Age-specific mortality trends in heart failure over 25 years: a retrospective Danish nationwide cohort study.

BACKGROUND: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups. METHODS: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years). FINDINGS: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8]). INTERPRETATION: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Synchronous Low-Grade Central Osteosarcoma and Ewing Sarcoma: A Rare Case Report.

A 23-year-old female patient presented with radicular back pain, perineal numbness, and urinary retention. The patient was diagnosed with cauda equina syndrome and magnetic resonance imaging (MRI) of the spine revealed an enhancing osseous lumbar lesion causing severe central stenosis. A core needle biopsy of the lumbar spine showed microscopic features compatible with a small round blue cell tumor. CD99 and FLI1 were positive in the tumor cells. Next-generation sequencing demonstrated a EWSR1::FLI1 fusion. Given these findings, the spine lesion was diagnosed as Ewing sarcoma. The patient underwent surgical decompression of L2. On further workup, an MRI revealed an ill-defined enhancing mass of the right distal femur. This area was biopsied, demonstrating a fibro-osseous lesion with osteoblast proliferation containing nuclear atypia, low mitotic activity, and SATB2 positivity, diagnosed as low-grade central osteosarcoma (LGCOS). The patient underwent resection, which showed a classic LGCOS by histomorphology. Although fluorescence in-situ hybridization study for MDM2 gene amplification was negative, the overall findings are most consistent with LGCOS. These neoplasms are considered to be synchronous due to the presentation of each entity within 6 months. Considering the aggregate yearly incidence of Ewing sarcoma (approximately 1 case per 750 000 per year) and LGCOS (approximately 1 case per 10 million per year), the aggregate yearly probability of developing both of these genetically unrelated tumors in a single individual is 1 per 7.5 trillion per year, and it is likely such an event has never happened in the past.

Sinonasal Oxalosis due to Fungal Rhinosinusitis: A Unique Case of a Destructive Pseudotumor.

Oxalosis refers to the accumulation of calcium oxalate crystals in various organs and tissues, most commonly due to Aspergillus infection involving the lung or sinonasal tract. Both invasive and noninvasive forms of fungal rhinosinusitis can be associated with calcium oxalate crystal deposition. Here, we report a unique case of sinonasal oxalosis presenting as a destructive lesion in the absence of invasive fungal disease. Due to the clinical and pathologic significance of calcium oxalate crystals as seen in this patient, specimens from the sinonasal tract should be evaluated for the presence of these crystals, which may be a surrogate marker for fungal infection and may also independently cause tissue destruction.

High-risk admission prior to transcatheter aortic valve replacement and subsequent outcomes.

BACKGROUND: Severe, symptomatic aortic stenosis may cause heart failure, acute myocardial infarction, or syncope; limited data exist on the occurrence of such events before transcatheter aortic valve replacement (TAVR) and their impact on subsequent outcomes. Thus, we investigated the association between a preceding event and outcomes after TAVR. METHODS: From 2014 to 2021 all Danish patients who underwent TAVR were included. Preceding events up to 180 days before TAVR were identified. A preceding event was defined as a hospitalization for heart failure, acute myocardial infarction, or syncope. The 1-year risk of all-cause death, and cardiovascular or all-cause hospitalization was compared for patients with versus without a preceding event using Kaplan-Meier, Aalen-Johansen, and in Cox regression analyses adjusted for patient characteristics. RESULTS: Of 5,851 patients included, 759 (13.0%) had a preceding event. The median age was 81 years in both groups. Male sex and frailty were more prevalent in patients with a preceding event (males: 64.7% vs 55.2%, frailty: 49.6% vs 40.6%). The most common type of preceding event was a hospitalization for heart failure (n = 524). For patients with a preceding event, the 1-year risk of death was 11.7% (95% CI: 9.4%-14.1%) versus 8.0% (95% CI: 7.2%-8.7%) for patients without. The corresponding adjusted hazard ratio (aHR) was 1.29 (95%CI: 1.01-1.64). Mortality was highest for patients with a preceding event of a heart failure admission (1-year risk: 13.5% [95%CI: 10.5%-16.5%]). Comparing patients with a preceding event to those without, the 1-year risk for cardiovascular rehospitalization was 15.0% versus 8.2% (aHR 1.60 [95%CI: 1.29-1.99]) and 57.6% versus 50.6% for all-cause rehospitalization (aHR 1.08 [95%CI: 0.87-1.20]). CONCLUSIONS: A hospitalization for heart failure, myocardial infarction, or syncope prior to TAVR was associated with a poorer prognosis and could represent a group to focus resource management on. Interventions to prevent preceding events and improvements in pre- and post-TAVR optimization of these patients are warranted.

