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Background: Acute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI. Methods: In a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age

Objective Patients with stress-related disorders and anxiety are at increased risk of developing cardiovascular disease. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We aimed to establish whether long-term stress (post-traumatic stress disorder, adjustment disorder) or anxiety is associated with OHCA in the general population.Methods We conducted a nested case–control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. Cases were OHCA patients with presumed cardiac causes. Each case was matched by age, sex and date of OHCA with 10 non-OHCA controls from the general population. HRs for OHCA were derived from Cox models after controlling for common OHCA risk factors. Stratified analyses were performed according to sex, age and pre-existing cardiovascular disease.Results We included 35 195 OHCAs and 351 950 matched controls (median age 72 years; 66.8% male). Long-term stress conditions were diagnosed in 324 (0.92%) OHCA cases and 1577 (0.45%) non-OHCA controls, and were associated with higher rate of OHCA (HR 1.44, 95% CI 1.27 to 1.64). Anxiety was diagnosed in 299 (0.85%) OHCA cases and 1298 (0.37%) controls, and was associated with increased rate of OHCA (HR 1.56, 95% CI1.37 to 1.79). We found no interaction with sex, age or history of cardiovascular diseases.Conclusion Patients with stress-related disorders or anxiety have an increased rate of OHCA. This association applies equally to men and women and is independent from the presence of cardiovascular disease. Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients.

Abstract Background High-dose influenza vaccines provide better protection against influenza infection than standard-dose in persons aged 65 years and above; however, in most countries, high-dose vaccines are not widely implemented. Assessing the relative effectiveness of high-dose compared to standard-dose vaccines on hospitalizations and mortality would enable more robust public health and cost-effectiveness estimates. This study aims to investigate the feasibility of conducting a pragmatic randomized clinical trial in Denmark comparing high-dose to standard-dose vaccines utilizing existing vaccination infrastructure and the Danish nationwide health registries for data collection. Methods The DANFLU-1 trial (NCT05048589) is a pragmatic, open-label, active-controlled randomized trial randomizing Danish citizens aged 65–79 years to either high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine. The study utilizes the infrastructure of a private vaccination provider (Danske Lægers Vaccinations Service) for recruitment, inclusion, randomization, and vaccination. All collection of baseline and follow-up data including safety monitoring is performed centrally by the Department of Cardiology at Herlev and Gentofte Hospital, Copenhagen, Denmark using the Danish nationwide health registries. The study aims to include 40,000 participants during the 2021/2022 influenza season. The primary endpoints address feasibility and include the number of participants enrolled, randomization balance, and representativeness compared to the Danish general population. Relative vaccine effectiveness will also be assessed, however, this feasibility study is not powered for clinical outcomes and may be affected by the COVID-19 pandemic. Discussion The DANFLU-1 study is investigating the feasibility of conducting a large-scale pragmatic clinical trial in Denmark utilizing existing infrastructure and the Danish nationwide registries. This will provide valuable insight, especially for potential future fully powered vaccine trials, but also for trials wishing to investigate other interventions. Trial registration Clinicaltrials.gov : NCT05048589 , registered September 17, 2021.

Background: Of patients undergoing transcatheter aortic valve replacement (TAVR), 80–90 % are at extreme, high, or intermediate risk. Patient selection considering futile outcomes in these groups is difficult as significant comorbidity burden is common. Thus, we examined 1-year mortality after TAVR according to age and comorbidities. Methods: Between 2008 and 2021 all Danish TAVR-patients were included. From a multivariate Cox-regression model, significant characteristics associated with 1-year all-cause mortality were identified. The study population was divided into four groups according to number of significant comorbidities present at baseline: Low (0 comorbidities), mild (1 comorbidity), moderate (2 comorbidities), and high (3 or more comorbidities). The 1-year risk of all-cause mortality with 95 % confidence intervals (CI) was estimated by each group. Results: In total, 7,104 patients underwent TAVR. Significant covariates associated with 1-year all-cause mortality were chronic kidney disease, heart failure, chronic obstructive pulmonary disease, peripheral artery disease, and age ≥ 85 years. The four baseline groups comprised low (n = 2,666), mild (n = 2,814), moderate (n = 1,246), and high comorbidity burden (n = 378). The 1-year risk of all-cause mortality was 5.5 % (95 %CI: 4.6–6.4 %) in the low baseline comorbidity burden group. Conversely, the 1-year risk of all-cause mortality was 25.0 % (95 %CI: 20.4–29.3 %) in the high baseline burden group. Conclusions: In a national sample of TAVR patients, readily available information on age and comorbidities, can be used to identify a high-risk group with 25 % 1-year mortality. This provides physicians and patients with an easy-to-understand view on 1-year prognosis after TAVR and may complement patient selection for improved long-term outcomes.

