Article

Association of Troponin T Detected With a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population

Division of Cardiology, University of Texas Southwestern Medical Center, 5909 Harry Hines Blvd, Dallas, TX 75390-9047, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 12/2010; 304(22):2503-12. DOI: 10.1001/jama.2010.1768
Source: PubMed

ABSTRACT

Detectable levels of cardiac troponin T (cTnT) are strongly associated with structural heart disease and increased risk of death and adverse cardiovascular events; however, cTnT is rarely detectable in the general population using standard assays.
To determine the prevalence and determinants of detectable cTnT in the population using a new highly sensitive assay and to assess whether cTnT levels measured with the new assay associate with pathological cardiac phenotypes and subsequent mortality.
Cardiac troponin T levels were measured using both the standard and the highly sensitive assays in 3546 individuals aged 30 to 65 years enrolled between 2000 and 2002 in the Dallas Heart Study, a multiethnic, population-based cohort study. Mortality follow-up was complete through 2007. Participants were placed into 5 categories based on cTnT levels.
Magnetic resonance imaging measurements of cardiac structure and function and mortality through a median of 6.4 (interquartile range, 6.0-6.8) years of follow-up.
In Dallas County, the prevalence of detectable cTnT (≥0.003 ng/mL) was 25.0% (95% confidence interval [CI], 22.7%-27.4%) with the highly sensitive assay vs 0.7% (95% CI, 0.3%-1.1%) with the standard assay. Prevalence was 37.1% (95% CI, 33.3%-41.0%) in men vs 12.9% (95% CI, 10.6%-15.2%) in women and 14.0% (95% CI, 11.2%-16.9%) in participants younger than 40 years vs 57.6% (95% CI, 47.0%-68.2%) in those 60 years and older. Prevalence of left ventricular hypertrophy increased from 7.5% (95% CI, 6.4%-8.8%) in the lowest cTnT category (<0.003 ng/mL) to 48.1% (95% CI, 36.7%-59.6%) in the highest (≥0.014 ng/mL) (P < .001); prevalence of left ventricular systolic dysfunction and chronic kidney disease also increased across categories (P < .001 for each). During a median follow-up of 6.4 years, there were 151 total deaths, including 62 cardiovascular disease deaths. All-cause mortality increased from 1.9% (95% CI, 1.5%-2.6%) to 28.4% (95% CI, 21.0%-37.8%) across higher cTnT categories (P < .001). After adjustment for traditional risk factors, C-reactive protein level, chronic kidney disease, and N-terminal pro-brain-type natriuretic peptide level, cTnT category remained independently associated with all-cause mortality (adjusted hazard ratio, 2.8 [95% CI, 1.4-5.2] in the highest category). Adding cTnT categories to the fully adjusted mortality model modestly improved model fit (P = .02) and the integrated discrimination index (0.010 [95% CI, 0.002-0.018]; P = .01).
In this population-based cohort, cTnT detected with a highly sensitive assay was associated with structural heart disease and subsequent risk for all-cause mortality.

Full-text

Available from: Anand Rohatgi, Feb 12, 2014
ORIGINAL CONTRIBUTION
Association of T roponin T Detected With a
Highly Sensitive Assay and Cardiac Structure
and Mortality Risk in the General Population
James A. de Lemos, MD
Mark H. Drazner, MD, MSc
Torbjorn Omland, MD, PhD
Colby R. Ayers, MS
Amit Khera, MD, MSc
Anand Rohatgi, MD
Ibrahim Hashim, PhD, MSc
Jarett D. Berry, MD, MS
Sandeep R. Das, MD, MPH
David A. Morrow, MD, MPH
Darren K. McGuire, MD, MHSc
C
ARDIAC TROPONINS T
(cTnT) and I are the pre-
ferred biomarkers for the
diagnosis of acute myocar-
dial infarction (MI).
1,2
Increasingly it
has been recognized that elevated
troponin levels may be detected in
other clinical scenarios in which
acute myocardial injury may occur
3,4
as well as in several chronic disease
states, including coronary artery dis-
ease (CAD), heart failure, and
chronic kidney disease (CKD).
5-7
Troponins T and I are also occasion-
ally detectable in individuals from
the general population using stan-
dard assays.
8-11
Although the preva-
lence in the population is low,
detectable troponin associates
strongly with structural heart dis-
ease
8
and an increased risk of death
and adverse cardiovascular events.
9-11
These findings suggest that troponin
See also p 2494.
Author Affiliations: Donald W. Reynolds Cardiovascu-
lar Clinical Research Center and Division of Cardiology
(Drs de Lemos, Drazner, Khera, Rohatgi, Berry, Das, and
McGuire and Mr Ayers) and Department of Pathology
(Dr Hashim), University of Texas SouthwesternMedical
Center, Dallas; Division of Medicine, Akershus Univer-
sity Hospital and Center for Heart Failure Research,
University of Oslo, Oslo, Norway (Dr Omland); and
Cardiovascular Division, Brigham and Women’s Hospi-
tal, Boston, Massachusetts (Dr Morrow).
Corresponding Author: James A. de Lemos, MD, Uni-
versity of Texas Southwestern Medical Center, 5909
Harry Hines Blvd, HA 9.133, Dallas, TX 75390-9047
(james.delemos@utsouthwestern.edu).
Context Detectable levels of cardiac troponin T (cTnT) are strongly associated with
structural heart disease and increased risk of death and adverse cardiovascular events;
however, cTnT is rarely detectable in the general population using standard assays.
Objectives To determine theprevalence and determinants of detectablecTnT inthe popu-
lation using a new highly sensitive assay and to assess whether cTnT levels measured with
the new assay associate with pathological cardiac phenotypes and subsequent mortality.
Design, Setting, and Participants Cardiac troponin T levels were measured using
both the standard and the highly sensitive assays in 3546 individuals aged 30 to 65
years enrolled between 2000 and 2002 in the Dallas Heart Study, a multiethnic, popu-
lation-based cohort study. Mortality follow-up was complete through 2007. Partici-
pants were placed into 5 categories based on cTnT levels.
Main Outcome Measures Magnetic resonance imaging measurements of car-
diac structure and function and mortality through a median of 6.4 (interquartile range,
6.0-6.8) years of follow-up.
Results In Dallas County, the prevalence of detectable cTnT (0.003 ng/mL) was 25.0%
(95% confidence interval [CI], 22.7%-27.4%) with the highly sensitive assay vs 0.7%
(95% CI, 0.3%-1.1%) with the standard assay. Prevalence was 37.1% (95% CI, 33.3%-
41.0%) in men vs 12.9% (95% CI, 10.6%-15.2%) in women and 14.0% (95% CI, 11.2%-
16.9%) in participants younger than 40 years vs 57.6% (95% CI, 47.0%-68.2%) in those
60 years and older. Prevalence of left ventricular hypertrophy increased from 7.5% (95%
CI, 6.4%-8.8%) in the lowest cTnT category (0.003 ng/mL) to 48.1% (95% CI, 36.7%-
59.6%) in the highest (0.014 ng/mL) (P .001); prevalence of left ventricular systolic
dysfunction and chronic kidney disease also increased across categories (P .001 for each).
During a median follow-up of 6.4 years, there were 151 total deaths, including 62 car-
diovascular disease deaths. All-cause mortality increased from 1.9% (95% CI, 1.5%-
2.6%) to 28.4% (95% CI, 21.0%-37.8%) across higher cTnT categories (P .001). Af-
ter adjustment for traditional risk factors, C-reactive protein level, chronic kidney disease,
and N-terminal pro-brain-type natriuretic peptide level, cTnT category remained inde-
pendently associated with all-cause mortality (adjusted hazard ratio, 2.8 [95% CI, 1.4-
5.2] in the highest category). Adding cTnT categories to the fully adjusted mortality model
modestly improved model fit (P=.02) and the integrated discrimination index (0.010 [95%
CI, 0.002-0.018]; P=.01).
Conclusion In this population-based cohort, cTnT detected with a highly sensitive
assay was associated with structural heart disease and subsequent risk for all-cause
mortality.
JAMA. 2010;304(22):2503-2512 www.jama.com
©2010 American Medical Association. All rights reserved. (Reprinted) JAMA, December 8, 2010—Vol 304, No. 22 2503
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 1
may be useful for detecting subclini-
cal cardiovascular disease and assess-
ing cardiovascular disease risk in the
general population; however, the low
prevalence of detection with stan-
dard assays would limit the utility of
troponin measurement for these
clinical applications.
8
Recently, a highly sensitive assay
for cTnT has been developed that
detects levels approximately 10-fold
lower than those detectable with the
standard assay. In patients with sus-
pected acute coronary syndromes, this
assay improves accuracy for the diag-
nosis of MI compared with the stan-
dard cTnT assay.
12
In patients with
chronic heart failure
13
and chronic
CAD,
14
circulating cTnT is detectable
in almost all individuals with the
highly sensitive assay, and higher lev-
els correlate strongly with increased
cardiovascular mortality. Here, we
report an evaluation of the highly sen-
sitive assay in a general population
cohort with detailed cardiovascular
phenotyping and long-term follow-up
for mortality.
METHODS
Study Population
The Dallas Heart Study (DHS) is a
multiethnic, population-based cohort
study of Dallas County residents. The
study was approved by the University
of Texas Southwestern institutional
review board, and all participants pro-
vided written informed consent.
