More on the Performance of High Sensitivity Troponin T and with Amino Terminal Pro BNP in Diabetes
Writer and Curator: Larry H. Bernstein, MD, FCAP
UPDATED on 8/7/2018
Siemens’ high-sensitivity Troponin I (TnIH) assaysgot FDA clearance for use in diagnosing acute myocardial infarction. (Cardiovascular Business) The first high-sensitivity Troponin T test was cleared last year, as MedPage Today reported.
SOURCE
This is the final up to date review of the status of hs troponin T (or I) with or without the combined use of the Brain Type Natriuretic Peptide or its Amino Terminal peptide precursor. In addition, a new identification of the role of the Atrial Natriuretic Peptide has been reported with respect to arrythmogenic activity. On the one hand, the diagnostic value of the NT-proBNP has been seen as disappointing, in part because of the question of what information is gained by the test in overt known congestive heart failure, and in part because of uncertainty about following the test during a short hospital stay. At least, this is the view of this reviewer. However, in the last several years there has been an emphasis on the value this test adds to prediction of adverse outcomes. In addition, there has been a hidden nvariable that has much to do with the original reference values that were established for age ranges, without any consideration of pathophysiology that might affect the values within those ranges, leading one to consider values in an aging population as normal, that might well be high. Why is this? Aging patients are more likely to have hypertension, and also the onset of type-2 diabetes mellitus, with cardiovascular disease consequences. Type-2 diabetes mellitus (T2DM), for instance, is associated with insulin resistance and also fat gain with generation of adipokines, but the is also a hyalinization of insulin forming beta-cells of the pancreas, and there is hyalinization of glomeruli (glomerulosclerosis) and afferent arteriolonephrosclerosis with expected decline in glomerular filtrattion rate and hypertension as well. Of course, this is also associated with hepatosteatosis. Nevertheless, a reference range is established that takes none of this pathophysiology into account. While a more reasonable approach has been pointed out, there has been no followup in the literature.
On the other hand, there has been much confusion over the restandardization of a high sensitivity troponin I or T test (hs-Tn(I or T). The reference range declines precipitously, and there is a good identification of patients who are for the most part disease free, but there is no delineation of patients who are at high risk of acute coronary syndrome with plaque rupture, vs a host of other cardiovascular conditions. These have no relationship to plaque rupture, but may be serious and require further evaluation. The question then becomes whether to admit for a hospital stay, to refer to clinic after an evaluation in the ICU without admission, or to do an extensive evaluation in the emergency department overnight before release for followup. There is still another dimension of this that has to do with prediction of outcomes using hs-Tn(s) with or without the natriuretic peptides. Another matter that is not for discussion in this article is the underutilization of hs-CRP. Originally used for a marker of sepsis in the 1970s, it has come to be tied in with identification of an ongoing inflammatory condition. Therefore, the existence of a known inflammatory condition in the family of autoimmune diseases, with one exception, might make it unnecessary.
The discussion is broken into three parts:
Part 1. New findings on the troponins.
Part 2. The use of combined hs-Tn with a natriuretic peptide (NT-proBNP)
Part 3. Atrial natriuretic peptide
Part 1. New findings on the troponins.
Troponin: more lessons to learn
| C Liebetrau,HM Nef,andCW.Hamm* |
| KerckhoffHeartandThoraxCenter;DepartmentofCardiology,BadNauheim, Germany; (GermanCentreforCardiovascularResearch),partnersite RheinMain,BadNauheim, Germany; and UniversityofGiessen,Medizinische KlinikI,KardiologieundAngiologie,Giessen,Germany European Hear tJournal http://dx.doi.org/10.1093/eurheartj/eht357This editorial refers to ‘Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays’, by P. Haafetal. http://dx.doi.org/10.1093/eurheartj/eht218Cardiac troponin entered our diagnostic armamentarium 20 years ago and – unlike any other biomarker –
Troponin started out as a marker of risk in unstable angina’, then was used
The recently introduced high-sensitivity cardiac troponin (hs-cTn) assays
After many years troponins were accepted as the gold standard in
The new generation of hs-cTn assays has
Moreover, low levels of measurable troponins
Several studies demonstrated that
Furthermore, hs-cTn has the potential
The additional determination of hs-cTn
The daily clinical challenge in using the highly sensitive assays is to
The troponin test lost its ‘pregnancy test’ quality with the different users.
