Download Prognostic Assessment of Elderly Patients with Symptoms of Heart

Clinical Chemistry 56:11
1718–1724 (2010)
Proteomics and Protein Markers
Prognostic Assessment of Elderly Patients with Symptoms
of Heart Failure by Combining High-Sensitivity Troponin
T and N-Terminal Pro–B-Type Natriuretic
Peptide Measurements
Urban Alehagen,1* Ulf Dahlström,1 Jens F. Rehfeld,2 and Jens P. Goetze2
BACKGROUND: N-terminal pro–B-type natriuretic peptide (NT-proBNP) is a useful biomarker in heart failure
assessment, whereas measurement of cardiac troponin
is central in the diagnosis of patients with acute coronary syndromes. This report examined the prognostic
use of combining high-sensitivity cardiac troponin T
(hs-cTnT) and NT-proBNP measurements in elderly
patients presenting to a primary care center with symptoms associated with heart failure.
METHODS:
A total of 470 elderly patients (age range
65– 86 years) presenting with symptoms of heart failure
were recruited from primary healthcare. In addition to
clinical examination and echocardiography, hs-cTnT
and NT-proBNP plasma concentrations were measured. All patients were followed for 10 years, and cardiovascular mortality was registered.
RESULTS:
By use of the hs-cTnT assay, 80.4% of the
population had plasma concentrations above the lower
detection limit of the assay. Of those displaying a
plasma concentration of hs-cTnT ⬎99th percentile
of a healthy population, 43% also had an NT-proBNP
concentration in the fourth quartile (⬎507 ng/L). In
the multivariate analysis, we observed a 2.5-fold increased risk for cardiovascular mortality in individuals
with a plasma NT-proBNP concentration ⬎507 ng/L
(P ⬍ 0.0001). Conversely, patients with hs-cTnT
⬎99th percentile displayed an approximately 2-fold
increased risk for cardiovascular mortality (P ⫽
0.0002). Combining the 2 biomarkers, NT-proBNP
concentrations ⬎507 ng/L with hs-cTnT ⬎99th percentile increased the risk 3-fold, even after adjustment
for clinical variables such as age, sex, impaired estimated glomerular filtration rate, and anemia (P ⬍
0.0001).
1
Department of Medical and Health Sciences, Linkoping University, Linkoping,
Sweden; 2 Department of Clinical Biochemistry, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark.
* Address correspondence to this author at: Department of Cardiology, Heart
Center, University of Linköping, SE-581 85 Linköping, Sweden. Fax ⫹46-13222324; e-mail [email protected].
1718
CONCLUSIONS: hs-cTnT and NT-proBNP measurements combined provide better prognostic information than using either biomarker separately in elderly
patients with symptoms associated with heart failure.
© 2010 American Association for Clinical Chemistry
The pathophysiological concept of heart failure has
changed dramatically during the last decade with increased understanding of a multiorgan neurohormonal response (1, 2 ) as well as activation of immunological (3, 4 ) and inflammatory systems (5–7 ). As a
consequence, new biomarkers for diagnosis and prognosis in heart failure have emerged (8 –10 ). The use of
biomarkers extends from diagnostic assessment to
identification of patients at high risk for hospitalization
or cardiovascular mortality. B-type natriuretic peptide
(BNP)3 and the N-terminal fragment of the biosynthetic precursor (N-terminal pro–B-type natriuretic
peptide [NT-proBNP]) have been intensively examined as heart failure biomarkers (11 ).
The relation between increased plasma concentrations of cardiac troponin T (cTnT) or cTnI and acute
coronary syndrome is firmly established (12, 13 ). Interestingly, cardiac troponin concentrations near the
99th percentile of a healthy population have recently
been suggested to be associated with risk for cardiovascular complications and death (14, 15 ). Thus, small
increases in plasma cardiac troponin concentrations
below those usually observed in myocardial infarction
may indicate “low-grade” myocardial damage due to
nonischemic mechanisms (16 –18 ). Because the sensitivity of the cardiac troponin assays has improved
greatly, it is possible to test whether such small increases in plasma concentrations can provide prognostic information also in heart failure (19 ). From the
Received December 13, 2009; accepted August 20, 2010.
