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After approval by the appropriate institutional review
boards, a prospective cohort study was performed. Potential participants included all individuals admitted to
an Olmsted County facility between November 6,
2002, and December 31, 2007, with a cTnT level of
0.03 ng/mL or higher (to convert to g/L, multiply
by 1). These persons were prospectively identified
Mayo Clin Proc. March 2012;87(3):247-254 doi:10.1016/j.mayocp.2011.11.013 2012 Mayo Foundation for Medical Education and Research
www.mayoclinicproceedings.org
247
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presence of competing risks, standard survival predictions may substantially overestimate the absolute
risk of the event of interest,10 death was treated as a
competing risk in the analyses of recurrent ischemic
events and heart failure, adopting the Fine and Gray
model for a subdistribution function.30 Stratified
proportional hazards models were used for all outcomes, allowing time-varying associations for the
cTnT categories. Adjusted risk differences and 95%
confidence intervals (CIs) among the cTnT tertiles at
predefined periods (0-30 days, 0-180 days, 0-12
months, and 0-24 months) were estimated for each
outcome.28,29 Lastly, adjusted HRs and 95% CIs in
cTnT tertiles were estimated using standard Cox
models, and effect modification by ST-segment elevation was tested. To assess whether the association
between cTnT and outcomes persists beyond 30
days, a landmark analysis was performed between 1
month and 24 months.
Missing values did not exceed 1% in any of the
covariates used in the regression analyses, except for
ejection fraction (22%), for which missing values
were imputed and analyzed with the multiple imputation method.31 The Harrell C statistic32 was used
to assess model discrimination; this represents the
area under the receiver operating characteristic
curve and accounts for time to event (death: 0.81;
95% CI, 0.79-0.83; recurrent ischemic event: 0.63;
95% CI, 0.60-0.66; and heart failure: 0.83; 95% CI,
0.82-0.85; based on fully adjusted models). An exponential association between cTnT and outcomes
was assessed but not detected. Analyses were performed using SAS statistical software, version 8.2
(SAS Institute Inc, Cary, NC).
RESULTS
A total of 1177 participants (mean age, 68 years;
44% women) were included in the analysis. Maximal cTnT was inversely and weakly correlated with
ejection fraction (rs0.25) and age (rs0.18)
but not with body mass index. In a subsample with
a cTnT value available at day 3 (n457 [39%]), a
strong correlation (rs0.94) was found with the
maximal measured cTnT level. Baseline clinical characteristics across cTnT tertiles are given in Table 1.
Higher cTnT levels were associated with younger
age, male sex, ST-segment elevation, Q waves, lower
ejection fraction, higher estimated glomerular filtration rate, and more frequent use of reperfusion or
revascularization during hospitalization.
During a mean SD follow-up of 1610
months, among the 1177 participants, 276 deaths
(23%) occurred, 341 patients (29%) experienced recurrent ischemic event, and 326 patients (28%) experienced heart failure. After multivariate adjustment, a
clear dose-response relationship was observed between cTnT tertiles and the cumulative incidence of
249
Characteristic
Cutoff cTnT level (ng/mL)b
Lower
(n396)
Middle
(n388)
Upper
(n393)
0.22
0.23-1.17
1.18
Sociodemographic variables
Age (y), mean SD
68.415.3
70.914.5
70.015.2
64.415.2
Female
519 (44)
198 (50)
193 (50)
128 (33)
White
1126 (96)
379 (96)
372 (96)
375 (95)
Hypertension
818 (70)
295 (75)
278 (72)
245 (62)
Hyperlipidemia
729 (62)
246 (62)
240 (62)
243 (62)
709 (60)
244 (62)
218 (56)
247 (63)
28.56.5
28.36.8
28.06.2
29.26.3
233 (18)
18 (5)
56 (14)
159 (41)
Q-wave MI
588 (55)
174 (49)
156 (44)
258 (69)
Anterior MI
446 (38)
153 (39)
118 (30)
175 (45)
Killip class 1
339 (29)
110 (28)
99 (26)
130 (33)
5313
5613
5413
5112
600 (51)
115 (29)
190 (49)
295 (75)
1 (0-3)
2 (0-4)
1 (0-3)
89 (23)
1 (0-2)
Diabetes mellitus
288 (25)
103 (26)
96 (24)
191 (16)
101 (26)
57 (15)
33 (8)
5924
5524
5823
6524
0.52 (0.16-1.75)
0.11 (0.07-0.16)
0.52 (0.34-0.76)
3.05 (1.75-5.76)
Troponin measurements
Maximal cTnT (ng/mL), median (IQR)
Time to maximal cTnT (d), median (IQR)
1 (0-2)
1 (0-2)
1 (1-3)
1 (0-2)
5 (4-7)
4 (3-6)
5 (4-7)
5 (4-7)
250
40
30
20
10
Upper tertile
Middle tertile
Lower tertile
0
0.0
0.5
1.0
Time (y)
1.5
2.0
0.0
0.5
1.0
Time (y)
1.5
2.0
0.0
0.5
1.0
Time (y)
1.5
2.0
FIGURE. Cumulative risk probabilities of all-cause death (A), recurrent ischemic event (B), and heart failure (C) across cardiac
troponin T tertiles, using the direct adjustment method based on stratified Cox models. Adjustment was made for age, sex,
ST-segment elevation myocardial infarction (MI), anterior MI, ejection fraction, Killip class, reperfusion or revascularization during
hospitalization, smoking, hypertension, hyperlipidemia, body mass index, Charlson index, and estimated glomerular filtration rate.
