Completed projects
N-3 and n-6 polyunsaturated fatty acids: metabolic pathways, interaction and risk of atrial fibrillation.
PhD project by Lotte Maxild Mortensen, Cand. Scient, PhD Student (January 2011- May 2017)
Postoperative New-Onset Atrial Fibrillation Following Cardiac Surgery with Special reference to Potential New Predictors.
PhD project by Jiwei GU, MD, PhD Student (March 2014- March 2017
Postoperative new onset atrial fibrillation (POAF) is a common complication following cardiac surgery and may develop in 10-65% of patients depending on the POAF definition, type of surgery and diagnostic method. Because POAF is associated with an increased risk of early and late mortality and morbidity, POAF prevention is a focus in many centers. Therefore, efforts to identify patients at an increased risk for POAF would be beneficial to take precautionary measures specifically in these high-risk patients to potentially decrease morbidity and mortality related to POAF. Therefore, a continuous awareness regarding possibilities to predict POAF is important. The cause of POAF is multifactorial, and therefore, multidirectional efforts are needed to be able to identify more high-risk patients. The overall aim of this PhD thesis is to identify potentially new predictors of POAF by performing three individual studies.
Objectives and hypotheses:
Study 1. To investigate whether ECG markers from routine pre-operative ECGs can be used in combination with clinical data to predict new-onset POAF following cardiac surgery. By combining the clinical data and small ECG-changes it proved easier to predict, which patients would develop POAF - an important observation that will call for confirmation through new prospective studies.
Study 2. The primary aim was to evaluate whether the storage time of transfused RBC is associated with the development of POAF in patients undergoing cardiac surgery. Furthermore, we aimed to investigate whether RBC transfusion in general is associated with an increased risk of POAF. The study showed that although RBC transfusion was generally associated with the development of POAF, spline analyses did not reveal any systematic patterns to support an increased risk of POAF in patients receiving RBC with increasing storage time.
Studiy 3. To evaluate whether concentrations of n-3 PUFA in atrial tissue and in the blood (plasma phospholipids) are associated with the development of POAF and whether concentrations in the atrial wall are reflected by concentrations in the blood. The study showed that nor total or individual n-3 PUFA in the atrial wall or in plasma phospholipids did predict the development of POAF, but there were significant correlations between the levels in atrial tissue and in plasma.
Conclusion:
ECG markers obtained from routine pre-operative ECG may be helpful in combination with specific clinical data in predicting new-onset POAF in patients undergoing cardiac surgery (Study I). Furthermore, RBC transfusion is also associated with an increased risk of POAF (Study II). However, the storage time of transfused allogeneic RBCs (Study II) and concentrations of n-3 PUFA in atrial tissue and in the blood (plasma phospholipids) did not predict the development of POAF (Study III). The results of the individual studies included in this thesis represent a multidirectional search for potential new predictors associated with the development of POAF in patients undergoing cardiac surgery. The results from study I in particular may be helpful for the development of future predictions models regarding the risk of new onset POAF.
Living with Atrial Fibrillation: Exploring the context, complexity, and magnitude of the patient perspective.
PhD project by Vibeke Høgh, RN, MCN, PhD Student (May 2011 - 2016)
The patient perspective of living with atrial fibrillation is important for the quality of care, because the patient is the only one who experiences the events in their journey as a whole. The patient perspective is, however, complex.
Atrial fibrillation is a serious health burden, considered an epidemic, and is associated with a variety of comorbidities and an increased risk of mortality. Patients with atrial fibrillation experience being neglected and left alone with doubts and questions related to the disease, although, in clinical practice they are often being considered as the non-complex (easy) patients.
The aim of this dissertation is to explore the complexity and magnitude of the context of the patient perspective of living in the journey with atrial fibrillation.
Using a case study design, this dissertation is based on three papers, with the following results.
Based on text analysis of 53 scientific research papers the concept of quality of life is seen aligned and reduced into assessable parameters in Paper 1. This may be a sign of an implicit societal agreement within the scientific research context, and a potential threat to valuable knowledge about the patient’s unique perspective. The importance of challenging definitions of, and arguments in methods applied for evaluating the concept of quality of life in a scientific context, is thereby emphasised.