Details of the study design and partici-
pant selection have been described
previously.
15
The random probability sample
included intentional oversampling of
black individuals to comprise 50% of
the cohort. Enrollment occurred
between July 2000 and September
2002, and data collection was per-
formed in 3 phases, beginning with an
initial in-home visit (n=6101) to col-
lect demographic information, medi-
cal history, blood pressure, and
anthropometric measurements. Par-
ticipants aged 30 to 65 years were
asked to participate in a second
in-home visit (n=3557) to collect
fasting blood and urine samples and
then a final visit at University of
Texas Southwestern Medical Center
(n= 2971) where dual-energy x-ray
absorptiometry (DEXA) scanning for
body composition, detailed cardiovas-
cular phenotyping by electron-beam
computed tomography (EBCT), and
cardiac and aortic magnetic resonance
imaging (MRI) were performed.
Sampling weights were calculated
for each participant to reflect differen-
tial probabilities of selection and attri-
tion of participants between visits.
These sampling weights permit the
generation of unbiased estimates of
population frequencies in Dallas
County (additional methods presented
in the eSupplement available at
http://www.jama.com).
15
The present
study includes all 3546 individuals with
cTnT levels measured using the highly
sensitive assay, including 2501 with car-
diac MRI and 2770 with EBCT.
Biomarker Assays
Blood was collected into EDTA
tubes, refrigerated at 4°C for 4 hours
or less, centrifuged, and the plasma
removed and stored at −70°C. Brain-
type natriuretic peptide,
16
N-terminal
pro-brain-type natriuretic peptide
(NT-proBNP),
16
and high-sensitivity
C-reactive protein (CRP)
17
were mea-
sured as previously described. Levels
of cTnT were measured previously
using a standard assay with a lower
limit of detection of 0.01 ng/mL
(Elecysys-2010 Troponin T; Roche
Diagnostics, Indianapolis, Indiana).
8
For the present study, cTnT levels
were measured using a highly sensi-
tive assay on an automated platform
(Elecsys-2010 Troponin T hs STAT,
Roche Diagnostics), with a lower
detection limit of 0.003 ng/mL and a
reported 99th percentile value in
apparently healthy individuals of
0.014 ng/mL.
18
Imaging Procedures
Detailed methods for MRI, EBCT, and
DEXA scans in the DHS have been
reported.
19-21
EBCT was performed in
duplicate on a single scanner (Ima-
tron Inc, San Bruno, California) to
assess coronary artery calcium (CAC),
with results averaged. Scans were
scored by the Agatston method and
classified as 0 to 10, 10 to 100,
100 to 400, and 400 Agatston
units.
19
DEXA was used to estimate
body composition, dividing total body
mass into bone, fat, and lean mass
components.
19
Cardiac and aortic MRI
was performed using a 1.5-Tesla sys-
tem (Intera; Philips Medical Systems,
Best, the Netherlands). Left ventricu-
lar mass, wall thickness, end diastolic
volume (LVEDV), and ejection frac-
tion (LVEF) were calculated from
short-axis sequences. Left ventricular
hypertrophy (LVH) was defined as
left ventricular mass greater than 89
g/m
2
in women and greater than 112
g/m
2
in men, based on a phenotypi-
cally normal subpopulation of the
DHS cohort.
20
Details of aortic MRI
and compliance methods are pre-
sented in the eSupplement.
Variable Definitions
Race/ethnicity was self-reported. Coro-
nary heart disease (CHD) was defined
as self-reported prior MI or revascular-
ization. Cardiovascular disease was de-
fined as CHD or self-reported history
of heart failure or stroke. For pur-
poses of categorizing baseline risk,
Framingham Risk Score (FRS) esti-
mates of 10-year CHD events were de-
termined using published algo-
rithms
22
with a correction for statin
treatment,
23
and participants were cat-
egorized into low-risk (10%), inter-
mediate-risk (10%-20%), and high-
risk (20%) categories; participants
with diabetes or CHD were catego-
rized into the high-risk group. Other
variable definitions are provided in the
eSupplement.
Mortality Follow-up
The National Death Index was que-
ried to determine participant mortal-
ity through December 31, 2007. Deaths
were classified as cardiovascular if they
included International Statistical Clas-
sification of Diseases, 10th Revision codes
I00-I99.
24
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
2504 JAMA, December 8, 2010—Vol 304, No. 22 (Reprinted) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 2
Statistical Analyses
Continuous variables are reported as me-
dian (interquartile range) and categori-
cal variables as proportions. The pre-
specified primary analyses assessed cTnT
level as an ordered categorical variable
with secondary analyses as a dichoto-
mous variable (detectable vs undetect-
able levels). For the analyses of cTnT as
a categorical variable, participants were
divided into 5 a priori–determined cat-
egories based on cTnT levels deter-
mined using the highly sensitive assay:
those with undetectable cTnT were
placed in the first category; those with
cTnT levels greater than or equal to the
previously reported 99th percentile value
(0.014 ng/mL) were placed in the fifth
category, and those with cTnT levels be-
tween 0.003 and 0.014 ng/mL were di-
vided into tertiles for categories 2
through 4. Demographic and clinical
variables and cardiovascular pheno-
types were compared across cTnT cat-
egories using the Jonckheere-Terpstra
trend test, which is a nonparametric
trend test for ordered classes.
25
Sensi-
tivity analyses were performed re-
stricted to participants without preva-
lent cardiovascular disease and those in
the lowest FRS category.
Logistic regression was used to iden-
tify variables independently associ-
ated with detectable cTnT. Candidate
variables tested included age, sex, race/
ethnicity, diabetes, hypertension, prior
MI, heart failure or angina, hospital-
ization within the past year, estimated
glomerular filtration rate, CAC, LVEF,
left ventricular mass, lean mass by
DEXA, and body surface area. Left ven-
tricular mass was replaced with LVEDV
and left ventricular wall thickness in a
second model.
All-cause and cardiovascular dis-
ease mortality were estimated using the
Nelson-Aalen estimator,
26
and cumu-
lative incidence curves were com-
pared across cTnT categories using the
log-rank test. Multivariable Cox pro-
portional hazards models were used
to determine associations of cTnT cat-
egories with mortality after serially ad-
justing for traditional risk factors plus
high-sensitivity CRP level, estimated
glomerular filtration rate, and NT-
proBNP level. Sensitivity analyses were
performed replacing cTnT categories
with cTnT as a log-transformed con-
tinuous variable, with undetectable val-
ues assigned a value just below the
lower detection limit of the assay (2.99
ng/mL). Time-dependent C statis-
tics
27
were calculated for models with
and without cTnT and compared using
bootstrap resampling, with model fit as-
sessed by the likelihood ratio test and
calibration by the Hosmer-Lemeshow
statistic. The integrated discrimina-
tion index (IDI) was calculated for the
addition of cTnT to each model.
28
The
IDI represents the improvement in av-
erage sensitivity minus any increase in
1 specificity when a variable is added
to a model.
Sample weighting was used for
determining the prevalence of detect-
able cTnT in Dallas County and in
subsets of the population (eSupple-
ment). For all other analyses evaluat-
ing associations within the DHS co-
hort, no sample weighting was used. All
P values are 2-sided; P .05 was con-
Table 1. Prevalence of Detectable Cardiac Troponin T (0.003 ng/mL) and Levels Greater
Than or Equal to the 99th Percentile Value (0.014 ng/mL) in the Dallas County Population
and in Selected Subgroups
Group
Sample
Size,
No.
cTnT Level, ng/mL
0.003 0.014
No. (%)
Sample
Weight–Adjusted
Prevalence, %
(95% CI) No. (%)
Sample
Weight–Adjusted
Prevalence, %
(95% CI)
Overall population 3546 957 (27.0) 25.0 (22.7-27.4) 122 (3.4) 2.0 (1.5-2.6)
Restricted population
Without CHD 3428 891 (26.0) 24.2 (21.8-26.5) 103 (3.0) 1.8 (1.2-2.4)
Without cardiovascular
disease
3277 813 (24.8) 23.7 (21.3-26.1) 82 (2.5) 1.9 (1.0-2.0)
Without cardiovascular
disease or CKD
a
3222 773 (24.0) 23.1 (20.7-25.5) 65 (2.3) 1.2 (0.8-1.7)
Without cardiovascular
disease, CKD, or
subclinical heart
disease
2554 510 (20.0) 19.3 (16.8-21.8) 43 (1.7) 1.1 (0.6-1.7)
Without cardiovascular
disease, CKD,
subclinical heart
disease, diabetes,
or hypertension
b
1854 292 (15.7) 16.2 (13.3-19.1) 16 (0.9) 0.6 (0.1-1.0)
Age, y
c
30-40 1156 172 (14.9) 14.0 (11.2-16.9) 20 (1.7) 1.0 (0.4-1.7)
40-50 1152 279 (24.2) 22.1 (18.1-26.2) 24 (2.1) 0.8 (0.3-1.3)
50-60 846 343 (40.5) 37.4 (32.4-42.3) 56 (6.6) 4.6 (2.6-6.6)
60-65 247 138 (55.9) 57.6 (47.0-68.2) 22 (8.9) 5.2 (2.2-8.2)
Sex
d
Men 1565 670 (42.8) 37.1 (33.3-41.0) 85 (5.4) 2.8 (1.9-3.7)
Women 1981 287 (14.5) 12.9 (10.6-15.2) 37 (1.9) 1.3 (0.6-2.0)
Self-reported race/ethnicity
e
Black 1828 599 (32.8) 34.4 (30.6-38.3) 94 (5.1) 4.7 (3.2-6.3)
White 1042 248 (23.8) 25.4 (21.8-29.0) 21 (2.0) 1.8 (0.9-2.7)
Hispanic 601 101 (16.8) 19.0 (14.5-23.5) 7 (1.2) 0.7 (0.1-1.3)
Other 75 9 (12.0) 8.7 (2.0-15.5) 0 0
Abbreviations: CI, confidence interval; CHD, coronary heart disease; CKD, chronic kidney disease; cTnT, cardiac tropo-
nin T.
a
Chronic kidney disease defined as an estimated glomerular filtration rate less than 60 mL/min per 1.73 m
2
.
b
Subclinical heart disease defined as left ventricular hypertrophy, left ventricular ejection fraction less than 55%, or a
coronary artery calcium score greater than 10.
c
P .001 for trend across age categories for the prevalence of detectable cTnT.
d
P .001 for comparisons of the prevalence of detectable cTnT by sex.
e
P .001 for comparison of the prevalence of detectable cTnT across racial/ethnic subgroups.
