Outcomes of out-of-hospital cardiac arrest in adult congenital heart disease: a Danish nationwide study.

AIMS: The risk, characteristics, and outcome of out-of-hospital cardiac arrest (OHCA) in patients with congenital heart disease (CHD) remain scarcely investigated. METHODS AND RESULTS: An epidemiological registry-based study was conducted. Using time-dependent Cox regression models fitted with a nested case-control design, hazard ratios (HRs) with 95% confidence intervals of OHCA of presumed cardiac cause (2001-19) associated with simple, moderate, and severe CHD were calculated. Moreover, using multiple logistic regression, we investigated the association between pre-hospital OHCA characteristics and 30-day survival and compared 30-day survival in OHCA patients with and without CHD. Overall, 43 967 cases (105 with simple, 144 with moderate, and 53 with severe CHD) and 219 772 controls (median age 72 years, 68.2% male) were identified. Any type of CHD was found to be associated with higher rates of OHCA compared with the background population [simple CHD: HR 1.37 (1.08-1.70); moderate CHD: HR 1.64 (1.36-1.99); and severe CHD: HR 4.36 (3.01-6.30)]. Pre-hospital cardiopulmonary resuscitation and defibrillation were both associated with improved 30-day survival in patients with CHD, regardless of CHD severity. Among patients with OHCA, simple, moderate, and severe CHD had a similar likelihood of 30-day survival compared with no CHD [odds ratio 0.95 (0.53-1.69), 0.70 (0.43-1.14), and 0.68 (0.33-1.57), respectively]. CONCLUSION: A higher risk of OHCA was found throughout the spectrum of CHD. Patients with and without CHD showed the same 30-day survival, which relies on the pre-hospital chain of survival, namely cardiopulmonary resuscitation and defibrillation.

Outcomes of prolonged dual anti-platelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A nationwide registry-based study.

BACKGROUND: Randomized controlled trials have shown a reduced risk of ischemic events and an increased risk of bleeding in patients treated with prolonged dual anti-platelet therapy (DAPT) beyond 12 months following acute coronary syndrome (ACS). We aimed to investigate outcomes of prolonged DAPT vs aspirin monotherapy (ASA) in a real-world population. METHODS AND RESULTS: Using nationwide registries, we identified all patients with ACS who underwent percutaneous coronary intervention and received 12-month DAPT between January 2013 and October 2016. Patients still on DAPT were compared to patients on ASA at index date (15 months after ACS-date) and followed for up to 2 years. Cox regression models were employed to calculate standardized risks of all-cause mortality, major adverse cardiovascular event (MACE), and major bleeding. The study included 7,449 patients, 1,901 on DAPT (median age 66, 72.1% male) and 5,548 on ASA (median age 65, 75.1% male). Standardized absolute 2-year risk of all-cause mortality, MACE, and major bleeding was 2.7%, 3.7%, and 5.4% for DAPT vs 2.2%, 3.8%, and 1.3% for ASA. DAPT was not associated with a significant standardized 2-year risk difference (SRD) of all-cause mortality (SRD: 0.5%, 95% confidence interval [CI]: -0.9 to 1.7) or MACE (SRD: -0.1%, 95% CI -1.8 to 1.6), but a significantly higher risk of major bleeding (SRD: 4.1%, 95% CI 1.8-6.6). CONCLUSIONS: In a nationwide cohort of ACS patients undergoing percutaneous coronary intervention, prolonged DAPT was not significantly associated with a reduced risk of all-cause mortality or MACE, but an increased risk of major bleeding. Future randomized controlled trials should investigate the optimal anti-platelet regimen in this patient group.

Severe mental illness is associated with increased mortality and severe course of COVID-19.

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.

Management of dyslipidaemia in individuals with severe mental illness: a population-based study in the Greater Copenhagen Area.

Background: Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in patients with SMI. Objectives: To assess management of dyslipidaemia in patients with SMI versus healthy controls (HCs) in 2005 and 2015. Design and methods: Using Danish registers, we identified adult patients with SMI in the Greater Copenhagen Area (schizophrenia spectrum disorders or bipolar disorder) with ⩾1 general practitioner contact in the year before 2005 and 2015, respectively, and HCs without SMI matched on age and gender (1:5). Outcomes were lipid-profile measurements, presence of dyslipidaemia and redemption of lipid-lowering pharmacotherapy. Differences in outcomes between patients with SMI and controls were measured with multivariable logistic regression. Results: We identified 7217 patients with SMI in 2005 and 9939 in 2015. After 10 years, patients went from having lower odds of lipid measurements to having higher odds of lipid measurements compared with HCs [odds ratio (OR)2005 0.70 (99% confidence interval (CI) 0.63-0.78) versus OR2015 1.34 (99% CI 1.24-1.44); p2005versus2015 < 0.01]. Patients had higher odds of dyslipidaemia during both years [OR2005 1.43 (99% CI 1.10-1.85) and OR2015 1.23 (99% CI 1.08-1.41)]. Patients went from having lower odds of receiving lipid-lowering pharmacotherapy to having higher odds of receiving lipid-lowering pharmacotherapy [OR2005 0.77 (99% CI 0.66-0.89) versus OR2015 1.37 (99% CI 1.24-1.51); p2005versus2015 < 0.01]. However, among persons at high cardiovascular risk, patients had lower odds of receiving lipid-lowering pharmacotherapy during both years, including subsets with previous acute coronary syndrome [OR2005 0.30 (99% CI 0.15-0.59) and OR2015 0.44 (99% CI 0.24-0.83)] and ischaemic stroke or transient ischaemic attack (TIA) [OR2005 0.43 (99% CI 0.26-0.69) and OR 2015 0.61 (99% CI 0.41-0.89)]. Conclusion: These results imply an increased general awareness of managing dyslipidaemia among patients with SMI in the primary prophylaxis of cardiovascular disease. However, secondary prevention with lipid-lowering drugs in patients with SMI at high cardiovascular risk may be lacking.

[Dyslipidaemia in patients with mental illness].

Dyslipidaemia is a modifiable cause of increased mortality in patients with mental illness. We described prevalence, aetiology and treatment of dyslipidaemia in patients with mental illness. Patients with mental illness have a higher prevalence of dyslipidaemia than the general population due to genetic predisposition, unhealthy lifestyle and/or psychotropic medications. Attention towards early identification of dyslipidaemia, close monitoring, and a low threshold for initiating treatment with lifestyle interventions and lipid-lowering agents are warranted in patients with mental illness.

Ethnic disparities in out-of-hospital cardiac arrest: A population-based cohort study among adult Danish immigrants.

Background: Ethnicity might impact out-of-hospital cardiac arrest (OHCA) risk, but it has scarcely been studied in Europe. We aimed to assess whether ethnicity influenced the risk of OHCA of cardiac cause in Danish immigrants and its interplay with risk factors for OHCA and socioeconomic status. Methods: This nationwide study included all immigrants between 18 and 80 years present in Denmark at some point between 2001 and 2020. Regions of origin were defined as Africa, Arabic countries, Asia, Eastern Europe, Latin America, and Western countries. OHCAs with presumed cardiac cause were identified from the Danish Cardiac Arrest Registry. Findings: Overall, among 1,011,565 immigrants, a total of 1,801 (0.2%) OHCAs (median age 64 (Q1-Q3 53-72) years, 72% males) occurred. The age- and sex- standardized (reference: Western countries) incidence of OHCA (/1,00,000 person-years) was 34.6 (27.8-43.4) in African, 34.1 (30.4-38.4) in Arabic, 33.5 (29.3-38.2) in Asian, 35.6 (31.9-39.6) in Eastern European, and 16.2 (9.0-27.2) in Latin American immigrants. When selecting Western origin as a reference, and after adjusting on OHCA risk factors, Arabic (HR 1.18, 95%CI 1.04-1.35; P=0.01), Eastern European (HR 1.28, 95%CI 1.13-1.46; P<0.001), and African origin (HR 1.34, 95%CI 1.10-1.63; P<0.01) were associated with higher risk of OHCA, whereas Latin American origin (HR 0.58, 95%CI 0.35-0.0.96; P=0.03) was associated with lower risk of OHCA. Comparable results were observed when adjusting on education level and economic status. Interpretation: This study emphasizes that ethnicity is associated with OHCA risk, even when considering traditional cardiac arrest risk factors. Funding: R Garcia received a grant from the Fédération Française de Cardiologie for his post-doctoral fellowship and this work was supported by the Novo Nordisk Foundation Tandem Programme 2022 (grant# 31364).

Risk of out-of-hospital cardiac arrest in patients with bipolar disorder or schizophrenia.

OBJECTIVE: Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated. METHODS: We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001-2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs. RESULTS: We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics-but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)-increased OHCA hazard compared with no use in both disorders. CONCLUSIONS: Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms.

Out-of-hospital cardiac arrest: 30-day survival and 1-year risk of anoxic brain damage or nursing home admission according to consciousness status at hospital arrival.

