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Aims: To assess the level of adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment using real-world data and to investigate the sociodemographic and clinical factors associated with discontinuation of GLP-1RAs., Methods: First-time users of GLP-1RAs with type 2 diabetes mellitus (T2DM), aged ≥18 years, in the period 2007 to 2020, were identified using Danish registries, allowing all participants a minimum of 18 months' follow-up. Adherence to GLP-1RA therapy (medication possession ratio >0.80) and discontinuation of GLP-1RA therapy was estimated at 6- and 12-month follow-ups. Multivariable cause-specific Cox regression was used to identify sociodemographic and clinical factors associated with risk of discontinuation., Results: In total, 44 343 first-time users of GLP-1RAs with T2DM were identified (mean age 58.6 years, 42.7% female, median duration of T2DM 6.8 years, median glycated haemoglobin level 65 mmol/mol). The absolute risk of discontinuing GLP-1RA treatment within 6 months was 14.2% (95% confidence interval [CI] 13.9-14.6) and 21.2% (95% CI 20.8-21.5) within 12 months. At 6 months, 50.4% were adherent to GLP-1RA therapy and at 12 months, 48.6% remained adherent. In the multivariable model, younger (<40 years) and older age (>75 years), higher Charlson Comorbidity Index score, lower household income, high school and longer university degree as educational attainment level, and longer diabetes duration were associated with a higher risk of discontinuing GLP-1RA treatment., Conclusion: Approximately one in five patients discontinued GLP-1RA therapy within the first 12 months and only half were adherent. Overall, lower socioeconomic status and higher comorbidity burden were associated with higher risk of discontinuing GLP-1RA treatment., (© 2024 John Wiley & Sons Ltd.)

Background: Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events., Methods and Results: Using Danish nationwide registries, all patients with first-time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis-to-ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90-day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5-year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07-1.35), 1.29 (95% CI, 1.13-1.47), and 1.40 (95% CI, 1.28-1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04-1.44) in the late ablation group compared with the early ablation group., Conclusions: In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early-compared with late-ablation patients.

Background: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time., Methods and Results: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80-2.39] and 2.93 [95% CI, 2.40-3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14-2.80] and 2.86 [95% CI, 2.32-3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33-3.10] and 3.30 [95% CI, 2.69-4.06] in 2012 to 2016)., Conclusions: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events.

Purpose: Layer-specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer-specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD., Methods: We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer-specific (endocardial-, whole-layer-, and epicardial-) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer-specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression., Results: Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS < 400 (endocardial GLS: -20.5 vs. -22.7%, whole-layer GLS: -17.7 vs. -19.4%, epicardial GLS: -15.3 vs. -16.9%, p < .001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR = 1.11 (1.03-1.20); whole-layer GLS: OR = 1.14 (1.04-1.24); epicardial GLS: OR = 1.16 (1.05-1.29), per 1% absolute decrease)., Conclusion: In this study population with patients suspected of CAD and normal systolic function, impaired layer-specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS., (© 2024 Wiley Periodicals LLC.)

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

Aim: To investigate the association between previous periodontal treatment and recurrent events after first-time myocardial infarction (MI)., Materials and Methods: From the Danish nationwide registries, patients with first-time MI between 2000 and 2015 were divided into three groups according to oral health care within 1 year prior to first-time MI. A multiple logistic regression model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to assess the 3-year risk of major adverse cardiovascular events (MACE)., Results: A total of 103,949 patients were included. Patients with treated periodontitis (PD) prior to first-time MI had an adjusted 3-year risk of MACE similar to patients presumed periodontally healthy (OR 0.97 [95% CI 0.92-1.03]). Patients with no prior dental visits were significantly older, had more comorbidities and showed significantly increased adjusted 3-year risks of MACE (OR 1.47 [95% CI 1.42-1.52]), cardiovascular death (OR 1.71 [95% CI 1.64-1.78]) and heart failure (OR 1.13 [95% CI 1.07-1.20]) compared with patients presumed periodontally healthy., Conclusions: Patients with treated PD 1 year prior to first-time MI had a similar risk of recurrent cardiovascular events as patients presumed periodontally healthy. No dental visit prior to first-time MI was an independent risk factor for recurrent events., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

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

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

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P =0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Aims: We aimed to evaluate the effect of acute hyperglycaemia and hypoglycaemia on cardiac function in patients with type 2 diabetes (T2D) and a control group., Materials and Methods: In a nonrandomized interventional study, insulin-treated patients with T2D (N = 21, mean ± SD age 62.8 ± 6.5 years, body mass index [BMI] 29.0 ± 4.2 kg/m 2 , glycated haemoglobin [HbA1c] 51.0 ± 5.4 mmol/mol [6.8 ± 0.5%]) and matched controls (N = 21, mean ± SD age 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m 2 , HbA1c 34.3 ± 3.3 mmol/L [5.3 ± 0.3%]) underwent one experimental day with plasma glucose (PG) clamped at three different 30-minute steady-state levels: (1) fasting plasma glucose (FPG); (2) hyperglycaemia (FPG + 10 mmol/L); and (3) hyperinsulinaemic hypoglycaemia (PG <3.0 mmol/L). Cardiac function was evaluated during each steady state by echocardiography., Results: Acute hyperglycaemia increased left ventricular (LV) ejection fraction from baseline in patients with T2D (mean [95% confidence interval] 4.5 percentage points [1.1; 7.9]) but not in controls (2.0 percentage points [-1.4; 5.4]). Mitral annular peak systolic velocity (s') increased during hyperglycaemia in both patients and controls (0.4 m/s [0.2;0.6] and 0.6 m/s [0.4; 0.8], respectively), whereas global longitudinal strain rate only increased in the controls (-0.05 s -1 [-0.12; 0.02] and -0.11 s -1 [-0.18; -0.03], respectively). All measures of LV systolic function increased markedly during hypoglycaemia (P <0.01 for all). No interaction between group and PG level on cardiac function was observed., Conclusions: Acute hyperglycaemia and hypoglycaemia increase LV systolic function, with no difference between patients with T2D and controls. Standardization of PG may improve reproducibility when evaluating LV systolic function in patients with T2D., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background Influenza infection may increase the risk of stroke and acute myocardial infarction (AMI). Whether influenza vaccination may reduce mortality in patients with hypertension is currently unknown. Methods and Results We performed a nationwide cohort study including all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007 to 2016 who were prescribed at least 2 different classes of antihypertensive medication (renin-angiotensin system inhibitors, diuretics, calcium antagonists, or beta-blockers). We excluded patients who were aged <18 years, >100 years, had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease. The exposure to influenza vaccination was assessed before each influenza season. The end points were defined as death from all-causes, from cardiovascular causes, or from stroke or AMI. For each influenza season, patients were followed from December 1 until April 1 the next year. We included a total of 608 452 patients. The median follow-up was 5 seasons (interquartile range, 2-8 seasons) resulting in a total follow-up time of 975 902 person-years. Vaccine coverage ranged from 26% to 36% during the study seasons. During follow-up 21 571 patients died of all-causes (3.5%), 12 270 patients died of cardiovascular causes (2.0%), and 3846 patients died of AMI/stroke (0.6%). After adjusting for confounders, vaccination was significantly associated with reduced risks of all-cause death (HR, 0.82; P <0.001), cardiovascular death (HR, 0.84; P <0.001), and death from AMI/stroke (HR, 0.90; P =0.017). Conclusions Influenza vaccination was significantly associated with reduced risks of death from all-causes, cardiovascular causes, and AMI/stroke in patients with hypertension. Influenza vaccination might improve outcome in hypertension.

Background It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first-degree family members with HF or dilated cardiomyopathy (DCM). Methods and Results Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre-existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first-degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5-year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8-10.7] versus 5.6% [95% CI, 5.0-6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13-1.64]). (HF 8.4% [95% CI, 7.0-9.8] versus 4.5% [95% CI, 4.1-5.0]); (adjusted HR, 1.49 [95% CI, 1.22-1.82]). However, familial HF/DCM was not significantly associated with an increased 5-year risk and rate of death (0.8% [95% CI, 0.4-1.2] versus 1.1% [95% CI, 0.8-1.3]); (adjusted HR, 0.80 [95% CI, 0.46-1.39]). Conclusions In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first-degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5-year incidence of HF compared with those without.

