Abstract
Background: Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed.
Objectives/Methods: The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation.
Results: Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk.
Conclusions: Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.
Keywords: Atrial Fibrillation, Haemorrhage, Bleeding Risk Score, Biomarkers, Atrial Fibrillation Complications, HAS-BLED score, Intracranial Haemorrhage, Anticoagulants.
[1]
Wakili, R.; Voigt, N.; Kääb, S.; Dobrev, D.; Nattel, S. Recent advances in the molecular pathophysiology of atrial fibrillation. J. Clin. Invest., 2011, 121(8), 2955-2968.
[2]
Dobrev, D.; Nattel, S. New antiarrhythmic drugs for treatment of atrial fibrillation. Lancet, 2010, 375(9721), 1212-1223.
[3]
Nattel, S.; Burstein, B.; Dobrev, D. Atrial remodeling and atrial fibrillation: mechanisms and implications. Circ Arrhythm Electrophysiol, 2008, 1(1), 62-73.
[4]
Frustaci, A.; Chimenti, C.; Bellocci, F.; Morgante, E.; Russo, M.A.; Maseri, A. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation, 1997, 96(4), 1180-1184.
[5]
Haïssaguerre, M.; Jaïs, P.; Shah, D.C.; Takahashi, A.; Hocini, M.; Quiniou, G.; Garrigue, S.; Le Mouroux, A.; Le Métayer, P.; Clémenty, J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N. Engl. J. Med., 1998, 339(10), 659-666.
[6]
de Vos, C.B.; Pisters, R.; Nieuwlaat, R.; Prins, M.H.; Tieleman, R.G.; Coelen, R.J.; van den Heijkant, A.C.; Allessie, M.A.; Crijns, H.J. Progression from paroxysmal to persistent atrial fibrillation clinical correlates and prognosis. J. Am. Coll. Cardiol., 2010, 55(8), 725-731.
[7]
Wolf, P.A.; Abbott, R.D.; Kannel, W.B. Atrial fibrillation as an independent risk factor for stroke: The Framingham study. Stroke, 1991, 22(8), 983-988.
[8]
Kannel, W.B.; Wolf, P.A.; Benjamin, E.J.; Levy, D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am. J. Cardiol., 1998, 82(8A), 2N-9N.
[9]
Zhang, W.; Brombosz, S.M.; Mendoza, J.L.; Moore, J.S. A high-yield, one-step synthesis of o-phenylene ethynylene cyclic trimer via precipitation-driven alkyne metathesis. J. Org. Chem., 2005, 70(24), 10198-10201.
[10]
Odutayo, A.; Wong, C.X.; Hsiao, A.J.; Hopewell, S.; Altman, D.G.; Emdin, C.A. Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ, 2016, 354, i4482.
[11]
Fang, M.C.; Singer, D.E.; Chang, Y.; Hylek, E.M.; Henault, L.E.; Jensvold, N.G.; Go, A.S. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation, 2005, 112(12), 1687-1691.
[12]
Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Arch. Intern. Med., 1998, 158(12), 1316-1320.
[13]
Goldsmith, I.L.G.; Blann, A.D.; Kumar, P.; Carter, P.; Patel, R.L. Endocardial damage is common in the left atrial appendage of patients with mitral valve disease: implications for left atrial thrombogenesis. Eur. Heart J., 1999, 20, 192.
[14]
Feng, D.; D’Agostino, R.B.; Silbershatz, H.; Lipinska, I.; Massaro, J.; Levy, D.; Benjamin, E.J.; Wolf, P.A.; Tofler, G.H. Hemostatic state and atrial fibrillation (the Framingham Offspring Study). Am. J. Cardiol., 2001, 87(2), 168-171.
[15]
Gustafsson, C.; Blombäck, M.; Britton, M.; Hamsten, A.; Svensson, J. Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke, 1990, 21(1), 47-51.
[16]
Hughes, M.; Lip, G.Y. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb. Haemost., 2008, 99(2), 295-304.
[17]
Lip, G.Y.; Nieuwlaat, R.; Pisters, R.; Lane, D.A.; Crijns, H.J. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest, 2010, 137(2), 263-272.
[18]
Benjamin, E.J.; Wolf, P.A.; D’Agostino, R.B.; Silbershatz, H.; Kannel, W.B.; Levy, D. Impact of atrial fibrillation on the risk of death: The Framingham heart study. Circulation, 1998, 98(10), 946-952.
[19]
Camm, A.J.; Kirchhof, P.; Lip, G.Y.; Schotten, U.; Savelieva, I.; Ernst, S.; Van Gelder, I.C.; Al-Attar, N.; Hindricks, G.; Prendergast, B.; Heidbuchel, H.; Alfieri, O.; Angelini, A.; Atar, D.; Colonna, P.; De Caterina, R.; De Sutter, J.; Goette, A.; Gorenek, B.; Heldal, M.; Hohloser, S.H.; Kolh, P.; Le Heuzey, J.Y.; Ponikowski, P.; Rutten, F.H.; Association, E.H.R.; Surgery, E.A.C-T.; Guidelines, E.C.P. Guidelines for the management of atrial fibrillation: The task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Europace, 2010, 12(10), 1360-1420.
[20]
Heeringa, J.; van der Kuip, D.A.; Hofman, A.; Kors, J.A.; van Herpen, G.; Stricker, B.H.; Stijnen, T.; Lip, G.Y.; Witteman, J.C. Prevalence, incidence and lifetime risk of atrial fibrillation: The rotterdam study. Eur. Heart J., 2006, 27(8), 949-953.
[21]
Wolf, P.A.; Benjamin, E.J.; Belanger, A.J.; Kannel, W.B.; Levy, D.; D’Agostino, R.B. Secular trends in the prevalence of atrial fibrillation: The Framingham Study. Am. Heart J., 1996, 131(4), 790-795.
[22]
Kim, E.J.; Yin, X.; Fontes, J.D.; Magnani, J.W.; Lubitz, S.A.; McManus, D.D.; Seshadri, S.; Vasan, R.S.; Ellinor, P.T.; Larson, M.G.; Benjamin, E.J.; Rienstra, M. Atrial fibrillation without comorbidities: Prevalence, incidence and prognosis (from the Framingham Heart Study). Am. Heart J., 2016, 177, 138-144.
[23]
Jabre, P.; Jouven, X.; Adnet, F.; Thabut, G.; Bielinski, S.J.; Weston, S.A.; Roger, V.L. Atrial fibrillation and death after myocardial infarction: A community study. Circulation, 2011, 123(19), 2094-2100.
[24]
McManus, D.D.; Hsu, G.; Sung, S.H.; Saczynski, J.S.; Smith, D.H.; Magid, D.J.; Gurwitz, J.H.; Goldberg, R.J.; Go, A.S.; Study, C.R.N.P. Atrial fibrillation and outcomes in heart failure with preserved versus reduced left ventricular ejection fraction. J. Am. Heart Assoc., 2013, 2(1), e005694.
