Internal and Emergency Medicine

, Volume 7, Supplement 3, pp 233–240

The risk stratification in atrial fibrillation

  • Domenico Prisco
  • Caterina Cenci
  • Elena Silvestri
  • Giacomo Emmi
  • Tommaso Barnini
  • Carlo Tamburini
SELECTED PAPERS – ATRIAL FIBRILLATION

Abstract

Atrial fibrillation (AF) is the most common rhythm disorder and represents a major public health problem because it carries an increased risk of arterial thromboembolism and ischemic stroke. Because the absolute benefit of antithrombotic therapy depends on the underlying risk of stroke, an accurate stratification of patients’ risk is needed to choose the appropriate antithrombotic strategy. Over the years, several stroke risk stratification models (RSMs) were developed based on the ‘classic’ risk factors for stroke such as increasing age, hypertension, diabetes mellitus, and left ventricular dysfunction. Among all RSMs, the CHADS2 score is the most popular and used one thanks to its simplicity and endorsement in several widely promulgated practice guidelines. Despite its validation in large datasets and specific population of AF patients, it has many limitations, especially due to the non-inclusion of several proven risk factors for stroke and to the classification of a large number of patients in the intermediate risk category, so creating ambiguity over the most appropriate antithrombotic therapy. Thus, the CHA2DS2-VASc score was introduced and was demonstrated to perform better than the CHADS2, even in a “real world” population of elderly AF patients. Recently, in view of the availability of new oral anticoagulant drugs, that can overcome the limitations of warfarin and allow a more personalized therapy, many efforts are being made to identify other possibilities to assess the thromboembolic risk in AF patients. It has been demonstrated that an increase in C-reactive protein and interleukin-6 and the presence of G20210A factor II gene polymorphism and hyper-homocysteinemia are independent risk factors for ischemic complications in AF patients. Even the presence of chronic renal disease and the daily AF burden, registered with implantable monitors, are associated with an increase risk of stroke. Finally, the assessment of thromboembolic risk should go hand in hand with the consideration of the risk of bleeding. For this purpose, it has been recently developed a practical bleeding risk score, the HAS-BLED, which was included in the last ESC guidelines for the risk stratification of AF patients before starting anticoagulant therapy.

