Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation.

BACKGROUND: The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF). METHODS: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9 years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression. RESULTS: Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile. CONCLUSIONS: A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.

Selective occlusion of splenic artery aneurysms with the coil packing technique: the impact of packing density on aneurysm reperfusion correlated between contrast-enhanced MR angiography and digital subtraction angiography.

PURPOSE: The aim was to evaluate the relationship between coil packing densities after splenic artery aneurysm (SAA) treatment using detachable microcoils and rates of SAA reperfusion and to suggest a post-treatment surveillance protocol using contrast-enhanced MRA. MATERIALS AND METHODS: Evaluated were 16 patients (4 men; mean age 46.7), who underwent true SAA embolization using detachable microcoils (Concerto, Medtronic). SAAs were treated by selective coil packing (CP) or stent-assisted coil exclusion (SAC). Contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA) were performed at 3 months post-procedure and correlated. RESULTS: Primary CP was used in 13 patients, while SAC was used in three patients. On follow-up, complete aneurysm occlusion was seen in seven patients (43.8%). Sac reperfusion occurred in nine patients (56.2%) and was demonstrated in all CE-MRA and six DSA studies. Mean aneurysm packing density was 20.10 ± 8.05% for the CP group and 32.90 ± 11.95% for the SAC group (p = 0.038). There was a significant difference in the incidence of aneurysm sac reperfusion on CE-MRA study between CP and SAC (9 vs. 0). No sac reperfusion was seen in aneurysms with packing densities ≥ 29%, irrespective of either embolization method. CONCLUSION: Favorable midterm results for coil packing of SAAs seem to depend on the coil packing density with a coil volume approximately a quarter of the aneurysm volume being most effective. Follow-up should involve the use of CE-MRA as this modality has been shown to be superior over DSA in detecting aneurysm reperfusion and coil compaction. LEVEL OF EVIDENCE: Level IV, therapeutic study.

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

OBJECTIVES: 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. MATERIALS AND METHODS: A total of 57 053 Danish men and women aged 50-64 years participating in the Diet, Cancer and Health cohort had an adipose tissue biopsy taken at baseline, and this was analysed for saturated fatty acids content by gas chromatography. Follow-up was registry based and in this case-cohort study we used all cases and a randomly drawn subcohort of 3500 participants representative for the entire cohort. RESULTS: Data were analysed using weighted Cox proportional hazards regression. During a median follow-up of 14.6 years, a total of 4722 cases of incident atrial fibrillation were diagnosed. For both men and women, no association between adipose tissue content of total saturated fatty acids and the risk of atrial fibrillation could be demonstrated. CONCLUSION: We did not find an association between adipose tissue content of total saturated fatty acids and the risk of incident atrial fibrillation.

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).

Omega-3 fatty acids and cardiac arrhythmias.

PURPOSE OF REVIEW: There 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 FINDINGS: On 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. SUMMARY: Marine 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.

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.

BST2/Tetherin Overexpression Modulates Morbillivirus Glycoprotein Production to Inhibit Cell-Cell Fusion.

The measles virus (MeV), a member of the genus Morbillivirus, is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus-cell and cell-cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell-cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell-cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell-cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype.

Patterns of adipose tissue fatty acids and the risk of atrial fibrillation: A case-cohort study.

Fatty acids in adipose tissue share dietary sources and metabolic pathways and therefore occur in patterns. The aim of the present study was to investigate the association between adipose tissue fatty acid patterns identified by the data-driven dimension-reducing method treelet transform and the risk of atrial fibrillation. A total of 57,053 Danish men and women aged 50-64 years participating in the Diet, Cancer and Health cohort had an adipose tissue biopsy taken at baseline. During a median follow-up of 14.6 years, a total of 4,710 participants developed atrial fibrillation or atrial flutter. Adipose tissue biopsies were analysed for fatty acid content by gas chromatography for all cases of atrial fibrillation and for a randomly drawn subcohort (n = 3,500) representative for the entire cohort. Hazard ratios with 95% confidence intervals for atrial fibrillation according to quintiles of factor scores were determined by weighted Cox proportional hazards regression analyses for men and women separately. From the 32 fatty acids measured, 7 major factors/patterns of fatty acids were identified using treelet transform. We found that a pattern consisting of n-6 polyunsaturated fatty acids (PUFA) (except linoleic acid) was associated with a lower hazard of atrial fibrillation. Patterns consisting of marine n-3 PUFA and containing n-9 fatty acids were associated with a lower hazard of atrial fibrillation in women. In conclusion, patterns of fatty acids in adipose tissue identified by treelet transform may be differentially associated with the risk of atrial fibrillation.