Hospital and emergency department discharge against medical advice in Western Australian Aboriginal children aged 0-4 years from 2002 to 2018: A cohort study.

BACKGROUND: Discharge against medical advice (DAMA) is a priority issue for the health system. Little is known about the factors associated with DAMA for Aboriginal and/or Torres Strait Islander (Aboriginal) children in Australia. OBJECTIVES: Investigate the associations between DAMA for hospital admissions and emergency department (ED) presentations and: (i) child, family and episode of service characteristics and (ii) 30-day readmission/ re-presentation. METHODS: We conducted a cohort study of Aboriginal children born in Western Australia (2002-2013) who had ≥1 hospital admissions (n = 16,931) or ED presentations (n = 26,546) within the first 5 years of life. The outcome of interest was hospital and ED DAMA and adjusted odds ratio were derived using multilevel mixed-effects logistic regression. RESULTS: In the Hospital Cohort, there were 43,149 hospitalisations for 16,931 children, with 684 hospitalisations (1.6%) recorded as DAMA. In the ED Cohort, there were 232,082 ED presentations in 26,546 children, with 10,918 ED presentations (4.7%) recorded as DAMA. DAMA occurring in hospitals between 2014 and 2018, the adjusted odds decreased by 75% compared to the period between 2002 and 2005. The adjusted odds of ED DAMA increased by 46% over the same period. Hospital admissions in regional and remote hospitals were almost seven times the adjusted odds of DAMA compared with hospital admissions in Perth metropolitan hospitals. The adjusted odds of ED DAMA decreased by 12% for ED presentations in regional and remote hospitals compared to those in Perth metropolitan hospitals. There was no evidence of hospital DAMA being associated with hospital readmission within 30 days and limited evidence of ED DAMA being associated with re-presenting to an ED within 30 days. CONCLUSIONS: The study identified several important determinants of DAMA, including admission status, triage status, location and calendar year. These findings could inform targeted measures to decrease DAMA, particularly in regional and remote communities.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

Temporal Trends in Noncardiovascular Morbidity and Mortality Following Acute Myocardial Infarction.

BACKGROUND: Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions. OBJECTIVES: This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI. METHODS: We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease. RESULTS: From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34]). CONCLUSIONS: Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials.

High risk of rehospitalization within one year following a pulmonary embolism-Insights from the Danish nationwide registries from 2000-2020.

AIM: To identify the absolute risk, causes and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE). METHODS AND RESULTS: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences, were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease (1-year AR: 9.5% (95% CI: 9.3%-9.8%)), followed by cardiovascular disease (1-year AR: 6.3% (95% CI: 5.9%-6.5%)), cancer (1-year AR: 6.0% (95% CI: 5.8%-6.4%)), venous thromboembolism (1-year AR: 5.2% (95% CI: 5.0%-5.2%)), and symptom diagnoses (1-year AR: 5.2% (95%CI: 5.0%-5.4%)). Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization. CONCLUSION: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization.

Risk of Worsening Heart Failure and All-Cause Mortality Following COVID-19 Vaccination in Patients With Heart Failure: A Nationwide Real-World Safety Study.