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) ( P interaction =0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Background Dietary vitamin K (K 1 and K 2 ) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K 1 and vitamin K 2 were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K 1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K 2 , the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K 2 intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K 1 or K 2 . The similar inverse associations with both vitamin K 1 and K 2 , despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Background We describe calendar time trends of patients with simple congenital heart disease. Methods and Results Using the nationwide Danish registries, we identified individuals diagnosed with isolated ventricular septal defect, atrial septal defect, patent ductus arteriosus, or pulmonary stenosis during 1977 to 2015, who were alive at 5 years of age. We reported incidence per 1 000 000 person-years with 95% CIs, 1-year invasive cardiac procedure probability and age at time of diagnosis stratified by diagnosis age (children ≤18 years, adults >18 years), and 1-year all-cause mortality stratified by diagnosis age groups (5-30, 30-60, 60+ years). We identified 15 900 individuals with simple congenital heart disease (ventricular septal defect, 35.2%; atrial septal defect, 35.0%; patent ductus arteriosus, 25.2%; pulmonary stenosis, 4.6%), of which 75.7% were children. From 1977 to 1986 and 2007 to 2015, the incidence rates increased for atrial septal defect in adults (8.8 [95% CI, 7.1-10.5] to 31.8 [95% CI, 29.2-34.5]) and in children (26.6 [95% CI, 20.9-32.3] to 150.8 [95% CI, 126.5-175.0]). An increase was only observed in children for ventricular septal defect (72.1 [95% CI, 60.3-83.9] to 115.4 [95% CI, 109.1-121.6]), patent ductus arteriosus (49.2 [95% CI, 39.8-58.5] to 102.2 [95% CI, 86.7-117.6]) and pulmonary stenosis (5.7 [95% CI, 3.0-8.3] to 21.5 [95% CI, 17.2-25.7]) while the incidence rates remained unchanged for adults. From 1977-1986 to 2007-2015, 1-year mortality decreased for all age groups (>60 years, 30.1%-9.6%; 30-60 years, 9.5%-1.0%; 5-30 years, 1.9%-0.0%), and 1-year procedure probability decreased for children (13.8%-6.6%) but increased for adults (13.3%-29.6%) were observed. Conclusions Increasing incidence and treatment and decreasing mortality among individuals with simple congenital heart disease point toward an aging and growing population. Broader screening methods for asymptomatic congenital heart disease are needed to initiate timely treatment and follow-up.

Background We examined whether primary prevention with statins and high adherence to statins reduce the associated risk of cardiovascular events or death in a low-risk population with type 2 diabetes mellitus (T2D). Methods and Results Using Danish nationwide registers, we included patients with new-onset T2D, aged 40 to 89 years, between 2005 and 2011, who were alive 18 months following the T2D diagnosis (index date). In patients who purchased statins within 6 months following T2D diagnosis, we calculated the proportion of days covered (PDC) within 1 year after the initial 6-month period. We studied the combined end point of myocardial infarction, stroke, or all-cause mortality, whichever came first, with Cox regression. Reported were standardized 5-year risk differences for fixed comorbidity distribution according to statin treatment history, stratified by sex and age. Among 77 170 patients, 42 975 (56%) were treated with statins, of whom 31 061 (72%) had a PDC ≥80%. In men aged 70 to 79 years who were treated with statins, the standardized 5-year risk was 22.9% (95% CI, 21.5%-24.3%), whereas the risk was 29.1% (95% CI, 27.4%-30.7%) in men not treated, resulting in a significant risk reduction of 6.2% (95% CI, 4.0%-8.4%), P <0.0001. The risk reduction associated with statins increased with advancing age group (women: age 40-49 years, 0.0% [95% CI, -1.0% to 1.0%]; age 80-89 years, 10.8% [95% CI, 7.2%-14.4%]). Standardizing to all patients treated with statins, PDC <80% was associated with increased risk difference (reference PDC ≥80%; PDC <20%, 4.2% [95% CI, 2.9%-5.6%]). Conclusions This study supports the use of statins as primary prevention against cardiovascular diseases or death in 18-month surviving low-risk patients with T2D, with the highest effect in the elderly and adherent patients.