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
©2010 American Medical Association. All rights reserved. (Reprinted) JAMA, December 8, 2010—Vol 304, No. 22 2505
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 3
sidered statistically significant. No ad-
justment was made for multiple com-
parisons. Statistical analyses were
performed using SAS version 9.2 (SAS
Institute Inc, Cary, North Carolina).
RESULTS
Prevalence of Detectable cTnT
The sample-weight–adjusted preva-
lence of detectable cTnT in Dallas
County adults was 25.0% (95% confi-
dence interval [CI], 22.7%-27.4%)
using the highly sensitive cTnT assay
and 0.7% (95% CI, 0.3%-1.1%) using
the standard assay. Among individu-
als without cardiovascular disease,
Table 2. Demographic Characteristics, Cardiovascular Risk Factors, and Cardiac Phenotypes Across Increasing Categories of Cardiac Troponin
T Level
Variable
cTnT Category, ng/mL
a
P for
Trend
0.003
(n = 2589)
0.003-0.00440
(n = 278)
0.00441-0.00657
(n = 279)
0.0066-0.0014
(n = 278)
0.0014
(n = 122)
cTnT 0.01 ng/mL with standard
assay, No./total (%)
0/2589 0/278 0/279 1/277 (0.4) 40/120 (33.3) .001
Age, median (IQR), y 41 (35-49) 47 (39-55) 49 (41-55) 52 (45-58) 53 (44-58) .001
Men, No./total (%) 895/2589 (34.6) 175/278 (62.9) 196/279 (70.3) 214/278 (77.0) 85/122 (69.7) .001
Race/ethnicity, No./total (%)
Black 1229/2589 (47.5) 150/278 (54.0) 173/279 (62.0) 182/278 (65.5) 94/122 (77.0) .001
White 794/2589 (30.7) 88/278 (31.7) 78/279 (28.0) 61/278 (21.9) 21/122 (17.2) .001
Hispanic 500/2589 (19.3) 37/278 (13.3) 27/279 (9.7) 30/278 (10.8) 7/122 (5.7) .001
Other 66/2589 (2.5) 3/278 (1.1) 1/279 (0.4) 5/278 (1.8) 0/278 .008
Hypertension, No./total (%) 694/2554 (27.2) 116/277 (41.9) 125/271 (46.1) 170/274 (62.0) 83/117 (70.9) .001
Blood pressure, median (IQR),
mm Hg
Systolic 119.7
(110.0-130.7)
127.0
(117.3-137.7)
126.0
(117.0-140.7)
134.3
(121.7-153.0)
136.7
(121.3-161.0)
.001
Diastolic 76.3 (70.7-83.0) 79.3 (73.0-85.0) 79.0 (72.7-86.0) 83.0 (75.3-89.0) 81.7 (74.0-89.3) .001
Diabetes, No./total (%) 200/2588 (7.7) 38/278 (13.7) 43/279 (15.4) 79/278 (28.4) 50/122 (41.0) .001
Fasting glucose, median (IQR),
mg/dL
92 (84-100) 94 (85-103) 94 (87-106) 99 (87-122) 99.5 (86-152) .001
Metabolic syndrome, No./total (%)
b
787/2589 (30.4) 96/278 (34.5) 107/279 (38.4) 136/278 (48.9) 63/122 (51.6) .001
Hypercholesterolemia, No./total (%) 282/2587 (10.9) 52/278 (18.7) 38/279 (13.6) 57/278 (20.5) 29/122 (23.8) .001
Lipids, median (IQR), mg/dL
Total cholesterol 176 (153-202) 180.5 (156-207) 179 (157-202) 176.5 (154-205) 175.5 (148-195) .50
LDL-C 103 (82-125) 107.5 (84-129) 108 (84-130) 104.5 (82-129) 96.5 (74-120) .66
HDL-C 48 (40-58) 45 (38-55) 46 (38-54) 45 (38-52) 44.5 (36-57) .001
Triglycerides 92 (66-142) 107 (72-158) 102 (72-153) 106.5 (74-170) 106 (74-170) .001
Current smoking, No./total (%) 787/2586 (30.4) 62/277 (22.4) 56/279 (20.1) 92/277 (33.2) 37/122 (30.3) .31
Cocaine use, No./total (%) 355/2589 (13.7) 28/278 (10.1) 37/279 (13.3) 40/278 (14.4) 13/122 (10.7) .55
Prior heart failure, No./total (%) 56/2589 (2.2) 12/278 (4.3) 16/279 (5.7) 22/278 (7.9) 23/122 (18.9) .001
Prior CHD, No./total (%) 52/2589 (2.0) 11/278 (4.0) 15/279 (5.4) 21/278 (7.6) 19/122 (15.6) .001
Prior CVD, No./total (%) 125/2589 (4.8) 25/278 (9.0) 30/279 (10.8) 49/278 (17.6) 40/122 (32.8) .001
Framingham risk score–estimated
10-y risk for CHD, No./total (%)
b
10% 2140/2537 (84.4) 196/275 (71.3) 183/269 (68.0) 118/273 (43.2) 43/117 (36.8) .001
10%-20% 121/2537 (4.8) 23/275 (8.4) 25/269 (9.3) 40/273 (14.7) 8/117 (6.8) .001
20% 276/2537 (10.9) 56/275 (20.4) 61/269 (22.7) 115/273 (42.1) 66/117 (56.4) .001
Body composition, median (IQR)
BMI
c
29.2 (25.1-34.4) 29.4 (26.0-33.9) 29.7 (26.5-35.0) 30.6 (27.0-35.0) 30.1 (25.4-37.7) .001
Lean mass, kg 52.4 (44.4-61.7) 58.8 (50.4-67.6) 62.9 (55.3-70.0) 63.3 (54.6-70.6) 60.8 (53.1-71.5) .001
Fat mass, kg 26.0 (19.0-35.0) 25.6 (18.1-32.9) 24.7 (18.8-32.7) 25.8 (18.0-32.5) 24.2 (16.7-33.5) .01
Estimated GFR, median (IQR),
mL/min per 1.73 m
2
99.5
(87.1-114.4)
93.0
(82.44-110.1)
93.4
(80.8-109.2)
87.3
(77.5-104.9)
88.0
(62.7-107.9)
.001
CKD stage, No./total (%)
1 1804/2588 (69.7) 158/278 (56.8) 161/279 (57.7) 124/278 (44.6) 58/122 (47.5) .001
2 767/2588 (29.6) 113/278 (40.6) 110/279 (39.4) 135/278 (48.6) 33/122 (27.0) .001
3 15/2588 (0.6) 6/278 (2.2) 6/279 (2.2) 18/278 (6.5) 16/122 (13.1) .001
4 0/2588 1/278 (0.4) 0/279 0/278 1/122 (0.8) .02
5 2/2588 (0.1) 0/278 2/279 (0.7) 1/278 (0.4) 14/122 (11.5) .001
(continued)
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
2506 JAMA, December 8, 2010—Vol 304, No. 22 (Reprinted) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 4
CKD, subclinical heart disease, diabe-
tes, or hypertension, the prevalence of
detectable cTnT with the highly sensi-
tive assay was 16.2% (95% CI, 13.3%-
19.1%) (T
ABLE 1). The prevalence of a
cTnT concentration of 0.014 ng/mL or
greater (the 99th percentile cutpoint for
diagnosis of MI) was 2.0% (95% CI,
1.5%-2.6%) in Dallas County adults and
1.9% (95% CI, 1.0%-2.0%) in those
without prior cardiovascular disease
(Table 1).
The prevalence of detectable cTnT
varied markedly with age, ranging from
14.0% (95% CI, 11.2%-16.9%) in par-
ticipants aged 40 to 50 years to 57.6%
(95% CI, 47.0%-68.2%) in those aged
60 to 65 years (P .001) (Table 1).
Large differences in prevalence were
also seen according to sex and race/
ethnicity: men were 3-fold more likely
to have detectable levels than women
(37.1% [95% CI, 33.3%-41.0%] vs
12.9% [95% CI, 10.6%-15.2%],
P .001), and black participants had a
significantly higher prevalence of de-
tectable cTnT than Hispanic or white
participants (P .001) (Table 1). The
prevalence of detectable cTnT strati-
fied by sex and race/ethnicity is shown
in eFigure 1.
