Search

BackgroundSurvival from out‐of‐hospital cardiac arrest (OHCA) varies across regions. The aim of this study was to evaluate the association between urbanization (rural, suburban, and urban areas), bystander interventions (cardiopulmonary resuscitation and defibrillation), and 30‐day survival from OHCAs in Denmark.Methods and ResultsWe included OHCAs not witnessed by ambulance staff in Denmark from January 1, 2016, to December 31, 2020. Patients were divided according to the Eurostat Degree of Urbanization Tool in rural, suburban, and urban areas based on the 98 Danish municipalities. Poisson regression was used to estimate incidence rate ratios. Logistic regression (adjusted for ambulance response time) tested differences between the groups with respect to bystander interventions and survival, according to degree of urbanization. A total of 21 385 OHCAs were included, of which 8496 (40%) occurred in rural areas, 7025 (33%) occurred in suburban areas, and 5864 (27%) occurred in urban areas. Baseline characteristics, as age, sex, location of OHCA, and comorbidities, were comparable between groups. The annual incidence rate ratio of OHCA was higher in rural areas (1.54 [95% CI, 1.48–1.58]) compared with urban areas. Odds for bystander cardiopulmonary resuscitation were lower in suburban (0.86 [95% CI, 0.82–0.96]) and urban areas (0.87 [95% CI, 0.80–0.95]) compared with rural areas, whereas bystander defibrillation was higher in urban areas compared with rural areas (1.15 [95% CI, 1.01–1.31]). Finally, 30‐day survival was higher in suburban (1.13 [95% CI, 1.02–1.25]) and urban areas (1.17 [95% CI, 1.05–1.30]) compared with rural areas.ConclusionsDegree of urbanization was associated with lower rates of bystander defibrillation and 30‐day survival in rural areas compared with urban areas. BACKGROUND: Survival from out-of-hospital cardiac arrest (OHCA) varies across regions. The aim of this study was to evaluate the association between urbanization (rural, suburban, and urban areas), bystander interventions (cardiopulmonary resuscitation and defibrillation), and 30-day survival from OHCAs in Denmark. METHODS AND RESULTS: We included OHCAs not witnessed by ambulance staff in Denmark from January 1, 2016, to December 31, 2020. Patients were divided according to the Eurostat Degree of Urbanization Tool in rural, suburban, and urban areas based on the 98 Danish municipalities. Poisson regression was used to estimate incidence rate ratios. Logistic regression (adjusted for ambulance response time) tested differences between the groups with respect to bystander interventions and survival, according to degree of urbanization. A total of 21 385 OHCAs were included, of which 8496 (40%) occurred in rural areas, 7025 (33%) occurred in suburban areas, and 5864 (27%) occurred in urban areas. Baseline characteristics, as age, sex, location of OHCA, and comorbidities, were comparable between groups. The annual incidence rate ratio of OHCA was higher in rural areas (1.54 [95% CI, 1.48–1.58]) compared with urban areas. Odds for bystander cardiopulmonary resuscitation were lower in suburban (0.86 [95% CI, 0.82–0.96]) and urban areas (0.87 [95% CI, 0.80–0.95]) compared with rural areas, whereas bystander defibrillation was higher in urban areas compared with rural areas (1.15 [95% CI, 1.01–1.31]). Finally, 30-day survival was higher in suburban (1.13 [95% CI, 1.02–1.25]) and urban areas (1.17 [95% CI, 1.05–1.30]) compared with rural areas. CONCLUSIONS: Degree of urbanization was associated with lower rates of bystander defibrillation and 30-day survival in rural areas compared with urban areas.

BACKGROUND: As heart failure therapeutic care becomes increasingly complex, a composite medical therapy score could be useful to conveniently summarize background medical therapy. We applied the composite medical therapy score developed by the Heart Failure Collaboratory (HFC) to the Danish heart failure with reduced ejection fraction population to evaluate its external validation including assessing the distribution of the score and its association with survival. METHODS: In a retrospective nationwide cohort study, we identified all Danish heart failure with reduced ejection fraction patients alive on July 1, 2018, and assessed their treatment doses. Patients were excluded if they did not have at least 365 days for up-titration of medical therapy prior to identification. The HFC score (range 0–8) accounts for use and dosing of multiple therapies prescribed to each patient. Risk-adjusted association between the composite score and all-cause mortality was examined. RESULTS: In total, 26 779 patients (mean age 71.9 years; 32% women) were identified. At baseline, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker was used in 77%, β-blocker in 81%, mineralocorticoid receptor antagonist in 30%, angiotensin receptor-neprilysin inhibitor in 2%, and ivabradine in 2%. The median HFC score was 4. After multivariable adjustment, higher HFC scores were independently associated with lower mortality (≥median versus P P CONCLUSIONS: Nationwide assessment of therapeutic optimization in heart failure with reduced ejection fraction using the HFC score was feasible and the score was strongly and independently associated with survival.

Alcohol is often cited to be a common cause of cardiomyopathy and heart failure. However, in most available population-based studies, a modest-to-moderate alcohol consumption has been associated with favorable effects on the cardiovascular system, including a lowered risk of heart failure, compared with no alcohol consumption. Available genetic epidemiological data have not supported a causal association between alcohol consumption and heart failure risk, suggesting that alcohol may not be a common cause of heart failure in the community. Data linking alcohol intake with cardiomyopathy risk are sparse, and the concept of alcoholic cardiomyopathy stems mainly from case series of selected patients with dilated cardiomyopathy, where a large proportion reported a history of excessive alcohol intake. This state-of-the-art paper addresses the current knowledge of the epidemiology of alcoholic cardiomyopathy and the role of alcohol intake in patients with non–alcohol-related heart failure. It also offers directions to future research in the area. The review questions the validity of current clinical teaching in the area. It is not well known how much alcohol is needed to cause disease, and the epidemiological pathways linking alcohol consumption to cardiomyopathy and heart failure are not well understood. Until more evidence becomes available, caution is warranted before labeling patients as having alcoholic cardiomyopathy due to a risk of neglecting other contributors, such as genetic causes of cardiomyopathy. In non–alcohol-related heart failure, it is unknown whether total abstinence is improving outcomes (compared with moderate drinking). Ideally, randomized clinical trials are needed to answer this question.

Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown. We used Danish population-based registers to systematically investigate whether the 41 most used individual antihypertensive drugs were associated with an altered risk of incident depression. Analyses of diuretics were included for comparisons. Participants were included in the study in January 2005 and followed until December 2015. Two different outcome measures were included: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants. Continued use of classes of angiotensin agents, calcium antagonists, and β-blockers was associated with significantly decreased rates of depression, whereas diuretic use was not. Individual drugs associated with decreased depression included 2 of 16 angiotensin agents: enalapril and ramipril; 3 of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations; and 4 of 15 β-blockers: propranolol, atenolol, bisoprolol, and carvedilol. No drug was associated with an increased risk of depression. In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents. This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.

Little is known about the occurrence of hypokalemia due to combination therapy for hypertension. Using data from Danish administrative registries, we investigated the association between different combinations of antihypertensive therapy and risk of developing hypokalemia. Using incidence density matching, 2 patients without hypokalemia were matched to a patient with hypokalemia (K

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

Background It 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 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.