Objective: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated., Methods: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs., Results: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%)., Conclusion: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Our aim was to investigate whether echocardiography may aid in identifying patients, specifically men, at risk of bradycardia as detected by implantable loop recorders (ILR) in patients evaluated for syncope and palpitations., Methods: We included ambulatory patients undergoing ILR implantation for syncope (84%), presyncope (9%), and palpitations (8%). Echocardiographic examination was performed prior to implantation (2.9 months [IQR 1.0-6.0 months]). Echocardiograms were analyzed for conventional and speckle tracking parameters. We examined time to first event of bradycardia, defined as (a) heart rate <30 beats/min and (b) ≥4 beats, including sinus arrest, asystole, sinoatrial block, and second- and third-degree atrioventricular nodal block. We applied Cox proportional hazards models., Results: A total of 285 patients we enrolled, and during a median time of 2.7 years [IQR 1.0, 3.3 years] of continuous heart rhythm monitoring, 84 (29%) had bradycardia detected by ILR. Patients with bradycardia were older (61 ± 19 years vs 55 ± 18 years, P = .01) and more frequently men (62% vs 44%, P = .01). Sex modified the association between echocardiographic parameters and bradycardia (P interaction <0.05 for all), such that left ventricular LV mass index (HR: 1.02 per 1g/m 2 increase [1.01-1.04], P < .001), LV ejection fraction (HR: 1.04 per 1% decrease [1.01-1.08], P = .02), and global longitudinal strain (HR: 1.09 per 1% decrease [1.01-1.19], P = .03) were associated with bradycardia in men but not women (P > .05 for all in female). After adjusting for baseline clinical characteristics, medical therapy, and loop indication, the abovementioned parameters remained significantly associated with incident bradycardia in men., Conclusion: Echocardiographic parameters of LV structure and function may potentially be more useful for predicting bradycardia in men than women, among patients undergoing ILR implantation for syncope, presyncope, and palpations., (© 2021 Wiley Periodicals LLC.)

Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow-up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (hyperkalemia) within 100 days of combination antihypertensive therapy initiation. A second potassium was measured 6 to 100 days after the episode of hyperkalemia. All-cause mortality within 90 days of the second potassium measurement was assessed using Cox regression. Mortality was examined for 8 predefined potassium intervals derived from the second measurement: 2.2 to 2.9 mmol/L (n=37), 3.0 to 3.4 mmol/L (n=184), 3.5 to 3.7 mmol/L (n=325), 3.8 to 4.0 mmol/L (n=791), 4.1 to 4.6 mmol/L (n=3533, reference), 4.7 to 5.0 mmol/L (n=1786), 5.1 to 5.5 mmol/L (n=720), and 5.6 to 7.8 mmol/L (n=244). Ninety-day mortality in the 8 strata was 37.8%, 21.2%, 14.5%, 9.6%, 6.3%, 6.2%, 10.0%, and 16.4%, respectively. The multivariable analysis showed that patients with concentrations >5.5 mmol/L after an episode of hyperkalemia had increased mortality risk compared with the reference (hazard ratio [HR], 2.27; 95% CI, 1.60-3.20; P <0.001). Potassium intervals 3.5 to 3.7 mmol/L and 3.8 to 4.0 mmol/L were also associated with increased risk of death (HR, 1.71; 95% CI, 1.23-2.37; P <0.001; HR, 1.36; 95% CI, 1.04-1.76; P <0.001, respectively) compared with the reference group. We observed a trend toward increased risk of death within the interval 5.1 to 5.5 mmol/L (HR, 1.29; 95% CI, 0.98-1.69). Potassium concentrations <4.1 mmol/L and >5.0 mmol/L were associated with increased risk of cardiovascular death. Conclusions Overcorrection of hyperkalemia to levels <4.1 mmol/L was frequent and associated with increased all-cause and cardiovascular mortality. Potassium concentrations >5.5 mmol/L were also associated with an increased all-cause and cardiovascular mortality.

Background Mortality is increased following a hospitalization for decompensated heart failure (HF), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for HF. Methods and Results From nationwide administrative registers, we identified all Danish patients who were diagnosed with HF from 2001 to 2016 and received angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β blocker within 120 days. Subsequent follow-up tracked progressive events of diuretic intensification and HF hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1-year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened HF controls and absolute 1-year mortality risks were calculated using Kaplan-Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow-up. One-year mortality was 18.0% after an intensification event, 22.6% after HF hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1-year death after an intensification event was 1.75 (95% CI, 1.66-1.85), and it was 2.28 (95% CI, 2.16-2.41) after HF hospitalization. Conclusions In a nationwide cohort of patients with HF, outpatient intensification events were associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.

