Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted

Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)

BACKGROUND: In hereditary angioedema, bradykinin is assumed to be the most important mediator of edema formation. OBJECTIVE: To assess whether the selective bradykinin receptor-2 antagonist Icatibant is effective in acute edema attacks of hereditary angioedema. METHODS: In this uncontrolled pilot study, 15 patients with 20 attacks were treated with Icatibant. The attacks were analyzed by using a standardized and validated visual analog scale measurement and compared with historical data of untreated attacks. Plasma bradykinin concentration was measured before and 4 hours after intravenous Icatibant treatment. RESULTS: Symptom intensity decreased within 4 hours after administration of Icatibant; the median time to onset of symptom relief was 1.50, 1.42, and 1.13 hours in the intravenous groups and 0.58 and 0.45 hours in the subcutaneous groups, respectively. The median difference in the 10-cm visual analog scale 4 hours after start of treatment was 4.11 cm (95% CI, 1.72-6.07). Compared with untreated attacks, Icatibant treatment reduced the mean (SD) time to onset of symptom relief by 97% from 42 +/- 14 to 1.16 +/- 0.95 hours (all groups combined). Median bradykinin concentration was 7-fold above the norm during acute attacks at 48.5 pmol/L and decreased to 18.0 pmol/L 4 hours after Icatibant infusion or injection. CONCLUSION: Icatibant was effective in treating acute attacks of hereditary angioedema. CLINICAL IMPLICATIONS: This is the first report demonstrating the clinical usefulness of antagonizing bradykinin binding to bradykinin receptor-2 in hereditary angioedema

Sex-related change in BMI of 15- to 16-year-old Norwegian girls in cross-sectional studies in 2002 and 2017

Background The prevalence of overweight and obesity (OWOB) has stabilized in some countries, but a portion of children with high body mass index (BMI) may have become heavier. This study aimed to describe the distributions of BMI and the point prevalence of OWOB in Norwegian adolescents in 2002 and 2017. Methods A cross-sectional study involving 15- to 16-year-old adolescents in Oppland, Norway, was undertaken in 2002 and 2017. We calculated their BMI, BMI z-scores (BMIz), and the prevalence of OWOB. Results The mean BMI increased from 20.7 to 21.4 (p < 0.001) for girls but remained unchanged at 21.5 vs 21.4 (p = 0.80) for boys. The prevalence of OWOB increased from 9 to 14% among girls (difference 5, 95% CI: 2, 8) and from 17 to 20% among boys (difference 3, 95% CI: − 1, 6%). The BMI density plots revealed similar shapes at both time points for both sexes, but the distribution for girls shifted to the right from 2002 to 2017. Conclusion Contrary to previous knowledge, we found that the increase in OWOB presented a uniform shift in the entire BMI distribution for 15–16-year-old Norwegian girls and was not due to a larger shift in a specific subpopulation in the upper percentiles