Univariable Associations
of cTnT Levels With Risk Factors
and Cardiovascular Phenotypes
Two-thirds of participants in the
highest cTnT category had undetect-
able cTnT levels with the standard
assay (T
ABLE 2). The prevalence of
hypertension increased from 27.2%
(95% CI, 25.5%-28.9%) to 70.9%
(95% CI, 61.8%-79.0%) and preva-
lence of diabetes from 7.7% (95% CI,
6.7%-8.8%) to 41.0% (95% CI,
32.2%-50.3%) across categories of
increasing cTnT levels. Estimated
glomerular filtration rate decreased
from 99.5 mL/min per 1.73 m
2
(95%
CI, 87.1-114.4) to 88.0 (95% CI,
62.7-107.9) mL/min per 1.73 m
2
(P .001 for trend) across categories
of higher cTnT levels, but smoking
status and levels of low-density lipo-
protein cholesterol did not change.
Although higher body mass index
was modestly associated with in-
creasing cTnT levels, DEXA mea-
surements of body composition dem-
onstrated discordant associations
with lean and fat mass: cTnT was
positively associated with lean mass
but inversely (and weakly) associated
with fat mass (Table 2).
Table 2. Demographic Characteristics, Cardiovascular Risk Factors, and Cardiac Phenotypes Across Increasing Categories of Cardiac Troponin
T Level (continued)
Variable
cTnT Category, ng/mL
a
P for
Trend
0.003
(n = 2589)
0.003-0.00440
(n = 278)
0.00441-0.00657
(n = 279)
0.0066-0.0014
(n = 278)
0.0014
(n = 122)
Left ventricular mass,
median (IQR), g
149.1
(125.1-177.5)
171.5
(146.1-198.5)
183.7
(156.3-212.3)
191.7
(159.0-227.3)
219.6
(176.9-266.4)
.001
Left ventricular mass/BSA,
median (IQR), g/m
2
77.4 (68.3-88.5) 86.3 (74.6-96.9) 89.2 (77.3-103.2) 92.1 (80.1-106.8) 103.8 (88.6-131.1) .001
LVH, No./total (%) 154/2043 (7.5) 22/213 (10.3) 40/232 (17.2) 60/232 (25.9) 38/79 (48.1) .001
LVEDV, median (IQR), mL 96.8 (83.7-112.1) 102.1 (85.7-118.7) 108.5 (94.5-122.8) 104.4 (86.8-130.1) 112.6 (92.4-143.7) .001
LVEDV/BSA, median (IQR), mL/m
2
50.7 (44.8-57.5) 50.8 (44.1-58) 52.6 (46.3-61.4) 51.8 (43.9-60.7) 54.5 (47.6-67.2) .001
LV wall thickness, median (IQR), mm 11.1 (10.1-12.3) 12.2 (11.1-13.4) 12.2 (11.2-13.4) 12.8 (11.7-14.5) 13.4 (12.0-15.3) .001
LVEF, median (IQR), % 73.3 (68.6-77.6) 72.8 (67.7-77.2) 71.8 (67.0-76.1) 70.1 (64.5-76.5) 72.6 (60.8-77.6) .001
LVEF 40%, No./total (%) 1/2044 (0.05) 0/213 3/232 (1.3) 6/232 (2.6) 4/79 (5.1) .001
Coronary artery calcium score,
Agatston units, No./total (%)
10 1712/2034 (84.2) 152/213 (71.4) 154/227 (67.8) 122/223 (54.7) 40/73 (54.8) .001
10-100 212/2034 (10.4) 29/213 (13.6) 32/227 (14.1) 46/223 (20.6) 5/73 (6.8) .001
100-400 77/2034 (3.8) 24/213 (11.3) 27/227 (11.9) 30/223 (13.5) 16/73 (21.9) .001
400 33/2034 (1.6) 8/213 (3.8) 14/227 (6.2) 25/223 (11.2) 12/73 (16.4) .001
Aortic wall thickness,
median (IQR), mm
1.62 (1.46-1.79) 1.71 (1.54-1.97) 1.77 (1.61-1.92) 1.84 (1.65-2.15) 1.85 (1.60-2.07) .001
Aortic compliance, median (IQR),
mL/mm Hg
25.1 (17.6-33.6) 21.8 (14.6-28.4) 19.9 (14.1-28.2) 17.6 (12.3-24.2) 15.6 (9.8-22.3) .001
High-sensitivity CRP, median (IQR),
mg/L
2.8 (1.1-7.1) 2.8 (1.2-6.2) 2.3 (1.0-6.0) 3.4 (1.3-7.1) 3.8 (1.7-9.1) .48
NT-proBNP, median (IQR), ng/L 28.2 (13.2-55) 27.4 (10.6-61.2) 24.3 (12.8-56.5) 39.2 (15.7-104.4) 104.9 (42.9-557.4) .001
BNP, median (IQR), pg/mL 2.8 (0-12.1) 3.1 (0-15) 3.1 (0-14.7) 3.9 (0-17.7) 17.5 (2.9-75.3) .001
Abbreviations: BMI, body mass index; BNP, brain-type natriuretic peptide; BSA, body surface area; CHD, coronary heart disease; CKD, chronic kidney disease; CRP, C-reactive protein;
cTnT, cardiac troponin T; CVD, cardiovascular disease; GFR, glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range; LDL-C, low-density lipo-
protein cholesterol; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; NT-proBNP, N-terminal pro-brain-type natri-
uretic peptide.
SI conversion factors: To convert total cholesterol, LDL-C, and HDL-C values to mmol/L, multiply by 0.0259; to convert triglyceride values to mmol/L, multiply by 0.0113; to convert
glucose values to mmol/L, multiply by 0.0555.
a
Denominator values reflect the number of participants with data available for the specific variable. Variation in the denominator reflects absent data for that variable.
b
Defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria (see eSupplement for detailed definition).
c
Calculated as weight in kilograms divided by height in meters squared.
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
©2010 American Medical Association. All rights reserved. (Reprinted) JAMA, December 8, 2010—Vol 304, No. 22 2507
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 5
Across cTnT categories, left ven-
tricular mass increased markedly, as
did left ventricular wall thickness, and
the proportion of individuals classi-
fied as having LVH increased from
7.5% (95% CI, 6.4%-8.8%) to 48.1%
(95% CI, 36.7%-59.6%) (P .001 for
trend). Modest increases in LVEDV
and decreases in LVEF were also seen
with higher cTnT levels. CAC score
and abdominal aortic wall thickness
increased while aortic compliance
decreased across higher cTnT catego-
ries (Table 2). Strong graded associa-
tions were also evident between
increasing severity of selected patho-
logic phenotypes and the prevalence
of detectable cTnT, including indexed
left ventricular mass, LVEF, CAC
score, and CKD (eFigure 2).
Self-reported heart failure, CHD,
and cardiovascular disease were more
frequent with higher cTnT levels
(Table 2). In sensitivity analyses ex-
cluding participants with cardiovascu-
lar disease (eTable 1), similar associa-
tions were observed between cTnT
categories and demographic variables,
risk factors, and cardiac phenotypes.
Additionally, when these analyses were
restricted to individuals predicted by the
FRS to be at low risk (estimated 10-
year risk of CHD 10% [n=2680]),
cTnT remained associated with mul-
tiple pathological cardiac phenotypes
(eTable 2).
Independent Determinants of
Detectable cTnT in the Population
In a multivariable logistic regression
model with detectable cTnT as the de-
pendent variable, male sex, older age,
black race, history of heart failure, lower
estimated glomerular filtration rate, and
higher left ventricular mass indepen-
dently associated with detectable cTnT,
whereas prior MI or angina, LVEF, CAC
score, lean mass, and body surface area
did not (C statistic of model, 0.81)
(eTable 3). When left ventricular mass
was replaced with left ventricular wall
thickness and LVEDV, the model per-
formed similarly and both wall thick-
ness and LVEDV remained associated
with detectable cTnT.
Association of cTnT With All-Cause
and Cardiovascular Mortality
Over a median follow-up period of 6.4
years (interquartile range, 6.0-6.8
years), 151 total deaths and 62 cardio-
vascular disease deaths occurred. Unad-
justed all-cause mortality occurred in
1.9% (95% CI, 1.5%-2.6%) of partici-
pants with undetectable cTnT vs 9.1%
(95% CI, 7.4%-11.1%) of those with
detectable cTnT (P .001) and
increased from 1.9% (95% CI, 1.5%-
2.6%) to 28.4% (95% CI, 21.0%-
37.8%) across higher cTnT categories
(P .001) (F
IGURE 1). Similar trends
were observed for cardiovascular dis-
ease mortality (Figure 1). Detectable
cTnT and increasing cTnT categories
remained associated with mortality after
excluding participants with cTnT
detected by the standard assay, as well
as those with prevalent CHD or car-
diovascular disease. Associations of
cTnT level with all-cause and cardio-
vascular disease mortality were consis-
tent in subgroups defined by sex, race/
ethnicity, age, hypertension, and
diabetes (F
IGURE 2, eFigure 3, eTable
4, and eTable 5).
