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Background: The risk of coronary heart disease associated with intake of individual trans fatty acids (TFAs) is not clear. Adipose tissue content of TFAs is a biomarker of TFA intake and metabolism. Objective: We investigated the rate of myocardial infarction (MI) associated with the adipose tissue content of total 18:1t, isomers of 18:1t (18:1 Δ6-10t and 18:1 Δ11t) and 18:2 Δ9c, 11t. Methods: A case-cohort study, nested within the Danish Diet, Cancer and Health cohort (n = 57,053), was conducted, which included a random sample (n = 3156) of the total cohort and all incident MI cases (n = 2148) during follow-up (14 years). Information on MI cases was obtained by linkage with nationwide registers and validated. Adipose tissue was taken from the participants buttocks and the fatty acid composition was determined by gas chromatography. Results: Women with higher adipose tissue content of total 18:1t had a 57% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.57; 95% confidence interval, 1.12–2.20; P-trend = 0.011) and women with higher content of 18:1 Δ6-10t had a 76% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.76; 95% confidence interval, 1.23–2.51; P-trend = 0.002). No association between 18:1 Δ11t content and MI rate was observed. In men, no associations between adipose tissue content of total 18:1t and 18:1 Δ6-10t and MI rate were observed. However, men with higher content of 18:1 Δ11t had a 48% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.48; 95% confidence interval, 1.17–1.86; P-trend = 0.003). Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men. Conclusions: Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men, whereas higher contents of isomers of 18:1t were associated with higher MI rates but the associations for individual 18:1t isomers differed, however, in women and men.

The objective of the present retrospective study was to assess long-term morbidity and postoperative complications after autogenous bone harvesting from the ascending mandibular ramus.Bone harvesting from the ascending mandibular ramus was conducted in a consecutive case series, including 325 patients, at The Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, Denmark from January 1, 2000 to December 31, 2010. Records and radiographs were retrospectively analyzed.Temporary neurosensory disturbances in the inferior alveolar nerve were found in 6.1% of the patients. Only 0.5% of the patients had permanent neurosensory disturbances. Severe hematoma occurred in 20 patients, while infection occurred in only 1 patient.Within the limitations of a retrospective case series study, the present study suggests that harvesting of autogenous bone from the ascending mandibular ramus is a safe surgical procedure with minimal donor site morbidity and few postoperative complications.

Aims The aim of this study was to investigate whether there is a similar mortality and thrombo-embolic risk, after an atrial ablation procedure, compared with an atrial fibrillation (AF) procedure. Methods and results Using data from nationwide Danish health registries, we identified patients aged 18–75 years undergoing a first-time atrial flutter or an AF ablation procedure in the period 2000–13. Cox proportional hazards regression was used to calculate hazard ratios (HRs) after 5 years of follow-up, adjusting for concomitant risk factors. A total of 1096 and 2266 patients underwent an ablation for atrial flutter or AF, respectively. Age distribution was similar in the two, but atrial flutter patients had more co-morbidities. During 5 years of follow-up, we observed 38 and 36 deaths in the atrial flutter and AF groups, corresponding to an almost two-fold higher mortality rate among atrial flutter patients [crude HR 1.92, 95% confidence interval (CI) 1.22–3.03]. The higher mortality rate persisted after adjustment for age, sex, diabetes mellitus, and hypertension (adjusted HR 1.68, 95% CI 1.05–2.69). The rate of thrombo-embolic events was similar in the two groups (crude HR 1.34, 95% CI 0.71–2.56; adjusted HR 1.22, 95% CI 0.62–2.41). Conclusion In this observational study, patients with atrial flutter had a significantly higher all-cause mortality rate compared with those with AF after an ablation procedure, but similar thrombo-embolic event rates. Future studies should elucidate the reason for this difference in mortality. [10.1093/europace/euw159][1] [1]: /lookup/doi/10.1093/europace/euw159

Background: Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. Methods: In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. Results: White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA2DS2VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). Conclusions: An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA2DS2VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence.

Background: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. Objective: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. Design: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. Results: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). Conclusion: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology. Am J Clin Nutr 2012;96:1354-61.

Principal component analysis (PCA) has been used extensively in the field of nutritional epidemiology to derive patterns that summarize food and nutrient intake, but interpreting it can be difficult. The authors propose the use of a new statistical technique, the treelet transform (TT), as an alternative to PCA. TT combines the quantitative pattern extraction capabilities of PCA with the interpretational advantages of cluster analysis and produces patterns involving only naturally grouped subsets of the original variables. The authors compared patterns derived using TT with those derived using PCA in a study of dietary patterns and risk of myocardial infarction among 26,155 male participants in a prospective Danish cohort. Over a median of 11.9 years of follow-up, 1,523 incident cases of myocardial infarction were ascertained. The 7 patterns derived with TT described almost as much variation as the first 7 patterns derived with PCA, for which interpretation was less clear. When the authors used multivariate Cox regression models to estimate relative risk of myocardial infarction, the significant risk factors were comparable whether the model was based on PCA or TT factors. The present study shows that TT may be a useful alternative to PCA in epidemiologic studies, leading to patterns that possess comparable explanatory power and are simple to interpret.

