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.

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 after out-of-hospital cardiac arrest in immigrants vs natives in Denmark.

AIMS: Ethnic disparities subsist in out-of-hospital cardiac arrest (OHCA) outcomes in the US, yet it is unresolved whether similar inequalities exist in European countries. This study compared survival after OHCA and its determinants in immigrants and non-immigrants in Denmark. METHODS: Using the nationwide Danish Cardiac Arrest Register, 37,622 OHCAs of presumed cardiac cause between 2001 and 2019 were included, 95% in non-immigrants and 5% in immigrants. Univariate and multiple logistic regression was used to assess disparities in treatments, return of spontaneous circulation (ROSC) at hospital arrival, and 30-day survival. RESULTS: Immigrants were younger at OHCA (median 64 [IQR 53-72] vs 68 [59-74] years; p < 0.05), had more prior myocardial infarction (15% vs 12%, p < 0.05), more diabetes (27% vs 19%, p < 0.05), and were more often witnessed (56% vs 53%; p < 0.05). Immigrants received similar bystander cardiopulmonary resuscitation and defibrillation rates to non-immigrants, but more coronary angiographies (15% vs 13%; p < 0.05) and percutaneous coronary interventions (10% vs 8%, p < 0.05), although this was insignificant after age-adjustment. Immigrants had higher ROSC at hospital arrival (28% vs 26%; p < 0.05) and 30-day survival (18% vs 16%; p < 0.05) compared to non-immigrants, but adjusting for age, sex, witness status, first observed rhythm, diabetes, and heart failure rendered the difference non-significant (odds ratios (OR) 1.03, 95% confidence interval (CI) 0.92-1.16 and OR 1.05, 95% CI 0.91-1.20, respectively). CONCLUSIONS: OHCA management was similar between immigrants and non-immigrants, resulting in similar ROSC at hospital arrival and 30-day survival after adjustments.

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).

External validation of the simple NULL-PLEASE clinical score in predicting outcomes of out-of-hospital cardiac arrest in the Danish population - A nationwide registry-based study.

AIM: The NULL-PLEASE score (Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood pH < 7.2, Lactate > 7.0 mmol/L, End-stage renal disease on dialysis, Age ≥85 years, Still resuscitation, and Extracardiac cause) may identify patients with out-of-hospital cardiac arrest (OHCA) unlikely to survive. We aimed to validate the NULL-PLEASE score in a nationwide setting. METHODS: We used Danish nationwide registry data from 2001 to 2019 and identified OHCA survivors with return of spontaneous circulation (ROSC) or ongoing cardiopulmonary resuscitation at hospital arrival. The primary outcome was 1-day mortality. Secondary outcomes were 30-day mortality and the combined outcome of 1-year mortality or anoxic brain damage. The risks of outcomes were estimated using logistic regression with a NULL-PLEASE score of 0 as reference (range 0-14). The predictive ability of the score was examined using the area under the receiver operating characteristics (AUCROC) curve. RESULTS: A total of 3,881 patients were included in the analyses. One-day mortality was 35%, 30-day mortality was 61%, and 68% experienced the combined outcome. For a NULL-PLEASE score ≥9 (n = 244) the absolute risks were: 1-day mortality: 80.7% (95% confidence interval [CI]: 75.8-85.7%); 30-day mortality: 98.0% (95% CI: 96.2-99.7%); and the combined outcome: 98.4% (95% CI: 96.8-100.0%). Corresponding AUCROC values were 0.800 (95% CI: 0.786-0.814) for 1-day mortality, 0.827 (95% CI: 0.814-0.840) for 30-day mortality, and 0.828 (95% CI: 0.815-0.841) for the combined outcome. CONCLUSIONS: In a nationwide OHCA-cohort, AUCROC values for the predictive ability of NULL-PLEASE were high for all outcomes. However, some survived even with high NULL-PLEASE scores.

[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.

Risk of out-of-hospital cardiac arrest in antidepressant drug users.

Conflicting results have been reported regarding the association between antidepressant use and out-of-hospital cardiac arrest (OHCA) risk. We investigated whether the use of antidepressants is associated with OHCA. METHODS: We conducted a nationwide nested case-control study to assess the association of individual antidepressant drugs within drug classes with the hazard of OHCA. Cases were defined as OHCA from presumed cardiac causes. Cox regression with time-dependent exposure and time-dependent covariates was conducted to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) overall and in subgroups defined by established cardiac disease and cardiovascular risk factors. Also, we studied antidepressants with and without sodium channel blocking or potassium channel blocking properties separately. RESULTS: During the study period from 2001 to 2015 we observed 10 987 OHCA cases, and found increased OHCA rate for high-dose citalopram (>20 mg) and high-dose escitalopram (>10 mg; HR:1.46 [95% CI:1.27-1.69], HR:1.43 [95% CI:1.16-1.75], respectively) among selective serotonin reuptake inhibitors (reference drug sertraline), and for high-dose mirtazapine (>30; HR:1.59 [95% CI:1.18-2.14]) among the serotonin-norepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine). Among tricyclic antidepressants (reference drug amitriptyline), no drug was associated with significantly increased OHCA rate. Increased OHCA rate was found for antidepressants with known potassium channel blocking properties (HR:1.14 [95% CI:1.05-1.23]), but for not those with sodium channel blocking properties. Citalopram, although not statistically significant, and mirtazapine were associated with increased OHCA rate in patients without cardiac disease and cardiovascular risk factors. CONCLUSION: Our findings indicate that careful titration of citalopram, escitalopram and mirtazapine dose may have to be considered due to drug safety issues.

