Increased long-term risk of heart failure and other adverse cardiac outcomes in dermatomyositis and polymyositis: Insights from a nationwide cohort.

BACKGROUND: Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. OBJECTIVES: To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. METHODS: Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996-2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). RESULTS: The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16-9.16%) vs 4.58% (3.79-5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94-12.71%) vs 7.07% (6.09-8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12-3.27%) vs 0.64% (0.40-0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64-39.21%) vs 16.57% (15.10-18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01-2.47]). CONCLUSION: Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.

Preheart failure comorbidities and impact on prognosis in heart failure patients: a nationwide study.

BACKGROUND: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. OBJECTIVES: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. METHODS: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51-74 and >74 years). RESULTS: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64-11.3), 51-74 years (23.3; 22.9-23.7), >74 years (58.5; 57.9-59.0); hazard ratios 245.18 (141.45-424.76), 45.85 (42.77-49.15) and 24.5 (23.64-25.68) for those ≤50, 51-74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). CONCLUSIONS: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.

Bystander cardiopulmonary resuscitation and survival in patients with out-of-hospital cardiac arrest of non-cardiac origin.

BACKGROUND: Knowledge about the effect of bystander cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA) of non-cardiac origin is lacking. We aimed to investigate the association between bystander CPR and survival in OHCA of presumed non-cardiac origin. METHODS: From the Danish Cardiac Arrest Registry and through linkage with national Danish healthcare registries we identified all patients with OHCA of presumed non-cardiac origin in Denmark (2001-2014). These were categorized further into OHCA of medical and non-medical cause. We analyzed temporal trends in bystander CPR and 30-day survival during the study period. Multiple logistic regression was used to examine the association between bystander CPR and 30-day survival and reported as standardized 30-day survival chances with versus without bystander CPR standardized to the prehospital OHCA-factors and patient characteristics of all patients in the study population. RESULTS: We identified 10,761 OHCAs of presumed non-cardiac origin. Bystander CPR was associated with a significantly higher 30-day survival chance of 3.4% (95% confidence interval [CI]: 2.9-3.9) versus 1.8% (95% CI: 1.4-2.2) without bystander CPR. A similar association was found in subgroups of both medical and non-medical OHCA. During the study period, the overall bystander CPR rates increased from 13.6% (95% CI: 11.2-16.5) to 62.7% (95% CI: 60.2-65.2). 30-day survival increased overall from 1.3% (95% CI: 0.7-2.6) to 4.0% (95% CI: 3.1-5.2). CONCLUSION: Bystander CPR was associated with a higher chance of 30-day survival among OHCA of presumed non-cardiac origin regardless of the underlying cause (medical/non-medical). Rates of bystander CPR and 30-day survival improved during the study period.

Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study.

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94). Conclusion: In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

BACKGROUND: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). OBJECTIVE: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. METHODS: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). RESULTS: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). CONCLUSIONS: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.

Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction.

BACKGROUND: Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk of first-time ischemic stroke and myocardial infarction (MI) are poorly understood. METHODS: All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause-specific Cox regression and g-formula methods to analyze long-term use. RESULTS: Amongst 214 998 individuals, during a median follow-up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08-1.19) and MI (HR 1.31, CI 1.23-1.39) after adjusting for age, sex, comorbidities and concomitant medication. High-dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21-1.42) and MI (HR 1.43, CI 1.30-1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84-1.24) or MI (HR 1.15, CI 0.92-1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%) greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI within a 6-month period. CONCLUSION: Use of PPIs was associated with increased risks of first-time ischemic stroke and MI, particularly amongst long-term users and at high doses.

Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide.

