Cardiac Troponin T Elevation After
Coronary Artery Bypass Grafting Is
Associated With Increased
One-Year Mortality
Sekar Kathiresan, MD, Stephen J. Servoss, MD, John B. Newell, AB, Dawn Trani,
Thomas E. MacGillivray, MD, Kent Lewandrowski, MD,
Elizabeth Lee-Lewandrowski, PhD, MPH, and James L. Januzzi, Jr., MD
The results of the present study extend the value of
assessing troponin T for the prediction of mortality rate
1 year after coronary artery bypass grafting; this study
supports previous work that demonstrated the value of
M yocardial necrosis, as demonstrated by cardiac
biomarker release, occurs almost universally
around the time of coronary artery bypass grafting
(CABG).1,2 Multiple mechanisms may cause myocar-
dial damage during CABG, including direct trauma
from surgical manipulation and myocardial ischemia
due to inadequacies in cardioprotection, coronary ar-
tery thrombosis, and acute loss of bypass grafts.3
Because some of these causes are unavoidable, it is
critical to determine the appropriate threshold of bi-
omarker release after CABG associated with wors-
ened in-hospital and longer-term prognoses. With re-
spect to in-hospital adverse events after CABG, we
previously reported that an increased level of troponin
T has greater discriminatory ability than the isoen-
zyme creatine kinase-MB (CK-MB).4 However, the
relation between increased concentrations of troponin
T after CABG and longer term adverse clinical out-
comes remains unknown. We determined whether in-
creased levels of troponin T after CABG are associ-
ated with increased mortality rates after 1 year.
METHODS
All study procedures were approved by the hospital
institutional review board. One hundred thirty-six
consecutive patients who underwent CABG without
concomitant valve surgery at the Massachusetts Gen-
eral Hospital (Boston, Massachusetts) between Octo-
ber and November 2000 were enrolled. Patients were
identified on admission to the cardiac surgical inten-
sive care unit, and a study coordinator blinded to the
results of cardiac markers collected clinical variables
in a prospective manner by chart review. Clinical
From the Cardiology Division, the Cardiac Surgery Division, and the
Clinical Chemistry Laboratories, Massachusetts General Hospital, Bos-
ton, Massachusetts. This study was supported in part by an unrestricted
grant from Roche Diagnostics Corporation, Indianapolis, Indiana.
Manuscript received December 9, 2003; revised manuscript received
and accepted June 18, 2004.
Address for reprints: James L. Januzzi, Jr., MD, Cardiology Divi-
sion, Massachusetts General Hospital, Bulfinch 019, 55 Fruit Street,
Boston, Massachusetts 02114. E-mail: jjanuzzi@partners.org.
©2004 by Excerpta Medica, Inc. All rights reserved.
The American Journal of Cardiology Vol. 94 October 1, 2004
ANP,
postoperative assessment of troponin T for the prediction
of in-hospital adverse outcome after coronary artery
bypass grafting. 䊚2004 by Excerpta Medica, Inc.
(Am J Cardiol 2004;94:879 – 881)
factors collected included demographics, medical his-
tory, previous medication use, cardiac catheterization
results, presenting cardiac syndrome, and, when avail-
able, preoperative levels of troponin T. Systemic hy-
pertension and hypercholesterolemia were defined as
treatment with antihypertensive and lipid-lowering
medications, respectively. A history of coronary artery
disease was defined as previous stable angina, myo-
cardial infarction, or percutaneous coronary interven-
tion. Information regarding surgical procedures, in-
cluding number of bypass grafts, bypass/ischemic
times, and intraoperative complications, was noted.
Blood samples were drawn on arrival to the surgi-
cal intensive care unit (“postop”) at 6 to 8 hours and
18 to 24 hours after surgery and were assayed for
CK-MB mass and troponin T (Elecsys CK-MB STAT
and Troponin T STAT Immunoassays, Roche Diag-
nostics Corporation, Indianapolis, Indiana) on an
Elecsys 1010 platform (Roche Diagnostics Corpora-
tion).
The results of troponin T were obtained in a
blinded fashion by the study investigators; however,
the physicians caring for the patients were not blinded
to the CK-MB results because this marker is routinely
measured at our institution after cardiac surgery. Data
on postoperative outcomes were assessed. In-hospital
end points are outlined in a previous report.4 Vital
status at 1 year from hospital discharge was obtained
by a telephone interview of the referring primary care
physician or cardiologist.
