(Circulation. 2000;102:1964.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Cardiac Troponin T Predicts Mortality in Patients With End-Stage Renal Disease
From the Institute of Clinical Chemistry (J.D., S.W., A.A., C.L.) and the Division of Nephrology (U.D., H.-P.B., K.H.N.), University Hospital Magdeburg, Germany.
Correspondence to Dr Jutta Dierkes, Institute of Clinical Chemistry, Leipziger Str 44, D-39120 Magdeburg, Germany. E-mail jutta.dierkes{at}medizin.uni-magdeburg.de
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Abstract |
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Background—Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T.
Methods and Results—Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3.04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration).
Conclusions—We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.
Key Words: mortality • morbidity • cardiovascular diseases
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Introduction |
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End-stage renal disease (ESRD) occurs in
120 000
patients in Europe and in 500 000 patients worldwide. ESRD is
associated with substantially reduced life expectancy,1
which has been estimated to be <50% of the life expectancy of a
person of the same age but with normal renal function.2
The main causes of death in patients with ESRD are vascular disease and
infections, accounting for 60% to 70% of deaths.3 Age
and predialysis diseases such as diabetes mellitus or manifest
atherosclerosis are believed to have a pronounced
effect on survival time during hemodialysis therapy.3 4
Although these factors contribute to the prediction of survival,
mortality rate remains high even in nondiabetic, young patients
starting renal replacement therapy.5 6 It therefore
remains a challenge to find markers allowing an improvement in risk
assessment, diagnosis, and therapeutic outcome. Two variables were recently suggested to be of predictive importance in these patients: total homocysteine (tHcy) and cardiac troponin T (cTNT), which are found to be elevated in 80% to 100% and 30% of the patients, respectively. Homocysteine is an amino acid of the methionine metabolism, and elevation of its plasma concentration has been shown to be predictive of cardiovascular disease (CVD) events in patients with ESRD.7 8 Troponin T is a constituent of the myocardium and is specifically released during myocardial damage and is then detectable in blood. The prognostic value of cTNT in patients with ESRD was recently investigated in small-scale studies but remained controversial.9 10 Therefore, we prospectively investigated these variables in 102 patients for 2 years. We assessed their prognostic values for total mortality and CVD events (fatal and nonfatal) in comparison to established risk factors.
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Methods |
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Patients were included who had ESRD, treated by chronic intermittent hemodialysis at the outpatient Dialysis Center for
4
weeks. Only patients who were clinically stable at study entry were
included into the study (no acute cardiovascular or
other disease within 4 weeks before the study). Out of 112 patients
treated with hemodialysis in the center at study entry, 102 (91%) were
recruited. Reasons for exclusion were age >85 years (n=6) and unstable
clinical status at study entry (n=4). Informed consent was obtained
from each patient. At baseline, prevalent diseases, weight and height,
blood pressure, and lifestyle habits (smoking, vitamin supplements,
medication, erythropoietin use) were recorded. The adequacy of
dialysis was assessed by calculating the Kt/V at study entry according
to the double-pool method. A Kt/V value of >1.2 is regarded as an
indicator of adequacy of dialysis.11 A predialysis blood
sample was taken for analysis of clinical-chemical
variables (blood count, electrolytes, albumin, protein,
creatinine, urea, glucose) and of risk-associated factors:
total cholesterol, HDL-cholesterol,
LDL-cholesterol, triglycerides, apolipoprotein
B, lipoprotein(a), tHcy, serum and red blood cell folate, vitamin
B12, and cTNT. Clinical-chemical variables,
tHcy, folate and vitamin B12 were measured at
study entry. cTNT and lipoprotein(a) were measured in aliquots of the
serum samples obtained at study entry that had been stored for nearly 2
years at -70°C. Results of the clinical-chemical variables and
lipids were made available to the clinicians in charge for the patients
by means of the routine laboratory charts. Results of tHcy and the
vitamins, however, were not included into the routine analysis
at that time and therefore were not available to the clinicians but
kept at the laboratory.
Follow-Up
Patients were followed for 2 years. End points were first fatal
or nonfatal CVD event or death from all causes. Outcome was
recorded by the nephrologists of the dialysis center who were
unaware of the results for tHcy, vitamins, cTnT, and lipoprotein(a)
until the final outcome status was recorded. If a patient had
changed dialysis center, information about CVD events or death was
obtained from the dialysis center where the patient had been treated (9
patients). Four patients received a kidney transplant; these patients
were followed until the date of transplantation and then
censored.
