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Morten Schmidt1,2, Sigrun Alba Johannesdottir Schmidt1,3, Kasper Adelborg1,4, Jens Sundbøll,1 Kristina Laugesen,1 Vera Ehrenstein,1 Henrik Toft Sørensen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Cardiology, Regional Hospital West Jutland, Herning, Denmark; 3Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, DenmarkAbstract: Denmark has a large network of population-based medical databases, which routinely collect high-quality data as a by-product of health care provision. The Danish medical databases include administrative, health, and clinical quality databases. Understanding the full research potential of these data sources requires insight into the underlying health care system. This review describes key elements of the Danish health care system from planning and delivery to record generation. First, it presents the history of the health care system, its overall organization and financing. Second, it details delivery of primary, hospital, psychiatric, and elderly care. Third, the path from a health care contact to a database record is followed. Finally, an overview of the available data sources is presented. This review discusses the data quality of each type of medical database and describes the relative technical ease and cost-effectiveness of exact individual-level linkage among them. It is shown, from an epidemiological point of view, how Denmark’s population represents an open dynamic cohort with complete long-term follow-up, censored only at emigration or death. It is concluded that Denmark’s constellation of universal health care, long-standing routine registration of most health and life events, and the possibility of exact individual-level data linkage provides unlimited possibilities for epidemiological research.Keywords: health care sector, political systems, population health, registries, epidemiology

Jens Sundbøll,1 Sandra Kruchov Thygesen,1 Katalin Veres,1 Donghua Liao,2 Jingbo Zhao,2 Hans Gregersen,3 Henrik Toft Sørensen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2GIOME Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3GIOME, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong KongBackground: It remains unclear whether constipation is associated with cancer. We evaluated the risk of malignancies in patients with constipation requiring hospitalization.Methods: Using Danish medical registries, we calculated cumulative incidences and standardized incidence ratios (SIRs) for cancer. SIRs were computed as the observed number of gastrointestinal (GI) cancers and selected non-GI cancers in patients with constipation compared with the expected number based on national incidence rates by sex, age, and calendar year (1978–2013).Results: We identified 1,75,901 patients with constipation (59% females, median age 54 years). The cumulative incidences of GI cancers and non-GI cancers after 15 years of follow-up were 2.5% and 2.6%, respectively. During the first year of follow-up, the SIR for any GI cancer was 5.0 (95% confidence interval (CI): 4.8–5.3), driven by colon and pancreas cancers and higher for younger age groups. Beyond 1 year of follow-up, the risk declined to near unity for colorectal cancer. The risk of other GI cancers (including cancers of the esophagus, stomach, small intestine, liver, and pancreas) remained moderately increased (overall SIR =1.3, 95% CI: 1.2–1.4). Except for ovarian cancer (SIR =7.3, 95% CI: 6.3–8.4), the risk of non-GI cancers was only slightly increased during the first year of follow-up and declined to unity thereafter.Conclusions: Patients with constipation had increased short-term risk of a diagnosis of GI cancer. Beyond 1 year of follow-up, a moderately elevated risk persisted only for GI cancers other than colorectal cancer. The risk of non-GI cancers was elevated only during the first year of follow-up, particularly for ovarian cancer.Keywords: constipation, cancer, cohort study

Kasper Adelborg,1 Jens Sundbøll,1,2 Morten Schmidt,1,3 Hans Erik Bøtker,2 Noel S Weiss,4 Lars Pedersen,1 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Cardiology, Regional Hospital West Jutland, Herning, Denmark; 4Department of Epidemiology, University of Washington, Seattle, WA, USA Background: Histamine H2 receptor activation promotes cardiac fibrosis and apoptosis in mice. However, the potential effectiveness of histamine H2 receptor antagonists (H2RAs) in humans with heart failure is largely unknown. We examined the association between H2RA initiation and all-cause mortality among patients with heart failure. Methods: Using Danish medical registries, we conducted a nationwide population-based active-comparator cohort study of new users of H2RAs and proton pump inhibitors (PPIs) after first-time hospitalization for heart failure during the period 1995−2014. Hazard ratios (HRs) for all-cause mortality and hospitalization due to worsening of heart failure, adjusting for age, sex, and time between heart failure diagnosis and initiation of PPI or H2RA therapy, index year, comorbidity, cardiac surgery, comedications, and socioeconomic status were computed based on Cox regression analysis. Results: Our analysis included 42,902 PPI initiators (median age 78 years, 46% female) and 3,296 H2RA initiators (median age 76 years, 48% female). Mortality risk was lower among H2RA initiators than PPI initiators after 1 year (26% vs 31%) and 5 years (60% vs 66%). In multivariable analyses, the 1-year HR was 0.80 (95% CI, 0.74–0.86) and the 5-year HR was 0.85 (95% CI, 0.80–0.89). These findings were consistent after propensity score matching and for ischemic and nonischemic heart failure, as for sex and age groups. The rate of hospitalization due to worsening of heart failure was lower among H2RA initiators than PPI initiators. Conclusion: In patients with heart failure, H2RA initiation was associated with 15%–20% lower mortality than PPI initiation. Keywords: heart failure, epidemiology, histamine H2 receptor, mortality

Background In addition to primary neurodegenerative processes, vascular disorders, such as stroke, can lead to parkinsonism. However, some cardiovascular risk factors, such as smoking and elevated cholesterol levels, are associated with reduced risk of Parkinson disease. We examined the risk of Parkinson disease and secondary parkinsonism in 1-year survivors of myocardial infarction (MI). Methods and Results We conducted a nationwide population-based matched cohort study using Danish medical registries from 1995 to 2016. We identified all patients with a first-time MI diagnosis and sampled a sex-, age-, and calendar year-matched general population comparison cohort without MI. Cox regression analysis was used to compute adjusted hazard ratios (aHRs) for Parkinson disease and secondary parkinsonism, controlled for matching factors and adjusted for relevant comorbidities and socioeconomic factors. We identified 181 994 patients with MI and 909 970 matched comparison cohort members (median age, 71 years; 62% men). After 21 years of follow-up, the cumulative incidence was 0.9% for Parkinson disease and 0.1% for secondary parkinsonism in the MI cohort. Compared with the general population cohort, MI was associated with a decreased risk of Parkinson disease (aHR, 0.80; 95% CI, 0.73-0.87) and secondary parkinsonism (aHR, 0.72; 95% CI, 0.54-0.94). Conclusions MI was associated with a 20% decreased risk of Parkinson disease and 28% decreased risk of secondary parkinsonism. Reduced risk may reflect an inverse relationship between cardiovascular risk factors and Parkinson disease.