Background— Recent data suggest that β-blockers are associated with prognostic advantages in heart failure (HF) patients without concomitant atrial fibrillation (AF), but not in HF patients with concomitant AF. We aimed to investigate associations between β-blocker treatment and cardiovascular outcome and mortality in AF patients with and without HF. Methods and Results— Three nationwide registries were used to identify patients with nonvalvular AF patients with or without concomitant HF. Patients were stratified into β-blocker users and β-blocker nonusers, and according to the presence of a HF diagnosis. We followed the patients ≤5 years after baseline. Six different cardiovascular outcomes were investigated, including all-cause mortality and fatal thromboembolic events. Crude event rates were ascertained and propensity-matched Cox regression was used to compare event rates according to β-blocker usage status. A total of 205 174 patients were included, where 39 741 patients had prevalent HF. In the latter subgroup of patients, the 1-year propensity-matched hazard ratio (HR) for all-cause mortality was 0.75 (95% confidence interval, 0.71–0.79; nontreated used as reference). For patients without concomitant HF, the propensity-matched HR for all-cause mortality was 0.78 (95% confidence interval, 0.71–0.76). Conclusions— In this large nationwide cohort study, evidence of a lower mortality with β-blocker therapy in AF patients with concomitant HF was observed. In addition, this association was accompanied with indications that β-blocker treatment is also associated with a better prognosis in AF patients without concomitant HF.

BACKGROUND: Pulmonary embolism (PE) is associated with a higher long-term mortality than deep vein thrombosis (DVT). This association may be related to inadequate antithrombotic therapy.METHODS: Incident VTE patients during the period 1997-2012 were identified in Danish nationwide registries. Two landmark populations were defined, consisting of patients alive at 30days (30d), and at 180days (180d) after discharge. Patients were classified according to anticoagulant usage at the landmark (30d: prescription purchase 0-30d post-discharge; 180d: prescription purchase in 0-30d and 90-180d). Mortality rates were compared using multivariate Cox regression.RESULTS: The 30d mortality risk among PE patients was high compared to DVT patients (19.9% vs. 4.4%). In the 30d-landmark population (n=62695), 34.9% of DVT patients and 21.3% of PE patients had not redeemed a prescription for anticoagulants. There was no material difference in 10-year mortality between anticoagulated PE patients and anticoagulated DVT patients. There was a higher 10-year mortality rate among non-anticoagulated PE patients compared to anticoagulated DVT patients (MRR: 1.26, 95% CI: 1.20-1.33). Findings in the 180d-landmark population also indicated materially similar 10-year mortality rates between anticoagulated PE patients and anticoagulated DVT patients.CONCLUSIONS: The 10-year mortality rate of patients surviving the initial 30d critical period following incident PE was not increased compared to patients with incident DVT, as long as patients initiated and persisted with anticoagulant therapy. Increased focus on antithrombotic therapy in PE patients and reasons for early therapy discontinuation may be warranted.

OBJECTIVE: The risk of ischemic stroke, systemic thromboembolism, and all-cause death among heart failure patients previously diagnosed with diabetes mellitus is poorly described. We evaluated the risk of these endpoints among heart failure patients without diagnosed atrial fibrillation according to the presence of diabetes mellitus.METHODS: Population-based nationwide cohort study of non-anticoagulated patients diagnosed with incident heart failure during 2000-2012, identified by record linkage between nationwide registries in Denmark. We calculated relative risks after 1year to evaluate the association between diabetes and risk of events in 39,357 heart failure patients, among whom 18.1% had diabetes. Analysis took into account competing risks of death.RESULTS: Absolute risks of all endpoints were higher in patients with diabetes compared to patients without diabetes after 1-year follow-up (ischemic stroke: 4.1% vs. 2.8%; systemic thromboembolism: 11.9% vs. 8.6%; all-cause death: 22.1% vs. 21.4%). Diabetes was significantly associated with an increased risk of ischemic stroke (adjusted relative risk [RR]: 1.27, 95% confidence interval [CI]: 1.07-1.51); systemic thromboembolism (RR: 1.20, 95% CI: 1.11-1.30); and all-cause death (RR: 1.17, 95% CI: 1.11-1.23). Additionally, time since diabetes diagnosis was associated with higher adjusted cumulative incidences of ischemic stroke, systemic thromboembolism, and all-cause death (p for trend, pCONCLUSIONS: Among heart failure patients without atrial fibrillation, diabetes was associated with a significantly increased risk of ischemic stroke, systemic thromboembolism, and all-cause death compared to those without diabetes, even after adjustment for concomitant cardiovascular risk factors. Increased focus on secondary prevention in heart failure patients with diabetes may be warranted.