Introduction: Pharmacotherapy with proarrhythmic or QT prolonging properties are known to augment the risk of malignant arrhythmias (e.g. TdP). We examined TdP risk drug usage prior to OHCA and how it may be associated with shockable rhythm and survival. Methods: Patients ≥18 years with an OHCA of cardiac origin were identified from the Danish Cardiac Arrest Registry (2001-2014). From nationwide registries TdP risk drug usage before OHCA according to CredibleMeds was assessed. We performed multivariable logistic regression to determine factors associated with TdP risk drug usage among OHCA patients and how usage may affect OHCA related factors (e.g. shockable rhythm or survival). Age and sex controls were identified (matching 1:5). Results: Overall, 10139 OHCA patients were identified, of which 43% were in treatment with a TdP risk drug 0-30 days before OHCA compared with 15% from the control population. Furthermore, this was significantly more than 61-90 days before OHCA (37%). Most common prescribed drugs with known risk of TdP were citalopram (31.1%), methadone (16.4%), and fluconazole (8.2%). OHCA patients in treatment with a TdP risk drug at the time of event had a significantly higher burden of comorbidities compared with OHCA patients not in treatment (e.g. cancer [19.3% and 8.7%], COPD [20.0% and 6.6%], psychiatric disease [21.9% and 13.5%], p Conclusion: Almost half of OHCA patients were in treatment with TdP risk drugs before OHCA. Subsequently, TdP risk drug usage did not modify the likelihood of presenting with a shockable rhythm as first recorded rhythm. However, this could partly be due to the large burden of comorbidities. Figure: Factors associated with TdP risk drug usage (adjusted for below mentioned factors).

Introduction: American studies have pointed out racial disparities regarding Out-of-Hospital Cardiac Arrest (OHCA) occurrence, but to date, no data exists among immigrants in Europe. Hypothesis: The risk of OHCA may vary according to region of origin among immigrants. Methods: This nationwide study included all immigrants identified from the Danish Cardiac Arrest Register with OHCA with presumed cardiac cause between 18 and 80 years from 2001 to 2014. Regions of origin were defined as Asia, Western countries, Eastern Europe, Africa, South America, and Arabic countries. Results: Overall, among 940,207 immigrants present in Denmark, a total of 1,724 (0.2%) OHCA (median 62 (IQR 50,71) years 70% males) were recorded. History of myocardial infarction, heart failure, and diabetes were present in 23%, 18%, and 16% respectively. 217 OHCA occurred in Asians, 673 in Westerners, 347 in Eastern Europeans, 107 in Africans, 19 in South Americans, and 361 in Arabic immigrants.Crude incidence rate (/ 100 000 person-years) was 15.2 (95%CI 9.14-23.7) in South American, 19.4 (95%CI 16.9-22.2) in Asian, 22.8 (95%CI 18.7-27.5) in African, 24.7 (95%CI 22.2-27.3) in Arabic, 26.2 (95%CI 23.5-29.1) in Eastern European and 32.4 (95%CI 30.0-34.9) in Western immigrants.After Cox regression, factors associated with OHCA were Eastern European origin (HR 1.28, 95%CI 1.13-1.47; P Conclusions: This is the first European study assessing the incidence of OHCA among immigrants according to their region of origin. Eastern European and African immigrants had a higher risk of OHCA compared to South American, Asian, Arabic and Western immigrants.

Introduction: In Denmark, survival after out-of-hospital cardiac arrest (OHCA) has increased markedly in the past years, from 3.9% in 2001 to 15.8% in 2019. Still, bystander defibrillation remains low, especially for OHCAs in residential areas. To improve bystander defibrillation, smartphone activated Citizen Responder (CR) Programs have expanded to nationwide coverage in Denmark during September 2017 to May 2020. Hypothesis: Implementation of CR programs in Denmark was associated with increased bystander CPR and defibrillation. Methods: We conducted an observational study of 15,308 OHCAs from the Danish Cardiac Arrest Registry from 2016-2019. App-based CR programs were implemented in four out of five Danish regions during the study period. All OHCAs were divided into two groups according to the date of CR implementation (“before” and “after CR” implementation). The groups were compared focusing on bystander defibrillation, bystander CPR and 30-day survival. Results: “Before CR” included 8,819 OHCAs and the “after CR” 6,489 OHCAs. The proportion of bystander CPR was 77.9% and 78.0% (p-value 0.91) for the before -and after CR implementation groups, respectively. The corresponding numbers for bystander defibrillation were 7.4% and 9.5% (p-value < 0.001), respectively. In residential OHCA, bystander defibrillation went from 4.0% to 6.3% (p-value Conclusion: We found no changes in bystander CPR or 30-day survival following implementation of CR programs in Denmark, but a significant increase in bystander defibrillation for all OHCAs. Importantly bystander defibrillation also increased significantly in residential locations, where the majority of OHCAs occur and where bystander defibrillation has remained low for decades.

Background Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple invasive procedures, including pulmonary valve replacement (PVR). Data on the long‐term risk of IE are sparse. Methods and Results In this observational cohort study, all patients with ToF born from 1977 to 2018 were identified using Danish nationwide registries and followed from date of birth until occurrence of first‐time IE, emigration, death, or end of study (December 31, 2018). The comparative risk of IE among patients with ToF versus age‐ and sex‐matched controls from the background population was assessed. Because of rules on anonymity, exact numbers cannot be reported if the number of patients is Conclusions Patients with ToF are associated with a substantially higher incidence of IE than the background population. In particular, PVR was associated with an increased incidence of IE. With an increasing life expectancy of these patients, intensified awareness, preventive measures, and surveillance of this patient group are decisive.

Background: Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2DM) and heart failure with reduced ejection fraction (HFrEF). Methods and Results: Using Danish nationwide databases between 2010-2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39,260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9,355 (24%) had T2DM. Carvedilol was used in 2,989 (32%) patients with TD2M and 10,411 (35%) of patients without T2DM. Users of carvedilol had a lower prevalence of atrial fibrillation (20% vs. 35%), but other characteristics appeared well-balanced between the groups. Totally 11,306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazards ratio 0.97 (0.90-1.05) in patients with T2DM versus 1.00 (0.95-1.05) for those without T2DM, p for difference =0.99. Rates of new-onset T2DM were lower in users of carvedilol vs. metoprolol; age, sex, and calendar year adjusted hazards ratio 0.83 (0.75-0.91), p Conclusion: In a contemporary clinical cohort of HFrEF patients with and without T2DM, carvedilol was not superior to metoprolol for long-term mortality reduction. However, carvedilol was associated with lowered risk of new-onset T2DM supporting the assertion that carvedilol have a more favorable metabolic profile than metoprolol overall.

Introduction: Myocardial infarction (MI) patients with atypical symptoms receive poor prehospital management and have high mortality. We studied the importance of emergency ambulance response and prehospital aspirin use for survival of these patients. Methods: In Copenhagen, Denmark, citizens can call a 24-h non-urgent medical helpline or an emergency number 1-1-2 (equivalent to 9-1-1) for medical assistance. The primary symptom/purpose of calls is registered at both services. We included calls regarding patients hospitalized with an MI up to 24 h after the call and categorized calls according to primary symptom of chest pain or atypical symptom. Mediation analysis was used to examine the effect of modifying prehospital management. Results: We identified 5,440 calls regarding MI patients, 4,127 (76%) with chest pain and 1,313 (24%) with atypical symptoms. Compared to MI patients with chest pain, patients with atypical symptoms were older (median 73 vs 67 years), more often female (44% vs 31%), and had more often called the medical helpline (46% vs 32%). Among MI patients, 30-day mortality was 2.8% for chest pain and 10.9% for atypical symptoms. In the mediation analysis, mortality increased slightly to 11.3%, an increase of 0.3% CI95% [-1.2%; 1.8%], when changing the probability of receiving emergency ambulances for MI patients with atypical symptoms to the probability for chest pain patients. Emergency ambulances were dispatched to 4.277 (79%) of the MI patients. Among these, 30-day mortality was 2.9% for patients with chest pain and 13.1% for atypical symptoms. Changing the probability of receiving aspirin for patients with atypical symptoms to the probability for patients with chest pain decreased mortality to 10.5%. A reduction of -2.6% CI95% [-5.1%; -0.1%]. Conclusion: MI patients presenting with atypical symptoms have high mortality. Results from the mediation analysis suggest that increased prehospital use of aspirin could improve survival for these patients.