In the 2019 European Society of Cardiology guidelines, chronic coronary syndrome (CCS) was introduced as a new term for stable coronary artery disease. Diagnosis, treatment and prevention of CCS have undergone major changes. In the diagnostic management of CCS, there is increased focus on non-invasive imaging modalities, including coronary CT angiography. Based on the risk of thrombosis and bleeding, choice and duration of antithrombotic treatment should be individualised, especially following coronary revascularisation.

Introduction: The incidence of cardiovascular events among cancer patients with bone metastases is poorly understood. We examined rates of cardiovascular events among cancer patients with bone metastases and mortality following such events., Methods: Using Danish health registries, we identified all Danish cancer patients diagnosed with bone metastases (1994-2013) and followed them from bone metastasis diagnosis. We computed incidence rates (IR) per 100 person-years and cumulative incidence for first-time inpatient hospitalization or outpatient clinic visit for cardiovascular events, defined as myocardial infarction, ischemic stroke, or venous thromboembolism (VTE). We also analyzed all-cause mortality rates including cardiovascular events as time-varying exposure with adjustment for age, sex, and Charlson Comorbidity Index score. All analyses were performed overall and stratified by cancer type (prostate, breast, lung, and other)., Results: We included 23,113 cancer patients with bone metastases. The cumulative incidence of cardiovascular events was 1.3% at 30 days, 3.7% at 1 year, and 5.2% at 5 years of follow-up. The highest IR was observed for VTE, followed by ischemic stroke and myocardial infarction, both overall and by cancer types. Lung cancer patients with bone metastases had the highest incidence of cardiovascular events followed by prostate and breast cancer. Occurrence of any cardiovascular event was a strong predictor of death (5 years following the event, the adjusted hazard ratio was 1.8 [95% confidence interval: 1.7-1.9])., Conclusion: Cancer patients with bone metastases had a substantial risk of developing cardiovascular events, and these events were associated with a subsequent increased mortality. Our findings underscore the importance of continuous optimized prevention of and care for cardiovascular disease among cancer patients with bone metastases., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: The prevalence of breast cancer survivors has increased due to dissemination of population-based mammographic screening and improved treatments. Recent changes in anti-hormonal therapies for breast cancer may have modified the risks of subsequent urological and genital cancers. We examine the risk of subsequent primary urological and genital cancers in patients with incident breast cancer compared with risks in the general population., Methods: Using population-based Danish medical registries, we identified a cohort of women with primary breast cancer (1990-2017). We followed them from one year after their breast cancer diagnosis until any subsequent urological or genital cancer diagnosis. We computed incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as the observed number of cancers relative to the expected number based on national incidence rates (by sex, age, and calendar year)., Results: Among 84,972 patients with breast cancer (median age 61 years), we observed 623 urological cancers and 1397 genital cancers during a median follow-up of 7.4 years. The incidence rate per 100,000 person-years was stable during follow-up (83 for urological cancers and 176 for genital cancers). The SIR was increased for ovarian cancer (1.37, 95% CI 1.23-1.52) and uterine cancer (1.37, 95% CI 1.25-1.50), but only during the pre-aromatase inhibitor era (before 2007). Moreover, the SIR of kidney cancer was increased (1.52, 95% CI 1.15-1.97), but only during 2007-2017. The SIR for urinary bladder cancer was marginally increased (1.15, 95% CI 1.04-1.28) with no temporal effects. No associations were observed for cervical cancer., Conclusion: Breast cancer survivors had higher risks of uterine and ovarian cancer than expected, but only before 2007, and of kidney cancer, but only after 2007. The risk of urinary bladder cancer was moderately increased without temporal effects, and we observed no association with cervical cancer.

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

Objectives: To assess the risks of myocardial infarction, stroke, peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter and heart failure in patients with constipation compared with a general population cohort., Design: Population-based matched cohort study., Setting: All Danish hospitals and hospital outpatient clinics from 2004 to 2013., Participants: Patients with a constipation diagnosis matched on age, sex and calendar year to 10 individuals without constipation from the general population., Main Outcomes Measures: Comorbidity-adjusted and medication-adjusted hazard ratios (aHRs) for cardiovascular outcomes based on Cox regression analysis., Results: 83 239 patients with constipation were matched to 832 384 individuals without constipation. The median age at constipation diagnosis was 46.5% and 41% were men. Constipation was strongly associated with venous thromboembolism (aHR 2.04, 95% CI 1.89 to 2.20), especially splanchnic venous thrombosis (4.23, 95% CI 2.45 to 7.31). Constipation was also associated with arterial events, including myocardial infarction (1.24, 95% CI 1.14 to 1.35), ischaemic stroke (1.50, 95% CI 1.41 to 1.60), haemorrhagic stroke (1.46, 95% CI 1.26 to 1.69), peripheral artery disease (1.34, 95% CI 1.20 to 1.50), atrial fibrillation or atrial flutter (1.27, 95% CI 1.20 to 1.34) and heart failure (1.52, 95% CI 1.42 to 1.62). The associations were strongest during the first year after the constipation diagnosis and strengthened with an increased number of laxative prescriptions., Conclusions: Constipation was associated with an increased risk of several cardiovascular diseases, in particular venous thromboembolism., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Myocardial infarction (MI) is a risk factor for venous thromboembolism (VTE). Although comorbidities affect MI prognosis, it is unclear whether they affect VTE risk after MI., Objectives: We examined the impact of comorbidity on VTE risk after MI., Methods: We used nationwide population-based registries to identify first-time hospitalizations for MI and subsequent occurrence of VTE in Denmark (1995-2013). We included a comparison cohort from the general population matched 5:1 with MI patients by sex, age, and comorbidities. We computed 30-day and 1- to 12-month cumulative risks, rates, and hazard ratios of VTE. We also assessed the interaction between MI and comorbidity, defined as excess VTE risk in patients with both MI and comorbidity, by computing interaction contrasts and attributable fractions relating to the interaction., Results: Thirty-day and 1- to 12-month VTE risks were 0.6% and 0.5% in the MI cohort (n = 160 338) and 0.03% and 0.3% in the comparison cohort (n = 792 384). The 30-day hazard ratio for VTE in the MI cohort was 23 (95% confidence interval, 20-27), which decreased during 1-year follow-up. Thirty days after MI, interactions between MI and comorbidity accounted for 16% and 39% of VTE rates in MI patients with low-to-moderate and high comorbidity, respectively. The interactions were driven primarily by hemiplegia and cancer., Conclusions: Thirty-day VTE risk was substantially increased after MI compared with the general population. Although the absolute VTE risk was low, comorbidity substantially increased this risk, especially hemiplegia and cancer. VTE prophylaxis might be indicated in such high-risk patients but warrants further investigation., (© 2020 International Society on Thrombosis and Haemostasis.)