Unexplained chest/epigastric pain is a common symptom in the general population. However, it has not previously been studied whether such pain could be a marker of subsequent gastrointestinal cancer. We aimed to estimate the risk of gastrointestinal cancers in a Danish 10-year follow-up study among patients with chest/epigastric pain, normal upper endoscopy, and no prior discharge diagnosis of ischemic heart disease (N = 386), compared with population controls (N = 3860). The overall 10-year risk of gastrointestinal cancer (stomach, colorectal, liver, and pancreas) was 2.9% for patients with unexplained chest/epigastric pain vs. 1.5% for controls. The adjusted relative risks or =1 year after upper endoscopy were 8.4 (95% confidence interval [CI], 2.6-27.5) and 1.2 (95% CI, 0.5-2.9), respectively. We found that patients with unexplained chest/epigastric pain have an increased risk of gastrointestinal cancer within the first year after upper endoscopy. Consequently, unexplained chest/epigastric pain might be an early gastrointestinal cancer symptom.

Background and Purpose—The CHA2DS2VASc score and the Essen Stroke Risk Score are respectively used for risk stratification in patients with atrial fibrillation and in patients with cerebrovascular incidents. We aimed to test the ability of the 2 scores to predict stroke recurrence, death, and cardiovascular events (stroke, transient ischemic attack, myocardial infarction, or arterial thromboembolism) in a nationwide Danish cohort study, among patients with incident ischemic stroke and no atrial fibrillation.Methods—We conducted a registry-based study in patients with incident ischemic stroke and no atrial fibrillation. Patients were stratified according to the CHA2DS2VASc score and the Essen Stroke Risk Score and were followed up until stroke recurrence or death. We estimated stratified incidence rates and hazard ratios and calculated the cumulative risks.Results—42 182 patients with incident ischemic stroke with median age 70.1 years were included. The overall 1-year incidence rates of recurrent stroke, death, and cardiovascular events were 3.6%, 10.5%, and 6.7%, respectively. The incidence rates, the hazard ratios, and the cumulative risk of all outcomes increased with increasing risk scores. C-statistics for both risk scores were around 0.55 for 1-year stroke recurrence and cardiovascular events and correspondingly for death around 0.67 for both scores.Conclusions—In this cohort of non–atrial fibrillation patients with incident ischemic stroke, increasing CHA2DS2VASc score and Essen Stroke Risk Score was associated with increasing risk of recurrent stroke, death, and cardiovascular events. Their discriminatory performance was modest and further refinements are required for clinical application. BACKGROUND AND PURPOSE: The CHA2DS2VASc score and the Essen Stroke Risk Score are respectively used for risk stratification in patients with atrial fibrillation and in patients with cerebrovascular incidents. We aimed to test the ability of the 2 scores to predict stroke recurrence, death, and cardiovascular events (stroke, transient ischemic attack, myocardial infarction, or arterial thromboembolism) in a nationwide Danish cohort study, among patients with incident ischemic stroke and no atrial fibrillation.METHODS: We conducted a registry-based study in patients with incident ischemic stroke and no atrial fibrillation. Patients were stratified according to the CHA2DS2VASc score and the Essen Stroke Risk Score and were followed up until stroke recurrence or death. We estimated stratified incidence rates and hazard ratios and calculated the cumulative risks.RESULTS: 42 182 patients with incident ischemic stroke with median age 70.1 years were included. The overall 1-year incidence rates of recurrent stroke, death, and cardiovascular events were 3.6%, 10.5%, and 6.7%, respectively. The incidence rates, the hazard ratios, and the cumulative risk of all outcomes increased with increasing risk scores. C-statistics for both risk scores were around 0.55 for 1-year stroke recurrence and cardiovascular events and correspondingly for death around 0.67 for both scores.CONCLUSIONS: In this cohort of non-atrial fibrillation patients with incident ischemic stroke, increasing CHA2DS2VASc score and Essen Stroke Risk Score was associated with increasing risk of recurrent stroke, death, and cardiovascular events. Their discriminatory performance was modest and further refinements are required for clinical application.