Previously published online at DOI: 10.1373/clinchem.2009.141341
3
Nonstandard abbreviations: BNP, B-type natriuretic peptide; NT-proBNP,
N-terminal pro–B-type natriuretic peptide; cTnT, cardiac troponin T; hs-cTnT,
high-sensitivity cTnT; EF, ejection fraction; AUC, area under the curve.
hs-cTnT and NT-proBNP in Heart Failure
American Acute Decompensated Heart Failure National Registry (ADHERE), it was reported that patients with acute heart failure and increased cTnT or
cTnI plasma concentrations displayed a 2.5-fold increased risk of death (20 ). However, this report was
based on troponin measurement using contemporary,
but not high-sensitivity, assays.
It has been suggested that using 2 biomarkers together in cardiovascular diagnosis and prognosis
may provide better risk information than using only 1
marker. For instance, this approach has been reported
in patients with stable coronary artery disease (15 ). The
aim of the present study was to evaluate if combined measurement of NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) provides useful prognostic information in an elderly population with symptoms associated
with heart failure in primary healthcare.
Materials and Methods
PATIENT POPULATION
We evaluated elderly patients with symptoms associated with heart failure seen in the primary healthcare
setting. The design of the study has already been published (21 ). In brief, all patients (n ⫽ 470) were between 65 and 87 years of age. All patients contacted the
primary health center because of symptoms (tiredness,
dyspnea, peripheral edema, or multiple symptoms). A
cardiologist visited the health center and reviewed all
records of patients with the above-listed symptoms.
The cardiologist met with the patients, performed a
clinical examination, and established a new patient
record. Patients in whom heart failure could not be
excluded were invited to participate in the study. All
patients included in the study were enrolled in 1996.
A new record was created and a clinical examination was carried out for each patient. We evaluated the
New York Heart Association (NYHA) functional class,
performed Doppler echocardiography, and took blood
samples. No patients were lost during follow-up, and all
patient deaths were recorded. The regional ethical review board in Linköping approved the study protocol.
DEFINITIONS
Cardiovascular mortality was defined as death caused
by heart failure, and/or fatal arrhythmia, sudden death,
ischemic heart disease, or cerebrovascular disease. Diabetes mellitus was defined as having a fasting blood
glucose ⬎7.0 mmol/L or already undergoing treatment
for diabetes (diet, oral therapy, or insulin). Hypertension was defined as a resting blood pressure ⬎140/90
mmHg, as measured in the right arm or having a prior
diagnosis of hypertension. Ischemic heart disease was
defined as a history of angina pectoris and/or treatment
for ischemic symptoms or on the basis of verified pre-
vious myocardial infarction. Dyspnea was defined
from the patient history, whereas presence of peripheral edema was defined from patient history and/or
clinical examination.
ECHOCARDIOGRAPHY
Doppler echocardiographic examinations (Acuson
XP-128c) were performed with the patient in the supine left position. Values for left ventricular systolic
function (22 ), expressed as ejection fraction (EF), were
categorized into 4 classes with interclass limits of 30%,
40%, and 50% (23, 24 ). Normal systolic function was
defined as EF ⱖ50%. Severely impaired systolic function was defined as EF ⬍30%.
BLOOD SAMPLES
The blood samples were obtained while the patients
were at rest in a supine position. All blood samples were
collected in plastic vials containing EDTA (ethylenediamine tetracetic acid). The samples were then placed
on ice before chilled centrifugation at 3000g and frozen
at ⫺70 °C, the temperature at which all samples were
kept until final analysis. The samples were only thawed
once (1997) before analyses of hs-cTnT (2009); in total,
there were 2 freeze-thaw cycles for the samples used in
this study.
NT-proBNP AND hs-cTnT ANALYSES
ProBNP 1–76 (NT-proBNP) was measured on the
Elecsys 2010 (Roche Diagnostics). This assay uses 2
polyclonal antibodies directed against amino acid sequences 1–21 and 39 –50, respectively. Total assay CV
was 4.8% at 220 ng/L and 2.1% at 4254 ng/L (n ⫽ 70).
hs-cTnT was also measured on the Elecsys 2010 platform using a new assay from Roche. This assay measures human troponin by using monoclonal antibodies
against amino acids 125–131 and 136 –147, respectively. The assay working range is reported as 3–10 000
ng/L, with an interassay CV according to the manufacturer of 3.1% at 24 ng/L and 1.3% at 300 ng/L. The
lower limit of quantification is 13 ng/L, the lowest limit
of detection is ⬍5 ng/L, and the limit of the blank is ⬍3
ng/L, as listed by the manufacturer. The 99th percentile
concentration limits as established in a healthy population were used for assay interpretation, and we
adopted the sex-specific 99th percentile limits reported
by Mingels et al. (males ⬎18 ng/L; females ⬎8 ng/L) in
our analyses (25 ).