Objective: We examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population., Design: Using population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990-2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs)., Results: Among 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2-5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6-10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990-2006 and 2007-2017, the 1-10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible., Conclusion: Breast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Detailed population-based data are essential to understanding the epidemiology of diabetes and its clinical course. This article describes the Funen Diabetes Database (FDDB). The purpose of the FDDB was to serve as a shared electronic medical record system for healthcare professionals treating patients with diabetes. The cohort can also be used for research., Participants: The FDDB covers a geographical area of almost 500 000 Danish inhabitants. It currently includes 3691 patients with type 1 diabetes, 19 085 patients with type 2 diabetes, 292 patients with other types of diabetes and 5992 patients with an unknown type of diabetes. Patients have been continuously enrolled from general practitioners and endocrinology departments in the Funen area in Denmark since 2003. Patients undergo a clinical work-up at their first diabetes contact and during follow-up visits. The information collected includes type of diabetes contact, blood pressure, height, weight, lifestyle factors (smoking, exercise), laboratory records (eg, haemoglobin A1c and cholesterol levels), results from foot examinations (eg, pulse, cutaneous sensitivity and ankle brachial index), results from eye examinations (eg, degree of retinopathy assessed by retinal photo and eye examination), glucose-lowering drugs and diabetic complications., Findings to Date: The FDDB cohort was followed for a total of 212 234 person-years up to 2016. A cross-sectional study described the prevalence of diabetic retinopathy and its associated risk factors. The clinical outcomes of patients with type 1 diabetes, type 2 diabetes and latent autoimmune diabetes in adults have been assessed. Linkage to population-based medical registries with complete follow-up has enabled the collection of extensive continuous data on general practice contacts, diagnoses and procedures from hospital contacts, medication use and mortality., Future Plans: The FDDB serves as a strong data resource that will be used in future studies of diabetes epidemiology with focus on occurrence, risk factors, treatment, complications and prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We examined if syncope was a marker of an occult cancer by comparing the risk in patients with a syncope episode with that of the general population., Methods: Using Danish population-based medical registries, we identified all patients diagnosed with syncope during 1994-2013 and followed them until a cancer diagnosis, emigration, death or end of follow-up, whichever came first. We computed cumulative risks and standardised incidence ratios (SIR) with 95% confidence intervals (CI)., Results: Among 208,361 patients with syncope, 20,278 subsequent cancers were observed. The 6-month cumulative risk of any cancer was 1.2%, increasing to 17.9 % for 1-20 years of follow-up. The highest cumulative risks after 6 months of follow-up were lung cancer (0.2%), colorectal cancer (0.2%), prostate cancer (0.1%) and brain cancer (0.1%). The 6-month SIR were 2.7 (95% CI: 2.4-3.0) for lung cancer, 2.0 (95% CI: 1.8-2.2) for colorectal cancer, 1.7 (95% CI: 1.5-1.9) for prostate cancer and 10.0 (95% CI: 8.6-11.4) for brain cancer., Conclusions: Syncope was a weak marker of an occult cancer. In short-term the highest cumulative risks were observed for lung, colorectal, prostate and brain cancers. An aggressive search for occult cancer in a patient with syncope is probably not warranted.

Background: An understanding of cardiovascular event rates and low-density lipoprotein cholesterol (LDL-C) levels and trajectories in patients with atherosclerotic cardiovascular disease is needed to evaluate treatment goals and adherence to guidelines., Methods: We conducted a population-based cohort study in the North and Central Denmark Regions. Patients with prevalent atherosclerotic cardiovascular disease (myocardial infarction, non-hemorrhagic stroke, or peripheral artery disease) during 2006-2009 were identified. All patients received lipid-lowering therapy (statins or ezetimibe) and had LDL-C levels ≥1.8 mmol/L at baseline (January 1, 2010). We followed patients for 6 years until a primary composite outcome of cardiovascular death, myocardial infarction, non-hemorrhagic stroke, hospitalization for unstable angina, or coronary revascularization. Additionally, we characterized changes in LDL-C levels and use of statins during follow-up., Results: The study included 10,772 patients (median age 69.2 years, 60.4% male). The overall event rate for the primary outcome was 62.7 (95% confidence interval: 59.2-66.2) per 1000 person-years. This event rate was higher among men than among women and increased with age and baseline LDL-C levels. Approximately 25% of patients with LDL-C measurements during follow-up achieved LDL-C levels below 1.8 mmol/L. Of the approximately two-thirds of patients using statins at the end of follow-up, nearly all patients (97%) received high-intensity therapy., Conclusions: In this population of patients with atherosclerotic cardiovascular disease, we found high cardiovascular event rates, which increased with baseline LDL-C levels. Although most patients were on high-intensity statin therapy at end of follow-up, only one-quarter reached the guideline-recommended target LDL-C level ≤ 1.8 mmol/L., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Fecal incontinence may be an early symptom of cancer, but its association with cancer remains unclear. We examined the risk of selected cancers, including colorectal cancer, other gastrointestinal cancers, hormone-related cancers, and lymphoma, in patients with fecal incontinence., Methods: Using Danish population-based registries, all patients with hospital-based diagnoses of fecal incontinence during 1995-2013 were identified. We calculated cumulative incidences of cancers. As a measure of relative risks, we computed standardized incidence ratios (SIRs), that is, the observed number of cancers relative to the expected number based on national incidence rates by sex, age, and calendar year., Results: Among 16 556 patients with fecal incontinence, the cumulative incidence of colorectal cancers, other gastrointestinal cancers, hormone-related cancers, and lymphoma each was less than 0.4% after 1 year. It increased to under 3% after 10 years. The SIR for any cancer during 19 years of follow-up was 1.12 [95% confidence interval (CI), 1.06-1.19]. The SIRs during the first year were 2.31 (95% CI, 1.65-3.13) for colorectal cancer, 1.56 (95% CI, 0.89-2.54) for other gastrointestinal cancers, 1.00 (95% CI, 0.72-1.35) for hormone-related cancers, and 2.02 (95% CI, 1.01-3.61) for lymphoma. Beyond 1 year, the SIR reached unity for other gastrointestinal cancers, hormone-related cancers, and lymphoma, while a reduced risk was observed for colorectal cancer (SIR = 0.77, 95% CI, 0.59-0.98)., Conclusions: Fecal incontinence was a marker of cancer, especially gastrointestinal cancers and lymphoma within 1 year, which presumably is driven partly by reverse causation. However, the absolute risks were low. Heightened diagnostic efforts may explain in part the increased short-term risk of colorectal cancers., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background Childhood weight trajectories may influence cardiometabolic traits and thereby the risk of venous thromboembolism ( VTE ) later in life. We examined whether overweight and changes in weight status during childhood were associated with risk of VTE in adulthood. Methods and Results We used Danish medical registries to conduct a population-based cohort study of Danish schoolchildren aged 7 to 13 years and born during 1930-1989. We calculated body-mass index ( BMI ) z-scores based on weight and height measurements. We estimated hazard ratios using Cox regressions to examine associations between changes in BMI z-scores from 7 to 13 years of age and the subsequent risk of VTE . Among 313 998 children, 5007 girls and 5397 boys were diagnosed with VTE as adults. Compared with children with a normal BMI (25th to 75th percentile category) at both ages, children with a BMI persistently above the 75th percentile had a 1.30- to 1.50-fold increased risk of VTE in adulthood. Children who experienced a BMI increase from the 25th to 75th or >75th to 90th percentile to a higher percentile category had a 1.35- to 1.70-fold increased risk of adulthood VTE . Children whose BMI percentile category decreased between 7 and 13 years of age had a VTE risk similar to that of children with a persistently normal BMI . Conclusions Risk of VTE in adulthood was higher in children with a persistently above-average BMI . Whereas weight gain from 7 to 13 years of age additionally increased VTE risk, remission from overweight by 13 years of age completely reverted the risk.

