Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation



      Inflammation and oxidative stress have been recently implicated in the pathophysiology of atrial fibrillation (AF). The aim of this study was to examine the potential benefit of vitamin C on the early recurrence rates and on inflammatory indices after successful cardioversion of persistent AF, as well as to investigate the time course of changes in these indices post-cardioversion.


      We prospectively studied 44 consecutive patients after successful electrical cardioversion of persistent AF. All patients received standard treatment and were randomised in one to one fashion to either oral vitamin C administration or no additional therapy. We followed-up the patients for 7 days performing successive measurements of white blood cell (WBC) count, C-reactive protein (CRP), fibrinogen, and ferritin levels.


      One week after successful cardioversion, AF recurred in 4.5% of patients in the vitamin C group and in 36.3% of patients in the control group (p=0.024). Compared to baseline values, inflammatory indices decreased after cardioversion in patients receiving vitamin C but did not change significantly in the control group. A significant variance was found in the serial measurements of WBC counts (F=5.86, p=0.001) and of fibrinogen levels (F=4.10, p=0.0084) in the two groups. In the vitamin C group CRP levels were lower on the seventh day (p<0.05). CRP and fibrinogen levels were higher in patients who relapsed into AF compared to patients who maintained sinus rhythm (F=2.77, p=0.044 and F=3.51, p=0.017, respectively).


