 to 2017, the proportion of patients with hypertension increased from 49% to 66%, the use of oral anticoagulants increased from 7% to 18%, and the use of platelet inhibitors decreased from 40% to 28%. The adjusted hazard ratio for 30-day mortality in 2016/2017 was 0.94 (95% CI 0.89-1.01) and 1-year mortality was 0.98 (95% CI 0.93-1.04) compared with 2004/2005.

Conclusion: The incidence of spontaneous ICH decreased from 2004 to 2017, with no clear trend in mortality. The risk profile of ICH patients changed substantially, with increasing proportions of hypertension and anticoagulant treatment. Given the high mortality rate of ICH, further advances in prevention and treatment are urgently needed.
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http://dx.doi.org/10.1111/ene.15110DOI Listing
January 2022

Perfusion imaging combined with coronary calcium scoring. A step further towards individualized medicine?

Int J Cardiol Heart Vasc 2021 Aug 28;35:100845. Epub 2021 Jul 28.

Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark.

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http://dx.doi.org/10.1016/j.ijcha.2021.100845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339334PMC
August 2021

Cross-sectional study of aortic valve calcification and cardiovascular risk factors in older Danish men.

Heart 2021 10 10;107(19):1536-1543. Epub 2021 Aug 10.

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

Objective: Aortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60-74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.

Methods: Participants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.

Results: 14 073 men aged 60-74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0-82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.

Conclusions: AVC was prevalent in the general population of men aged 60-74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.

Trial Registration Number: NCT03946410 and ISRCTN12157806.
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http://dx.doi.org/10.1136/heartjnl-2021-319023DOI Listing
October 2021

Heart failure and atrial fibrillation - does heart failure subtype matter?

Int J Cardiol 2021 10 6;341:46-47. Epub 2021 Aug 6.

Department of Medicine, Boston University School of Medicine, MA, USA; Department of Epidemiology, Boston University School of Public Health, MA, USA.

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http://dx.doi.org/10.1016/j.ijcard.2021.08.006DOI Listing
October 2021

Population-Based Risk Factors for Ascending, Arch, Descending, and Abdominal Aortic Dilations for 60-74-Year-Old Individuals.

J Am Coll Cardiol 2021 07;78(3):201-211

Elitary Research Centre CIMA, Odense University Hospital, Odense, Denmark; Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.

Background: Aortic dilations (ectasias and aneurysms) may occur on any segment of the aorta. Pathogenesis varies between locations, suggesting that etiology and risk factors may differ. Despite this discrepancy, guidelines recommend screening of the whole aorta if 1 segmental dilation is discovered.

Objectives: The purpose of this study was to determine the most dominant predictors for dilations at the ascending, arch, descending, and abdominal part of the aorta, and to establish comprehensive risk factor profiles for each aortic segment.

Methods: Individuals aged 60-74 years were randomly selected to participate in DANCAVAS I+II (Danish Cardiovascular Multicenter Screening Trials). Participants underwent cardiovascular risk assessments, including blood samples, blood pressure readings, medical records, and noncontrast computed tomography scans. Adjusted odds ratios for potential risk factors of dilations were estimated by multivariate logistic analyses.

Results: The study population consisted of 14,989 participants (14,235 men, 754 women) with an average age of 68 ± 4 years. The highest adjusted odd ratios for having any aortic dilation were observed when coexisting aortic dilations were present. Other noteworthy predictors included coexisting iliac dilations, hypertension, increasing body surface area, male sex, familial disposition, and atrial fibrillation, which were present in various combinations for the different aortic parts. Smoking and acute myocardial infarction were inversely associated with ascending and abdominal dilations. Diabetes was a shared protective factor.

Conclusions: Risk factors differ for aortic dilations between locations. The most dominant predictor for having a dilation at any aortic segment is the presence of an aortic dilation elsewhere. This supports current guidelines when recommending a full screening of the aorta if a focal aortic dilation is discovered.
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http://dx.doi.org/10.1016/j.jacc.2021.04.094DOI Listing
July 2021

Prevalence and extent of coronary artery calcification in the middle-aged and elderly population.

Eur J Prev Cardiol 2021 Jun 28. Epub 2021 Jun 28.

Department of Clinical Research, University of Southern Denmark, Winsløwparken 19, 5000 Odense C, Denmark.

Aims: Coronary artery calcification (CAC) measured on cardiac computed tomography (CT) is an important risk marker for cardiovascular disease (CVD) and has been included in the prevention guidelines. The aim of this study was to describe CAC score reference values in the middle-aged and elderly population and to develop a freely available CAC calculator.

Methods And Results: All participants from two population-based cardiac CT screening cohorts (DanRisk and DANCAVAS) were included. The CAC score was measured as a part of a screening session. Positive CAC scores were log-transformed and non-parametrically regressed on age for each gender, and percentile curves were transposed according to proportions of zero CAC scores. Men had higher CAC scores than women, and the prevalence and extend of CAC increased steadily with age. An online CAC calculator was developed, http://flscripts.dk/cacscore. After entering sex, age, and CAC score, the CAC score percentile and the coronary age are depicted including a figure with the specific CAC score and 25%, 50%, 75%, and 90% percentiles. The specific CAC score can be compared to the entire background population or only those without prior CVD.

Conclusion: This study provides modern population-based reference values of CAC scores in men and woman and a freely accessible online CAC calculator. Physicians and patients are very familiar with blood pressure and lipids, but unfamiliar with CAC scores. Using the calculator makes it easy to see if a CAC value is low, moderate, or high, when a physician in the future communicate and discusses a CAC score with a patient.
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http://dx.doi.org/10.1093/eurjpc/zwab111DOI Listing
June 2021

Polygenic Risk Score-Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain.

Circ Genom Precis Med 2021 06 25;14(3):e003298. Epub 2021 May 25.

Department of Clinical Genetics (M.N.), Aarhus University Hospital, Denmark.

Background: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography on a suspicion of obstructive CAD.