The positive predictive value of an infective endocarditis diagnosis is approximately 80% in the Danish National Patient Registry. However, since infective endocarditis is a heterogeneous disease implying long-term intravenous treatment, we hypothesiszed that the positive predictive value varies by length of hospital stay. A total of 100 patients with first-time infective endocarditis in the Danish National Patient Registry were identified from January 2010 - December 2012 at the University hospital of Aarhus and regional hospitals of Herning and Randers. Medical records were reviewed. We calculated the positive predictive value according to admission length, and separately for patients with a cardiac implantable electronic device and a prosthetic heart valve using the Wilson score method. Among the 92 medical records available for review, the majority of the patients had admission length ⩾2 weeks. The positive predictive value increased with length of admission. In patients with admission length <2 weeks the positive predictive value was 65% while it was 90% for admission length ⩾2 weeks. The positive predictive value was 81% for patients with a cardiac implantable electronic device and 87% for patients with a prosthetic valve. The positive predictive value of the infective endocarditis diagnosis in the Danish National Patient Registry is high for patients with admission length ⩾2 weeks. Using this algorithm, the Danish National Patient Registry provides a valid source for identifying infective endocarditis for research.

Background: The occurrence of myocardial infarction (MI), ischemic stroke, and hemorrhagic stroke has decreased in recent years, but trends in seasonal occurrence remain unclear., Methods: Using Danish healthcare databases, we identified all patients with a first-time MI, ischemic stroke, or hemorrhagic stroke during the study period (1977-2016). We summarized monthly cases for each disease separately and computed the peak-to-trough ratio as a measure of seasonal occurrence of one cycle. To examine trends over time in seasonal occurrence, we computed the peak-to-trough ratio for each of the 40 years. We also quantified the amount of bias arising from random error in peak-to-trough ratios., Results: Before consideration of bias, the peak-to-trough ratio of summarized monthly cases was 1.11 (95% confidence interval [CI] = 1.10, 1.12) for MI, 1.08 (95% CI = 1.07, 1.09) for ischemic stroke, and 1.12 (95% CI = 1.10, 1.14) for hemorrhagic stroke. The peak-to-trough ratio of MI occurrence increased from 1.09 (95% CI = 1.04, 1.15) in 1977 to 1.16 (95% CI = 1.09, 1.23) in 1999. The trend then remained stable. The peak-to-trough ratio of ischemic stroke occurrence declined continuously during the study period, dropping from 1.12 (95% CI = 1.02, 1.24) in 1977 to 1.06 (95% CI = 1.00, 1.12) in 2016. The peak-to-trough ratio of hemorrhagic stroke occurrence remained stable over time. However, after adjusting for potential bias, time trends in peak-to-trough ratios were almost flat., Conclusions: We found no substantial seasonality for MI, ischemic stroke, or hemorrhagic stroke occurrence during 1977-2016. Modest peak-to-trough ratios should be interpreted after considering bias induced by random variation.

Background: Venous thromboembolism can be a presenting symptom of cancer, but the association between lower limb arterial thrombosis and cancer is unknown. We therefore examined cancer risk and prognosis of cancer in patients with lower limb arterial thrombosis., Methods: Using nationwide population-based Danish medical registries, we identified all patients diagnosed with first-time lower limb arterial thrombosis (1994-2013) and followed them until the occurrence of any subsequent cancer diagnosis, emigration, death, or November 30, 2013, whichever came first. We computed standardized incidence ratios with 95% confidence intervals as the observed number of cancers relative to the expected number based on national incidence rates by sex, age, and calendar year. To examine the prognostic impact of lower limb arterial thrombosis on all-cause mortality after cancer, we constructed a matched comparison cohort of patients who had cancer without lower limb arterial thrombosis., Results: Among 6600 patients with lower limb arterial thrombosis, we observed 772 subsequent cancers. The risk of any cancer was 2.5% after 6 months of follow-up, increasing to 17.9% after 20 years. During the first 6 months of follow-up, the standardized incidence ratio of any cancer was 3.28 (95% confidence interval, 2.79-3.82). The standardized incidence ratio remained elevated during 7 to 12 months (1.42; 95% confidence interval, 1.09-1.83) and beyond 12 months (1.14; 95% confidence interval, 1.05-1.24). The strongest associations were found for lung cancer and other smoking-related cancers. Lower limb arterial thrombosis also was associated with increased all-cause mortality after colon, lung, urinary bladder, and breast cancer, but not after prostate cancer., Conclusions: Lower limb arterial thrombosis was a marker of occult cancer, especially lung cancer, and was an adverse prognostic factor for mortality in common cancers.