Background Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results We prospectively enrolled 373 patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. All patients underwent a speckle tracking echocardiographic examination a median of 2 days (interquartile range, 1-3 days) after the percutaneous coronary intervention. We assessed a novel viability index, the ESL index, defined as follows: [-100×(peak positive systolic strain/peak negative strain in cardiac cycle)]. We also calculated ESL duration, defined as time from onset of QRS complex on the ECG to time of peak positive systolic strain. Both parameters were averaged from 18 myocardial segments. During a median follow-up of 5.3 years (interquartile range, 2.5-6.0 years), 145 (39%) experienced major adverse cardiovascular events, a composite of incident heart failure, new myocardial infarction, and all-cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% versus 5.0±4.1% and 43±33 ms versus 33±24 ms, respectively; P <0.001 for both). In Cox proportional hazard models, the ESL index (hazard ratio, 1.27 per 1% increase; 95% CI, 1.13-1.43; P <0.001) and ESL duration (hazard ratio, 1.49 per 1-ms increase; 95% CI, 1.15-1.92; P =0.002) yielded prognostic information on major adverse cardiovascular events. Both associations remained significant after adjusting for clinical, echocardiographic, and invasive confounders. Conclusions Assessment of ESL after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction yields independent and significant prognostic information on the future risk of cardiovascular events.

Background: Atopic dermatitis (AD) is associated with many autoimmune diseases, in part due to overlapping genetic risk loci. While parental atopic disease is an important risk for AD in the offspring, little is known on the putative associations between parental autoimmune disease and AD in their children., Materials and Methods: All children born between 1996 and 2011 who received a diagnosis of AD in the hospital system before their fifth birthday were matched 1 : 10 with children from the general population. Maternal and paternal autoimmune diseases were assessed using registry-based data. Conditional logistic regression was performed on the relationships between parental autoimmune diseases and AD in their children., Results: A total of 8589 children with AD were matched with controls. One or more autoimmune disease was identified in 5.89% (506/8589) of mothers to AD children and 3.67% (315/8589) of fathers to AD children compared to 4.85% (4163/85 890) and 3.28% (2816/85 890) in parents of control children. Maternal autoimmune disease but not paternal autoimmune disease was associated with AD in the offspring (odds ratio [OR] 1.20 [95% confidence interval (CI) 1.20-1.32] and OR 1.08 [0.96-1.22], respectively), Two or more maternal autoimmune diseases, maternal dermatologic autoimmune disease and maternal digestive autoimmune disease were all also associated with AD development in her children (1.96 [95% CI 1.36-2.84], OR 1.60 [95% CI 1.24-2.07] and OR 1.24 [95% CI 1.06-1.45], respectively)., Conclusions: The risk of AD is influenced by many factors including atopy status and filaggrin gene mutations. In this matched case-control study, maternal autoimmune disease was associated with AD diagnosis in the offspring. Maternal dermatologic and digestive autoimmune diseases were most closely associated with subsequent AD diagnosis in the offspring., (© 2019 European Academy of Dermatology and Venereology.)

Background: Maternal prenatal psychiatric disease has been identified as a possible risk factor for atopic dermatitis development in her children. We quantified the associations between maternal and paternal psychiatric disease and the development of atopic dermatitis in their offspring using nationwide registries., Methods: All children in Denmark born between 1 January 1996 and 31 December 2011 who developed atopic dermatitis prior to their fifth birthday were identified and individually matched 1:10 with controls from the general population and with children receiving care in a similar ambulatory/hospital setting. Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals., Results: A total of 8602 children with atopic dermatitis were matched with controls. Rates of parental psychiatric care were similar in the atopic dermatitis and control groups. When compared to the general population, weak associations were found between childhood atopic dermatitis and maternal history of depression [OR 1.18 (95% confidence interval: 1.12-1.26)], alcohol abuse [OR 1.37 (1.17-1.60)] and illicit drug use [OR 1.34 (1.14-1.60)]. However, associations became insignificant when the paediatric ambulatory/hospital control group was used [OR 1.05 (0.99-1.13)], [OR 1.14 (0.98-1.34)] and [OR 1.03 (0.88-1.22)], respectively. No paternal psychiatric disease or prenatal maternal psychiatric disease associated with the AD development in the offspring., Conclusions: While we found no consistent associations between maternal or paternal psychiatric disease and the subsequent development of atopic dermatitis in their offspring, children of parents with substance abuse issues may be more likely to receive an atopic dermatitis diagnosis., (© 2018 European Academy of Dermatology and Venereology.)