Paper 2 demonstrates clinically relevant lower physical components of health status in participants from the Danish Diet, Cancer and Health study diagnosed with atrial fibrillation and/or atrial flutter compared with the remaining participants in the cohort. The results are based on generic standardised questionnaires on a population based level. Therefore, the results need to be related to the individual patient’s situation in order to be applied in clinical practice.
Paper 3 demonstrates how balancing responsibility, navigating the system, adjusting to the situation, and recognition of bodily reactions are essential for the lived experience of being recently diagnosed with atrial fibrillation, and how lived experience is associated with self-reported health status assessed by both diseasespecific and generic standardised questionnaires on the individual level.
In conclusion:
A person-centred and holistic perspective on the patient journey is required for providing patients living with atrial fibrillation with the needed individualised care and treatment across organisational sector boundaries.
The person-centred and holistic view is important in order to respect patients shifting perspective between illness and wellbeing when living with a chronic condition, essential for upholding the patient’s dignity, balancing responsibility and strengthening the patient’s autonomy.
The journey needs to be considered as an ongoing process of transition.
This dissertation contributes to the insight into how the synergy of combining both qualitative and quantitative data sources, can elaborate on the full story on the patient perspective. This knowledge is essential across organisational sector boundaries for healthcare professional and researchers engaged in caring for patients living with atrial fibrillation, and other chronic conditions.
Thromboembolism and death in patients with atrial flutter
Phd project by Henrik Vadmann, MD, PhD Student (September 2010 - April 2016)
The incidence of atrial flutter is higher in patients with obesity, hypertension and diabetes mellitus and increases with age. With the aging of the general population and the increased prevalence of lifestyle disease, such as obesity, hypertension and diabetes mellitus, the prevalence of atrial flutter is expected to increase in the years to come. Contrary to atrial fibrillation (AF), the thromboembolic and mortality risks associated with atrial flutter are sparsely investigated.
The overall aim of this PhD dissertation was to examine the thromboembolic and mortality risks associated with atrial flutter compared with those of AF. First, we conducted a systematic review of the current literature investigating the thromboembolic risk associated with atrial flutter, and second, we investigated the thromboembolic and mortality risks in atrial flutter compared with AF after an ablation procedure in a Danish nationwide cohort. Third, we investigated the risk of death and development of heart failure and new arrhythmia after an atrial flutter ablation procedure.
The systematic review included both retrospective and prospective studies. From this review, we could conclude that patients with atrial flutter had a high risk of thromboembolic events. In the nationwide cohort studies, we found 1,096 (33%) patients with an incident atrial flutter and 2,266 with an incident AF ablation procedure between 1 January 2000 and 31 December 2013. We found a nonsignificant increase in the risk of thromboembolic events (hazard ratio (HR) 1.34, 95% confidence interval (CI) 0.71-2.41), heart failure (HR 1.14, 95% CI 0.76-1.71) and development of a new arrhythmia. However, there is a significantly higher mortality risk (HR 1.85, 95% CI 1.29-2.66) in patients with atrial flutter than in AF patients after an ablation procedure. In patients who developed heart failure there was a significant increase in mortality risk in patients with atrial flutter (HR 2.97, 95% CI 1.11-7.91).
In conclusion, in the literature we found an elevated risk of thromboembolic events in patients with atrial flutter. In a Danish cohort, we found a higher all-cause mortality in patients with atrial flutter than in AF patients after an ablation procedure. The risk of developing heart failure or a new arrhythmia was similar between atrial flutter and AF.
Atrial fibrillation: Risk and prognosis in critical illness
PhD project by Jacob Gamst, MD, PhD Student (1 November 2011-October 2014)
The objective of this project is to elucidate to what extent infectious diseases could be considered an initiating factor of atrial fibrillation (AF) and to investigate the prognostic impact of pre-existing AF and its treatment in patients admitted to the intensive care unit or hospitalised with pneumonia. The project will be based on data from the unique Danish healthcare registries and will provide important new knowledge on the causes and complications of AF.
