Thomas Andersen Rix

Validity of the diagnoses atrial fibrillation and atrial flutter in a Danish patient registry

Objectives. To assess the validity of the diagnoses of atrial fibrillation (AF) and atrial flutter (AFL) for men and women recorded in the Danish National Patient Registry, and to assess the relative distribution of AF and AFL. Design. Review of medical records for incident cases of AF and/or AFL in the Diet, Cancer, and Health cohort study. Participants were enrolled in 1993–97 with 13.6 years of follow-up until 30 December, 2009. Results. The positive predictive value of the combined diagnosis of AF and/or AFL was 92.6% (95% CI 88.8%; 95.2%) with no significant difference between sexes (men 93.7% (133/142), women 90.8% (129/142)). The proportion of AFL either alone or in combination with AF was significantly higher in men than in women (13.5% (18/133) vs. 5.4% (7/129), p =0.03). The positive predictive value of the specified diagnosis of AFL was 57.5% for men (46/80) and 29.6% for women (8/27). Conclusions. This study shows that the validity of the diagnosis of AF and/or AFL is high and may be used for registry-based studies. A specified diagnosis of AFL was rarely used and was not reliable to distinguish between cases of AF and AFL.

Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs

Background:  During euglycemia acute hyperinsulinemia diminishes the cytokine response to endotoxin [Lipopolysaccharide (LPS)] exposure. In this study we elucidated whether acute hyperglycemia and hyperinsulinemia modify the cytokine content in several organs during LPS challenge in a porcine model.

A U-shaped association between consumption of marine n-3 fatty acids and development of atrial fibrillation/atrial flutter—a Danish cohort study

AIMS Previous studies have suggested a lower risk of atrial fibrillation (AF) with higher intakes of fish and marine n-3 polyunsaturated fatty acids (PUFAs), but the results have been inconsistent. The aim was to investigate the association between consumption of marine n-3 PUFA and development of AF. METHODS AND RESULTS A total of 57 053 Danish participants 50-64 years of age were enrolled in the Diet, Cancer, and Health Cohort Study between 1993 and 1997. Dietary intake of fish and marine n-3 PUFA was assessed by a semi-quantitative food frequency questionnaire. In total, 3345 incident cases of AF occurred over 13.6 years. Multivariate Cox regression analyses (3284 cases and 55 246 participants) using cubic splines showed a U-shaped association between consumption of marine n-3 PUFA and risk of incident AF, with the lowest risk of AF at a moderate intake of 0.63 g/day. For quintiles of marine n-3 PUFA intake, a 13% statistically significant lower risk of AF was seen in the middle vs. lowest quintile: Q1 reference, Q2 HR 0.92 (95% CI 0.82-1.03), Q3 HR 0.87 (95% CI 0.78-0.98), Q4 HR 0.96 (95% CI 0.86-1.08), and Q5 HR 1.05 (95% CI 0.93-1.18). Intake of total fish, fatty fish, and the individual n-3 PUFA eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid also showed U-shaped associations with incident AF. CONCLUSION We found a U-shaped association between consumption of marine n-3 PUFA and risk of incident AF, with the lowest risk close to the median intake of total marine n-3 PUFA (0.63 g/day).

Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation: a Danish cohort study

Objective Consumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to investigate this further by measurements of marine n-3 PUFA in adipose tissue. Design Cohort study. Setting A total of 57 053 Danish participants 50–64 years of age were enrolled into the Diet, Cancer and Health Cohort Study. Patients A randomly drawn subcohort of 3440 participants with available data from baseline adipose tissue biopsies. Interventions Exposure was the adipose tissue content of marine n-3 PUFA, which reflects the endogenous exposure and is also an objective marker of the long-term dietary intake. Main outcome measures Incident AF during follow-up. Results 179 cases of AF occurred over 13.6 years. Multivariate, sex-stratified Cox proportional hazards regression analyses using cubic splines showed a monotonic, negative, dose-response trend, but not statistically significant association, between total marine n-3 PUFA in adipose tissue and incident AF. A similar trend towards a lower risk of AF was seen in the second (HR 0.87, 95% CI 0.60 to 1.24) and third tertiles (HR 0.77, 95% CI 0.53 to 1.10) of marine n-3 PUFA compared with the lowest tertile. Similar trends, but also not statistically significant, were found separately for eicosapentaenoic, docosahexaenoic and docosapentaenoic acids. Conclusions There was no statistically significant association between the content of marine n-3 PUFA in adipose tissue and the development of AF; however, data showed a monotonic, negative dose-response trend suggestive of a negative association.

Omega-3 fatty acids and cardiac arrhythmias.