Importance: The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is used clinically for stroke risk stratification in atrial fibrillation (AF). Its usefulness in a population of patients with heart failure (HF) is unclear.Objective: To investigate whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in a cohort of patients with HF with and without AF.Design, Setting, and Population: Nationwide prospective cohort study using Danish registries, including 42 987 patients (21.9% with concomitant AF) not receiving anticoagulation who were diagnosed as having incident HF during 2000-2012. End of follow-up was December 31, 2012.Exposures: Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk), stratified by concomitant AF at baseline. Analyses took into account the competing risk of death.Main Outcomes and Measures: Ischemic stroke, thromboembolism, and death within 1 year after HF diagnosis.Results: In patients without AF, the risks of ischemic stroke, thromboembolism, and death were 3.1% (n = 977), 9.9% (n = 3187), and 21.8% (n = 6956), respectively; risks were greater with increasing CHA2DS2-VASc scores as follows, for scores of 1 through 6, respectively: (1) ischemic stroke with concomitant AF: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%; without concomitant AF: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7% and (2) all-cause death with concomitant AF: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%; without concomitant AF: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%. At high CHA2DS2-VASc scores (≥4), the absolute risk of thromboembolism was high regardless of presence of AF (for a score of 4, 9.7% vs 8.2% for patients without and with concomitant AF, respectively; overall PConclusions and Relevance: Among patients with incident HF with or without AF, the CHA2DS2-VASc score was associated with risk of ischemic stroke, thromboembolism, and death. The absolute risk of thromboembolic complications was higher among patients without AF compared with patients with concomitant AF at high CHA2DS2-VASc scores. However, predictive accuracy was modest, and the clinical utility of the CHA2DS2-VASc score in patients with HF remains to be determined.

To evaluate effectiveness and safety of rivaroxaban versus warfarin or dabigatran etexilate in a prospective cohort of routine care non-valvular atrial fibrillation (AF) patients during February 2012 to August 2014.We identified in nationwide health registries a cohort of AF patients who were new-users of rivaroxaban 15 mg (R15) or 20 mg (R20); dabigatran 110 mg (D110) or 150 mg (D150); or warfarin. Propensity-adjusted Cox regression was used to compare outcome rates in four settings: 'R15 vs. warfarin'; 'R15 vs. D110'; 'R20 vs. warfarin'; and 'R20 vs. D150'.Rivaroxaban users (R15: n = 776; R20: n = 1629) were older and with more comorbidities than warfarin (n = 11 045) and dabigatran users (D110: n = 3588; D150: n = 5320). Rivaroxaban 15-mg users had the overall highest crude mortality rate. After propensity adjustment, rivaroxaban had lower stroke rates vs. warfarin (R15: hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.26-0.82; R20 HR: 0.72, 95%CI: 0.51-1.01), and similar stroke rates vs. dabigatran. The bleeding rate was similar to warfarin and moderately higher vs. dabigatran (R15 vs. D110 HR: 1.28, 95%CI: 0.82-2.01; R20 vs. D150 HR: 1.81, 95%CI: 1.25-2.62). The mortality rate was higher vs. dabigatran (R15 vs. D110 HR: 1.43, 95%CI: 1.13-1.81; R20 vs. D150 HR: 1.52, 95%CI: 1.06-2.19).Rivaroxaban was associated with similar or lower stroke rates, but higher bleeding and mortality rates. Channeling of rivaroxaban towards elderly and less healthy patients may have generated residual confounding. In particular, our findings cannot stand alone when deciding which oral anticoagulant to prescribe. Copyright © 2016 John WileySons, Ltd.

Background: Several population-based studies have reported blood glucose levels and blood pressure to be risk factors for the development of diabetic retinopathy. These studies were initiated more than two decades ago and may therefore reflect the treatment and population composition of a previous era, suggesting new studies of the present population with diabetes. Aim and methods: This cross-section study included 656 people with type 1 diabetes and 328 with type 2 diabetes. Crude prevalence rates of proliferative diabetic retinopathy, clinically significant macular oedema and several specific retinal lesions were assessed, together with their association to a simplified and internationally approved retinal grading. Results: The point prevalence of proliferative retinopathy was found to be 0.8% and 0.3% for type 1 and type 2 diabetes. Equivalent prevalence rates of clinically significant macular oedema were 7.9% and 12.8%, respectively. The most frequently occurring retinal manifestations increased in number until retinopathy level 3, and then decreased. Conclusion: The point prevalence of proliferative retinopathy is lower than that found in previous studies, whereas it is increased for clinically significant macular oedema. These data suggest different risk factors for these clinical entities. Background: Several population-based studies have reported blood glucose levels and blood pressure to be risk factors for the development of diabetic retinopathy. These studies were initiated more than two decades ago and may therefore reflect the treatment and population composition of a previous era, suggesting new studies of the present population with diabetes. Aim and methods: This cross-section study included 656 people with type 1 diabetes and 328 with type 2 diabetes. Crude prevalence rates of proliferative diabetic retinopathy, clinically significant macular oedema and several specific retinal lesions were assessed, together with their association to a simplified and internationally approved retinal grading. Results: The point prevalence of proliferative retinopathy was found to be 0.8% and 0.3% for type 1 and type 2 diabetes. Equivalent prevalence rates of clinically significant macular oedema were 7.9% and 12.8%, respectively. The most frequently occurring retinal manifestations increased in number until retinopathy level 3, and then decreased. Conclusion: The point prevalence of proliferative retinopathy is lower than that found in previous studies, whereas it is increased for clinically significant macular oedema. These data suggest different risk factors for these clinical entities.