STATISTICAL ANALYSES
Descriptive data are presented as percentages or mean
and SD. In the case of continuous variables, comparative analyses were performed by using the Student unpaired 2-sided t-test, whereas the ␹2 test was used for
discrete variables. Correlation was evaluated by using
Clinical Chemistry 56:11 (2010) 1719
the Pearson product–moment correlation coefficient.
Cox proportional hazard regression analyses as well as
a Kaplan–Meier analysis were used to analyze the risk
of mortality during the follow-up period. Censored patients were patients who were still alive at the end of the
study period or who had died of causes other than cardiovascular disease. Completed patients comprised
those who had died from cardiovascular disease.
A P value ⬍0.05 was considered statistically significant. To evaluate the possible additive prognostic effects of biomarkers in multivariate analysis, weighted
variables, obtained by summing each variable value in
the multivariate setting multiplied by the ␤ coefficients
of the multivariate Cox proportional hazard regression
function determined for each variable set, were analyzed by ROC analysis using the method of DeLong et
al. (26 ). All data were analyzed by using standard software packages (Statistica v. 9.1, Statsoft; Analyse-it
v.2.21, Analyse-it Software).
Table 1. Baseline characteristics of the
study population.a
n
1720 Clinical Chemistry 56:11 (2010)
73 (5.6)
M/F
242/228
Body mass index, mean (SD)
27 (4.3)
History
Smokers
151 (32)
Diabetes
100 (21)
Hypertension
412 (88)
NYHA class I
213 (45)
NYHA class II
204 (43)
NYHA class III
53 (11)
Medication
Results
In the study population, there was an approximately
equal distribution of sexes (245 men vs 225 women):
20% of study participants had diabetes and almost 90%
had been diagnosed with hypertension according to
present guidelines (Table 1). The total study population was followed for 10 years (mean 3199 days, SD
1094). The cause of death was determined by autopsy
in 10 patients; information given in the death certificates issued by the physician(s) in charge of the patient
was used to establish cause of death for all other cases.
Patients who survived during the follow-up period
were observed during a mean observation period of
3465 days (SD 796), and those who did not survive the
full 10 years were observed during a mean follow-up
period of 2027 days (SD 1080). During the 10-year
follow-up, 177 patients suffered all-cause mortality
(37%) and 119 patients suffered a cardiovascular death
(25%). There was a significant but poor correlation
between hs-cTnT and NT-proBNP concentrations
(r ⫽ 0.22, P ⬍ 0.0001). When examining only patients
with left ventricular dysfunction (e.g., EF ⬍40%), a
higher correlation (r ⫽ 0.42, P ⬎ 0.0001) was seen. In
the total cohort, 378 patients (80.4%) had a plasma
hs-cTnT concentration above the lower detection limit
(5 ng/L). A difference between male and females
patients was observed for hs-cTnT concentrations
(males: mean 16 ng/L, females: mean 11 ng/L; t ⫽ 2.59,
P ⫽ 0.03). In patients with a plasma hs-cTnT concentration above the 99th percentile of a healthy population, 43% (74/172) also displayed a plasma NTproBNP concentration in the fourth quartile. The
different quartiles of hs-cTnT and NT-proBNP are
470
Age, mean (SD)
Angiotensin-converting enzyme
inhibitors
156 (33)
␤ receptor blocker
189 (40)
Digitalis
47 (10)
Diuretics
207 (44)
Examinations
Increased cardio-thoracic ratio
EF ⬍40%
a
b
207 (44)
55 (12)
eGFRb ⬍60, mL
200 (42)
NT-proBNP, ng/L
220 (0–18 707)
hs-cTnT, ng/L
9.33 (3.0–220.3)
Data are n (%) or median (range) unless otherwise indicated.
eGFR, estimated glomerular filtration rate [Modification of Diet in Renal
Disease (MDRD) formula].
shown in Table 2. Of those in the first quartile of hscTnT, 10% had died of CV mortality and 11% in the
corresponding group of NT-proBNP. In the fourth
quartiles, the corresponding figures were 45% and 53%
for hs-cTnT and NT-proBNP, respectively. Among patients presenting with symptoms of heart failure and
left ventricular dysfunction (EF ⬍40%), 61.8% (34/55)
had a plasma hs-cTnT concentration above the 99th
Table 2. The different quartiles of hs-cTnT
and NT-proBNP.