Introduction: Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is recommended following PCI for ACS. The optimal choice of P2Y 12 inhibitor remains debated. We compared effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in a large, nationwide cohort of patients with ACS undergoing PCI. Methods: Registry-based study of first-time ACS patients who underwent PCI ≤7 days of admission and redeemed a prescription of a P2Y 12 inhibitor ≤30 days of the index event. The primary outcome was major adverse cardiovascular events (MACE): a composite of cardiovascular death, recurrent myocardial infarction, stroke, or repeat revascularization at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate standardized absolute and relative risks for outcomes across age, sex, comorbidity, bleeding, and concomitant anticoagulant therapy distributions. Results: We included 26,997 patients; 6,585 were discharged on clopidogrel, 18,425 on ticagrelor, and 1,987 on prasugrel. Corresponding median ages were 70, 64, and 59 years (p Conclusion: Ticagrelor and prasugrel were associated with lower risk of MACE than clopidogrel but did not significantly differ from each other. Ticagrelor was associated with a lower risk of bleeding than both clopidogrel and prasugrel.

Introduction: Hypotensive events and drops in systolic blood pressure (SBP-drop) are frequent in patients with acute heart failure (AHF). We investigated SBP-drop and associations with outcomes and whether treatment with the vasodilator serelaxin affected the association between SBP-drops and outcomes. Methods: Analyses of data from four randomized, controlled trials investigating serelaxin as an intervention in patients hospitalized with AHF. Main inclusion criteria were SBP 125-180 mmHg, pulmonary congestion, elevated NT-proBNP. SBP-drops (predefined as an SBP-value below 100 mmHg and/or a drop of 40 mmHg from baseline) were prospectively registered during the first 48 hours of hospitalization. Outcomes were a composite outcome (worsening heart failure, hospital readmission for heart failure or all-cause mortality through 14 days) and 180-day mortality. Results: Overall, 2558/11226 (23%) patients had an SBP-drop, with a median time from randomization to event of 15 (6-25) hours. In multivariable analyses, SBP-drop was associated with 180-day mortality (hazard ratio 1.21, 95% CI 1.05-1.39; p=0.009) and the composite outcome (1.29 (1.13-1.49); p Conclusions: SBP-drops in hospitalized patients treated for AHF is an independent risk factor for adverse short- and long-term outcomes, and its occurrence highlights the need for careful monitoring and urgent treatment. However, in patients treated with serelaxin under careful observation, SBP-drops were not associated with worse outcome.

Introduction: Multiple citizen responder (CR) programs worldwide which dispatch laypersons to out-of-hospital cardiac arrest (OHCA) to perform cardiopulmonary resuscitation (CPR) and use of automated external defibrillators (AEDs) were affected by the COVID-19 outbreak in 2020, but little is known about how the pandemic affected CR activation and initiation of bystander CPR and defibrillation. In Denmark, the CR program continued to run during lockdown but with the recommendation to perform chest-compression-only CPR in contrast to standard CPR including ventilations. We hypothesized that bystander interventions as CPR and AED usage decreased during the first COVID-19 lockdown in two regions of Denmark in the spring of 2020. Methods: All OHCAs from January 1, 2020 to June 30, 2020 with CR activation from the Danish Cardiac Arrest Registry and the National Citizen Responder database. Bystander CPR, AED usage, and CRs’ alarm acceptance rate during the national lockdown from March 11, 2020 to April 20, 2020 were compared with the non-lockdown period from January 1, 2020 to March 10, 2020 and from April 21 to June 30, 2020. Results: A total of 6,120 CRs were alerted in 443 (23/100.000 inhabitants) cases of presumed OHCA of which 256 (58%) were confirmed cardiac arrests. Bystander CPR remained equally high in the lockdown period compared with non-lockdown period (99% vs. 92%, p=0.07). Likewise, there was no change in bystander defibrillation (9% vs. 14%, p=0.4). There was a slight increase in the number of CRs who accepted an alarm (7 per alarm, IQR 4) during lockdown compared with non-lockdown period (6 per alarm, IQR 4), p=0.0001. The proportion of patients achieving return of spontaneous circulation at hospital arrival was also unchanged (lockdown 23% vs non-lockdown 23%, p=1.0) (Table 1). Conclusion: Bystander initiated resuscitation rates did not change during the first COVID-19 lockdown in Denmark for OHCAs where CRs were activated through a smartphone app.

Introduction: Case reports and smaller observational studies have suggested an association between monoclonal gammopathy of undetermined significance (MGUS) and various cardiovascular diseases. We aimed to explore the association of MGUS with a broad spectrum of incident cardiovascular disease further, using the Danish nationwide administrative databases. Methods: Between 1995-2018, all patients eighteen years and older with MGUS were matched (10:1) with controls from the general population based on age and sex. Patients with a diagnosis of multiple myeloma were excluded. Incident cardiovascular diseases were identified using ICD coding. Hazard ratios for cardiovascular outcomes were calculated using Cox proportional hazard regression. Results: Patients with MGUS (n= 8,445, mean age 69.9 years, 51.3% male) had a higher risk of developing most cardiovascular diseases after multivariable adjustment, including heart failure (HR 1.65, 95% CI 1.51-1.81), atrial fibrillation (HR 1.47, 95% CI 1.37-1.58), acute myocardial infarction (HR 1.24, 95% CI 1.08- 1.43), stroke (HR 1.25, 95% CI 1.12-1.40), aortic aneurysm (HR 1.49, 95% CI 1.23-1.80), aortic stenosis (HR 1.72, 95% CI 1.52-1.96), aortic regurgitation (HR 1.70, 95% CI 1.36-2.12), conduction disease (HR 1.52, 95% CI 1.25-1.82), pericarditis (HR 1.62, 95% CI 1.03-2.55), peripheral arterial disease (HR 1.86, 95% CI 1.61-2.14), cor pulmonale (HR 2.32, 95% CI 1.76-3.06), venous thromboembolism (HR 1.29, 95% CI 1.12-1.48), and implantation of a cardiac pacemaker or defibrillator (HR 1.34, 95% CI 1.14-1.59). Conclusions: MGUS is associated with a broad spectrum of cardiovascular diseases, with somewhat greater risk estimates observed for cardiovascular disorders that have previously been associated with infiltrative diseases (such as heart failure, pulmonary hypertension, aortic valvular disease, atrial fibrillation, and conduction abnormality) than for atherosclerotic and thrombotic disorders. Further studies are warranted to understand the underlying mechanisms.

Introduction: Cardiopulmonary resuscitation (CPR) and early defibrillation are two of the most important factors for survival after out-of-hospital cardiac arrest (OHCA). However, little is known whether bystander interventions and survival are impaired in rural areas compared to more urbanized areas in Denmark. We hypothesized that bystander interventions and survival are lower in rural areas compared to urbanized areas. Methods: We included all non-EMS witnessed OHCAs with known GPS-location in Denmark (January 1, 2016 to December 31, 2019) and geocoded them according to county. All counties in Denmark were classified either as urban, suburban, or rural according to the degree of urbanization tool defined by the European Statistical Agency. Results: A total of 16,670 OHCAs were included, of which 4,555 (27%), 5,457 (33%), and 6,658 (40%) arrests occurred in urban, suburban, and rural areas respectively. The median age (73 vs. 74 vs. 73 years, p=0.003), ambulance response time (6 vs. 7 vs. 8 minutes, p Conclusion: Degree of urbanization was associated with increased rates of bystander CPR in rural areas. Despite this, ROSC and 30-day survival were higher in urban and suburban areas compared to rural areas which could not be explained by cardiac arrest characteristics.

