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Background: Recent studies have shown that anticholinergic medications are associated with cardiovascular disease. Little is known about how discontinuation of anticholinergic medication affects this association. We investigated how baseline anticholinergic load and change in anticholinergic load associates with major adverse cardiovascular events (MACE) on four different scales., Methods: We included all geriatric outpatients aged 65 and older in Denmark between January 2011 and December 2018. Data were sourced from Danish national registries. Anticholinergic drug exposure was assessed at first contact to the outpatient clinic (baseline) and changes were assessed at 180 days after outpatient contact. Anticholinergic scales were the CRIDECO Anticholinergic Load Scale, Anticholinergic Drugs Scale, Anticholinergic Cognitive Burden and a scale by the Danish Institute of Rational Pharmacotherapy. Multivariate analyses were conducted to investigate the 1- and 5-year risk of MACE by baseline anticholinergic load and changes in anticholinergic load after 180 days., Results: We included a total of 64 378 patients in the analysis of baseline anticholinergic load and 54 010 patients remained after 180 days for inclusion in the analysis of change in anticholinergic load. At baseline the mean age was 81.7 year (SD 7.5) and 68% were women. Higher level of anticholinergic load on any scale associated with greater risk of MACE in a dose response pattern. There were no association between reduction in anticholinergic load and risk of MACE., Conclusion: While anticholinergic load at baseline was associated with MACE, reducing anticholinergic load did not lower the risk of MACE indicating the association may not be causal., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Coronary computed tomography angiography (CCTA) can guide downstream preventive treatment and improve patient prognosis, but its use in relation to education level remains unexplored., Methods: This nationwide register-based cohort study assessed all residents in Denmark between 2008 and 2018 without coronary artery disease (CAD) and 50-80 years of age (n = 1 469 724). Residents were divided according to four levels of education: low, lower-mid, higher-mid, and high. Outcomes were CCTA, functional testing, invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE)., Results: Individuals with the lowest education level underwent CCTA (absolute risk [AR] 3.95% individuals aged ≥50-59, AR 3.62% individuals aged ≥60-69, and AR 2.19% individuals aged ≥70-80) less often than individuals of lower-mid (AR 4.16%, AR 3.90%, and AR 2.41%), higher-mid (AR 4.38%, AR 4.30%, and AR 2.45%) and highest education level (AR 3.98%, AR 4.37%, and AR 2.30%). Similar differences were observed for functional testing. Conversely, use of ICA, and risks of revascularization and MACCE were more common among individuals of lowest education level. Among patients examined with CCTA (n = 50 234), patients of lowest education level less often underwent functional testing and more likely initiated preventive medication, underwent ICA, revascularization, and experienced MACCE., Conclusion: Despite tax-financed healthcare in Denmark, individuals of lowest education level were less likely to undergo CCTA and functional testing than persons of higher education level. Invasive coronary angiography utilization, revascularization, and MACCE risks were higher for individuals of lowest education level. Among CCTA-examined patients, patients of lowest education level were more likely to initiate preventive medication and had the highest risks of revascularization and MACCE when compared to higher education level groups. These findings suggest that the preventive potential of CCTA is underutilized in individuals of lower education level, a proxy for socioeconomic status. Socioeconomic differences in CAD assessment, care, and outcomes are likely even larger without tax-financed healthcare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: Patients with peripheral artery disease (PAD) represent a high-risk population with increased morbidity and mortality. We aimed to examine trends in myocardial infarction (MI), PAD and adverse clinical outcomes from years 2000 to 2019., Methods: This nationwide Danish-based registry study included all patients with MI from years 2000-2019. Patients with PAD were compared to patients without PAD. Temporal changes in PAD prevalence over time was examined using the Cochrane-Armitage trend test, and Cox regression was used to test for between-group significance in all care and outcome measures., Results: A total of 196,635 patients experienced an MI within the study time frame; the prevalence of PAD over time showed a slight increase (p < 0.01). Patients with MI and a concurrent PAD diagnosis