AIM: To investigate the association between consciousness status at hospital arrival and long-term outcomes in out-of-hospital cardiac arrest (OHCA) patients. METHODS: OHCAs between 18-100 years of age were identified from the Danish Cardiac Arrest Registry during 2005-2014. Patients with return of spontaneous circulation (ROSC) or ongoing cardiopulmonary resuscitation (CPR) at hospital arrival were included. Thirty-day survival was evaluated using Kaplan-Meier estimates. Risk of anoxic brain damage or nursing home admission and return to work among 30-day survivors were evaluated using Aalen-Johansen estimates and cause-specific Cox regression. RESULTS: Upon hospital arrival of 13,953 OHCA patients, 776 (5.6%) had ROSC and were conscious (Glasgow Coma Score [GCS]>8), 5205 (37.3%) had ROSC, but were comatose (GCS ≤ 8), and 7972 (57.1%) had ongoing CPR. Thirty-day survival according to status at hospital arrival among patients that were conscious, comatose, or had ongoing CPR was 89.0% (95% confidence interval [CI] 86.8%-91.2%), 39.0% (95% CI 37.6%-40.3%), and 1.2% (95% CI 1.0%-1.4%), respectively. Among 30-day survivors, 1-year risks of new onset anoxic brain damage or nursing home admission according to consciousness status were 2.4% (95% CI 1.2%-3.6%), 12.9% (95% CI 11.4%-14.3%), and 19.4% (95% CI 11.3%-27.4%), respectively. Among 30-day working-age survivors, more than 65% in each group returned to work within 5 years. CONCLUSION: Consciousness status at hospital arrival was strongly associated with 30-day survival in OHCA patients. Among 30-day survivors, a minority was diagnosed with anoxic brain damage or admitted to a nursing home and the majority returned to work independent of consciousness status at hospital arrival.

Dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A Danish nationwide cohort study.

INTRODUCTION: To investigate the patterns of dose reduction of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF). MATERIALS AND METHODS: Using Danish nationwide registries, we identified all non-valvular AF patients initiated on standard-dose NOAC during 2011-2017 who were followed until dose reduction. The absolute risk of dose reduction was presented as cumulative incidence both overall and according to baseline characteristics. Moreover, to assess baseline comorbidities related to dose reduction, adjusted Cox regression models were used. In subgroup analysis, we investigated dose reduction following acute myocardial infarction and/or percutaneous coronary intervention (MI/PCI), chronic kidney disease (CKD), turned 80 years, intracranial hemorrhage, peripheral bleeding, ischemic stroke, cancer, bone fracture, and antiplatelet treatment start. RESULTS: Of 24,489 patients included, 12.2% experienced dose reduction during the study period. Dabigatran treatment, higher age at inclusion, high CHA2DS2-VASc score, and high HAS-BLED score were related to higher risk of dose reduction. Baseline ischemic heart disease (IHD), heart failure, cancer, CKD, chronic obstructive pulmonale disease (COPD), and hypertension were independent predictors of dose reduction. In subgroup analysis with six-month follow-up, MI/PCI, CKD, intracranial hemorrhage, peripheral bleeding, and antiplatelet treatment therapy were strongly associated with dose reduction. CONCLUSIONS: Dose reduction of NOACs was observed in 12.2% of AF patients during 2011-2017 and was associated with dabigatran treatment, advanced age at baseline, high CHA2DS2-VASc score, and high HAS-BLED score. Among comorbidities, IHD, heart failure, cancer, CKD, COPD, and hypertension predicted dose reduction independently. During six-month follow-up, MI/PCI showed the strongest association with dose reduction.

Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy-A nationwide study in patients with osteoarthritis.

Osteoarthritis (OA) and the non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve OA-associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative registers to examine NSAID use between 1996 and 2015 by Danish patients with OA aged ≥18 years. Using adjusted Cox proportional hazard analyses, we calculated the risk of the composite outcome of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke/TIA, and of each outcome separately, up to 5 years after OA diagnosis. Of 533 502 patients included, 64.3% received NSAIDs and 38 226 (7.2%) experienced a cardiovascular event during follow-up. Compared with non-use, all NSAIDs were associated with increased risk of the composite outcome: hazard ratio (HR) for rofecoxib, 1.90 (95% confidence interval, 1.74-2.08); celecoxib, 1.47 (1.34-1.62); diclofenac, 1.44 (1.36-1.54); ibuprofen, 1.20 (1.15-1.25); and naproxen, 1.20 (1.04-1.39). Similar results were seen for each outcome separately. When celecoxib was used as reference, ibuprofen (HRs: 0.81 [CI: 0.74-0.90]) and naproxen (HRs: 0.81 [0.68-0.97]) exhibited a lower cardiovascular risk, even when low doses were compared. Low-dose naproxen and ibuprofen were associated with the lowest risks of the composite outcome compared to no NSAID use: HRs: 1.12 (1.07-1.19) and 1.16 (0.92-1.42), respectively. In patients with OA, we found significant differences in cardiovascular risk among NSAIDs. Naproxen and ibuprofen appeared to be safer compared to celecoxib, also when we examined equivalent low doses. In terms of cardiovascular safety, naproxen and ibuprofen, at the lowest effective doses, may be the preferred first choices among patients with OA needing pain relief.