In total, 4 patients were censored for the outcome "total mortality," all because of transplantation, and 21 patients were censored for the outcome "cardiovascular events," including those censored because of transplantation (n=4) and patients who died of other causes without having a cardiovascular event (n=17).
Definition of Baseline Diseases
CVD at baseline was considered if the patient had had a
myocardial infarction or unstable angina pectoris, if angiographically
proven hemodynamically relevant stenosis
(>50% of the luminal diameter) was present, or if the patient had
undergone bypass surgery or angioplasty. Cerebrovascular disease was
considered if the patient had a history of transient ischemic
attacks, stroke verified by computer tomography, or carotid artery
stenosis >70% verified by Doppler ultrasound.
Peripheral vascular disease was diagnosed by intermittent
claudication, combined with angiographically or sonographically proven
stenosis of the major arteries of the lower limbs or ulcers
caused by atherosclerotic stenosis or surgery for this
disorder. Hypertension was defined either as use of antihypertensive
drugs or a blood pressure >160/95 mm Hg.
Definition of Outcome Variables
Mortality
In case of death, the underlying cause and the date of death
were noted. Causes of death were categorized as CVD (sudden death,
myocardial infarction, heart failure, stroke, peripheral
arterial disease), infections (pneumonia, sepsis, viral
infections), tumors, and other causes. In 9 of 28 deaths (32%), the
underlying cause of death was verified by autopsy. In all cases, the
causes of death were verified by clinicians not involved in this study;
however, in a few cases, the cause of death could not be established
and was recorded as unknown.
Cardiovascular Events
Cardiac events were sudden death, acute myocardial infarction
(AMI), newly observed unstable angina pectoris (UAP), or requirement
for coronary bypass surgery or angioplasty. AMI was diagnosed
if at least 2 of the following criteria were fulfilled: clinical
status, elevated laboratory variables (heart enzymes, myoglobin),
and ECG changes. Catheterization was performed in
suspected AMI or UAP. Surgical revascularization
was performed after AMI, in UAP, or after clinical signs detected by
catheterization and if the patient’s general status
was eligible to perform surgery. Cerebrovascular events were stroke,
ischemic insults, or newly diagnosed >70% stenosis of
the extracranial carotid. Strokes and ischemic insults were
always verified by CT. Peripheral atherosclerotic disease
was diagnosed in occlusive peripheral disease stage IV
according to Fontaine or by angiographically or sonographically
detected >50% stenosis of the major arteries of the lower
limbs.
All cardiovascular events were verified by clinicians not involved in the study.
Statistical Analysis
Values are presented as mean±SD or as median with 5th
and 95th percentiles. In a first analysis, differences at
baseline were investigated between those who had a new CVD event and
those who remained without CVD within the follow-up period and between
those who died and those who were alive after 2 years, with the
Mann-Whitney U test used for skewed variables and the
Student’s t test used for normally distributed
variables. Discrete variables were compared by the
2 test. Observed survival was computed by the
Kaplan-Meier method. Cox proportional-hazards regression
analysis was used to examine the baseline variables that
were predictive of total mortality and cardiovascular
events. The models included those variables that showed significant
differences in the univariate analyses. Adjustments
were then made for baseline variables that were a priori
considered to be important predictors of mortality and
cardiovascular morbidity: age, time on dialysis,
baseline diabetes, and cerebrovascular disease. Results are
reported as relative risk (hazard ratios) with the respective 95%
confidence interval. A probability value of 0.05 was considered to be
significant, and all tests were 2-sided. All analyses were
carried out with SPSS version 8.0.
Analytical Methods
Routine clinical-chemical variables were measured by
standardized methods on autoanalyzers (Hitachi 747, Roche
Diagnostics) at the start of the study.
Plasma tHcy was determined in EDTA-plasma at study entry with a high-performance liquid chromatography method with fluorescence detection.12 Test tubes were immediately cooled and centrifuged, and the plasma was separated from the blood cells within 30 minutes. The upper reference limit of tHcy is 15 µmol/L, based on the mean±2 SD in a healthy population. Vitamin B12 and serum folate were analyzed with commercial test kits (Abbott IMx, Abbott Laboratories).