Background: The risk of prenatal, obstetric and birth complications in mothers with atopic dermatitis (AD), along with treatment use during pregnancy, is unknown., Objectives: To examine the associations between prenatal, obstetric and birth complications in mothers with AD and describe the dermatologic care received during pregnancy., Methods: Mother-child pairs, in which the mother had a history of AD, were identified through the Danish Medical Birth Registry and matched 1 : 10 with non-AD pairs. Data on dermatologic treatment and prenatal, obstetric and birth complications were obtained through linkage via nationwide registers. Multiple logistic regression was performed., Results: We identified 10 668 births from 1997 through 2014 to women with AD. Women with a hospital/ambulatory contact for AD during pregnancy had increased topical corticosteroid and ultraviolet therapy use during pregnancy compared to prior. However, overall, women with AD received decreased dermatologic therapy during pregnancy compared to prior. In adjusted analysis, maternal AD was inversely associated with gestational diabetes [OR 0.79, 95% CI (0.68-0.92)], but positively associated with premature rupture of membranes [1.15 (1.05-1.27)] and staphylococcal neonatal septicemia [2.45 (1.33-4.49)]-albeit the latter was rare. These associations did not meet statistical significance in sub-analysis where body mass index data were available. No associations were found with preeclampsia, prematurity or non-staphylococcal neonatal septicaemia., Conclusions: Women with AD during pregnancy mainly used topical corticosteroids and ultraviolet therapy to control their disease. While premature rupture of membranes and staphylococcal neonatal septicaemia were over-represented in maternal AD, no associations were found with any other significant prenatal, obstetric or birth outcome., (© 2018 European Academy of Dermatology and Venereology.)

Background: Cancer-associated mortality is increased in psoriasis. However, little is known about the risk of less common cancers., Objective: We aimed to evaluate the risk of less common cancers in patients with psoriasis compared to persons without psoriasis using a nationwide cohort study., Methods: Between 1 January 2008 and 31 December 2012, we identified all Danish patients with a first-time hospital diagnosis of a less common cancer defined as <100 new cases/year/100.000 persons in Denmark. The primary endpoint was the occurrence of a diagnosis of cancer., Results: We included 4 361 869 individuals. Of these, 58 138 were classified as having psoriasis. After adjusting for age, sex, socio-economic status and healthcare consumption, we found significantly elevated hazard ratios for cancers of bone and cartilage (HR 4.97 [2.32-10.62], P < 0.0001) in patients with psoriasis on systemic treatment., Conclusion: We provide further evidence of an increased cancer of bone and cartilage risk in patients with psoriasis., (© 2017 European Academy of Dermatology and Venereology.)

Background: Limited data are available on return to work and subsequent detachment from employment after admission for myocardial infarction (MI)., Methods and Results: Using individual-level linkage of data from nationwide registries, we identified patients of working age (30-65 years) discharged after first-time MI in the period 1997 to 2012, who were employed before admission. To assess the cumulative incidence of return to work and detachment from employment, the Aalen Johansen estimator was used. Incidences were compared with population controls matched on age and sex. Logistic regression was applied to estimate odds ratios for associations between detachment from employment and age, sex, comorbidities, income, and education level. Of 39 296 patients of working age discharged after first-time MI, 22 394 (56.9%) were employed before admission. Within 1 year 91.1% (95% confidence interval [CI], 90.7%-91.5%) of subjects had returned to work, but 1 year after their return 24.2% (95% CI, 23.6%-24.8%) were detached from employment and received social benefits. Detachment rates were highest in patients aged 60 to 65 and 30 to 39 years, and significantly higher in patients with MI compared with population controls. Predictors of detachment were heart failure (odds ratio 1.20 [95% CI, 1.08-1.34]), diabetes mellitus (odds ratio 1.13 [95% CI, 1.01-1.25]), and depression (odds ratio 1.77 [95% CI, 1.55-2.01]). High education level and high income favored continued employment., Conclusions: Despite that most patients returned to work after first-time MI, about 1 in 4 was detached from employment after 1 year. Several factors including age and lower socioeconomic status were associated with risk of detachment from employment., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Common loss-of-function mutations in filaggrin gene (FLG) represent a strong genetic risk factor for atopic dermatitis (AD). Homozygous mutation carriers typically display ichthyosis vulgaris (IV) and many have concomitant AD. Previously, homozygous, but not heterozygous, filaggrin gene mutations have been associated with squamous cell carcinomas., Objective: The first objective was to examine the association between FLG mutations and actinic keratosis (AK). The second objective was to investigate the occurrence of AK in patients with IV and AD, respectively., Methods: FLG mutation status in patients with AK was compared with controls from the general population. Furthermore, based on nationwide data from Danish registers, we compared the risk of AK in patients with IV, AD and psoriasis, respectively., Results: The prevalence of homozygous FLG mutations was significantly higher in the AK group (n = 4, 0.8%) in comparison with the control group (n = 18, 0.2%), whereas the prevalence of heterozygous FLG mutations was lower. In hospital registry data, patients with AD exhibited an increased risk of AK than did psoriasis controls (adjusted OR 1.46; [95% CI 1.12-1.90]), whereas no difference in risk was observed between patients with IV and AD., Conclusions: This study indicates an increased susceptibility to AK in individuals with homozygous, but not heterozygous, FLG mutations and in patients with AD compared to psoriasis. Whether a reduction or absence of epidermal filaggrin could contribute to the susceptibility to AK in patients with IV and AD is unknown and additional research is needed to further explore this relationship., (© 2017 European Academy of Dermatology and Venereology.)