[25]
O’Neal, W.T.; Tanner, R.M.; Efird, J.T.; Baber, U.; Alonso, A.; Howard, V.J.; Howard, G.; Muntner, P.; Soliman, E.Z. Atrial fibrillation and incident end-stage renal disease: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Int. J. Cardiol., 2015, 185, 219-223.
[26]
Kim, Y.H.; Roh, S.Y. The mechanism of and preventive therapy for stroke in patients with atrial fibrillation. J. Stroke, 2016, 18(2), 129-137.
[27]
Yamamoto, M.; Seo, Y.; Kawamatsu, N.; Sato, K.; Sugano, A.; Machino-Ohtsuka, T.; Kawamura, R.; Nakajima, H.; Igarashi, M.; Sekiguchi, Y.; Ishizu, T.; Aonuma, K. Complex left atrial appendage morphology and left atrial appendage thrombus formation in patients with atrial fibrillation. Circ Cardiovasc Imaging, 2014, 7(2), 337-343.
[28]
Friedman, G.D.; Loveland, D.B.; Ehrlich, S.P., Jr Relationship of stroke to other cardiovascular disease. Circulation, 1968, 38(3), 533-541.
[29]
Fuster, V.; Rydén, L.E.; Cannom, D.S.; Crijns, H.J.; Curtis, A.B.; Ellenbogen, K.A.; Halperin, J.L.; Le Heuzey, J.Y.; Neal Kay, G.; Lowe, J.E.; Bertil Olsson, S.; Prystowsky, E.N.; Tamargo, J.L.; Wann, S. Guidelines for the management of patients with atrial fibrillation. Executive summary. Rev. Esp. Cardiol., 2006, 59(12), 1329.
[30]
Britton, M.; Gustafsson, C. Non-rheumatic atrial fibrillation as a risk factor for stroke. Stroke, 1985, 16(2), 182-188.
[31]
Wolf, P.A.; Kannel, W.B.; McGee, D.L.; Meeks, S.L.; Bharucha, N.E.; McNamara, P.M. Duration of atrial fibrillation and imminence of stroke: The Framingham study. Stroke, 1983, 14(5), 664-667.
[32]
Lin, H.J.; Wolf, P.A.; Kelly-Hayes, M.; Beiser, A.S.; Kase, C.S.; Benjamin, E.J.; D’Agostino, R.B. Stroke severity in atrial fibrillation. The Framingham study. Stroke, 1996, 27(10), 1760-1764.
[33]
Hart, R.G.; Pearce, L.A.; Rothbart, R.M.; McAnulty, J.H.; Asinger, R.W.; Halperin, J.L. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. J. Am. Coll. Cardiol., 2000, 35(1), 183-187.
[34]
Sage, J.I.; Van Uitert, R.L. Risk of recurrent stroke in patients with atrial fibrillation and non-valvular heart disease. Stroke, 1983, 14(4), 537-540.
[35]
Treseder, A.S.; Sastry, B.S.; Thomas, T.P.; Yates, M.A.; Pathy, M.S. Atrial fibrillation and stroke in elderly hospitalized patients. Age Ageing, 1986, 15(2), 89-92.
[36]
Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther., 2001, 69(3), 89-95.
[37]
Becker, R.C. Biomarkers in atrial fibrillation: investigating biologic plausibility, cause, and effect. J. Thromb. Thrombolysis, 2005, 19(1), 71-75.
[38]
Huxley, R.R.; Alonso, A.; Lopez, F.L.; Filion, K.B.; Agarwal, S.K.; Loehr, L.R.; Soliman, E.Z.; Pankow, J.S.; Selvin, E. Type 2 diabetes, glucose homeostasis and incident atrial fibrillation: The atherosclerosis risk in Communities study. Heart, 2012, 98(2), 133-138.
[39]
Wang, T.J.; Parise, H.; Levy, D.; D’Agostino, R.B., Sr; Wolf, P.A.; Vasan, R.S.; Benjamin, E.J. Obesity and the risk of new-onset atrial fibrillation. JAMA, 2004, 292(20), 2471-2477.
[40]
Wanahita, N.; Messerli, F.H.; Bangalore, S.; Gami, A.S.; Somers, V.K.; Steinberg, J.S. Atrial fibrillation and obesity--results of a meta-analysis. Am. Heart J., 2008, 155(2), 310-315.
[41]
Tsang, T.S.; Barnes, M.E.; Miyasaka, Y.; Cha, S.S.; Bailey, K.R.; Verzosa, G.C.; Seward, J.B.; Gersh, B.J. Obesity as a risk factor for the progression of paroxysmal to permanent atrial fibrillation: A longitudinal cohort study of 21 years. Eur. Heart J., 2008, 29(18), 2227-2233.
[42]
Zacharias, A.; Schwann, T.A.; Riordan, C.J.; Durham, S.J.; Shah, A.S.; Habib, R.H. Obesity and risk of new-onset atrial fibrillation after cardiac surgery. Circulation, 2005, 112(21), 3247-3255.
[43]
Abed, H.S.; Samuel, C.S.; Lau, D.H.; Kelly, D.J.; Royce, S.G.; Alasady, M.; Mahajan, R.; Kuklik, P.; Zhang, Y.; Brooks, A.G.; Nelson, A.J.; Worthley, S.G.; Abhayaratna, W.P.; Kalman, J.M.; Wittert, G.A.; Sanders, P. Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation. Heart Rhythm, 2013, 10(1), 90-100.
[44]
Thanassoulis, G.; Massaro, J.M.; O’Donnell, C.J.; Hoffmann, U.; Levy, D.; Ellinor, P.T.; Wang, T.J.; Schnabel, R.B.; Vasan, R.S.; Fox, C.S.; Benjamin, E.J. Pericardial fat is associated with prevalent atrial fibrillation: The Framingham heart study. Circ Arrhythm Electrophysiol, 2010, 3(4), 345-350.
[45]
Rabkin, S.W. The relationship between epicardial fat and indices of obesity and the metabolic syndrome: A systematic review and meta-analysis. Metab. Syndr. Relat. Disord., 2014, 12(1), 31-42.
[46]
Hatem, S.N.; Sanders, P. Epicardial adipose tissue and atrial fibrillation. Cardiovasc. Res., 2014, 102(2), 205-213.
[47]
Venteclef, N.; Guglielmi, V.; Balse, E.; Gaborit, B.; Cotillard, A.; Atassi, F.; Amour, J.; Leprince, P.; Dutour, A.; Clément, K.; Hatem, S.N. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipofibrokines. Eur. Heart J., 2015, 36(13), 795-805a.
[48]
Mahajan, R.; Brooks, A.G.; Shipp, N. Epicardial fat infiltration of atrial musculature creates the substrate for atrial fibrillation in obesity. Heart Rhythm, 2012, 9, S124.