Cardiac marker levels were log-transformed, and
comparisons of mean levels of cardiac marker be-
tween patients alive and those dead at 1 year were
made by multivariate analysis of variance with post
hoc Bonferroni’s corrected pairwise comparisons.
These tests were conducted with SYSTAT 10 (SPSS,
Inc. Chicago, Illinois). To analyze the prognostic in-
fluence of an increased level of troponin T, marker
levels were log-transformed and divided into quin-
tiles. Multivariable analysis using stepwise Cox’s pro-
portional hazards regression was performed to identify
independent covariates of event-free survival rate at 1
0002-9149/04/$–see front matter 879
doi:10.1016/j.amjcard.2004.06.022
 TABLE 1 Baseline Characteristics of the Subjects (n ⫽ 136) TABLE 2 Cardiac Marker Levels at Different Time Points After
CABG, Expressed as a Function of Mortality (n ⫽ 7) Versus
Age (yrs) 67 ⫾ 12 No Mortality (n ⫽ 129)
Men 77%
Medical history Death No Death
Diabetes 34% Marker and Timing (n ⫽ 7) (n ⫽ 129) p Value
Systemic hypertension 75%
Hypercholesterolemia 86% Troponin T
Tobacco use 42% Postop 6.4 (1.3–10.7) 1.0 (0.60–1.5) 0.07
Coronary artery disease 67% 6–12 h 7.4 (2.0–9.8) 1.3 (0.76–1.9) 0.02
Previous acute myocardial infarction 35% 18–24 h 7.8 (3.6–16.1) 0.76 (0.42–1.26) 0.02
Valve disease 5% CK-MB
Congestive heart failure 15% Postop 79.6 (35–109) 42.2 (29–85) 0.50
Percutaneous coronary intervention 18% 6–12 h 77.9 (33–97) 47.2 (28–80) 0.40
Extent of coronary artery disease, vessels 2.6 ⫾ 0.7 18–24 h 46.0 (21–117) 21.6 (13–42) 0.12
Extent of coronary artery disease Data are presented as median (interquartile range) (in nanograms per
1 vessel 10% milliliter).
2 vessels 17%
3 vessels or left main artery 73%
Ejection fraction (%) 42 ⫾ 23
Presenting syndrome
Congestive heart failure 13%
in patients stratified by vital status are presented in
Unstable angina pectoris 39% Table 2.
Stable angina pectoris 18% In the patients who died during the 1-year follow-
Non–ST-segment elevation myocardial infarction 20% up, the immediate postop, 6- to 12-hour, and 18- to
ST-segment elevation myocardial infarction 9%
Cardiac arrest 2%
24-hour median (and interquartile ranges) levels of
Previous medication use troponin T were 6.4 ng/ml (1.3 to 10.7), 7.4 ng/ml (2.0
Aspirin 94% to 9.8), and 7.8 ng/ml (3.6 to 16.1), respectively,
␤ blocker 83% which were significantly higher than comparably
Statins 76% timed levels of troponin T in patients who survived:
Nitrates 69%
Heparin 39%
1.0 ng/ml (0.6 to 1.5), 1.3 ng/ml (0.76 to 1.9), and 0.76
Surgical details ng/ml (0.42 to 1.26), respectively. The differences in
Repeat surgery 8% levels of troponin T between patients who were alive
No. of vessels grafted 3.4 ⫾ 1.3 and those who were dead at 1 year were significant for
Data are presented as mean ⫾ SD or number (percentage). the 6- to 12- and 18- to 24-hour specimens (each p
⬍0.05). Identically timed CK-MB values did not dif-
fer significantly between patients who were alive and
those who were dead at 1 year.
year. The primary dependent variable was 1-year mor- Multivariable analysis suggested that an 18- to
tality rate. The primary independent variable was an 24-hour postoperative level of troponin T in the high-
increased level of troponin T in any of the 3 postop- est log quintile (ⱖ1.58 ng/ml) was the strongest pre-
erative samples. Other independent variables included dictor of a 1-year mortality rate (odds ratio 5.45, 95%
the results of CK-MB testing, demographics, present- confidence interval 4.5 to 232.5, p ⬍0.0001), whereas
ing syndrome, cardiovascular risk factors, medication CK-MB results added no independent information.
