Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding:A Danish population-based cohort study

OBJECTIVES: We examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). METHODS: This population‐based cohort study used data from Danish health registries. We identified all patients with a first‐time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person‐years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA(2)DS(2)VASc score, and Charlson Comorbidity Index score. RESULTS: We identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow‐up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1‐1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2‐2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7–1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1‐2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1‐4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3–2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7–3.9). CONCLUSION: In patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications

Mortality Risk Among Heart Failure Patients With Depression:A Nationwide Population-Based Cohort Study

BACKGROUND: The prevalence of depression is 4‐ to 5‐fold higher in heart failure patients than in the general population. We examined the influence of depression on all‐cause mortality in patients with heart failure. METHODS AND RESULTS: Using Danish medical registries, this nationwide population‐based cohort study included all patients with a first‐time hospitalization for heart failure (1995–2014). All‐cause mortality risks and 19‐year mortality rate ratios were estimated based on Cox regression analysis, adjusting for age, sex, time period, comorbidity, and socioeconomic status. The analysis included 9636 patients with and 194 887 patients without a diagnosis of depression. Compared with patients without a history of depression, those with depression had higher 1‐year (36% versus 33%) and 5‐year (68% versus 63%) mortality risks. Overall, the adjusted mortality rate ratio was 1.03 (95% CI 1.01–1.06). Compared with no depression, the adjusted mortality rate ratios for mild, moderate, and severe depression, as defined by diagnostic codes, were 1.06 (95% CI 1.00–1.13), 1.03 (95% CI 0.99–1.08), and 1.02 (95% CI 0.96–1.09), respectively. In a subcohort of patients, the mortality rate ratios were modified by left ventricular ejection fraction, with adjusted mortality rate ratios of 1.17 (95% CI, 1.05–1.31) for ≤35%, 0.98 (95% CI 0.81–1.18) for 36% to 49%, and 0.96 (95% CI 0.74–1.25) for ≥50%. Results were consistent after adjustment for alcohol abuse and smoking. CONCLUSIONS: A history of depression was an adverse prognostic factor for all‐cause mortality in heart failure patients with left ventricular ejection fraction ≤35% but not for other heart failure patients

Seventeen-Year Nationwide Trends in Antihypertensive Drug Use in Denmark.

Recent trends in use of antihypertensive drugs are unknown. From Danish nationwide prescription data, we obtained information on primary care use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, aldosterone receptor antagonists, and calcium channel blockers. During 1999 to 2015, the use of antihypertensive drugs per 1,000 inhabitants/day increased from 184 to 379 defined daily doses (DDD), corresponding to a rise in the prevalence proportion of users from ≈20% to ≈35%. From 1999 to 2015, a notable increase was observed for angiotensin-converting enzyme inhibitors (from 29 to 105 DDD per 1,000 inhabitants/day ≈260%) and angiotensin II receptor blockers (from 13 to 73 DDD per 1,000 inhabitants/day ≈520%). For diuretics the use remained stable, with a slight decrease (from 89 to 81 DDD per 1,000 inhabitants/day ≈-10%). The use of aldosterone receptor antagonists increased until 2007 and remained unchanged at around 3.5 DDD per 1,000 inhabitants/day thereafter (average change ≈65%). The use of beta blockers doubled during the study period (from 17 to 34 DDD per 1,000 inhabitants/day ≈100%), entirely driven by increasing use of metoprolol. Similar trends were observed for calcium channel blockers (from 34 to 82 DDD per 1,000 inhabitants/day ≈140%), where amlodipine drove the overall increase. In conclusion, antihypertensive drug use has increased remarkably during the past 2 decades

The Danish Myelodysplastic Syndromes Database:Patient Characteristics and Validity of Data Records

BACKGROUND: The Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for epidemiological research and the quality of registered variables remains to be investigated. OBJECTIVE: To describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records. METHODS: We performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010–2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard. RESULTS: Overall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88–95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after. CONCLUSION: In this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment