Correction: Migraine and risk of premature myocardial infarction and stroke among men and women: A Danish population-based cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1004238.].

Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study.

BACKGROUND: Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. OBJECTIVE: The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. METHODS: A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996-2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195). RESULTS: Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LIMITATIONS: Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. CONCLUSION: Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls.

Cardiovascular safety of using non-steroidal anti-inflammatory drugs for gout: a Danish nationwide case-crossover study.

Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. We conducted a nationwide, population-based case-crossover study of all Danes ≥ 18 years of age with first-time gout during 1997-2020, who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac.

Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure: a nationwide Danish study.

AIMS: Transcatheter closure of patent foramen ovale (PFO) is the recommended stroke prevention treatment in patients ≤60 years with cryptogenic ischemic stroke and PFO. Atrial fibrillation or flutter (AF) is a known potential procedure-related complication, but long-term risk of developing AF remains unknown. This paper studied the long-term risk of developing AF following PFO closure. METHODS AND RESULTS: A Danish nationwide cohort study was conducted. During 2008-2020, this study identified a PFO closure cohort, a PFO diagnosis cohort without PFO closure, and a general population comparison cohort matched 10:1 to the PFO closure cohort on age and sex. The outcome was first-time AF diagnosis. Risk of AF and multivariable-adjusted hazard ratio (HR) of the association between PFO closure or PFO diagnosis and AF were calculated. A total of 817 patients with PFO closure, 1224 with PFO diagnosis, and 8170 matched individuals were identified. The 5 year risk of AF was 7.8% [95% confidence interval (CI): 5.5-10] in the PFO closure cohort, 3.1% (95% CI: 2.0-4.2) in the PFO diagnosis cohort, and 1.2% (95% CI: 0.8-1.6) in the matched cohort. The HR of AF comparing PFO closure with PFO diagnosis was 2.3 (95% CI: 1.3-4.0) within the first 3 months and 0.7 (95% CI: 0.3-1.7) thereafter. The HR of AF comparing PFO closure with the matched cohort was 51 (95% CI: 21-125) within the first 3 months and 2.5 (95% CI: 1.2-5.0) thereafter. CONCLUSION: Patent foramen ovale closure was not associated with any substantial increased long-term risk of developing AF beyond the well-known procedure-related short-term risk.

Migraine and risk of premature myocardial infarction and stroke among men and women: A Danish population-based cohort study.

BACKGROUND: Migraine carries risk of myocardial infarction (MI) and stroke. The risk of premature MI (i.e., among young adults) and stroke differs between men and women; previous studies indicate that migraine is mainly associated with an increased risk of stroke among young women. The aim of this study was to examine impact of migraine on the risk of premature (age ≤60 years) MI and ischemic/hemorrhagic stroke among men and women. METHODS AND FINDINGS: Using Danish medical registries, we conducted a nationwide population-based cohort study (1996 to 2018). Redeemed prescriptions for migraine-specific medication were used to identify women with migraine (n = 179,680) and men with migraine (n = 40,757). These individuals were matched on sex, index year, and birth year 1:5 with a random sample of the general population who did not use migraine-specific medication. All individuals were required to be between 18 and 60 years old. Median age was 41.5 years for women and 40.3 years for men. The main outcome measures to assess impact of migraine were absolute risk differences (RDs) and hazard ratios (HRs) with 95% confidence intervals (CIs) of premature MI, ischemic, and hemorrhagic stroke, comparing individuals with migraine to migraine-free individuals of the same sex. HRs were adjusted for age, index year, and comorbidities. The RD of premature MI for those with migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.3% (95% CI [-0.1%, 0.6%]; p = 0.061) for men. The adjusted HR was 1.22 (95% CI [1.14, 1.31]; p < 0.001) for women and 1.07 (95% CI [0.97, 1.17]; p = 0.164) for men. The RD of premature ischemic stroke for migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.5% (95% CI [0.1%, 0.8%]; p < 0.001) for men. The adjusted HR was 1.21 (95% CI [1.13, 1.30]; p < 0.001) for women and 1.23 (95% CI [1.10, 1.38]; p < 0.001) for men. The RD of premature hemorrhagic stroke for migraine versus no migraine was 0.1% (95% CI [0.0%, 0.2%]; p = 0.011) for women and -0.1% (95% CI [-0.3%, 0.0%]; p = 0.176) for men. The adjusted HR was 1.13 (95% CI [1.02, 1.24]; p = 0.014) for women and 0.85 (95% CI [0.69, 1.05]; p = 0.131) for men. The main limitation of this study was the risk of misclassification of migraine, which could lead to underestimation of the impact of migraine on each outcome. CONCLUSIONS: In this study, we observed that migraine was associated with similarly increased risk of premature ischemic stroke among men and women. For premature MI and hemorrhagic stroke, there may be an increased risk associated with migraine only among women.