Methods: In this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease), we included 1617 consecutive patients with stable chest symptoms and no history of CAD referred for coronary computed tomography angiography. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped, and their PRSs were calculated. All patients underwent coronary computed tomography angiography. Patients with a suspected ≥50% stenosis also underwent invasive coronary angiography with fractional flow reserve. A combined end point of obstructive CAD was defined as a visual invasive coronary angiography stenosis >90%, fractional flow reserve <0.80, or a quantitative coronary analysis stenosis >50% if fractional flow reserve measurements were not feasible.

Results: The PRS was associated with obstructive CAD independent of CRFs (adjusted odds ratio, 1.8 [95% CI, 1.5-2.2] per SD). The PRS had an area under the curve of 0.63 (0.59-0.68), which was similar to that for age and sex. Combining the PRS with CRFs led to a CRF+PRS model with area under the curve of 0.75 (0.71-0.79), which was 0.04 more than the CRF model (=0.0029). By using pretest probability (pretest probability) cutoffs at 5% and 15%, a net reclassification improvement of 15.8% (=3.1×10) was obtained, with a down-classification of risk in 24% of patients (211 of 862) in whom the pretest probability was 5% to 15% based on CRFs alone.

Conclusions: Adding a PRS improved risk stratification of obstructive CAD beyond CRFs, suggesting a modest clinical potential of using PRSs to guide diagnostic testing in the contemporary clinical setting. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02264717.
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http://dx.doi.org/10.1161/CIRCGEN.120.003298DOI Listing
June 2021

Association Between Bipolar Disorder or Schizophrenia and Oral Anticoagulation Use in Danish Adults With Incident or Prevalent Atrial Fibrillation.

JAMA Netw Open 2021 05 3;4(5):e2110096. Epub 2021 May 3.

Comprehensive Life Resources, Tacoma, Washington.

Importance: Individuals with bipolar disorder or schizophrenia have a higher risk of adverse outcomes from cardiovascular diseases. Oral anticoagulation therapy (OAT) for patients with atrial fibrillation (AF) is needed for stroke prevention, but whether patients with bipolar disorder or schizophrenia face disparities in receiving this therapy is unknown.

Objective: To assess whether bipolar disorder or schizophrenia is associated with a lower rate of OAT initiation in patients with incident AF and lower prevalence of OAT in those with prevalent AF.

Design, Setting, And Participants: A nationwide cohort study of Danish patients with AF was conducted from January 1, 2005, to December 31, 2016, and data were analyzed from January 1 to June 15, 2020. Data from national registries included information on all redeemed prescriptions and all hospital contacts of all patients with incident or prevalent AF (age, 18-100 years) and increased risk status, defined by a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) risk score greater than or equal to 2.

Exposures: Hospital diagnosis of bipolar disorder or schizophrenia.

Main Outcomes And Measures: Adjusted proportion differences for OAT initiation and OAT prevalence, comparing individuals with and without bipolar disorder or schizophrenia.

Results: Patients included with incident AF (n = 147 810) had a mean (SD) age of 76.9 (10.1) years, 78 577 (53.2%) were women, 1208 (0.8%) had bipolar disorder, and 572 (0.4%) had schizophrenia. Accounting for age, sex, and calendar time, bipolar disorder and schizophrenia were associated with significantly lower frequency of OAT initiation within 90 days after incident AF (bipolar disorder: -12.7%; 95% CI, -15.3% to -10.0%; schizophrenia: -24.5%; 95% CI, -28.3% to -20.7%) and lower OAT prevalence in patients with prevalent AF (bipolar disorder: -11.6%; 95% CI, -13.9% to -9.3% schizophrenia: -21.6%; 95% CI, -24.8% to -18.4%). Adjusting for socioeconomic factors and other comorbid conditions attenuated these associations, particularly for patients with bipolar disorder. However, schizophrenia continued to be associated with a with a lower rate of OAT initiation (-15.5%, 95% CI, -19.3% to -11.7%) and a -12.8% (95% CI, -15.9% to -9.7%) lower OAT prevalence. These associations were also present after the introduction of non-vitamin K antagonists (adjusted proportion difference in 2013-2016: -12.4%; 95% CI, -18.7% to -6.1% for initiation and -10.1%; 95% CI, -13.8% to -6.4% for prevalence).

Conclusions And Relevance: In this study, patients with bipolar disorder or schizophrenia were less likely to receive OAT in the setting of AF. For patients with bipolar disorder, this deficit was largely associated with socioeconomic factors and comorbidities, especially toward the end of the study period. For patients with schizophrenia, disparities in this stroke prevention therapy persistently exceeded what could be explained by other patient characteristics.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.10096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129823PMC
May 2021

Quality of care and risk of incident atrial fibrillation in patients with newly-diagnosed heart failure: A nationwide cohort study.

Eur Heart J Qual Care Clin Outcomes 2021 May 7. Epub 2021 May 7.

Danish Center for Clinical Health Services Research, Aalborg University, Aalborg, Denmark.

Aims: Incident atrial fibrillation (AF) is an adverse prognostic indicator in heart failure (HF); identifying modifiable targets may be relevant to reduce the incidence and morbidity of AF. Therefore, we examined the association between quality of HF care and risk of AF.

Methods And Results: Using the Danish Heart Failure Registry, we conducted a nationwide registry-based cohort study of all incident HF patients diagnosed between 2008 and 2018 and without history of AF. Quality of HF care was assessed by seven process performance measures, including echocardiographic examination, New York Heart Association classification, treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid antagonists, physical training, and patient education. In the main analysis, we examined adherence with all measures in a cohort of 25,100 patients (mean age 68.5 ± 13.2 years; 33.6% women). The median follow-up was 3.1 years. Cox proportional hazard regressions estimated the hazard ratios (HRs) with 95% confidence intervals (95% CIs) between the number of fulfilled measures and incident AF. In a multivariable-adjusted analysis with 0 fulfilled performance measures as reference, the HRs (95% CIs) were 1: 0.78 (0.61-1.00), 2: 0.63 (0.49-0.80), 3: 0.53 (0.36-0.80), 4: 0.64 (0.44-0.94), 5: 0.56 (0.39-0.82), 6: 0.51 (0.35-0.74), and 7: 0.49 (0.33-0.73), with a significant decreasing linear trend (p < 0.001).