BACKGROUND: Patients with heart failure are vulnerable to the SARS-CoV-2 infection. However, limited evidence exists on the safety of the SARS-CoV-2 mRNA vaccines in this patient population. The objective of this study was to investigate the risk of all-cause mortality, worsening heart failure, venous thromboembolism, and myocarditis associated with the mRNA vaccines in patients with heart failure. METHODS: Using Danish nationwide registries, 2 cohorts were constructed: (1) all prevalent heart failure patients in 2019 aged 40 to 95 years and (2) all prevalent heart failure patients in 2021 aged 40 to 95 years, who were vaccinated with either of the 2 mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the 2 cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure. To estimate standardized absolute risks, outcome-specific Cox regression analyses were performed. RESULTS: The total study population comprised 101 786 patients. The median age of the study population was 74 years (interquartile range, 66-81). The standardized risk of all-cause mortality within 90 days was 2.23% (95% CI, 2.10%-2.36%) in the vaccinated cohort and 2.56% (95% CI, 2.43%-2.70%) in the unvaccinated cohort (90-day risk difference, -0.33% [95% CI, -0.52% to -0.15%]). The standardized risk of worsening heart failure within 90 days was 1.10% (95% CI, -1.01% to 1.19%) in the 2021 (vaccinated) cohort and 1.08% (95% CI, 0.99%-1.17%) in the 2019 (unvaccinated) cohort (risk difference, 0.02% [95% CI, -0.11% to 0.15%]). No significant differences were found regarding venous thromboembolism or myocarditis. CONCLUSIONS: Receiving an mRNA vaccine was not associated with an increased risk of worsening heart failure, myocarditis, venous thromboembolism, or all-cause mortality.

Frailty, Treatments, and Outcomes in Older Patients With Myocardial Infarction: A Nationwide Registry-Based Study.

Background Guidelines recommend that patients with myocardial infarction (MI) receive equal care regardless of age. However, withholding treatment may be justified in elderly and frail patients. This study aimed to investigate trends in treatments and outcomes of older patients with MI according to frailty. Methods and Results All patients aged ≥75 years with first-time MI during 2002 to 2021 were identified through Danish nationwide registries. Frailty was categorized using the Hospital Frailty Risk Score. One-year risk and hazard ratios (HRs) for days 0 to 28 and 29 to 365 were calculated for all-cause death. A total of 51 022 patients with MI were included (median, 82 years; 50.2% women). Intermediate/high frailty increased from 26.7% in 2002 to 2006 to 37.1% in 2017 to 2021. Use of treatment increased substantially regardless of frailty: for example, 28.1% to 48.0% (statins), 21.8% to 33.7% (dual antiplatelet therapy), and 7.6% to 28.0% (percutaneous coronary intervention) for high frailty (all P-trend <0.001). One-year death decreased for low frailty (35.1%-17.9%), intermediate frailty (49.8%-31.0%), and high frailty (62.8%-45.6%), all P-trend <0.001. Age- and sex-adjusted 29- to 365-day HRs (2017-2021 versus 2002-2006) were 0.53 (0.48-0.59), 0.62 (0.55-0.70), and 0.62 (0.46-0.83) for low, intermediate, and high frailty, respectively (P-interaction=0.23). When additionally adjusted for treatment, HRs attenuated to 0.74 (0.67-0.83), 0.83 (0.74-0.94), and 0.78 (0.58-1.05), respectively, indicating that increased use of treatment may account partially for the observed improvements. Conclusions Use of guideline-based treatments and outcomes improved concomitantly in older patients with MI, irrespective of frailty. These results indicate that guideline-based management of MI may be reasonable in the elderly and frail.

Outcomes of out-of-hospital cardiac arrest in adult congenital heart disease: a Danish nationwide study.