Individual-Level Socioeconomic Position and Long-Term Prognosis in Danish Heart-Transplant Recipients.

Socioeconomic deprivation can limit access to healthcare. Important gaps persist in the understanding of how individual indicators of socioeconomic disadvantage may affect clinical outcomes after heart transplantation. We sought to examine the impact of individual-level socioeconomic position (SEP) on prognosis of heart-transplant recipients. A population-based study including all Danish first-time heart-transplant recipients (n = 649) was conducted. Data were linked across complete national health registers. Associations were evaluated between SEP and all-cause mortality and first-time major adverse cardiovascular event (MACE) during follow-up periods. The half-time survival was 15.6 years (20-year period). In total, 330 (51%) of recipients experienced a first-time cardiovascular event and the most frequent was graft failure (42%). Both acute myocardial infarction and cardiac arrest occurred in ≤5 of recipients. Low educational level was associated with increased all-cause mortality 10-20 years post-transplant (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.19-3.19). During 1-10 years post-transplant, low educational level (adjusted HR 1.66, 95% CI 1.14-2.43) and low income (adjusted HR 1.81, 95% CI 1.02-3.22) were associated with a first-time MACE. In a country with free access to multidisciplinary team management, low levels of education and income were associated with a poorer prognosis after heart transplantation.

Impact of lifestyle and socioeconomic position on use of non-steroidal anti-inflammatory drugs: A population-based cohort study.

PURPOSE: Lifestyle and socioeconomic position may confound the link between non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events, if associated with NSAID use. We examined this association. METHODS: We conducted a cohort study of all adult first-time responders to the Danish National Health Surveys of 2010, 2013, or 2017 without an NSAID prescription within 3 months before survey completion (n = 407 395). Study exposures were weight, smoking status, alcohol consumption, binge drinking frequency, physical activity level, marital status, highest achieved level of education, income, and employment status. We used a Cox model to compute hazard ratios of time to first redemption of an NSAID prescription and a cumulative odds model to compute odds ratios (ORs) of redeeming one additional NSAID prescription in the year after survey completion. RESULTS: Total follow-up time was 1 931 902 years. The odds of redeeming one additional NSAID prescription in the year after survey completion varied within all categories of lifestyle and socioeconomic position. The largest ORs were observed within categories of weight (1.70, 95% CI: 1.65-1.74 for obesity vs. normal weight), smoking status (1.24, 95% CI: 1.21-1.27 for current vs. never use), and education (1.44, 95% CI: 1.39-1.49 for primary or other vs. university or higher education). The Cox model showed consistent results. CONCLUSIONS: Markers of unhealthy lifestyle and low socioeconomic position were associated with initiation and prolonged NSAID use. Consideration of lifestyle and socioeconomic markers as potential confounders in NSAID studies is therefore recommended.