Background: Psoriasis and periodontitis are chronic inflammatory disorders with overlapping inflammatory pathways, but data on risk of periodontitis in psoriasis are scarce and a possible pathogenic link is poorly understood., Objective: We investigated the association between psoriasis and periodontitis in a nationwide cohort study., Methods: All Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2011 (n = 5,470,428), including 54 210 and 6988 patients with mild and severe psoriasis, and 6428 with psoriatic arthritis, were linked through administrative registers. Incidence rate ratios (IRRs) were estimated by Poisson regression., Results: Incidence rates of periodontitis per 10 000 person-years were 3.07 (3.03-3.12), 5.89 (1.07-6.84), 8.27 (5.50-12.45) and 11.12 (7.87-15.73) for the reference population, mild psoriasis, severe psoriasis and psoriatic arthritis respectively. Adjusted IRRs were (1.66; 1.43-1.94) for mild psoriasis, (2.24; 1.46-3.44) for severe psoriasis and (3.48; 2.46-4.92) for psoriatic arthritis. Similar results were found when a case-control design was applied., Conclusions: We found a significant psoriasis-associated increased risk of periodontitis, which was highest in patients with severe psoriasis and psoriatic arthritis., (© 2016 European Academy of Dermatology and Venereology.)

Recent guidelines governing anti-diabetic medications increasingly advocate metformin as first-line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug-naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1-year risk of acute dialysis was based on g-standardization of cause-specific Cox regression models for acute dialysis, end-stage renal disease and death. One-year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1-121.3) and 142.7 per 100 000 (95% CI, 118.3-168.0) for sulphonylurea and metformin, respectively. The metformin-associated 1-year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9-88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06-2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin., (© 2016 John Wiley & Sons Ltd.)

Background: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with severe psoriasis treated with systemic anti-inflammatory drugs., Methods: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy., Results: A total of 6902 patients (9662 treatment exposures) with a maximum follow-up of 5 years were included. Incidence rates per 1000 patients-years for cardiovascular events were 4.16, 6.28, 6.08, 18.95 and 14.63 for biological drugs, methotrexate, cyclosporine, retinoid and other therapies respectively. Relative to other therapies, methotrexate (HR 0.53; CI 0.34-0.83) was associated with reduced risk of the composite endpoint and a comparable but non-significant protective effect was observed with biological drugs (HR 0.58; CI 0.30-1.10), whereas no protective effect was apparent with cyclosporine (HR 1.06; CI 0.26-4.27) and retinoids (HR 1.80; CI 1.03-2.96). Tumour necrosis factor inhibitors (HR 0.46; CI 0.22-0.98) were linked to reduced event rates, whereas the interleukin-12/23 inhibitor ustekinumab (HR 1.52; CI 0.47-4.94) was not., Conclusion: Systemic anti-inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events during long-term follow-up compared to patients treated with other antipsoriatic therapies. The treatment strategy in patients with severe psoriasis may have an impact on cardiovascular outcomes and randomized trials to evaluate the cardiovascular safety and efficacy of systemic antipsoriatic therapies are called for., (© 2014 European Academy of Dermatology and Venereology.)