Background: Histamine H 2 receptor activation promotes cardiac fibrosis and apoptosis in mice. However, the potential effectiveness of histamine H 2 receptor antagonists (H2RAs) in humans with heart failure is largely unknown. We examined the association between H2RA initiation and all-cause mortality among patients with heart failure., Methods: Using Danish medical registries, we conducted a nationwide population-based active-comparator cohort study of new users of H2RAs and proton pump inhibitors (PPIs) after first-time hospitalization for heart failure during the period 1995-2014. Hazard ratios (HRs) for all-cause mortality and hospitalization due to worsening of heart failure, adjusting for age, sex, and time between heart failure diagnosis and initiation of PPI or H2RA therapy, index year, comorbidity, cardiac surgery, comedications, and socioeconomic status were computed based on Cox regression analysis., Results: Our analysis included 42,902 PPI initiators (median age 78 years, 46% female) and 3,296 H2RA initiators (median age 76 years, 48% female). Mortality risk was lower among H2RA initiators than PPI initiators after 1 year (26% vs 31%) and 5 years (60% vs 66%). In multivariable analyses, the 1-year HR was 0.80 (95% CI, 0.74-0.86) and the 5-year HR was 0.85 (95% CI, 0.80-0.89). These findings were consistent after propensity score matching and for ischemic and nonischemic heart failure, as for sex and age groups. The rate of hospitalization due to worsening of heart failure was lower among H2RA initiators than PPI initiators., Conclusion: In patients with heart failure, H2RA initiation was associated with 15%-20% lower mortality than PPI initiation., Competing Interests: Disclosure The authors report no conflicts of interest in this work

The connection between the heart and mind has been studied since Sir William Harvey observed more than 350 years ago that negative emotions adversely affect the heart. Today, we know that diseases of the mind can affect the heart and, conversely, that heart diseases can cause both physical and mental diseases of the brain. To explore this relation further, we examined how previous depression affects survival in patients with myocardial infarction (MI) (study II), and how the occurrence of MI affects the risk of ischemic and hemorrhagic stroke (study III) and dementia (study IV). These studies were preceded by a validation study including all major cardiovascular diagnoses in the Danish National Patient Registry (study I). Studies II-IV are population-based cohort studies, of which studies III-IV are matched cohort studies. We identified antidepressant use from prescription registries and used nationwide databases to identify study populations and retrieve data on outcomes and comorbidity. 
In study I (2010-2012), we reviewed a total of 2,153 medical records from one university hospital and two regional hospitals in the Central Denmark Region. We randomly sampled up to 100 cases for each cardiovascular diagnosis. Medical record review served as reference standard to compute the positive predictive value for each diagnosis. For first-time MI, the positive predictive value was 97% (95% CI 91%-99%) and exceeded 90% for the most common cardiovascular disease entities. 
In study II (1995-2014), we identified 170,771 patients with first-time MI. Previous depression was identified by either a depression diagnosis or the use of antidepressants. Patients with MI and a previous depression diagnosis had higher 19-year mortality risks (87% vs. 78%). The overall adjusted mortality rate ratio was 1.11 (95% CI 1.07-1.15), increasing to 1.22 (95% CI 1.17-1.27) when including the use of antidepressants in the definition of depression. The association was stronger in patients with recent depression but was not influenced by depression severity or type of MI.
In study III (1980-2009), we identified 258,806 patients with a first-time MI and 1,244,773 sex-, age-, and calendar year-matched individuals from the general population, and followed them for development ischemic or hemorrhagic stroke. During the first 30 days after MI, the adjusted stroke rate ratio was 31.9 (95% CI 28.4-35.8) for ischemic stroke, 21.8 (95% CI 16.6-28.5) for intracerebral hemorrhage (ICH), and 16.6 (95% CI 8.7-32.0) for subarachnoid hemorrhage (SAH) compared with the general population. The adjusted stroke rate ratio remained increased during 31 to 365 days (3-fold for ischemic stroke, 2-fold for ICH, and 1.5-fold for SAH). During the following 1-30 years, the risk remained 1.6-fold increased for ischemic stroke but decreased to near unity for ICH and SAH.
In study IV (1980-2012), we identified 314,911 patients with first-time MI and 1,573,193 sex-, age-, and calendar year-matched individuals from the general population and followed 1-year survivors for development of dementia. Compared with the general population cohort, MI patients were not at increased risk of all-cause dementia (adjusted hazard ratio = 1.01, 95% CI 0.98-1.03). In subgroups of dementia, we observed no substantial association with Alzheimer's disease (adjusted hazard ratio = 0.92, 95% CI 0.88-0.95) or other dementias (adjusted hazard ratio = 0.98, 95% CI 0.95-1.01). However, patients with MI had an increased risk of vascular dementia (adjusted hazard ratio = 1.35, 95% CI 1.28-1.43). 
In conclusion, we found that preceding depression was associated with moderately increased mortality after MI, and that 
was associated with an increased risk of stroke and vascular dementia, but not dementia from other causes., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Increased risk of dementia after myocardial infarction (MI) may be mediated by shared risk factors (eg, atherosclerosis) and post-MI stroke. We examined risk of dementia in 1-year survivors of MI., Methods: Using Danish medical registries, we conducted a nationwide population-based cohort study of all patients with first-time MI and a sex-, birth year-, and calendar year-matched general population comparison cohort without MI (1980-2012). Cox regression analysis was used to compute 1- to 35-year adjusted hazard ratios (aHRs) for dementia, controlled for matching factors and adjusted for comorbidities and socioeconomic status., Results: We identified 314 911 patients with MI and 1 573 193 matched comparison cohort members randomly sampled from the general population (median age, 70 years; 63% male). After 35 years of follow-up, the cumulative incidence of all-cause dementia in the MI cohort was 9% (2.8% for Alzheimer disease, 1.6% for vascular dementia, and 4.5% for other dementias). Compared with the general population cohort, MI was not associated with all-cause dementia (aHR, 1.01; 95% confidence interval [CI], 0.98-1.03). Risk of Alzheimer disease (aHR, 0.92; 95% CI, 0.88-0.95) and other dementias (aHR, 0.98; 95% CI, 0.95-1.01) also approximated unity. However, MI was associated with higher risk of vascular dementia (aHR, 1.35; 95% CI, 1.28-1.43), which was substantially strengthened for patients experiencing stroke after MI (aHR, 4.48; 95% CI, 3.29-6.12)., Conclusions: MI was associated with higher risk of vascular dementia throughout follow-up, and this association was stronger in patients with stroke. The risk of Alzheimer disease and other dementias was not higher in patients with MI., (© 2017 American Heart Association, Inc.)