Hs-cTnT cutoff
value, ng/L
NT-proBNP cutoff
value, ng/L
Quartile 1
⬍5.69
⬍110
Quartile 2
5.69–9.33
110–220
Quartile 3
9.33–15.3
220–507
Quartile 4
⬎15.3
⬎507
hs-cTnT and NT-proBNP in Heart Failure
percentile, and 67.3% (37/55) displayed a plasma NTproBNP concentration in the fourth quartile.
Cardiovascular mortality was evaluated in the entire study population; the results are presented in
Kaplan–Meier analyses in Fig. 1. Of patients who died
from cardiovascular disease during the follow-up period, 60.5% had plasma hs-cTnT concentrations
⬎99th percentile. Regarding the NT-proBNP concentrations, 52.5% of patients with plasma NT-proBNP
concentrations in the fourth quartile suffered a cardiovascular death compared with 10.9% among patients
with a plasma concentration in the first quartile. When
combining the 2 biomarkers in patients with a plasma
hs-cTnT concentration ⬎99th percentile and a plasma
NT-proBNP concentration in the fourth quartile,
62.2% had died a cardiovascular death during the
follow-up period. The results of cardiovascular mortality based on quartiles of the biomarkers are presented
in Tables 2 and 3. In the univariate Cox proportional
hazard regression comparing concentrations above
and below the cutoff, a 3.5- to 4.5-fold increased risk
was indicated by either of the biomarkers. When comparing patients in whom both biomarkers were above
the threshold with patients in whom both biomarkers
were below the threshold, a 5-fold increase in the risk
of cardiovascular mortality was seen (Table 3). In the
multivariate Cox regression, both hs-cTnT and NTproBNP concentrations above the cutoff indicate more
than 2 times the increased risk of cardiovascular mortality. However, combining the 2 biomarkers and analyzing those patients in whom both biomarkers were
above the cutoff values increased the risk by a factor 3
(Table 4). A ROC analysis was also performed by using
a 3-step model; step 1 consisted of clinical variables
only (symptoms: tiredness, dyspnea, previous or
present ischemic heart disease, diabetes, NYHA functional class III, male sex, age 70 –75 or ⬎75 years; signs:
rales, jugular distension, peripheral edema). Step 2
consisted of clinical variables plus NT-proBNP concentrations, and step 3 included clinical variables plus
NT-proBNP ⫹ hs-cTnT measurement. A difference in
area under the curve (AUC) values between model step
1 (AUC 0.78) and step 3 (AUC 0.84) (95% CI 0.01–
0.10, P ⫽ 0.009) could be shown.
Discussion
There is now solid evidence that measurement of
cardiac-derived natriuretic peptides and their biosynthetic precursors are useful in the evaluation of patients
with heart failure. By comparison, cardiac troponins
have a central role in diagnosing patients with acute
coronary syndromes. Recent data suggest that troponin measurement may have prognostic value, even in
heart failure patients who otherwise do not display
Fig. 1. A Kaplan–Meier analysis illustrating the survival from cardiovascular mortality in the study population during 10 years of follow-up.
The population was subdivided as follows: (A) NT-proBNP quartiles (quartile 3 vs quartile 4: P ⬍ 0.0001); (B) 99th percentile of
hs-cTnT (hs-cTnT ⬍99% vs hs-cTnT ⬎99%: P ⬍ 0.0001); and (C)
NT-proBNP quartiles and 99th percentile of hs-cTnT. Group 1:
NT-proBNP ⬍ quartile 4, hs-cTnT ⬍99th percentile; group
2: NT-proBNP in quartile 4, hs-cTnT ⬍99th percentile; group 3:
NT-proBNP ⬍ quartile 4, hs-cTnT ⬎99th percentile; group 4:
NT-proBNP in quartile 4, hs-cTnT ⬎99th percentile.
Clinical Chemistry 56:11 (2010) 1721
Table 3. Cardiovascular mortality in different patient groups depending on concentration of NT-proBNP
or hs-cTnT.
a
Univariate Cox proportional
hazard regression analysis,
hazard ratio (95% CI)
P
Cardiovascular
mortality, %
NT-proBNP in quartile 4 (⬎507 ng/L) vs
NT-proBNP ⱕ507 ng/L
4.31 (3.00–6.18)
⬍0.0001; ␹2: 61.8
52.5 vs 16.2
hs-cTnT ⬎99% gender specific vs hs-cTnT ⬍99%
gender specifica
3.15 (2.18–4.55)
⬍0.0001; ␹2: 39.3
41.9 vs 15.8
Both NT-proBNP in quartile 4 (⬎507 ng/L) ⫹
hs-cTnT ⬎99% gender specific vs NT-proBNP
ⱕ507 ng/L ⫹ hs-cTnT ⬍99% gender specifica
4.70 (3.25–6.81)
⬍0.0001; ␹2: 63.1
62.2 vs 18.4
hs-cTnT 99% gender specific: male patients: 18 ng/L, female patients 8 ng/L.