Surgical innovations are often introduced for their expected long-term benefits, but the decision to abandon the existing treatment must be based on the available short-term data and rational judgment. We present a framework for monitoring the introduction of a surgical intervention with long-term consequences and failure-time endpoints. The framework is based on Bayesian methods, and formally combines study data, clinical opinion, and external evidence to construct a posterior survival function from which intuitive summary statistics can be extracted to aid decision making. It incorporates learning effects and is adaptable to a wide variety of settings. The methods are illustrated on survival data from a cohort of 325 consecutive neonates treated for simple transposition of the great arteries with either the Senning or the Switch operation during the period 1978-1998. Udgivelsesdato: FEB 10 Surgical innovations are often introduced for their expected long-term benefits, but the decision to abandon the existing treatment must be based on the available short-term data and rational judgment. We present a framework for monitoring the introduction of a surgical intervention with long-term consequences and failure-time endpoints. The framework is based on Bayesian methods, and formally combines study data, clinical opinion, and external evidence to construct a posterior survival function from which intuitive summary statistics can be extracted to aid decision making. It incorporates learning effects and is adaptable to a wide variety of settings. The methods are illustrated on survival data from a cohort of 325 consecutive neonates treated for simple transposition of the great arteries with either the Senning or the Switch operation during the period 1978-1998.

Summary Background There is a perception among physicians that lack of routine monitoring with non-vitamin K antagonist oral anticoagulants (NOACs) may lead to poor adherence to medication. We studied adherence during the first year of usage in a cohort of patients with newly diagnosed non-valvular atrial fibrillation (AF) started on the NOAC, dabigatran etexilate. Methods and results Nationwide Danish patient and prescription purchase registries were used to identify newly diagnosed AF patients taking dabigatran, comorbidities, and refill patterns under a twice-daily, one pill regimen. Adherence was characterized among remaining users (N = 2960) after 1 year using the proportion of days covered (PDC), gap rates and restart rates. The overall 1-year PDC was 83.9%, with 76.8% of patients having a 1-year PDC in excess of 80%. Patients with a CHA2DS2-VASc score ≥ 2 were more adherent to medication regimes than patients with a CHA2DS2-VASc score of 1 (PDC ratio, 1.12; 95% confidence interval [CI], 1.08–1.17) and generally patients with higher morbidity showed more adherence. Patients with prior bleeding were not less adherent to medication regimes than patients with no prior bleeding (PDC ratio, 1.02; 95% CI, 0.98–1.06). The overall gap rate was 1.4 gaps per year. There were no clear tendencies in gap rates among subgroups, although patients with higher morbidity tended to have slightly more, but shorter, gap periods. Conclusions More than 75% of patients were showed > 80% adherence to medication regimes during the first year. Patients with higher morbidity, including patients with a higher risk of stroke or bleeding, exhibited better adherence. This improvement may be attributable to more regular contact with the healthcare system.

Background— Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Methods and Results— Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39–0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33–1.03) and 0.55 (95% confidence interval, 0.37–0.82), respectively. Conclusions— Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients.

The risk of ischemic stroke/thromboembolic events after an intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) who are on warfarin treatment is poorly characterized. The aim of this study was to assess the association between the risk of ischemic stroke/thromboembolic events and ICH.Linkage of three Danish nationwide administrative registries in the period between 1999 and 2012 identified patients with AF on warfarin treatment. Event-rate ratios of stroke/thromboembolic events, major bleeding, and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched OR was calculated for ICH occurrences within 0 to 3 months relative to the 3 to 6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.We studied 58,815 patients with AF (median age, 72.6 years; 60% men). When compared with the non-ICH group, the ICH group was at increased risk for stroke/systemic embolism/transient ischemic attack (TIA) (rate ratio, 3.67; 95% CI, 3.12-4.31) and mortality (rate ratio, 5.55; 95% CI, 5.20-5.92), but not for major bleeding (rate ratio, 1.06; 95% CI, 0.81-1.39). The matched OR of ICH occurrences prior to a stroke/systemic embolism/TIA was 4.33 (95% CI, 2.44-8.15). The rate ratio of claimed warfarin prescriptions post- and pre-ICH event was 0.28 (95% CI, 0.24-0.33).In this large-scale study of patients with AF treated with warfarin, first-time ICH was associated with an increased rate of ischemic stroke/systemic embolism/TIA and mortality compared with the non-ICH group. There was a decrease in the warfarin-prescription purchase rate in the post-ICH period compared with pre-ICH, which may partly explain the excess risk.