Recent trends in use of antihypertensive drugs are unknown. From Danish nationwide prescription data, we obtained information on primary care use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, aldosterone receptor antagonists, and calcium channel blockers. During 1999 to 2015, the use of antihypertensive drugs per 1,000 inhabitants/day increased from 184 to 379 defined daily doses (DDD), corresponding to a rise in the prevalence proportion of users from ≈20% to ≈35%. From 1999 to 2015, a notable increase was observed for angiotensin-converting enzyme inhibitors (from 29 to 105 DDD per 1,000 inhabitants/day ≈260%) and angiotensin II receptor blockers (from 13 to 73 DDD per 1,000 inhabitants/day ≈520%). For diuretics the use remained stable, with a slight decrease (from 89 to 81 DDD per 1,000 inhabitants/day ≈-10%). The use of aldosterone receptor antagonists increased until 2007 and remained unchanged at around 3.5 DDD per 1,000 inhabitants/day thereafter (average change ≈65%). The use of beta blockers doubled during the study period (from 17 to 34 DDD per 1,000 inhabitants/day ≈100%), entirely driven by increasing use of metoprolol. Similar trends were observed for calcium channel blockers (from 34 to 82 DDD per 1,000 inhabitants/day ≈140%), where amlodipine drove the overall increase. In conclusion, antihypertensive drug use has increased remarkably during the past 2 decades., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients with atrial fibrillation or flutter (AFF) are at increased risk of ischemic stroke, but their risk of other thromboembolic events remains less clear., Methods: During 2004-2013, we conducted a nationwide population-based cohort study using Danish medical registries. We identified all patients with first-time AFF and sampled a sex-, age-, and calendar year-matched general population comparison cohort without AFF. For myocardial infarction, peripheral embolism, ischemic stroke, hemorrhagic stroke, deep venous thrombosis, and pulmonary embolism, we computed cumulative risks and adjusted incidence rate ratios (aIRRs) adjusted for comorbidity and medication., Results: The study population consisted of 103,989 patients with AFF and 519,935 individuals without AFF from the general population. Ten-year cumulative risks in the AFF cohort were 3.5% for myocardial infarction, 0.5% for peripheral embolism, 6.7% for ischemic stroke, 1.3% for hemorrhagic stroke, 1.0% for deep venous thrombosis, and 1.3% for pulmonary embolism. During the first 30days following AFF, aIRRs were markedly (4 to 16-fold) increased for all outcomes and similarly elevated for myocardial infarction (aIRR=8.0, 95% confidence interval (CI): 6.8-9.5) and ischemic stroke (aIRR=9.9, 95% CI: 8.5-11.5). Thereafter, aIRRs decreased gradually, reaching unity after 5years for myocardial infarction, deep venous thrombosis, and pulmonary embolism, but remained 1.6 to 3.5-fold increased for peripheral embolism, ischemic stroke, and hemorrhagic stroke., Conclusions: AFF was a risk factor for all arterial and venous outcomes during the first year of follow-up, but only for peripheral embolism, ischemic stroke, and hemorrhagic stroke thereafter., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To examine the association between vagotomy and multiple sclerosis., Methods: We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis., Results: Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population., Interpretation: We found no association between vagotomy and later risk of late onset multiple sclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background The prognostic impact of previous depression on myocardial infarction survival remains poorly understood. Aims To examine the association between depression and all-cause mortality following myocardial infarction. Method Using Danish medical registries, we conducted a nationwide population-based cohort study. We included all patients with first-time myocardial infarction (1995-2014) and identified previous depression as either a depression diagnosis or use of antidepressants. We used Cox regression to compute adjusted mortality rate ratios (aMRRs) with 95% confidence intervals. Results We identified 170 771 patients with first-time myocardial infarction. Patients with myocardial infarction and a previous depression diagnosis had higher 19-year mortality risks (87% v. 78%). The overall aMRR was 1.11 (95% CI 1.07-1.15) increasing to 1.22 (95% CI 1.17-1.27) when including use of antidepressants in the depression definition. Conclusions A history of depression was associated with a moderately increased all-cause mortality following myocardial infarction., Competing Interests: Declaration of interestNone., (© The Royal College of Psychiatrists 2017.)

Background and Purpose: The long-term risk of specific stroke subtypes among heart failure patients is largely unknown. We examined short-term and long-term risk of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in heart failure patients and in a general population comparison cohort., Methods: In this nationwide cohort study (1980-2012), we used Danish population-based medical registries to identify and follow (1) all patients hospitalized for the first time with heart failure and (2) a birth year-, sex-, and calendar year-matched general population comparison cohort. Age-, sex-, and comorbidity-adjusted stroke rate ratios were computed based on Cox regression analysis., Results: We included 289 353 patients with heart failure and 1 446 765 individuals from the general population in the analysis. One- and 5-year risks among heart failure patients were 1.4% and 3.9% for ischemic stroke, 0.2% and 0.5% for ICH, and 0.03% and 0.07% for SAH. The 30-day adjusted stroke rate ratio was increased markedly for ischemic stroke (5.08; 95% confidence interval, 4.58-5.63] and was also elevated for ICH (2.13; 95% confidence interval, 1.53-2.97) and SAH (3.52; 95% confidence interval, 1.54-8.08). Between 31 days and 30 years, risk of all stroke subtypes remained positively associated with heart failure (1.5- to 2.1-fold for ischemic stroke, 1.4- to 1.8-fold for ICH, and 1.1- to 1.7-fold for SAH) in comparison with the general population cohort., Conclusions: Heart failure was associated with increased short-term and long-term risk of all stroke subtypes, suggesting that heart failure is a potent and persistent risk factor for ischemic stroke, ICH, and SAH., (© 2017 American Heart Association, Inc.)

Olfactory identification abilities in adolescents have been reported inferior compared with adults. Though this seems to be the case when comparing identification abilities using tests validated on-and for-adults, odor familiarity has been hypothesized to affect identification abilities in younger participants. However, this has never been thoroughly tested. The aims of this study were to investigate patterns in odor familiarity differences between adolescents and adults, and to investigate if an adolescent familiarity-based modification of an identification test could lead to similar identification scores in adolescents and adults. In total, 411 adolescent participants and 320 adult participants were included in the study. Odor familiarity ratings were obtained for 125 odors. A modified version of the "Sniffin' Sticks" identification test was created and validated on 72 adolescents based on adolescent familiarity scores. This test was applied to 82 normosmic adults and 167 normosmic adolescents. Results show a lower familiarity for spices and environmental odors, and a higher familiarity for candy odors in adolescents. The identification abilities in adults and adolescents were equal after familiarity-based modification. We conclude that changes in odor familiarity from adolescence to adulthood do not develop evenly for all odors, but are dependent on odor-object category., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Arterial and venous thromboembolism are common causes of morbidity and mortality in the Western world. Mental disorders are also highly prevalent with a lifetime risk of experiencing any psychiatric disease ranging between 32 % and 37 %. Depression and schizophrenia may increase the risk of thromboembolism through genetic, behavioral, and biological mechanisms. Treatment of psychiatric patients with psychotropic drugs is imperative to improve quality of life and to reduce morbidity and mortality. However, studies have shown that psychotropic drugs themselves may modify the risk of arterial and venous thromboembolism, which should be taken into consideration when using these drugs in clinical practice. This association is, however, multifactorial, complex and susceptible to several confounding factors. Psychotropic drugs are widely prescribed, also among patients with cardiovascular disease. Therefore, understanding the association with thromboembolism and the underlying pathophysiological mechanisms is of major importance and will be reviewed in this chapter.