AIMS: The risk, characteristics, and outcome of out-of-hospital cardiac arrest (OHCA) in patients with congenital heart disease (CHD) remain scarcely investigated. METHODS AND RESULTS: An epidemiological registry-based study was conducted. Using time-dependent Cox regression models fitted with a nested case-control design, hazard ratios (HRs) with 95% confidence intervals of OHCA of presumed cardiac cause (2001-19) associated with simple, moderate, and severe CHD were calculated. Moreover, using multiple logistic regression, we investigated the association between pre-hospital OHCA characteristics and 30-day survival and compared 30-day survival in OHCA patients with and without CHD. Overall, 43 967 cases (105 with simple, 144 with moderate, and 53 with severe CHD) and 219 772 controls (median age 72 years, 68.2% male) were identified. Any type of CHD was found to be associated with higher rates of OHCA compared with the background population [simple CHD: HR 1.37 (1.08-1.70); moderate CHD: HR 1.64 (1.36-1.99); and severe CHD: HR 4.36 (3.01-6.30)]. Pre-hospital cardiopulmonary resuscitation and defibrillation were both associated with improved 30-day survival in patients with CHD, regardless of CHD severity. Among patients with OHCA, simple, moderate, and severe CHD had a similar likelihood of 30-day survival compared with no CHD [odds ratio 0.95 (0.53-1.69), 0.70 (0.43-1.14), and 0.68 (0.33-1.57), respectively]. CONCLUSION: A higher risk of OHCA was found throughout the spectrum of CHD. Patients with and without CHD showed the same 30-day survival, which relies on the pre-hospital chain of survival, namely cardiopulmonary resuscitation and defibrillation.

Frailty and Recurrent Hospitalization After Transcatheter Aortic Valve Replacement.

Background For frail patients with limited life expectancy, time in hospital following transcatheter aortic valve replacement is an important measure of quality of life; however, data remain scarce. Thus, we aimed to investigate frailty and its relation to time in hospital during the first year after transcatheter aortic valve replacement. Methods and Results From 2008 to 2020, all Danish patients who underwent transcatheter aortic valve replacement and were alive at discharge were included. Using the validated Hospital Frailty Risk Score, patients were categorized in the low, intermediate, and high frailty groups. Time in hospital and mortality up to 1 year are reported according to frailty groups. In total, 3437 (57.6%), 2277 (38.1%), and 257 (4.3%) were categorized in the low, intermediate, and high frailty groups, respectively. Median age was ≈81 years. Female sex and comorbidity burden were incrementally higher across frailty groups (low frailty: heart failure, 24.1%; stroke, 7.2%; and chronic kidney disease, 4.5%; versus high frailty: heart failure, 42.8%; stroke, 34.2%; and chronic kidney disease, 29.2%). In the low frailty group, 50.5% survived 1 year without a hospital admission, 10.8% were hospitalized >15 days, and 5.8% of patients died. By contrast, 26.1% of patients in the high frailty group survived 1 year without a hospital admission, 26.4% were hospitalized >15 days, and 15.6% died within 1 year. Differences persisted in models adjusted for sex, age, frailty, and comorbidity burden (excluding overlapping comorbidities). Conclusions Among patients undergoing transcatheter aortic valve replacement, frailty is strongly associated with time in hospital and mortality. Prevention strategies for frail patients to reduce hospitalization burden could be beneficial.

Porocarcinoma with YAP1-NUTM1 fusion presenting as a NUT immunohistochemistry-positive lymph node metastasis.

INTRODUCTION: Porocarcinoma is a rare, malignant adnexal tumor that recently has been shown to contain YAP1-NUTM1 and YAP1-MAML2 fusion transcripts, with nuclear protein in testis (NUT) immunohistochemistry (IHC) positivity in a subset of these tumors. Consequently, NUT IHC may either aid in the differential diagnosis, or represent a confounding factor depending on the clinical scenario. Here, we present a case of NUTM1-rearranged sarcomatoid porocarcinoma of the scalp presenting as a NUT IHC-positive lymph node metastasis. CASE REPORT: A mass was excised from the right neck level 2 region with a lymph node initially diagnosed as metastatic NUT carcinoma with unknown primary site. An enlarging scalp mass was identified 4 months later, excised and diagnosed as NUT-positive carcinoma. Additional molecular testing was performed to detect the fusion partner in the NUTM1 rearrangement, confirming a YAP1-NUTM1 fusion. Given this molecular data along with the histopathologic characteristics, the clinicopathologic picture was retrospectively determined to be most consistent with a primary sarcomatoid porocarcinoma of the scalp with metastasis to a right neck lymph node and the right parotid. DISCUSSION: Porocarcinoma is a rare entity, and typically only enters the differential diagnosis when the clinical consideration is a cutaneous neoplasm. In an alternative clinical scenario such as the approach to tumors of the head and neck, porocarcinoma is not typically a consideration. In the latter scenario, as seen in our case, positivity with NUT IHC led to the initial misdiagnosis of NUT carcinoma. This case represents an important presentation of porocarcinoma that will occur not infrequently, and pathologists must be aware of this presentation to avoid this pitfall.