Conclusion: In patients with incident HF, fulfillment of guideline-based process performance measures was associated with decreased long-term risk of AF. This study supports initiatives to improve the quality of care for patients with HF to prevent incident AF.
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http://dx.doi.org/10.1093/ehjqcco/qcab036DOI Listing
May 2021

Prognostic importance of left atrial size measured by non-contrast cardiac computed tomography - A DANCAVAS study.

Int J Cardiol 2021 04 30;328:220-226. Epub 2020 Dec 30.

Department of Cardiology, Odense University Hospital, Odense, Denmark; Odense University Hospital, Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense, Denmark.

Background: Enlargement of left atrium (LA) is a valuable marker of cardiovascular events, and LA size is readily available while performing non-contrast cardiac computed tomography (NCCT) for preventive purposes. We aimed to evaluate the predictive value of a single LA area from NCCT in a population-based cohort.

Method: Mainly men aged 60-75 years from DANCAVAS were included. Traditional risk factors were recorded, and an NCCT scan performed at baseline. Coronary artery calcifications (CAC) score and the largest LA area were measured. LA was indexed to body surface area and categorised into four groups. Data on incident atrial fibrillation (AF), thromboembolic events, heart failure (HF) and death were obtained from Danish national registries.

Results: In total, 14,557 individuals were eligible, excluding those without LA measurement (N = 232) and with heart valve replacement (N = 197). Known AF or HF were respectively excluded from follow-up. Median follow-up time was 2.1 to 3.4 years. In total, 304 developed AF, 149 had thromboembolism, 129 developed HF and 482 died. In adjusted analysis, LA enlargement was associated with AF (HR (95% CI): large 1.99 (1.46-2.71) and very large LA 3.77 (2.31-6.14)) and HF (large 2.40 (1.50-3.85) and very large LA 6.54 (4.07-10.51)). A very large LA significantly increased mortality (HR: 2.01 (1.44-2.82)), and was associated with a two-fold increased risk of thromboembolism; however, not significantly in adjusted analysis (p = 0.09).

Conclusion: We demonstrated that determination of LA area from NCCT was an important predictor of AF, HF and death. This knowledge could inform current risk assessment beyond CAC score.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.029DOI Listing
April 2021

The Cost-Effectiveness of One-Time Opportunistic Screening for Atrial Fibrillation in Different Age Cohorts of Inhabitants in Denmark Aged 65 Years and Above. A Markov Modelled Analysis.

Eur Heart J Qual Care Clin Outcomes 2020 Dec 18. Epub 2020 Dec 18.

Pfizer Denmark, Health & Value, Ballerup, Denmark.

Aim: The objective was to evaluate the cost-effectiveness of one-time opportunistic screening for AF in general practice in citizens aged ≥65 years in Denmark compared to a no-screening alternative following current Danish practice.

Methods And Results: A decision tree and a Markov model were designed to simulate costs and quality-adjusted life years (QALYs) in a hypothetical cohort of citizens aged ≥65 years equivalent to the Danish population (1 M citizens) over the course of 19 years, using a healthcare and societal perspective. Share of detected AF patients following opportunistic screening was retrieved from a recent Danish screening study, whereas the risk stroke and bleedings in AF patients were based on population data from national registries and their associated costs was obtained from published national registry studies.The present study showed that one-time opportunistic screening for AF was more costly, but also more effective compared to a no-screening alternative. The analysis predicts that one-time opportunistic screening of all Danes aged ≥65 years potentially can identify an additional 10,300 AF patients and prevent 856 strokes in the period considered. The incremental cost of such a screening program is €56.4 M, with a total gain of 6,000 QALYs, resulting in an incremental cost-effectiveness ratio of €9,400 per QALY gained.

Conclusion: Opportunistic screening in general practice in citizens aged ≥65 years in Denmark is cost-effective compared to a willingness-to-pay threshold of €22,000. The study and its findings support a potential implementation of opportunistic screening for AF at the general practitioner level in Denmark.
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http://dx.doi.org/10.1093/ehjqcco/qcaa092DOI Listing
December 2020

Death of a Partner and Risks of Ischemic Stroke and Intracerebral Hemorrhage: A Nationwide Danish Matched Cohort Study.

J Am Heart Assoc 2020 12 17;9(23):e018763. Epub 2020 Nov 17.

Diagnostic Centre University Research Clinic for Innovative Patient Pathways Silkeborg Regional Hospital Silkeborg Denmark.

Background Stress has been reported to trigger stroke, and the death of a loved one is a potentially extremely stressful experience. Yet, previous studies have yielded conflicting findings of whether bereavement is associated with stroke risk, possibly because of insufficient distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH). We therefore examined the associations between bereavement and IS and ICH separately in contemporary care settings using nationwide high-quality register resources. Methods and Results The study cohort included all Danish individuals whose partner died between 2002 and 2016 and a reference group of cohabiting individuals matched 1:2 on sex, age, and calendar time. Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and corresponding 95% CIs during up to 5 years follow-up. During the study period, 278 758 individuals experienced partner bereavement, of whom 7684 had an IS within the subsequent 5 years (aHR, 1.11; CI, 1.08-1.14 when compared with nonbereaved referents) and 1139 experienced an ICH (aHR, 1.13; CI, 1.04-1.23). For ICH, the estimated association tended to be stronger within the initial 30 days after partner death (aHR, 1.66; CI, 1.06-2.61), especially in women (aHR, 1.99; CI, 1.06-3.75), but the statistical precision was low. In absolute numbers, the cumulative incidence of IS at 30 days was 0.73 per 1000 in bereaved individuals versus 0.63 in their referents, and the corresponding figures for ICH were 0.13 versus 0.08. Conclusions Statistically significant positive associations with partner bereavement were documented for both IS and ICH risk, for ICH particularly in the short term. However, absolute risk differences were small.
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http://dx.doi.org/10.1161/JAHA.120.018763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763796PMC
December 2020

Individual, expected diameters of the ascending aorta and prevalence of dilations in a study-population aged 60-74 years: a DANCAVAS substudy.

