Atrial Fibrillation in Relationship to Plasma Biomarkers

The general objective of this study is to:

A. To identify novel plasmatic biomarkers associated with prevalent/incident atrial fibrillation in patients with high risk for AF and stroke.

B. To assess predictive ability of novel plasmatic biomarkers (especially apelin and miRNAs) on prevalent/incident atrial fibrillation in patients with high risk for AF and stroke.

C. To validate predictive models from previous studies based on comorbidities, age, sex, BMI, NT-proBNP, FGF-23, IGF-1 and IGFBP-1 on prevalent/incident AF in patients with high risk for AF and stroke.

Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with an increased risk of stroke, heart failure, and mortality. Despite the high prevalence, AF may be asymptomatic and consequently unrecognized. Detection of asymptomatic AF is challenging as only a minority of the patients is diagnosed during standard examinations with a 12 - lead ECG or a 24h ECG Holter monitoring. Furthermore, prolonged ECG monitoring is costly and can be inconvenient for the patients. Documented AF causes 15% of ischemic strokes. However, approximately 25% of ischemic strokes is of an unknown etiology. It is believed that undetected asymptomatic AF is responsible for some of these strokes.

Plasmatic biomarkers might be of importance in the early diagnosis of AF. Several plasmatic biomarkers have been studied in order to find an association with AF. Cardiac biomarkers such as natriuretic peptides and high-sensitivity troponins are increased in patients with AF. A novel biomarker that is depending on left atrial stretching and ionotropic effects is apelin. In our previous research we discovered that apelin is associated with AF, negatively correlates with AF burden, but only in patients without reduced LVEF. Similarly, parameters reflecting thrombogenesis, such as Fibrinogen and fibrin D-dimer were also found to be associated with the arrhythmia. Other protein biomarkers have been studied in relation to AF incidence. Insulin-like growth factor-binding protein 1 (IGFBP-1) and Insulin-like growth factor 1 (IGF-1) have shown an association with higher risk of incident AF. Previous research also indicated Fibroblast growth factor 23 (FGF-23) to be associated with AF.

However, biomarkers, such as the inflammatory markers high-sensitivity CRP have shown conflicting results.

Finally, in the last years, circulating microRNAs emerged as a promising biomarker of AF, having important function in suppression of messenger RNA responsible for electric and structural remodeling of the left atria.

In our previous case-matched study we discovered that selected miRNAs were associated with paroxysmal AF.

Eligibility Criteria:
Inclusion Criteria:

General inclusion criteria:

* AGE \> 50 years
* No history of supraventricular arrhythmia
* Sinus rhythm at inclusion
* CHADSVASc score \> 2 in men (\> 3 in female)
* More than 3 specific criteria for inclusion
* Written informed consent is obtained before any study-related assessment is performed

Specific inclusion criteria:

* Age \> 65
* Age \> 75
* BMI \> 30
* Heart failure with preserved LVEF (according to ESC GL for HF)
* Ischemic stroke
* Left atrial diameter \> 45mm
* Chronic obstructive pulmonary disease
* Arterial hypertension
* PR interval \> 200ms
* History of MI or (objective evidence of) chronic coronary syndrome
* Peripheral artery disease
* Thyroid disease

Exclusion Criteria:

* History of any supraventricular or ventricular arrhythmia (excluding premature contractions and 1st degree AV block)
* Therapy with anticoagulants at the time of inclusion
* Acute coronary syndrome less than 1 month prior to inclusion
* History of cardiac surgery
* Diabetes mellitus type 2
* Reduced LVEF (\<50%)
* Acute or decompensated heart failure at the time of inclusion
* Cardiomyopathy
* Systemic inflammatory disease or acute inflammatory disease
* Active malignancy
* Alcoholism (≥ 8 drinks/week)
* Renal Disease (Dialysis/ transplant/ CrCl \< 1ml/s)
* Liver disease (cirrhosis/ transaminase \> 3x ULT/ bilirubin \> 2x ULT)
* Severe or moderate mitral stenosis
* Pregnancy