Introduction: As heart failure (HF) therapeutic care becomes increasingly complex, determining optimal medical therapy (OMT) can be challenging. The HF Collaboratory consortium developed a scoring system to assist with standardization of comparing OMT within and across trials. We evaluated the score in the Danish HF population. Methods: In a retrospective nationwide cohort study, we identified all Danish HF patients alive on July 1, 2018. Patients were excluded if they were diagnosed after July 1, 2017 to allow a minimum of 365 days for up-titration of medical therapy. Treatment doses were estimated by analysis of consecutive claimed prescriptions. An integer-based composite medical therapy score (range 0-10) was designed to consider use and dosing of multiple therapies prescribed to each patient ( Panel A ). Risk-adjusted association was assessed between the composite score and subsequent death. Results: In total, 26,779 patients (median age 73y; 32% women) were identified. At baseline, ACEi/ARB was used in 77%, β-blocker in 81%, MRA in 30%, ARNi in 2%, SGLT2i in 2%, and ivabradine in 2%. The median composite medical therapy score was 4 (and was consistently 4 from January 2016-July 2018). During median follow-up of 1.5 years, 3,326 deaths occurred. After accounting for demographics, comorbidities, loop diuretic use, HF diagnosis setting, and time since HF diagnosis, higher composite scores were independently associated with lower mortality (≥median vs Panel B ). Conclusions: Nationwide assessment of therapeutic optimization in HF using a composite medical therapy score was feasible and the score was independently associated with survival. These data suggest that most patients can achieve a score of 4 or more in current clinical care.

Background: Patients with severe mental illness (SMI) including schizophrenia, bipolar disorder, and severe depression have earlier onset of cardiovascular risk factors, predisposing to worse future heart failure (HF) compared with the general population. We investigated associations between the presence/absence of SMI and long-term HF outcomes. Methods: We identified patients with HF with and without SMI in the Duke University Health System from 2002 to 2017. Using multivariable Cox regression, we examined the primary outcome of all-cause mortality. Secondary outcomes included rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation. Results: We included 20 906 patients with HF (SMI, n=898; non-SMI, n=20 008). Patients with SMI presented clinically 7 years earlier than those without SMI. We observed an interaction between SMI and sex on all-cause mortality ( P =0.002). Excess mortality was observed among men with SMI compared with men without SMI (hazard ratio, 1.36 [95% CI, 1.17–1.59]). No association was observed among women with and without SMI (hazard ratio, 0.97 [95% CI, 0.84–1.12]). Rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation were similar between patients with and without SMI (6.1% versus 7.9%, P =0.095). Patients with SMI receiving these procedures for HF experienced poorer prognosis than those without SMI (hazard ratio, 2.12 [95% CI, 1.08–4.15]). Conclusions: SMI was associated with adverse HF outcome among men and not women. Despite equal access to procedures for HF between patients with and without SMI, those with SMI experienced excess postprocedural mortality. Our data highlight concurrent sex- and mental health-related disparities in HF prognosis, suggesting that patients with SMI, especially men, merit closer follow-up.

It has been a challenge to verify the dose of exercise that will produce the maximum health benefits in hypertension. This study aimed to explore the association between level of daily physical activity, all-cause mortality and cardiovascular outcome at different blood pressure levels. A random sample of 18 974 white men and women aged 20 to 98 years were examined in a prospective cardiovascular population study. Self-reported activity level in leisure-time was drawn from the Physical Activity Questionnaire (level I: inactivity; II: light activity; and III: moderate/high-level activity). Blood pressure was defined as normal blood pressure: P P

Background and Purpose— After pneumonectomy or lobectomy, at least 1 blind pulmonary vein is left with potential risk of postoperative thromboembolic incidents. We investigated the risk of stroke within this population compared with background and pulmonary wedge resections controls. Methods— We identified 12 965 patients with pneumonectomy or lobectomy and 6400 patients with wedge resection using data from Danish nationwide registries from 1996 to 2016. In multivariate Poisson regression analysis, we estimated incidence rate ratios of stroke for patients undergoing lobectomy or pneumonectomy versus background population controls and patients who underwent wedge resection. We stratified our analysis by days: 0 to 30, 31 to 90, 91 to 180, and 180 to 365 after surgery and performed a subgroup analysis in patients with lung cancer. Results— The incidence rate of stroke was 10.6 per 1000 person-years for time exposed for pneumonectomy or lobectomy and 2.3 per 1000 person-years for patients not exposed for pneumonectomy or lobectomy. In the 0- to 30-day multivariate Poisson regression analysis, compared with the background population, pneumonectomy or lobectomy was associated with an increased risk of stroke both patients with and without atrial fibrillation (incidence rate ratios [IRR]) of 4.66 (95% CI, 2.04–7.12) and 5.43 (95% CI, 3.99–7.41), respectively. Similarly, in patients with lung cancer, the first 30 days after pneumonectomy or lobectomy remained a risk factor for stroke for patients with (IRR, 2.94; 95% CI, 1.39–6.25) and for patients without atrial fibrillation (IRR, 2.56; 95% CI, 1.86–3.59).When compared with wedge resection, 0 to 30 days after lobectomy or pneumonectomy was also associated with increased risk of stroke (IRR, 2.63; 95% CI, 1.19–5.81); however, this association was insignificant in patients with lung cancer (IRR, 2.98; 95% CI, 0.72–12.29). Conclusions— Patients undergoing pneumonectomy or lobectomy had an increased 30 days risk of stroke. Whether the pulmonary vein stump is a risk factor for stroke and whether preventive strategies are relevant require further investigation.

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

Background Citizen responder programs are implemented worldwide to dispatch volunteer citizens to participate in out‐of‐hospital cardiac arrest resuscitation. However, the risk of injuries in relation to activation is largely unknown. We aimed to assess the risk of physical injury for dispatched citizen responders. Methods and Results Since September 2017, citizen responders have been activated through a smartphone application when located close to a suspected cardiac arrest in the Capital Region of Denmark. A survey was sent to all activated citizen responders, including a specific question about risk of acquiring an injury during activation. We included all surveys from September 1, 2017, to May 15, 2020. From May 15, 2019, to May 15, 2020, we followed up on all survey nonresponders by phone call, e‐mail, or text messages to examine if nonresponders were at higher risk of severe or fatal injuries. In 1665 suspected out‐of‐hospital cardiac arrests, 9574 citizen responders were dispatched and 76.6% (7334) answered the question regarding physical injury. No injury was reported by 99.3% (7281) of the responders. Being at risk of physical injury was reported by 0.3% (24), whereas 0.4% (26) reported an injury (25 minor injuries and 1 severe injury [ankle fracture]). When following up on nonresponders (2472), we reached 99.1% (2449). No one reported acquired injuries, and only 1 reported being at risk of injury. Conclusions We found low risk of physical injury reported by volunteer citizen responders dispatched to out‐of‐hospital cardiac arrest. Risk of injury should be considered and monitored as a safety measure in citizen responder programs.