In a series of Cox proportional haz-
ards models adjusting for traditional
Figure 1. Unadjusted Nelson-Aalen Curves for All-Cause and Cardiovascular Mortality
40
30
20
All-cause mortality
10
No. at risk
cTnT
Detectable
Undetectable
0
957
2589
12
945
2584
24
933
2576
36
914
2570
48
903
2554
60
887
2552
72
651
1995
Months
Cumulative Incidence
of Overall Death, %
cTnT
Detectable
Undetectable
cTnT category, ng/mL
0.003-0.00440
0.0014
0.0066-< 0.0014
0.00441-0.00657
<0.003 (undetectable)
40
30
20
10
0
No. at risk
0.0014
0.0066-< 0.0014
0.00441-0.00657
0.003-0.00440
<0.003
0
122
278
279
278
2589
12
117
273
278
277
2584
24
115
267
276
275
2576
36
109
261
271
273
2570
48
101
258
271
273
2554
60
94
254
268
271
2552
72
64
182
209
196
1995
Months
20
15
10
Cardiovascular disease mortality
5
0
No. at risk
cTnT
Detectable
Undetectable
0
957
2589
12
945
2584
24
933
2576
36
914
2570
48
903
2554
60
887
2552
72
651
1995
Months
Cumulative Incidence
of Cardiovascular Death, %
cTnT
Detectable
Undetectable
cTnT category, ng/mL
0.003-0.00440
0.0014
0.0066-< 0.0014
0.00441-0.00657
<0.003 (undetectable)
20
15
10
5
No. at risk
0.0014
0.0066-< 0.0014
0.00441-0.00657
0.003-0.00440
<0.003
0
122
278
279
278
2589
12
117
273
278
277
2584
24
115
267
276
275
2576
36
109
261
271
273
2570
48
101
258
271
273
2554
60
94
254
268
271
2552
72
64
182
209
196
1995
Months
0
0
P .001 for all between-group comparisons by the log-rank test. Detectable cardiac troponin T (cTnT) levels
are 0.003 ng/mL or greater by the highly sensitive assay. Y-axes shown in blue indicate the range from 0% to
20%.
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
2508 JAMA, December 8, 2010—Vol 304, No. 22 (Reprinted) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 6
risk factors (model 1) and further ad-
justing for high-sensitivity CRP level
(model 2), higher cTnT categories dem-
onstrated a graded association with all-
cause and cardiovascular disease mor-
tality. The addition of cTnT to the
baseline models significantly im-
proved the C statistic (0.818 vs 0.793;
P= .001), IDI (0.044 [95% CI, 0.025-
0.063]; P .001), and model fit
(P .001) (T
ABLE 3). Only modest at-
tenuation of the hazards was seen with
further adjustment for CKD catego-
ries (model 3). Although more signifi-
cant attenuation was seen with addi-
tional adjustment for NT-proBNP level
(model 4), cTnT in the fourth cat-
egory (hazard ratio [HR], 2.0 [95% CI,
1.2-3.4]) and fifth category (HR, 2.8
[95% CI, 1.4-5.2]) remained indepen-
dently associated with all-cause mor-
tality in the fully adjusted models, and
the addition of cTnT improved model
fit (P=.02) and the IDI (0.010 [95% CI,
0.002-0.018]; P=.01) but not the C sta-
tistic (0.827 [95% CI, 0.789-0.864] vs
0.821 [95% CI, 0.783-0.859]); P=.12)
(Table 3). In contrast, in the same fully
adjusted model, cTnT level measured
with the standard assay did not asso-
ciate with all-cause mortality and did
not improve model fit, the IDI, or the
C statistic (P .15 for each). NT-
proBNP level was associated with all-
cause (P .001) and cardiovascular dis-
ease (P .001) mortality in the fully
adjusted model, but high-sensitivity
CRP level was not (P =.44 for all-
cause mortality and P=.28 for cardio-
vascular disease mortality). Sensitiv-
ity analyses using log-transformed cTnT
as a continuous variable yielded quali-
tatively similar results, including in the
fully adjusted all-cause mortality model
(HR per log unit change, 1.5 [95% CI,
1.1-1.9]; P= .006).
COMMENT
Circulating cardiac troponin T is detect-
able in approximately 25% of adults
aged 30 to 65 years in the general popu-
lation using a novel highly sensitive
assay, with wide variation in its preva-
lence according to age, sex, and race/
ethnicity. Higher levels of cTnT mea-
sured with the highly sensitive assay,
well below the detection range of stan-
dard assays, are associated with car-
diac structural abnormalities includ-
ing LVH (both left ventricular wall
thickening and dilation) and left ven-
tricular systolic dysfunction. These asso-
ciations were consistent in lower-risk
subgroups defined by the absence of
known cardiovascular disease or a low
FRS category. Moreover, higher cTnT
levels demonstrate a graded associa-
tion with all-cause and cardiovascular
disease mortality independent of tra-
ditional risk factors, renal function, and
levels of other biomarkers such as high-
sensitivity CRP and NT-proBNP.
The important contributions of
chronic sources of myocardial injury to
troponin release have become increas-
ingly evident as troponin measure-
ments have been applied to ambula-
tory patient populations, particularly
with highly sensitive assays. For ex-
ample, nearly 100% of clinical trial par-
ticipants with stable chronic heart fail-
ure and CAD had detectable cTnT levels
using a highly sensitive assay.
13,14
We applied the highly sensitive as-
say to a randomly sampled general
population cohort with a large propor-
tion of women and ethnic minorities
and found that cTnT was commonly de-
tectable in adults at levels well below
the detection limit of a standard assay.
Although several prior studies have
measured levels of troponins in gen-
eral population cohorts, they have used
standard troponin assays that are much
less sensitive than the assay used in the
present study.
8-11,29
For instance, the
prevalence of detectable cTnT with a
standard assay in this same young DHS
cohort was only 0.7%.
8,29
The finding
that male sex, older age, and black race
are associated with higher troponin lev-
els has been suggested previously, but
prior studies used less-sensitive assays
Figure 2. Unadjusted Hazard Ratios for All-Cause Mortality Associated With Detectable
Cardiac Troponin T (0.003 ng/mL) in Selected Subgroups
0.1 100101.0
HR (95% CI)
Subgroup
Sample
Size, No.
Deaths,
No.
Entire cohort 3546 151
Standard cTnT (–) 3505 135
No CVD 3277 109
No CVD or DM 2939 79
No CVD or CKD 3222 96
Men 1565 91
Women 1981 60
Black 1828 116
White 1042 27
Hispanic 601 6
<45
1898 42
45
1648 109
Yes 410 46
No 3135 105
Yes 1188 95
No 2305 50
Yes 314 36
No 2485 70
<10
2680 64
10-20 217 13
>20
574 67
FRS risk, %
LVH
Hypertension
Diabetes
Age, y
Race/ethniciy
Sex
Comorbid disease
CKD indicates chronic kidney disease; cTnT, cardiac troponin T; CVD, cardiovascular disease; DM, diabetes
mellitus; FRS, Framingham Risk Score; LVH, left ventricular hypertrophy.
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
©2010 American Medical Association. All rights reserved. (Reprinted) JAMA, December 8, 2010—Vol 304, No. 22 2509
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 7
and had a low rate of detectable tro-
ponins, precluding adequately pow-
ered multivariable analyses.
8,9,29,30
In univariable analyses, cTnT was as-
sociated with multiple cardiac risk fac-
tors, measures of atherosclerosis bur-
den, and cardiac structural phenotypes,
most notably left ventricular mass and
wall thickness. In multivariable analy-
ses, diabetes, hypertension, worse re-
nal function, and increased left ven-
tricular mass, wall thickness and
chamber dilation, but not CAC score,
remained independent determinants of
detectable cTnT. These findings should
be interpreted in the context of prior
studies investigating standard tropo-
nin assays in elderly individuals from
the general population
29
as well as in
patients with chronic CAD,
31
which
suggest that chronic elevation of tro-
ponin levels is mediated to a greater ex-
tent by indices of heart failure (such as
higher left ventricular mass, lower
LVEF, or increased NT-proBNP lev-
els) than indices of atherosclerosis or
ischemia. In the Prevention of Events
with Angiotensin Converting Enzyme
Inhibition (PEACE) trial, which ap-
plied a highly sensitive assay to pa-
tients with chronic CAD, cTnT was as-
sociated with death and heart failure but
not MI.
14
In contrast, in patients with
acute coronary syndromes, low levels
of troponin correlate with angio-
graphic evidence of greater lesion se-
verity and complexity
32
and identify pa-
tients at greater risk for ischemic
complications than for death or heart
failure.
33,34
Taken together, these find-
ings suggest important differences in the
pathophysiology of troponin release in
the chronic compared with the acute
setting.
Prior studies have described associa-
tions between increased troponin lev-
els detected with standard assays and
future risk for mortality.
9-11
Here, we re-
port that these associations extend to
much lower troponin levels not de-
tected with assays in current clinical
Table 3. Multivariable-Adjusted Associations Between Cardiac Troponin T Categories and All-Cause and Cardiovascular Mortality
Events,
No.