Keywords

Atrial fibrillation Stroke Thromboembolism Bleeding Risk factors 

References

  1. 1.
    Hersi A, Wyse DG (2005) Management of atrial fibrillation. Curr Probl Cardiol 30:175–234PubMedCrossRefGoogle Scholar
  2. 2.
    Go AS, Hylek EM, Phillips KA et al (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. JAMA 285:2370–2375PubMedCrossRefGoogle Scholar
  3. 3.
    Miyasaka Y, Barnes ME, Gersh BJ et al (2006) Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 114:119–125PubMedCrossRefGoogle Scholar
  4. 4.
    Lip GY, Tse HF, Lane DA (2012) Atrial fibrillation. Lancet 379:648–661PubMedCrossRefGoogle Scholar
  5. 5.
    Wolf PA, Abbott RD, Kannel WB (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22:983–988PubMedCrossRefGoogle Scholar
  6. 6.
    Fuster V, Ryden LE, Asinger RW et al (2001) ACC/AHA/ESC Guidelines 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 European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the management of patients with Atrial Fibrillation) developed in collaboration with North American Society of Pacing and Electrophysiology. Eur Heart J 22:1852–1923PubMedCrossRefGoogle Scholar
  7. 7.
    Lip GY (2012) Can we predict stroke in atrial fibrillation? Clin Cardiol 35:21–27PubMedCrossRefGoogle Scholar
  8. 8.
    Gage BF, van Walraven C, Pearce L et al (2004) Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 110:2287–2292PubMedCrossRefGoogle Scholar
  9. 9.
    Stroke Risk in Atrial Fibrillation Working Group (2008) Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke 39:1901–1910CrossRefGoogle Scholar
  10. 10.
    Lip GY, Halperin JL (2010) Improving stroke risk stratification in atrial fibrillation. Am J Med 123:484–488PubMedCrossRefGoogle Scholar
  11. 11.
    Hughes M, Lip GYH, Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care (2008) Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 99:295–304PubMedGoogle Scholar
  12. 12.
    Hart RG, Pearce LA, Mc Bride R et al (1999) Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAFI-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 30:1223–1229PubMedCrossRefGoogle Scholar
  13. 13.
    Hart RG, Pearce LA, Rothbart RM et al (2000) Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 35:183–187PubMedCrossRefGoogle Scholar
  14. 14.
    Wang TJ, Massaro JM, Levy D et al (2003) A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. J Am Med Assoc 290:1049–1056CrossRefGoogle Scholar
  15. 15.
    Van Latum JC, Koudstaal PJ, Venables GS et al (1995) Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with non rheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group. Stroke 26:801–806PubMedCrossRefGoogle Scholar
  16. 16.
    Cabin HS, Clubb KS, Hall C et al (1990) Risk for systemic embolization of atrial fibrillation without mitral stenosis. Am J Cardiol 65:1112–1116PubMedCrossRefGoogle Scholar
  17. 17.
    The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators (1998) Patients with non valvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. J Am Geriat Soc 279:1273–1277Google Scholar
  18. 18.
    Petersen P (1990) Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Arch Int Med 150:819–821CrossRefGoogle Scholar
  19. 19.
    Nakagami H, Yamamoto K, Ikeda U et al (1998) Mitral regurgitation reduces the risk of stroke in patients with non rheumatic atrial fibrillation. Am Heart J 136:528–532PubMedCrossRefGoogle Scholar
  20. 20.
    Aronow WS, Gutstein H, Hsieh FY (1989) Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. Am J Cardiol 63:366–367PubMedCrossRefGoogle Scholar
  21. 21.
    Aronow WS, Ahn C, Kronzon I (1998) Risk factors for new thromboembolic stroke in patients ≤62 years of age with chronic atrial fibrillation. Am J Cardiol 82:119–121PubMedCrossRefGoogle Scholar
  22. 22.
    Fang MC, Go AS, Chang Y, The ATRIA Study Group et al (2008) Comparison of risk stratification schemes to predict thromboembolism in people with non-valvular atrial fibrillation. J Am Coll Cardiol 51:810–815PubMedCrossRefGoogle Scholar
  23. 23.
    Baruch L, Gage BF, Horrow J et al (2007) Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified? Stroke 38:2459–2463PubMedCrossRefGoogle Scholar
  24. 24.
    van Staa TP, Setakis E, Di Tanna GL et al (2011) A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. J Thromb Haemost 9:39–48PubMedCrossRefGoogle Scholar
  25. 25.
