Predicting Adverse Events beyond Stroke and Bleeding with the ABC-Stroke and ABC-Bleeding Scores in Patients with Atrial Fibrillation: The Murcia AF ProjectFunding This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, through the Instituto de Salud Carlos III after independent peer review (research grant: PI17/01375 cofinanced by the European Regional Development Fund) and group CB16/11/00385 from CIBERCV.
Background The ABC (age, biomarkers, and clinical history)-stroke and ABC-bleeding are biomarker-based scores proposed to predict stroke and bleeding, but non-specificity of biomarkers is common, predicting different clinical events at the same time. We assessed the predictive performance of the ABC-stroke and ABC-bleeding scores, for outcomes beyond ischemic stroke and major bleeding, in a cohort of atrial fibrillation (AF) patients.
Methods We included AF patients stable on vitamin K antagonists for 6 months. The ABC-stroke and ABC-bleeding were calculated and the predictive values for myocardial infarction (MI), acute heart failure (HF), a composite of cardiovascular events, and all-cause deaths were compared.
Results We included 1,044 patients (49.2% male; median age 76 [71–81] years). During 6.5 (4.3–7.9) years, there were 58 (5.6%) MIs, 98 (9.4%) acute HFs, 167 (16%) cardiovascular events, and 418 (40%) all-cause deaths. There were no differences in mean ABC-stroke and ABC-bleeding scores in patients with/without MI (p = 0.367 and p = 0.286, respectively); both scores were higher in patients with acute HF, cardiovascular events, or death (all p < 0.05). Predictive performances for the ABC-stroke and ABC-bleeding scores were similar, ranging from “poor” for MI (c-indexes ∼0.54), “moderate” for acute HF and cardiovascular events (c-indexes ∼0.60 and ∼0.64, respectively), and “good” for all-cause mortality (c-indexes > 0.70). Clinical usefulness whether assessed by ABC-stroke or ABC-bleeding was similar for various primary endpoints.
Conclusion In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict “sick” patients or poor prognosis overall.
Keywordsatrial fibrillation - biomarkers - mortality - myocardial infarction - heart failure - ABC-stroke - ABC-bleeding - risk prediction
A.C.-C. interpreted the analyzed data and drafted the manuscript; J.M.R.-C. acquired the data, performed statistical analyses, and drafted the manuscript; F.M. and G.Y.H.L. conceived and designed the research, drafted the manuscript, and made critical revision; V.V. drafted the manuscript and made critical revision; V.R. conceived and designed the research, acquired the data, drafted the manuscript, and made critical revision. All authors gave final approval of the manuscript.
* Both authors contributed equally.
** Drs. Roldán and Lip are joint senior authors.
Note: The review process for this article was fully handled by Christian Weber, Editor-in-Chief.
Received: 06 April 2020
Accepted: 24 April 2020
07 June 2020 (online)
Georg Thieme Verlag KG
Stuttgart · New York
- 1 Andersson T, Magnuson A, Bryngelsson I-L. , et al. All-cause mortality in 272,186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study. Eur Heart J 2013; 34 (14) 1061-1067
- 2 January CT, Wann LS, Calkins H. , et al. 2019 AHA/ACC/HRS focused update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
- 3 Kirchhof P, Benussi S, Kotecha D. , et al; ESC Scientific Document Group. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37 (38) 2893-2962
- 4 Lip GYH, Banerjee A, Boriani G. , et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018; 154 (05) 1121-1201
- 5 Violi F, Soliman EZ, Pignatelli P, Pastori D. Atrial fibrillation and myocardial infarction: a systematic review and appraisal of pathophysiologic mechanisms. J Am Heart Assoc 2016; 5 (05) e003347
- 6 Gorenek Chair B, Halvorsen S, Kudaiberdieva G. , et al. Atrial fibrillation in acute heart failure: a position statement from the Acute Cardiovascular Care Association and European Heart Rhythm Association of the European Society of Cardiology. Eur Heart J Acute Cardiovasc Care 2020; DOI: 10.1177/2048872619894255.