Introduction: Although type 2 diabetes (T2DM) is one of the strongest risk factors for heart failure (HF), there is limited data on contemporary lifetime risk estimates in this segment. Incident HF appears to be decreasing in the general population, but little is known how the risk has changed over time in patients with T2DM. The increasing prevalence and rapidly evolving management of T2DM has furthered interest in the epidemiological relationship between HF and T2DM. We therefore sought to investigate the lifetime risk of HF in people with T2DM and how the long term risk of HF has changed over time in patients with T2DM. Hypothesis: We assessed the hypothesis that there would be a statistically significant reduction in the ten- year risk of HF among patients with T2DM over time in all age groups except the youngest ( Methods: We employed the Danish nationwide databases which included information on all Danish citizens’ hospitalizations, outpatient visits, and medication use since 1978 (diagnoses) and 1995 (medications). Using this data, we calculated the cumulative incidence of HF among patients with T2DM who were free from HF at age 30, 40, 50, 60, and 70 years, respectively. We censored people at time of emigration or at Dec 31, 2017 and we used Aalen-Johnsen estimators to adjust for the competing risk of death. Results: A total of 473,685 patients (47% women) had a diagnosis of T2DM between Jan 1, 1995 and Dec 31, 2017. Of those who were free from HF before T2DM onset, 21,030 were diagnosed before the age of 30; 33,786 before age 40; 55,537 before 50 years of age; 85,108 before age 60; and 98,631 before age 70. During follow-up, 48,026 (10%) were diagnosed with HF and 133,561 were censored for death. The cumulative life-time risk of developing HF among people with diabetes at age 50 was 24% (95% CI 21-27%) in females and 27% (25-29%) in men, p for difference Conclusion: The lifetime risk of HF among patients with T2DM exceeds 1 in 4 for both men and women. There was, however, a decrease in ten-year cumulative incidence of HF over time among patients with T2DM in all age groups.

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 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.

Introduction: Peripartum cardiomyopathy (PPCM) is a form of systolic heart failure that occurs during pregnancy or in the early post-partum period. Obesity is known to be associated with other forms of heart failure in young adults, however it is unclear if it is also a risk factor for the development of PPCM. Objectives: To investigate the association of body mass index (BMI) with PPCM and heart failure in the years following childbirth. Methods: We conducted a retrospective review of pregnant women in the Danish National Patient Registry between 2004 - 2017. Baseline characteristics and other risk factors were obtained at the first prenatal visit (occurring at 8-11 weeks post-conception). Women were followed until the end of the study period, emigration, or death. Logistic regression was performed, adjusting for age as well as other known risk factors for PPCM. Cox proportional hazards analysis was used to assess the long-term risk of development of heart failure. Results: There were 403,820 pregnancies evaluated in 300,892 women, with an average age of 29 years. The average BMI was 24.4 kg/m2, with 21.6% classified as overweight (BMI 25 - 30 kg/m2) and 12.8% as obese (BMI > 30 kg/m2). The rate of PPCM was 0.1 per 1,000 in normal weight and overweight groups, and 0.3 per 1,000 in the obese women. After adjustment for age, ethnicity, smoking status, gestational diabetes, and presence of preeclampsia, there was a statistically significant increased risk of the development of PPCM up to 6 months after childbirth in patients who had class I (odds ratio [OR] 2.25, 95% CI 1.08-4.68) but not class II/III obesity (OR 1.63, 95% CI 0.60-4.43). This elevated risk persisted during long term follow up, with hazard ratios of 2.43 (95% CI 1.55 - 3.80) in women with class I obesity and 3.20 (95% CI 1.93 - 5.30) in women with class II/III obesity. Conclusions: High early pregnancy BMI is associated with elevated risk of development of peripartum cardiomyopathy even after adjustment for traditional risk factors. This risk of heart failure persists for several years after childbirth.

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

Background: Heart failure (HF) in patients with type 2 diabetes mellitus (T2D) has received growing attention. We examined the effect of HF development on prognosis compared with other cardiovascular or renal diagnoses in patients with T2D. Methods and Results: Patients with new T2D diagnosis patients were identified between 1998 and 2015 through Danish nationwide registers. At yearly landmark timepoints after T2D diagnosis, we estimated the 5-year risks of death, 5-year risk ratios, and decrease in lifespan within 5 years associated with the development of HF, ischemic heart disease, stroke, peripheral artery disease, and chronic kidney disease. A total of 153 403 patients with newly diagnosed T2D were followed for a median of 9.7 years (interquartile range, 5.8–13.9) during which 48 087 patients died. The 5-year risk ratio of death associated with HF development 5 years after T2D diagnosis was 3 times higher (CI, 2.9–3.1) than patients free of diagnoses (CI, 2.9–3.1). Five-year risk ratios were lower for ischemic heart disease (1.3 [1.3–1.4]), stroke (2.2 [2.1–2.2]), chronic kidney disease (1.7 [1.7–1.8]), and peripheral artery disease (2.3 [2.3–2.4]). The corresponding decrease in lifespan within 5 years when compared with patients free of diagnoses (in months) was HF 11.7 (11.6–11.8), ischemic heart disease 1.6 (1.5–1.7), stroke 6.4 (6.3–6.5), chronic kidney disease 4.4 (4.3–4.6), and peripheral artery disease 6.9 (6.8–7.0). HF in combination with any other diagnosis imposed the greatest risk of death and decrease in life span compared with other combinations. Supplemental analysis led to similar results when stratified according to age, sex, and comorbidity status, and inclusion period. Conclusions: HF development, at any year since T2D diagnosis, was associated with the highest 5-year absolute and relative risk of death, and decrease in lifespan within 5 years, when compared with development of other cardiovascular or renal diagnoses.

Background: Influenza infection is a serious event for patients with heart failure (HF). Little knowledge exists about the association between influenza vaccination and outcome in patients with HF. This study sought to determine whether influenza vaccination is associated with improved long-term survival in patients with newly diagnosed HF. Methods: We performed a nationwide cohort study including all patients who were >18 years of age and diagnosed with HF in Denmark in the period of January 1, 2003, to June 1, 2015 (n=134 048). We collected linked data using nationwide registries. Vaccination status, number, and frequency during follow-up were treated as time-varying covariates in time-dependent Cox regression. Results: Follow-up was 99.8% with a median follow-up time of 3.7 years (interquartile range, 1.7–6.8 years). The vaccination coverage of the study cohort ranged from 16% to 54% during the study period. In unadjusted analysis, receiving ≥1 vaccinations during follow-up was associated with a higher risk of death. After adjustment for inclusion date, comorbidities, medications, household income, and education level, receiving ≥1 vaccinations was associated with an 18% reduced risk of death (all-cause: hazard ratio, 0.82; 95% CI, 0.81–0.84; P P Conclusions: In patients with HF, influenza vaccination was associated with a reduced risk of both all-cause and cardiovascular death after extensive adjustment for confounders. Frequent vaccination and vaccination earlier in the year were associated with larger reductions in the risk of death compared with intermittent and late vaccination.

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1–4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78–1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67–1.01; P value for interaction=0.023). Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Background: The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation. Methods: All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of χ 2 analysis. Results: Median age of the study population was 63 years (range, 21–84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003–1.06; P =0.03). An optimal age cutoff for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and ICD in patients ≤70 years of age (HR, 0.70; 95% CI, 0.51–0.96; P =0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68–1.62; P =0.84). For patients ≤70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3–2.5) and nonsudden death rate was 2.7 (95% CI, 2.1–3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8–3.2) and nonsudden death rate was 5.4 (95% CI, 3.7–7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant ( P =0.01). Conclusions: In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ≤70 years yielded the highest survival for the population as a whole. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00542945.