The project consists of three substudies. Study 1 is a case-control-study including all incident cases of AF in the North and Central Denmark regions and population-based control persons from 1999 through 2010. The study will assess to what extent the risk of AF is increased in the period following infections. Infections treated during hospital admission and infections treated in the community setting will be analysed separately. The study will further investigate whether influenza vaccinations affect the risk of developing AF. Studies 2 and 3 are cohort studies. Study 2 includes all hospital admissions with pneumonia in the North and Central Denmark regions from 1997 through 2012, while study 3 includes all admissions to any intensive care unit in Denmark from 2005 through 2011. These studies will evaluate the influence of pre-existing AF on the prognosis in these patient populations, estimated by the risk of suffering an arterial thromboembolism or death in the time following admission. The studies will also examine the effect of anticoagulant and heart rhythm modifying medications in patients with AF.
The project will be conducted in close collaboration between the departments of Cardiology and Anaesthesiology at Aalborg University Hospital and the Department of Clinical Epidemiology at Aarhus University Hospital.
Fish, Marine n-3 Fatty Acids and the Development of Atrial Fibrillation
PhD project by Thomas Andersen Rix, MD, PhD (March 2010-June 2013)
Atrial fibrillation (AF) is a common heart rhythm disorder that increases in prevalence with age to about 10% at the age of 80 and accounts for about 20% of all strokes. Some studies have suggested beneficial effects of marine n-3 polyunsaturated fatty acids (PUFA) – socalled fish oils – on AF, whereas other studies have not been able to demonstrate such an effect. This project is based on the Diet, Cancer, and Health Cohort Study which included 57,053 Danish men and women at the age of 50 to 64. The overall aim was to investigate the association between marine n-3 PUFA and the risk of deloping AF. Thomas Andersen Rix’ hypothesis was that intake of marine n-3 PUFA reduces the risk of incident AF.
In Study I, the diagnosis of AF and/or atrial flutter (AFL) in the Danish National Patient Registry was validated by reviewing hospital medical records from the first registration in a sex-stratified random sample of 150 men and 150 women. The validity of the diagnosis of AF and/or AFL was high for both sexes, with an overall positive predictive value of 92.6% (95% CI 88.8 – 95.2%). The proportion of AF, AFL, or both at the time of first registration was assessed. The specific diagnosis of AFL evaluated separately, however, was not reliable in discriminating between AF and AFL. Our data confirm that the diagnosis of AF and/or AFL (referred to as ‘AF’) is suitable for record-linkage.
In Study II, the dietary intake of fish and marine n-3 PUFA was assessed by a 192-item food frequency questionnaire. A total of 3,345 incident cases of AF were registered during 13.6 years of follow-up. In multivariate, sex-stratified Cox regression analyses, the research group found a U-shaped association between consumption of marine n-3 PUFA and the development of AF, with the lowest risk close to the median intake (0.63 g/day). Similar associations were found for intake of fish, fatty fish, and each of the individual marine n-3 PUFA.
In Study III, the fatty acid profile of marine n-3 PUFA in baseline adipose tissue biopsies was assessed as a measure of the endogenous exposure including dietary intake during the preceding 1-3 years. The study population was restricted to 3,440 participants in a randomly drawn, sex-stratified subcohort of the full cohort. A total of 190 incident cases of AF occurred during 13.6 years of follow-up. The research group did not find a 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. Similar results were found for the individual marine n-3 PUFA.
Overall, the findings of this project indicate that a moderate intake of fish and marine n-3 PUFA (600 mg/day) may be preferable for primary prevention of AF compared with a low intake. At high intakes, however, Study II indicated a higher risk of AF. In contrast, the considerably smaller and possibly underpowered Study III showed no statistically significant association in adipose tissue, but a trend towards a negative dose-response association which needs to be further explored. However, at the present time there is not sufficient data to recommend consuming fish to prevent AF.
Gradually Changing Seasonal Variation of Cardiovascular Diseases in Denmark
PhD project by Anette Luther Christensen, MSc, PhD (August 2009-October 2012)
The incidence of stroke in patients with atrial fibrillation (AF) is higher in winter than in summer. This seasonal variation and changes over time were examined by biostatistician Anette Luther Christensen in a PhD project.
The project followed almost 300,000 Danes with AF, analysing seasonal variations based on daily countings of incident cases of stroke. A new statistical model often used within econometrics was applied in the project to describe the seasonal variation. Results show that the increased risk of suffering a stroke in AF patients in winter compared with summer has diminished over time.
The study provides an insight into the cause of stroke in AF patients and thus a basis for improving preventive treatment.