The cTNT concentration was measured in aliquots of serum samples stored at -70°C for nearly 2 years, with a second-generation test system with improved sensitivity (Roche Diagnostics, Mannheim, Germany). The upper reference limit of this test was 0.04 ng/mL.
Blinding
The laboratory staff and the researchers in the laboratory were
unaware of the baseline clinical status of the patients until the study
was completed. The clinical data including baseline and outcome status
of the patient was recorded by the clinicians, who were unaware of
the laboratory results of tHcy, vitamins, cTnT, and lipoprotein(a). The
blinding was realized by keeping the patients’ clinical data files
apart from the laboratory results files until the study was
completed.
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Results |
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Data on age, duration of dialysis, and baseline diseases of the patients are given in Table 1
. Of
102 patients, cTNT was above the limit of detection in 85 (83%)
patients and was above the reference limit of 0.04 ng/mL in 40 (38%)
patients. The concentration of tHcy exceeded the upper reference limit
of 15 µmol/L in 100 (98%) of the 102 patients.
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Total Mortality
After a follow-up period of 2 years (104 weeks), 28 patients (14
men and 14 women) had died. CVD was the main cause of death (n=11,
39%), followed by infections (n=9, 32%). Other causes of death were
tumors (n=2), unknown (n=3), and other causes (lung embolism, n=1;
acute pancreatitis, n=1; and discontinuation of dialysis, n=1). CVD
cases died of acute myocardial infarction (n=4), heart failure (n=5),
stroke (n=1), and peripheral vascular disease (n=1).
In a crude analysis performed with the Mann-Whitney
U test, there was no significant difference in age, time on
dialysis, blood pressure, or any of the lipids or lipoproteins measured
between patients who died and patients who survived. Significant lower
concentrations of creatinine and albumin but higher
concentrations of glucose, tHcy, and cTNT were measured in those who
died compared with patients who survived (Table 2). Furthermore, significantly more
patients with preexisting cerebrovascular disease and patients with
diabetes mellitus (type 1 or 2) died during follow-up.
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We calculated hazard ratios for total mortality by Cox regression
modeling. In the univariate Cox regression model,
creatinine, albumin, glucose, tHcy greater than the
median (33.6 µmol/L), baseline diabetes and cerebrovascular
disease, and cTNT were significantly associated with total mortality.
After adjustment for age, time on dialysis, baseline diabetes and
cerebrovascular disease, albumin, tHcy and cTNT were
significantly associated with mortality (Table 2
). Quartiles of tHcy were significantly
associated with mortality (Table 4). The
Figure shows the association of cTNT with
survival.
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Sensitivity and Specificity of cTNT
Cardiac troponin T concentrations >0.10 ng/mL were measured in 12
patients. Of these 12 patients, 10 died during the follow-up period.
Out of 40 patients showing cTNT concentrations >0.04 ng/mL, 18
patients died. Thus, the sensitivity of elevated cTNT for predicting
all-cause mortality was 83% at concentrations >0.10 ng/mL and 45% at
concentrations >0.04 ng/mL. Out of those with nondetectable cTNT
concentrations (n=17), all patients were alive after 2 years, leading
to a specificity of 100%.
New Events of CVD
During the follow-up period of 104 weeks, 33 patients had 1 new
fatal or nonfatal event of CVD (n=14 coronary, n=8
cerebrovascular, and n=13 peripheral vascular events). Two
patients had >1 event of CVD. In total, 18 of the 33 patients with CVD
events died (n=11 of CVD causes [n=9 related to coronary heart
disease], n=5 of infections, n=1 of a tumor, and n=1 of an unknown
cause).
There was no significant difference (by comparing the baseline data with the Mann-Whitney U test) between those with an event and those without an event with regard to age, time on dialysis, baseline coronary heart disease, tHcy and related variables, or cTNT. Significant differences were observed in triglyceride, glucose, and HDL-cholesterol levels. Higher HDL-cholesterol appeared to be protective. Patients with CVD event during follow-up had significantly more frequent baseline cerebrovascular disease and diabetes mellitus (type 1 or 2).
In the univariate Cox regression analysis, baseline
diabetes, cerebrovascular disease, glucose, and
triglycerides were associated with event-free follow-up. In
the adjusted model, only glucose and triglycerides were
significantly associated with event-free follow-up (Table 3).