Int J Cardiovasc Imaging 2021 Mar 26;37(3):971-980. Epub 2020 Oct 26.

Center of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark.

To determine individual, expected normal diameters of the ascending aorta (AAo) and prevalence of dilations based upon an absolute cut-off point (≥ 40 mm) and individual cut-off point (≥ 25% than expected normal). Non-contrast computed tomography (CT) scans were obtained in 14,993 individuals (95.0% male, mean age 67.8 ± 3.8). A sub-group (n = 291) had AAo diameter measured by transthoracic echocardiography. A prediction formula for AAo diameters was created from multivariate linear regression analysis based upon gender, age, and body surface area. An index was made by dividing observed diameters with predicted diameters. A size-index ≥ 1.25 was defined as dilated. Prevalence of AAo dilations among males and females using 40 mm as cut-off point were 10.6% and 2.1% (p < 0.001), respectively, while 3.3% and 2.6% (p = 0.305) using the size-index ≥ 1.25, respectively. Proportion of agreement between cases of AAo dilations from the size-index and 40 mm was 93.0%. Using the size-index as 'golden standard' for dilation, the sensitivity and specificity using 40 mm as cut-off point for males were 100.0% and 92.4%, respectively, while 75.0% and 99.9%, respectively, for females. For males and females, the positive predicted values were 31.3% and 93.8%, respectively; the negative predicted values were 100.0% and 99.3%, respectively. An absolute echocardiographic size-criterion of 40 mm entails a significant number of females with missed AAo dilation, and a large number of males are mistaken to have dilated AAo. Thus, AAo diameters should be evaluated in relation to gender, age and BSA. This study provides a formula for potential clinical implementation.
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http://dx.doi.org/10.1007/s10554-020-02081-3DOI Listing
March 2021

[Arrhythmia-inducedheartfailure].

Ugeskr Laeger 2020 09;182(40)

Tachycardia, atrial fibrillation and premature ventricular contractions can trigger a reversible cardiomyopathy, which can result in clinical heart failure. The diagnosis is retrospective and based on recovery of left ventricular ejection fraction following appropriate arrhythmia management. The arrhythmia can be fully or partly responsible for the reduced ejection fraction depending on coexisting structural heart disease. Early and aggressive treatment targeting the arrhythmia as described in this review, is important to prevent complications including persistent pathophysiological changes.
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September 2020

Trends in excess mortality associated with atrial fibrillation over 45 years (Framingham Heart Study): community based cohort study.

BMJ 2020 08 11;370:m2724. Epub 2020 Aug 11.

Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA 02118, USA

Objective: To assess temporal trends in the association between newly diagnosed atrial fibrillation and death.

Design: Community based cohort study.

Setting: Framingham Heart Study cohort, in 1972-85, 1986-2000, and 2001-15 (periods 1-3, respectively), in Framingham, MA, USA.

Participants: Participants with no atrial fibrillation, aged 45-95 in each time period, and identified with newly diagnosed atrial fibrillation (or atrial flutter) during each time period.

Main Outcome Measures: The main outcome was all cause mortality. Hazard ratios for the association between time varying atrial fibrillation and all cause mortality were calculated with adjustment for time varying confounding factors. The difference in restricted mean survival times, adjusted for confounders, between participants with atrial fibrillation and matched referents at 10 years after a diagnosis of atrial fibrillation was estimated. Meta-regression was used to test for linear trends in hazard ratios and restricted mean survival times over the different time periods.

Results: 5671 participants were selected in time period 1, 6177 in period 2, and 6174 in period 3. Adjusted hazard ratios for all cause mortality between participants with and without atrial fibrillation were 1.9 (95% confidence interval 1.7 to 2.2) in time period 1, 1.4 (1.3 to 1.6) in period 2, and 1.7 (1.5 to 2.0) in period 3 (P=0.70). Ten years after diagnosis of atrial fibrillation, the adjusted difference in restricted mean survival times between participants with atrial fibrillation and matched referents decreased by 31%, from -2.9 years (95% confidence interval -3.2 to -2.5) in period 1, to -2.1 years (-2.4 to -1.8) in period 2, to -2.0 years (-2.3 to -1.7) in period 3 (P=0.03).

Conclusions: No evidence of a temporal trend in hazard ratios for the association between atrial fibrillation and all cause mortality was found. The mean number of life years lost to atrial fibrillation at 10 years had improved significantly, but a two year gap compared with individuals without atrial fibrillation still remained.
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http://dx.doi.org/10.1136/bmj.m2724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418071PMC
August 2020

Thoracic Bone Mineral Density Derived from Cardiac CT Is Associated with Greater Fracture Rate.

Radiology 2020 09 14;296(3):499-508. Epub 2020 Jul 14.

From the Department of Cardiology, Hospital Unit West, Gl.landevej 61, Herning 7400, Denmark (J. Therkildsen, L.N., M.B., S.W.); Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven-University of Leuven, Belgium (H.S.J.); Department of Clinical Engineering, Aarhus University Hospital, Aarhus, Denmark (J. Thygesen); Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark (P.I.); Department of Cardiology, Regional Hospital of Silkeborg, Silkeborg, and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (L.F.); Department of Radiology, Regional Hospital of Silkeborg, Silkeborg, Denmark (C.I.); Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (B.L.L.); Department of Rheumatology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Denmark (E.M.H., H.S.J.); and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (S.W.).