Out-of-hospital cardiac arrest and differential risk of cardiac and non-cardiac QT-prolonging drugs in 37 000 cases.

AIMS: Drugs that prolong the QT interval, either by design (cardiac QT-prolonging drugs: anti-arrhythmics) or as off-target effect (non-cardiac QT-prolonging drugs), may increase the risk of ventricular arrhythmias and out-of-hospital cardiac arrest (OHCA). Risk mitigation measures were instituted, in particular, surrounding prescription of cardiac QT-prolonging drugs. We studied OHCA risk of both drug types in current clinical practice. METHODS: Using data from large population-based OHCA registries in the Netherlands and Denmark, we conducted two independent case-control studies. OHCA cases with presumed cardiac causes were matched on age/sex/index date with up to five non-OHCA controls. We calculated odds ratios (ORs) for the association of cardiac or non-cardiac QT-prolonging drugs with OHCA risk using conditional logistic regression analyses. RESULTS: We identified 2503 OHCA cases and 10 543 non-OHCA controls in the Netherlands, and 35 017 OHCA cases and 175 085 non-OHCA controls in Denmark. Compared to no use of QT-prolonging drugs, use of non-cardiac QT-prolonging drugs (Netherlands: cases: 3.0%, controls: 1.9%; Denmark: cases: 14.9%, controls: 7.5%) was associated with increased OHCA risk (Netherlands: OR 1.37 [95% CI: 1.03-1.81]; Denmark: OR 1.63 [95% CI: 1.57-1.70]). The association between cardiac QT-prolonging drugs (Netherlands: cases: 4.0%, controls: 2.5%; Denmark: cases: 2.1%, controls: 0.9%) and OHCA was weaker (Netherlands: OR 1.17 [95% CI: 0.92-1.50]; Denmark: OR 1.21 [95% CI: 1.09-1.33]), although users of cardiac QT-prolonging drugs had more medication use and comorbidities associated with OHCA risk than users of non-cardiac QT-prolonging drugs. CONCLUSION: In clinical practice, cardiac QT-prolonging drugs confer lower OHCA risk than non-cardiac QT-prolonging drugs, although users of the former have higher a priori risk. This is likely due to risk mitigation measures surrounding prescription of cardiac QT-prolonging drugs.

Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40 000-cases across two countries.

AIMS: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA-risk of opioids in the community. METHODS: We conducted 2 population-based case-control studies separately in the Netherlands (2009-2018) and Denmark (2001-2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non-OHCA-controls according to age, sex and OHCA-date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 5473 OHCA-cases matched with 21 866 non-OHCA-controls in the Netherlands, and 35 017 OHCA-cases matched with 175 085 non-OHCA-controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA-risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8-2.5]; Denmark: OR 1.8 [95% CI 1.5-2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5-2.1]; Denmark: OR 1.6 [95% CI 1.5-1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4-4.8], Pinteraction  < .0001; Denmark: OR 2.3 [95% CI: 2.0-2.5], Pinteraction  < .0001). CONCLUSION: Use of opioids is associated with increased OHCA-risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids.

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.

Contacts With the Health Care System Before Out-of-Hospital Cardiac Arrest.

Background It remains challenging to identify patients at risk of out-of-hospital cardiac arrest (OHCA). We aimed to examine health care contacts in patients before OHCA compared with the general population that did not experience an OHCA. Methods and Results Patients with OHCA with a presumed cardiac cause were identified from the Danish Cardiac Arrest Registry (2001-2014) and their health care contacts (general practitioner [GP]/hospital) were examined up to 1 year before OHCA. In a case-control study (1:9), OHCA contacts were compared with an age- and sex-matched background population. Separately, patients with OHCA were examined by the contact type (GP/hospital/both/no contact) within 2 weeks before OHCA. We included 28 955 patients with OHCA. The weekly percentages of patient contacts with GP the year before OHCA were constant (25%) until 1 week before OHCA when they markedly increased (42%). Weekly percentages of patient contacts with hospitals the year before OHCA gradually increased during the last 6 months (3.5%-6.6%), peaking at the second week (6.8%) before OHCA; mostly attributable to cardiovascular diseases (21%). In comparison, there were fewer weekly contacts among controls with 13% for GP and 2% for hospital contacts (P<0.001). Within 2 weeks before OHCA, 57.8% of patients with OHCA had a health care contact, and these patients had more contacts with GP (odds ratio [OR], 3.17; 95% CI, 3.09-3.26) and hospital (OR, 2.32; 95% CI, 2.21-2.43) compared with controls. Conclusions The health care contacts of patients with OHCA nearly doubled leading up to the OHCA event, with more than half of patients having health care contacts within 2 weeks before arrest. This could have implications for future preventive strategies.