elicited a heavier burden of comorbidities. The primary MACE endpoint showed significant decreases in both patients with and without PAD (p < 0.01); the decrease was more marked in patients without a concurrent PAD diagnosis (p < 0.01) alongside with 1-year all-cause mortality (p < 0.01). There was a slight increase in initiation of preventive pharmacotherapy with a prominent increase in initiation of P2Y12-inhibitors post discharge in patients without PAD in comparison to patients with PAD, and the same pattern applied for lipid lowering agents (p < 0.01). Also, there was an increase in revascularization in patients with MI but more markedly in patients without coexisting PAD., Conclusions: Despite significant decreases in MACE and mortality and significant increases in guideline-recommended care and revascularization over time for MI patients both with and without PAD, improvement in all these measures was less prominent in patients with MI and concomitant PAD., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF., Methods and Results: From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14-365 days from concomitant treatment were identified. To be included, a second measurement was required within 6-30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5-4.0 mmol/L (n = 709), 4.1-4.6 mmol/L (n = 1,204, reference), 4.7-5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49-3.70) and 3.5-4.0 mmol/L (HR: 1.81; 95% CI: 1.54-2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality., Conclusion: Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6-30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5-4.0 mmol/L)., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The long-term cardiovascular risk for patients examined with coronary computed tomography angiography (CCTA) to rule out coronary heart disease compared with population controls remains unexplored. A nationwide register-based study including first-time CCTA-examined patients between 2007 and 2017 in Denmark alive 180 days post-CCTA was conducted. We evaluated 5-year outcomes of myocardial infarction (MI) or revascularization and all-cause mortality in 3 distinct CCTA-groups: (1) no post-CCTA preventive pharmacotherapy use (cholesterol-lowering drugs, antiplatelets, or anticoagulants); (2) post-CCTA preventive pharmacotherapy use; and (3) revascularization or MI within 180 days post-CCTA. For each patient group, population controls were matched on age, gender, and calendar year. Absolute risks standardized to the age, gender, selected co-morbidity, and anti-anginal pharmacotherapy distributions of the specific CCTA-examined patients and respective controls were obtained from multivariable Cox regression. Of 110,599 CCTA-examined patients, (1) 48,231 patients were not prescribed preventive pharmacotherapy 180 days post-CCTA; (2) 42,798 patients were prescribed preventive pharmacotherapy within 180 days post-CCTA; and (3) 19,570 patients were diagnosed with MI or revascularized within 180 days post-CCTA. For patient groups 1 to 3 versus respective controls, 5-year MI or revascularization risks were <0.1% versus 2.0%, <0.1% versus 3.8%, and 19.0% versus 2.5%, all p<0.001. Five-year all-cause mortality were 2.8% versus 4.2%, 5.5% versus 8.8%, and 6.7% versus 8.5%, all p <0.001. In conclusion, the 5-year MI or revascularization risk can be considered very low for CCTA-examined patients without ischemic events within 180 days post-CCTA. Conversely, CCTA-examined patients with MI or revascularization events within 180 days post-CCTA have significantly elevated 5-year MI or revascularization risk., Competing Interests: Disclosures K. Kragholm: Speaker's honoraria from Novartis. P. Sogaard: Speaker for GE Healthcare, advisory board member (Novartis Pharmaceuticals Corp., Astra Zeneca Pharmaceuticals, Biotronik), research grants Wics, Bayer, and GE Healthcare. T. Zaremba: speaker's fee from AstraZeneca. C. Byrne: Speaker's honoraria from Bayer. L. Kober: Speakers honorarium from Novo, Novartis AstraZeneca and Boehringer. These disclosures are unrelated to the topic of the current manuscript and have not influenced the design and conduct of the study, nor in the collection, analysis, and interpretation of the data, and finally, not in the preparation, review, or submission of the manuscript. All other authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Chemoradiotherapy (CRT) may induce myocardial dysfunction, congestive heart failure, and impaired physical performance in patients with esophageal cancer (EC). We aimed to investigate left ventricular (LV) function at rest and during stress, using echocardiography (echo) and a cardiopulmonary exercise (CPX) test both before and immediately after completing CRT., Material and Methods: Consecutive EC patients referred for curative treatment were enrolled. Patients attended either