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If only fatal CVD events (n=11) were included in the analysis, cTNT and glucose were strongly related to CVD mortality in the adjusted Cox regression model (hazard ratio [HR] 7.31 [1.85 to 28.83] for cTNT >0.05 ng/mL, HR 1.42 [1.08 to 1.87] for a 1-mmol/L increase of glucose, respectively), whereas albumin and tHcy greater than median were weakly related to CVD mortality (HR 0.77 [0.58 to 1.03] for a 2-g/L increase of albumin, HR 3.51 [0.89 to 14.02] for tHcy greater than median, respectively).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This prospective study investigated predictors for CVD and total mortality in patients with ESRD. The analysis revealed that established risk factors for CVD, unlike in populations with normal renal function, were only weakly related to CVD events and total mortality. In contrast, tHcy and particularly cTNT were closely related to total mortality.
Total homocysteine has been shown to be related to CVD events in populations with normal renal function,13 14 to mortality in patients with coronary heart disease,15 and to CVD events in patients with non–insulin-dependent diabetes mellitus.16 Three prospective studies have shown that tHcy is associated with CVD events in dialysis7 8 or predialysis patients.17 In the present study, we did not observe an association between CVD events and tHcy but a strong and independent association with total mortality. The lack of association between tHcy and CVD in patients with ESRD is difficult to explain but may be due to a dominant interference of renal failure as the primary determinant of tHcy concentrations, thus superimposing potential atherogenic processes that link tHcy with CVD. On the other hand, tHcy elevations were associated with total mortality. Potential underlying mechanisms might be an association of tHcy with inadequate nutrition and consequent vitamin deficiencies, wasting, or infections, all of which can increase all-cause morbidity and mortality.18 A biological explanation may be the concomitant increase in the precursor S-adenosylhomocysteine, which is a strong inhibitor of enzymatic methyl esterification of erythrocyte membrane proteins, thus reducing protein repair and contributing to structural damage of membrane proteins in uremia.19 However, our finding is in keeping with a recent study in patients with non–insulin-dependent diabetes mellitus, which reports that tHcy was related to all-cause mortality but not to cardiovascular mortality.20
Increased concentrations of cTNT have been shown to be associated with survival after myocardial infarction21 or in UAP22 in patients with normal renal function. The present study shows that in patients with ESRD, a single elevated cTNT value is strongly predictive of long-term mortality. This association was independent of baseline heart disease. In fact, among 12 patients with cTNT levels >0.10 ng/mL, 10 had died within 2 years (sensitivity 83%), whereas all 17 patients with undetectable cTNT concentrations were still alive (specificity 100% at this cutoff).
The cTNTs were only recently introduced into routine diagnostic strategies, and their prognostic value is still under investigation. For patients with ESRD, 2 recent studies9 23 with limited sample sizes and observation periods indicate that elevated cardiac troponin levels predict mortality. This finding, however, could not be reproduced in a recent study by Möckel et al.10 Our data are obtained from a larger patient group and a longer observation period and confirms the association between elevated cTNT and mortality. Furthermore, it shows that the prognostic power grows considerably as the follow-up period is extended.
The specificity of cTNT in patients with ESRD has been questioned, arguing that elevated levels might be due to cross-reactivity with skeletal muscle troponin T.24 However, the expression of cTNT isoforms in skeletal muscle of patients with ESRD has also been discussed.25 26 Furthermore, the second-generation troponin T assay used in the present study does not show cross-reactivity with skeletal muscle troponin.26 The data therefore suggest that the cTNT elevations in 40% of the patients truly reflect minor myocardial damage regardless of whether heart disease has been diagnosed at baseline. Patients with minor myocardial damage may consequently be more susceptible to infections and other causes of death. The lack of association between cTNT and CVD events, on the other hand, is explained by the fact that only 42% of all CVD events were cardiac events and that the remaining 58% (peripheral or cerebral events) are unlikely to affect cTNT concentrations.
It should be noted that other established risk parameters
were less useful in prediction of mortality or CVD events. These were
the conventional lipid parameters, including
lipoprotein(a), which had been proposed to be of prognostic
value.27 Only CVD events were modestly associated with
baseline glucose and triglycerides. However, this risk
increase was substantially lower than the 7-fold mortality risk
increase seen if cTNT exceeded 0.1 ng/mL.