[49]
Aimé-Sempé, C.; Folliguet, T.; Rücker-Martin, C.; Krajewska, M.; Krajewska, S.; Heimburger, M.; Aubier, M.; Mercadier, J.J.; Reed, J.C.; Hatem, S.N. Myocardial cell death in fibrillating and dilated human right atria. J. Am. Coll. Cardiol., 1999, 34(5), 1577-1586.
[50]
Zuk, P.A.; Zhu, M.; Mizuno, H.; Huang, J.; Futrell, J.W.; Katz, A.J.; Benhaim, P.; Lorenz, H.P.; Hedrick, M.H. Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng., 2001, 7(2), 211-228.
[51]
Rangappa, S.; Fen, C.; Lee, E.H.; Bongso, A.; Sim, E.K. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann. Thorac. Surg., 2003, 75(3), 775-779.
[52]
Ausma, J.; Wijffels, M.; van Eys, G.; Koide, M.; Ramaekers, F.; Allessie, M.; Borgers, M. Dedifferentiation of atrial cardiomyocytes as a result of chronic atrial fibrillation. Am. J. Pathol., 1997, 151(4), 985-997.
[53]
Gupta, S.; de Lemos, J.A. Use and misuse of cardiac troponins in clinical practice. Prog. Cardiovasc. Dis., 2007, 50(2), 151-165.
[54]
Omland, T.; de Lemos, J.A.; Sabatine, M.S.; Christophi, C.A.; Rice, M.M.; Jablonski, K.A.; Tjora, S.; Domanski, M.J.; Gersh, B.J.; Rouleau, J.L.; Pfeffer, M.A.; Braunwald, E. A sensitive cardiac troponin T assay in stable coronary artery disease. N. Engl. J. Med., 2009, 361(26), 2538-2547.
[55]
Hijazi, Z.; Siegbahn, A.; Andersson, U.; Granger, C.B.; Alexander, J.H.; Atar, D.; Gersh, B.J.; Mohan, P.; Harjola, V.P.; Horowitz, J.; Husted, S.; Hylek, E.M.; Lopes, R.D.; McMurray, J.J.; Wallentin, L.; Investigators, A. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation, 2014, 129(6), 625-634.
[56]
Wallentin, L.; Hijazi, Z.; Andersson, U.; Alexander, J.H.; De Caterina, R.; Hanna, M.; Horowitz, J.D.; Hylek, E.M.; Lopes, R.D.; Asberg, S.; Granger, C.B.; Siegbahn, A.; Investigators, A. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and other thromboembolic events in Atrial Fibrillation (ARISTOTLE) trial. Circulation, 2014, 130(21), 1847-1858.
[57]
Liu, T.; Li, G.; Li, L.; Korantzopoulos, P. Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion: a meta-analysis. J. Am. Coll. Cardiol., 2007, 49(15), 1642-1648.
[58]
Levin, E.R.; Gardner, D.G.; Samson, W.K. Natriuretic peptides. N. Engl. J. Med., 1998, 339(5), 321-328.
[59]
Inoue, S.; Murakami, Y.; Sano, K.; Katoh, H.; Shimada, T. Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation. J. Card. Fail., 2000, 6(2), 92-96.
[60]
Wozakowska-Kapłon, B. Effect of sinus rhythm restoration on plasma brain natriuretic peptide in patients with atrial fibrillation. Am. J. Cardiol., 2004, 93(12), 1555-1558.
[61]
Wang, Z.; Lu, Y.; Yang, B. MicroRNAs and atrial fibrillation: new fundamentals. Cardiovasc. Res., 2011, 89(4), 710-721.
[62]
Ellinor, P.T.; Lunetta, K.L.; Albert, C.M.; Glazer, N.L.; Ritchie, M.D.; Smith, A.V.; Arking, D.E.; Müller-Nurasyid, M.; Krijthe, B.P.; Lubitz, S.A.; Bis, J.C.; Chung, M.K.; Dörr, M.; Ozaki, K.; Roberts, J.D.; Smith, J.G.; Pfeufer, A.; Sinner, M.F.; Lohman, K.; Ding, J.; Smith, N.L.; Smith, J.D.; Rienstra, M.; Rice, K.M.; Van Wagoner, D.R.; Magnani, J.W.; Wakili, R.; Clauss, S.; Rotter, J.I.; Steinbeck, G.; Launer, L.J.; Davies, R.W.; Borkovich, M.; Harris, T.B.; Lin, H.; Völker, U.; Völzke, H.; Milan, D.J.; Hofman, A.; Boerwinkle, E.; Chen, L.Y.; Soliman, E.Z.; Voight, B.F.; Li, G.; Chakravarti, A.; Kubo, M.; Tedrow, U.B.; Rose, L.M.; Ridker, P.M.; Conen, D.; Tsunoda, T.; Furukawa, T.; Sotoodehnia, N.; Xu, S.; Kamatani, N.; Levy, D.; Nakamura, Y.; Parvez, B.; Mahida, S.; Furie, K.L.; Rosand, J.; Muhammad, R.; Psaty, B.M.; Meitinger, T.; Perz, S.; Wichmann, H.E.; Witteman, J.C.; Kao, W.H.; Kathiresan, S.; Roden, D.M.; Uitterlinden, A.G.; Rivadeneira, F.; McKnight, B.; Sjögren, M.; Newman, A.B.; Liu, Y.; Gollob, M.H.; Melander, O.; Tanaka, T.; Stricker, B.H.; Felix, S.B.; Alonso, A.; Darbar, D.; Barnard, J.; Chasman, D.I.; Heckbert, S.R.; Benjamin, E.J.; Gudnason, V.; Kääb, S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat. Genet., 2012, 44(6), 670-675.
[63]
Patton, K.K.; Ellinor, P.T.; Heckbert, S.R.; Christenson, R.H.; DeFilippi, C.; Gottdiener, J.S.; Kronmal, R.A. N-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: The cardiovascular health study. Circulation, 2009, 120(18), 1768-1774.
[64]
Fonseca, A.C.; Brito, D.; Pinho e Melo, T.; Geraldes, R.; Canhão, P.; Caplan, L.R.; Ferro, J.M. N-terminal pro-brain natriuretic peptide shows diagnostic accuracy for detecting atrial fibrillation in cryptogenic stroke patients. Int. J. Stroke, 2014, 9(4), 419-425.
[65]
Bergwerff, M.; Gittenberger-de Groot, A.C.; Wisse, L.J.; DeRuiter, M.C.; Wessels, A.; Martin, J.F.; Olson, E.N.; Kern, M.J. Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus. Virchows Arch., 2000, 436(1), 12-19.
[66]
Sinner, M.F.; Pfeufer, A.; Akyol, M.; Beckmann, B.M.; Hinterseer, M.; Wacker, A.; Perz, S.; Sauter, W.; Illig, T.; Näbauer, M.; Schmitt, C.; Wichmann, H.E.; Schömig, A.; Steinbeck, G.; Meitinger, T.; Kääb, S. The non-synonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: Results from a systematic candidate gene-based analysis of KCNH2 (HERG). Eur. Heart J., 2008, 29(7), 907-914.