Abstract Aims Despite adequate treatment, recent studies have hypothesized that malaria may affect long‐term cardiovascular function. We aimed to investigate the long‐term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark. Methods Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all‐cause death (1 January 1994 to 1 January 2017). The population was age‐ and sex‐matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion. Results We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow‐up was 9.8 years (interquartile range 3.9–16.4 years). Event rates per 1000 person‐years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all‐cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21–2.09], P = 0.001), but not MI (HR: 1.00 [0.72–1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74–1.35], P = 0.98) or all‐cause death (HR 1.11 [0.94–1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14–2.36], P = 0.008). Conclusion Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF.

Background Guideline‐recommended disease‐modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin‐converting enzyme inhibitors/angiotensin‐II receptor blockers (ACEi/ARB), β‐blockers (BB), and mineralocorticoid receptor antagonists. Methods and Results Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups:

Background: The incidence rates and importance of traditional risk factors in dilated cardiomyopathy among first-degree relatives are unknown. Methods and Results: We identified all probands with dilated cardiomyopathy (n = 13,714, mean age at diagnosis 63 years) from the Danish nationwide registries between 1994 and 2017. Incidence rates among first-degree relatives (n = 29,671, mean age 38 years) and for up to 10 age- and sex-matched controls were calculated. Totally 233 (0.8%) first-degree relatives and 285 (0.1%) controls developed dilated cardiomyopathy during a median follow-up of 8.2 (Q1-Q3 4.4–13.3) years. Incidence rates (per 100,000 person-years) were 86.4 (95% confidence interval 73.9–101.0) and 111.1 (79.4–128.7) for first-degree relatives aged

Background and purpose — Extensive research and national multidisciplinary programs have striven to introduce uniform standards of treatment and mitigate mortality and adverse events after hip fracture surgery over the past decades. A large-scale overview of temporal developments in hip fracture surgery and care is warranted. Patients and methods — We studied Danish patients aged ≥ 60 years, sustaining their first ever hip fracture between 1997 and 2017. Patients were identified from the Danish National Patient Registry (DNPR). Incidence rates of first hip fracture were calculated per 1,000 patient-years and stratified by age group and sex. Information on pre-injury living settings, comorbidities, and medications were obtained from national administrative registers. Type of fracture and treatment choice were recorded, and patients were followed for 1 year to observe mortality, readmission, and surgical complications. Results — Data from 153,058 patients was analyzed. Incidence rate decreased in both sexes, but only led to a reduction in the annual number of hip fractures in the female population. Choice of surgery shifted away from sliding hip screws and parallel implants (SHS-PI), towards intramedullary nailing and hemi-/arthroplasties for trochanteric and femoral neck fractures, respectively. Pre-injury diagnosed morbidity and 1-year readmissions increased contrary to mortality. Median age remained stable around 83 (IQR 77–88) for women and 80 (IQR 73–86) for men. Interpretation — Over the past 2 decades important aspects of hip fracture management have improved. However, sex differences were observed, and men remain more vulnerable than women in terms of morbidity, mortality, and incidence rate.

Summary: Background: Low socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment. Methods: Through nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020). Findings: We included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups. Interpretation: Despite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes. Funding: The work was funded by unrestricted grants from ‘Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond’ and ‘Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond’.

Background Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. Methods and Results Patients with atrial fibrillation on OAC therapy who had a first‐time ischemic stroke were identified in the Danish Stroke Registry (2005–2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio 3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0–58 points), and the risk of very severe stroke (0–14 points) was analyzed by multivariable logistic regression. One‐year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%], therapeutic [43%], supratherapeutic [11%]), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%], and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR], 2.06 [95% CI, 1.28–3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60–2.57]) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1‐year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29–2.13]); HR, 1.55 [95% CI, 1.08–2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76–2.15]; OR, 0.73 [95% CI, 0.37–1.43], respectively) and was not associated with 1‐year mortality (HR, 1.09 [95% CI, 0.83–1.44]; HR, 0.82 [95% CI, 0.57–1.18], respectively) than appropriate DOAC. Conclusions Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first‐line therapy over VKA.