      These findings suggest that vitamin C reduces the early recurrence rates after cardioversion of persistent AF and attenuates the associated low-level inflammation. These effects indicate that therapeutic approaches targeting at inflammation and oxidative stress may exert favourable effects on atrial electrical remodeling.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to International Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Tsang T.S.M.
        • Gersh B.J.
        Atrial fibrillation: an old disease, a new epidemic.
        Am J Med. 2002; 113: 432-435
        • Jahangir A.
        • Munger T.M.
        • Packer D.L.
        • Crijns J.G.M.
        Atrial fibrillation.
        in: Podrid P.J. Kowey P.R. Cardiac arrhythmia: mechanisms, diagnosis and management. 2nd ed. Lippincott Williams and Wilkins, Philadelphia2001: 457-499
        • Allessie M.
        • Ausma J.
        • Schotten U.
        Electrical, contracticle and structural remodeling during atrial fibrillation.
        Cardiovasc Res. 2002; 54: 230-246
        • Tieleman R.G.
        • Van Gelder I.C.
        • Crijns H.J.G.M.
        • et al.
        Early recurrences of atrial fibrillation after electrical cardioversion: a result of fibrillation-induced electrical remodeling of the atria?.
        J Am Coll Cardiol. 1998; 31: 167-173
        • Chung M.K.
        • Martin D.O.
        • Sprecher D.
        • et al.
        C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation.
        Circulation. 2001; 104: 2886-2891
        • Dernellis J.
        • Panaretou M.
        C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation.
        Acta Cardiol. 2001; 56: 375-380
        • Aviles R.J.
        • Martin D.O.
        • Apperson-Hansen C.
        • et al.
        Inflammation as a risk factor for atrial fibrillation.
        Circulation. 2003; 108: 3006-3010
        • Mihm M.J.
        • Yu F.
        • Carnes C.A.
        • et al.
        Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation.
        Circulation. 2001; 104: 174-180
        • Carnes C.A.
        • Chung M.K.
        • Nakayama T.
        • et al.
        Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.
        Circ Res. 2001; 89: e32-e38
        • Kim Y.H.
        • Lee J.H.
        • Lim do S.
        • et al.
        Gene expression profiling of oxidative stress on atrial fibrillation in humans.
        Exp Mol Med. 2003; 35: 336-349
        • Lin P.H.
        • Lee S.H.
        • Su C.P.
        • Wei Y.H.
        Oxidative damage to mitochondrial DNA in atrial muscle of patients with atrial fibrillation.
        Free Radic Biol Med. 2003; 35: 1310-1318
        • Korantzopoulos P.
        • Galaris D.
        • Papaioannides D.
        • Kokkoris S.
        C-reactive protein and oxidative stress in atrial fibrillation.
        Int J Cardiol. 2003; 88: 103-104
        • Korantzopoulos P.
        • Kolettis T.
        • Siogas K.
        • Goudevenos J.
        Atrial fibrillation and electrical remodeling: the potential role of inflammation and oxidative stress.
        Med Sci Monit. 2003; 9: RA225-RA229
        • Korantzopoulos P.
        • Galaris D.
        The protective role of vitamin C on endothelial dysfunction.
        J Clin Basic Cardiol. 2003; 6: 3-6
        • Johnston C.S.
        • Cox S.K.
        Plasma-saturating intakes of vitamin C confer maximal antioxidant protection to plasma.
        J Am Coll Nutr. 2001; 20: 623-627
        • Gabay C.
        • Kushner I.
        Acute-phase proteins and other systemic responses to inflammation.
        N Engl J Med. 1999; 340: 448-454
        • Van Wagoner D.R.
        Molecular basis of atrial fibrillation: a dream or a reality?.
        J Cardiovasc Electrophysiol. 2003; 14: 667-669
        • Van Wagoner D.R.
        Electrophysiological remodeling in human atrial fibrillation.
        Pacing Clin Electrophysiol. 2003; 26: 1572-1575
        • Shinagawa K.
        • Derakhchan K.
        • Nattel S.
        Pharmacological prevention of atrial tachycardia induced remodeling as a potential therapeutic strategy.
        Pacing Clin Electrophysiol. 2003; 26: 752-764
        • Siu C.W.
        • Lau C.P.
        • Tse H.F.
        Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion.
        Am J Cardiol. 2003; 92: 1343-1345
        • Young-Xu Y.
        • Jabbour S.
        • Goldberg R.
        • et al.
        Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease.
        Am J Cardiol. 2003; 92: 1379-1383
        • Korantzopoulos P.
        • Kountouris E.
        • Kolettis T.
        • Siogas K.
        Anti-inflammatory and antioxidant actions of statins may favorably affect atrial remodeling in atrial fibrillation.
        Am J Cardiol. 2004; 93: 1200
        • Dernellis J.
        • Panaretou M.
        Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation.
        Eur Heart J. 2004; 25: 1100-1107
        • Li-Saw-Hee F.L.
        • Blann A.D.
        • Gurney D.
        • Lip G.Y.H.
        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: 1741-1747
        • Abdelhadi R.H.
        • Gurm H.S.
        • Van Wagoner D.R.
        • Chung M.K.
        Relation of an exaggerated rise in white blood cells after coronary bypass or cardiac valve surgery to development of atrial fibrillation postoperatively.
        Am J Cardiol. 2004; 93: 1176-1178
        • Block G.
        • Jensen C.
        • Dietrich M.
        • Norkus E.P.
        • Hudes M.
        • Packer L.
        Plasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant supplementation.
        J Am Coll Nutr. 2004; 23: 141-147
        • Manios E.G.
        • Mavrakis H.E.
        • Kanoupakis E.M.
        • et al.
        Effects of amiodarone and diltiazem on persistent atrial fibrillation conversion and recurrence rates: a randomized controlled study.
        Cardiovasc Drugs Ther. 2003; 17: 31-39
        • Madrid A.H.
        • Bueno M.G.
        • Rebollo J.M.
        • et al.
        Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study.
        Circulation. 2002; 106: 331-336
        • Ueng K.C.
        • Tsai T.P.
        • Yu W.C.
        • et al.
        Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation: results of a prospective and controlled study.
        Eur Heart J. 2003; 24: 2090-2098
        • Korantzopoulos P.
        • Kolettis T.
        • Kountouris E.
        • Siogas K.
        Atrial remodeling in persistent atrial fibrillation: the potential role of aldosterone.
        Eur Heart J. 2004; 25: 1086