Objective: Danish medical registries are widely used for cardiovascular research, but little is known about the data quality of cardiac interventions. We computed positive predictive values (PPVs) of codes for cardiac examinations, procedures and surgeries registered in the Danish National Patient Registry during 2010-2012., Design: Population-based validation study., Setting: We randomly sampled patients from 1 university hospital and 2 regional hospitals in the Central Denmark Region., Participants: 1239 patients undergoing different cardiac interventions., Main Outcome Measure: PPVs with medical record review as reference standard., Results: A total of 1233 medical records (99% of the total sample) were available for review. PPVs ranged from 83% to 100%. For examinations, the PPV was overall 98%, reflecting PPVs of 97% for echocardiography, 97% for right heart catheterisation and 100% for coronary angiogram. For procedures, the PPV was 98% overall, with PPVs of 98% for thrombolysis, 92% for cardioversion, 100% for radiofrequency ablation, 98% for percutaneous coronary intervention, and 100% for both cardiac pacemakers and implantable cardiac defibrillators. For cardiac surgery, the overall PPVs was 99%, encompassing PPVs of 100% for mitral valve surgery, 99% for aortic valve surgery, 98% for coronary artery bypass graft surgery, and 100% for heart transplantation. The accuracy of coding was consistent within age, sex, and calendar year categories, and the agreement between independent reviewers was high (99%)., Conclusions: Cardiac examinations, procedures and surgeries have high PPVs in the Danish National Patient Registry., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: Antithrombotic drugs are widely used in the prevention and treatment of cardiovascular diseases; yet, nationwide long-term usage trends remain unexplored. We examined long-term trends in the use of antithrombotic drugs in Denmark., Methods: Using nationwide prescription data, we obtained information on primary care use of antiplatelet drugs, vitamin K antagonists (VKA), non-vitamin K antagonist oral anticoagulants (NOAC), heparins and fondaparinux during 1999-2014., Results: During the 16-year period, the use of antithrombotic drugs per 1000 inhabitants/day increased from 64 to 96 defined daily doses (DDD), and the prevalence proportion of users doubled from 5.1% to 9.6% of the Danish population. From 1999 to 2014, there was an increased use of both antiplatelet drugs (from 60 to 79 DDD per 1000 inhabitants/day) and VKA (from 4 to 9 DDD per 1000 inhabitants/day). NOAC was marketed in 2008 and had an abrupt rise in use to 8 DDD per 1000 inhabitants/day in 2014. The use of heparins and fondaparinux increased slightly during the study period (from 0 to 0.6 DDD per 1000 inhabitants/day). Hospital use of antithrombotic drugs also increased during the study period, but constituted a minor part of the total use (4 DDD per 1000 inhabitants/day in 2014)., Conclusions: Considerable changes have occurred in the use of antithrombotic drugs during the past 16 years, including the introduction of several new and increasingly used treatment modalities such as NOAC. The trends in use of individual drugs correlate well with the publication of landmark studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: The majority of cardiovascular diagnoses in the Danish National Patient Registry (DNPR) remain to be validated despite extensive use in epidemiological research. We therefore examined the positive predictive value (PPV) of cardiovascular diagnoses in the DNPR., Design: Population-based validation study., Setting: 1 university hospital and 2 regional hospitals in the Central Denmark Region, 2010-2012., Participants: For each cardiovascular diagnosis, up to 100 patients from participating hospitals were randomly sampled during the study period using the DNPR., Main Outcome Measure: Using medical record review as the reference standard, we examined the PPV for cardiovascular diagnoses in the DNPR, coded according to the International Classification of Diseases, 10th Revision., Results: A total of 2153 medical records (97% of the total sample) were available for review. The PPVs ranged from 64% to 100%, with a mean PPV of 88%. The PPVs were ≥90% for first-time myocardial infarction, stent thrombosis, stable angina pectoris, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, takotsubo cardiomyopathy, arterial hypertension, atrial fibrillation or flutter, cardiac arrest, mitral valve regurgitation or stenosis, aortic valve regurgitation or stenosis, pericarditis, hypercholesterolaemia, aortic dissection, aortic aneurysm/dilation and arterial claudication. The PPVs were between 80% and 90% for recurrent myocardial infarction, first-time unstable angina pectoris, pulmonary hypertension, bradycardia, ventricular tachycardia/fibrillation, endocarditis, cardiac tumours, first-time venous thromboembolism and between 70% and 80% for first-time and recurrent admission due to heart failure, first-time dilated cardiomyopathy, restrictive cardiomyopathy and recurrent venous thromboembolism. The PPV for first-time myocarditis was 64%. The PPVs were consistent within age, sex, calendar year and hospital categories., Conclusions: The validity of cardiovascular diagnoses in the DNPR is overall high and sufficient for use in research since 2010., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The prevalence of depression is 4- to 5-fold higher in heart failure patients than in the general population. We examined the influence of depression on all-cause mortality in patients with heart failure., Methods and Results: Using Danish medical registries, this nationwide population-based cohort study included all patients with a first-time hospitalization for heart failure (1995-2014). All-cause mortality risks and 19-year mortality rate ratios were estimated based on Cox regression analysis, adjusting for age, sex, time period, comorbidity, and socioeconomic status. The analysis included 9636 patients with and 194 887 patients without a diagnosis of depression. Compared with patients without a history of depression, those with depression had higher 1-year (36% versus 33%) and 5-year (68% versus 63%) mortality risks. Overall, the adjusted mortality rate ratio was 1.03 (95% CI 1.01-1.06). Compared with no depression, the adjusted mortality rate ratios for mild, moderate, and severe depression, as defined by diagnostic codes, were 1.06 (95% CI 1.00-1.13), 1.03 (95% CI 0.99-1.08), and 1.02 (95% CI 0.96-1.09), respectively. In a subcohort of patients, the mortality rate ratios were modified by left ventricular ejection fraction, with adjusted mortality rate ratios of 1.17 (95% CI, 1.05-1.31) for ≤35%, 0.98 (95% CI 0.81-1.18) for 36% to 49%, and 0.96 (95% CI 0.74-1.25) for ≥50%. Results were consistent after adjustment for alcohol abuse and smoking., Conclusions: A history of depression was an adverse prognostic factor for all-cause mortality in heart failure patients with left ventricular ejection fraction ≤35% but not for other heart failure patients., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Purpose: Improved survival after myocardial infarction (MI) has increased the number of patients at risk of post-MI stroke. We examined risks of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in patients with MI compared with the general population., Methods: We conducted a nationwide population-based cohort study using Danish medical registries. During 1980 to 2009, we identified all patients with a first-time inpatient diagnosis of MI and formed a sex- and age-matched comparison cohort. We computed cumulative stroke risks and adjusted stroke rate ratios with 95% confidence intervals (CIs)., Results: We identified 258 806 patients with an MI and 1 244 773 individuals from the general population. For patients with MI, the cumulative stroke risks after 1 to 30 years were 12.6% for ischemic stroke, 1.2% for ICH, and 0.24% for SAH. During the first 30 days after MI, the adjusted stroke rate ratio was 30-fold increased for ischemic stroke (31.9; 95% CI, 28.4-35.8), 20-fold for ICH (21.8; 95% CI, 16.6-28.5), and 15-fold for SAH (16.6; 95% CI, 8.7-32.0). The adjusted stroke rate ratio remained increased during 31 to 365 days (3-fold for ischemic stroke, 2-fold for ICH, and 1.5-fold for SAH). During the ensuing 1 to 30 years, the risks remained increased for ischemic stroke (1.6; 95% CI, 1.6-1.6) but decreased to near unity for ICH (1.1; 95% CI, 1.0-1.2) and SAH (1.1; 95% CI, 0.94-1.2)., Conclusions: MI was a risk factor for all stroke subtypes during the first year of follow-up, but only for ischemic stroke thereafter., (© 2016 American Heart Association, Inc.)