Event Rate at 6 y,
% (95% CI)
HR (95% CI)
a
Model 1 Model 2 Model 3 Model 4
All-cause mortality
cTnT category, ng/mL
0.003 52 1.9 (1.5 to 2.6) 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference]
0.003-0.00440 9 2.9 (1.5 to 5.8) 1.2 (0.6 to 2.4) 1.2 (0.6 to 2.4) 1.1 (0.5 to 2.3) 1.0 (0.5 to 2.1)
0.00441-0.00657 17 5.3 (3.2 to 8.9) 2.0 (1.1 to 3.5) 2.0 (1.1 to 3.6) 1.9 (1.1 to 3.4) 1.7 (1.0 to 3.1)
0.0066-0.0014 31 11.5 (8.1 to 16.0) 2.7 (1.7 to 4.5) 2.8 (1.7 to 4.6) 2.5 (1.5 to 4.1) 2.0 (1.2 to 3.4)
0.0014 34 28.4 (21.0 to 37.8) 6.7 (4.0 to 11.3) 6.7 (4.0 to 11.2) 4.8 (2.7 to 8.7) 2.8 (1.4 to 5.2)
C statistic for models
Without highly
sensitive cTnT assay
0.793
(0.757 to 0.829)
0.793
(0.757 to 0.829)
0.806
(0.769 to 0.842)
0.821
(0.783 to 0.859)
With highly sensitive cTnT assay 0.818
(0.782 to 0.854)
0.818
(0.782 to 0.853)
0.823
(0.788 to 0.858)
0.827
(0.789 to 0.864)
P value, bootstrap .001 .001 .02 .12
P value, likelihood ratio test .001 .001 .001 .02
IDI 0.044
(0.025 to 0.063)
0.044
(0.026 to 0.062)
0.024
(0.011 to 0.040)
0.010
(0.002 to 0.018)
P value for IDI .001 .001 .001 .01
Cardiovascular mortality
cTnT category, ng/mL
0.003 16 0.5 (0.3 to 0.9) 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference]
0.003-0.00440 4 1.5 (0.6 to 3.9) 1.6 (0.5 to 4.9) 1.6 (0.5 to 4.9) 1.4 (0.5 to 4.3) 1.2 (0.4 to 3.8)
0.00441-0.00657 7 2.8 (1.4 to 5.9) 2.4 (0.9 to 6.1) 2.5 (1.0 to 6.3) 2.1 (0.8 to 5.3) 1.7 (0.7 to 4.4)
0.0066-0.0014 17 6.0 (3.7 to 9.7) 4.6 (2.1 to 10.0) 4.7 (2.1 to 10.2) 3.5 (1.6 to 7.7) 2.4 (1.1 to 5.5)
0.0014 15 14.4 (8.9 to 22.8) 8.5 (3.7 to 19.4) 8.4 (3.7 to 19.2) 4.5 (1.7 to 11.8) 1.7 (0.6 to 5.1)
C statistic for model
Without highly sensitive cTnT assay 0.832
(0.789 to 0.874)
0.833
(0.791 to 0.876)
0.865
(0.820 to 0.910)
0.889
(0.844 to 0.932)
With highly sensitive cTnT assay 0.868
(0.826 to 0.909)
0.869
(0.828 to 0.909)
0.882
(0.841 to 0.923)
0.893
(0.849 to 0.936)
P value, bootstrap .004 .005 .05 .28
P value, likelihood ratio test .001 .001 .02 .37
IDI 0.027
(0.012 to 0.042)
0.029
(0.014 to 0.044)
0.010
(−0.003 to 0.021)
0.005
(−0.003 to 0.013)
P value for IDI .001 .001 .10 .24
Abbreviations: CI, confidence interval; cTnT, cardiac troponin T; HR, hazard ratio; IDI, integrated discrimination index.
a
Models include participants with complete data for all variables (n= 3459). Model 1 adjusted for age, race/ethnicity, sex, diabetes, hypertension, hypercholesterolemia, low high-density
lipoprotein cholesterol level, and current smoking. Model 2 adjusted for variables in model 1 plus log-transformed values of high-sensitivity C-reactive protein. Model 3 adjusted for
variables in model 2 plus chronic kidney disease categories. Model 4 adjusted for variables in model 3 plus log-transformed values of N-terminal pro-brain-type natriuretic peptide.
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
2510 JAMA, December 8, 2010—Vol 304, No. 22 (Reprinted) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 8
use. Indeed, only one-third of the par-
ticipants in the highest cTnT category
had cTnT levels measurable with the
standard-generation cTnT assay. Higher
cTnT levels associated strongly with fu-
ture risk for total and cardiovascular
disease mortality, and consistent asso-
ciations were observed in individuals
without prior cardiovascular disease
and those who would be deemed at low
risk based on the FRS. Associations with
mortality were only modestly attenu-
ated after adjustment for traditional risk
factors, high-sensitivity CRP level, and
CKD. Further adjustment for levels of
NT-proBNP, which was also associ-
ated with total and cardiovascular dis-
ease death in this cohort, resulted in
more substantial attenuation of the HRs,
suggesting that NT-proBNP and cTnT
provide partly overlapping informa-
tion concerning cardiac structural and
functional abnormalities. However,
even after full adjustment, cTnT in the
highest 2 categories remained indepen-
dently associated with all-cause mor-
tality, with adjusted HRs in a range that
would suggest potential clinical util-
ity.
35
The addition of cTnT to a variety
of risk prediction models increased
model fit and the IDI, a metric of dis-
crimination.
The present findings suggest that fu-
ture studies should be performed to as-
sess whether measurement of cTnT lev-
els with a highly sensitive assay adds
value to traditional cardiovascular risk
factors as well as measures of renal func-
tion and NT-proBNP levels for risk as-
sessment in the general population. In
the fully adjusted model, which in-
cluded NT-proBNP levels and renal
function, improvements in the C sta-
tistic and the IDI with cTnT were small,
and the clinical significance of changes
of this magnitude are not clear. Fu-
ture studies will need to evaluate clini-
cal performance metrics, such as net re-
classification improvement, in data sets
with long-term follow-up for nonfatal
end points, to fully evaluate the incre-
mental value of measurement of cTnT
levels. In addition, appropriate diag-
nostic and therapeutic responses would
need to be defined before population-
based screening could be recom-
mended. However, our data showing as-
sociations with LVH and other cardiac
structural abnormalities as well as with
mortality among individuals classified
at low risk using the FRS suggest that
low levels of cTnT may identify sub-
clinical structural heart disease and con-
tributors to cardiovascular disease risk
not fully captured by current risk-
assessment tools. The independent and
additive associations of cTnT and NT-
proBNP suggest that combinations of
these 2 markers may perform better
than either marker alone.
Our finding of a high prevalence of
detectable cTnT in the general popu-
lation has important, and complex,
implications for the use of highly sen-
sitive troponin assays for diagnosing
acute MI in the hospital setting. Among
patients with clinical presentations sus-
picious for MI, higher-sensitivity assays
improve diagnostic sensitivity, particu-
larly early after presentation, but reduce
specificity.
12,36
When applied to patients
with a high clinical suspicion for MI,
the net result is improved accuracy.
However, if applied to individuals with
a lower likelihood of MI, but with fac-
tors associated with higher cTnT lev-
els such as older age, male sex, black
race, hypertension, diabetes, CKD, and
LVH, the results of the highly sensitive
troponin assays will have lower speci-
ficity, and false-positive diagnoses of MI
will be more common. Because cur-
rent guidelines recommend more inten-
sive treatment for patients with sus-
pected acute coronary syndromes who
have elevated troponin levels,
1,2
it is pos-
sible that widespread application of
highly sensitive assays without inte-
grating new approaches to discrimi-
nate acute injury
37
will expose some
patients to unnecessary risk and
expense. Additional investigation is
needed before the full clinical implica-
tions of highly sensitivity troponin
assays can be determined.
This study has several strengths. The
sampling strategy used for the DHS per-
mits generation of unbiased popula-
tion estimates of the prevalence of de-
tectable cTnT among Dallas County
adults. The availability of cardiac MRI
and EBCT data in this large population-
based cohort allows detailed cardiac
phenotypes to be assessed for their as-
sociations with cTnT. The measure-
ment of cTnT by standard as well as
highly sensitive assays allows demon-
stration of the incremental value of the
novel assay.
This study also has several limita-
tions that merit comment. First, not all
participants completed cardiac imaging
studies. Second, adjudicated nonfatal
outcome data are not yet available for
the DHS; thus, full evaluation of the in-
cremental value of measuring cTnT lev-
els for risk prediction over currently
available risk assessment algorithms
such as the FRS could not be per-
formed. Third, only a single baseline
measurement of cTnT level and other
covariates was performed. Finally, the
number of cardiovascular deaths was
relatively small, limiting statistical
power for this outcome.
CONCLUSIONS
Using a highly sensitivity assay, cTnT
was detectable in approximately 25%
of adults in the general population and
was associated with structural heart dis-
ease and risk of subsequent all-cause
mortality. Higher cTnT levels, below the
detection range of currently available
assays, may be considered a marker of
“end organ” cardiovascular damage
from a variety of risk factors and patho-
logical cardiac and vascular processes.
Author Contributions: Dr de Lemos had full access to
all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: de Lemos, McGuire.
Acquisition of data: de Lemos, Khera, Hashim, McGuire.
Analysis and interpretation of data: de Lemos, Drazner,
Omland, Ayers, Khera, Rohatgi, Berry, Das, Morrow,
McGuire.
Drafting of the manuscript: de Lemos.
Critical revision of the manuscript for important in-
tellectual content: de Lemos, Drazner, Omland, Ayers,
Khera, Rohatgi, Hashim, Berry, Das, Morrow, McGuire.
Statistical analysis: Ayers.