INTRODUCTION: The mental health prognosis following a venous thromboembolism in youth has not been investigated comprehensively. Using psychotropic drug purchase as a proxy for mental health status, we investigated this issue in a large cohort of young incident venous thromboembolism patients.METHODS: Using Danish nationwide administrative registries from the period 1997-2010, we identified 4,132 patients aged 13-33 years with a first-time venous thromboembolism diagnosis and no history of psychotropic drug usage. We sampled comparison cohort of random general population controls, matched individually in a 1:5 ratio based on sex and birth year. Participants were followed in prescription purchase registries for their first psychotropic drug purchase.RESULTS: Among young venous thromboembolism case cases, the 1-year risk of psychotropic drug purchase was 7.1% (95% confidence interval [CI] 6.3, 7.9) and the 5-year risk 22.1% (95% CI 20.7, 23.5). This was substantially higher than among population controls, with 1- and 5-year risk differences relative to the controls of 4.7% (95% CI 3.9, 5.5), and 10.8% (95% CI 9.4, 12.3), respectively. Adjustment for the effects of recent pregnancy or somatic provocations attenuated risk differences to 4.1% (95% CI 3.5, 5.1) after 1year and 9.6% (95% CI 8.3, 11.2) after 5years.CONCLUSIONS: A venous thromboembolism diagnosis in youth is associated with a poorer mental health prognosis: one in five patients are prescribed psychotropic medication within the first 5year after diagnosis.

Background This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both "new starters" on dabigatran and "switchers" to dabigatran from warfarin. Methods We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments. Results Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15). Conclusions In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.

Background/Objectives:The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR).Subjects/Methods:This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression.Results:After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours.Conclusions:No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.European Journal of Clinical Nutrition advance online publication, 19 March 2014; doi:10.1038/ejcn.2014.28.

Dabigatran may provide less protection against myocardial infarction than vitamin K antagonists (VKAs) in patients with atrial fibrillation. This may be particularly evident among "switchers" to dabigatran from VKA, as a result of discontinuation effects.We identified in nationwide Danish registries a cohort of VKA-naïve "new starters" on dabigatran (110 mg twice daily [bid] and 150 mg bid dose regimes) or warfarin, and a cohort of prior VKA-experienced "switchers" to dabigatran or "continuers" on warfarin. Cohorts were followed for an average of 16.0 months. Adjusted Cox regression models were used to compare event rates. Relative to warfarin, there was a nonsignificant trend to lower myocardial infarction rates with dabigatran among VKA-naïve users (110 mg hazard ratio [HR] 0.71; 95% confidence interval [CI], 0.47-1.07; 150 mg HR 0.94; 95% CI, 0.62-1.41); however, there was a nonsignificant trend to increased myocardial infarction rates among prior VKA-experienced users (110 mg HR 1.45; 95% CI, 0.98-2.15; 150 mg HR 1.30; 95% CI 0.84-2.01). An increased myocardial infarction rate relative to warfarin among prior VKA-experienced users was clearly significant during the early follow-up period of60 days (110 mg HR 3.01; 95% CI, 1.48-6.10; 150 mg HR 2.97; 95% CI, 1.31-6.73). Comparable results were obtained for a composite end point (myocardial infarction, unstable angina, or cardiac arrest) among both VKA-naïve and prior VKA-experienced users.In this large-scale nationwide cohort study, we found that switching to dabigatran increased the risk of myocardial infarction compared with continued warfarin usage in the early period after switching. Caution may be warranted, especially when switching prior VKA-experienced patients with atrial fibrillation to dabigatran.

Objective The primary aim of the study was to evaluate the association between adipose tissue arachidonic acid (AA) content and the risk of myocardial infarction (MI). The secondary aim was to assess the correlation between adipose tissue AA and dietary intake of AA and linoleic acid (LA). Methods We conducted a case-cohort study nested within the Danish prospective Diet, Cancer and Health (DCH) study. After appropriate exclusions, the study included 2134 incident MI cases. Gluteal adipose tissue biopsies were collected at recruitment, and the fatty acid composition was determined by gas chromatography. A weighted Cox proportional hazards model was used to evaluate the association between adipose tissue AA content and the risk of MI. Results After adjusting for confounders we found a positive association between adipose tissue AA content and the risk of MI. Hazard ratios (HR) of MI relative to the lowest quintile of adipose tissue AA content, increased across quintiles; second quintile (HR 1.19 95%CI: 0.97–1.45), third (HR 1.24 95%CI: 1.02–1.52), fourth (HR 1.28 95%CI: 1.03–1.60), and fifth quintile (HR 1.39 95%CI: 1.10–1.77). Adipose tissue AA levels were not correlated with dietary intake of AA ( r =0.03, 95%CI: −0.01, 0.06) and weakly negatively correlated with dietary intake of LA ( r =−0.12, 95%CI: −0.15, −0.08). Conclusions The adipose tissue content of AA was positively associated with the risk of MI but did not correlate with dietary intake of neither AA nor LA.

BACKGROUND: Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).METHODS: Population-based cohort study of patients diagnosed with incident heart failure during 2000-2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.RESULTS: 39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08-1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35-1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86-1.15 and 0.94, 95% CI: 0.89-1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.CONCLUSIONS: Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.

