Pia Cordsen

Objectives: To examine how the lifetime risks of atrial fibrillation and of complications after atrial fibrillation changed over time. Design: Danish, nationwide, population based cohort study. Setting: Population of Denmark from 1 January 2000 to 31 December 2022. Participants: 3.5 million individuals (51.7% women and 48.3% men) who did not have atrial fibrillation at 45 years of age or older were followed up until incident atrial fibrillation, migration, death, or end of follow-up, whichever came first. All 362 721 individuals with incident atrial fibrillation (46.4% women and 53.6% men), but with no prevalent complication, were further followed up until incident heart failure, stroke, or myocardial infarction. Main outcome measures: Lifetime risk of atrial fibrillation and lifetime risks of complications after atrial fibrillation over two prespecified periods (2000-10 v 2011-22). Results: The lifetime risk of atrial fibrillation increased from 24.2% in 2000-10 to 30.9% in 2011-22 (difference 6.7% (95% confidence interval 6.5% to 6.8%)). After atrial fibrillation, the most frequent complication was heart failure with a lifetime risk of 42.9% in 2000-10 and 42.1% in 2011-22 (−0.8% (−3.8% to 2.2%)). Individuals with atrial fibrillation lost 14.4 years with no heart failure. The lifetime risks of stroke and of myocardial infarction after atrial fibrillation decreased slightly between the two periods, from 22.4% to 19.9% for stroke (−2.5% (−4.2% to −0.7%)) and from 13.7% to 9.8% for myocardial infarction (−3.9% (−5.3% to −2.4%). No evidence was reported of a differential decrease between men and women. Conclusion: Lifetime risk of atrial fibrillation increased over two decades of follow-up. In individuals with atrial fibrillation, about two in five developed heart failure and one in five had a stroke over their remaining lifetime after atrial fibrillation diagnosis, with no or only small improvement over time. Stroke risks and heart failure prevention strategies are needed for people with atrial fibrillation.

Background: The incidence of atrial fibrillation (AF) shows substantial temporal trends, but the contribution of birth cohort effects is unknown. These effects refer to the relationship between birth year and the likelihood of developing AF. We aimed to assess trends in cumulative incidence of diagnosed AF across birth cohorts and to disentangle the effects of age, birth cohort and calendar period by using age–period–cohort analyses. Methods: In a Danish nationwide population-based cohort study, 4.7 million individuals were selected at a given index age (45, 55, 65 and 75 years) free of AF and followed up for diagnosed AF. For each index age, we assessed trends in 10-year cumulative incidence of AF across six 5-year birth cohorts. An age–period–cohort model was estimated using Poisson regression with constrained spline functions collapsing data into 1-year intervals across ages and calendar years. Results: Cumulative incidence of AF diagnosis increased across birth cohorts for all index ages (p_trend<0.001). Compared with the first birth cohort, the diagnosed AF incidence rate ratio in the last birth cohort was 3.0 (95% CI 2.9 to 3.2) for index age 45 years, 2.9 (2.8 to 3.0) for 55 years, 2.8 (2.7 to 2.8) for 65 years and 2.7 (2.6 to 2.7) for 75 years. Age–period–cohort analyses showed substantial birth cohort effects independent of age, with no clear period effect. Compared with individuals born in 1930, the diagnosed AF incidence rate was 0.125 smaller among individuals born in 1885 and was four times larger among individuals born in 1975. Conclusion: Substantial birth cohort effects, independent of age and calendar period, influence trends in diagnosed AF incidence.

BACKGROUND: We aimed to investigate whether socioeconomic status (SES) was associated with functional outcome in patients with ischemic stroke treated with reperfusion therapy (intravenous thrombolysis and/or thrombectomy). METHODS: This nationwide cohort study included reperfusion-treated patients with ischemic stroke ≥18 years registered in the Danish Stroke Registry between 2015 and 2018. Functional outcome was determined by the modified Rankin Scale score 90 days after stroke. SES was defined by educational attainment, family income, and employment status before stroke. SES data were available from Statistics Denmark and linked on the individual level with data from the Danish Stroke Registry. Uni- and multivariable ordinal logistic regression was performed for each socioeconomic parameter individually (education, income, and employment) to estimate the common odds ratios (cORs) for lower 90-day modified Rankin Scale scores. RESULTS: A total of 5666 patients were included. Mean age was 68.7 years (95% CI, 68.3–69.0), and 38.4% were female. Low SES was associated with lower odds for achieving lower 90-day modified Rankin Scale score: Low versus high education, cOR, 0.69 (95% CI, 0.61–0.79), low versus high income, cOR, 0.59 (95% CI, 0.53–0.67), and unemployed versus employed, cOR, 0.70 (95% CI, 0.58–0.83). Inequalities were reduced after adjusting for age, sex, and immigrant status, except for unemployed versus employed patients, adjusted cOR, 0.66 (95% CI, 0.54–0.80). No statistically significant differences remained after adjusting for potentially mediating variables (eg, stroke severity, prestroke modified Rankin Scale, and smoking). CONCLUSIONS: Socioeconomic inequalities were observed in functional outcome after reperfusion treated ischemic stroke. In particular, prestroke unemployment was negatively associated with good functional outcome. A more adverse prognostic profile among patients with low SES appeared to explain the majority of these inequalities.