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.

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.

Association Between ECG Abnormalities and Fatal Cardiovascular Disease Among Patients With and Without Severe Mental Illness.

Background ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. Methods and Results We cross-linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10-year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (P<0.001). Severe mental illness was associated with fatal CVD across no (HR, 2.17; 95% CI, 1.95-2.43), minor (HR, 1.90; 95% CI, 1.49-2.42), and major (HR, 1.40; 95% CI, 1.26-1.55) ECG abnormalities compared with controls. Across age- and sex-specific subgroups, SMI patients with ECG abnormalities but no CVD at baseline had highest standardized 10-year absolute risks of fatal CVD. Conclusions ECG abnormalities conferred a poorer prognosis among patients with SMI compared with controls without mental illness. SMI patients with ECG abnormalities but no CVD represent a high-risk population that may benefit from greater surveillance and risk management.

Association of beta-blockers and first-registered heart rhythm in out-of-hospital cardiac arrest: real-world data from population-based cohorts across two European countries.

AIMS: Conflicting results have been reported regarding the effect of beta-blockers on first-registered heart rhythm in out-of-hospital cardiac arrest (OHCA). We aimed to establish whether the use of beta-blockers influences first-registered rhythm in OHCA. METHODS AND RESULTS: We included patients with OHCA of presumed cardiac cause from two large independent OHCA-registries from Denmark and the Netherlands. Beta-blocker use was defined as exposure to either non-selective beta-blockers, ß1-selective beta-blockers, or α-ß-dual-receptor blockers within 90 days prior to OHCA. We calculated odds ratios (ORs) for the association of beta-blockers with first-registered heart rhythm using multivariable logistic regression. We identified 23 834 OHCA-patients in Denmark and 1584 in the Netherlands: 7022 (29.5%) and 519 (32.8%) were treated with beta-blockers, respectively. Use of non-selective beta-blockers, but not ß1-selective blockers, was more often associated with non-shockable rhythm than no use of beta-blockers [Denmark: OR 1.93, 95% confidence interval (CI) 1.48-2.52; the Netherlands: OR 2.52, 95% CI 1.15-5.49]. Non-selective beta-blocker use was associated with higher proportion of pulseless electrical activity (PEA) than of shockable rhythm (OR 2.38, 95% CI 1.01-5.65); the association with asystole was of similar magnitude, although not statistically significant compared with shockable rhythm (OR 2.34, 95% CI 0.89-6.18; data on PEA and asystole were only available in the Netherlands). Use of α-ß-dual-receptor blockers was significantly associated with non-shockable rhythm in Denmark (OR 1.21; 95% CI 1.03-1.42) and not significantly in the Netherlands (OR 1.37; 95% CI 0.61-3.07). CONCLUSION: Non-selective beta-blockers, but not ß1-selective beta-blockers, are associated with non-shockable rhythm in OHCA.

Socioeconomic differences in coronary procedures and survival after out-of-hospital cardiac arrest: A nationwide Danish study.

AIM: It remains unclear whether socioeconomic differences exist in post-resuscitation care in out-of-hospital cardiac arrests (OHCA). We aimed to examine socioeconomic differences in coronary procedures and survival after OHCA. METHODS: OHCA patients ≥30 years of cardiac cause with a hospital admission from the Danish Cardiac Arrest Registry, 2001-2014, were divided according to quartiles of household income (lowest, low, high, highest). Associations of income, coronary procedures and 30-day survival were examined by age-standardized incidence rates and incidence rate ratios (IRR), and by logistic regression. RESULTS: A total of 6105 patients were included. Higher-income patients were younger, males and had less comorbidity-burden. Higher-income patients had higher incidence rates for coronary angiographies both day 0-1 and day 2-7 after OHCA (day 0-1: highest: IRR 1.79, 95%CI 1.46-2.21; high: IRR 1.28, 95%CI 1.10-1.51; low: IRR 1.05, 95%CI 0.90-1.23), compared to lowest. Fifty-four percentage of the patients undergoing a coronary angiography received percutaneous-coronary-intervention or coronary-artery-bypass-grafting with no difference among three of the four groups, but lower IRR in low-income patients (IRR 0.74, 95%CI 0.61-0.89) compared to lowest. Higher-income patients had also higher odds for 30-day survival compared to lowest, both in patients with (highest: OR 1.61, 95%CI 1.12-2.32; high: OR 1.13, 95%CI 0.80-1.60; low: OR 1.14, 95%CI 0.81-1.61) and without (highest: OR 2.54, 95%CI 1.83-3.53; high: OR 1.41, 95%CI 1.06-1.87; low: OR 1.12, 95%CI 0.86-1.47) coronary angiography day 0-1. CONCLUSION: Higher-income patients were found associated with more performed coronary angiographies after OHCA, and higher odds for 30-day survival.

Electrocardiogram Characteristics and Their Association With Psychotropic Drugs Among Patients With Schizophrenia.

BACKGROUND: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia. METHODS: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39). CONCLUSIONS: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group.

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.

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.