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Atrial fibrillation in the Tromsø Study 1986-2016


Image caption Picture: Igor Rogov/mostphotos.com

The overarching goal of this extensive research project is to comprehensively investigate atrial fibrillation within the Tromsø Study 1986 to 2016. The study seeks to elucidate the natural history of atrial fibrillation and its subtypes, evaluate its association with risk factors, estimate the effect of joint interventions in a counterfactual setting, and assess the impact of atrial fibrillation on various health outcomes. The findings are anticipated to provide crucial insights into atrial fibrillation prevention, management, and prognosis while addressing knowledge gaps in the field.

Project period: 2012 - present

Background
Atrial fibrillation is an increasingly common arrhythmia in our ageing population significantly diminishing the quality of life and imposing substantial economic and healthcare burdens, including stroke, heart attacks, heart failure, and premature death. Although atrial fibrillation prevalence and incidence are increasing worldwide, many aspects of this new epidemic of cardiovascular disease concerning both atrial fibrillation occurrence, progression and management are not fully elucidated. This project aims to cover some of the important knowledge gaps and to study the natural history of atrial fibrillation in a Norwegian population over time with a focus on sex differences. The project is based on the population-based Tromsø Study 1986-2016. Main advantages are the longitudinal design, repeated risk factor measurements, validated follow-up information, and the large sample size.

Aims
The project will explore secular trends in the incidence of atrial fibrillation over recent decades and will estimate the contribution of risk factors. As a part of this project, we will also emulate a RCT to estimate the effect of joint interventions on modifiable risk factors in a counterfactual setting. Further, the project will evaluate socioeconomic status and its role in atrial fibrillation development. The two comorbid conditions atrial fibrillation and heart failure frequently coexist and complicate the course and treatment of each other. The direction of cause and effect with the conditions is yet to be fully elucidated. Important is also to study the risk of stroke for atrial fibrillation patients related to the introduction of direct oral anticoagulants as an alternative to warfarin in Norway in 2011; and the risk of heart attack and if it is dependent on the type of heart attack (with or without ST-elevation) for atrial fibrillation patients. Special attention will be paid to atrial fibrillation subtypes.

Specific aims (with reference publication list below):

  • To explore the association between atrial fibrillation and palpitations, inflammatory biomarkers, uric acid, and diastolic dysfunction (1-4).
  • To assess the association between atrial fibrillation and stroke or cognitive decline (5,6).
  • To assess the role of physical activity (7,8)
  • To investigate the impact of body mass index on longer‐term risk of atrial fibrillation and the impact of change in body mass index over time (9).
  • To explore individual long-term blood pressure trends and evaluate how blood pressure trends impact the incidence of atrial fibrillation in women and men (10).
  • To explore sex-specific associations between blood pressure, hypertension, and the risk of incident atrial fibrillation subtypes, including paroxysmal, persistent, and permanent atrial fibrillation, in a general population (11).
  • To use the parametric g-formula to estimate the long-term risk of atrial fibrillation by sex and education under hypothetical interventions on six modifiable risk factors (12).
  • To explore sex-specific trends in the incidence of atrial fibrillation in a general population, and the impact of changes in risk factor levels over a period from 1986 to 2016 (13). 
  • To explore sex-specific associations between individual long-term trends of pulse pressure and future risk of atrial fibrillation.
  • To evaluate if socioeconomic status is associated with the development of AF, and to which extent classical risk factors are mediators.
  • To assess the risk of incident heart failure and underlying risk factors of heart failure in atrial fibrillation subtypes, as well as their joint influence on mortality in both women and men.
  • To study the associations of psychological problems such as depression and anxiety, and health related quality of life with the future risk of atrial fibrillation, and to explore psychological profile and quality of life of patients with paroxysmal/persistent versus permanent atrial fibrillation.
  • To evaluate if the association between AF and heart attack is dependent on the type of heart attack (with or without ST-elevation), and to estimate the effect of time since first diagnosis of AF.
  • To explore change in the risk of stroke among atrial fibrillation patients related to the introduction of direct oral anticoagulants as an alternative to warfarin in 2011.

The members of the research group are actively involved in two significant international studies on atrial fibrillation: NEXAF, AFFECT-EU and GENAF.

NEXAF – The Norwegian Exercise and Atrial Fibrillation Initiative, is a research initiative that aims to improve knowledge on effects of exercise in individuals with atrial fibrillation. NEXAF consist of both clinical and epidemiological studies, with national and international collaboration, addressing how different subgroups of atrial fibrillation patients could benefit from exercise intervention.

AFFECT-EU – Digital, Risk-Based Screening for Atrial Fibrillation in the European Community project is an EU-funded consortium including 25 partners from academia and industry. AFFECT-EU`s major goal is the development of a risk-based, accurate, and ready for implementation atrial fibrillation screening algorithm, using digital devices, for early atrial fibrillation detection in the community. AFFECT-EU will fill in the AF screening knowledge gaps by integrating information from independent studies entering the project including the Tromsø Study data. These data will be used to implement a risk-based AF screening approach and to provide evidence on the superiority of AF screening using a robust community screening strategy for reducing AF-related morbidity and mortality.