This uncertainty probably has the paradigm that
This is more than understandable, with acute chest pain using
What is a relevant change in concentrations compatible with acute myocardial necrosis and
Changes in serial measurements between 20% and 200% have been debated, and
it might be helpful in distinguishing AMI from other causes of cardiac troponin elevation. Do we obtain any helpful directives from experts and guidelines for our daily practice?
This was and still is the rule, but
The ‘Study Group on Biomarkers in Cardiology’ suggested
However, this group of experts could also not find a substitute for the missing data
The story is just too complex:
Therefore, any study that helps us to see better through the fog is welcome here. Haaf et al. have now presented the results of their study of
The authors examine 1117 consecutive patients presenting with acute chest pain.
Eighty-two patients (7.3%) died during the 2-year follow-up. The main finding of the study is that
These results of APACE remain in contrast to recent findings from a GUSTO IV cohortof 1335 patients with ACS (Table1). Table1 Studies investigating high sensitivity troponins for long-term prognosisVariable APACE (n 5 1117) GUSTO IV (n 5 1335) PEACE (n 5 3567)
Patient cohort Unstable Unstable Stable Blood sampling On admission,1,2,3,6h 48h after No. of patients with detection limit 883 (79.1%) UKN UKN No. of patients with hs-cTnT. No. of patients with hs-cTnI (Abbott). No.of patients with hs-cTnI (Abbott). No. of patients with NSTEMI 170 (15.2%) 100 (100%) 0 (0%) Follow-up 24 months 12 months 5.2 years Non-fatal AMI UKN UKN 209 (5.9%) Mortality or primary endpoint 82 (7.3%) 119(8.9%) 203 (5.7%)
Key findings cTnT better than cTnI cTnI ¼cTnT cTnI better than cTnT Single cTn sample sufficient NSTEMI defined in the GUSTO IV trial:
the prognostic capacity of four different sensitive cardiac troponin assays were compared
In total, 119 patients (8.9%) died during the 1-year follow-up. Looking at their
Contrasting results have also been reported in patients(n 1/4 3.623)
from the PEACE trial (Table1). During a median follow-up period of 5.2 years,
Concentrations of hs-cTnI (Abbott Diagnostics) at or above
This study revealed that
Hs-cTnI provided incremental prognostication information
In contrast to the APACE results, only hs-cTnI, but
Is there a real difference between cardiac troponin T and cardiac troponin I
The question arises of whether there is a true clinically relevant
Given the biochemical and analytical differences,the two
While minor biological differences between cTnT and cTnI are
This is a provocative theory, but appears premature in our opinion.
In the present study, hs-cTnT (Roche Diagnostics) outperformed
We don’t know how hs-cTnI from Abbott Diagnostics
The number of patients and endpoints provided
It is far too early to favour one high sensitivity assay over the other. The findings need confirmation. Implications for clinical practiceThere is no doubt that high-sensitivity assays
What is new?
However, the question of which troponin might be preferable
Part 2. ability of high-sensitivity cTnT and NT pro-BNP to predict cardiovascular events and death in patients with T2DMHillis GS; Welsh P; Chalmers J; Perkovic V; Chow CK; Li Q; Jun M; Neal B; Zoungas S; Poulter N; Mancia G; Williams B; Sattar N; Woodward M OBJECTIVECurrent methods of risk stratification in patients with
The current study assesses the ability of
to improve the prediction of cardiovascular events and death in patients with type 2 diabetes. RESEARCH DESIGN AND METHODSA nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTSSeven hundred nine (18%) patients experienced a
(composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and
In Cox regression models, adjusting for all established risk predictors,
The addition of either marker improved 5-year risk classification for cardiovascular events
Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted. CONCLUSIONSNT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the
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