Background The outcomes of emergent noncardiac, nonintracranial surgery in patients with previous stroke remain unknown. Methods All emergency surgeries performed in Denmark (2005 to 2011) were analyzed according to time elapsed between previous ischemic stroke and surgery. The risks of 30-day mortality and major adverse cardiovascular events were estimated as odds ratios (ORs) and 95% CIs using adjusted logistic regression models in a priori defined groups (reference was no previous stroke). In patients undergoing surgery immediately (within 1 to 3 days) or early after stroke (within 4 to 14 days), propensity-score matching was performed. Results Of 146,694 nonvascular surgeries (composing 98% of all emergency surgeries), 5.3% had previous stroke (mean age, 75 yr [SD = 13]; 53% women, 50% major orthopedic surgery). Antithrombotic treatment and atrial fibrillation were more frequent and general anesthesia less frequent in patients with previous stroke (all P < 0.001). Risks of major adverse cardiovascular events and mortality were high for patients with stroke less than 3 months (20.7 and 16.4% events; OR = 4.71 [95% CI, 4.18 to 5.32] and 1.65 [95% CI, 1.45 to 1.88]), and remained increased for stroke within 3 to 9 months (10.3 and 12.3%; OR = 1.93 [95% CI, 1.55 to 2.40] and 1.20 [95% CI, 0.98 to 1.47]) and stroke more than 9 months (8.8 and 11.7%; OR = 1.62 [95% CI, 1.43 to 1.84] and 1.20 [95% CI, 1.08 to 1.34]) compared with no previous stroke (2.3 and 4.8% events). Major adverse cardiovascular events were significantly lower in 323 patients undergoing immediate surgery (21%) compared with 323 successfully propensity-matched early surgery patients (29%; P = 0.029). Conclusions Adverse cardiovascular outcomes and mortality were greatly increased among patients with recent stroke. However, events were higher 4 to 14 days after stroke compared with 1 to 3 days after stroke.

Introduction: Survival from out-of-hospital cardiac arrest (OHCA) remains low and with major regional variation. This study explored differences in patients, care, and survival in patients with OHCA in North Carolina (NC), Washington State (WA), and Denmark. Methods: We identified a total of 17,277 adult patients with OHCA from the Cardiac Arrest Registry to Enhance Survival (CARES) registry and the Danish Cardiac Arrest Register of presumed cardiac cause from 2013-2014. Patients were categorized into three regions: two states in the United States (NC, 9.1 million inhabitants, WA, 7.5 million inhabitants) and the country of Denmark (5.8 million inhabitants). Outcomes of cardiopulmonary resuscitation (CPR) and defibrillation performed by either professional first responder or lay bystanders prior to emergency medical service (EMS) arrival, as well as overall survival. Data were analyzed using multivariable logistic regression analyses adjusted for age, sex, calendar year, location of arrest and witnessed status. Results: Patients in NC and WA were younger and had more racial variation compared to Denmark. Survival was 9.3% in NC, 14.5% in WA and 13.3% in Denmark. Using the Danish cohort as reference, the odds for bystander CPR and defibrillation in NC (CPR: OR 0.41, 95%CI 0.38-0.44; defibrillation: OR 0.30, 95%CI 0.23-0.38) and WA (CPR: OR 0.71, 95%CI 0.65-0.77; defibrillation: OR 0.41, 95%CI 0.31-0.53) were lower, respectively. CPR and defibrillation performed by either a bystander or a professional first responder prior to EMS arrival were higher in NC (CPR: OR 2.67, 95%CI 2.43-2.93; defibrillation: OR 2.72 95%CI 2.30-3.21), but not in WA (CPR: OR 1.01, 95%CI 0.92-1.11; defibrillation OR 0.73, 95%CI 0.58-0.90), respectively. Compared with Denmark, survival was lower in NC (OR 0.39, 95%CI 0.34-0.45) and WA (OR 0.83, 95%CI 0.72-0.95). Conclusion: Survival following OHCA was higher in Denmark and WA than in NC, and was associated with higher rates of bystander CPR and defibrillation. However, CPR and defibrillation prior to EMS arrival, mainly from professional first responders, was significantly higher in NC. A combination of both bystander and first responder interventions may be the optimal approach to improve outcomes of cardiac arrest.

Introduction: Bystander defibrillation has increased in public locations but remained stagnated around 2% in private homes, where most out-of-hospital cardiac arrests (OHCAs) occur. Hypothesis: Dispatching citizen responders through a smartphone application can increase bystander defibrillation in residential OHCAs. Methods: From September 2017-2018, a total of 23,117 (1,284/100,000) citizen responders and 5,225 (290/100,000) automated external defibrillators (AEDs) were registered in the Capital Region of Denmark (1.8 mil. inhabitants). In case of suspected OHCA, up to 20 citizen responders Results: Of 433 consecutive OHCAs included, 354 (81.8%) were residential OHCAs. Compared with citizen responders in public locations, those in residential areas were a median of 100m further away from OHCAs but were equally likely to arrive before EMS (~40% of both residential and public OHCAs). A total of 9.3% (33 of 354) of all residential OHCAs were bystander defibrillated. Citizen responders were responsible for 75.8% (25 out of 33) of all bystander defibrillated OHCAs in residential areas compared to 50.0% (13 out of 26) of all bystander defibrillated OHCAs in public areas (Table 1). Conclusions: Dispatched citizen responders arrived before EMS in 40.1% (142 of 354) of all residential OHCAs and performed three out of four of all bystander defibrillated OHCAs in residential areas.

Background and Purpose— We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups. Methods— We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR. Results— A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97–1.56), 1.26 (95% CI, 1.14–1.40), 1.18 (95% CI, 1.07–1.31), 1.11 (95% CI, 0.87–1.42), 2.01 (95% CI, 1.14–3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and 2 , respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m 2 ; hazard ratios 0.57 (95% CI, 0.43–0.76), 0.57 (95% CI, 0.51–0.64), 0.48 (95% CI, 0.44–0.54), 0.60 (95% CI, 0.45–0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m 2 , respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR2 ; hazard ratio 1.18 (95% CI, 0.58–2.40). Conclusions— In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m 2 .

Introduction: Survival after out-of-hospital cardiac arrest (OHCA) is dependent on early defibrillation. To increase bystander defibrillation in OHCAs, a first-responder program dispatching lay rescuers (Heart Runners) through a smartphone application (Heart Runner-app) was implemented in the Capital Region of Denmark. We investigated the proportion of Heart Runners arriving prior to the Emergency Medical Services (EMS) and rates of bystander defibrillation. Methods: The Capital Region of Denmark comprises 1.8 mil. inhabitants and 19,048 Heart Runners were registered. In cases of suspected OHCA, the Heart Runner-app was activated by the Emergency Medical Dispatch Center. Up to 20 Heart Runners < 1.8 km from the OHCA were dispatched to either start cardiopulmonary resuscitation (CPR) or to retrieve and use a publicly accessible automated external defibrillator (AED). Through an electronic survey, Heart Runners reported if they arrived before EMS and if they applied an AED. OHCAs where at least one Heart Runner arrived before EMS were compared with OHCAs where EMS arrived first. All OHCAs from September 2017 to May 2018, where Heart Runners had been dispatched, were included. Results: Of 399 EMS treated OHCAs, 78% (n=313/399) had a matching survey. A Heart Runner arrived before EMS in 47% (n=147/313) of the cases, and applied an AED in 41% (n=61/147) of these cases. Rate of bystander defibrillation was 2.5-fold higher compared to cases where the EMS arrived first (Table 1). Conclusions: By activation of the Heart Runner-app, Heart Runners arrived prior to EMS in nearly half of all the OHCA cases. Bystander defibrillation rate was significantly higher when Heart Runners arrived prior to EMS.

