Abstract Background Little updated population-based evidence exists of temporal trends in infective endocarditis (IE). Methods For the 1994–2011 period, we used Danish nationwide registries to ...identify cases with first-time IE and to estimate the population size. We calculated the incidence rate of IE in 3-year intervals. To evaluate time trends in incidence, we used the 1994–1996 period as reference and computed incidence ratios and 95% confidence intervals (CI) as the incidence in each of the subsequent 3-year intervals divided by the incidence in the reference period. Results We identified 5486 incident IE patients (65% men) and the mean age at diagnosis was 63 years. Men tended to be younger at diagnosis than women; 62 years vs. 65 years. Mean age at IE diagnosis steadily increased from 57 years in 1994–1996 to 65 years in 2009–2011. The IE incidence rate increased from 3.93 per 100,000 person-years in 1994–1996 to 7.55 per 100,000 person-years in 2009–2011, corresponding to an incidence ratio of 1.92 (95% CI: 1.74–2.12). The increase in incidence over time was more pronounced in men (2.28, 95% CI: 2.02–2.59) than in women (1.39, 95% CI: 1.18–1.64). We observed no increase in incidence over time for subjects younger than 50 years, whereas the incidence increased substantially over time for elderly patients, with the highest incidence ratio of 3.38 (95% CI: 2.55–4.52) for patients more than 80 years at IE onset. Conclusion The incidence of IE increased over time particularly among men and for the older age groups.
Diuretics and renin–angiotensin–aldosterone system inhibitors are central in the treatment of hypertension, but may cause serum potassium abnormalities. We examined mortality in relation to serum ...potassium in hypertensive patients.
From Danish National Registries, we identified 44 799 hypertensive patients, aged 30 years or older, who had a serum potassium measurement within 90 days from diagnosis between 1995 and 2012. All-cause mortality was analysed according to seven predefined potassium levels: <3.5 (hypokalaemia), 3.5–3.7, 3.8–4.0, 4.1–4.4, 4.5–4.7, 4.8–5.0, and >5.0 mmol/L (hyperkalaemia). Outcome was 90-day mortality, estimated with multivariable Cox proportional hazard model, with the potassium interval of 4.1–4.4 mmol/L as reference. During 90-day follow-up, mortalities in the seven strata were 4.5, 2.7, 1.8, 1.5, 1.7, 2.7, and 3.6%, respectively. Adjusted risk for death was statistically significant for patients with hypokalaemia hazard ratio (HR): 2.80, 95% confidence interval (95% CI): 2.17–3.62, and hyperkalaemia (HR: 1.70, 95% CI: 1.36–2.13). Notably, normal potassium levels were also associated with increased mortality: K: 3.5–3.7 mmol/L (HR: 1.70, 95% CI: 1.36–2.13), K: 3.8–4.0 mmol/L (HR: 1.21, 95% CI: 1.00–1.47), and K: 4.8–5.0 mmol/L (HR: 1.48, 95% CI: 1.15–1.92). Thus, mortality in relation to the seven potassium ranges was U-shaped, with the lowest mortality in the interval of 4.1–4.4 mmol/L.
Potassium levels outside the interval of 4.1–4.7 mmol/L were associated with increased mortality risk in patients with hypertension.
Despite wide dissemination, use of automated external defibrillators (AEDs) in community settings is limited. We assessed how AED accessibility affected coverage of cardiac arrests in public ...locations.