In conclusion, we observed a strong association of tHcy and, particularly, cTNT with all-cause-mortality in patients with ESRD. Both deviations may be important for subsequent therapeutic strategies. tHcy can be reduced by vitamin supplementation.28 29 Nonetheless, even if tHcy concentrations cannot be normalized in patients with ESRD, vitamin supplementation may reduce mortality and morbidity. Concerning cTNT, preventive inhibition of platelet aggregation may be beneficial in analogy to patients with UAP.30 The clinical benefit of such approaches, however, remains to be proven.
Received March 23, 2000; revision received June 1, 2000; accepted June 1, 2000.
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References |
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|---|
1. Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Ann Intern Med. 1994;121:62–70.
2.
Byrne C, Vernon P, Cohen JJ. Effect of age and
diagnosis on survival of older patients beginning chronic dialysis.
JAMA. 1994;271:34–36.
3. Mallick NP, Jones E, Selwood N. The European (European Dialysis and Transplantation Association-European Renal Association) Registry. Am J Kidney Dis. 1995;25:176–187.[Medline] [Order article via Infotrieve]
4. Kjellstrand CM, Hylander B, Collins AC. Mortality on dialysis: on the influence of early start, patient characteristics, and transplantation and acceptance rates. Am J Kidney Dis. 1990;15:483–490.[Medline] [Order article via Infotrieve]
5. Schrander-vd Meer AM, van Saase JL, Roodvoets RP, et al. Mortality in patients receiving renal replacement therapy, a single center study. Clin Nephrol. 1995;43:174–179.[Medline] [Order article via Infotrieve]
6. Agodoa LY, Eggers PW. Renal replacement therapy in the United States: data from the United States renal data system. Am J Kidney Dis. 1995;25:119–133.[Medline] [Order article via Infotrieve]
7. Bostom AG, Shemin D, Verhoef P, et al. Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients: a prospective study. Arterioscler Thromb Vasc Biol. 1997;11:2554–2558.
8.
Moustapha A, Naso A, Nahlawi M, et al.
Prospective study of hyperhomocysteinemia as an adverse
cardiovascular risk factor in end-stage renal disease.
Circulation. 1998;97:138–141.
9. Porter GA, Norton T, Bennett WB. Troponin T, a predictor of death in chronic haemodialysis patients. Eur Heart J. 1998;19(suppl N);N34–N37.
10.
Möckel M, Schindler R, Knorr L, et al.
Prognostic value of cardiac troponin T and I elevations in renal
disease patients without acute coronary syndromes: a 9-month
outcome analysis. Nephrol Dial Transplant. 1999;14:1489–1495.
11. NKF-DOQI Clinical Practice Guidelines for Hemodialysis Adequacy: National Kidney Foundation. Am J Kidney Dis. 1997;30(suppl 3):S15–S166.
12. Vester B, Rasmussen K. High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Eur J Clin Chem Clin Biochem. 1991;29:549–554.[Medline] [Order article via Infotrieve]
13.
Boushey CJ, Beresford SA, Omenn GS, et al. A
quantitative assessment of plasma homocysteine as a risk factor for
vascular disease: probable benefits of increasing folic acid intakes.
JAMA. 1995;274:1049–1057.
14. Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet. 1995;346:1395–1398.[Medline] [Order article via Infotrieve]
15.
Nygard O, Nordrehaug JE, Refsum H, et al. Plasma
homocysteine levels and mortality in patients with coronary
heart disease. N Engl J Med. 1997;337:230–236.
16.
Hoogeveen EK, Kostense PJ, Beks PJ, et al.
Hyperhomocysteinemia is associated with an increased risk of
cardiovascular disease, especially in
non-insulin-dependent diabetes mellitus: a population-based study.
Arterioscler Thromb Vasc Biol. 1998;18:133–138.
17.
Jungers P, Massy ZA, Khoa TN, et al. Incidence
and risk factors of atherosclerotic cardiovascular
accidents in predialysis chronic renal failure patients: a prospective
study. Nephrol Dial Transplant. 1997;12:2597–2602.
18. Owen WF. Nutritional status and survival in end-stage renal disease patients. Miner Electrolyte Metab. 1998;24:72–81.[Medline] [Order article via Infotrieve]
19. Perna AF, Ingrosso D, Zappia V, et al. Enzymatic methyl esterification of erythrocyte membrane proteins is impaired in chronic renal failure: evidence for high levels of the natural inhibitor S-adenosylhomocysteine. J Clin Invest. 1993;91:2497–2503.