Obtained funding: de Lemos, McGuire.
Administrative, technical, or material support: Hashim.
Study supervision: de Lemos.
Financial Disclosures: Dr de Lemos reported receiv-
ing research grants from Roche Diagnostics and
Biosite/Inverness and receiving consulting fees
and/or lecture honoraria from Tethys Biomedical,
Johnson & Johnson, Roche Diagnostics, Biosite/
Inverness, Siemens, AstraZeneca, Pfizer, BMS/sanofi-
aventis, and Merck/Schering. Dr Drazner reported
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
©2010 American Medical Association. All rights reserved. (Reprinted) JAMA, December 8, 2010—Vol 304, No. 22 2511
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 9
receiving consulting fees from Biosite/Inverness and
lecture honoraria from GlaxoSmithKline. Dr Omland
reported receiving research support and lecture
honoraria from Roche Diagnostics and Abbott Labo-
ratories. Dr Morrow reported receiving honoraria for
educational presentations from Beckman-Coulter, CV
Therapeutics, and Eli Lilly and receiving consulting
fees from Beckman-Coulter, Boerhinger Ingelheim,
Instrumentation Laboratories, Menarini, Merck,
sanofi-aventis, Servier, Roche Diagnostics, Siemens,
and AstraZeneca. The TIMI Study Group, which sup-
ports Dr Morrow’s salary, has received significant
research grant support from Accumetrics, Amgen,
AstraZeneca, Beckman Coulter, Bristol-Myers Squibb,
CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and
Co, GlaxoSmithKline, Integrated Therapeutics, Merck
and Co, Merck-Schering Plough Joint Venture,
Nanosphere, Novartis Pharmaceuticals, Nuvelo,
Ortho-Clinical Diagnostics, Pfizer, Roche Diag-
nostics, sanofi-aventis, Siemens, and Singulex. Dr
McGuire reported receiving grant support from
GlaxoSmithKline; receiving consulting fees from
Tethys Bioscience, Biosite, F. Hoffmann LaRoche/
Genentech, Cardiovascular Therapeutics,
AstraZeneca, Novo Nordisk, Daiichi-Sankyo, Mitsubi-
shi Tanabe Pharma, Johnson & Johnson, and sanofi-
aventis; and receiving lecture honoraria from Pfizer
and Takeda. No other authors reported disclosures.
Funding/Support: Grant support for the Dallas Heart
Study was provided by the Donald W. Reynolds Foun-
dation and by US Public Health Service General Clinical
Research Center grant M01-RR00633 from National In-
stitutes of Health (NIH)/NCRR-CR. This study was sup-
ported in part by the North and Central Texas Clinical
and Translational Science Initiative (NIH grant UL1
RR024982). Financial and materials support for mea-
surements of cardiac troponin T (cTnT) levels in the
present study were provided by Roche Diagnostics (In-
dianapolis, Indiana). Roche Diagnostics also previously
provided materials and support for measurement of lev-
els of cTnT, N-terminal pro-brain-type natriuretic pep-
tide, and C-reactive protein in the Dallas Heart Study.
Role of the Sponsor: Roche Diagnostics and the NIH
had no role in the design and conduct of the study;
the collection, management, analysis, and interpre-
tation of the data; or the preparation, review, or ap-
proval of the manuscript.
Online-Only Material: The eSupplement, eFigures 1-3,
and eTables 1-5 are available at http://www.jama
.com.
Additional Contributions: We thank Jerry Ashmore,
MT, and Barbara Morgan, MT, BS, MEd, for perform-
ing the highly sensitive cardiac troponin T assays and
Helen Hobbs, MD, Teresa Eversole, BS, and Kathleen
Wilkinson, MS, for their leadership of the Dallas Heart
Study. The affiliation for all additional contributors listed
is University of Texas Southwestern Medical Center,
Dallas. Partial salary support was provided to Barbara
Morgan and Jerry Ashmore.
REFERENCES
1. Anderson JL, Adams CD, Antman EM, et al. ACC/
AHA 2007 guidelines for the management of pa-
tients with unstable angina/non-ST-Elevation myo-
cardial infarction. J Am Coll Cardiol. 2007;50(7):
e1-e157.
2. Morrow DA, Cannon CP, Jesse RL, et al. National
Academy of Clinical Biochemistry Laboratory Medi-
cine Practice Guidelines: clinical characteristics and uti-
lization of biochemical markers in acute coronary
syndromes. Clin Chem. 2007;53(4):552-574.
3. Konstantinides S, Geibel A, Olschewski M, et al.
Importance of cardiac troponins I and T in risk strati-
fication of patients with acute pulmonary embolism.
Circulation. 2002;106(10):1263-1268.
4. Peacock WF IV, De Marco T, Fonarow GC, et al.
Cardiac troponin and outcome in acute heart failure.
N Engl J Med. 2008;358(20):2117-2126.
5. Eggers KM, Lagerqvist B, Venge P, et al. Persis-
tent cardiac troponin I elevation in stabilized patients
after an episode of acute coronary syndrome pre-
dicts long-term mortality. Circulation. 2007;116
(17):1907-1914.
6. Horwich TB, Patel J, MacLellan WR, Fonarow GC.
Cardiac troponin I is associated with impaired hemo-
dynamics, progressive left ventricular dysfunction, and
increased mortality rates in advanced heart failure.
Circulation. 2003;108(7):833-838.
7. Apple FS, Murakami MM, Pearce LA, Herzog CA.
Predictive value of cardiac troponin I and T for sub-
sequent death in end-stage renal disease. Circulation.
2002;106(23):2941-2945.
8. Wallace TW, Abdullah SM, Drazner MH, et al.
Prevalence and determinants of troponin T elevation
in the general population. Circulation. 2006;113
(16):1958-1965.
9. Daniels LB, Laughlin GA, Clopton P, et al. Mini-
mally elevated cardiac troponin T and elevated N-
terminal pro-B-type natriuretic peptide predict mor-
tality in older adults. J Am Coll Cardiol. 2008;
52(6):450-459.
10. Zethelius B, Johnston N, Venge P. Troponin I as
a predictor of coronary heart disease and mortality in
70-year-old men. Circulation. 2006;113(8):1071-
1078.
11. Blankenberg S, Zeller T, Saarela O, et al. Contri-
bution of 30 biomarkers to 10-year cardiovascular risk
estimation in 2 population cohorts. Circulation. 2010;
121(22):2388-2397.
12. Reichlin T, Hochholzer W, Bassetti S, et al. Early
diagnosis of myocardial infarction with sensitive car-
diac troponin assays. NEnglJMed. 2009;361(9):
858-867.
13. Latini R, Masson S, Anand IS, et al. Prognostic value
of very low plasma concentrations of troponin T in pa-
tients with stable chronic heart failure. Circulation.
2007;116(11):1242-1249.
14. Omland T, de Lemos JA, Sabatine MS, et al. A
sensitive cardiac troponin T assay in stable coronary
artery disease. N Engl J Med. 2009;361(26):2538-
2547.
15. Victor RG, Haley RW, Willett DL, et al. The Dal-
las Heart Study: a population-based probability sample
for the multidisciplinary study of ethnic differences in
cardiovascular health. Am J Cardiol. 2004;93(12):
1473-1480.
16. de Lemos JA, McGuire DK, Khera A, et al. Screen-
ing the population for left ventricular hypertrophy
and left ventricular systolic dysfunction using natri-
uretic peptides. Am Heart J. 2009;157(4):746-
753.
17. Khera A, McGuire DK, Murphy SA, et al. Race and
gender differences in C-reactive protein levels. JAm
Coll Cardiol. 2005;46(3):464-469.
18. Giannitsis E, Kurz K, Hallermayer K, et al. Ana-
lytical validation of a high-sensitivity cardiac tropo-
nin T assay. Clin Chem. 2010;56(2):254-261.
19. Das SR, Drazner MH, Dries DL, et al. Impact
of body mass and body composition on circulating
levels of natriuretic peptides: results from the Dallas
Heart Study. Circulation. 2005;112(14):2163-
2168.
20. Drazner MH, Dries DL, Peshock RM, et al. Left
ventricular hypertrophy is more prevalent in blacks than
whites in the general population: the Dallas Heart
Study. Hypertension. 2005;46(1):124-129.
21. Abdullah SM, Khera A, Das SR, et al. Relation
of coronary atherosclerosis determined by electron
beam computed tomography and plasma levels
of N-terminal pro-brain natriuretic peptide in a
multiethnic population-based sample (the Dallas
Heart Study). Am J Cardiol. 2005;96(9):1284-
1289.
22. National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treat-
ment of High Blood Cholesterol in Adults (Adult
Treatment Panel III). Third Report of the National
Cholesterol Education Program (NCEP) Expert Panel
on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (Adult Treatment Panel
III) final report. Circulation. 2002;106(25):3143-
3421.
23. See R, Lindsey JB, Patel MJ, et al. Application of
the screening for Heart Attack Prevention and Edu-
cation Task Force recommendations to an urban
population. Arch Intern Med. 2008;168(10):1055-
1062.
24. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart
disease and stroke statistics—2010 update: a report
from the American Heart Association [published cor-
rection appears in Circulation. 2010;121(12):e260].
Circulation. 2010;121(7):e46-e215.
25. Jonckheere AR, Bower GH. Non-parametric trend
tests for learning data. Br J Math Stat Psychol. 1967;
20(2):163-186.