Background: Although troponin elevation is associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19), prognostic implications of serial troponin testing are lacking. We investigated the association between serial troponin measurements and adverse COVID-19 outcomes. Methods: Using Danish registries, we identified COVID-19 patients with a high-sensitivity troponin measurement followed by a second measurement within 1–24 h. All measurements during follow-up were also utilized in subsequent time-varying analyses. We assessed all-cause mortality associated with the absence/presence of myocardial injury (≥1 troponin measurement >99th percentile upper reference limit) and absence/presence of dynamic troponin changes (>20% relative change if first measurement elevated, >50% relative change if first measurement normal). Results: Of 346 included COVID-19 patients, 56% had myocardial injury. Overall, 20% had dynamic troponin changes. In multivariable Cox regression models, myocardial injury was associated with all-cause mortality (HR = 2.56, 95%CI = 1.46–4.51), as were dynamic troponin changes (HR = 1.66, 95%CI = 1.04–2.64). We observed a low incidence of myocardial infarction (4%) and invasive coronary procedures (4%) among patients with myocardial injury. Conclusions: Myocardial injury and dynamic troponin changes determined using serial high-sensitivity troponin testing were associated with poor prognosis among patients with COVID-19. The risk of developing myocardial infarction requiring invasive management during COVID-19 hospitalization was low.

Background Our objective was to investigate stroke severity and subsequent rate of mortality among patients with and without atrial fibrillation (AF). Contemporary data on stroke severity and prognosis in patients with AF are lacking. Methods and Results First‐time ischemic stroke patients from the Danish Stroke Registry (January 2005–December 2016) were included in an observational study. Patients with AF were matched 1:1 by sex, age, calendar year, and CHA2DS2‐VASc score with patients without AF. Stroke severity was determined by the Scandinavian Stroke Scale (0–58 points). The rate of death was estimated by Kaplan‐Meier plots and multivariable Cox regression. Among 86 458 identified patients with stroke, 17 205 had AF. After matching, 14 662 patients with AF and 14 662 patients without AF were included (51.8% women; median age, 79.6 years [25th–75th percentile, 71.8–86.0]). More patients with AF had very severe stroke (0–14 points) than patients without AF (13.7% versus 7.9%, P

Abstract Background The prevalence of both atrial fibrillation (AF) and malignancies are increasing in the elderly, but incidences of new onset AF in different cancer subtypes are not well described.The objectives of this study were therefore to determine the incidence of AF in different cancer subtypes and to examine the association of cancer and future AF. Methods Using national databases, the Danish general population was followed from 2000 until 2012. Every individual aged > 18 years and with no history of cancer or AF prior to study start was included. Incidence rates of new onset AF were identified and incidence rate ratios (IRRs) of AF in cancer patients were calculated in an adjusted Poisson regression model. Results A total of 4,324,545 individuals were included in the study. Cancer was diagnosed in 316,040 patients. The median age of the cancer population was 67.0 year and 51.5% were females. Incidences of AF were increased in all subtypes of cancer. For overall cancer, the incidence was 17.4 per 1000 person years (PY) vs 3.7 per 1000 PY in the general population and the difference increased with age. The covariate adjusted IRR for AF in overall cancer was 1.46 (95% confidence interval (CI) 1.44–1.48). The strength of the association declined with time from cancer diagnosis (IRR0-90days = 3.41 (3.29–3.54), (IRR-180 days-1 year = 1.57 (CI 1.50–1.64) and (IRR2–5 years = 1.12 (CI 1.09–1.15). Conclusions In this nationwide cohort study we observed that all major cancer subtypes were associated with an increased incidence of AF. Further, cancer and AF might be independently associated.