[67]
Anderson, J.L.; Allen Maycock, C.A.; Lappé, D.L.; Crandall, B.G.; Horne, B.D.; Bair, T.L.; Morris, S.R.; Li, Q.; Muhlestein, J.B. Frequency of elevation of C-reactive protein in atrial fibrillation. Am. J. Cardiol., 2004, 94(10), 1255-1259.
[68]
Wazni, O.; Martin, D.O.; Marrouche, N.F.; Shaaraoui, M.; Chung, M.K.; Almahameed, S.; Schweikert, R.A.; Saliba, W.I.; Natale, A. C reactive protein concentration and recurrence of atrial fibrillation after electrical cardioversion. Heart, 2005, 91(10), 1303-1305.
[69]
Luan, Y.; Guo, Y.; Li, S.; Yu, B.; Zhu, S.; Li, S.; Li, N.; Tian, Z.; Peng, C.; Cheng, J.; Li, Q.; Cui, J.; Tian, Y. Interleukin-18 among atrial fibrillation patients in the absence of structural heart disease. Europace, 2010, 12(12), 1713-1718.
[70]
Chung, M.K.; Martin, D.O.; Sprecher, D.; Wazni, O.; Kanderian, A.; Carnes, C.A.; Bauer, J.A.; Tchou, P.J.; Niebauer, M.J.; Natale, A.; Van Wagoner, D.R. C-reactive protein elevation in patients with atrial arrhythmias: Inflammatory mechanisms and persistence of atrial fibrillation. Circulation, 2001, 104(24), 2886-2891.
[71]
Leftheriotis, D.I.; Fountoulaki, K.T.; Flevari, P.G.; Parissis, J.T.; Panou, F.K.; Andreadou, I.T.; Venetsanou, K.S.; Iliodromitis, E.K.; Kremastinos, D.T. The predictive value of inflammatory and oxidative markers following the successful cardioversion of persistent lone atrial fibrillation. Int. J. Cardiol., 2009, 135(3), 361-369.
[72]
Roldán, V.; Marín, F.; Martínez, J.G.; García-Herola, A.; Sogorb, F.; Lip, G.Y. Relation of interleukin-6 levels and prothrombin fragment 1+2 to a point-based score for stroke risk in atrial fibrillation. Am. J. Cardiol., 2005, 95(7), 881-882.
[73]
Mihm, M.J.; Yu, F.; Carnes, C.A.; Reiser, P.J.; McCarthy, P.M.; Van Wagoner, D.R.; Bauer, J.A. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation, 2001, 104(2), 174-180.
[74]
Kallergis, E.M.; Manios, E.G.; Kanoupakis, E.M.; Mavrakis, H.E.; Arfanakis, D.A.; Maliaraki, N.E.; Lathourakis, C.E.; Chlouverakis, G.I.; Vardas, P.E. Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: Biochemical assessment of collagen type-I turnover. J. Am. Coll. Cardiol., 2008, 52(3), 211-215.
[75]
Fu, R.; Wu, S.; Wu, P.; Qiu, J. A study of blood soluble P-selectin, fibrinogen, and von Willebrand factor levels in idiopathic and lone atrial fibrillation. Europace, 2011, 13(1), 31-36.
[76]
Asakura, H.; Hifumi, S.; Jokaji, H.; Saito, M.; Kumabashiri, I.; Uotani, C.; Morishita, E.; Yamazaki, M.; Shibata, K.; Mizuhashi, K. Prothrombin fragment F1 + 2 and thrombin-antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation. Blood Coagul. Fibrinolysis, 1992, 3(4), 469-473.
[77]
Zethelius, B.; Johnston, N.; Venge, P. Troponin I as a predictor of coronary heart disease and mortality in 70-year-old men: a community-based cohort study. Circulation, 2006, 113(8), 1071-1078.
[78]
Fox, C.S.; Parise, H.; D’Agostino, R.B., Sr; Lloyd-Jones, D.M.; Vasan, R.S.; Wang, T.J.; Levy, D.; Wolf, P.A.; Benjamin, E.J. Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. JAMA, 2004, 291(23), 2851-2855.
[79]
Arnar, D.O.; Thorvaldsson, S.; Manolio, T.A.; Thorgeirsson, G.; Kristjansson, K.; Hakonarson, H.; Stefansson, K. Familial aggregation of atrial fibrillation in Iceland. Eur. Heart J., 2006, 27(6), 708-712.
[80]
Xu, Y.; Tuteja, D.; Zhang, Z.; Xu, D.; Zhang, Y.; Rodriguez, J.; Nie, L.; Tuxson, H.R.; Young, J.N.; Glatter, K.A.; Vázquez, A.E.; Yamoah, E.N.; Chiamvimonvat, N. Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts. J. Biol. Chem., 2003, 278(49), 49085-49094.
[81]
Tuteja, D.; Xu, D.; Timofeyev, V.; Lu, L.; Sharma, D.; Zhang, Z.; Xu, Y.; Nie, L.; Vázquez, A.E.; Young, J.N.; Glatter, K.A.; Chiamvimonvat, N. Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol., 2005, 289(6), H2714-H2723.
[82]
Tuteja, D.; Xu, D.; Timofeyev, V.; Lu, L.; Sharma, D.; Zhang, Z.; Xu, Y.; Nie, L.; Vázquez, A.E.; Young, J.N.; Glatter, K.A.; Chiamvimonvat, N. Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol., 2005, 289(6), H2714-H2723.
[83]
Holm, H.; Gudbjartsson, D.F.; Arnar, D.O.; Thorleifsson, G.; Thorgeirsson, G.; Stefansdottir, H.; Gudjonsson, S.A.; Jonasdottir, A.; Mathiesen, E.B.; Njølstad, I.; Nyrnes, A.; Wilsgaard, T.; Hald, E.M.; Hveem, K.; Stoltenberg, C.; Løchen, M.L.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K. Several common variants modulate heart rate, PR interval and QRS duration. Nat. Genet., 2010, 42(2), 117-122.
[84]
Luo, X.; Pan, Z.; Xiao, J.; Zhang, J.; Lu, Y.; Yang, B. Critical role of microRNAs miR-26 and miR-101 in atrial electrical remodeling in experimental atrial fibrillation. Circulation, 2010, 122, A19345.
[85]
Wang, Z.; Lu, Y.; Yang, B. MicroRNAs and atrial fibrillation: new fundamentals. Cardiovasc. Res., 2011, 89(4), 710-721.
[86]
Venugopal, S.K.; Jiang, J.; Kim, T.H.; Li, Y.; Wang, S.S.; Torok, N.J.; Wu, J.; Zern, M.A. Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 298(1), G101-G106.