symptoms of ischemic heart disease (27 ). With the introduction of high-sensitivity assays, this perspective
can now be tested. We therefore evaluated the use of
NT-proBNP and hs-cTnT measurement and the possible benefit of using additive prognostic information
concerning cardiovascular mortality in a primary
healthcare population.
In the study population, a substantial fraction displayed plasma hs-cTnT concentrations above the lowest level of detection, even in the absence of ischemic
heart disease symptoms. This finding resembles earlier
results (28, 29 ). By using the less-sensitive assays in the
earlier studies, however, only a small part of the heart
failure population displayed plasma cTnT concentrations above the lower limit of detection. By using new
assays with increased sensitivity, the cardiac troponin
concentrations can now be determined at concentrations that may reflect discrete/early myocardial damage
(30 ). Whether presence of the cardiac troponins in
plasma is due to cardiomyocyte apoptosis or is a consequence of other pathophysiological processes still remains to be determined (14 ). Sex-specific cutoff values have also been reported, where male patients
have higher concentrations values compared with
female patients (25, 30 ). The precise sex differences
still need to be examined in reference individuals
Table 4. Cox proportional regression hazard analyses including clinical variables influencing cardiovascular
mortality in an elderly population followed for 10 years.
Hazard
ratio
Model I,
95% CI
P
Hazard
ratio
Age ⬎75 years
1.69
1.14–2.52
0.009
1.84
1.24–2.73 0.002
1.69
1.13–2.54
0.01
Male sex
1.52
1.02–2.26
0.04
1.72
1.14–2.58 0.01
1.60
1.08–2.39
0.02
NYHA III
1.96
1.22–3.15
0.005
2.42
1.52–3.86 0.0002
2.33
1.45–3.75
0.0005
EF ⬍40%
1.55
0.96–2.50
0.07
2.04
1.29–3.22 0.002
1.63
1.01–2.64
0.05
Ischemic heart disease
0.82
0.55–1.20
0.31
0.91
0.62–1.33 0.62
0.83
0.56–1.22
0.34
Body mass index ⬎27 kg/m
2
Model II,
95% CI
P
Hazard Model III,
ratio
95% CI
P
1.12
0.76–1.67
0.56
1.10
0.74–1.63 0.63
1.17
0.79–1.74
0.43
eGFRa ⬍60 mL
1.38
0.92–2.08
0.12
1.22
0.80–1.84 0.36
1.29
0.85–1.95
0.24
Diabetes
2.15
1.43–3.24
0.0002
1.71
1.13–2.58 0.01
2.02
1.35–3.03
0.0007
Hemoglobin ⬍120 g/L
1.80
0.97–3.35
0.06
1.52
0.81–2.83 0.19
1.54
0.83–2.86
0.18
NT-proBNP in quartile 4 (⬎507 ng/L)
2.56
1.95–4.49 ⬍0.0001
—
—
—
—
—
—
hs-cTnT ⬎99%
—
—
—
2.24
NT-proBNP in quartile 4 ⫹ hs-cTnT ⬎99%
—
—
—
—
a
—
—
1.46–3.43 0.0002
—
—
3.09
2.00–4.79 ⬍0.0001
eGFR, estimated glomerular filtration rate [Modification of Diet in Renal Disease (MDRD) formula]. hs-cTnT ⬎99%: sex-specific 99th percentile cutoffs in a healthy
population (males: 18 ng/L; females: 8 ng/L) were used in our study. NT-proBNP quartile 4: We used a lower-boundary concentration for the fourth quartile of
the plasma concentration of NT-proBNP (507 ng/L) as a cutoff in the study population. Model I: Clinical variables analyzed together with the fourth quartile of
NT-proBNP. Model II: Various clinical variables analyzed together with the 99th sex-specific hs-cTnT percentile. Model III: Various clinical variables analyzed
together with the fourth quartile of NT-proBNP ⫹ 99th sex-specific hs-cTnT percentile at the same time.
1722 Clinical Chemistry 56:11 (2010)
hs-cTnT and NT-proBNP in Heart Failure
(i.e., not patients), but the difference was nevertheless noted also in this study.