definitive CRT or neoadjuvant CRT with subsequent surgery. The evaluation included cardiac biomarkers, electrocardiogram, echo, and CPX test. The primary endpoint was changes in left ventricular (LV) global longitudinal strain (GLS) at rest. Secondary endpoints were LV ejection fraction (LVEF), LV diastolic function, LVEF and GLS at peak exercise, and maximal oxygen consumption (VO 2max) . The trial was registered with ClinicalTrials.gov (NCT03619317)., Results: Among 47 patients enrolled (94% male; median age 67 years, range 50-86 years), cardiac examinations were performed a median of three days [Interquartile range (IQR (1-5))] before CRT and one day [IQR (0-6)] after CRT. At rest, GLS and LVEF decreased, 17.6 vs. 16.4% and 56.4 vs. 55.1%, respectively ( p  = 0.004; p  = 0.030). Furthermore, an absolute decrease of at least 5% in LVEF and 2.5% in GLS was noted in 21% of the patients. Signs of LV diastolic dysfunction increased from 13 to 21% ( p = ns). VO 2max significantly decreased; 21.2 ml/kg/min vs. 18.8 ml/kg/min ( p  < 0.001)., Conclusion: LV function and physical performance decreased in EC patients after CRT, and the LV systolic reserve capacity declined. This study highlighted that EC treatment was associated with early cardiac side effects, which may have clinical and prognostic implications.

Importance: Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps., Objective: To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI)., Design, Setting, and Participants: In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021., Exposures: APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery)., Main Outcomes and Measures: All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods., Results: Of 10 292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF., Conclusions and Relevance: In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.

Aim: Left bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data., Methods and Results: Using ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p < 0.001). There was no association between the PR interval and HF after adjustment., Conclusion: Prolonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF., Competing Interests: Competing interests: KHK reports to have received speaker’s honoraria from Novartis and research grant from the Laerdal Foundation. SMH has received support from the Danish Heart Foundation, The Danish Foundation Trygfonden and AstraZeneca. PS reports having received research grants from GE Health Care and BIOTRONIK. CP reports receiving speaking fees from H Lundbeck., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Atherosclerotic cardiovascular disease (ASCVD) may have unique risk factors in women. Most women have a history of pregnancy; common adverse pregnancy outcomes (APOs) appear to be associated with ASCVD, but prior studies have limitations., Objective: To assess whether APOs are associated with increased ASCVD risk independently of traditional risk factors., Design, Setting, and Participants: The APO history among participants in the Women's Health Initiative, a large multiethnic cohort of postmenopausal women, was assessed. The associations of 5 self-reported APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight [ie, birth weight less than 2.49 kg], high birth weight [ie, birth weight greater than 4.08 kg], and preterm delivery by 3 weeks or more) with ASCVD were analyzed, adjusting for traditional ASCVD risk factors. Data were collected and analyzed in 2017., Exposures: APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight, high birth weight, and preterm delivery)., Main Outcomes and Measures: Adjudicated ASCVD., Results: A total of 48 113 Women's Health Initiative participants responded to the survey; the median (interquartile range) age at time of enrollment was 60.0 (55.0-64.0) years. A total of 13 482 participants (28.8%) reported 1 or more APOs. Atherosclerotic cardiovascular disease was more frequent in women who reported an APO compared with those without APOs (1028 of 13 482 [7.6%] vs 1758 of 30 522 [5.8%]). Each APO, analyzed separately, was significantly associated with ASCVD, and gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and preterm delivery remained significant after adjustment for traditional ASCVD risk factors. When all APOs were analyzed together, hypertensive disorders of pregnancy (odds ratio, 1.27; 95% CI, 1.15-1.40) and low birth weight (odds ratio, 1.12; 95% CI, 1.00-1.26) remained independently associated with ASCVD. All findings were materially unchanged by additional adjustment for parity, body mass index, and socioeconomic factors., Conclusions and Relevance: In this large multiethnic cohort of women, hypertensive disorders of pregnancy and low birth weight were independently associated with ASCVD after adjustment for risk factors and other APOs.