Nucleated Red Blood Cell Emergence-Time in Newborn Lambs Following a Dose of Darbepoetin Alfa.

BACKGROUND: Nucleated red blood cells (NRBC) are very uncommon in the blood of children and adults, but small numbers are not rare in neonates on the day of birth. Elevated NRBC counts in neonates can be seen following erythropoietin dosing. Limited studies in human neonates suggest the time-interval between erythropoietin dosing and the first appearance of NRBC in the blood (the "NRBC emergence-time") is in excess of 24 hours. METHODS: We made serial blood counts (Sysmex veterinary analyzer) on ten newborn lambs; five were dosed with darbepoetin (10 µg/kg), and five were dosed with a vehicle-control to assess the NRBC emergence time under relatively controlled laboratory conditions. RESULTS: The first appearance of NRBC was at 24 h (2757 ± 3210 NRBC/µL vs. 0/µL in controls). Peak was 48-72 h (16,758 ± 8434/µL vs. 0/µL in controls), followed by fewer at 96 hours (7823 ± 7114/µL vs. 0/µL in controls). Similarly, reticulocytes peaked at 48-72 h (113,094 ± 3210/µL vs. 10,790 ± 5449/µL in controls), with no changes in platelets or leukocytes. CONCLUSION: The NRBC emergence time in newborn lambs is similar to reports from newborn humans. By extrapolation, if a neonate has a high NRBC at birth, the erythropoietic stimulus likely occurred within the interval 24 to perhaps 96+ hours prior to birth.

Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

AIMS: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls. METHODS AND RESULTS: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD. CONCLUSION: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.

Long-term mortality, cardiovascular events, and bleeding in stable patients 1 year after myocardial infarction: a Danish nationwide study.

AIMS: Outcomes after myocardial infarction (MI) improved during recent decades alongside better risk factor management and implementation of guideline-recommended treatments. However, it is unknown whether this applies to stable patients who are event-free 1 year after MI. METHODS AND RESULTS: Using nationwide Danish registries, we included all patients with first-time MI during 2000-17 who survived 1 year free from bleeding and cardiovascular events (n = 82 108, median age 64 years, 68.2% male). Follow-up started 1 year after MI and continued through January 2022. Crude risks of mortality, cardiovascular events, and bleeding were estimated in consecutive 3-year periods. Standardized risks were calculated with respect to the distribution of age, sex, comorbidities, and treatments in the latter period. Guideline-recommended treatment use increased during the study period: e.g. statins (68.6-92.5%) and percutaneous coronary intervention (23.9-68.2%). The crude 5-year risks of outcomes decreased (all P-trend <0.001): Mortality, 18.6% (95% confidence interval [CI]: 17.9-19.2) to 12.5% (CI: 11.9-13.1); Recurrent MI, 7.5% (CI: 7.1-8.0) to 5.5% (CI: 5.1-6.0); Bleeding, 3.9% (CI: 3.6-4.3) to 2.7% (CI: 2.4-3.0). Crude 5-year risk of mortality in 2015-17 was as low as 2.6% for patients aged <60 years. Use of guideline-recommended treatments was associated with improved outcomes: After standardization for changes in treatments, 5-year risk of mortality in 2000-02 was 15.5% (CI: 14.9-16.2). CONCLUSIONS: For patients who were event-free 1 year after MI, the long-term risks of mortality, cardiovascular events, and bleeding decreased significantly, along with an improved use of guideline-recommended treatments between 2000 and 2017. In the most recent period, 1 year after MI, the risk of additional events was lower than previously reported.