Background It remains challenging to identify patients at risk of out‐of‐hospital cardiac arrest (OHCA). We aimed to examine health care contacts in patients before OHCA compared with the general population that did not experience an OHCA. Methods and Results Patients with OHCA with a presumed cardiac cause were identified from the Danish Cardiac Arrest Registry (2001–2014) and their health care contacts (general practitioner [GP]/hospital) were examined up to 1 year before OHCA. In a case‐control study (1:9), OHCA contacts were compared with an age‐ and sex‐matched background population. Separately, patients with OHCA were examined by the contact type (GP/hospital/both/no contact) within 2 weeks before OHCA. We included 28 955 patients with OHCA. The weekly percentages of patient contacts with GP the year before OHCA were constant (25%) until 1 week before OHCA when they markedly increased (42%). Weekly percentages of patient contacts with hospitals the year before OHCA gradually increased during the last 6 months (3.5%–6.6%), peaking at the second week (6.8%) before OHCA; mostly attributable to cardiovascular diseases (21%). In comparison, there were fewer weekly contacts among controls with 13% for GP and 2% for hospital contacts (P

Background There are limited data on the lifetime risk of heart failure (HF) in people with type 2 diabetes and how incidence has changed over time. We estimated the cumulative incidence and incidence rates of HF among Danish adults with type 2 diabetes between 1995 and 2018 using nationwide data. Methods and Results In total, 398 422 patients (49% women) with type 2 diabetes were identified. During follow‐up, 36 400 (9%) were diagnosed with HF and 121 459 (30%) were censored due to death. Using the Aalen‐Johansen estimators, accounting for the risk of death, the estimated residual lifetime risk of HF at age 50 years was calculated as 24% (95% CI 22%–27%) in women and 27% (25%–28%) in men. During the observational period, the proportion of patients treated with statins, angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers, and metformin increased from 60%. Similarly, the annual incidence rates of HF decreased significantly, with declines being greater in older versus younger individuals (5% versus 2% in age >50 versus ≤50 years, respectively; P

Background Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple invasive procedures, including pulmonary valve replacement (PVR). Data on the long‐term risk of IE are sparse. Methods and Results In this observational cohort study, all patients with ToF born from 1977 to 2018 were identified using Danish nationwide registries and followed from date of birth until occurrence of first‐time IE, emigration, death, or end of study (December 31, 2018). The comparative risk of IE among patients with ToF versus age‐ and sex‐matched controls from the background population was assessed. Because of rules on anonymity, exact numbers cannot be reported if the number of patients is

Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new‐onset HFrEF treated with either carvedilol or metoprolol for all‐cause mortality until the end of 2018. Follow‐up started 120 days after initial HFrEF diagnosis to allow initiation of guideline‐directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well‐balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow‐up. We observed no mortality differences between carvedilol and metoprolol, multivariable‐adjusted hazard ratio (HR) 0.97 (0.90–1.05) in patients with T2D versus 1.00 (0.95–1.05) for those without T2D, P for difference =0.99. Rates of new‐onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75–0.91), P

Background Guideline‐based cardioprotective medical therapy is intended to reduce the burden of adverse cardiovascular and limb outcomes in patients with peripheral artery disease (PAD). However, contemporary data describing trends in use of medication remains limited. The present study, therefore, aims to investigate changes in use of cardioprotective medication in PAD. Methods and Results By using Danish national healthcare registries, we identified all patients with first‐time diagnosis of PAD (1997–2016) and classified them into two groups: (1) PAD+ that includes all patients with PAD with a history of cardiovascular disease, ie, myocardial infarction, atrial fibrillation, and stroke (n=162 627); and (2) PAD (n=87 935) that comprise patients without a history of cardiovascular disease. We determined the use of medication in the first 12 months after the incident diagnosis of PAD and estimated age standardized 1‐year mortality rates. Our results showed increase in use of cardioprotective medication throughout the study period in both groups. However, PAD+ had a higher use of medication (acetylsalicylic acid, 3.5%–48.4%; Clopidogrel, 0%–17.6%; vitamin K antagonists, 0.9%–7.8%; new oral anticoagulants, 0.0%–10.1%; Statins, 1.9%–58.1%; angiotensin‐converting enzyme inhibitors, 1.2%–20.6%), compared with PAD (acetylsalicylic acid, 2.9%–54.4%; Clopidogrel, 0%–11.9%; vitamin K antagonists, 0.9%–2.4%; new oral anticoagulants, 0.0%–3.4%; Statins, 1.5%–56.9%; angiotensin‐converting enzyme, 0.9%–17.2%), respectively. Furthermore, 1‐year mortality rates in PAD declined with increased use of medications during study. Conclusions In this nationwide study, use of cardioprotective medication increased considerably with time, but compared to patients with other atherosclerotic diseases, there remains an underuse of guideline‐based medical therapy in patients with PAD.