Introduction: Individuals affected by atrial fibrillation (AF) often present with multiple comorbidities that challenge their clinical management and worsen the prognosis. Characterizing the network structure of comorbid chronic conditions in AF patients may provide insights to better tailor medical and care management. Purpose: To examine and compare the network structure of comorbidities in older people with and without AF. Methods: Cross-sectional data derived from the Danish National Patient Register (period 2012–2017) were examined. Patients 60+ years old by 1. January 2017 with AF were selected and matched by age and sex to non-AF controls. Chronic conditions coded according to the International Classification of Diseases, 10th revision were retrieved and grouped into 60 clinically relevant disease categories for old age. Network analysis was applied to construct the disease networks and the centrality index of expected influence was measured to estimate the disease interconnectedness in each network. The difference in network structure and disease centrality between AF and non-AF patients was formally assessed through network comparison tests. Results: A total of 96,117 AF patients (72 years old; 45% women) were identified and matched with 96,117 non-AF controls. The most prevalent chronic conditions in AF were hypertension (55.1%), large bowel diseases (36.4%) and ischemic heart disease (36.0%). A significant difference of global network structure was observed between AF and non-AF patients (p<0.001) (Figure1). Chronic obstructive pulmonary disease, depression, inflammatory arthropathy, chronic kidney disease and peripheral neuropathy had a higher connectivity with other diseases in the AF vs. non-AF patients (p<0.001). By contrast, hypertension, heart failure and stroke were more interconnected in the non-AF patients (p<0.001). Among AF patients, network differences were further observed between age categories (60–79 vs 80+ years) in male and female subgroups. Conclusions: Older AF patients exhibited a complex network structure of chronic conditions that differed from age- and sex- matched non-AF patients. The network-based identification of highly co-morbid diseases in AF can improve our understanding of AF-related chronic conditions and potentially enhance prioritization and a personalized care for older patients with AF. Funding Acknowledgement: Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation programme

Background: Reperfusion therapies (thrombolysis and thrombectomy) are of paramount importance for the recovery after ischemic stroke. We aimed to investigate if socioeconomic status (SES) was associated with the chance of receiving reperfusion therapy for ischemic stroke in a country with tax-funded health care. Methods: This nationwide register-based cohort study included patients with ischemic stroke registered in the Danish Stroke Registry between 2015 and 2018. SES was determined by prestroke educational attainment, income level, and employment status. Data on SES was obtained from Statistics Denmark and linked on an individual level with data from the Danish Stroke Registry. Risk ratios (RR) for receiving reperfusion therapies were calculated using univariate and multivariable Poisson regression with robust variance. Results: A total of 37 187 ischemic stroke patients were included. Low SES, as defined by education, income and employment status, was associated with lower treatment rates. The socioeconomic gradient was most pronounced according to employment status, with intravenous thrombolysis rates of 23.7% versus 15.8%, and thrombectomy rates of 5.1% versus 2.8% for employed versus unemployed patients. When the analyses were restricted to patients with timely hospital arrival, and adjusted for age, sex and immigrant status, low SES according to income and employment remained unfavorable for the likelihood of receiving intravenous thrombolysis: adjusted RR, 0.90 (95% CI, 0.86–0.95) for low versus high income, and adjusted RR, 0.77 (95% CI, 0.71–0.84) for unemployed versus employed patients. Similarly, low SES according to income and employment status remained unfavorable for the likelihood of receiving thrombectomy: adjusted RR, 0.83 (95% CI, 0.72–0.95) for low versus high income and adjusted RR, 0.68 (95% CI, 0.53–0.88) for unemployed versus employed patients. Conclusions: Socioeconomic inequalities in reperfusion treatment rates among ischemic stroke patients prevail, even in a country with tax-funded universal health care.

Objective: Prior work estimated excess death rates associated with atrial fibrillation (AF) in heart failure (HF) with hazard ratios (HR). The aim was to estimate the life-years lost after newly diagnosed AF in HF patients. Methods: Among patients diagnosed with HF in 2008– 2018 in the nationwide Danish Heart Failure Registry, we compared patients with incident AF to referents matched on age, sex, and time since HF. We estimated the marginal hazard ratio (HR) for death and marginal difference in restricted mean survival times (RMST) between AF cases and referents at 10 years after AF diagnosis. We adjusted for sex, age at AF diagnosis, clinical and lifestyle risk factors, and medications. Results: Among 4463 AF cases and 17,792 referents (mean age 73.7 years, 29% women), the HR was 1.41 (95% CI 1.38; 1.44) but there was evidence of non-proportional hazards. The difference in RMST was − 18.2 months (95% CI − 16.8; − 19.6) at 10 years after AF diagnosis. There were differences in life-years lost between patients diagnosed with AF > 1 year and ≤ 1 year after HF (− 25.7 months, 95% CI − 23.7; − 27.7 vs − 10.4 months, 95% CI − 8.2; − 12.5, p < 0.001), women and men (− 20.3 months, 95% CI − 17.7; − 21.9 vs − 17.2 months, 95% CI − 15.5; − 19.0, p = 0.05), patients with low, medium, and high CHA₂DS₂-VASc (10.3 months, 95% CI − 4.6; − 16.1 vs − 18.5 months, 95% CI − 16.7; − 20.4 vs 22.1, 95% CI − 18.8; − 22.3, p = 0.002). Conclusion: HF patients with incident AF lost on average 1.5 life-years over 10 years after AF. Life-years lost were larger among patients diagnosed with AF > 1 year after HF, women, and patients with higher CHA₂DS₂-VASc.