MedicalResearch.com Interview with:
Stefan Kiechl, MD and
Karin Willeit, MD
Department of Neurology
Medical University Innsbruck
MedicalResearch.com: What is the background for this study?
Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major contributor to thromboembolic stroke and population morbidity and mortality. Aside from well-established risk factors such as age, heart failure, and hypertension, inflammation has been suggested to play a significant role in the pathogenesis of AF. This is evidenced by histologic studies that found marked inflammatory infiltrates in atrial biopsies of AF patients and by epidemiological studies demonstrating an association of circulatory inflammation markers with incident AF. Of note, an increased endocardial expression of vascular intercellular adhesion molecule 1 (VCAM-1), a mediator of leukocyte trafficking, during rapid atrial pacing was demonstrated which was shown to contribute to an inflammatory and prothrombotic environment within atrial tissue.
Because it is still unclear whether inflammation related to AF is primarily a systemic or localized phenomenon, we sought to examine the association of 13 baseline inflammation markers with incident atrial fibrillation in the prospective population-based Bruneck Study and to replicate key findings in a second cohort, the SAPHIR Study.
MedicalResearch.com: What are the main findings?
Response: In the Bruneck Study, 117 out of 880 participants free of AF at the 1990 baseline examination developed atrial fibrillation during the 20-year follow-up period.
In univariable analysis, we observed a significant association between soluble VCAM-1 and osteoprotegerin with incident AF, which was lost for osteoprotegerin after age-adjustment. Other baseline markers including matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of NF-κB ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance. In multivariable analysis, the association between soluble VCAM-1 and incident AF remained significant (HR for a 1-SD higher soluble VCAM-1 level [95%CI], 1.34 [1.11-1.62]; P=0.03). The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide, internally consistent in various subgroups, and successfully replicated in the Saphir Study (age/sex-adjusted and multivariable OR for a 1-SD higher sVCAM-1 level [95%CI], 1.91 [1.24-2.96] and 2.59 [1.45-4.60]; P=0.003 and P=0.001). Of note, negative findings in the Bruneck Study extended to 75 other markers of systemic inflammation and immune activation that were measured during the 2000 study evaluation.
MedicalResearch.com: What should readers take away from your report?
Response: Levels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset atrial fibrillation in the general community. The present study is supportive of the emerging concept that local atrial inflammation reflected by soluble VCAM-1 potentially is more relevant in AF than systemic inflammation.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Future studies should examine whether soluble VCAM-1 has the potential to improve existing risk scores for atrial fibrillation.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Karin Willeit MD, Raimund Pechlaner MD, PhD, Peter Willeit MD, PhD, Philipp Skroblin PhD, Bernhard Paulweber MD, Christiana Schernthaner MD, Thomas Toell MD, Georg Egger MD, Siegfried Weger MD, Martin Oberhollenzer MD, Ludmilla Kedenko MD, Bernhard Iglseder MD, Enzo Bonora MD, PhD, Georg Schett MD, Manuel Mayr MD, PhD, Johann Willeit MD, Stefan Kiechl MD
JAMA Cardiology Published online March 29, 2017
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