use, extent of CAD, ejection fraction, repeat CABG, Survival curves for patients with high levels (top
type of cardioplegia, and other clinical factors, as quintile in the 18- to 24-hour specimen) and low levels
described previously.4 Cox’s regression analysis used (quintiles 2 through 5 in the 18- to 24-hour specimen) of
forward stepwise regression. An independent variable troponin T are displayed in Figure 1. Most patients who
was removed from the model only when its corre- died were in the highest log quintile of troponin T.
sponding regression parameter was not significantly
different from 0 at p ⬎0.1. Cox’s regression analysis DISCUSSION
was conducted with BMDP 7 (BMDP Statistical Soft- In the present study, we describe for the first time a
ware, Inc., Saugus, Massachusetts). For all significant correlation between levels of troponin T after CABG and
covariates of event-free survival rate, 95% confidence longer term adverse outcomes. In univariate and multi-
intervals were computed. All p values were 2-sided, variable modeling, the level of troponin T after CABG
and a p value ⬍0.05 was considered statistically sig- was the single best predictor of mortality rate at 1 year
nificant. and was superior to CK-MB for this indication.
The clinical significance of release of cardiac bi-
RESULTS omarkers after cardiac procedures has been a subject
Of 136 patients, 2 (1.5%) were lost to follow-up. of controversy and has generally been defined by
The 2 patients lost to follow-up were imputed to be relating marker levels to clinical outcomes.5– 8 Two
alive and free of complications. Baseline demograph- recent studies have established a relation between
ics of the study patients are listed in Table 1 and are CK-MB after CABG and worsened medium-term out-
comparable to those in previous studies on outcomes comes.9,10 However, the sensitivity and specificity of
after CABG. Seven patients (5%) died during the CK-MB in the 2 analyses were limited. In previous
1-year follow-up. The mean levels of cardiac markers studies, troponin I was found to be superior to CK-MB

880 THE AMERICAN JOURNAL OF CARDIOLOGY姞 VOL. 94 OCTOBER 1, 2004


FIGURE 1. Kaplan-Meier survival curves show that patients with
low levels of troponin T (solid line) have a lower risk of mortality
during the first year after CABG than do those with troponin T
levels >1.58 ng/ml at 18 to 24 hours after CABG (dashed line).
for prediction of in-hospital complications after car-
diac surgery.11,12 Fellahi et al13 studied the value of
testing troponin I to predict long-term outcomes
among 202 patients who underwent elective CABG
and reported that a troponin I level ⱖ13 ng/ml on the
first day after surgery was associated with a 7.3-fold
increased risk of death within 2 years after CABG.
Our results are remarkably similar for testing of tro-
ponin T and suggest a superiority of troponin T over
CK-MB for predicting longer term risk, in addition to
short-term prognostication of impending complica-
tions after surgery.
Our results suggest that routine biomarker screen-
ing with troponin T after CABG is justified. Patients
with increased levels of troponin T after CABG may
merit more intensive monitoring during the index hos-
pitalization and increased scrutiny for ischemic com-
plications after discharge. Further, strategies to pre-
vent perioperative myocardial necrosis may be
optimally tested with the evaluation of troponin T
levels after surgery. For example, we previously re-
ported that off-pump CABG may offer greater cardio-
protection as shown by the smaller amount of troponin
release with off-pump compared with conventional
CABG.14 If these long-term outcome results are con-
firmed in additional prospective studies, the biochem-
ical definition of myocardial infarction after CABG
should moved to the troponin standard.
Our study has limitations. First, the 1-year fol-
low-up by telephone interview of referring physicians
may have missed clinical outcomes. However, vital
status was confirmed in all but 2 patients, and the
addition of additional clinical events would most
likely have improved the prognostic value of testing
for serum troponin T. Second, although our study is
the first to assess results of troponin T and 1-year
mortality rates after CABG, a larger sample would
encourage greater confidence in the specific troponin
T prognostic threshold that identifies patients as being
at high risk for impending complications. A recent
study that examined troponin T in relation to in-
hospital myocardial infarction after CABG found a
troponin T level ⬎3.4 ng/ml to have the greatest
diagnostic accuracy for the prediction of early com-
plications.15 Third, not all patients in the study had an
assessment of preoperative levels of troponin T.
1. Bonnefoy E, Filley S, Kirkorian G, Guidollet J, Roriz R, Robin J, Touboul P.
Troponin I, troponin T, or creatine kinase-MB to detect perioperative myocardial
damage after coronary artery bypass surgery. Chest 1998;114:482– 486.