GENAF - GENetics in Atrial Fibrillation (GENAF) is a study that investigates hereditary causes of atrial fibrillation. The study primarily focuses on individuals who have developed atrial fibrillation before the age of 50, as it is known that the heritability of the disease is highest in this group. The genetic analyses are conducted on routine blood samples taken from the study participants. Norwegian researchers collaborate with scientists from countries including Denmark, Sweden, and the USA. By identifying genes related to atrial fibrillation, we can gain more insights into the progression of the disease, leading to a better understanding of how to both prevent and treat it. This knowledge may make it easier to determine who would benefit from different treatments, and it can contribute to the development of improved and more specific medications.

Members

Ekaterina Sharashova (Principal investigator)
Hilde Espnes
Linn Nilsen
Maja-Lisa Løchen
Tom Wilsgaard
Inger Njølstad
Ellisiv B. Mathiesen
Sweta Tiwari
Bente Morseth
Audhild Nyrnes

Publications
  1. Nyrnes A, Njølstad I, Mathiesen EB, Wilsgaard T, Hansen JB, Skjelbakken T, Jørgensen L, Løchen ML. Inflammatory biomarkers as risk factors for future atrial fibrillation. An eleven-year follow-up of 6315 men and women: the Tromsø Study. Gend Med. 2012;9:536-547.
  2. Nyrnes A, Mathiesen EB, Njølstad I, Wilsgaard T, Løchen ML. Palpitations are predictive of future atrial fibrillation. An 11-year follow-up of 22,815 men and women: the Tromsø Study. Eur J Prev Cardiol. 2013;20:729-36.
  3. Nyrnes A, Toft I, Njølstad I, Mathiesen EB, Wilsgaard T, Hansen JB, Løchen ML. Uric acid is associated with future atrial fibrillation: an 11-year follow- up of 6308 men and women--the Tromsø Study. Europace. 2014;16:320-326.
  4. Tiwari S, Schirmer H, Jacobsen BK, Hopstock LA, Nyrnes A, Heggelund G, Njølstad I, Mathiesen EB, Løchen ML. Association between diastolic dysfunction and future atrial fibrillation in the Tromsø Study from 1994 to 2010. Heart. 2015;101:1302-8.
  5. Tiwari S, Løchen ML, Jacobsen BK, Hopstock LA, Nyrnes A, Njølstad I, Mathiesen EB, Schirmer H. CHA2DS2-VASc score, left atrial size and atrial fibrillation as stroke risk factors in the Tromsø Study. Open Heart. 2016;3:e000439.
  6. Tiwari S, Løchen ML, Jacobsen BK, Hopstock LA, Nyrnes A, Njølstad I, Mathiesen EB, Arntzen KA, Ball J, Stewart S, Wilsgaard T, Schirmer H. Atrial fibrillation is associated with cognitive decline in stroke-free subjects: the Tromsø Study. Eur J Neurol. 2017;24:1485-1492.
  7. Morseth B, Graff-Iversen S, Jacobsen BK., Jørgensen L, Nyrnes A, Thelle DS, Vestergaard P, Løchen ML. Physical activity, resting heart rate, and atrial fibrillation: the Tromsø Study. Eur Heart J 2016 ;37:2307-2313.
  8. Morseth B, Løchen ML, Ariansen I, Myrstad M, Thelle DS. The ambiguity of physical activity, exercise and atrial fibrillation. Eur J Prev Cardiol 2018;25:624-636.
  9. Ball J, Løchen ML, Wilsgaard T, Schirmer H, Hopstock L, Morseth B, Mathiesen EB, Njølstad I, Tiwari S, Sharashova E. Sex Differences in the Impact of Body Mass Index on the Risk of Future Atrial Fibrillation: Insights From the Longitudinal Population-Based Tromsø Study. J Am Heart Assoc 2018;7:e008414.
  10. Sharashova E, Wilsgaard T, Ball J, Morseth B, Gerdts E, Hopstock LA, Mathiesen EB, Schirmer H, Løchen ML. Long-term blood pressure trajectories and incident atrial fibrillation in women and men: the Tromsø Study. Eur Heart J 2020;41:1554-1562.
  11. Espnes H, Ball J, Løchen ML, Wilsgaard T, Njølstad I, Mathiesen EB, Gerdts E, Sharashova E. Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study. J Clin Med 2021;10:1514.
  12. Nilsen L, Sharashova E, Løchen ML, Danaei G, Wilsgaard T. Hypothetical interventions and risk of atrial fibrillation by sex and education: application of the parametric g-formula in the Tromsø Study. Eur J Prev Cardiol 2023:zwad240. 
  13. Sharashova E, Gerdts E, Ball J, Espnes H, Jacobsen BK, Kildal S, Mathiesen EB, Njølstad I, Rosengren A, Schirmer H, Wilsgaard T, Løchen ML. Sex-specific time trends in incident atrial fibrillation and the contribution of risk factors: the Tromsø Study 1994-2016. Eur J Prev Cardiol 2023;30:72-81.