Purpose. To compare patients with increased risk of bleeding who received combined blood reinfusion and femoral nerve block in total knee replacement (TKR) to regular patients treated routinely with respect to pain relief, blood loss, and knee function. Methods. In a consecutive series of 67 patients who underwent unilateral TKR, 12 patients with increased risk of bleeding owing to cardiac disease or previous thromboembolic events received continuous femoral nerve block and blood reinfusion, without tranexamic acid (TA) injection. The remaining 55 patients were controls who received standard postoperative treatment (TA injection, local injection of analgesics, and suction drainage without reinfusion). The volume of blood loss (drained or reinfused), pain score (using a visual analogue scale) and knee function (using the Knee Society Score [KSS]) in the 2 groups were compared. Results. In the study group, patients were 5 years older and tended to have a lower preoperative KSS function score (35 vs. 45, p=0.08) and a higher function-related pain score (6.5 vs. 6, p=0.10). The mean volume of drained blood wasted in the study group did not differ significantly from the mean total volume of drained blood in the control group (235 vs. 300 ml, p=0.14). Similarly, the mean decrease in postoperative haemoglobin concentration did not differ significantly between the respective groups (2.1 vs. 2.1 mmol/l, p=0.97). A significantly greater proportion of patients received allogenic blood transfusion in the study group than in controls (3/12 vs. 2/55, pConclusion. In TKR patients with increased risk of bleeding, blood reinfusion combined with femoral nerve block is safe and comparable to standard methods of pain control (local injection of analgesics).

IntroductionDiets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissue fatty acids and changes in anthropometry.Methods34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WC(BMI)), adjusting for confounders.Results7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men and women, respectively. Fatty acid patterns with high levels of TFA tended to be positively associated with changes in weight and WC for both sexes. Patterns with high levels of n-6 LC-PUFA tended to be negatively associated with changes in weight and WC in men, and positively associated in women. Associations with patterns with high levels of n-3 LC-PUFA were dependent on the context of the rest of the fatty acid pattern.ConclusionsAdipose tissue fatty acid patterns with high levels of TFA may be linked to weight gain, but patterns with high n-3 LC-PUFA did not appear to be linked to weight loss. Associations depended on characteristics of the rest of the pattern.

The purpose was to elucidate the association between parity and the incidence of diabetes using national register data.The study population consisted of all Danish women with a singleton delivery in 1982/1983 (n = 100,669), who subsequently had 74,966 deliveries. The included women were followed up via registries until the end of 2006 for subsequent deliveries, diagnosis of diabetes and death/emigration.A total of 2021 cases (2.0%) were diagnosed with diabetes in connection with hospitalization or outpatient treatment during follow-up. Analyses were adjusted for fetal weight and duration of gestation, both at index pregnancy. Cox regression analysis with parity as a time-varying exposure, stratified in two age groups, showed an association between parity and risk of a diagnosis of diabetes. In women33 years of age, parity 2, 3 and 4 + were associated with an increased risk of being diagnosed with diabetes compared with parity 1 [relative risks: 1.6 (95% confidence interval 1.1-2.3), 2.8 (1.8-4.3) and 2.5 (1.3-4.8), respectively]. Among women33 years of age, parity 2 was associated with a significantly lower risk of diabetes diagnosis compared with parity 1, whereas parity 4 + was associated with a significantly higher risk of diabetes diagnosis compared with parity 1.The study shows that the risk of diabetes diagnosis increases with parity in young Danish women. This may support a causal association between diabetes and parity.

Aim: Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have shown markedly elevated levels of NT-pro-BNP in patients with ESRD, while the prognostic value of elevated levels of NT-pro-BNP in patients with ESRD is largely unknown. The aim of the present study was to examine if the level of NT-pro-BNP predicts mortality in patients with ERSD and CVD. Methods: We prospectively followed 206 patients with ESRD and documented CVD. Levels of NT-pro-BNP were measured at baseline, and patients were followed for 2 years or until they reached the predefined endpoint of all-cause mortality. Results: During follow-up, the total mortality was 44% (90/206). Patients who died were followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut off value for NT-pro-BNP was determined. Patients with values of NT-pro-BNP above 12.200 pg/ml had a 3 times higher risk of death than patients below the cut-off value (HR 3.05 95% CI 1.96 - 4.77, p < 0.0001). Conclusion: In spite of generally elevated levels of NT-pro-BNP, NT-pro-BNP is still an independent predictor of mortality and might add prognostic information in patients with ESRD and documented CVD. Aim: Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have shown markedly elevated levels of NT-pro-BNP in patients with ESRD, while the prognostic value of elevated levels of NT-pro-BNP in patients with ESRD is largely unknown. The aim of the present study was to examine if the level of NT-pro-BNP predicts mortality in patients with ERSD and CVD. Methods: We prospectively followed 206 patients with ESRD and documented CVD. Levels of NT-pro-BNP were measured at baseline, and patients were followed for 2 years or until they reached the predefined endpoint of all-cause mortality. Results: During follow-up, the total mortality was 44% (90/206). Patients who died were followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut off value for NT-pro-BNP was determined. Patients with values of NT-pro-BNP above 12.200 pg/ml had a 3 times higher risk of death than patients below the cut-off value (HR 3.05 95% CI 1.96 - 4.77, p < 0.0001). Conclusion: In spite of generally elevated levels of NT-pro-BNP, NT-pro-BNP is still an independent predictor of mortality and might add prognostic information in patients with ESRD and documented CVD.