[87]
Shan, H.; Zhang, Y.; Lu, Y.; Zhang, Y.; Pan, Z.; Cai, B.; Wang, N.; Li, X.; Feng, T.; Hong, Y.; Yang, B. Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines. Cardiovasc. Res., 2009, 83(3), 465-472.
[88]
Adam, O.; Löhfelm, B.; Thum, T.; Gupta, S.K.; Puhl, S.L.; Schäfers, H.J.; Böhm, M.; Laufs, U. Role of miR-21 in the pathogenesis of atrial fibrosis. Basic Res. Cardiol., 2012, 107(5), 278.
[89]
Cardin, S.; Guasch, E.; Luo, X.; Naud, P.; Le Quang, K.; Shi, Y.; Tardif, J.C.; Comtois, P.; Nattel, S. Role for MicroRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure. Circ Arrhythm Electrophysiol, 2012, 5(5), 1027-1035.
[90]
Li, M.; Zhang, J. Circulating MicroRNAs: Potential and emerging biomarkers for diagnosis of cardiovascular and cerebrovascular diseases. BioMed Res. Int., 2015, 2015, 730535.
[91]
Romaine, S.P.R.; Tomaszewski, M.; Condorelli, G.; Samani, N.J. MicroRNAs in cardiovascular disease: An introduction for clinicians. Heart, 2015, 101(12), 921-928.
[92]
Stoicea, N.; Du, A.; Lakis, D.C.; Tipton, C.; Arias-Morales, C.E.; Bergese, S.D. The MiRNA journey from theory to practice as a CNS biomarker. Front. Genet., 2016, 7, 11.
[93]
Faruq, O.; Vecchione, A. microRNA: Diagnostic Perspective. Front. Med. (Lausanne), 2015, 2, 51.
[94]
European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm A.J.; Kirchhof, P.; Lip, G.Y.; Schotten, U.; Savelieva, I.; Ernst, S.; Van, Gelder, I.C.; Al-Attar, N.; Hindricks, G.; Prendergast, B.; Heidbuchel, H.; Alfieri, O.; Angelini, A.; Atar, D.; Colonna, P.; De Caterina, R.; De Sutter, J.; Goette, A.; Gorenek, B.; Heldal, M.; Hohloser, S.H.; Kolh, P.; Le Heuzey, J.Y.; Ponikowski, P.; Rutten, F.H. Guidelines for the management of atrial fibrillation: The task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur. Heart J., 2010, 19, 2369-2429.
[95]
Lip, G.Y.; Nieuwlaat, R.; Pisters, R.; Lane, D.A.; Crijns, H.J. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest, 2010, 137(2), 263-272.
[96]
Nakamura, Y.; Nakamura, K.; Fukushima-Kusano, K.; Ohta, K.; Matsubara, H.; Hamuro, T.; Yutani, C.; Ohe, T. Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis. Thromb. Res., 2003, 111(3), 137-142.
[97]
Fukuchi, M.; Watanabe, J.; Kumagai, K.; Katori, Y.; Baba, S.; Fukuda, K.; Yagi, T.; Iguchi, A.; Yokoyama, H.; Miura, M.; Kagaya, Y.; Sato, S.; Tabayashi, K.; Shirato, K. Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage. J. Am. Coll. Cardiol., 2001, 37(5), 1436-1442.
[98]
Li-Saw-Hee, F.L.; Blann, A.D.; Gurney, D.; Lip, G.Y. Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function. Eur. Heart J., 2001, 22(18), 1741-1747.
[99]
Nakajima, K. The relationship between left atrial thrombus and hematological markers in patients with chronic non-rheumatic atrial fibrillation. Nippon Ronen Igakkai Zasshi, 2000, 37(11), 903-907.
[100]
Nakagawa, K.; Hirai, T.; Shinokawa, N.; Uchiyama, Y.; Kameyama, T.; Takashima, S.; Fujiki, A.; Asanoi, H.; Inoue, H. Relation of fibrillatory wave amplitude with hemostatic abnormality and left atrial appendage dysfunction in patients with chronic nonrheumatic atrial fibrillation. Jpn. Circ. J., 2001, 65(5), 375-380.
[101]
Nakajima, K. The relationship between left atrial thrombus and hematological markers in patients with chronic non-rheumatic atrial fibrillation. Nippon Ronen Igakkai Zasshi, 2000, 37(11), 903-907.
[102]
Somlói, M.; Tomcsányi, J.; Nagy, E.; Bodó, I.; Bezzegh, A. D-dimer determination as a screening tool to exclude atrial thrombi in atrial fibrillation. Am. J. Cardiol., 2003, 92(1), 85-87.
[103]
Eikelboom, J.; Hijazi, Z.; Oldgren, J.; Andersson, U.; Connolly, S.J.; Ezekowitz, M.D.; Reilly, P.A.; Yusuf, S.; Wallentin, L.; Siegbahn, A. D-dimer is prognostic for stroke, major bleeding and death during anticoagulation of atrial fibrillation - a RELY substudy. Circulation, 2010, 122, A18321.
[104]
Christersson, C.; Schollin, M.; Alexander, J.H.; Bersh, B.J.; Horowitz, J.; Hylek, E.M.; Mohan, P.; Granger, C.B.; Wallentin, L.; Siegbahn, A. Increased levels of D-dimer in atrial fibrillation identify patients with higher risk of thromboembolic events and death. European Heart Journal (Vol. 33, No. Suppl 1, pp. 969-969).
[105]
Alvarez-Perez, F.J.; Castelo-Branco, M.; Alvarez-Sabin, J. Usefulness of measurement of fibrinogen, D-dimer, D-dimer/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke. J. Neurol. Neurosurg. Psychiatry, 2011, 82(9), 986-992.
[106]
Freestone, B.; Chong, A.Y.; Nuttall, S.; Blann, A.D.; Lip, G.Y. Soluble E-selectin, von Willebrand factor, soluble thrombomodulin, and total body nitrate/nitrite product as indices of endothelial damage/dysfunction in paroxysmal, persistent, and permanent atrial fibrillation. Chest, 2007, 132(4), 1253-1258.
[107]
Hanson, E.; Jood, K.; Karlsson, S.; Nilsson, S.; Blomstrand, C.; Jern, C. Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke. J. Thromb. Haemost., 2011, 9(2), 275-281.
[108]
Choudhury, A.; Chung, I.; Blann, A.D.; Lip, G.Y. Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P-selectin as indexes of platelet function in atrial fibrillation: a comparison of “healthy control subjects” and “disease control subjects” in sinus rhythm. J. Am. Coll. Cardiol., 2007, 49(19), 1957-1964.
[109]
Tsang, T.S.; Gersh, B.J.; Appleton, C.P.; Tajik, A.J.; Barnes, M.E.; Bailey, K.R.; Oh, J.K.; Leibson, C.; Montgomery, S.C.; Seward, J.B. Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women. J. Am. Coll. Cardiol., 2002, 40(9), 1636-1644.