The effect of activated protein C on plasma cytokine levels in a porcine model of acute endotoxemia.

OBJECTIVE: To assess the anti-inflammatory effects of recombinant human activated protein C (rhAPC) in a porcine model of acute endotoxemia. DESIGN AND SETTING: Animal randomized controlled study at the Laboratory of Clinical Institute, Aarhus University Hospital. SUBJECTS: Eighteen female landrace pigs (30 kg). INTERVENTIONS: By pairwise randomization, pigs were given either LPS or LPS and rhAPC. Both groups received a stepwise increasing LPS infusion for 30[Symbol: see text]min; whereafter the infusion continued at a lower rate (300 min LPS in both groups). The LPS+rhAPC group received rhAPC (100 microg/kg per hour) 15 min before the LPS infusion began and throughout the trial period. RESULTS: While rhAPC showed no modifying effects on peak plasma levels of pro- or anti-inflammatory cytokines (TNF-alpha, IL-6, IL-8, IL-10), TNF-alpha and IL-10 peaked significantly later in the rhAPC-treated animals. The profibrinolytic effects of rhAPC were confirmed by decreased plasminogen activator inhibitor 1 levels, while no differences were found in other coagulation markers, hemodynamic, metabolic, or leukocyte data between the two groups. CONCLUSIONS: We found no significant effect of rhAPC on plasma levels of either pro- or anti-inflammatory cytokines in this porcine model of acute endotoxemia. However, TNF-alpha and IL-10 peaked significantly later in the rhAPC-treated animals.

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.

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.

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.

RACE to protect brains.

INTRODUCTION: Rapid-access carotid endarterectomy (RACE) is an evidence-based treatment for symptomatic carotid stenosis. Our vascular centre aims to provide this service within 48 h of symptoms in appropriate patients. This study audits safety and efficacy of the first year of RACE. SUBJECTS AND METHODS: A clear trust protocol was publicised for the RACE pathway. A prospective database was established for all carotid endarterectomies (CEAs) performed. Outcomes were compared between elective (ECE) and rapid-access operations. RESULTS: In 1 year, 96 patients received CE; 20 were performed urgently. There were no significant differences in age or gender between ECE and RACE groups. Twenty-three (30%) of ECE were for asymptomatic stenoses; no other significant differences in surgical indication were seen. Of symptomatic ECE, 43% were for completed stroke versus 55% for RACE. Median delay between diagnosis and surgery was 113 days for elective and 2 days for RACE patients. There was one death following ECE (1.3%) and one stroke after RACE (5%), all not significant. Anaesthetic method did not influence outcome. The main reasons for delaying surgery in RACE patients were optimisation of patient fitness and availability of theatre time. CONCLUSIONS: The RACE pathway dramatically reduces delay without compromising patient safety. In the first year of service, we have treated 50% of suitable patients within 48 h. Further education of patients and colleagues should reduce delay and improve outcomes for symptomatic carotid disease.

Pre-operative risk scores for the prediction of outcome in elderly people who require emergency surgery.

BACKGROUND: The decision on whether to operate on a sick elderly person with an intra-abdominal emergency is one of the most difficult in general surgery. A predictive risk-score would be of great value in this situation. METHODS: A Medline search was performed to identify those predictive risk-scores relevant to sick elderly patients in whom emergency surgery might be life-saving. RESULTS: Many of the risk scores for surgical patients include the operative findings or require tests which are not available in the acute situation. Most of the relevant studies include younger patients and elective surgery. The Glasgow Aneurysm Score and Hardman Index are specific to ruptured aortic aneurysm while the Boey Score and the Hacetteppe Score are specific to perforated peptic ulcer. The Reiss Index and Fitness Score can be used pre-operatively if the elements of the score can be completed in time. The ASA score, which includes a significant element of subjective clinical judgement, can be augmented with factors such as age and urgency of surgery but no test has a negative predictive value sufficient to recommend against surgical intervention without clinical input. CONCLUSION: Risk scores may be helpful in sick elderly patients needing emergency abdominal surgery but an experienced clinical opinion is still essential.