Out-of-Hospital Cardiac Arrest in Patients With and Without Psychiatric Disorders: Differences in Use of Coronary Angiography, Coronary Revascularization, and Implantable Cardioverter-Defibrillator and Survival.

Background Healthcare disparities for psychiatric patients are common. Whether these inequalities apply to postresuscitation management in out-of-hospital cardiac arrest (OHCA) is unknown. We investigated differences in in-hospital cardiovascular procedures following OHCA between patients with and without psychiatric disorders. Methods and Results Using the Danish nationwide registries, we identified patients admitted to the hospital following OHCA of presumed cardiac cause (2001-2015). Psychiatric disorders were identified using hospital diagnoses or redeemed prescriptions for psychotropic drugs. We calculated age- and sex-standardized incidence rates and incidence rate ratios (IRRs) of cardiovascular procedures during post-OHCA admission in patients with and without psychiatric disorders. Differences in 30-day and 1-year survival were assessed by multivariable logistic regression in the overall population and among 2-day survivors who received acute coronary angiography (CAG). We included 7288 hospitalized patients who had experienced an OHCA: 1661 (22.8%) had a psychiatric disorder. Compared with patients without psychiatric disorders, patients with psychiatric disorders had lower standardized incidence rates for acute CAG (≤1 day post-OHCA) (IRR, 0.51; 95% CI, 0.45-0.57), subacute CAG (2-30 days post-OHCA) (IRR, 0.40; 95% CI, 0.30-0.52), and implantable cardioverter-defibrillator implantation (IRR, 0.67; 95% CI, 0.48-0.95). Conversely, we did not detect differences in coronary revascularization among patients undergoing CAG (IRR, 1.11; 95% CI, 0.94-1.30). Patients with psychiatric disorders had lower survival even among 2-day survivors who received acute CAG: (odds ratio of 30-day survival, 0.68; 95% CI, 0.52-0.91; and 1-year survival, 0.66; 95% CI, 0.50-0.88). Conclusions Psychiatric patients had a lower probability of receiving post-OHCA CAG and implantable cardioverter-defibrillator implantation compared with nonpsychiatric patients but the same probability of coronary revascularization among patients undergoing CAG. However, their survival was lower irrespective of angiographic procedures.

Out-of-hospital cardiac arrest in patients with psychiatric disorders - Characteristics and outcomes.

AIMS: To investigate whether the recent improvements in pre-hospital cardiac arrest-management and survival following out-of-hospital cardiac arrest (OHCA) also apply to OHCA patients with psychiatric disorders. METHODS: We identified all adult Danish patients with OHCA of presumed cardiac cause, 2001-2015. Psychiatric disorders were defined by hospital diagnoses up to 10 years before OHCA and analyzed as one group as well as divided into five subgroups (schizophrenia-spectrum disorders, bipolar disorder, depression, substance-induced mental disorders, other psychiatric disorders). Association between psychiatric disorders and pre-hospital OHCA-characteristics and 30-day survival were assessed by multiple logistic regression. RESULTS: Of 27,523 OHCA-patients, 4772 (17.3%) had a psychiatric diagnosis. Patients with psychiatric disorders had lower odds of 30-day survival (0.37 95% confidence interval 0.32-0.43) compared with other OHCA-patients. Likewise, they had lower odds of witnessed status (0.75 CI 0.70-0.80), bystander cardiopulmonary resuscitation (CPR) (0.77 CI 0.72-0.83), shockable heart rhythm (0.37 95% CI, 0.33-0.40), and return of spontaneous circulation (ROSC) at hospital arrival (0.66 CI 0.59-0.72). Similar results were seen in all five psychiatric subgroups. The difference in 30-day survival between patients with and without psychiatric disorders increased in recent years: from 8.4% (CI 7.0-10.0%) in 2006 to 13.9% (CI 12.4-15.4%) in 2015 and from 7.0% (4.3-10.8%) in 2006 to 7.0% (CI 4.5-9.7%) in 2015, respectively. CONCLUSION: Patients with psychiatric disorders have lower survival following OHCA compared to non-psychiatric patients and the gap between the two groups has widened over time.