Whether minor myocardial damage takes place in
heart failure patients has recently been discussed by
Latini and Masson (9 ). The Kaplan–Meier analysis of
the proportion of cardiovascular mortality of the 2 biomarkers supports this (Fig. 1). However, the underlying pathophysiology of low plasma troponin T concentrations during heart failure still deserves to be
explored further. Notably, the heart failure syndrome
constitutes more than reduced ejection fraction of the
left ventricle, including changes in renal function and
other organs.
Both the univariate and multivariate Cox regression show that the prognostic information concerning
risk of cardiovascular death by use of hs-cTnT is as
reliable as NT-proBNP (Tables 3 and 4). Combining
the 2 biomarkers may further improve the identification of patients with increased myocardial wall tension
and minor myocardial damage, even in the absence of
ischemic symptoms. In both the univariate and multivariate evaluations, the increased risk was detected
even with the long observation time. Notably, a long
follow-up period often results in reduced importance
of cardiovascular events, since other conditions gain a
greater influence on total mortality (Table 4). In the
ROC analysis, the additive information from using
both biomarkers was significant and suggests a combined use of 2 biomarkers in clinical practice. The Cox
proportional hazard regression analysis also showed
additive information by using both markers (hazard
ratio increased from 2- to 3-fold).
The Val-Heft study reported similar results in
terms of additive prognostic information by using hscTnT measurement and a natriuretic peptide (14 ).
However, there are several important differences between that study and ours. First, the mean age of the
study population was ⬎10 years older than the population in the Val-Heft study. Second, there were unequal proportions of men and women in the Val-Heft
study that were not present in our study. Third, the
mean EF in the Val-Heft study was 27%, whereas the
majority of individuals in our population did not display impaired cardiac function according to Doppler
echocardiography. Fourth, in the Val-Heft study, the
natriuretic peptide assay used was BNP by a manual
indirect method (Shionogi, Shionoria assay), whereas
we used NT-proBNP. Fifth, the Val-Heft study used
the median as a cutoff, whereas we used the presently
recommended cutoff for diagnosing myocardial damage (i.e., the 99th percentile) (31 ). Consequently, our
cohort conforms better with the everyday clinical population. Finally, the patients identified by use of the
combined biomarker approach represent a high-risk
population (Fig. 1C). These patients should therefore
be handled as such, which suggests the use of a heart
failure outpatient clinic with a more aggressive treatment regimen (32 ). The choice of cutoff values of NTproBNP is based on the plasma concentration in the
study population. However, the fourth quartile of NTproBNP (⬎507 ng/L) is not far from the guidelines on
how to diagnose heart failure given by the European
Society of Cardiology, where a plasma concentration
⬎400 ng/L could be regarded as “uncertain diagnosis,”
and a concentration ⬎2000 ng/L gives the diagnosis
“chronic heart failure likely” if there are signs and
symptoms of heart failure (33 ). This could indicate
that the evaluated study population is representative
of the patients with signs/symptoms found in the
community.
Our study presents data that are based on
community-living elderly patients, i.e., the group seen
most frequently by clinicians in daily practice. In the
literature, the vast majority of studies report on a different age-group than the one that is most usually encountered in patients with heart failure in the community. Our study conforms better in this regard. We have
shown that hs-cTnT is a powerful prognostic indicator
for CV mortality among individuals with symptoms
associated with heart failure, even without overt ischemic symptoms. When the 2 biomarkers hs-cTnT and
NT-proBNP are combined, more information becomes available from this patient group, who often has
many comorbidities.
Author Contributions: All authors confirmed they have contributed to
the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design,
acquisition of data, or analysis and interpretation of data; (b) drafting
or revising the article for intellectual content; and (c) final approval of
the published article.
Authors’ Disclosures of Potential Conflicts of Interest: Upon
manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: None declared.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: Grants from the County Council of Östergötland, The Swedish Heart and Lung Foundation, and the strategic
research area “Inflammation, atherosclerosis and ischemic heart disease—new strategies for prevention, diagnosis and treatment,”
which is sponsored by the County Council of Östergötland and the
University of Linköping.
Expert Testimony: None declared.
Role of Sponsor: The funding organizations played no role in the
design of study, choice of enrolled patients, review and interpretation
of data, or preparation or approval of manuscript.
Acknowledgments: We thank laboratory technicians Lone Olsen
and Jan Kirkeby Simonsen for laboratory assistance with the highsensitivity troponin T measurements.
Clinical Chemistry 56:11 (2010) 1723
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