Abstract
Inflammation is associated with the development of atrial fibrillation (AF). Activity in hematopoietic tissues, which produce inflammatory leukocytes, is closely related to systemic inflammation, arterial inflammation and cardiovascular events, but its relationship to AF is unknown. Using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging, we examined the relationships between AF, splenic metabolic activity and vascular inflammation. We conducted a cross sectional study of 70 participants: 35 with AF, who were matched (by age, sex and history of active cancer) to 35 controls without AF. Splenic metabolic activity and vascular aortic inflammation were measured by the mean FDG maximum standard uptake values (SUV Max) by PET. We examined (1) the association between AF and splenic activity, and (2) AF and aortic inflammation. The mean age of the population was 68.13 (standard deviation (SD) 8.98) years and 46 (65 %) participants were male. Splenic activity was higher in AF participants [2.31 (SD 0.45) vs. 2.07 (SD 0.37), p = 0.024], and remained significant after adjusting for demographic and clinical covariates. Aortic inflammation was also higher in AF participants [2.22 (SD 0.44) vs. 1.91 (SD 0.44), p = 0.004], and remained significant on multivariable analysis. Aortic inflammation and splenic activity were highly correlated (Pearson R = 0.61, p < 0.001). Atrial fibrillation is associated with higher hematopoietic tissue activation and arterial inflammation. Further studies are needed to clarify the mechanisms by which this cardio-splenic axis is implicated in AF.
Similar content being viewed by others
References
Lip GY, Brechin CM, Lane DA (2012) The global burden of atrial fibrillation and stroke: a systematic review of the epidemiology of atrial fibrillation in regions outside North America and Europe. Chest 142:1489–1498
Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ et al (2014) Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129:837–847
January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC Jr, Cigarroa JE et al (2014) AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 64(21):e1–e76
Guo Y, Lip GY, Apostolakis S (2012) Inflammation in atrial fibrillation. J Am Coll Cardiol 60:2263–2270
Waterhouse DF, Cahill RA, Sheehan F, McCreery C (2008) Prediction of calculated future cardiovascular disease by monocyte count in an asymptomatic population. Vasc Health Risk Manag 4:177–187
Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P et al (2012) CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 60:1512–1520
Seita J, Weissman IL (2010) Hematopoietic stem cell: self-renewal versus differentiation. Wiley interdiscip Rev Syst Biol Med 2:640–653
Emami H, Singh P, MacNabb M, Vucic E, Lavender Z, Rudd JH et al (2015) Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans. JACC Cardiovasc Imaging 8:121–130
Swirski FK, Nahrendorf M (2013) Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 339:161–166
Tapp LD, Shantsila E, Wrigley BJ, Pamukcu B, Lip GY (2012) The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction. J thromb Haemost 10:1231–1241
Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D et al (2011) CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J 32:84–92
Kim CH (2010) Homeostatic and pathogenic extramedullary hematopoiesis. J Blood Med 1:13–19
Siu CW, Watson T, Lai WH, Lee YK, Chan YH, Ng KM et al (2010) Relationship of circulating endothelial progenitor cells to the recurrence of atrial fibrillation after successful conversion and maintenance of sinus rhythm. Europace 12:517–521
Conen D, Ridker PM, Everett BM, Tedrow UB, Rose L, Cook NR et al (2010) A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women. Eur Heart J 31:1730–1736
Marott SC, Nordestgaard BG, Zacho J, Friberg J, Jensen GB, Tybjaerg-Hansen A et al (2010) Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals from the general population. J Am Coll Cardiol 56:789–795
Heidt T, Sager HB, Courties G, Dutta P, Iwamoto Y, Zaltsman A et al (2014) Chronic variable stress activates hematopoietic stem cells. Nat Med 20:754–758
Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS et al (2012) Myocardial infarction accelerates atherosclerosis. Nature 487:325–329
Rienstra M, Sun JX, Magnani JW, Sinner MF, Lubitz SA, Sullivan LM et al (2012) White blood cell count and risk of incident atrial fibrillation (from the Framingham Heart Study). Am J Cardiol 109:533–537
Suzuki A, Fukuzawa K, Yamashita T, Yoshida A, Sasaki N, Emoto T et al (2015) Circulating interMediate Cd14++Cd16+ monocytes are increased in patients with atrial fibrillation and reflect functional remodeling of left atrium. J Am Coll Cardiol 65:A466 (conference abstract)
Li J, Solus J, Chen Q, Rho YH, Milne G, Stein CM et al (2010) Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm 7:438–444
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M et al (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438
Khatami S, Brummer E, Stevens DA (2001) Effects of granulocyte–macrophage colony stimulating factor (GM-CSF) in vivo on cytokine production and proliferation by spleen cells. Clin Exp Immunol 125:198–201
Marcus GM, Smith LM, Glidden DV, Wilson E, McCabe JM, Whiteman D et al (2008) Markers of inflammation before and after curative ablation of atrial flutter. Heart Rhythm 5:215–221
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None of the authors report any relevant disclosures or conflicts of interest related to this study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Joseph, P., Ishai, A., MacNabb, M. et al. Atrial fibrillation is associated with hematopoietic tissue activation and arterial inflammation. Int J Cardiovasc Imaging 32, 113–119 (2016). https://doi.org/10.1007/s10554-015-0766-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10554-015-0766-z