26. Colosimo E, Ferreira F, Oliveira M, Sousa C. Em-
pirical comparisons between Kaplan-Meier and Nelson-
Aalen survival function estimators. J Stat Computa-
tion Computing. 2002;72(4):299-308.
27. Antolini L, Boracchi P, Biganzoli E. A time-
dependent discrimination index for survival data. Stat
Med. 2005;24(24):3927-3944.
28. Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr,
Vasan RS. Evaluating the added predictive ability of a
new marker. Stat Med. 2008;27(2):157-172, 207-
212.
29. Eggers KM, Lind L, Ahlström H, et al. Prevalence
and pathophysiological mechanisms of elevated car-
diac troponin I levels in a population-based sample of
elderly subjects. Eur Heart J. 2008;29(18):2252-
2258.
30. Apple FS, Quist HE, Doyle PJ, et al. Plasma 99th
percentile reference limits for cardiac troponin and cre-
atine kinase MB mass for use with European Society
of Cardiology/American College of Cardiology con-
sensus recommendations. Clin Chem. 2003;49
(8):1331-1336.
31. Eggers KM, Lagerqvist B, Oldgren J, Venge P,
Wallentin L, Lindahl B. Pathophysiologic mecha-
nisms of persistent cardiac troponin I elevation in sta-
bilized patients after an episode of acute coronary
syndrome. Am Heart J. 2008;156(3):588-594.
32. Wong GC, Morrow DA, Murphy S, et al. Eleva-
tions in troponin T and I are associated with abnor-
mal tissue level perfusion: a TACTICS-TIMI 18
substudy. Circulation. 2002;106(2):202-207.
33. Morrow DA, Cannon CP, Rifai N, et al. Ability of
minor elevations of troponins I and T to predict
benefit from an early invasive strategy in patients
with unstable angina and non-ST elevation myocar-
dial infarction. JAMA. 2001;286(19):2405-2412.
34. Lindahl B, Diderholm E, Lagerqvist B, Venge P,
Wallentin L. Mechanisms behind the prognostic value
of troponin T in unstable coronary artery disease: a
FRISC II substudy. J Am Coll Cardiol. 2001;38
(4):979-986.
35. Morrow DA, de Lemos JA. Benchmarks for the
assessment of novel cardiovascular biomarkers.
Circulation. 2007;115(8):949-952.
36. Keller T, Zeller T, Peetz D, et al. Sensitive tropo-
nin I assay in early diagnosis of acute myocardial
infarction. N Engl J Med. 2009;361(9):868-877.
37. Morrow DA, Antman EM. Evaluation of high-
sensitivity assays for cardiac troponin. Clin Chem. 2009;
55(1):5-8.
TROPONIN T AND CARDIAC STRUCTURE AND MORTALITY RISK
2512 JAMA, December 8, 2010—Vol 304, No. 22 (Reprinted) ©2010 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013
Page 10
  • Source
    • "Remarkably, circulating levels of CRP and BNP firmly established to be strongly associated with CV disease were concluded to only modestly improve CV risk assessment when evaluated together with traditional CV risk factors [6, 10, 11]. In a more recent report, levels of high-sensitivity troponin T (hsTnT) were associated with CV mortality but only marginally imporved a traditional risk factor model in the Dallas Heart Study [12]. In a similar fashion, plasma levels of apoA-I are not always superior to HDL-cholesterol as a predictor of CV risk [13]. "
    [Show abstract] [Hide abstract] ABSTRACT: Several protein biomarkers, including cardiac troponin T, cardiac troponin I, B-type natriuretic peptide, C-reactive protein and apolipoprotein A-I, are widely employed in the evaluation of cardiovascular disease. Several of such potential biomarkers, or their multiscores, have been assessed over the last years for the prediction of cardiovascular risk but only a few of them have been validated for clinical use. Substantial improvement in the cardiovascular risk prediction and reclassification relative to traditional models therefore remains a difficult task presently unresolved. Hence, a potential importance of alternative approaches which may rely on novel proteomic biomarkers among others. Plasma or serum concentrations of numerous proteins were measured using proteomic approaches to establish their relationships with cardiovascular disease; none of them was however evaluated for cardiovascular risk prediction and subject stratification in rigorous large-scale studies. Thus, further research is needed to identify novel candidates that can improve cardiovascular risk prediction, subject stratification and standard care. Proteomics will undoubtedly remain a key approach to address this major clinical and scientific challenge.
    Full-text · Article · Mar 2016 · Cardiovascular Drugs and Therapy
  • Source
    • "Second, other cardiac biomarkers, such as N-terminal pro-brain natriuretic peptide, and echocardiographic parameters, were not used as variables in the statistical analysis in the present study although it is known that the presence of heart failure and elevated levels of brain natriuretic peptide are associated with the elevation of hs-TnT levels [7,21,22]. Third, it is possible that the hazard of elevated hs-TnT may have been underestimated because patients in the OACIS registry with hs-TnT levels of 0.008 ng/mL were used as reference group, in contrast to several studies that have used patients with undetectable hs-TnT (<0.003 ng/mL) as a reference91011 . Finally, the optimal bloodsampling period for hs-TnT measurements after STEMI should be evaluated, because hs-TnT was negatively correlated with the blood-sampling period which indicated that about 21% (r = À0.46, "
    [Show abstract] [Hide abstract] ABSTRACT: Background: It is unclear whether serum high-sensitive troponin T (hs-TnT) levels at the convalescent stage of ST-elevation myocardial infarction (STEMI) are associated with long-term mortality. Methods: This study enrolled a total of 2944 consecutive STEMI patients who were registered in the Osaka Acute Coronary Insufficiency Study between 2000 and 2009, and whose hs-TnT levels were evaluated at the convalescent stage. Patients were divided into four hs-TnT category groups according to the results of survival classification and regression tree (CART) analysis. The impact of hs-TnT levels on 5-year mortality was evaluated using multivariate Cox regression analysis. Results: Only one patient had hs-TnT level below the detection limit of the assay (<0.003 ng/mL). The median hs-TnT level was 0.025 (quartile 0.011–0.083) ng/mL. During the median follow-up period of 1782 days, 188 patients died. Survival CART analysis revealed that the 1st, 2nd, and 3rd discriminating hs-TnT levels to discern 5-year mortality were 0.028, 0.008, and 1.340 ng/mL, respectively. The adjusted hazard ratios for the medium-low (0.009–0.028 ng/mL), medium-high (0.029–1.340 ng/mL), and high-risk (�1.341 ng/mL) groups were 3.03 (95% confidence interval 1.18–7.77, p = 0.021), 4.29 (1.63–11.28, p = 0.003), and 8.68 (2.20– 34.27, p = 0.002), respectively. Integrated discrimination improvement (IDI) analysis revealed that incorporation of this hs-TnT classification scheme with other clinical variables statistically improved the discriminatory accuracy for 5-year mortality, with a time-dependent IDI of 0.0076 (p = 0.033). Conclusions: hs-TnT levels at the convalescent stage were associated with long-term mortality in STEMI patients. Even subclinical elevation of hs-TnT levels was associated with increased 5-year mortality.
    Full-text · Article · Sep 2015 · Journal of Cardiology
  • Source
    • "However, not one patient in our study had severe renal dysfunction or autoimmune disease. Currently, there is no evidence that one can distinguish between cell death by necrosis [24] reflecting irreversible myocardial damage or apoptosis [25], but an increased hs-TnT is associated with adverse prognosis in other cardiac conditions [8] [9] [16]. Fig. 2. High-sensitive TnT and the relationship with NT-proBNP and hs-CRP. "
    [Show abstract] [Hide abstract] ABSTRACT: Adult congenital heart disease (ACHD) patients are at risk of late complications including arrhythmias, heart failure and sudden death. High-sensitive troponin-T (hs-TnT) is the standard for diagnosing acute coronary syndrome, but is also associated with cardiac function and prognosis in other cardiac diseases. We aimed to describe hs-TnT level in ACHD patients, and determine its relationship with cardiac function and other biomarkers. Consecutive ACHD patients, visiting the outpatient clinic, underwent echocardiography, exercise testing and venipuncture on the same day. In total 587 patients were included (median age 33 [IQR 25-41] years, 58% male, 90% NYHA class I). hs-TnT was above the detection limit of 5ng/L in 241 patients (41%), of whom 47 (8%) had hs-TnT levels above the 99th percentile of normal of 14ng/L. hs-TnT levels were highest in patients with a systemic RV or pulmonary hypertension. Patients with normal or non-detectable hs-TnT were younger (32 [IQR 24-40] years) than patient with elevated hs-TnT (42 [IQR 36-60] years, p<0.001). The prevalence of hs-TnT ≥14ng/L was higher in patients with NYHA ≥II (36%, p<0.001), systemic systolic dysfunction (38%, p<0.001), non-sinus rhythm (43%, p<0.001) and elevated pulmonary pressures (39%, p<0.001). hs-TnT was correlated with NT-proBNP (r=0.400, p<0.001). hs-TnT above the 99th percentile of normal is observed in a non-trivial portion of stable ACHD patients, especially in those with a systemic RV or elevated pulmonary pressures. Since this biomarker of myocardial damage is related to NT-proBNP and ventricular function, its potential predictive value in ACHD patients seems promising and further investigation of underlying mechanisms is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · International Journal of Cardiology
Show more

Similar Publications