We identified cardiac arrests in public locations (1994-2011) in terms of location and time and viewed them in relation to the location and accessibility of all AEDs linked to the emergency dispatch center as of December 31, 2011, in Copenhagen, Denmark. AED coverage of cardiac arrests was defined as cardiac arrests within 100 m (109.4 yd) of an AED and further categorized according to AED accessibility at the time of cardiac arrest. Daytime, evening, and nighttime were defined as 8 am to 3:59 pm, 4 to 11:59 pm, and midnight to 7:59 am, respectively. Of 1864 cardiac arrests in public locations, 61.8% (n=1152) occurred during the evening, nighttime, or weekends. Of 552 registered AEDs, 9.1% (n=50) were accessible at all hours, and 96.4% (n=532) were accessible during the daytime on all weekdays. Regardless of AED accessibility, 28.8% (537 of 1864) of all cardiac arrests were covered by an AED. Limited AED accessibility decreased coverage of cardiac arrests by 4.1% (9 of 217) during the daytime on weekdays and by 53.4% (171 of 320) during the evening, nighttime, and weekends.
Limited AED accessibility at the time of cardiac arrest decreased AED coverage by 53.4% during the evening, nighttime, and weekends, which is when 61.8% of all cardiac arrests in public locations occurred. Thus, not only strategic placement but also uninterrupted AED accessibility warrant attention if public-access defibrillation is to improve survival after out-of-hospital cardiac arrest.
Abstract
Alzheimer's disease is a neurodegenerative disorder in which the pathological accumulation of amyloid-β and tau begins years before symptom onset. Emerging evidence suggests that β-blockers ...(β-adrenergic antagonists) increase brain clearance of these metabolites by enhancing CSF flow. Our objective was to determine whether β-blocker treatments that easily cross the blood–brain barrier reduce the risk of Alzheimer's disease compared to less permeable β-blockers.
Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with β-blockers were included in the analysis. People with indications for β-blocker use other than hypertension (e.g. heart failure) were only retained in a sensitivity analysis. β-blockers were divided into three permeability groups: low, moderate and high. We used multivariable cause-specific Cox regression to model the effect of β-blocker blood–brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics and socioeconomic variables. Death was modelled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment.
In a cohort of 69 081 (median age = 64.4 years, 64.8% female) people treated with β-blockers for hypertension, highly blood–brain barrier-permeable β-blockers were associated with reduced risk of Alzheimer's disease versus low permeability β-blockers (−0.45%, P < 0.036). This effect was specific to Alzheimer's diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low blood–brain barrier-permeable patients also detected a decreased Alzheimer's risk (−0.92%, P < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (−0.57%, P < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment.
Our results suggest that amongst people taking β-blockers for hypertension, treatment with highly blood–brain barrier permeable β-blockers reduces the risk of Alzheimer's disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable β-blockers protect against Alzheimer's disease by promoting waste brain metabolite clearance.
Beaman et al. report that among people taking β-blockers for hypertension, treatment with highly blood–brain barrier permeable β-blockers reduces the risk of Alzheimer's disease compared to low permeability drugs, possibly by promoting brain waste clearance via the glymphatic system.
Patients with heart failure (HF) may be at increased risks of cancer, but the magnitude of risk for various cancer subtypes is insufficiently investigated.
Using the Danish Nationwide administrative ...databases between 1997 and 2017, we estimated the prevalence, incidence and relative risk for all-cause cancer in new-diagnosed HF vs. age and sex-matched controls (up to 5 controls per HF case) before and after adjustment for comorbidities.
Among the 167,633 people in the heart failure group and 837,126 individuals in the control group, there was a higher prevalence of several comorbidities, including cancer (17% vs. 10%) in the HF group; odds ratio 1.72 (1.70–1.75). Patients with heart failure also had higher cancer incidence (cancer incidence rate 3.02 2.97–3.07 per 100 person-years), compared with controls (cancer incidence rate 1.89 1.88–1.90); hazards ratio 1.38 (1.36–1.40). However, after adjustment for comorbidities the increased risk of malignancy was greatly attenuated (hazards ratio 1.14 1.12–1.16 for incident all-cause cancer) and dissipated altogether after additional adjustment for medications (multivariable adjusted hazards ratio 0.93 0.91–0.96 for all-cause cancer). In a homogeneous cohort of patients with ischemic heart disease, the increased risk of all-cause cancer was only marginally increased after adjustment for baseline comorbidities (hazards ratio 1.05 1.02–1.08).