Background: Out-of-hospital cardiac arrest (OHCA) is often the first manifestation of unrecognised cardiac disease. ECG abnormalities encountered in primary care settings may be warning signs of OHCA., Objective: We examined the association between common ECG abnormalities and OHCA in a primary care setting., Methods: We cross-linked individuals who had an ECG recording between 2001 and 2011 in a primary care setting with the Danish Cardiac Arrest Registry and identified OHCAs of presumed cardiac cause., Results: A total of 326 227 individuals were included and 2667 (0,8%) suffered an OHCA. In Cox regression analyses, adjusted for age and sex, the following ECG findings were strongly associated with OHCA: ST-depression without concomitant atrial fibrillation (HR 2.79; 95% CI 2.45 to 3.18), left bundle branch block (LBBB; HR 3.44; 95% CI 2.85 to 4.14) and non-specific intraventricular block (NSIB; HR 3.15; 95% CI 2.58 to 3.83). Also associated with OHCA were atrial fibrillation (HR 1.89; 95% CI 1.63 to 2.18), Q-wave (HR 1.75; 95% CI 1.57 to 1.95), Cornell and Sokolow-Lyon criteria for left ventricular hypertrophy (HR 1.56; 95% CI 1.33 to 1.82 and HR 1.27; 95% CI 1.12 to 1.45, respectively), ST-elevation (HR 1.40; 95% CI 1.09 to 1.54) and right bundle branch block (HR 1.29; 95% CI 1.09 to 1.54). The association between ST-depression and OHCA diminished with concomitant atrial fibrillation (HR 1.79; 95% CI 1.42 to 2.24, p < 0.01 for interaction). Among patients suffering from OHCA, without a known cardiac disease at the time of the cardiac arrest, 14.2 % had LBBB, NSIB or ST-depression., Conclusions: Several common ECG findings obtained from a primary care setting are associated with OHCA., Competing Interests: Competing interests: SMH is supported by an unrestricted grant from The Danish foundation TrygFonden and the Danish Heart Foundation. KK reports having received grants from the Danish Heart Foundation, The Fund of Herta Christensen and the Laerdal Foundation. FKL reports having an unrestricted research grants from The Danish foundation TrygFonden and the Laerdal Foundation. CT-P reported serving as a consultant for Cardiome, Merck, Sanofi, Daiichi, and Bristol-Myers Squibb and receiving grants or grants pending from Bristol-Myers Squibb. Dr Holst is an employee of Novo Nordisk. JHS reported serving as a consultant for Medtronic, receiving speaker fee from Medtronic, JHS also reported receiving research grants from Medtronic and Gilead. LK reports personal fees from Novartis and Sanofi.

BACKGROUND Leptospirosis is a zoonosis transmitted through urine of infected animals. Symptoms range from mild influenza-like symptoms to severe pulmonary hemorrhagic syndrome (SPHS); the latter are often fatal. The serogroup distribution in Denmark has changed from 1988 to 2012, with Icterohaemorrhagiae and Sejroe now being predominant. CASE REPORT A 45-year-old Danish woman living in an area endemic for Hanta virus, without prior medical history, was admitted because of lower back pain radiating to the left hip, fever, headache, nausea, and malaise. Two weeks before admission she had been bitten by a mouse or a rat. Blood tests revealed raised white cells and CRP, electrolyte imbalances, raised creatinine, low thrombocytes, and a slightly decreased clotting factor (II, VII, and X). Treatment with broad-spectrum intravenous antibiotics and supporting therapy was initiated very quickly. Eight hours after admission she died from respiratory failure where severe hemoptysis was observed. Leptospiral DNA was later detected in a urine sample. CONCLUSIONS This case represents leptospirosis with severe pulmonary hemorrhagic syndrome. In spite of immediate treatment with broad-spectrum antibiotics, the patient died a few hours after hospital admission., Competing Interests: Conflicts of Interest: None declared