BACKGROUND: Atopic dermatitis (AD) has been linked with psychiatric disease in adults. However, the exact relationship and its consequences have been insufficiently studied. Our aim of this study was to assess the association between depression, anxiety, and AD in adults and examine the risk of hospitalization and suicide. METHODS: We utilized questionnaire data from a large general population study with data on social habits and psychiatric symptoms to compare prevalences of depression, anxiety, suicidal ideation, and anxiety attacks, in adults with and without a history of AD. Additionally, we used nationwide hospital/clinic registry and prescription data to examine the risk of anxiety and depression in Danish adults with mild and moderate-severe AD, as well as the risk of hospitalization and suicide. RESULTS: In the general population study, those with AD reported clinician-diagnosed depression and anxiety more often than non-AD subjects, and had an increased prevalence of suicidal ideation and depressive symptoms. In the health registry study, moderate-severe AD patients had increased risk of antidepressant and anxiolytic medication use, while patients with mild AD only had increased risk of anxiolytic medication use. There was no increased risk of hospitalization or outpatient contacts due to depression or anxiety, or risk of suicide in AD patients. CONCLUSIONS: Depression, anxiety, and suicidal ideation are more common among AD individuals, but do not lead to psychiatric consultations, hospitalization, or suicide.

Poor agreement in questionnaire-based diagnostic criteria for adult atopic dermatitis is a challenge when examining cardiovascular comorbidity.

BACKGROUND: The association between atopic dermatitis (AD) and cardio-metabolic risk factors is not yet established. Furthermore, no validated questionnaire-based method of identifying adults with AD is currently available. OBJECTIVES: To assess the cardio-metabolic risk in adults with a history of AD using 3 different questionnaire-based diagnostic criteria. METHODS: We utilized data from a general population study including questionnaire data and objective measurements of 9656 Danish adults. To identify adults with a history of AD, we used a question regarding physician-diagnosed AD and 2 versions of the UK Working Party Diagnostic Criteria. Associations between AD status and cardio-metabolic endpoints were estimated using survey weighted logistic and linear regression analysis. RESULTS: We identified 462 (4.8%) adults with self-reported physician-diagnosed AD, whereas 903 (9.4%) and 226 (2.3%) had AD according to the UK Working Party Criteria when at least 2 and 3of 4 minor criteria were fulfilled. The populations were not comparable in terms of occurrence of cardio-metabolic risk factors. For example, the prevalence of obesity was lower in participants with physician-diagnosed AD but overall higher in UK 2/4 and UK 3/4. CONCLUSION: Due to the heterogeneity in the captured study populations in terms of the studied outcomes and absence of a gold standard, no conclusions regarding the cardio-metabolic risk in adults with AD in a general population could be made. This study serves as an example of the challenges that are often encountered in questionnaire-based epidemiologic studies and highlights the need of better definitions for this patient group.

Initiation of anticoagulation in atrial fibrillation: which factors are associated with choice of anticoagulant?

BACKGROUND: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). METHODS: Using Danish nationwide registry data, we identified AF patients initiating either a VKA or a NOAC from 22 August 2011 until 30 September 2016. We compared patient characteristics including age, gender, comorbidities, concomitant pharmacotherapy and CHA2 DS2 -VASc and HAS-BLED scores in patients initiated on a VKA, dabigatran, rivaroxaban or apixaban. Differences were examined using multivariable logistic regression models. RESULTS: The study population comprised 51 981 AF patients of whom 19 989 (38.5%) were initiated on a VKA, 13 242 (25.5%) on dabigatran, 8475 (16.3%) on rivaroxaban and 10 275 (19.8%) on apixaban. Those patients initiated on apixaban had higher mean ± SD CHA2 DS2 -VASc scores than those initiated on a VKA (3.1 ± 1.6 vs. 2.9 ± 1.6). Those initiated on dabigatran had lower mean CHA2 DS2 -VASc scores (2.7 ± 1.6) than all other groups. Patients with a history of a prior stroke were significantly more likely to be initiated on a NOAC compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28-1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67-0.77). CONCLUSIONS: Atrial fibrillation patients who were initiated on apixaban had higher stroke risk scores than patients initiated on VKAs. Interestingly, opposite results were found for dabigatran.

Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder, which may persist into adulthood; however, the prevalence of comorbidities in patients with AD is not well characterized. AD is considered a systemic disorder like psoriasis, which has raised a need for data on the comorbidity profile of patients with AD, to assess the potential risks, benefits, and complications in management of patients with AD. We described the occurrence of medical and psychiatric comorbidities and associated risk factors in adults with AD compared with psoriasis and the general population. METHODS: All Danish individuals aged ≥18 years with a hospital (inpatient or ambulatory) diagnosis of AD or psoriasis during the study period (January 1, 1995-December 31, 2012) were linked in administrative registers. RESULTS: Overall, prevalence of smoking and alcohol abuse was higher among patients with AD than the general population, but lower than psoriasis patients. Similarly, patients with AD had more risk factors and higher prevalence of comorbidity than the general population, but lower prevalence and reduced risk compared to psoriasis patients, except for use of anxiolytics, which was higher in severe AD. Prevalence of diabetes was lower in AD than psoriasis patients as well as general population controls. CONCLUSIONS: Despite an increased risk of various medical and psychiatric comorbidities compared to general population controls, adult patients with AD had markedly lower prevalence of cardiovascular disease than psoriasis patients. However, prevalence of psychiatric comorbidity and tobacco smoking was alarmingly high in severe patients with AD, which might be target for intervention in patient management.

Rosacea and gastrointestinal disorders: a population-based cohort study.

BACKGROUND: Rosacea is a common inflammatory facial skin condition. Recent genetic and epidemiological studies have suggested pathogenic links between rosacea and gastrointestinal disorders, but data are limited. OBJECTIVES: The objective was to investigate the association between rosacea and coeliac disease (CeD), Crohn disease (CD), ulcerative colitis (UC), Helicobacter pylori infection (HPI), small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS), respectively. METHODS: We performed a nationwide cohort study. A total of 49 475 patients with rosacea and 4 312 213 general population controls were identified using nationwide administrative registers. We established the prevalence of the aforementioned disorders, and used Cox regression analysis to obtain hazard ratios (HRs) of the risk of new-onset CeD, CD, UC, HPI, SIBO and IBS, respectively, in patients with rosacea. RESULTS: The prevalence of CeD, CD, UC, HPI, SIBO and IBS, respectively, was higher among patients with rosacea when compared with the control subjects. Adjusted HRs revealed significant associations between rosacea and CeD (HR 1·46, 1·11-1·93), CD (HR 1·45, 1·19-1·77), UC (HR 1·19, 1·02-1·39), and IBS (HR 1·34, 1·19-1·50), respectively, but not HPI (HR 1·04, 0·96-1·13) or SIBO (HR 0·71, 0·18-1·86). CONCLUSIONS: Rosacea is associated with certain gastrointestinal diseases, but the possible pathogenic link is unknown. Gastrointestinal complaints in patients with rosacea should warrant clinical suspicion of disease.

Risk of self-harm and nonfatal suicide attempts, and completed suicide in patients with psoriasis: a population-based cohort study.

BACKGROUND: Psoriasis is a common inflammatory skin disease, and inflammation may affect suicidal behaviour. Current data on the incidence and risk of suicidal behaviour in patients with psoriasis are scarce. OBJECTIVES: We investigated the association between psoriasis and the risk of self-harm and suicide attempts and suicides. METHODS: All Danish patients aged ≥ 18 years with mild or severe psoriasis (cases) from 1 January 1997 to 31 December 2011 were matched on age, sex and calendar time 1 : 5 with healthy controls. The outcome was a diagnosis of self-harm or a nonfatal suicide attempt, or completed suicide. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated by Poisson regression models. RESULTS: The study cohort comprised 408 663 individuals, including 57 502 and 11 009 patients with mild and severe psoriasis, respectively. In total 280 cases of self-harm or suicide attempts, and 574 suicides occurred during follow-up. There was no increased risk of self-harm or suicide attempts in patients with mild psoriasis (IRR 1·01, 95% CI 0·17-2·01), but this risk was significantly increased in severe psoriasis (IRR 1·69, 95% CI 1·00-2·84). There was no increased risk of suicides in mild (IRR 1·05, 95% CI 0·84-1·32) or severe psoriasis (IRR 0·78, 95% CI 0·45-1·36). Similar results were found when suicides were confirmed by official forensic investigations, and when psoriasis was compared with atopic dermatitis. CONCLUSIONS: We found limited evidence to suggest an increased risk of self-harm and nonfatal suicide attempts in patients with psoriasis. Importantly, after adjustment for psoriatic arthritis this risk was no longer significantly increased. The risk of completed suicide was also not increased, regardless of psoriasis severity.