- 7 Esteve-Pastor MA, Roldán V, Rivera-Caravaca JM, Ramírez-Macías I, Lip GYH, Marín F. The use of biomarkers in clinical management guidelines: a critical appraisal. Thromb Haemost 2019; 119 (12) 1901-1919
- 8 Borre ED, Goode A, Raitz G. , et al. Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review. Thromb Haemost 2018; 118 (12) 2171-2187
- 9 Hijazi Z, Lindbäck J, Alexander JH. , et al; ARISTOTLE and STABILITY Investigators. 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
- 10 Hijazi Z, Oldgren J, Lindbäck J. , et al; ARISTOTLE and RE-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet 2016; 387 (10035): 2302-2311
- 11 Rivera-Caravaca JM, Esteve-Pastor MA. Heart failure and cardiac events: is a consecutive measurement of biomarkers a simple and practical approach?. Thromb Haemost 2019; 119 (12) 1891-1893
- 12 Rivera-Caravaca JM, Marín F, Vilchez JA. , et al. Refining stroke and bleeding prediction in atrial fibrillation by adding consecutive biomarkers to clinical risk scores. Stroke 2019; 50 (06) 1372-1379
- 13 Thygesen K, Alpert JS, Jaffe AS. , et al; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018; 72 (18) 2231-2264
- 14 Kimenai DM, Henry RMA, van der Kallen CJH. , et al. Direct comparison of clinical decision limits for cardiac troponin T and I. Heart 2016; 102 (08) 610-616
- 15 Lyngbakken MN, Myhre PL, Røsjø H, Omland T. Novel biomarkers of cardiovascular disease: applications in clinical practice. Crit Rev Clin Lab Sci 2019; 56 (01) 33-60
- 16 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44 (03) 837-845
- 17 Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26 (06) 565-574
- 18 Lip GY, Lane D, Van Walraven C, Hart RG. Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation. Stroke 2006; 37 (09) 2294-2300
- 19 Daubert MA, Jeremias A. The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manag 2010; 6: 691-699
- 20 Aimo A, Januzzi Jr JL, Vergaro G. , et al. Prognostic value of high-sensitivity troponin T in chronic heart failure: an individual patient data meta-analysis. Circulation 2018; 137 (03) 286-297
- 21 Agewall S, Giannitsis E, Jernberg T, Katus H. Troponin elevation in coronary vs. non-coronary disease. Eur Heart J 2011; 32 (04) 404-411
- 22 Kelley WE, Januzzi JL, Christenson RH. Increases of cardiac troponin in conditions other than acute coronary syndrome and heart failure. Clin Chem 2009; 55 (12) 2098-2112
- 23 Lan NSR, Bell DA, McCaul KA. , et al. High-sensitivity cardiac troponin i improves cardiovascular risk prediction in older men: HIMS (The Health in Men Study). J Am Heart Assoc 2019; 8 (05) e011818
- 24 Maalouf R, Bailey S. A review on B-type natriuretic peptide monitoring: assays and biosensors. Heart Fail Rev 2016; 21 (05) 567-578
- 25 Courand P-Y, Harbaoui B, Bècle C, Mouly-Bertin C, Lantelme P. Plasma NT-proBNP mirrors the deleterious cardiovascular and renal continuum in hypertension. Eur J Prev Cardiol 2017; 24 (05) 452-459
- 26 Federico C. Natriuretic peptide system and cardiovascular disease. Heart Views 2010; 11 (01) 10-15
- 27 Maries L, Manitiu I. Diagnostic and prognostic values of B-type natriuretic peptides (BNP) and N-terminal fragment brain natriuretic peptides (NT-pro-BNP). Cardiovasc J Afr 2013; 24 (07) 286-289
- 28 Grote Beverborg N, van Veldhuisen DJ, van der Meer P. Anemia in heart failure: still relevant?. JACC Heart Fail 2018; 6 (03) 201-208
- 29 Iversen PO, Woldbaek PR, Tønnessen T, Christensen G. Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J Physiol Regul Integr Comp Physiol 2002; 282 (01) R166-R172
- 30 Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev 2002; 16 (02) 87-96
- 31 Goddard AF, James MW, McIntyre AS, Scott BB. ; British Society of Gastroenterology. Guidelines for the management of iron deficiency anaemia. Gut 2011; 60 (10) 1309-1316