Introduction: Use of automated external defibrillators (AEDs) for early defibrillation in out-of-hospital cardiac arrest (OHCA) substantially increases chance of survival. Aim: To examine the relationship between number of nearby accessible AEDs and chance of bystander defibrillation. Methods: All OHCAs (2008-2016), and all publicly available AEDs (2007-2016) in Copenhagen were identified. The route distances between OHCAs and AEDs were calculated to determine the number of accessible AEDs ≤100m of an OHCA (OHCA coverage). Multiple logistic regression was performed to identify the adjusted Odds Ratios (ORs) of OHCA characteristics, including the number of AEDs covering an OHCA, on bystander defibrillation. The regression model was evaluated using receiver operator characteristics (ROC). Multiple logistic regression was also used to determine the predicted probability (through a 2000 iteration bootstrap approach) of bystander defibrillation for public vs. residential OHCAs, according to the number of accessible AEDs covering the OHCA, defined as covered by 0, 1 or >1 AED. Results: There were 1830 AEDs registered in Copenhagen. Of 2500 OHCAs, 75.2% (n=1879) occurred in residential locations of which 98.1% were not covered by an AED, 1.7% were covered by 1 AED only, and 0.2% were covered by >1 AED. The corresponding figures for public OHCAs (n=621, 24.8%) were 87.5%, 9.0%, and 3.5%, respectively. Overall, the number of accessible AEDs covering the OHCA, public location, bystander witnessed arrest and bystander CPR were significantly associated with bystander defibrillation (OR (95%CI): 1.75 (1.24-2.46); 4.25 (2.75-6.57); 3.12 (1.84-5.27); 2.33 (1.44-3.75), respectively. (ROC=82%)). The predicted probability of bystander defibrillation for public OHCAs was 12.2% (95%CI: 9.5-14.9) with no AED covering the OHCA, 24.7% (95%CI: 18.2-31.3) with 1 AED, and 39.8% (95%CI: 23.4-56.7) with >1 AED. The corresponding figures for residential OHCAs were 2.1% (95%CI: 1.5-2.8), 4.3% (95%CI: 2.5-6.8), and 4.0% (95%CI: 0.9-10.8), respectively. Conclusions: Rates of bystander defibrillation significantly improved with increasing number of accessible AEDs covering the OHCA, especially for public OHCAs.

Background: Our aims were to determine the incidence of symptomatic deep venous thrombosis (DVT) and pulmonary embolism (PE) that required inpatient or outpatient treatment, and to identify specific risk factors associated with DVT/PE in patients who had undergone surgery for a fracture distal to the knee. Methods: Using individual linkage of nationwide registries, we included all Danish patients who had undergone surgery for a fracture distal to the knee between 1999 and 2011. Patients were followed for 180 days from discharge. Event rates of DVT/PE were calculated, and significant risk factors were identified with use of multivariable Cox regression analyses. Routine postdischarge antithrombotic chemoprophylaxis was not given to these patients. Results: The study included 57,619 patients, 594 of whom had a venous thromboembolic event during the follow-up period. Thirty-nine (6.6%) of the 594 events were death due to PE. The overall event rate during the 180-day study period was 1.0%. The incidence rate was 7.28 events per 100 person-years before discharge, decreasing to a stable level below one event per 100 person-years in week 13 to 14 after discharge. Use of oral contraception by patients eighteen to fifty years of age (hazard ratio [HR] = 5.23, 95% confidence level [CI] = 3.35 to 8.18), previous DVT (HR = 6.27, 95% CI = 4.18 to 9.40), previous PE (HR = 5.45, 95% CI = 3.05 to 9.74), coagulopathy (HR = 2.47, 95% CI = 1.07 to 5.72), and peripheral artery disease (HR = 2.34, 95% CI = 1.20 to 4.56) were the factors associated with the highest risk of postoperative DVT/PE. Also, increasing age, increasing body mass index, cancer, and treatment with nonsteroidal anti-inflammatory drugs were associated with a significantly increased risk of DVT/PE. Conclusions: The incidence of DVT/PE was low following surgery for fractures distal to the knee; however, the risk was increased in the presence of a number of risk factors. This study suggests that specific groups of patients undergoing surgery for a fracture distal to the knee might benefit from postdischarge antithrombotic treatment. Level of Evidence: Progostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background— First-time syncopal episodes usually occur in adults of working age, but their impact on occupational safety and employment remains unknown. We examined the associations of syncope with occupational accidents and termination of employment. Methods and Results— Through linkage of Danish population-based registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3 410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were identified, with a median age 48.4 years (first to third quartiles, 33.0–59.5), and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up of 3.2 years (first to third quartiles, 2.0–4.5), 622 people with syncope had an occupational accident requiring hospitalization (2.1/100 person-years). In multiple Poisson regression analysis, the incidence rate ratio in the employed syncope population was higher than in the employed general population (1.44; 95% confidence interval [CI], 1.33–1.55) and more pronounced in people with recurrences (2.02; 95% CI, 1.47–2.78). The 2-year risk of termination of employment was 31.3% (95% CI, 30.4%–32.3%), which was twice the risk of the reference population (15.2%; 95% CI, 14.7%–15.7%), using the Aalen–Johansen estimator. Factors associated with termination of employment were age Conclusions— In this nationwide cohort, syncope was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold higher risk of termination of employment compared with the employed general population.

Background— Although increased dissemination of automated external defibrillators (AEDs) has been associated with more frequent AED use, the trade-off between the number of deployed AEDs and coverage of cardiac arrests remains unclear. We investigated how volunteer-based AED dissemination affected public cardiac arrest coverage in high- and low-risk areas. Methods and Results— All public cardiac arrests (1994–2011) and all registered AEDs (2007–2011) in Copenhagen, Denmark, were identified and geocoded. AED coverage of cardiac arrests was defined as historical arrests ≤100 m from an AED. High-risk areas were defined as those with ≥1 arrest every 2 years and accounted for 1.0% of the total city area. Of 1864 cardiac arrests, 18.0% (n=335) occurred in high-risk areas throughout the study period. From 2007 to 2011, the number of AEDs and the corresponding coverage of cardiac arrests increased from 36 to 552 and from 2.7% to 32.6%, respectively. The corresponding increase for high-risk areas was from 1 to 30 AEDs and coverage from 5.7% to 51.3%, respectively. Since the establishment of the AED network (2007–2011), few arrests (n=55) have occurred ≤100 m from an AED with only 14.5% (n=8) being defibrillated before the arrival of emergency medical services. Conclusions— Despite the lack of a coordinated public access defibrillation program, the number of AEDs increased 15-fold with a corresponding increase in cardiac arrest coverage from 2.7% to 32.6% over a 5-year period. The highest increase in coverage was observed in high-risk areas (from 5.7% to 51.3%). AED networks can be used as useful tools to optimize AED placement in community settings.

METHOD: Two thousand and fifty-nine healthy individuals aged 41, 51, 61 and 71 years examined in 1993, were divided in age, SCORE and Framingham risk score (FRS) groups. Subclinical vascular damage (SVD) was defined as carotid-femoral pulse wave velocity (cfPWV) at least 12 m/s, carotid atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n = 229).RESULTS: With increasing age, SCORE or FRS risk group, prevalence of cfPWV at least 12 m/s (5.2, 14.5, 35.3, 53.5% or 4.4, 15.6, 50.9, 66.1% or 4.0, 9.5, 32.1, 56.1%), atherosclerotic plaque (4.0, 19.0, 35.3, 53.5% or 3.5, 16.8, 43.7, 55.9%, or 6.6, 7.6, 9.8, 20.0%) and albuminuria (7.9, 8.7, 11.4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P CONCLUSION: SVD and especially atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 0.73/1.06 mg/mmol (men/women) added prognostic information in individuals aged 51 or 61 years or with moderate or intermediate risk.

