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Vascular Calcification and not Arrhythmia in Idiopathic Atrial Fibrillation Associates with Sex Differences in Diabetic Microvascular Injury miRNA Profiles

Author(s):

Elton AMP Dudink*, Barend W Florijn , Bob Weijs, Jacques MGJ Duijs , Justin GLM Luermans, Frederique ECM Peeters , Leon J Schurgers , Joachim E Wildberger, Uli Schotten , Roel Bijkerk , Harry JGM Crijns and Anton Jan van Zonneveld   Pages 1 - 8 ( 8 )

Abstract:


Background: Atrial fibrillation (AF) in patients without concomitant cardiovascular pathophysiological disease, is called idiopathic atrial fibrillation (iAF). Nonetheless, iAF patients have often times subclinical coronary (micro) vascular dysfunction and, particularly in women, a higher prevalence of subsequent cardiovascular comorbidities. Previously, we identified a plasma miRNA association with diabetes and microvascular injury in diabetic nephropathy (DN) patients. Therefore, in this study we assessed whether plasma levels of these diabetic, microvascular injury associated miRNAs reflect microvascular integrity in iAF patients, associated with the presence of paroxysmal arrhythmia or instead are determined by concealed coronary artery disease. Methods: Circulating levels of a pre-selected set of diabetic, (micro) vascular injury associated miRNAs, were measured in 59 iAF patients compared to 176 sinus rhythm (SR) controls. Furthermore, the presence of coronary artery and aortic calcification in each patient was assessed using cardiac computed tomography angiography (CCTA). Results: Paroxysmal arrhythmia in iAF patients did not result in significant miRNA expression profile differences in iAF patients compared to SR controls. Nonetheless, coronary artery calcification (CAC) was associated with higher levels of miRNAs-103, -125a-5p, -221 and -223 in men. In women, CAC was associated with higher plasma levels of miRNA-27a and miRNA-126 and correlated with Agatston scores. Within the total population, ascending aortic calcification (AsAC) patients displayed increased plasma levels of miRNA-221, while women, in particular, demonstrated a descending aorta calcification (DAC) associated increase in miRNA-212 levels. Conclusions: Diabetic microvascular injury associated miRNAs in iAF are associated with subclinical coronary artery disease in a sex-specific way and confirm the notion that biological sex identifies iAF subgroups that may require dedicated clinical care.

Keywords:

Atrial fibrillation, vascular calcification, sex-differences, microRNA

Affiliation:

Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Department of Cardiology, P. Debyelaan 25, 6229 HX, Maastricht, Leiden University Medical Center and Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Albinusdreef 2, 2333 ZA, Leiden, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Department of Cardiology, P. Debyelaan 25, 6229 HX, Maastricht, Leiden University Medical Center and Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Albinusdreef 2, 2333 ZA, Leiden, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Department of Cardiology, P. Debyelaan 25, 6229 HX, Maastricht, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Department of Cardiology, P. Debyelaan 25, 6229 HX, Maastricht, Maastricht University and Cardiovascular Research Institute Maastricht, Department of Biochemistry, Universiteitssingel 50, 6229 ER, Maastricht, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Department of Radiology and Nuclear Medicine, P. Debyelaan 25, 6229 HX, Maastricht, Maastricht University and Cardiovascular Research Institute Maastricht, Department of Physiology, Universiteitssingel 50, 6229 ER, Maastricht, Leiden University Medical Center and Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Albinusdreef 2, 2333 ZA, Leiden, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Department of Cardiology, P. Debyelaan 25, 6229 HX, Maastricht, Leiden University Medical Center and Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Albinusdreef 2, 2333 ZA, Leiden



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