Birkebeiner II Study

Study Overview
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Brief Summary
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Prolonged endurance exercise is associated with an elevated risk of atrial fibrillation (AF). The mechanisms governing this increased risk remains elusive. This study aim to detail the specific traits of elderly subjects with AF conducting endurance training by comparing elderly participators in the Birkebeiner cross country ski race(an indicator of prolonged endurance exercise practice) with and without AF to a not-so-trained control group.

Detailed Description
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In recent years endurance sports with high intensity and participation in competition have been increasingly popular among middle aged and older people. The Birkebeiner studies are investigations of elderly non-professional athletes (65 years or older at enrollment in 2009/10) participating in the Birkebeiner cross-country ski race. It consists of Birkebeiner Aging Study, BIAS and the Birkebeiner Atrial Fibrillation, (BAF-study). The BAF-study investigated the association between prolonged endurance sport practice and the risk of AF by comparing the cohort of veteran cross-country skiers to a control population drawn from the Health and Environment Study in Oslo (HELMILO 2009). The main findings of the Birkebeiner study so far have been that participation in the Birkebeiner cross-country ski race (an indicator of prolonged endurance exercise practice) is associated with an elevated risk of atrial fibrillation (AF) among men ≥ 65 years, and that this risk correlates with the cumulated amount of endurance-training. Similar findings were seen amongst female athletes. This increased risk of AF was shown independent of other known significant comorbidities (such as hypertension and diabetes), indicating that endurance-training at this level itself is an independent risk factor. Regular physical exercise is an important factor when it comes to successful ageing. However, dose-relationship of physical exercise in a longer perspective is poorly studied. Atrial fibrillation is associated with increased risk of stroke, heart failure, dementia and death. The mechanisms governing the increased risk of AF in elderly subjects undergoing endurance-training remains elusive. This study aim to detail the specific traits of elderly subjects with AF conducting endurance-training in comparison with trained and not-so-trained control groups. Thus, generating knowledge that can form the basis for better prevention and treatment of AF in this group.

Official Title
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Birkebeiner II Study Investigating the Mechanisms of Atrial Fibrillation in Elderly Performing Endurance Training

Conditions
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Atrial Fibrillation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Already included in the Birkebeiner studies or Health and environment study in Oslo (HELMILO) Born 1960 and earlier Exclusion Criteria: Born before 1935. Earlier heart valve surgery. MI (Mitral Insufficiency)≥ grade 3 Ejection Fraction (EF) <35%

Ages Eligible for Study
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Minimum Age: 58 Years
Maximum Age: 83 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Birkebeiner with AF<br>Persons already included in the Birkebeiner Aging Study (BIAS) (completed the Birkebeiner cross-country ski race in 2009/10 born 1945 and earlier) and BAF-study (completed the Birkebeiner cross-country ski race in 1999 and was born in 1960 and earlier) with AF. | |
| Birkebeiner without AF<br>Persons already included in the Birkebeiner Aging Study (BIAS) (completed the Birkebeiner cross-country ski race in 2009/10 born 1945 and earlier) and BAF-study (completed the Birkebeiner cross-country ski race in 1999 and was born in 1960 and earlier) without AF | |
| Control with AF<br>Persons included in HELMILO 2009 (Health and Environment Study in Oslo 2009), born 1960 and earlier with AF | |
| Control without AF<br>Persons included in HELMILO 2009 (Health and Environment Study in Oslo 2009), born 1960 and earlier without AF | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in atrial function and presence of atrial fibrillation in veteran endurance athletes | Volume changes (ml) in the three phases of atrial function, measured by triplane echocardiography. | Cross sectional study. Measured at time for inclusion. | 
| Changes in atrial function and presence of atrial fibrillation in veteran endurance athletes | 2D strain (%) in the three phases of atrial function, measured by triplane echocardiography. | Cross sectional study. Measured at time for inclusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in right ventricular volumes (ml) in veteran endurance athletes | Measured by 2D echocardiography | Cross sectional study. Measured at time for inclusion. | 
| Changes in p-wave (p-wave duration (msec), morphology and axis) in veteran endurance athletes | Measured by ECG derived vector cardiograms. | Cross sectional study. Measured at time for inclusion. | 
| Changes in R-R variability (msec) in veteran endurance athletes | Measured by Holter ECG recordings | Cross sectional study. Measured at time for inclusion. | 
| Presence of 171 genetic variants known to be associated with atrial fibrillation in veteran endurance athletes. | Measured by genome-wide genotyping and next generation sequencing in the combination with Sanger sequencing. | Cross sectional study. Measured at time for inclusion. | 
| Changes in biochemical markers associated with atrial fibrosis and inflammation in veteran endurance athletes. | IL-1alfa, -1ra, -4,-6,-10, -17A, -17F, -21, -22, -23, -25, -31, -33, IFN-gamma TNF-alfa, IP-10, G-CSF, GM-CSF, MCP-1, MIP-1alfa, MIP-1beta, TIMP-1-4, MMP 1-3,7-10 and 12, measured by luminex multiplex technology | Cross sectional study. Measured at time for inclusion. | 
| European Heart Rhythm Association (EHRA) score of atrial fibrillation related symptoms in veteran endurance athletes. | Measured by European Heart Rhythm Association symptom score which is a classification of AF-related symptoms. The score ranges from I-no symptoms to IV-disabling symptoms. | Cross sectional study. Measured at time for inclusion. |