OBJECTIVE To investigate the association between maternal use of sulfamethizole near term and the risk of neonatal jaundice. METHODS We conducted a nationwide population-based retrospective cohort study using Danish registers. All Danish women giving birth between 1995 and 2007 were included from the Danish Fertility Database. Women redeeming a prescription for sulfamethizole up to 4 weeks before giving birth were identified from the National Prescription Register. The primary outcome was the number of neonates diagnosed with jaundice between birth and age 28 days identified in the National Hospital Register. Risk of neonatal jaundice was calculated as odds ratios (ORs) with linear logistic regression with and without adjustment for confounders. RESULTS We identified 841,900 births. Of 1,823 (0.2%) neonates exposed to sulfamethizole up to 4 weeks before birth, 197 (10.8%) developed neonatal jaundice. The OR of developing neonatal jaundice after exposure to sulfamethizole was 2.35 (95% confidence interval [CI] 2.02-2.72). Adjustment for maternal age, education, household income, parity, and period of conception left OR unchanged at 2.29 (95% CI 1.97-2.67). After further adjustment for gestational age, the risk associated with sulfamethizole was rendered insignificant (OR 1.03, 95% CI 0.86-1.22). Narrowing exposure time to the last week before birth did not change the estimates. Broken into gestational age groups, the rate of neonates with jaundice after exposure was similar to the rate of unexposed neonates with jaundice. CONCLUSIONS We found no association between redeeming a prescription of sulfamethizole near term and increased risk of neonatal jaundice. We showed that the presumed association is the result of preterm birth, which can be caused by maternal urinary tract infection. LEVEL OF EVIDENCE II.

Background We examined all‐cause mortality and long‐term thromboembolic risk (ischemic stroke, transient ischemic attack, systemic thromboembolism) in patients with and without familial atrial fibrillation ( AF ). Methods and Results Using Danish nationwide registry data, we identified all patients diagnosed with AF (1995–2012) and divided them into those with familial AF (having a first‐degree family member with a prior AF admission) and those with nonfamilial AF . We paired those with and without familial AF according to age, year of AF diagnosis, and sex in a 1:1 match. Using cumulative incidence and multivariable Cox models, we examined the risk of long‐term outcomes. We identified 8658 AF patients (4329 matched pairs) with and without familial AF . The median age was 50 years (interquartile range 43–54 years), and 21.4% were women. Compared with nonfamilial AF patients, those with familial AF had slightly less comorbid illness but similar overall CHA 2 DS 2 ‐ VAS c score ( P =0.155). Median follow‐up was 3.4 years (interquartile range 1.5–6.5 years). Patients with familial AF had risk of death and thromboembolism similar to those with nonfamilial AF (adjusted hazard ratio 0.91 [95% CI 0.79–1.04] for death and 0.90 [95% CI 0.71–1.14] for thromboembolism). Conclusions Although family history of AF is associated with increased likelihood for development of AF , once AF developed, long‐term risks of death and thromboembolic complications were similar in familial and nonfamilial AF patients.

Background— The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. Methods and Results— We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49–1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52–1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22–1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28–1.55]). Conclusions— The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.

OBJECTIVES: The aim of the present study was to determine whether carvedilol-treated chronic heart failure patients have a different prognosis when stratified for a specific combination of a gain-of-function genotype of the adrenergic β-1 receptor gene (ADRB1) (Arg389-homozygous), two gain-of-function genotypes of the angiotensinogen gene (AGT) (Thr174-homozygous and Thr235-homozygous), and a downregulated genotype of the adrenergic β-2 receptor gene (ADRB2) (Gln27-carrier). METHODS: Genotyping of 618 patients was carried out using the Sequenoms MassARRAY genotyping system. Outcome was all-cause mortality and statistics were calculated using a multivariable Cox proportional hazards model. Internal validation was performed using the bootstrap procedure. RESULTS: Eighty-seven of the 618 patients included in the study were treated with carvedilol. There was a significant interaction between the outcome of carvedilol treatment and the combination of the gain-of-function ADRB1 genotype (Arg389-homozygous) and the gain-of-function AGT genotype (Thr174-homozygous) (Pinteraction=0.003; hazard ratio 2.19, 95% confidence interval 1.26-3.78, P=0.005). There was also a significant interaction when the downregulated ADRB2 genotype (Gln27-carrier) was added to the ADRB1/AGT combination (Pinteraction=0.0005; hazard ratio 2.67, 95% confidence interval 1.51-4.72, P=0.0007). Two hundred and four patients were treated with metoprolol. There was no interaction between metoprolol treatment and the specific genotype combinations as there was no difference in the overall survival. The validity of the results was supported by the bootstrap procedure. CONCLUSION: We found a doubling of the hazard of mortality in carvedilol-treated patients with the combination of the gain-of-function ADRB1 genotype (Arg389-homozygous), the gain-of-function AGT genotype (Thr174-homozygous), and the downregulated ADRB2 genotype (Gln27-carrier). This might be valuable when stratifying chronic heart failure patients to the right β-blocker therapy.

Markers of subclinical target organ damage (TOD) increase cardiovascular (CV) risk prediction beyond traditional risk factors. We wanted to establish thresholds for three markers of TOD based on absolute CV risk in different risk chart categories.In a cohort of 1968 healthy patients, we measured urine albumin creatine ratio (UACR), pulse wave velocity (PWV), left ventricular mass index (LVMI) and traditional risk factors. Patients were categorized according to Systemic Coronary Evaluation (SCORE), European Society of Hypertension/European Society of Cardiology (ESH/ESC) risk chart and Framingham risk score (FRS) and three corresponding endpoints were recorded: CV death (SCORE-endpoint), a composite of CV death and nonfatal myocardial infarction and stroke (ESH/ESC-endpoint), and a composite that also included hospital admissions for ischemic heart disease, heart failure, peripheral arterial disease and transient cerebral ischemic attack (FRS-endpoint). During a median follow of 12.8 years events totaled 81 SCORE-, 153 ESH/ESC-endpoints and 280 FRS-endpoints. Thresholds for UACR, PWV and LVMI are presented using 10-year risk threshold of more than 5% (SCORE-endpoint), more than 10%(ESH/ESC-endpoint) and more than 20%(FRS-endpoint), which indicated high risk and eligibility for primary prevention. As an example, the threshold was 0.83 mg/mmol, 13.7 m/s and 119 g/m for UACR, PWV and LVMI, respectively, for patients at moderate added risk according to ESH/ESC risk chart.Thresholds for UACR, PVW and LVMI based on absolute risk have primarily impact on risk stratification in patients with intermediate risk. The thresholds for PWV and LVMI in patients with moderate risk according to the ESH/ESC risk chart were similar to currently applied thresholds whereas the threshold for UACR was considerable lower than the threshold for microalbuminuria.

Background— Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment. Methods and Results— Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90–360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40). Conclusions— High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.

Objective: We have previously demonstrated that markers of subclinical organ damage (SOD) improve cardiovascular risk prediction in healthy individuals. We wanted to investigate whether this additive effect of SOD was due to inaccurate blood pressure (BP) measurement or whether ambulatory BP (AMBP) added further to risk prediction. Methods: In a population cohort of 1385 Danish individuals free of cardiovascular disease and diabetes, we recorded traditional risk factors, AMBP and pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular mass index (LVMI) and carotid atherosclerotic plaques at baseline. A composite cardiovascular endpoint (CEP) consisting of cardiovascular death and nonfatal myocardial infarction and stroke was recorded in national registries. Results: During a median follow-up of 12.8 years, a total of 119 CEPs occurred. In categorical analysis, presence of SOD as well as masked hypertension increased sensitivity of Systemic Coronary Risk Estimation from 73.9 to 89.1% (P