- 32 Cases A, Egocheaga MI, Tranche S. , et al. Anemia of chronic kidney disease: protocol of study, management and referral to nephrology. Nefrologia 2018; 38 (01) 8-12
- 33 Sato Y, Fujimoto S, Konta T. , et al. Anemia as a risk factor for all-cause mortality: obscure synergic effect of chronic kidney disease. Clin Exp Nephrol 2018; 22 (02) 388-394
- 34 Sankaran VG, Weiss MJ. Anemia: progress in molecular mechanisms and therapies. Nat Med 2015; 21 (03) 221-230
- 35 Kohne E. Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int 2011; 108 (31-32): 532-540
- 36 Ajmal A, Gessert CE, Johnson BP, Renier CM, Palcher JA. Effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on hemoglobin levels. BMC Res Notes 2013; 6: 443
- 37 Lee G, Choi S, Kim K, Yun J-M, Son JS, Jeong S-M. , et al. Association between changes in hemoglobin concentration and cardiovascular risks and all-cause mortality among young women. J Am Heart Assoc 2018; 7 (16) e008147-e
- 38 Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol Dial Transplant 2000; 15 (Suppl. 03) 14-18
- 39 Weiss HJ, Lages B, Hoffmann T, Turitto VT. Correction of the platelet adhesion defect in delta-storage pool deficiency at elevated hematocrit--possible role of adenosine diphosphate. Blood 1996; 87 (10) 4214-4222
- 40 Anil T. Red blood cells and relation to thrombosis. In: Gemert AWMMK-v, ed. Transfusion Medicine and Scientific Developments. IntechOpen; : July 5th 2017; 2017
- 41 Udani SM, Koyner JL. The effects of heart failure on renal function. Cardiol Clin 2010; 28 (03) 453-465
- 42 Warren B, Rebholz CM, Sang Y. , et al. Diabetes and trajectories of estimated glomerular filtration rate: a prospective cohort analysis of the atherosclerosis risk in communities study. Diabetes Care 2018; 41 (08) 1646-1653
- 43 Berg UB. Long-term followup of renal morphology and function in children with recurrent pyelonephritis. J Urol 1992; 148 (5 Pt 2): 1715-1720
- 44 Lee JH, Kwon H, Park YW, Cho I-C, Min SK. Relationship of estimated glomerular filtration rate with lower urinary tract symptoms/benign prostatic hyperplasia measures in middle-aged men with moderate to severe lower urinary tract symptoms. Urology 2013; 82 (06) 1381-1385
- 45 Gillen DL, Worcester EM, Coe FL. Decreased renal function among adults with a history of nephrolithiasis: a study of NHANES III. Kidney Int 2005; 67 (02) 685-690
- 46 Yap E, Salifu M, Ahmad T, Sanusi A, Joseph A, Mallappallil M. Atypical causes of urinary tract obstruction. Case Rep Nephrol 2019; 2019: 4903693
- 47 Rivera-Caravaca JM, Roldán V, Esteve-Pastor MA. , et al. Long-term stroke risk prediction in patients with atrial fibrillation: comparison of the ABC-stroke and CHA2DS2-VASc scores. J Am Heart Assoc 2017; 6 (07) e006490
- 48 Esteve-Pastor MA, Rivera-Caravaca JM, Roldan V. , et al. Long-term bleeding risk prediction in ‘real world’ patients with atrial fibrillation: comparison of the HAS-BLED and ABC-bleeding risk scores. The Murcia Atrial Fibrillation Project. Thromb Haemost 2017; 117 (10) 1848-1858
- 49 Proietti M, Mujovic N, Potpara TS. Optimizing stroke and bleeding risk assessment in patients with atrial fibrillation: a balance of evidence, practicality and precision. Thromb Haemost 2018; 118 (12) 2014-2017
- 50 Ban N, Siegfried CJ, Apte RS. Monitoring neurodegeneration in glaucoma: therapeutic implications. Trends Mol Med 2018; 24 (01) 7-17
- 51 Hijazi Z, Wallentin L, Siegbahn A. , et al. 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
- 52 Hijazi Z, Oldgren J, Andersson U. , et al. 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
- 53 Ruff CT, Giugliano RP, Braunwald E. , et al. Cardiovascular biomarker score and clinical outcomes in patients with atrial fibrillation: a subanalysis of the ENGAGE AF-TIMI 48 randomized clinical trial. JAMA Cardiol 2016; 1 (09) 999-1006