20. Stehouwer CDA, Gall MA, Hougaard P, et al. Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria. Kidney Int. 1999;55:308–314.[Medline] [Order article via Infotrieve]
21.
Ohman EM, Armstrong PW, Christenson RH, et al.
Cardiac troponin T levels for risk stratification in acute myocardial
infarction. N Engl J Med. 1996;335:1333–1341.
22.
Strubbs P, Collinson P, Moseley D, et al.
Prospective study of the role of cardiac troponin T in patients
admitted with unstable angina. BMJ. 1996;313:262–264.
23. Martin GS, Becker BN, Schulman G. Cardiac troponin-I accurately predicts myocardial injury in renal failure. Nephrol Dial Transplant. 1998;7:1709–1712.
24.
McLaurin MD, Apple FS, Voss EM, et al. Cardiac
troponin I, cardiac troponin T, and creatine kinase MB in dialysis
patients without ischemic heart disease: evidence of cardiac
troponin T expression in skeletal muscle. Clin Chem. 1997;43:976–982.
25.
Haller C, Hehelein J, Remppis A, et al. Cardiac
troponin T in patients with end-stage renal disease: absence of
expression in truncal skeletal muscle. Clin Chem. 1998;44:930–938.
26.
Ricchiuti V, Voss EM, Ney A, et al. Cardiac
troponin T isoforms expressed in renal diseased skeletal muscle will
not cause false-positive results by the second generation cardiac
troponin T assay by Boehringer Mannheim. Clin Chem. 1998;44:1919–1924.
27.
Cressman MD, Heyka RJ, Paganini EP, et al.
Lipoprotein(a) is an independent risk factor for
cardiovascular disease in hemodialysis patients.
Circulation. 1992;86:475–482.
28. Bostom AG, Shemin D, Lapane KL, et al. High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients. Kidney Int. 1996;49:147–152.[Medline] [Order article via Infotrieve]
29. Dierkes J, Domrose U, Ambrosch A, et al. Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease. Clin Nephrol. 1999;51:108–115.[Medline] [Order article via Infotrieve]
30.
Hamm CW, Heeschen C, Goldmann B, et al. Benefit
of abciximab in patients with refractory unstable angina in relation to
serum troponin T levels: c7E3 Fab Antiplatelet Therapy in Unstable
Refractory Angina (CAPTURE) Study Investigators. N Engl
J Med. 1999;340:1623–1629.
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R Sharma, D C Gaze, D Pellerin, R L Mehta, H Gregson, C P Streather, P O Collinson, and S J D Brecker Cardiac structural and functional abnormalities in end stage renal disease patients with elevated cardiac troponin T Heart, June 1, 2006; 92(6): 804 - 809. [Abstract] [Full Text] [PDF]
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 T. W. Wallace, S. M. Abdullah, M. H. Drazner, S. R. Das, A. Khera, D. K. McGuire, F. Wians, M. S. Sabatine, D. A. Morrow, and J. A. de Lemos Prevalence and Determinants of Troponin T Elevation in the General Population Circulation, April 25, 2006; 113(16): 1958 - 1965. [Abstract] [Full Text] [PDF]
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 H. Bozbas, A. Yildirir, and H. Muderrisoglu Cardiac enzymes, renal failure and renal transplantation. Clin. Med. Res., March 1, 2006; 4(1): 79 - 84. [Abstract] [Full Text] [PDF]
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 D. Satran, C. R. Henry, and T. D. Henry Reply J. Am. Coll. Cardiol., February 7, 2006; 47(3): 691 - 691. [Full Text] [PDF]
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|
 C. R. Henry, D. Satran, B. Lindgren, C. Adkinson, C. I. Nicholson, and T. D. Henry Myocardial Injury and Long-term Mortality Following Moderate to Severe Carbon Monoxide Poisoning JAMA, January 25, 2006; 295(4): 398 - 402. [Abstract] [Full Text] [PDF]
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N. A. Khan, B. R. Hemmelgarn, M. Tonelli, C. R. Thompson, and A. Levin Prognostic Value of Troponin T and I Among Asymptomatic Patients With End-Stage Renal Disease: A Meta-Analysis Circulation, November 15, 2005; 112(20): 3088 - 3096. [Abstract] [Full Text] [PDF]