    Lip GYH, Lim HS (2007) Atrial fibrillation and stroke prevention. Lancet Neurol 6:981–993PubMedCrossRefGoogle Scholar
  26. 26.
    Atrial Fibrillation Investigators (1994) Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 154:1449–1457CrossRefGoogle Scholar
  27. 27.
    Stroke Prevention in Atrial Fibrillation Investigators (1995) Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation: the Stroke Prevention in Atrial Fibrillation Study. J Stroke Cerebrovasc Disord 5:147–157CrossRefGoogle Scholar
  28. 28.
    Stroke Prevention in Atrial Fibrillation investigators (1996) Adjusted dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomized clinical trial. Lancet 348:633–638CrossRefGoogle Scholar
  29. 29.
    Singer DE, Albers G, Dalen J et al (2004) Antithrombotic therapy in atrial fibrillation. The Seventh ACCP Conference of Antithrombotic and Thrombolytic Therapy. Chest 126:429–456CrossRefGoogle Scholar
  30. 30.
    National Collaborating Centre for Chronic Conditions Atrial Fibrillation (2006) National Clinical Guideline for Management in Primary and Secondary Care. London Royal College of PhysiciansGoogle Scholar
  31. 31.
    Singer DE, Albers GW, Dalen JE et al (2008) Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133:546S–592SPubMedCrossRefGoogle Scholar
  32. 32.
    Fuster V, Ryden LE, Cannom DS et al (2006) Task Force on Practice Guidelines, American College of Cardiology/American Heart Association; Committee for Practice Guidelines, European Society of Cardiology; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J 27:1979–2030PubMedCrossRefGoogle Scholar
  33. 33.
    Gage BF, Waterman AD, Shannon W et al (2001) Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 285:2864–2870CrossRefGoogle Scholar
  34. 34.
    Kim YD, Cha MJ, Kim J et al (2011) Increases in cerebral atherosclerosis according to CHADS2 scores in patients with stroke with nonvalvular atrial fibrillation. Stroke 42:930–934PubMedCrossRefGoogle Scholar
  35. 35.
    Ruiz-Nodar JM, Marín F, Manzano-Fernández S et al (2011) An evaluation of the CHADS2 stroke risk score in patients with atrial fibrillation who undergo percutaneous coronary revascularization. Chest 139:1402–1409PubMedCrossRefGoogle Scholar
  36. 36.
    Keogh C, Wallace E, Dillon C et al (2011) Validation of the CHADS2 clinical prediction rule to predict ischaemic stroke. A systematic review and meta-analysis. Thromb Haemost 106:528–538PubMedCrossRefGoogle Scholar
  37. 37.
    Karthikeyan G, Eikelboom JW (2010) The CHADS2 score for stroke risk stratification in atrial fibrillation: friend or foe? Thromb Haemost 104:45–48PubMedCrossRefGoogle Scholar
  38. 38.
    Lip GY, Nieuwlaat R, Pisters R et al (2010) 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 137:263–272PubMedCrossRefGoogle Scholar
  39. 39.
    Oelsen JB, Lip GY, Hansen ML et al (2011) Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 342:124CrossRefGoogle Scholar
  40. 40.
    Olesen JB, Fauchier L, Lane DA et al (2012) Risk factors for stroke and thromboembolism in relation to age among patients with atrial fibrillation. The Loire Valley Atrial Fibrillation Project. Chest 141:147–153PubMedCrossRefGoogle Scholar
  41. 41.
    Poli D, Antonucci E, Grifoni E et al (2009) Stroke risk in atrial fibrillation patients on warfarin. Predictive ability of risk stratification schemes for primary and secondary prevention. Thromb Haemost 101:367–372PubMedGoogle Scholar
  42. 42.
    The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC) (2010) Guidelines for the management of atrial fibrillation. Eur Heart J 31:2369–2429CrossRefGoogle Scholar
  43. 43.
    Sato H, Ishikawa K, Kitabatake A, Japan Atrial Fibrillation Stroke Trial Group et al (2006) Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke 37:447–451PubMedCrossRefGoogle Scholar
  44. 44.
    Lip GY, Frison L, Halperin JL et al (2010) Identifying patients at high risk for stroke despite anticoagulation. A comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. Stroke 41:2731–2738PubMedCrossRefGoogle Scholar
  45. 45.
    Poli D, Lip GYH, Antonucci E et al (2011) Stroke risk stratification in a “real-world” elderly anticoagulated atrial fibrillation population. J Cardiovasc Electrophysiol 22:25–30PubMedCrossRefGoogle Scholar
  46. 46.
    You JJ, Singer DE, Howard PA et al (2012) Antithrombotic Therapy for Atrial Fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based Clinical Practice Guidelines. Chest 141:531–575CrossRefGoogle Scholar