Background Osteoporosis is a prevalent, under-diagnosed, and treatable disease associated with increased fracture risk. Bone mineral density (BMD) derived from cardiac CT may be used to determine fracture rate. Purpose To assess the association between fracture rate and thoracic BMD derived from cardiac CT. Materials and Methods This prospective cohort study included consecutive participants referred for cardiac CT for evaluation of ischemic heart disease between September 2014 and March 2016. End of follow-up was June 30, 2018. In all participants, volumetric BMD of three thoracic vertebrae was measured by using quantitative CT software. The primary and secondary outcomes were any incident fracture and any incident osteoporosis-related fracture registered in the National Patient Registry, respectively. Hazard ratios were assessed by using BMD categorized as very low (<80 mg/cm), low (80-120 mg/cm), or normal (>120 mg/cm). The study is registered at (identifier: NCT02264717). Results In total, 1487 participants (mean age, 57 years ± 9; age range, 40-80 years; 52.5% women) were included, of whom 179 (12.0%) had very low BMD. During follow-up (median follow-up, 3.1 years; interquartile range, 2.7-3.4 years; range, 0.2-3.8 years), 80 of 1487 (5.3%) participants were diagnosed with an incident fracture and in 31 of 80 participants, the fracture was osteoporosis related. In unadjusted Cox regressions analyses, very low BMD was association with a greater rate of any fracture (hazard ratio, 2.6; 95% confidence interval [CI]: 1.4, 4.7; = .002) and any osteoporosis-related fracture (hazard ratio, 8.1; 95% CI: 2.4, 26.7; = .001) compared with normal BMD. After adjusting for age and sex, very low BMD remained associated with any fracture (hazard ratio, 2.1; 95% CI: 1.1, 4.2) and any osteoporosis-related fracture (hazard ratio, 4.0; 95% CI: 1.1, 14.6). Conclusion Routine cardiac CT can be used to help measure thoracic bone mineral density (BMD) to identify individuals who have low BMD and a greater fracture rate. © RSNA, 2020 See also the editorial by Bredella in this issue.
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http://dx.doi.org/10.1148/radiol.2020192706DOI Listing
September 2020

Role for machine learning in sex-specific prediction of successful electrical cardioversion in atrial fibrillation?

Open Heart 2020 06;7(1)

Department of Cardiology, Viborg Regional Hospital, Viborg, Denmark.

Objective: Electrical cardioversion is frequently performed to restore sinus rhythm in patients with persistent atrial fibrillation (AF). However, AF recurs in many patients and identifying the patients who benefit from electrical cardioversion is difficult. The objective was to develop sex-specific prediction models for successful electrical cardioversion and assess the potential of machine learning methods in comparison with traditional logistic regression.

Methods: In a retrospective cohort study, we examined several candidate predictors, including comorbidities, biochemistry, echocardiographic data, and medication. The outcome was successful cardioversion, defined as normal sinus rhythm immediately after the electrical cardioversion and no documented recurrence of AF within 3 months after. We used random forest and logistic regression models for sex-specific prediction.

Results: The cohort comprised 332 female and 790 male patients with persistent AF who underwent electrical cardioversion. Cardioversion was successful in 44.9% of the women and 49.9% of the men. The prediction errors of the models were high for both women (41.0% for machine learning and 48.8% for logistic regression) and men (46.0% for machine learning and 44.8% for logistic regression). Discrimination was modest for both machine learning (0.59 for women and 0.56 for men) and logistic regression models (0.60 for women and 0.59 for men), although the models were well calibrated.

Conclusions: Sex-specific machine learning and logistic regression models showed modest predictive performance for successful electrical cardioversion. Identifying patients who will benefit from cardioversion remains challenging in clinical practice. The high recurrence rate calls for thoroughly informed shared decision-making for electrical cardioversion.
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http://dx.doi.org/10.1136/openhrt-2020-001297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307540PMC
June 2020

Randomised trial of telephone counselling to improve participants' adherence to prescribed drugs in a vascular screening trial.

Basic Clin Pharmacol Toxicol 2020 Dec 16;127(6):477-487. Epub 2020 Jul 16.

Department of Cardiology, Diagnostic Centre, Regional Hospital Central Jutland, Silkeborg, Denmark.

A total of 1446 participants, 65- to 74-year-old men diagnosed with abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD) or high blood pressure (HB) in the Viborg Vascular (VIVA) screening trial, were consecutively included and randomised to a telephone counselling (TC) or no TC 3 months after being screened positive. Data from VIVA were linked to data from Danish registers from 2007 to 2016. The primary outcome was a composite outcome of proportion of days covered by statin, antithrombotic drugs and antihypertensive agents and for each specific drug class at 6-month follow-up. The same outcomes were assessed at 12 and 60 months and considered secondary outcomes. Outcome measures are reported as risk differences (RD). There were no differences between the groups in relation to the composite of all three drug classes over 6 months of follow-up, RD = 4.1 (95% CI: -1.0; 9.1). A significant increase in redeemed statin prescriptions was observed in the intervention group at 6 months, RD = 9.8% (CI 95%: 0.5; 19.0). There was no intervention effect observed after 12 and 60 months. TC 3 months after screening improved adherence to statin at 6-month follow-up, but had no effect on the composite treatment, statins, antithrombotic or antihypertensive treatment over 60 months of follow-up.
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http://dx.doi.org/10.1111/bcpt.13459DOI Listing
December 2020

Association of aortic valve calcification and vitamin K antagonist treatment.

Eur Heart J Cardiovasc Imaging 2020 07;21(7):718-724

Department of Cardiology, Odense University Hospital, J. B. Winsløws Vej 4, 5000 Odense, Denmark.

Aims: Vitamin K antagonists (VKAs) are suspected of causing aortic valve calcification (AVC). The objective of this study was to clarify whether patients undergoing VKA treatment have increased AVC scores compared to patients treated with new oral anticoagulants (NOACs) and patients who never have been treated with VKA/NOAC.

