Comparison of Cardiac Troponins I and T Measured with High-Sensitivity Methods for Evaluation of Prognosis in Atrial Fibrillation: An ARISTOTLE Substudy Ziad Hijazi, 1,2* Agneta Siegbahn, 1,3 Ulrika Andersson, 1 Bertil Lindahl, 1,2 Christopher B. Granger, 4 John H. Alexander, 4 Dan Atar, 5 Bernard J. Gersh, 6 Michael Hanna, 7 Veli-Pekka Harjola, 8 John Horowitz, 9 Steen Husted, 10 Elaine M. Hylek, 11 Renato D. Lopes, 4 John J.V. McMurray, 12 and Lars Wallentin 1,2 BACKGROUND: Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the comple- mentary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prog- nostic value of cTnI and cTnT concentrations in pa- tients with AF. METHODS: Samples were collected. At the time of ran- domization, we analyzed cTnI and cTnT concentrations of 14 806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fi- brillation (ARISTOTLE) trial using high-sensitivity as- says. Correlations (Spearman), determinants (multivari- able linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. RESULTS: Concentrations of cTnI and cTnT were corre- lated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, 99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, 99th per- centile in 34.4%)]. Renal impairment was the most im- portant factor affecting the concentrations of both tro- ponins. cTnI increase was more associated with heart failure, vascular disease, and persistent/permanent AF, and cTnT with age, male sex, and diabetes. Over a me- dian 1.9 years of follow-up, patients with both troponins above the median had significantly higher risk for stroke/ systemic embolism [hazard ratio (HR) 1.72 (95% CI 1.31–2.27)], cardiac death [3.14 (2.35– 4.20)], and myo- cardial infarction [2.99 (1.78 –5.03)] than those with both troponins below median (all P  0.005). Interme- diate risks were observed when only 1 troponin was above the median. When combined with clinical information, each marker provided similar prognostication and had comparable c-index. CONCLUSIONS: cTnI and cTnT concentrations are mod- erately correlated and measurable in plasma of most AF patients. The risk of stroke and cardiovascular events is highest when both troponins are above median concen- trations. Each troponin provides comparable prognostic information when combined with clinical risk factors. ClinicalTrials.gov/NCT00412984 © 2014 American Association for Clinical Chemistry Atrial fibrillation (AF) 13 constitutes a major risk factor for stroke and death (1, 2 ). Measurement of cardiac tro- ponin, clinically used as a sensitive indicator of myocar- dial damage (3, 4 ), adds independent information in AF populations regarding risk of stroke, other cardiovascular events, and mortality (5). High-sensitivity troponin as- says, which enable detection of very low troponin con- centrations with high precision, have recently been dem- onstrated to allow detection of troponin in almost all patients with AF and to add independent prognostic in- formation beyond established clinical risk factors includ- ing the CHA 2 DS 2 VASc score (which assigns 1 point each for a history of congestive heart failure, hypertension, 1 Uppsala Clinical Research Center, 2 Department of Medical Sciences, Cardiology, and 3 Department of Medical Sciences, Clinical Chemistry, Uppsala University, Upp- sala, Sweden; 4 Duke University, Medical Center, Durham, NC; 5 Department of Cardiology, Oslo University Hospital and Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway; 6 Mayo Clinic College of Medicine, Rochester, MN; 7 Bristol-Myers Squibb, Princeton, NJ; 8 Division of Emergency Care, Department of Medicine, Helsinki University Central Hospital, Helsinki, Fin- land; 9 University of Adelaide, Adelaide, Australia; 10 Medical Department, Hospital Unit West, Herning/Holstbro, Denmark; 11 Boston University Medical Center, Bos- ton, MA; 12 BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, U.K. * Address correspondence to this author at: Uppsala Clinical Research Center, Uppsala University, Uppsala Science Park, SE-752 37 Uppsala, Sweden. Fax +46-(0)-18-51-55- 70; e-mail ziad.hijazi@ucr.uu.se. Received May 30, 2014; accepted October 23, 2014. Previously published online at DOI: 10.1373/clinchem.2014.226936 © 2014 American Association for Clinical Chemistry 13 Nonstandard abbreviations: AF, atrial fibrillation; cTnI, cardiac troponin I; cTnT, cardiac troponin T; ARISTOTLE, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrilla- tion; ISTH, International Society on Thrombosis and Hemostasis; UCR, Uppsala Clinical Research Center; NT-proBNP, N-terminal pro–B-type natriuretic peptide; NRI, net reclassification improve- ment; HR, hazard ratio; PEACE, Prevention of Events with Angiotensin-Converting Enzyme. Clinical Chemistry 61:2 368–378 (2015) Proteomics and Protein Markers 368 Downloaded from https://academic.oup.com/clinchem/article/61/2/368/5611381 by guest on 13 December 2021