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N. A. Abbas, R. I. John, M. C. Webb, M. E. Kempson, A. N. Potter, C. P. Price, S. Vickery, and E. J. Lamb Cardiac Troponins and Renal Function in Nondialysis Patients with Chronic Kidney Disease Clin. Chem., November 1, 2005; 51(11): 2059 - 2066. [Abstract] [Full Text] [PDF]
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 H.H.H. Feringa, J.J. Bax, O. Schouten, and D. Poldermans Ischemic heart disease in renal transplant candidates: Towards non-invasive approaches for preoperative risk stratification Eur J Echocardiogr, October 1, 2005; 6(5): 313 - 316. [Abstract] [Full Text] [PDF]
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R. Sharma, D. Pellerin, D.C. Gaze, J.S. Shah, C.P. Streather, P.O. Collinson, and S.J. Brecker Dobutamine stress echocardiography and cardiac troponin T for the detection of significant coronary artery disease and predicting outcome in renal transplant candidates Eur J Echocardiogr, October 1, 2005; 6(5): 327 - 335. [Abstract] [Full Text] [PDF]
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M. E. Suliman, P. Barany, K. Kalantar-Zadeh, B. Lindholm, and P. Stenvinkel Homocysteine in uraemia--a puzzling and conflicting story Nephrol. Dial. Transplant., January 1, 2005; 20(1): 16 - 21. [Full Text] [PDF]
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E. R. Perna, S. M. Macin, J. P. C. Canella, N. Augier, J. L. R. Stival, J. R. Cialzeta, A. E. Pitzus, E. H. Garcia, R. Obregon, M. Brizuela, et al. Ongoing Myocardial Injury in Stable Severe Heart Failure: Value of Cardiac Troponin T Monitoring for High-Risk Patient Identification Circulation, October 19, 2004; 110(16): 2376 - 2382. [Abstract] [Full Text] [PDF]
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A. Boulier, I. Jaussent, N. Terrier, F. Maurice, J.-P. Rivory, L. Chalabi, A.-M. Boularan, C. Delcourt, A.-M. Dupuy, B. Canaud, et al. Measurement of circulating troponin Ic enhances the prognostic value of C-reactive protein in haemodialysis patients Nephrol. Dial. Transplant., September 1, 2004; 19(9): 2313 - 2318. [Abstract] [Full Text] [PDF]
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E. Giannitsis, H. A. Katus, J. H.C. Diris, C. M. Hackeng, M. P. van Dieijen-Visser, J. P. Kooman, Y. M. Pinto, and W. T. Hermens Troponin T Release in Hemodialysis Patients * Response Circulation, July 20, 2004; 110(3): e25 - e26. [Full Text] [PDF]
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B. Hocher, R. Ziebig, R. Krause, G. Asmus, H.-H Neumayer, L. Liefeldt, and J.-P. Stasch Relaxin Is an Independent Risk Factor Predicting Death in Male Patients With End-Stage Kidney Disease Circulation, May 18, 2004; 109(19): 2266 - 2268. [Abstract] [Full Text] [PDF]
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A. Scholze, C. Rinder, J. Beige, R. Riezler, W. Zidek, and M. Tepel Acetylcysteine Reduces Plasma Homocysteine Concentration and Improves Pulse Pressure and Endothelial Function in Patients With End-Stage Renal Failure Circulation, January 27, 2004; 109(3): 369 - 374. [Abstract] [Full Text] [PDF]
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J. Ishii, W. Cui, F. Kitagawa, T. Kuno, Y. Nakamura, H. Naruse, Y. Mori, T. Ishikawa, Y. Nagamura, T. Kondo, et al. Prognostic Value of Combination of Cardiac Troponin T and B-Type Natriuretic Peptide after Initiation of Treatment in Patients with Chronic Heart Failure Clin. Chem., December 1, 2003; 49(12): 2020 - 2026. [Abstract] [Full Text] [PDF]
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B. Hocher, R. Ziebig, C. Altermann, R. Krause, G. Asmus, C.-M. Richter, T. Slowinski, P. Sinha, and H.-H. Neumayer Different Impact of Biomarkers as Mortality Predictors among Diabetic and Nondiabetic Patients Undergoing Hemodialysis J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2329 - 2337. [Abstract] [Full Text] [PDF]