For the analyses of recurrent ischemic events and heart failure, death was considered a competing event.
Thus, the present data provide novel information on the prognostic value of cTnT after MI. We
studied a population-based cohort of incident MI
patients, relying on standardized criteria to define
MI, and evaluated nonfatal cardiovascular end
TABLE 2. Multivariate-Adjusted Absolute Risk Differences: Excess Events per 100 Patients for Death,
Recurrent Ischemic Event, and Heart Failure Among cTnT Tertiles at Different Time Points During Follow-upa
Excess events (95% CI) during follow-up period
cTnT tertile comparison
0-30 d
0-180 d
0-12 mo
0-24 mo
Death
Upper vs lower
5.8 (1.4-10.2)
Middle vs lower
Upper vs middle
6.9 (2.5-11.2)
7.9 (2.6-13.2)
8.7 (3.1-14.4)
6.8 (1.5-12.1)
5.2 (0.2-10.3)
7.6 (1.1-14.0)
Middle vs lower
Upper vs middle
Heart failureb
Upper vs lower
6.9 (1.4-12.4)
7.7 (1.8-13.6)
9.9 (1.1-18.7)
Middle vs lower
Upper vs middle
5.8 (0.8-10.7)
Risk differences were estimated at the end of the periods. Adjustment was made for age, sex, ST-segment elevation MI, anterior MI,
ejection fraction, Killip class, reperfusion or revascularization during hospitalization, smoking, hypertension, hyperlipidemia, body mass
index, Charlson index, and estimated glomerular filtration rate. CI confidence interval; cTnT cardiac troponin T; MI myocardial
infarction.
b
With death considered a competing event.
Mayo Clin Proc. March 2012;87(3):247-254 doi:10.1016/j.mayocp.2011.11.013
www.mayoclinicproceedings.org
251
TABLE 3. Adjusted HRs (95% CIs) of Death, Recurrent Ischemic Event, and Heart Failure in cTnT Tertiles at
Different Periods During Follow-up
HR (95% CI) by cTnT Tertile
Event
Lower
Middle
Upper
Death
First 30 d (n94)
1 (reference)
0.79 (0.46-1.36)
1.80 (1.04-3.13)
1-24 mo (n170)
1 (reference)
1.47 (1.02-2.11)
1.74 (1.06-2.84)
Overall (N264)
1 (reference)
1.22 (0.90-1.66)
1.83 (1.26-2.66)
1 (reference)
1.32 (0.86-2.05)
1.72 (1.07-2.75)
1-24 mo (n181)
1 (reference)
1.22 (0.84-1.78)
1.12 (0.71-1.75)
Overall (N334)
1 (reference)
1.26 (0.95-1.68)
1.35 (0.98-1.87)
Heart failure
First 30 d (n260)
1 (reference)
1.01 (0.70-1.45)
1.48 (1.02-2.15)
1-24 mo (n65)
1 (reference)
2.02 (0.96-4.24)
1.92 (0.86-4.31)
Overall (N325)
1 (reference)
1.11 (0.79-1.57)
1.51 (1.06-2.14)
Models are adjusted for age, sex, current and former smoking, ST-segment elevation myocardial infarction, anterior myocardial
infarction, ejection fraction, Killip class, reperfusion or revascularization during hospitalization, hypertension, hyperlipidemia, body mass
index, Charlson index, and estimated glomerular filtration rate. CI confidence interval; cTnT cardial troponin T; HR hazard ratio.
points and death ascertained with similar rigor using the complete (inpatient and outpatient) medical
records in the community. The use of a contemporary cohort of unselected patients from a geographically defined population is an important strength
because of its relevance to real-world clinical practice. Indeed, it was previously demonstrated that the
external validity of studies based on clinical trial
participants is questionable,38 whereas studies that
use administrative or registry data often lack essential clinical details and are hence more prone to misclassification bias and confounding.42,43 Importantly, the same cTnT assay was used throughout
the entire study period. Moreover, we applied advanced analytical methods to assess absolute measures of association between cTnT and outcomes. In
doing so, we were able to demonstrate not only that
cTnT is predictive of death, recurrent ischemic
events, and heart failure but also to report the differences in the results obtained from absolute and
relative risk estimates and between short-term and
long-term outcomes. We also found exploratory evidence of a stronger association between cTnT and
recurrent ischemic event in nonST-segment elevation than in ST-segment elevation MI, which is consistent with previous reports.3 Indeed, in patients
with nonST-segment elevation MI, angiographic
data suggest the presence of complex plaques, more
thrombi, more extensive disease, and reduced
Thrombolysis in Myocardial Infarction flow grades
when troponin levels are elevated.44,45
Potential limitations of this study are important
to consider. Even though Olmsted County is be-
252
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