Methods And Results: We included participants from the population-based DANCAVAS trial (n = 15 048). Information on confounders was collected, and the AVC scores were measured on non-contrast computed tomography scans. The participants' medication data, including VKA and NOAC data, were collected from the Danish National Health Service Prescription Database. The final population consisted of 14 604 participants (67.4 years, 95% men) of whom 873 had been treated with VKA and 602 with NOAC. The association between AVC score and duration of anticoagulant use was investigated in an adjusted zero-inflated negative binomial regression model. For every year treated with VKA, the AVC score increased, on average, by 6% [ratio of expected counts (RECs) = 1.06; 95% confidence interval (CI) 1.02-1.10] compared to non-use. The results were consistent in sensitivity analyses excluding patients with known cardiovascular disease and statin users (REC = 1.07; 95% CI 1.02-1.11 and REC = 1.10; 95% CI 1.03-1.17, respectively). NOAC treatment was not significantly associated with AVC score in any of the corresponding models (REC = 1.03, 1.02, and 0.96).

Conclusion: Compared to no treatment with anticoagulants, VKA use was associated with increased AVC score, while a similar association could not be established for NOAC.
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http://dx.doi.org/10.1093/ehjci/jeaa065DOI Listing
July 2020

Survival, Prevalence, Progression and Repair of Abdominal Aortic Aneurysms: Results from Three Randomised Controlled Screening Trials Over Three Decades.

Clin Epidemiol 2020 23;12:95-103. Epub 2020 Jan 23.

Department of Public Health and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Aim: The prevalence and mortality of abdominal aortic aneurysms (AAA) has been reported to decline. The aim of this study is to compare survival, prevalence, and repair rate of AAA in Denmark in the 1990s, the 2000s and the 2010s - and to examine any change in factors known to influence the prevalence.

Methods: Baseline status and up to 5-year outcomes of 34,079 general population men aged 65-74 were obtained from three RCTs; the Viborg study (1994-1998, n=4,860), the Viborg Vascular (VIVA) trial (2008-2011, n=18,748), and the Danish Cardiovascular (DANCAVAS) trial (2015-2018, n=10,471). After the millennium (VIVA and DANCAVAS) men with AAA were further offered low dose aspirin and statins. Follow-up data were not available for the DANCAVAS trial yet.

Results: Across the three decades, the AAA prevalence was 3.8% (Reference), 3.3% (p<0.001) and 4.2% (p=0.882), the proportion of smokers were 62%, 42% and 34% (p<0.001) amongst men with AAA, but AAA risk associations with smoking increased during the decades suggesting increased tobacco consumption of smokers. In addition, the proportions of attenders with ischemic heart disease or stroke increased significantly. The aneurysmal progression rate in the 1990s was 2.90 vs 2.98 mm/year in the 2000s (p=0.91). The need for preventive AAA repair increased insignificantly in the 2000s (Age adj. HR= 1.29, 95% C.I.: 0.95; 1.71, p=0.10), and mortality of men with screen-detected AAA was lower in the 2000s compared to the 1990s (Age-adj. HR= 0.28, 95% C.I.: 0.22; 0.36, p<0.001).

Conclusion: The Danish prevalence of AAA today compares to the nineties. Unchanged aneurysmal progression rates combined with improved survival of men at risk of AAA leave them in longer time to develop an AAA, be diagnosed and to need later aneurysmal repair or experience rupture.

Clinical Trial Registrations: Viborg study: No possibility of registration in the nineties. VIVA: NCT00662480, URL: https://clinicaltrials.gov/show/NCT00662480, DANCAVAS: ISRCTN12157806, URL: http://www.isrctn.com/ISRCTN12157806.
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http://dx.doi.org/10.2147/CLEP.S238502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986168PMC
January 2020

Effect of a Physiotherapist-Guided Home-Based Exercise Intervention on Physical Capacity and Patient-Reported Outcomes Among Patients With Acute Pulmonary Embolism: A Randomized Clinical Trial.

JAMA Netw Open 2020 02 5;3(2):e200064. Epub 2020 Feb 5.

Diagnostic Center, Department of Cardiology, Silkeborg Regional Hospital, Silkeborg, Denmark.

Importance: Survivors of acute pulmonary embolism (PE) experience long-term negative physical and mental consequences, but the effects of rehabilitation on outcomes among these patients have not been investigated.

Objective: To investigate the effect of a rehabilitation intervention, comprising an 8-week home-based exercise program and nurse consultations, on physical capacity and patient-reported outcomes among patients with acute PE.

Design, Setting, And Participants: This multicenter randomized clinical superiority trial was conducted at 4 regional hospitals and 1 university hospital in Denmark. The 140 consecutively included participants had been diagnosed with an acute PE between April 2016 and February 2018 and had 6 months of follow-up. An intention-to-treat analysis was conducted.

Intervention: Patients in the control group received a brief nurse consultation, while patients in the exercise group participated in an 8-week home-based exercise program in addition to receiving nurse consultations.

Main Outcomes And Measures: The primary outcome was the Incremental Shuttle Walk Test, and secondary outcomes were the Pulmonary Embolism Quality of Life and the EuroQol-5 Dimensions-3 Levels questionnaires, self-reported number of sick-leave days, and self-reported use of psychotropic drugs.

Results: A total of 140 patients (90 [64.3%] men) were included, with a mean (SD) age of 61 (11) years. Of 70 participants (50.0%) randomized to each group, 69 participants (49.3%) received the intervention and 68 (48.6%) received the control intervention. Both groups achieved improvements in all outcomes (eg, mean [SD] improvement on Incremental Shuttle Walk Test: control group, 78 (127) m; intervention group, 104 [106] m; median [interquartile range] improvement on Pulmonary Embolism Quality of Life: control group, -17 [-22 to -11] points; intervention group, -20 [-24 to -15] points). Between-group differences were nonsignificant. The mean differences between the intervention group and the control group were 25 m (95% CI, -20 to 70 m; P = .27) on the Incremental Shuttle Walk Test, 3.0 points (95% CI, -3.7 to 9.9 points; P = .39) on the Pulmonary Embolism Quality of Life questionnaire, and 0.017 point (95% CI, -0.032 to 0.065 point; P = .50) on the EuroQol-5 Dimensions-3 Levels questionnaire. Of the 27 patients in the intervention group on sick leave at baseline, 24 (88.9%) reported fit-for-duty at the 6-month follow-up, and of 18 patients in the control group on sick leave, 17 (94.4%) reported fit-for-duty at the 6-month follow up. The between-group risk difference was not significant (5.5 points; P = .49).