  47. 47.
    Ridker PM, Cushman M, Stampfer MJ et al (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979PubMedCrossRefGoogle Scholar
  48. 48.
    Rost NS, Wolf PA, Kase CS et al (2001) Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham Study. Stroke 32:2575–2579PubMedCrossRefGoogle Scholar
  49. 49.
    Thambidorai SK, Parakh K, Martin DO et al (2004) Relation of C-reactive protein correlates with risk of thromboembolism in patients with atrial fibrillation. Am J Cardiol 94:805–807PubMedCrossRefGoogle Scholar
  50. 50.
    Conway DS, Buggins P, Hughes E et al (2004) Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J 148:462–466PubMedCrossRefGoogle Scholar
  51. 51.
    Pengo V, Filippi B, Biasiolo A et al (2002) Association of the G20210A mutation in the factor II gene with systemic embolism in nonvalvular atrial fibrillation. Am J Cardiol 90:545–547PubMedCrossRefGoogle Scholar
  52. 52.
    Poli D, Antonucci E, Cecchi E et al (2005) Culprit factors for the failure of well conducted warfarin therapy to prevent ischemic events in patients with atrial fibrillation: the role of homocysteine. Stroke 36:2159–2163PubMedCrossRefGoogle Scholar
  53. 53.
    Glotzer TV, Daoud EG, Wyse DG et al (2009) The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol 2:474–480PubMedCrossRefGoogle Scholar
  54. 54.
    Boriani G, Botto GL, Padeletti L et al (2011) Improving stroke risk stratification using the CHADS2 and CHA2DS2-VASc risk scores in patients with paroxysmal atrial fibrillation by continuous arrhythmia burden monitoring. Stroke 42:1768–1770PubMedCrossRefGoogle Scholar
  55. 55.
    Lee M, Saver JL, Liao HW et al (2010) Low glomerular filtration rate and risk of stroke: meta-analysis. BMJ 341:4249CrossRefGoogle Scholar
  56. 56.
    Watanabe H, Watanabe T, Sasaki S et al (2009) Close bidirectional relationship between chronic kidney disease and atrial fibrillation: the Niigata preventive medicine study. Am Heart J 158:629–636PubMedCrossRefGoogle Scholar
  57. 57.
    Garcia DA, Lopes RD, Hylek EM (2010) New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb Haemost 104:1099–1105PubMedCrossRefGoogle Scholar
  58. 58.
    Lip GYH, Andreotti F, Fauchier L et al (2011) Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis. Europace 13:723–746PubMedCrossRefGoogle Scholar
  59. 59.
    Lip GY, Zarifis J, Watson RD et al (1996) Physician variation in the management of patients with atrial fibrillation. Heart 75:200–205PubMedCrossRefGoogle Scholar
  60. 60.
    Pisters R, Lane DA, Nieuwlaat R et al (2010) A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 138:1093–1100PubMedCrossRefGoogle Scholar
  61. 61.
    Gage BF, Yan Y, Milligan PE et al (2006) Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 151:713–719PubMedCrossRefGoogle Scholar
  62. 62.
    Holmes DR, Reddy VY, Turi ZG, PROTECT AF Investigators et al (2009) Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 374:534–542PubMedCrossRefGoogle Scholar
  63. 63.
    Laupacis A, Albers G, Dalen J et al (1998) Antithrombotic therapy in atrial fibrillation. Chest 114:579–589CrossRefGoogle Scholar
  64. 64.
    Laupacis A, Boysen G, Connolly S et al (1994) Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Int Med 154:1449–1457CrossRefGoogle Scholar
  65. 65.
    Lip GY, Lowe GD (1996) ABC of atrial fibrillation. Anti-thrombotic treatment for atrial fibrillation. Br Med J 312:45–49CrossRefGoogle Scholar
  66. 66.
    Van Walraven C, Hart RG, Wells GA et al (2003) A clinical prediction rule to identify patients with atrial fibrillation and a low risk for stroke while taking aspirin. Arch Int Med 163:936–943CrossRefGoogle Scholar
  67. 67.
    The Stroke Prevention in Atrial Fibrillation Investigators Predictors of thromboembolism in atrial fibrillation (1992) Predictors of thromboembolism in atrial fibrillation:I. Clinical features of patients at risk. Ann Int Med 116:1–5Google Scholar

Copyright information

© SIMI 2012

Authors and Affiliations

  • Domenico Prisco
    • 1
    • 2
  • Caterina Cenci
    • 1
  • Elena Silvestri
    • 1
    • 2
  • Giacomo Emmi
    • 2
  • Tommaso Barnini
    • 2
  • Carlo Tamburini
    • 2
  1. 1.Department of Medical and Surgical Critical CareUniversity of FlorenceFlorenceItaly
  2. 2.SOD Patologia Medica, DAI BiomedicinaAOU CareggiFlorenceItaly

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