Background: Psoriasis is a common chronic disease, mediated by type 1 and 17 helper T cell-driven inflammation. Epidemiological studies have demonstrated a wide range of comorbidities and increased mortality rates. However, the current evidence on psoriasis-related mortality is limited and nationwide data have not been presented previously., Methods: In a nationwide population-based cohort we evaluated all-cause and cause-specific death rates in patients with psoriasis as compared to the general population., Results: The entire Danish population aged 18 and above, corresponding to a total of 5,458,627 individuals (50.7% female, 40.9 years ± 19.7), including 94,069 with mild psoriasis (53% female, 42.0 ± 17.0 years) and 28,253 with severe psoriasis (53.4% female, 43.0 ± 16.5 years), was included. A total of 884,661 deaths were recorded, including 10 916 in patients with mild psoriasis and 3699 in patients with severe psoriasis. The age at time of death varied by psoriasis status, i.e. 76.5 ± 14.0, 74.4 ± 12.8 and 72.0 ± 13.4 years, for the general population, mild psoriasis and severe psoriasis respectively. In general, the highest death rates were observed in patients with severe psoriasis. Overall death rates per 1000 patient years were 13.8 [confidence interval (CI) 13.8-13.8], 17.0 (CI 16.7-17.3) and 25.4 (CI 24.6-26.3) for the general population, patients with mild psoriasis and patients with severe psoriasis respectively., Conclusion: This nationwide population-based study of cause-specific death rates in patients with psoriasis demonstrated reduced lifespan and increased rates of all examined specific causes of death in patients with psoriasis compared to the general population., (© 2014 European Academy of Dermatology and Venereology.)

Aim: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited., Methods: Danish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP-4 inhibitors, GLP-1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all-cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality. Rate ratios (RR) were calculated using time-dependent multivariable Poisson regression analysis., Results: A total of 40 028 patients (59% men, mean age 60 ± 13 years) used metformin with SU (n = 25 092), DPP-4 inhibitor (n = 11 138), GLP-1 agonist (n = 4345) or insulin (n = 6858). Crude incidence rates per 1000 patient years for the combined end point were 18 (SU), 10 (DPP-4 inhibitor), 8 (GLP-1 agonist) and 21 (insulin). In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point. For metformin + GLP-1 agonist, the RR for mortality was 0.77 (0.51-1.17), for CV mortality 0.89 (0.47-1.68), and for the combined end point 0.82 (0.55-1.21)., Conclusion: Incretin-based drugs combined with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline differences., (© 2014 John Wiley & Sons Ltd.)

Background: Metabolic disorders are relatively uncommon in young women, but may increase with obesity. The associations between body mass index (BMI) and risks of diabetes, hypertension, and dyslipidemia in apparently healthy, young women have been insufficiently investigated, and are the aims of this study., Methods and Results: Women giving birth during the years 2004-2009, with no history of cardiovascular disease, renal insufficiency, pregnancy-associated metabolic disorders, diabetes, hypertension, or dyslipidemia were identified in nationwide registers. Women were categorized as underweight (BMI<18.5 kg/m(2)), normal weight (BMI=18.5 to <25 kg/m(2)), overweight (BMI=25 to <30 kg/m(2)), obese-I (BMI=30 to <35 kg/m(2)), obese-II (BMI=35 to <40 kg/m(2)), and obese-III (BMI≥40 kg/m(2)). We assessed risks by Poisson regression models (adjusted for age, calendar year; reference=normal weight). The cohort comprised 252 472 women with a median age of 30.4 years (IQR=27.2;33.7) and a median follow-up of 5.5 years (IQR=3.9;6.8). In total, 2029 women developed diabetes, 3133 women developed hypertension, and 1549 women developed dyslipidemia. Rate ratios (RRs) of diabetes were: 0.84 (95% confidence interval [CI]=0.62 to 1.14) for underweight, 2.63 (CI=2.36 to 2.93) for overweight, 4.83 (CI=4.27 to 5.47) for obese grade-I, 7.17 (CI=6.10 to 8.48) for obese grade-II, and 6.93 (CI=5.47 to 8.79) for obese grade-III women. For hypertension, corresponding RRs were 0.86 (CI=0.69 to 1.09), 1.82 (CI=1.67 to 1.98), 2.81 (CI=2.52 to 3.13), 3.92 (CI=3.36 to 4.56), and 5.69 (CI=4.71 to 6.89), and for dyslipidemia, RRs were 1.18 (CI=0.85 to 1.65), 2.01 (CI=1.75 to 2.31), 3.11 (CI=2.61 to 3.70), 4.64 (CI=3.66 to 5.87), and 3.72 (CI=2.53 to 5.48)., Conclusions: In this nationwide study of fertile, apparently healthy women, pre-pregnancy BMI was strongly associated with an increased risk of diabetes, hypertension, and dyslipidemia within 5.5 years following childbirth.