Background and Purpose: The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH)., Methods: We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption ≤90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders., Results: We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30-day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09-1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality., Conclusions: Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH., (© 2016 American Heart Association, Inc.)

The paroxysmal supraventricular tachycardias (SVT) are commonly encountered arrhythmias and include atrioventricular nodal re-entrant tachycardia, atrioventricular reciprocating tachycardia, and focal atrial tachycardia. These tachycardias share several clinical features as well as similar management strategies. The probable mechanism of paroxysmal SVT can often be diagnosed from the clinical findings and a 12-lead ECG. This review describes the initial evaluation and treatment of patients with paroxysmal SVT, including distinctive features from the most important differential diagnoses.

A 64-year-old previously healthy woman consulted her general practitioner because of recurrent episodes of right-sided monocular transient visual loss (ie, amaurosis fugax). At first, these symptoms were followed over time, but as the attacks worsened, and were accompanied by dizziness and general discomfort, the patient was admitted to the department of neurology for further investigations. CT of the brain was normal; however, during admission, the patient developed rapid atrial fibrillation and was transferred to the department of cardiology. Transthoracic echocardiography revealed a massive tumour on the atrial side of the anterior mitral valve leaflet, partly obstructing the mitral valve inflow. The tumour was excised and a biological prosthetic mitral valve inserted. The tumour was histologically determined to be a highly malignant dedifferentiated chondrosarcoma. After 6 months, the tumour relapsed and expanded aggressively to completely obstruct the mitral valve inflow, ultimately leading to cardiac arrest and death., (2015 BMJ Publishing Group Ltd.)

Background: The prognostic impact of preadmission use of calcium channel blockers (CCBs) and beta blockers (BBs) on stroke mortality remains unclear. We aimed to examine whether preadmission use of CCBs or BBs was associated with improved short-term mortality following ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH)., Methods: We conducted a nationwide population-based cohort study using Danish medical registries. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012 and their comorbidities. We defined CCB/BB use as current use, former use, or non-use. Current use was further classified as new or long-term use. We used Cox regression modeling to compute 30-day mortality rate ratios (MRRs) with 95% confidence intervals (CIs), controlling for potential confounders., Results: We identified 100,043 patients with a first-time stroke. Of these, 83,736 (83.7%) patients had ischemic stroke, 11,779 (11.8%) had ICH, and 4,528 (4.5%) had SAH. Comparing current users of CCBs or BBs with non-users, we found no association with mortality for ischemic stroke [adjusted 30-day MRR = 0.99 (95% CI: 0.94-1.05) for CCBs and 1.01 (95% CI: 0.96-1.07) for BBs], ICH [adjusted 30-day MRR = 1.05 (95% CI: 0.95-1.16) for CCBs and 0.95 (95% CI: 0.87-1.04) for BBs], or SAH [adjusted 30-day MRR = 1.05 (95% CI: 0.85-1.29) for CCBs and 0.89 (95% CI: 0.72-1.11) for BBs]. Former use of CCBs or BBs was not associated with mortality., Conclusions: Preadmission use of CCBs or BBs was not associated with 30-day mortality following ischemic stroke, ICH, or SAH.

A 22-year-old woman recently diagnosed with granulomatosis with polyangiitis (GPA) was admitted to the department of cardiology due to chest pain and shortness of breath. The ECG showed widespread mild PR-segment depression, upwardly convex ST-segment elevation, and T-wave inversion. The troponin T level was elevated at 550 ng/L. Transthoracic echocardiography showed basal inferoseptal thinning and hypokinesis, mild pericardial effusion, and an overall preserved left ventricular ejection fraction of 55%. Global longitudinal strain, however, was clearly reduced. Cardiac magnetic resonance imaging (MRI) showed findings consistent with myocarditis but the etiology of the apical hypokinesis could not be determined with certainty and may well have been due to a myocardial infarction, a notion supported by a coronary angiogram displaying slow flow in the territory of the left anterior descending artery. Finally, an endomyocardial biopsy confirmed the diagnosis of myocarditis. The cardiac symptoms subsided upon treatment with high-dose prednisolone and rituximab.

A 67-year-old man underwent surgery under general anaesthesia to obtain a biopsy from a tumour in the left maxillary sinus. Before the procedure a mucosal detumescence containing epinephrine and cocaine was applied onto the nasal mucosa. Shortly after termination of anaesthesia the patient developed tachycardia and an abrupt rise in blood pressure followed by a drop to critical levels. The patient turned pale and clammy but denied chest pain at any time. An ECG showed inferolateral ST-segment elevation, and troponin T was elevated at 0.773 ng/mL. An acute coronary angiography demonstrated normal coronary arteries; however, left ventriculography showed apical ballooning of the left ventricle, and the diagnosis of takotsubo cardiomyopathy was made. This was confirmed by a subsequent transthoracic echocardiography. Four days later the patient had complete resolution of the symptoms, and a new echocardiography showed normalisation of the left ventricular systolic function with no signs of apical ballooning.