[110]
Hijazi, Z.; Wallentin, L.; Siegbahn, A.; Andersson, U.; Christersson, C.; Ezekowitz, J.; Gersh, B.J.; Hanna, M.; Hohnloser, S.; Horowitz, J.; Huber, K.; Hylek, E.M.; Lopes, R.D.; McMurray, J.J.; Granger, C.B. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the prevention of stroke in subjects with atrial fibrillation). J. Am. Coll. Cardiol., 2013, 61(22), 2274-2284.
[111]
Shimizu, H.; Murakami, Y.; Inoue, S.; Ohta, Y.; Nakamura, K.; Katoh, H.; Sakne, T.; Takahashi, N.; Ohata, S.; Sugamori, T.; Ishibashi, Y.; Shimada, T. High plasma brain natriuretic polypeptide level as a marker of risk for thromboembolism in patients with nonvalvular atrial fibrillation. Stroke, 2002, 33(4), 1005-1010.
[112]
Yukiiri, K.; Hosomi, N.; Naya, T.; Takahashi, T.; Ohkita, H.; Mukai, M.; Masugata, H.; Murao, K.; Ueno, M.; Nakamura, T.; Dobashi, H.; Miki, T.; Kuroda, Y.; Kohno, M. Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke. BMC Neurol., 2008, 8, 45.
[113]
Rodríguez-Yáñez, M.; Sobrino, T.; Blanco, M.; de la Ossa, N.P.; Brea, D.; Rodríguez-González, R.; Leira, R.; Dávalos, A.; Castillo, J. High serum levels of pro-brain natriuretic peptide (pro BNP) identify cardioembolic origin in undetermined stroke. Dis. Markers, 2009, 26(4), 189-195.
[114]
Rost, N.S.; Biffi, A.; Cloonan, L.; Chorba, J.; Kelly, P.; Greer, D.; Ellinor, P.; Furie, K.L. Brain natriuretic peptide predicts functional outcome in ischemic stroke. Stroke, 2012, 43(2), 441-445.
[115]
Hijazi, Z.; Oldgren, J.; Andersson, U.; Connolly, S.J.; Ezekowitz, M.D.; Hohnloser, S.H.; Reilly, P.A.; Vinereanu, D.; Siegbahn, A.; Yusuf, S.; Wallentin, L. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: A randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) substudy. Circulation, 2012, 125(13), 1605-1616.
[116]
Eggers, K.M.; Lind, L.; Ahlström, H.; Bjerner, T.; Ebeling Barbier, C.; Larsson, A.; Venge, P.; Lindahl, B. Prevalence and pathophysiological mechanisms of elevated cardiac troponin I levels in a population-based sample of elderly subjects. Eur. Heart J., 2008, 29(18), 2252-2258.
[117]
Pirat, B.; Atar, I.; Ertan, C.; Bozbas, H.; Gulmez, O.; Müderrisoglu, H.; Ozin, B. Comparison of C-reactive protein levels in patients who do and do not develop atrial fibrillation during electrophysiologic study. Am. J. Cardiol., 2007, 100(10), 1552-1555.
[118]
Hijazi, Z.; Lindbäck, J.; Alexander, J.H.; Hanna, M.; Held, C.; Hylek, E.M.; Lopes, R.D.; Oldgren, J.; Siegbahn, A.; Stewart, R.A.; White, H.D.; Granger, C.B.; Wallentin, L. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur. Heart J., 2016, 37(20), 1582-1590.
[119]
Conway, D.S.; Buggins, P.; Hughes, E.; Lip, G.Y. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. J. Am. Coll. Cardiol., 2004, 43(11), 2075-2082.
[120]
Crandall, M.A.; Horne, B.D.; Day, J.D.; Anderson, J.L.; Muhlestein, J.B.; Crandall, B.G.; Weiss, J.P.; Lappé, D.L.; Bunch, T.J. Atrial fibrillation and CHADS2 risk factors are associated with highly sensitive C-reactive protein incrementally and independently. Pacing Clin. Electrophysiol., 2009, 32(5), 648-652.
[121]
Bernhardt, P.; Schmidt, H.; Hammerstingl, C.; Lüderitz, B.; Omran, H. Patients with atrial fibrillation and dense spontaneous echo contrast at high risk a prospective and serial follow-up over 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging. J. Am. Coll. Cardiol., 2005, 45(11), 1807-1812.
[122]
Conway, D.S.; Buggins, P.; Hughes, E.; Lip, G.Y. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am. Heart J., 2004, 148(3), 462-466.
[123]
Lip, G.Y.; Patel, J.V.; Hughes, E.; Hart, R.G. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: Relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke, 2007, 38(4), 1229-1237.
[124]
Hermida, J.; Lopez, F.L.; Montes, R.; Matsushita, K.; Astor, B.C.; Alonso, A. Usefulness of high-sensitivity C-reactive protein to predict mortality in patients with atrial fibrillation (from the Atherosclerosis Risk in Communities [ARIC] Study). Am. J. Cardiol., 2012, 109(1), 95-99.
[125]
Psychari, S.N.; Apostolou, T.S.; Sinos, L.; Hamodraka, E.; Liakos, G.; Kremastinos, D.T. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am. J. Cardiol., 2005, 95(6), 764-767.
[126]
Goswami, K.C.; Yadav, R.; Rao, M.B.; Bahl, V.K.; Talwar, K.K.; Manchanda, S.C. Clinical and echocardiographic predictors of left atrial clot and spontaneous echo contrast in patients with severe rheumatic mitral stenosis: a prospective study in 200 patients by transesophageal echocardiography. Int. J. Cardiol., 2000, 73(3), 273-279.
[127]
Wollert, K.C.; Kempf, T. GDF-15 in heart failure: Providing insight into end-organ dysfunction and its recovery? Eur. J. Heart Fail., 2012, 14(11), 1191-1193.
[128]
Lind, L.; Wallentin, L.; Kempf, T.; Tapken, H.; Quint, A.; Lindahl, B.; Olofsson, S.; Venge, P.; Larsson, A.; Hulthe, J.; Elmgren, A.; Wollert, K.C. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: Results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study. Eur. Heart J., 2009, 30(19), 2346-2353.
[129]
Anand, I.S.; Kempf, T.; Rector, T.S.; Tapken, H.; Allhoff, T.; Jantzen, F.; Kuskowski, M.; Cohn, J.N.; Drexler, H.; Wollert, K.C. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the valsartan heart failure trial. Circulation, 2010, 122(14), 1387-1395.
[130]
Zhou, Y.M.; Li, M.J.; Zhou, Y.L.; Ma, L.L.; Yi, X. Growth differentiation factor-15 (GDF-15), novel biomarker for assessing atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease. Int. J. Clin. Exp. Med., 2015, 8(11), 21201-21207.
[131]
Go, A.S.; Chertow, G.M.; Fan, D.; McCulloch, C.E.; Hsu, C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med., 2004, 351(13), 1296-1305.