Conclusions And Relevance: An 8-week rehabilitation intervention with exercise added to nurse consultations did not show significantly better outcomes than nurse consultations alone. However, because of a ceiling effect on the primary outcome of physical capacity and an inclusion of patients with a low comorbidity burden and low PE disease severity, definitive conclusions could not be drawn. Initiating an exercise intervention shortly after pulmonary embolism was safe and without adverse events.

Trial Registration: ClinicalTrials.gov Identifier: NCT02684721.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.0064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049077PMC
February 2020

Twenty-year time trends in use of evidence-based heart failure drug therapy in Denmark.

Basic Clin Pharmacol Toxicol 2020 Jul 14;127(1):30-38. Epub 2020 Feb 14.

Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

European guidelines for heart failure (HF) have continuously incorporated new evidence since the first publication in 1995. We aimed to explore time trends in utilisation of pharmacological treatment for HF and dispensing of recommended dosages among patients with a first-time diagnosis of HF. We performed a historical cohort study of patients with a first-time HF diagnosis from 1997 to 2015, identified in the Danish National Patient Registry. Dispensed pharmacological treatment included angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor blockers (MRAs), digoxin and diuretics. Furthermore, we estimated the proportion of patients receiving the recommended target dosages 1 year after the diagnosis. The utilisation increased and correlated with publication of landmark studies, and among patients diagnosed in 2015, approximately two of three received ACEI/ARB and beta-blocker, respectively. Less than half of the patients redeeming prescriptions for ACEIs, ARBs, beta-blockers or MRAs received the recommended target dosages. The utilisation of pharmacological therapy for HF appears to be correlated with the publications of landmark Phase III clinical trials. However, a high proportion of patients do not receive the recommended target dosages. Despite improvements over time, a substantial gap appears to remain between guideline recommendations and pharmacological therapy in routine care.
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http://dx.doi.org/10.1111/bcpt.13392DOI Listing
July 2020

Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden.

J Am Heart Assoc 2020 02 25;9(3):e014795. Epub 2020 Jan 25.

Department of Biomedicine Aarhus University Aarhus Denmark.

Background Polygenic risk scores (PRSs) based on risk variants from genome-wide association studies predict coronary artery disease (CAD) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18-segment model and characterized by stenosis severity and composition (soft [0%-19% calcified], mixed-soft [20%-49% calcified], mixed-calcified [50%-79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS, coronary artery calcium score increased by 78% (=4.1e-26) and segment stenosis score increased by 16% (=2.4e-29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [OR: 1.78, =5.6e-16), calcified (OR: 1.69, =6.5e-17), mixed-calcified (OR: 1.67, =7.3e-9), mixed-soft (OR: 1.45, =1.6e-6), and soft plaques (OR: 1.49, =2.5e-6), and a higher prevalence of plaque in each coronary vessel (all <1.0e-4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all >0.05). Conclusions Our results suggest that polygenic risk based on large genome-wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.
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http://dx.doi.org/10.1161/JAHA.119.014795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033858PMC
February 2020

Depression and Uptake of Oral Anticoagulation Therapy in Patients With Atrial Fibrillation: A Danish Nationwide Cohort Study.

Med Care 2020 03;58(3):216-224

Research Unit for General Practice.

Background: Oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF) is a highly important preventive intervention, perhaps especially in those with comorbid depression, who have a worse prognosis. However, OAT may pose particular challenges in depressed patients.

Objectives: To assess whether AF patients with depression have lower OAT uptake.

Methods: This nationwide register-based 2005-2016 cohort study of all Danes with AF and OAT indication (CHA2DS2VASc stroke risk score ≥2) assessed OAT initiation within 90 days in those with incident AF (N=147,162) and OAT prevalence in those with prevalent AF (N=192,656). The associations of depression with both outcomes were estimated in regression analyses with successive adjustment for socioeconomic characteristics and somatic and psychiatric comorbidity.

Results: Comorbid depression was significantly associated with lower frequency of OAT initiation in incident AF patients {adjusted proportion differences (aPDs): -6.6% [95% confidence interval (CI), -7.4 to -5.9]} and lower prevalence of OAT [aPD: -4.2% (95% CI, -4.7 to -3.8)] in prevalent AF patients. Yet, the OAT uptake increased substantially during the period, particularly in depressed patients [aPD for OAT prevalence in 2016: -0.8% (95% CI, -1.6 to -0.0)].

Conclusions: Comorbid depression was associated with a significantly lower OAT uptake in patients with AF, which questions whether depressed patients receive sufficient support to manage this consequential cardiac condition. However, a substantial increase in the overall OAT uptake and a decrease of the depression-associated deficit in OAT were seen over the period during which OAT was developed through the introduction of new oral anticoagulation therapy.
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http://dx.doi.org/10.1097/MLR.0000000000001268DOI Listing
March 2020

Trends in preadmission oral anticoagulant use and clinical outcome in atrial fibrillation patients admitted with acute stroke in Denmark.

Eur Heart J Qual Care Clin Outcomes 2020 04;6(2):112-120

Department of Clinical Medicine, Danish Center for Clinical Heath Services Research, Aalborg University Hospital, Søndre Skovvej 15, 9000 Aalborg, Denmark.

Aims: Use of oral anticoagulation (OAC) therapy has increased in recent years among patients with atrial fibrillation (AF). However, it remains uncertain whether this translates into improved clinical outcomes. We aimed to examine time trends in preadmission OAC use and clinical outcomes among AF patients admitted with stroke.