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C. deFilippi, S. Wasserman, S. Rosanio, E. Tiblier, H. Sperger, M. Tocchi, R. Christenson, B. Uretsky, M. Smiley, J. Gold, et al. Cardiac Troponin T and C-Reactive Protein for Predicting Prognosis, Coronary Atherosclerosis, and Cardiomyopathy in Patients Undergoing Long-term Hemodialysis JAMA, July 16, 2003; 290(3): 353 - 359. [Abstract] [Full Text] [PDF]
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R. Ziebig, A. Lun, B. Hocher, F. Priem, C. Altermann, G. Asmus, H. Kern, R. Krause, B. Lorenz, R. Mobes, et al. Renal Elimination of Troponin T and Troponin I Clin. Chem., July 1, 2003; 49(7): 1191 - 1193. [Full Text] [PDF]
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P. Ammann, M. Maggiorini, O. Bertel, E. Haenseler, H. I. Joller-Jemelka, E. Oechslin, E. I. Minder, H. Rickli, and T. Fehr Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2004 - 2009. [Abstract] [Full Text] [PDF]
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B. J. Freda, W. H. W. Tang, F. Van Lente, W. F. Peacock, and G. S. Francis Cardiac troponins in renal insufficiency: Review and clinical implications J. Am. Coll. Cardiol., December 18, 2002; 40(12): 2065 - 2071. [Abstract] [Full Text] [PDF]
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C. W. Hamm, E. Giannitsis, and H. A. Katus Cardiac Troponin Elevations in Patients Without Acute Coronary Syndrome Circulation, December 3, 2002; 106(23): 2871 - 2872. [Full Text] [PDF]
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F. S. Apple, M. M. Murakami, L. A. Pearce, and C. A. Herzog Predictive Value of Cardiac Troponin I and T for Subsequent Death in End-Stage Renal Disease Circulation, December 3, 2002; 106(23): 2941 - 2945. [Abstract] [Full Text] [PDF]
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C. Lowbeer, A. Gutierrez, S. A. Gustafsson, R. Norrman, J. Hulting, and A. Seeberger Elevated cardiac troponin T in peritoneal dialysis patients is associated with CRP and predicts all-cause mortality and cardiac death Nephrol. Dial. Transplant., December 1, 2002; 17(12): 2178 - 2183. [Abstract] [Full Text] [PDF]
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S. Fredericks, J. F. Murray, N. D. Carter, A. M.S. Chesser, S. Papachristou, M. M. Yaqoob, P. O. Collinson, D. Gaze, and D. W. Holt Cardiac Troponin T and Creatine Kinase MB Content in Skeletal Muscle of the Uremic Rat Clin. Chem., June 1, 2002; 48(6): 859 - 868. [Abstract] [Full Text] [PDF]
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C. A. Herzog Dismal long-term survival of dialysis patients after acute myocardial infarction: can we alter the outcome? Nephrol. Dial. Transplant., January 1, 2002; 17(1): 7 - 10. [Full Text] [PDF]
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M. J. Quinn and D. J. Moliterno Troponins in Acute Coronary Syndromes: More TACTICS for an Early Invasive Strategy JAMA, November 21, 2001; 286(19): 2461 - 2462. [Full Text] [PDF]
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S. Fredericks, J. F. Murray, M. Bewick, R. Chang, P. O. Collinson, N. D. Carter, and D. W. Holt Cardiac Troponin T and Creatine Kinase MB Are Not Increased in Exterior Oblique Muscle of Patients with Renal Failure Clin. Chem., June 1, 2001; 47(6): 1023 - 1030. [Abstract] [Full Text] [PDF]
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G. K. Davis, R. Labugger, J. E. Van Eyk, and F. S. Apple Cardiac Troponin T Is Not Detected in Western Blots of Diseased Renal Tissue Clin. Chem., April 1, 2001; 47(4): 782 - 783. [Full Text] [PDF]
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D. S. Ooi, D. Zimmerman, J. Graham, and G. A. Wells Cardiac Troponin T Predicts Long-Term Outcomes in Hemodialysis Patients Clin. Chem., March 1, 2001; 47(3): 412 - 417. [Abstract] [Full Text] [PDF]
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