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

Abstract Background The risk of peripheral artery disease (PAD) in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is an important and inadequately addressed issue. Our aim is to examine the impact of DM on risk of PAD in patients with different degrees of CAD characterized by coronary angiography (CAG). Methods Using nationwide registers we identified all patients aged ≥18 years, undergoing first time CAG between 2000 and 2012. Patients were categorized into DM/Non-DM group, and further classified into categories according to the degree of CAD i.e., no-vessel disease, single-vessel disease, double-vessel disease, triple-vessel disease, and diffuse disease. Risk of PAD was estimated by 5-year cumulative-incidence and adjusted multivariable Cox-regression models. Results We identified 116,491 patients undergoing first-time CAG. Among these, a total of 23.969 (20.58%) had DM. Cumulative-incidence of PAD among DM patients vs. non-DM were 8.8% vs. 4.9% for no-vessel disease, 8.2% vs. 4.8% for single-vessel disease, 10.2% vs. 6.0% for double-vessel disease, 13.0% vs. 8.4% for triple-vessel disease, and 6.8% vs. 6.1% for diffuse disease, respectively. For all patients with DM, the cox-regression analysis yielded significantly higher hazards of PAD compared with non-DM patients with HR 1.70 (no-vessel disease), 1.96 (single-vessel disease), 2.35 (double-vessel disease), 2.87 (triple-vessel disease), and 1.46 (diffuse disease), respectively (interaction-p 0.042). Conclusion DM appears to be associated with increased risk of PAD in patients with and without established CAD, with increasing risk in more extensive CAD. This observation indicates awareness on PAD risk in patients with DM, especially among patients with advanced CAD.

Abstract Background To investigate the incidence and the mortality-rates of systemic sclerosis (SSc), its primary causes of death, and the temporal trends in events in Denmark during the last decades. Methods Using the Danish National Patient Registry, we identified all persons aged ≥18 years with a first-time diagnosis of SSc (ICD-10 code M34, excluding M34.2) between 1995 and 2015. Results A total of 2778 incident SSc cases were identified. The mean age at time of SSc diagnosis was 56 (standard deviation 15) years and 76% were women. The overall incidence rate (per 1,000,000 person-years) of diagnosed SSc was 24.4 (95% confidence interval 23.6–25.4), with a slight increase over the study period, age- and sex-adjusted incidence rate ratio 1.02 (95% confidence interval 1.01–1.02) per 1-year increase. The 1-year all-cause mortality rate per 100 person-years decreased from 6.1 (3.1–12.2) in 1995 to 5.3 (2.5–11.1) in 2015, sex- and age-adjusted hazard ratio 0.96 (95% CI 0.94–0.98) per 1-year increase. Over the period, the average age at SSc diagnosis increased and the proportion of women decreased, whereas the burden of comorbidities increased. One fifth of all deaths were attributable to cardiovascular causes, a fourth to pulmonary diseases, and 15% were due to cancer. Conclusions Within the last few decades, the incidence of SSc has increased and the 1-year mortality rate has decreased slightly in Denmark. Almost half of all deaths were attributable to cardiopulmonary causes.

Background Patients with chronic diseases are at higher risk of requiring domiciliary and nursing home care, but how different chronic diseases compare in terms of risk is not known. We examined initiation of domiciliary care and nursing home admission among patients with heart failure (HF), stroke, COPD and cancer. Methods Patients with a first-time hospitalization for HF, stroke, COPD or cancer from 2008–2016 were identified. Patients were matched on age and sex and followed for five years. Results 111,144 patients, 27,786 with each disease, were identified. The median age was 69 years and two thirds of the patients were men. The 5-year risk of receiving domiciliary care was; HF 20.9%, stroke 25.2%, COPD 24.6% and cancer 19.3%. The corresponding adjusted hazard ratios (HRs), with HF patients used as reference, were: stroke 1.35[1.30–1.40]; COPD 1.29[1.25–1.34]; and cancer 1.19[1.14–1.23]. The five-year incidence of nursing home admission was 6.6% for stroke, and substantially lower in patients with HF(2.6%), COPD(2.6%) and cancer (1.5%). The adjusted HRs were (HF reference): stroke, 2.44 [2.23–2.68]; COPD 1.01 [0.91–1.13] and cancer 0.76 [0.67–0.86]. Living alone, older age, diabetes, chronic kidney disease, depression and dementia predicted a higher likelihood of both types of care. Conclusions In patients with HF, stroke, COPD or cancer 5-year risk of domiciliary care and nursing home admission, ranged from 19–25% and 1–7%, respectively. Patients with stroke had the highest rate of domiciliary care and were more than twice as likely to be admitted to a nursing home, compared to patients with the other conditions.