[132]
Santopinto, J.J.; Fox, K.A.; Goldberg, R.J.; Budaj, A.; Piñero, G.; Avezum, A.; Gulba, D.; Esteban, J.; Gore, J.M.; Johnson, J.; Gurfinkel, E.P. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: Findings from the global registry of acute coronary events (GRACE). Heart, 2003, 89(9), 1003-1008.
[133]
Iguchi, Y.; Kimura, K.; Kobayashi, K.; Aoki, J.; Terasawa, Y.; Sakai, K.; Uemura, J.; Shibazaki, K. Relation of atrial fibrillation to glomerular filtration rate. Am. J. Cardiol., 2008, 102(8), 1056-1059.
[134]
Schmidt, M.; Rieber, J.; Daccarett, M.; Marschang, H.; Sinha, A.M.; Biggar, P.; Jung, P.; Ketteler, M.; Brachmann, J.; Rittger, H. Relation of recurrence of atrial fibrillation after successful cardioversion to renal function. Am. J. Cardiol., 2010, 105(3), 368-372.
[135]
Berkowitsch, A.; Kuniss, M.; Greiss, H.; Wójcik, M.; Zaltsberg, S.; Lehinant, S.; Erkapic, D.; Pajitnev, D.; Pitschner, H.F.; Hamm, C.W.; Neumann, T. Impact of impaired renal function and metabolic syndrome on the recurrence of atrial fibrillation after catheter ablation: a long term follow-up. Pacing Clin. Electrophysiol., 2012, 35(5), 532-543.
[136]
Go, A.S.; Fang, M.C.; Udaltsova, N.; Chang, Y.; Pomernacki, N.K.; Borowsky, L.; Singer, D.E.; Investigators, A.S. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: The anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation, 2009, 119(10), 1363-1369.
[137]
Hohnloser, S.H.; Hijazi, Z.; Thomas, L.; Alexander, J.H.; Amerena, J.; Hanna, M.; Keltai, M.; Lanas, F.; Lopes, R.D.; Lopez-Sendon, J.; Granger, C.B.; Wallentin, L. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur. Heart J., 2012, 33(22), 2821-2830.
[138]
Newman, D.J.; Thakkar, H.; Edwards, R.G.; Wilkie, M.; White, T.; Grubb, A.O.; Price, C.P. Serum cystatin C measured by automated immunoassay: A more sensitive marker of changes in GFR than serum creatinine. Kidney Int., 1995, 47(1), 312-318.
[139]
Laterza, O.F.; Price, C.P.; Scott, M.G. Cystatin C: an improved estimator of glomerular filtration rate? Clin. Chem., 2002, 48(5), 699-707.
[140]
Imai, A.; Komatsu, S.; Ohara, T.; Kamata, T.; Yoshida, J.; Miyaji, K.; Shimizu, Y.; Takewa, M.; Hirayama, A.; Deshpande, G.A.; Takahashi, O.; Kodama, K. Serum cystatin C is associated with early stage coronary atherosclerotic plaque morphology on multidetector computed tomography. Atherosclerosis, 2011, 218(2), 350-355.
[141]
Hijazi, Z.; Oldgren, J.; Andersson, U.; Connolly, S.J.; Ezekowitz, M.D.; Hohnloser, S.H.; Reilly, P.A.; Siegbahn, A.; Yusuf, S.; Wallentin, L. Cystatin C is prognostic for
stroke, death and bleeding during anticoagulation of atrial
fibrillation - a RELY substudy. Circulation, 2011. AHA 124, A12492.
[142]
Gudbjartsson, D.F.; Arnar, D.O.; Helgadottir, A.; Gretarsdottir, S.; Holm, H.; Sigurdsson, A.; Jonasdottir, A.; Baker, A.; Thorleifsson, G.; Kristjansson, K.; Palsson, A.; Blondal, T.; Sulem, P.; Backman, V.M.; Hardarson, G.A.; Palsdottir, E.; Helgason, A.; Sigurjonsdottir, R.; Sverrisson, J.T.; Kostulas, K.; Ng, M.C.; Baum, L.; So, W.Y.; Wong, K.S.; Chan, J.C.; Furie, K.L.; Greenberg, S.M.; Sale, M.; Kelly, P.; MacRae, C.A.; Smith, E.E.; Rosand, J.; Hillert, J.; Ma, R.C.; Ellinor, P.T.; Thorgeirsson, G.; Gulcher, J.R.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature, 2007, 448(7151), 353-357.
[143]
Gretarsdottir, S.; Thorleifsson, G.; Manolescu, A.; Styrkarsdottir, U.; Helgadottir, A.; Gschwendtner, A.; Kostulas, K.; Kuhlenbäumer, G.; Bevan, S.; Jonsdottir, T.; Bjarnason, H.; Saemundsdottir, J.; Palsson, S.; Arnar, D.O.; Holm, H.; Thorgeirsson, G.; Valdimarsson, E.M.; Sveinbjörnsdottir, S.; Gieger, C.; Berger, K.; Wichmann, H.E.; Hillert, J.; Markus, H.; Gulcher, J.R.; Ringelstein, E.B.; Kong, A.; Dichgans, M.; Gudbjartsson, D.F.; Thorsteinsdottir, U.; Stefansson, K. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann. Neurol., 2008, 64(4), 402-409.
[144]
Gudbjartsson, D.F.; Holm, H.; Gretarsdottir, S.; Thorleifsson, G.; Walters, G.B.; Thorgeirsson, G.; Gulcher, J.; Mathiesen, E.B.; Njølstad, I.; Nyrnes, A.; Wilsgaard, T.; Hald, E.M.; Hveem, K.; Stoltenberg, C.; Kucera, G.; Stubblefield, T.; Carter, S.; Roden, D.; Ng, M.C.; Baum, L.; So, W.Y.; Wong, K.S.; Chan, J.C.; Gieger, C.; Wichmann, H.E.; Gschwendtner, A.; Dichgans, M.; Kuhlenbäumer, G.; Berger, K.; Ringelstein, E.B.; Bevan, S.; Markus, H.S.; Kostulas, K.; Hillert, J.; Sveinbjörnsdóttir, S.; Valdimarsson, E.M.; Løchen, M.L.; Ma, R.C.; Darbar, D.; Kong, A.; Arnar, D.O.; Thorsteinsdottir, U.; Stefansson, K. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat. Genet., 2009, 41(8), 876-878.
[145]
Xu, H.; Tang, Y.; Liu, D.Z.; Ran, R.; Ander, B.P.; Apperson, M.; Liu, X.S.; Khoury, J.C.; Gregg, J.P.; Pancioli, A.; Jauch, E.C.; Wagner, K.R.; Verro, P.; Broderick, J.P.; Sharp, F.R. Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke. J. Cereb. Blood Flow Metab., 2008, 28(7), 1320-1328.