Purpose of reviewThere are suggestions of effects of marine omega-3 polyunsaturated fatty acids (PUFAs) in relation to ventricular arrhythmia and sudden cardiac death and, more recently, also of possible effects related to atrial fibrillation. Recent findingsOn the basis of the recently published human studies, this article not only focusses primarily on recent developments and current knowledge on the effect of marine omega-3 PUFAs on atrial fibrillation, but also provides a status for their effects on ventricular arrhythmias. SummaryMarine omega-3 PUFAs may protect against ventricular arrhythmias, and there is growing evidence for an effect of marine omega-3 PUFAs in the prevention and treatment of atrial fibrillation. Further studies are needed to establish which patients are more likely to benefit from omega-3 PUFAs, the timing of treatment, and the dosages.

Fish, Marine n−3 Fatty Acids, and Atrial Fibrillation – Experimental Data and Clinical Effects

Marine n−3 polyunsaturated fatty acids (PUFA) may have beneficial effects in relation to atrial fibrillation (AF) with promising data from experimental animal studies, however, results from studies in humans have been inconsistent. This review evaluates the mechanisms of action of marine n−3 PUFA in relation to AF based on experimental data and provides a status on the evidence obtained from observational studies and interventional trials. In conclusion, there is growing evidence for an effect of marine n−3 PUFA in prevention and treatment of AF. However, further studies are needed to establish which patients are more likely to benefit from n−3 PUFA, the timing of treatment, and dosages.

Adipose tissue content of saturated fatty acids and atrial fibrillation: A case-cohort study

The aim of this study was to investigate the association between adipose tissue content of total saturated fatty acids including myristic (C14:0), palmitic (C16:0) and stearic (C18:0) acid, as a measure of exposure to saturated fatty acids and the risk of incident atrial fibrillation.

Effect of Dietary Intake of Saturated Fatty Acids on the Development of Atrial Fibrillation and the Effect of Replacement of Saturated With Monounsaturated and Polyunsaturated Fatty Acids

The aim of the present study was to explore substitution of intake of saturated fatty acids (FAs) with monounsaturated and polyunsaturated FAs and incident atrial fibrillation (AF) in men and women. A total of 57,053 Danish participants aged 50 to 64 years were enrolled in the Diet, Cancer and Health cohort study in 1993 to 1997 and completed a semiquantitative food frequency questionnaire at baseline. Follow-up was registry-based and data were analyzed using Cox proportional hazards regression. The statistical model was formulated in such a way that 1 g/day of saturated FAs was replaced with 1 g/day of monounsaturated or polyunsaturated FAs while keeping total fat intake, total energy intake, and energy intake from protein and carbohydrates constant. During a median follow-up of 17 years, 5,175 incident cases of AF occurred. In men, there was a higher hazard of AF when total n-3 polyunsaturated FAs replaced dietary saturated FAs-hazard ratio per 1-g substitution of FAs of 1.08 (95% confidence interval 1.02 to 1.14) in a model adjusted for lifestyle factors. For other substitutions of FAs (monounsaturated, total or n-6 polyunsaturated FAs), no consistent nor statistically significant associations were found. In conclusion, we found a moderately higher risk of AF in men, but not in women, when total n-3 polyunsaturated FAs replaced dietary saturated FAs. Substitution of saturated FAs with monounsaturated, total or n-6 polyunsaturated FAs was not associated with the risk of AF.

Natural Killer Cell Functions and Subsets After In Vitro Stimulation with IL-2 and IL-12, with Special Emphasis on Intracellular IFN-γ and NK-Cell Cytotoxicity

Materials and methods:  Isolated cryopreserved human peripheral blood mononuclear cells (PBMCs) were stimulated with IL‐2 and IL‐12. This stimulation has previously been shown to activate NK cells. Cell cytotoxicity was measured by flow cytometry after incubation with k562 cells. This method was compared to the current standard 51Cr release assay. Cells were treated with BFA to accumulate IFN‐γ, stained for surface markers, permeabilized and stained for intracellular IFN‐γ. Flow cytometry was then performed to measure intracellular IFN‐γ production in PBMC, especially in NK cells. Results:  We have demonstrated that stimulation with IL‐2 and IL‐12 is effective in increasing the number of IFN‐γ‐positive cells. There is a distinct difference between the CD3‐CD56dim and the CD3‐CD56bright subsets, with a much greater proportion of IFN‐γ‐positive cells in the CD3‐CD56bright subset. The effects of stimulation with IL‐2 and IL‐12 on cytotoxicity will be presented, as will the relation between IFN‐γ production and cytotoxicity. In addition, we will present results of these assays applied to porcine cells. Discussion:  In combination, these tests will address NK cell function by combining cytotoxicity with IFN‐γ production in NK cell subsets. The results will demonstrate whether this could serve as a useful tool in describing NK‐cell function, which could be of value in clinical and experimental settings.