Background: The incidence of infective endocarditis (IE) has increased in recent decades. Societal lockdown including reorganization of the healthcare system during the COVID-19 pandemic may influence the incidence of IE. This study sets out to investigate the incidence of IE during the Danish national lockdown. Methods: In this nationwide cohort study, patients admitted with IE in either one of two periods A) A combined period of 1 January to 7 May for 2018 and 2019, or B) 1 January to 6 May 2020, were identified using Danish nationwide registries. Weekly incidence rates of IE admissions for the 2018/2019-period and 2020-period were computed and incidence rate ratios (IRR) for 2020-incidence vs 2018/2019-incidence were calculated using Poisson regression analysis. Results: In total, 208 (67.3% men, median age 74.1 years) and 429 (64.1% men, median age 72.7 years) patients were admitted with IE in 2020 and 2018/2019, respectively. No significant difference in incidence rates were found comparing the 2020-period and 2018/2019-period (IRR: 0.96 (95% CI: 0.82–1.14). The overall incidence rate pre-lockdown (week 1–10: 1 January to 11 March 2020) was 14.2 IE cases per 100,000 person years (95% CI: 12.0–16.9) as compared with 11.4 IE cases per 100,000 person years (95% CI: 9.1–14.1) during lockdown (week 11–18: 12 March to 6 May 2020) corresponding to an IRR of 0.80 (95% CI: 0.60–1.06) and thus no significant difference pre- versus post-lockdown. Conclusion: In this nationwide cohort study, no significant difference in the incidence of IE admissions during the national lockdown due to the COVID-19 pandemic was found.

Abstract Background The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. Methods Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. Results One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996–2012 and 2002–2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70–4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02–1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54–3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78–5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. Conclusion All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

It is unclear whether psoriasis is a progressive disease that requires early aggressive intervention. This population-based study identified patients with psoriasis and psoriatic arthritis (PsA). Survival analysis and Kaplan–Meier life table techniques were used. The study comprised 10,011 psoriasis patients (severe n = 4,618), and 1,269 patients also had PsA. Incidence of PsA increased with duration of cutaneous symptoms (p = 0.0001). Psoriasis diagnosed before age 20 or 30 years, respectively, suggested a lower risk of PsA than psoriasis diagnosed after age 50 years, yet age at first cutaneous symptoms did not predict development of PsA. No clear association with disease severity was found. PsA incidence appeared stable with longer duration of psoriasis, but further data are needed to firmly establish the relationship with age of psoriasis onset.

Psoriasis is an immune-mediated inflammatory disease, which, in studies among adults, have been shown to cluster with autoimmune disease. The aim of this cross-sectional register study was to examine possible associations between 9 pre-selected autoimmune diseases and psoriasis in children and adolescents. The study population consisted of all individuals living in Denmark, age under 18 years on 31 December 2012. A total of 1,925 children and adolescents with psoriasis and 1,194,712 without psoriasis were identified. Psoriatic arthritis (adjusted odds ratio (OR) 10.08; 7.97–12.74), rheumatoid arthritis (adjusted OR 6.61; 2.75–15.87) and vitiligo (adjusted OR 4.76; 1.71–13.20) showed strong associations with psoriasis. In addition to increased risk of selected autoimmune diseases, the presence of psoriasis was associated with increased risk of multiple concurrent autoimmune diseases compared with children and adolescents with­out psoriasis. Clinicians should be aware of extracutaneous symptoms when treating children and adole­scents with psoriasis.

Abstract Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p

The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012 were examined. There was a female predominance ranging between 50.0% (2007) and 55.4% (2009), and the mean age at time of diagnosis was 47.7–58.7 years. A total of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak incidence of 199.5 in 2010. Incidence rates were higher for women, and patients aged 60–69 years, respectively. Use of systemic non-biologic agents, i.e. methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA) increased over the study course, and were used in 15.0% of all patients. Biologic agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were utilized in 2.7% of patients. On a national level, incidence of psoriasis fluctuated during the 10-year study course. The relationship between psoriasis incidence and age appeared to be relatively linear, and disease prevalence was comparable to that in other European countries.

Psoriasis has been associated with increased risk of myocardial infarction (MI) in some, but not all, studies. This study investigated the risk of MI in patients with psoriasis and psoriatic arthritis in Denmark. All residents aged ≥18 years from 1 January 2008 through 31 December 2012 were included. Adjusted hazard ratios (HRs) did not show an increased risk of MI in patients with mild psoriasis (HR 1.02; 95% confidence interval (95% CI) 0.96–1.09), whereas the risk was slightly increased in patients with severe psoriasis (HR 1.21; 1.07–1.37). Stratified by age, there was no increased risk of MI in any specific age group, regardless of severity. Limited to first-time MI, the risk was increased only in patients with severe psoriasis aged

Background Cardiovascular involvement in systemic sclerosis (SSc) comprises a wide range of manifestations with prevalence and incidence that remain uncertain. Methods and Results In the Danish administrative registries between 1995 and 2015, all patients aged ≥18 years with a first diagnosis of SSc were matched by age and sex with controls (1:5) from the general population. Prevalence of cardiovascular diseases at the time of the SSc diagnosis and incidence during follow‐up were assessed by in‐ and outpatient discharge diagnoses. Conditional logistic and Cox proportional hazards regression models were used respectively to calculate odds ratios for prevalent cardiovascular diseases and hazard ratios (HRs) for incident diseases associated with SSc. Patients with SSc (n=2778; 76% women; mean±SD age: 55±15 years) had more established cardiovascular risk factors than their respective controls at baseline, including greater prevalence of hypertension (31.2% versus 21.0%, P

The data presented in this article is supplemental data related to the research article entitled “Automated external defibrillator accessibility is crucial for bystander defibrillation and survival: a registry-based study” (Karlsson et al., 2019). We present detailed data concerning: 1) the type of location for deployed and registered automated external defibrillators (AEDs) in the nationwide Danish AED Network; 2) the number of registered AEDs in the nationwide Danish AED Network, and changes in AED registration (according to year and type of AED location); 3) the number of AEDs being withdrawn from the AED network between the years 2007–2016. We also report data on baseline cardiac arrest-related characteristics of out-of-hospital cardiac arrests (OHCAs) that occurred in Copenhagen, Denmark, between 2008 and 2016. Cardiac arrest-related characteristics are further described according to AED accessibility (accessible vs. inaccessible AED at the time of OHCA) for OHCAs covered by an AED (AED ≤200 m route distance of an OHCA). Finally, we report data on distance to the nearest accessible AED for bystander defibrillated OHCAs covered by an AED ≤200 m route distance where the AED was inaccessible at the time of OHCA. Keywords: Cardiac arrest, Resuscitation, Automated external defibrillator, Survival

BACKGROUND:The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. METHODS:1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. RESULTS:Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p

Background Whether there is an association between sleep apnea (SA) and the risk of developing heart failure (HF) is unclear. Furthermore, it has never been established whether continuous positive airway pressure (CPAP) therapy can prevent development of HF. We aimed to investigate SA patients’ risk of developing HF and the association of CPAP therapy. Methods and Results Using nationwide databases, the entire Danish population was followed from 2000 until 2012. patients with SA receiving and not receiving CPAP therapy were identified and compared with the background population. The primary end point was first‐time hospital contact for HF and adjusted incidence rate ratios of HF were calculated using Poisson regression models. Among 4.9 million individuals included, 40 485 developed SA during the study period (median age: 53.4 years, 78.5% men) of whom 45.2% received CPAP therapy. Crude rates of HF were increased in all patients with SA relative to the background population. In the adjusted model, the incidence rate ratios of HF were increased in the untreated SA patients of all ages, compared with the background population. Comparing the CPAP‐treated patients with SA with the untreated patients with SA showed significantly lower incidence rate ratios of HF among older patients. Conclusions In this nationwide cohort study, SA not treated with CPAP was associated with an increased risk of HF in patients of all ages. Use of CPAP therapy was associated with a lower risk of incident HF in patients >60 years of age, suggesting a protective effect of CPAP therapy in the elderly.