No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy.To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients.This Danish 10-year cohort study focused on UCEP patients (n = 386), diagnosed in 1992-93. Ten age- and gender-matched controls were selected per patient from Denmark's Civil Registration System (n = 3860). Kaplan-Meier analysis and Cox's regression analysis was used to calculate the risk of hospitalization for peptic ulcer, oesophagitis, pancreatitis or gallstone.Compared with controls, the adjusted relative risks among UCEP patients1 andor = 1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and 1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.2-59.2) and 1.9 (95% CI 0.7-5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8).UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or gallstone could be underlying early UCEP symptoms. However, the long-term association remained strong for pancreatitis and gallstone, suggesting a genuine excess risk.

BACKGROUND: No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy. AIM: To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients. METHODS: This Danish 10-year cohort study focused on UCEP patients (n = 386), diagnosed in 1992-93. Ten age- and gender-matched controls were selected per patient from Denmark's Civil Registration System (n = 3860). Kaplan-Meier analysis and Cox's regression analysis was used to calculate the risk of hospitalization for peptic ulcer, oesophagitis, pancreatitis or gallstone. RESULTS: Compared with controls, the adjusted relative risks among UCEP patients or = 1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and 1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.2-59.2) and 1.9 (95% CI 0.7-5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8). CONCLUSIONS: UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or gallstone could be underlying early UCEP symptoms. However, the long-term association remained strong for pancreatitis and gallstone, suggesting a genuine excess risk.

BACKGROUND: Stroke in patients with heart failure is associated with poor outcomes. Risk stratification schemes may improve clinical decision making in this patient population. This study investigated whether female sex is a risk factor for stroke in patients with heart failure in sinus rhythm.METHODS: This is a population-based cohort study of patients diagnosed with heart failure during 2000 to 2012, identified by record linkage between nationwide Danish registries. Our primary outcome was stroke, and secondary outcome was thromboembolic event. We used relative risks (RRs) after 1 and 5 years to compare males with females within each of the following age groups: 50 to 59 years, 60 to 69 years, 70 to 79 years, 80 to 89 years, and 90+ years. Analyses took into account the competing risks of death.RESULTS: During the study period, 84,142 patients were diagnosed with heart failure, of which 39,946 (47.5%) were females. At 5-year follow-up, female sex was associated with a lower risk of stroke compared with males (adjusted overall hazard ratio 0.91, 95% CI 0.85-0.96). The observed lower risks of stroke in females were not present in the older age groups, where the competing risk of death was substantial among males in particular. When considering a more broadly defined thromboembolic end point, a decreased risk among females persisted across nearly all age groups after 5-year follow-up (adjusted overall hazard ratio 0.93, 95% CI 0.91-0.96).CONCLUSIONS: We found an association between female sex and decreased stroke risk in patients with heart failure, which persisted after adjustment for concomitant cardiovascular risk factors. The association was attenuated with increasing age, possibly because of competing risks of death.

Background The bleeding risk among patients with atrial fibrillation is higher early after initiating therapy with vitamin K antagonists (VKAs). Evidence is limited on how prior VKA experience affects bleeding risk when initiating novel oral anticoagulant therapy. We investigated this among patients with atrial fibrillation initiating dabigatran therapy. Methods By using nationwide Danish prescription and patient registries, we identified 11,315 first-time dabigatran users with atrial fibrillation. Warfarin controls were matched in a 2:1 ratio according to VKA experience status. The average follow-up time was 13 months. Across the 6 combinations of treatment (dabigatran 110 mg, dabigatran 150 mg, and warfarin) and VKA experience status (naive or experienced), VKA-naive warfarin initiators had the highest rate of any bleeding event. Cox regressions adjusted for baseline characteristics showed reductions relative to this group ranging from 19% for VKA-experienced dabigatran 110 mg users (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-1.00) to 41% for VKA-experienced dabigatran 150 mg users (HR, 0.59; 95% CI, 0.46-0.75). Among switchers to dabigatran from warfarin, when comparing with warfarin-persisting users, the rate of any bleeding was nonsignificantly decreased for switchers to dabigatran 150 mg (HR, 0.80; 95% CI, 0.62-1.03) but not for switchers to dabigatran 110 mg (HR, 1.12; 95% CI, 0.90-1.41). Results for major bleeding were similar. Crude rates of fatal, intracranial, and gastrointestinal bleeding were low. Conclusions VKA-naive warfarin initiators had the highest overall bleeding rate. We found no evidence of marked excess of overall bleeding events when comparing dabigatran with warfarin users, irrespective of prior VKA experience.