Temporal trends in major cardiovascular events following first-time myocardial infarction in the reperfusion era - a Danish nationwide cohort study from 2000 to 2017.

AIM: We investigated temporal trends in major cardiovascular events following first-time myocardial infarction (MI) and trends in revascularization and pharmacotherapy from 2000 to 2017. METHODS AND RESULTS: Using nationwide registries, we identified 120 833 Danish patients with a first-time MI between 2000 and 2017. We investigated 30-day and 1-year mortality and the 1-year risk of first-time admission for heart failure (HF) and recurrent MI. Patients were younger with a higher prevalence of hypertension and diabetes in 2015-2017 compared with 2000-2002. The patients were predominantly male (65.6%), and the median age declined by 3 years through the periods. Percutaneous coronary interventions within 7 days after first-time MI increased significantly (2000: 11.4% vs. 2017: 68.6%; Ptrend < 0.001). Cardiovascular medication after first-time MI changed significantly in the same period. Absolute risks and adjusted rates of outcomes were significantly lower in 2015-2017 compared with 2000-2002: 30-day mortality: 6.5% vs. 14.1% [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.48-0.55); 1-year mortality 10.7% vs. 21.8% (HR 0.52, 95% CI: 0.50-0.55); recurrent MI: 4.0% vs. 7.8% (HR 0.56, 95% CI: 0.51-0.62); and first-time admission for HF: 2.9% vs. 3.7% (HR 0.82, 95% CI: 0.73-0.92). The rates of 30-day/1-year mortality and recurrent MI showed significantly decreasing trends (Ptrend < 0.001). The rates of first-time admission for HF were borderline significant (Ptrend = 0.045). CONCLUSION: From 2000 to 2017, we observed a decreasing risk of recurrent MI, first-time admission for HF, and all-cause mortality in patients with a first-time MI. In the same period, we observed a high rate of guideline-recommended pharmacological treatment after first-time MI as well as increasing rate of early revascularization in Denmark. TRANSLATIONAL PERSPECTIVES: The results from the current study portrait the risk of all-cause mortality, recurrent MI, and first-time admission for HF in a real-life setting with a very high utilization of early revascularization and guideline-recommended pharmacological therapy. We observed a temporal trend of improved survival, reduced risk of recurrent MI, as well as reduced risk of first-time admission for HF after first-time MI from 2000 through 2017. We observed an increase in the overall use of revascularization, as well as early revascularization and use of guideline-recommended pharmacotherapy. Our study reveals important results from real-life, nationwide data, showing a reduced risk of cardiovascular outcomes after first-time MI during the past 20 years. Current guidelines are based on results from clinical trials. Our real-life results add additionally important knowledge on patients' prognosis after first-time MI and underline the importance of treating MI according to guideline recommendations.

Seasonal influenza vaccine uptake among patients with cardiovascular disease in Denmark, 2017-2019.

BACKGROUND: Influenza vaccination protects against morbidity and mortality in patients with cardiovascular disease (CVD). We aimed to describe influenza vaccine uptake in patients with CVD in a universal-access healthcare system. METHODS: Using nationwide Danish registries, we included all patients with prevalent CVD, defined as heart failure (HF), atrial fibrillation (AF), ischemic heart disease (IHD), or stroke during three consecutive influenza seasons (October-December 2017-2019). The outcome was relative frequency of influenza vaccination across strata of patient characteristics. RESULTS: There was an average of 397 346 patients with CVD yearly during 2017-2019. Vaccine uptake was 45.6% for the whole population and ranged from 55.0% in AF to 61.8% in HF among patients aged ≥65 years. Among patients aged <65 years, uptake was 32.6% in HF, 19.0% in AF, 21.1% in IHD, and 18.3% in stroke. There was a lower uptake with decreasing age: 21.6% in HF, 5.5% in AF, 7.4% in IHD, and 6.3% in stroke among males aged <45 years, as opposed to 25.5% in HF, 11.5% in AF, 13.8% in IHD, and 12.1% in stroke for males aged 45-54 years. In the further stratified analyses, uptake ranged from a low of 2.5% for males <45 years with AF who were not vaccinated the previous season to a high of 87.0% for females ≥75 years with IHD who were vaccinated the previous season. CONCLUSION: Seasonal influenza vaccine uptake is suboptimal among patients with CVD, even in a universal-access healthcare system with free-of-charge vaccinations. Vaccine uptake was particularly low among young patients.