The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM).Through Danish nationwide registries, patients with NVAF and a PPM were identified from 2001 to 2012. Changes in concomitant pharmacotherapy and comorbidities were tested using the Cochran-Armitage trend test and linear regression. Patients with NVAF were identified to calculate the proportional amount of PPM implants.A total of 12,231 NVAF patients with a PPM were included in the study, 55.6% of which were men. Median age was 78 years (interquartile range 70-84). From 2001 to 2012, the number of NVAF patients with a PPM increased from 850 to 1344, while the number of NVAF patients increased from 67,478 to 127,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p

Warfarin is a cornerstone for the prevention of thromboembolism in atrial fibrillation (AF), and several efforts have been taken to increase its usage and safety, including risk stratification schemes. Our aim was to investigate the temporal trends in initiation of warfarin and its effects on incidence of bleeding and thromboembolism in patients with new-onset atrial fibrillation 1996-2011.All patients with a first-time diagnosis of non-valvular atrial fibrillation were identified from nationwide administrative registries. Trends were determined by linear regression.In total 153,682 patients were included. Initiation of warfarin increased from 14% to 41% (p1, where the annual decline was -0.12% (95%CI: -0.161; -0.084)) for those treated with warfarin and -0.073% (95%CI: -0.116;-0.030)) for those not treated with warfarin. Bleeding increased from 3.3% to 3.9% (p = 0.043). For those with a CHA2DS2VASc score >1 annual bleeding rates increased by 0.095% (95%CI: -0.025; -0.165) in warfarin treated and by 0.056% (95%CI: -0.013; -0.100) in patients not treated with warfarin.Warfarin use increased by nearly a 3-fold between 1996 and 2011. During the same period, thromboembolic events declined by a third and bleeding increased by a fifth, suggesting a beneficial effect associated with higher warfarin use. Notably, a small decline in thromboembolic events and increase in bleeding events was observed for the untreated population, suggesting a changing risk profile of AF patients.

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease associated with a wide range of comorbidities, including cardiovascular disease, but its association with heart failure (HF) is not fully clear. We investigated the risk of incident HF in a nationwide cohort of patients with RA. Methods and ResultsThe study comprised the entire Danish population aged ≥18 years followed from January 1, 2008 until first hospitalization for HF, emigration, December 31, 2012, or death. Information on comorbidity, medication, and socioeconomic status was identified by individual‐level linkage of administrative registers. Patients with a rheumatologist diagnosis of RA between 1978 and 2008 were included. The primary study outcome was incident HF defined as first hospital admission for HF. Incidence rates of HF per 1000 person‐years were calculated and incidence rate ratios adjusted for age, sex, calendar year, comorbidity, medications, socioeconomic status, smoking, and alcohol consumption were estimated. A total of 4 305 225 subjects with no history of HF were eligible for analysis at the study start. Of these subjects, 24 343 developed RA and 50 623 were hospitalized for HF. Overall incidence rates of incident HF were 2.43 and 6.64 for the reference population (n=49 879) and patients with RA (n=744), respectively. Correspondingly, the fully adjusted incidence rate ratio for incident HF was increased in patients with RA with incidence rate ratio 1.30 (95% confidence interval, 1.17–1.45). ConclusionsIn this cohort study, RA was associated with an increased hospitalization for HF. These findings add significantly to the existing evidence of RA as a clinically relevant risk factor for HF.

BackgroundWe examined all‐cause mortality and long‐term thromboembolic risk (ischemic stroke, transient ischemic attack, systemic thromboembolism) in patients with and without familial atrial fibrillation (AF). Methods and ResultsUsing Danish nationwide registry data, we identified all patients diagnosed with AF (1995–2012) and divided them into those with familial AF (having a first‐degree family member with a prior AF admission) and those with nonfamilial AF. We paired those with and without familial AF according to age, year of AF diagnosis, and sex in a 1:1 match. Using cumulative incidence and multivariable Cox models, we examined the risk of long‐term outcomes. We identified 8658 AF patients (4329 matched pairs) with and without familial AF. The median age was 50 years (interquartile range 43–54 years), and 21.4% were women. Compared with nonfamilial AF patients, those with familial AF had slightly less comorbid illness but similar overall CHA2DS2‐VASc score (P=0.155). Median follow‐up was 3.4 years (interquartile range 1.5–6.5 years). Patients with familial AF had risk of death and thromboembolism similar to those with nonfamilial AF (adjusted hazard ratio 0.91 [95% CI 0.79–1.04] for death and 0.90 [95% CI 0.71–1.14] for thromboembolism). ConclusionsAlthough family history of AF is associated with increased likelihood for development of AF, once AF developed, long‐term risks of death and thromboembolic complications were similar in familial and nonfamilial AF patients.