2. Jacquet L, Noirhomme P, El Khoury G, Goenen M, Philippe M, Col J, Dion
R. Cardiac troponin I as an early marker of myocardial damage after coronary
bypass surgery. Eur J Cardiothorac Surg 1998;13:378 –384.
3. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction rede-
fined—a consensus document of the Joint European Society of Cardiology/
American College of Cardiology Committee for the redefinition of myocardial
infarction. J Am Coll Cardiol 2000;36:959 –969.
4. Januzzi JL, Lewandrowski K, MacGillivray TE, Newell JB, Kathiresan S,
Servoss SJ, Lee-Lewandrowski E. A comparison of cardiac troponin T and
creatine kinase-MB for patient evaluation after cardiac surgery. J Am Coll
Cardiol 2002;39:1518 –1523.
5. Califf RM, Abdelmeguid AE, Kuntz RE, Popma JJ, Davidson CJ, Cohen EA,
Kleiman NS, Mahaffey KW, Topol EJ, Pepine CJ, et al. Myonecrosis after
revascularization procedures. J Am Coll Cardiol 1998;31:241–251.
6. Harrington RA, Lincoff AM, Califf RM, Holmes DR Jr, Berdan LG,
O’Hanesian MA, Keeler GP, Garratt KN, Ohman EM, Mark DB, et al. Charac-
teristics and consequences of myocardial infarction after percutaneous coronary
intervention: insights from the Coronary Angioplasty Versus Excisional Atherec-
tomy Trial (CAVEAT). J Am Coll Cardiol 1995;25:1693–1699.
7. Tardiff BE, Califf RM, Tcheng JE, Lincoff AM, Sigmon KN, Harrington RA,
Mahaffey KW, Ohman EM, Teirstein PS, Blankenship JC, et al. Clinical out-
comes after detection of elevated cardiac enzymes in patients undergoing percu-
taneous intervention. IMPACT-II Investigators. Integrilin (eptifibatide) to Mini-
mize Platelet Aggregation and Coronary Thrombosis-II. J Am Coll Cardiol
1999;33:88 –96.
8. Kugelmass AD, Cohen DJ, Moscucci M, Piana RN, Senerchia C, Kuntz RE,
Baim DS. Elevation of the creatine kinase myocardial isoform following other-
wise successful directional coronary atherectomy and stenting. Am J Cardiol
1994;74:748 –754.
9. Klatte K, Chaitman BR, Theroux P, Gavard JA, Stocke K, Boyce S, Bartels C,
Keller B, Jessel A. Increased mortality after coronary artery bypass graft surgery
is associated with increased levels of postoperative creatine kinase-myocardial
band isoenzyme release: results from the GUARDIAN trial. J Am Coll Cardiol
2001;38:1070 –1077.
10. Costa MA, Carere RG, Lichtenstein SV, Foley DP, de Valk V, Lindenboom
W, Roose PC, van Geldorp TR, Macaya C, Castanon JL, et al. Incidence,
predictors, and significance of abnormal cardiac enzyme rise in patients treated
with bypass surgery in the arterial revascularization therapies study (ARTS).
Circulation 2001;104:2689 –2693.
11. Benoit MO, Paris M, Silleran J, Fiemeyer A, Moatti N. Cardiac troponin I: its
contribution to the diagnosis of perioperative myocardial infarction and various
complications of cardiac surgery. Crit Care Med 2001;29:1880 –1886.
12. Eigel P, van Ingen G, Wagenpfeil S. Predictive value of perioperative cardiac
troponin I for adverse outcome in coronary artery bypass surgery. Eur J Cardio-
thorac Surg 2001;20:544 –549.
13. Fellahi JL, Gue X, Richomme X, Monier E, Guillou L, Riou B. Short- and
long-term prognostic value of postoperative cardiac troponin I concentration in
patients undergoing coronary artery bypass grafting. Anesthesiology 2003;99:
270 –274.
14. Kathiresan S, MacGillivray TE, Lewandrowski K, Servoss SJ, Lewandrowski
E, Januzzi JL Jr. Off-pump coronary bypass grafting is associated with less
myocardial injury than coronary bypass surgery with cardiopulmonary bypass.
Heart Surg Forum 2003;6:E174 –E178.
15. Carrier M, Pellerin M, Perrault LP, Solymoss BC, Pelletier LC. Troponin
levels in patients with myocardial infarction after coronary artery bypass grafting.
Ann Thorac Surg 2000;69:435– 440.
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