Impact of hemoglobin A1c level on the association between non-steroidal anti-inflammatory drug use and cardiovascular events in patients with type 2 diabetes: A population-based cohort study.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) should be used cautiously in patients with type 2 diabetes. We examined whether the cardiovascular risks associated with NSAID use depended on HbA1c level in patients with type 2 diabetes. METHODS: We conducted a population-based cohort study of all adult Danes with a first-time HbA1c measurement ≥48 mmol/mol during 2012-2020 (n = 103 308). We used information on sex, age, comorbidity burden, and drug use to calculate time-varying inverse probability of treatment weights. After applying these weights in a pooled logistic regression, we estimated hazard ratios (HRs) of the association between use of NSAIDs (ibuprofen, naproxen, or diclofenac) and cardiovascular events (a composite of myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, and all-cause death). We stratified all analyses by HbA1c level (<53 or ≥53 mmol/mol). RESULTS: For ibuprofen use, the HR of a cardiovascular event was 1.53 (95% confidence interval [CI]: 1.34-1.75) in patients with HbA1c <53 and 1.24 (95% CI: 1.00-1.53) in patients with HbA1c ≥53 mmol/mol. For naproxen use, the HR was 1.14 (95% CI: 0.59-2.21) in patients with HbA1c <53 and 1.30 (95% CI: 0.49-3.49) in patients with HbA1c ≥53 mmol/mol. For diclofenac use, the HR was 2.40 (95% CI: 1.62-3.56) in patients with HbA1c <53 and 2.89 (95% CI: 1.65-5.04) in patients with HbA1c ≥53 mmol/mol. CONCLUSIONS: In patients with type 2 diabetes, glycemic dysregulation did not affect the cardiovascular risk associated with NSAID use.

Ability of the DANCAMI to predict the risk ischemic stroke and mortality in patients with atrial fibrillation/flutter.

OBJECTIVES: Comparison of the danish comorbidity index for acute myocardial infarction (DANCAMI), the charlson comorbidity index (CCI), the elixhauser comorbidity index (ECI), and the CHA2DS2-VASc score to predict ischemic stroke, cardiovascular mortality, and all-cause mortality after atrial fibrillation/flutter. MATERIALS AND METHODS: A population-based cohort study of all Danish patients with incident atrial fibrillation/flutter during 2000-2020 (n=361,901). C-Statistics were used to evaluate the discriminatory performance for predicting 1 and 5-year risks of the outcomes for a baseline model (including age and sex) +/- the individual indices. RESULTS: For the DANCAMI, the 5-year risk did not increase with comorbidity burden for ischemic stroke (5.9% for low vs. 5.6% for severe) but did increase for cardiovascular mortality (10% for low vs. 16% for severe) and all-cause mortality (33% for low vs. 61% for severe). C-Statistics for predicting 5-year ischemic stroke risk were similar for all models (0.64). C-Statistics for predicting 5-year cardiovascular mortality risk were also similar for the baseline (0.76), the DANCAMI (0.77), the CCI (0.76), the ECI (0.76), and the CHA2DS2-VASc (0.76) models. C-Statistics for predicting 5-year all-cause mortality risk were lower for the baseline (0.71) and the CHA2DS2-VASc (0.71) models than for the DANCAMI (0.75), the CCI (0.74), and the ECI (0.74) models. The 1-year C-Statistics were comparable. CONCLUSION: The DANCAMI predicted ischemic stroke and cardiovascular mortality risks similar to the CCI, the ECI, and the CHA2DS2-VASc. The DANCAMI predicted all-cause mortality risk similar to the CCI and the ECI, but better than the baseline and the CHA2DS2-VASc.

Trends in the incidence and mortality of intracerebral hemorrhage, and the associated risk factors, in Denmark from 2004 to 2017.

BACKGROUND AND PURPOSE: The distribution of the major modifiable risk factors for intracerebral hemorrhage (ICH) changes rapidly. These changes call for contemporary data from large-scale population-based studies. The aim of the present study was to examine trends in incidence, risk factors, and mortality in ICH patients from 2004 to 2017. METHODS: In a population-based cohort study, we calculated age- and sex-standardized incidence rates (SIRs), incidence rates (IRs) stratified by age and sex per 100,000 person-years, and trends in risk profiles. We estimated absolute mortality risk, and the Cox proportional hazards regression multivariable-adjusted hazard ratios for 30-day and 1-year mortality. RESULTS: We included 16,902 patients (53% men; median age 75 years) from 2004 to 2017. The SIR of ICH decreased from 33 (95% confidence interval [CI] 32-34) in 2004/2005 to 28 (95% CI 27-29) in 2016/2017. Among patients aged ≥70 years, the IR decreased from 137 (95% CI 130-144) in 2004/2005 to 112 (95% CI 106-117) in 2016/2017. The IR in patients aged <70 years was unchanged. From 2004 to 2017, the proportion of patients with hypertension increased from 49% to 66%, the use of oral anticoagulants increased from 7% to 18%, and the use of platelet inhibitors decreased from 40% to 28%. The adjusted hazard ratio for 30-day mortality in 2016/2017 was 0.94 (95% CI 0.89-1.01) and 1-year mortality was 0.98 (95% CI 0.93-1.04) compared with 2004/2005. CONCLUSION: The incidence of spontaneous ICH decreased from 2004 to 2017, with no clear trend in mortality. The risk profile of ICH patients changed substantially, with increasing proportions of hypertension and anticoagulant treatment. Given the high mortality rate of ICH, further advances in prevention and treatment are urgently needed.

Rapid Rule-Out of Myocardial Infarction After 30 Minutes as an Alternative to 1 Hour: The RACING-MI Cohort Study.

STUDY OBJECTIVE: The aim of this study was to investigate whether myocardial infarction can be safely ruled in or out after 30 minutes as an alternative to 1 hour. METHODS: This was a prospective, single-center clinical study enrolling patients admitted to the emergency department. Patients with chest pain suggestive of myocardial infarction were eligible for inclusion. There was no walk-in to the emergency department, and patients with highly elevated out-of-hospital troponin were transferred directly to an invasive heart center. High-sensitivity troponin I was measured at admission (0 hour), 30 minutes, 1 hour, and 3 hours. Diagnostic performance was assessed using the sensitivity and negative predictive value (primary endpoints) as measures of ability to rule out myocardial infarction. Specificity and positive predictive value of myocardial infarction were used as measures for the ability to rule in myocardial infarction (secondary endpoints). RESULTS: In total, 1,003 patients qualified for analysis. Median age was 64 (interquartile range 52 to 74) years, and 42% were women. Myocardial infarction was confirmed in 9% of patients. In the validation cohort (n=503), the 0-h/30-min algorithm assigned 242 (48%) patients to rule out, 54 (11%) to rule in, and 207 (41%) to the observational zone. This resulted in a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (95% confidence interval 98.5% to 100%), specificity of 96.7% (94.7% to 98.2%), and positive predictive value of 72.2% (58.4% to 83.5%). In comparison, the 0-h/1-h algorithm performed with a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (98.5% to 100%), specificity of 97.2% (95.2% to 98.5%), and positive predictive value of 75.5% (61.7% to 86.2%). CONCLUSION: The accelerated 0-h/30-min algorithm allowed for safe rule-out of myocardial infarction 30 minutes after admission. The rule-in ability of the 0-h/30-min algorithm was comparable to that of the 0-h/1h algorithm.

The West Jutland Tele-Electrocardiogram Registry (WEJU-tECG): content, data quality, and research potential.

AIM: To present the content, data quality, and research potential of the West Jutland Tele-Electrocardiogram Registry (WEJU-tECG). METHODS: Danish patients reporting symptoms indicating heart disease in the prehospital setting are subjected to a 12-lead tele-electrocardiogram (ECG) in the ambulance, which is digitally sent to a local tele-centre. WEJU-tECG is a newly established Danish registry containing information from the individual tele-ECGs received at the Regional Hospital West Jutland tele-centre. RESULTS: WEJU-tECG holds extracted information from all tele-ECGs with a valid Civil Personal Register number between 2011 and 2020. WEJU-tECG contains information on patient characteristics, tele-ECG data (including a computerised tele-ECG interpretation), vital signs, and time information. A unique Civil Personal Register number allows individual-level linkage between WEJU-tECG and other Danish registries and enables complete follow-up. WEJU-tECG contains 43,696 tele-ECGs from 29,489 different patient contacts among 20,280 different patients. WEJU-tECG contains 5566 patients with ST-segment deviations. The median age is 67 years and 45% are women. Completeness is highest for time information (100% for all variables), tele-ECG data (99% for heart rate, the specific intervals and axes, and QRS duration, and 86% for J-point deviation), and patient characteristics (100% for all variables). Completeness is lowest for vital signs (13% for systolic, diastolic, and mean arterial blood pressure, and 12% for blood oxygen saturation). The computerised tele-ECG interpretation had a negative predictive value of 80% for ST-segment elevation myocardial infarction and 94% for non-ST-segment elevation myocardial infarction and a positive predictive value of 45% for ST-segment elevation myocardial infarction and 32% for non-ST-segment elevation myocardial infarction. CONCLUSIONS: WEJU-tECG is a novel population-based tele-ECG registry with high research potential.

SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis.

OBJECTIVE: To examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes. METHODS: This nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use. RESULTS: The study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users. CONCLUSIONS: ACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic. TRIAL REGISTRATION NUMBER: EUPAS34887.

Trends in first-time hospitalization, management, and short-term mortality in acute myocardial infarction-related cardiogenic shock from 2005 to 2017: A nationwide cohort study.

BACKGROUND: Cardiogenic shock remains the leading cause of in-hospital death in acute myocardial infarction (AMI). Because of temporary changes in management of cardiogenic shock with widespread implementation of early revascularization along with increasing attention to the use of mechanical circulatory devices, complete and longitudinal data are important in this subject. The objective of this study was to examine temporal trends of first-time hospitalization, management, and short-term mortality for patients with AMI-related cardiogenic shock (AMICS). METHODS: Using nationwide medical registries, we identified patients hospitalized with first-time AMI and cardiogenic shock from January 1, 2005, through December 31, 2017. We calculated annual incidence proportions of AMICS. Thirty-day mortality was estimated with use of Kaplan-Meier estimator comparing AMICS and AMI-only patients. Multivariable Cox regression models were used to assess mortality rate ratios. RESULTS: We included 101,834 AMI patients of whom 7,040 (7%) had AMICS. The median age was 72 (interquartile range: 62-80) for AMICS and 69 (interquartile range: 58-79) for AMI-only patients. The gender composition was similar between AMICS and AMI-only patients (male: 64% vs 63%). The annual incidence proportion of AMICS decreased slightly over time (2005: 7.0% vs 2017: 6.1%, P for trend < .0001). In AMICS, use of coronary angiography increased between 2005 and 2017 from 48% to 71%, as did use of left ventricular assist device (1% vs 10%) and norepinephrine (30% to 70%). In contrast, use of intra-aortic balloon pump (14% vs 1%) and dopamine (34% vs 20%) decreased. Thirty-day mortality for AMICS patients was 60% (95% CI: 59-61) and substantially higher than the 8% (95% CI: 7.8-8.2) for AMI-only patients (mortality rate ratio: 11.4, 95% CI: 10.9-11.8). Over time, the mortality decreased after AMICS (2005: 68% to 2017: 57%, P for temporal change in adjusted analysis < .0001). CONCLUSIONS: We observed a slight decrease in AMICS hospitalization over time with changing practice patterns. Thirty-day mortality was markedly higher for patients with AMICS compared with AMI only, yet our results suggest improved 30-day survival over time after AMICS.

Time-dependent incidence and risk for myocardial infarction in patients with alcoholic cirrhosis.

BACKGROUND: It remains unsettled whether alcoholic cirrhosis is a risk factor for myocardial infarction (MI). METHODS: We used data from nationwide healthcare registries to study all Danes diagnosed with alcoholic cirrhosis in 1996-2014, and five controls were matched to each of them on gender and age. We excluded everyone with ischaemic heart disease and used Cox regression to estimate the incidence rate ratio of MI adjusted for potential cardiovascular confounders. Further, we described the MI-risk with non-MI death as a competing risk. RESULTS: We included 22 867 patients (67% men) with a median age of 57 years. During the first year of follow-up, their incidence rate ratio of MI was increased to 1.24 (95% CI: 0.94-1.62), driven by the effect among women (2.13, 95% CI: 1.17-3.87) and those with most severe cirrhosis (1.32, 95% CI: 0.91-1.90). After the first year, the overall incidence rate ratio fell to (0.89, 95% CI: 0.76-1.05). Patients were more likely to die from non-MI causes (33.7% vs 1.0%), which protected them against MI. The overall 1-year MI-risk was similar in patients and controls: 0.38% (95% CI: 0.30-0.47%) vs 0.34% (95% CI: 0.31-0.38%). After five years of follow-up, male patients had lower MI-risk than their controls, whereas women with cirrhosis had an increased MI-risk throughout follow-up. CONCLUSIONS: The incidence rate of MI was increased the first year following a diagnosis of alcoholic cirrhosis, in particular in women and those with most severe liver disease. Due to the competing risk of non-MI mortality, the MI-risk was not increased.

Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.

BACKGROUND: Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation. OBJECTIVE: To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation. METHODS: Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review. RESULTS: We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors. LIMITATIONS: Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data. CONCLUSION: Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.

Atopic eczema and major cardiovascular outcomes: A systematic review and meta-analysis of population-based studies.

BACKGROUND: Atopic eczema is a common inflammatory skin disease. Various inflammatory conditions have been linked to cardiovascular disease, a major cause of global mortality and morbidity. OBJECTIVE: We sought to systematically review and meta-analyze population-based studies assessing associations between atopic eczema and specific cardiovascular outcomes. METHODS: MEDLINE, Embase, and Global Health were searched from inception to December 2017. We obtained pooled estimates using random-effects meta-analyses. We used a multivariate Bayesian meta-regression model to estimate the slope of effect of increasing atopic eczema severity on cardiovascular outcomes. RESULTS: Nineteen relevant studies were included. The effects of atopic eczema reported in cross-sectional studies were heterogeneous, with no evidence for pooled associations with angina, myocardial infarction, heart failure, or stroke. In cohort studies atopic eczema was associated with increased risk of myocardial infarction (n = 4; relative risk [RR], 1.12; 95% CI, 1.00-1.25), stroke (n = 4; RR, 1.10; 95% CI, 1.03-1.17), ischemic stroke n = 4; RR, 1.17; 95% CI, 1.14-1.20), angina (n = 2; RR, 1.18; 95% CI, 1.13-1.24), and heart failure (n = 2; RR, 1.26; 95% CI, 1.05-1.51). Prediction intervals were wide for myocardial infarction and stroke. The risk of cardiovascular outcomes appeared to increase with increasing severity (mean RR increase between severity categories, 1.15; 95% credibility interval, 1.09-1.21; uncertainty interval, 1.04-1.28). CONCLUSION: Significant associations with cardiovascular outcomes were more common in cohort studies but with considerable between-study heterogeneity. Increasing atopic eczema severity was associated with increased risk of cardiovascular outcomes. Improved awareness among stakeholders regarding this small but significant association is warranted.

Higher Risk of Vascular Dementia in Myocardial Infarction Survivors.

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

Positive predictive value of infective endocarditis in the Danish National Patient Registry: a validation study.

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

Risk of venous thromboembolism in patients with mycosis fungoides and parapsoriasis: A Danish nationwide population-based cohort study.

BACKGROUND: Mycosis fungoides (MF) and parapsoriasis are characterized by malignant proliferation and chronic inflammation, which may affect the risk for venous thromboembolism (VTE). OBJECTIVES: To examine the risk for VTE in patients with MF and parapsoriasis. METHODS: We conducted a nationwide population-based cohort study in Denmark to examine the relative risk (RR) of VTE in 525 patients with MF and 634 patients with parapsoriasis compared with that in sex- and age-matched controls from the general population. RESULTS: In patients with MF, the 10-year absolute risk for VTE was 3.4% (95% confidence interval [CI], 2.0-5.4). The adjusted RRs were 2.41 (95% CI, 1.49-3.90) for VTE and 4.01 (95% CI, 2.16-7.46) for pulmonary embolism. Notably, within the first 5 years after diagnosis with MF, the RR of pulmonary embolism was increased 6.7-fold (to 6.71 [95% CI, 2.86-15.72]). Patients with parapsoriasis had a 2.7-fold increased RR of VTE (to 2.67 [95% CI, 1.32-5.40]) in the absence of other established VTE risk factors. LIMITATIONS: We had no information regarding disease stage of MF and prescribed drugs. CONCLUSION: Patients with MF and parapsoriasis had an increased RR of VTE, although the absolute risk remained low. These findings should increase awareness of comorbidities in patients with MF and parapsoriasis.