Patients with heart failure had a slightly increased risk of various cancer subtypes, but the risks were mainly driven by comorbidities.
•Whether heart failure patients have an increased cancer risk is not well-known.•We observed that patients with heart failure had increased unadjusted cancer risk.•Adjusted for multiple factors, the risks were almost completely attenuated.
Aims
With improvement in survival of chronic heart failure (HF), the clinical importance of co‐morbidity is increasing. The aim of this study was to assess the incidence and risk of cancer and ...all‐cause mortality in a large Danish HF cohort.
Methods and results
A total of 9307 outpatients with verified HF without a prior diagnosis of cancer (27% female, mean age 68 years, 89% with LVEF <45%) were included in the study. A diagnosis of any cancer and all‐cause mortality was obtained from Danish national registries. Outcome was compared with the general Danish population. Overall and type‐specific risk of cancer was analysed in an adjusted Poisson and Cox regression analysis. The 975 diagnoses of cancer in the HF cohort and 330 843 in the background population corresponded to incidence rates per 10 000 patient‐years of 188.9 95% confidence interval (CI) 177.2–200.6 and 63.0 (95% CI 63.0–63.4), respectively. When stratified by age, incidence rates were increased in all age groups in the HF cohort. Risk of any type of cancer was increased, with an incidence rate ratio of 1.24 (95% CI 1.15–1.33, c < 0.0001). Type‐specific analysis demonstrated an increased hazard ratio for all major types of cancer except for prostate cancer. All‐cause mortality was higher in HF patients with cancer compared with cancer patients from the background population.
Conclusions
Patients with HF have an increased risk of cancer, which persists after the first year after the diagnosis of HF, and their prognosis is worse compared with that of cancer patients without HF.
Psoriasis has been associated with increased risk of myocardial infarction (MI) in some, but not all, studies. This study investigated the risk of MI in patients with psoriasis and psoriatic ...arthritis in Denmark. All residents aged ≥18 years from 1 January 2008 through 31 December 2012 were included. Adjusted hazard ratios (HRs) did not show an increased risk of MI in patients with mild psoriasis (HR 1.02; 95% confidence interval (95% CI) 0.96-1.09), whereas the risk was slightly increased in patients with severe psoriasis (HR 1.21; 1.07-1.37). Stratified by age, there was no increased risk of MI in any specific age group, regardless of severity. Limited to first-time MI, the risk was increased only in patients with severe psoriasis aged <50 years (HR 1.52; 1.03-2.25). The same applied to patients without psoriatic arthritis (severe psoriasis aged <50 years; HR 1.74; 1.11-2.72). In analyses restricted to patients with psoriatic arthritis, age-specific strata did not show any association between psoriatic arthritis and MI risk.
Aims
The impact of insulin secretagogues (ISs) on long-term major clinical outcomes in type 2 diabetes remains unclear. We examined mortality and cardiovascular risk associated with all available ISs ...compared with metformin in a nationwide study.
Methods and results
All Danish residents >20 years, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years) by individual-level linkage of nationwide registers. All-cause mortality, cardiovascular mortality, and the composite of myocardial infarction (MI), stroke, and cardiovascular mortality associated with individual ISs were investigated in patients with or without previous MI by multivariable Cox proportional-hazard analyses including propensity analyses. A total of 107 806 subjects were included, of whom 9607 had previous MI. Compared with metformin, glimepiride (hazard ratios and 95% confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide 1.05 (0.94-1.16) and 0.90 (0.68-1.20) and repaglinide and 0.97 (0.81-1.15) and 1.29 (0.86-1.94) were not statistically different from metformin in both patients without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint.
Conclusion
Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other ISs.
Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after ...gastrointestinal bleeding in patients with atrial fibrillation? Methods This Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models. Study answer and limitations 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment. What this study adds Among patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding. Funding, competing interests, data sharing This study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share.
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