Methods And Results: We used nationwide registries to perform a follow-up study of 14 999 patients with AF who were admitted with acute stroke to a Danish hospital between 2008 and 2016. The proportion of AF-related stroke was 16.1% in 2008 and 17.6% in 2016. Among patients with AF-related stroke, the overall proportion of preadmission OAC users increased from 22.6% in 2008 to 41.5% in 2016. Between 2008 and 2016, the proportion of patients with AF admitted with severe stroke declined from 32.4% to 27.4% [adjusted odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.75-0.81], the median length of hospital stay (LOS) decreased from 12 to 8 days (adjusted hazard ratio of discharge = 1.32, 95% CI: 1.30-1.34) and 30-day mortality decreased from 19.2% to 13.7% (adjusted OR = 0.72, 95% CI: 0.68-0.75).

Conclusion: The incidence of AF-related strokes remains high although preadmission use of OAC has increased substantially in recent years. Despite the proportion of OAC users almost doubled from 2008 to 2016, a sizeable proportion of AF patients is still without OAC when admitted with stroke. The increased use of OAC has been accompanied by a lower proportion of patients with severe stroke, shorter LOS, and lower mortality.
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http://dx.doi.org/10.1093/ehjqcco/qcz063DOI Listing
April 2020

Sex Differences in the Association Between Bone Mineral Density and Coronary Artery Disease in Patients Referred for Cardiac Computed Tomography.

J Clin Densitom 2021 Jan-Mar;24(1):55-66. Epub 2019 Sep 24.

Department of Cardiology, Hospital Unit West, Herning, Denmark.

Atherosclerosis and osteoporosis are both common and preventable diseases. Evidence supports a link between coronary artery disease (CAD) and low bone mineral density (BMD). This study aimed to assess the association between thoracic spine BMD and CAD in men and women with symptoms suggestive of CAD. This cross-sectional study included 1487 (mean age 57 years (range 40-80), 47% men) patients referred for cardiac computed tomography (CT). Agatston coronary artery calcium score (CACS), CAD severity (no, mild, moderate, and severe), vessel involvement (no, 1-, 2-, and 3/left main disease), and invasive measurements were evaluated. BMD of three thoracic vertebrae was measured using quantitative CT. We used the American college of radiology cut-off values for lumbar spine BMD to categorize patients into very low (<80 mg/cm), low (80-120 mg/cm), or normal BMD (>120 mg/cm). BMD as a continuous variable was included in the linear regression analyses to assess associations between CACS (CACS=0, CACS 1- 399, and CACS ≥ 400) and BMD, and CAD severity and BMD. Significant lower BMD was present with increasing CACS and stenosis degree unadjusted. Multivariate linear regression analyses in women revealed a significant correlation between BMD and CACS groups (β = -4.06, p<0.05), but no correlation between BMD and CAD severity (β = -1.59, p = 0.14). No association was found between BMD and CACS (β = -1.50, p = 0.36) and CAD severity (β = 0.07, p = 0.94) in men. BMD is significantly correlated to CACS after adjusting for confounders in women, but not in men, suggesting a possible sex difference in pathophysiology.
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http://dx.doi.org/10.1016/j.jocd.2019.09.003DOI Listing
October 2021

[Psychological, neurological and cell-mediated mechanisms by mindfulness-based therapy].

Ugeskr Laeger 2019 Jul;181(30)

In this review, we present clinical studies on mindfulness-based therapy (MBT) with a focus on mediating mechanisms for its health promoting effects. These constitute awareness, self-compassion, regulation of dysfunctional patterns of thoughts and emotions, neural network and cellular processes. Among cellular processes are inflammation, oxidative stress, mitochondrial dysfunction and telomere shortening, which all contribute to the molecular pathophysiology of several of today's lifestyle diseases. Finally, we address applications, where strong evidence exists for the clinical impact of MBT.
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July 2019

Comparison of Acute Versus Subacute Coronary Angiography in Patients With NON-ST-Elevation Myocardial Infarction (from the NONSTEMI Trial).

Am J Cardiol 2019 09 24;124(6):825-832. Epub 2019 Jun 24.

Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.

The optimal timing of coronary angiography (CAG) in high-risk patients with acute coronary syndrome without persisting ST-segment elevation (NST-ACS) remains undetermined. The NON-ST-Elevation Myocardial Infarction trial aimed to compare outcomes in NSTE-ACS patients randomized to acute CAG (STEMI-like approach) with patients randomized to medical therapy and subacute CAG. We randomized 496 patients with suspected NST-ACS based on symptoms and significant regional ST depressions and/or elevated point-of-care troponin T (POC-cTnT) (≥50 ng/l) to either acute CAG (<2 hours, n = 245) or subacute CAG (<72 hours, n = 251). The primary end point was a composite of all-cause death, reinfarction, and readmission with congestive heart failure within 1 year from randomization. A final acute coronary syndrome (ACS) diagnosis was assigned to 429 (86.5%) patients. The median time from randomization to revascularization was 1.3 hours in the acute CAG group versus 51.1 hours in the subacute CAG group (p <0.001). The composite end point occurred in 25 patients (10.2%) in the acute CAG group and 29 (11.6%) in the subacute CAG group, p = 0.62. The acute CAG group had a 1-year all-cause mortality of 5.7% compared with 5.6% in the subacute CAG group, p = 0.96. In conclusion, neither the composite end point of all-cause death, reinfarction, and readmission with congestive heart failure nor mortality differed between an acute and subacute CAG approach in NSTE-ACS patients. However, identification of NSTE-ACS patients in the prehospital phase and direct triage to an invasive center is feasible, safe and may facilitate early diagnosis and revascularization.
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http://dx.doi.org/10.1016/j.amjcard.2019.06.007DOI Listing
September 2019

Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): Study design for a controlled study of diagnostic accuracy.

Am Heart J 2019 09 1;215:114-128. Epub 2019 May 1.

Department of Cardiology, Hospital Unit West, Gl. Landevej 61, Herning, Denmark. Electronic address:

Background: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), rubidium positron emission tomography (Rb-PET), and CT-derived fractional flow reserve (FFR) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using Rb-PET as reference standard.

Methods: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI Rb-PET, FFR, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion.

Discussion: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.
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http://dx.doi.org/10.1016/j.ahj.2019.03.016DOI Listing
September 2019
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