[146]
Grau, A.J.; Buggle, F.; Becher, H.; Zimmermann, E.; Spiel, M.; Fent, T.; Maiwald, M.; Werle, E.; Zorn, M.; Hengel, H.; Hacke, W. Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies. Neurology, 1998, 50(1), 196-203.
[147]
Zeng, L.; Liu, J.; Wang, Y.; Wang, L.; Weng, S.; Tang, Y.; Zheng, C.; Cheng, Q.; Chen, S.; Yang, G.Y. MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia. Front. Biosci. (Elite Ed.), 2011, 3, 1265-1272.
[148]
Gan, C.S.; Wang, C.W.; Tan, K.S. Circulatory microRNA-145 expression is increased in cerebral ischemia. Genet. Mol. Res., 2012, 11(1), 147-152.
[149]
Tan, K.S.; Armugam, A.; Sepramaniam, S.; Lim, K.Y.; Setyowati, K.D.; Wang, C.W.; Jeyaseelan, K. Expression profile of MicroRNAs in young stroke patients. PLoS One, 2009, 4(11), e7689.
[150]
Wazni, O.M.; Tsao, H.M.; Chen, S.A.; Chuang, H.H.; Saliba, W.; Natale, A.; Klein, A.L. Cardiovascular imaging in the management of atrial fibrillation. J. Am. Coll. Cardiol., 2006, 48(10), 2077-2084.
[151]
Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Arch. Intern. Med., 1998, 158(12), 1316-1320.
[152]
Banerjee, A.; Taillandier, S.; Olesen, J.B.; Lane, D.A.; Lallemand, B.; Lip, G.Y.; Fauchier, L. Ejection fraction and outcomes in patients with atrial fibrillation and heart failure: The loire valley atrial fibrillation project. Eur. J. Heart Fail., 2012, 14(3), 295-301.
[153]
Sandhu, R.K.; Hohnloser, S.H.; Pfeffer, M.A.; Yuan, F.; Hart, R.G.; Yusuf, S.; Connolly, S.J.; McAlister, F.A.; Healey, J.S. Relationship between degree of left ventricular dysfunction, symptom status, and risk of embolic events in patients with atrial fibrillation and heart failure. Stroke, 2015, 46(3), 667-672.
[154]
Di Tullio, M.R.; Sacco, R.L.; Sciacca, R.R.; Homma, S. Left atrial size and the risk of ischemic stroke in an ethnically mixed population. Stroke, 1999, 30(10), 2019-2024.
[155]
Leung, D.Y.; Davidson, P.M.; Cranney, G.B.; Walsh, W.F. Thromboembolic risks of left atrial thrombus detected by transesophageal echocardiogram. Am. J. Cardiol., 1997, 79(5), 626-629.
[156]
Tsai, L.M.; Lin, L.J.; Teng, J.K.; Chen, J.H. Prevalence and clinical significance of left atrial thrombus in nonrheumatic atrial fibrillation. Int. J. Cardiol., 1997, 58(2), 163-169.
[157]
Stöllberger, C.; Chnupa, P.; Kronik, G.; Brainin, M.; Finsterer, J.; Schneider, B.; Slany, J. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation. ELAT Study Group. Embolism in Left Atrial Thrombi. Ann. Intern. Med., 1998, 128(8), 630-638.
[158]
Zabalgoitia, M.; Halperin, J.L.; Pearce, L.A.; Blackshear, J.L.; Asinger, R.W.; Hart, R.G. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. J. Am. Coll. Cardiol., 1998, 31(7), 1622-1626.
[159]
Mügge, A.; Kühn, H.; Nikutta, P.; Grote, J.; Lopez, J.A.; Daniel, W.G. Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: identification of a subgroup of patients at increased embolic risk. J. Am. Coll. Cardiol., 1994, 23(3), 599-607.
[160]
Inoue, Y.Y.; Alissa, A.; Khurram, I.M.; Fukumoto, K.; Habibi, M.; Venkatesh, B.A.; Zimmerman, S.L.; Nazarian, S.; Berger, R.D.; Calkins, H.; Lima, J.A.; Ashikaga, H. Quantitative tissue-tracking cardiac magnetic resonance (CMR) of left atrial deformation and the risk of stroke in patients with atrial fibrillation. J. Am. Heart Assoc., 2015, 4(4), 4.
[161]
Kong, B.; Liu, Y.; Hu, H.; Wang, L.; Fan, Y.; Mei, Y.; Liu, W.; Liao, J.; Liu, D.; Xing, D.; Huang, H. Left atrial appendage morphology in patients with atrial fibrillation in China: Implications for stroke risk assessment from a single center study. Chin. Med. J. (Engl.), 2014, 127(24), 4210-4214.
[162]
Kimura, T.; Takatsuki, S.; Inagawa, K.; Katsumata, Y.; Nishiyama, T.; Nishiyama, N.; Fukumoto, K.; Aizawa, Y.; Tanimoto, Y.; Tanimoto, K.; Jinzaki, M.; Fukuda, K. Anatomical characteristics of the left atrial appendage in cardiogenic stroke with low CHADS2 scores. Heart Rhythm, 2013, 10(6), 921-925.
[163]
Lupercio, F. Left atrial appendage morphology and stroke risk in patients with atrial fibrillation: a meta-analysis. J. Am. Coll. Cardiol., 2016, 67, 713-713.
[164]
Rodríguez-Yáñez, M.; Sobrino, T.; Blanco, M.; de la Ossa, N.P.; Brea, D.; Rodríguez-González, R.; Leira, R.; Dávalos, A.; Castillo, J. High serum levels of pro-brain natriuretic peptide (pro BNP) identify cardioembolic origin in undetermined stroke. Dis. Markers, 2009, 26(4), 189-195.
[165]
Hijazi, Z.; Aulin, J.; Andersson, U.; Alexander, J.H.; Gersh, B.; Granger, C.B.; Hanna, M.; Horowitz, J.; Hylek, E.M.; Lopes, R.D.; Siegbahn, A.; Wallentin, L.; Investigators, A. Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. Heart, 2016, 102(7), 171056-171059.
[166]
Hijazi, Z.; Lindbäck, J.; Alexander, J.H.; Hanna, M.; Held, C.; Hylek, E.M.; Lopes, R.D.; Oldgren, J.; Siegbahn, A.; Stewart, R.A.; White, H.D.; Granger, C.B.; Wallentin, L. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur. Heart J., 2016, 37(20), 1582-1590.
[167]
Seppälä, I.; Kleber, M.E.; Bevan, S.; Lyytikäinen, L.P.; Oksala, N.; Hernesniemi, J.A.; Mäkelä, K.M.; Rothwell, P.M.; Sudlow, C.; Dichgans, M.; Mononen, N.; Vlachopoulou, E.; Sinisalo, J.; Delgado, G.E.; Laaksonen, R.; Koskinen, T.; Scharnagl, H.; Kähönen, M.; Markus, H.S.; März, W.; Lehtimäki, T. Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke. Sci. Rep., 2016, 6, 1056-1059.
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