Age- and sex-specific trends in the incidence of myocardial infarction in Denmark, 2005 to 2021.

BACKGROUND AND AIMS: Few studies have determined whether the declining incidence of myocardial infarction carries into the current decade, and how it is affected by age and sex. We aimed to determine age- and sex-specific changes in myocardial infarction incidence in Denmark from 2005 through 2021. METHODS: First-time myocardial infarction admissions in adults aged ≥18 years were identified through Danish nationwide registries. Incidence rates per 100,000 persons with 95% confidence intervals (CI) were calculated across calendar year, sex, and age groups (≤49, 50-69, 70-84, ≥85 years). We also presented incidence rate ratios (IRR) with 95% CIs for 2019-2021 compared to 2005-2007. RESULTS: From January 1, 2005, through August 4, 2021, there were 116,481 incident acute myocardial infarctions in approximately 4.5 million Danes aged ≥18 years. Overall incidence rate of myocardial infarction per 100,000 persons decreased in both sexes from 2005 through 2021 (females: 143 to 80; males: 243 to 174) and across all age groups. The steepest declines in incidence were observed for ages ≥85 years (males: 55%, IRR: 0.45 [0.41-0.49]; females: 58%, IRR: 0.42 [0.39-0.45]) and 70-84 years (males: 46%, IRR: 0.54 [0.52-0.57]; females: 52%, IRR: 0.48 [0.46-0.51]). Rates also declined significantly for ages 50-69 (males: 19%, IRR: 0.81 [0.79-0.84]; females: 17%, IRR: 0.83 [0.78-0.88]) and ≥49 years (males: 30%, IRR: 0.70 [0.64-0.76]; females: 37%, IRR: 0.63 [0.54-0.74]). CONCLUSIONS: Declines in the incidence of myocardial infarction continued into the current decade across age groups and sex. However, significantly steeper absolute and relative declines were observed among the oldest age groups (≥70 years).

Longitudinal Analysis of Circulating Markers of Bone Turnover Across Multiple Decades in Osteoporotic Women.

PURPOSE: The objective of this study was to analyze changes in serum markers of bone turnover across multiple decades in osteoporotic women compared with nonosteoporotic controls, to determine their utility as potential predictors for osteoporosis. Early prediction of those at risk for osteoporosis can enable early intervention before the irreversible loss of critical bone mass. METHODS: Serum samples were obtained from 20 women given the diagnosis of osteoporosis after age 46 years and 20 age-matched women with normal bone mineral density from 4 time points in their life (ages 25-31, 32-38, 39-45, and 46-60 years). Serum levels of bone turnover markers (propeptide of type I collagen, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, C-terminal telopeptide of type I collagen, sclerostin, osteoprotegerin, osteopontin, and 25-OH vitamin D) were measured using commercially available arrays and kits. We used logistic regression to assess these individual serum markers as potential predictors of osteoporosis, and mixed-effects modeling to assess the change in bone turnover markers between osteoporotic and control groups over time, then performed fivefold cross-validation to assess the classification ability of the models. RESULTS: Markers of bone turnover, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, sclerostin, and osteocalcin were all independent predictors at multiple time points; osteopontin was an independent predictor in the 39- to 45-year age group. Receiver operating characteristic analyses demonstrated moderately strong classification ability at all time points. Sclerostin levels among groups diverged over time and were higher in the control group than the osteoporotic group, with significant differences observed at time points 3 and 4. CONCLUSIONS: Serum markers of bone turnover may be used to estimate the likelihood of osteoporosis development in individuals over time. Although prospective validation is necessary before recommending widespread clinical use, this information may be used to identify patients at risk for developing low bone mineral density long before traditional screening would ostensibly take place. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.