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David Plaut: Off the Cuff

Myocardial Infarction
January 6, 2015 10:41 AM by David Plaut

Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an essential role in diagnosis, risk stratification, guiding management and clinical decision making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) has evolved to be the cornerstone for diagnosis of MI. The current criteria for MI diagnosis include a rise and/or fall in cTn with at least one value above the 99th percentile of the upper reference limit.

Sethi et al. reviewed 15 studies with a total of 8,628 patients. HsTrop T (Hoffman-La Roche Ltd) and hsTrop I (Siemens) had sensitivities of 0.89 and 0.90 and specificities of 0.79 and 0.89, respectively. Interestingly, there was no statistically significant difference in the area under the curve between hsTrop conventional Trop at the 99th percentile.


Biener et al. followed 635 patients with a hs-cTnT >99th percentile admission value were enrolled. Of these, 572 patients qualified for evaluation with rising patterns (n=254), falling patterns (n=224) or falling patterns following an initial rise (n=94).During 407days of follow-up, we observed 74 deaths, 17 recurrent AMI, and 79 subjects with a composite of death/AMI. Admission values >14ng/L were associated with a higher rate of adverse outcomes.  Neither rising nor falling changes increased the AUC of baseline values. “Neither rising nor falling hs-cTnT changes improve the prognostic performance of elevated hs-cTnT admission. However, rising values are more likely associated with the decision for earlier invasive strategy.”  DP notes that all patients had an elevated hs-TnI upon admission. The study did not include patients with a ‘normal’ hs-TnI.


Vasc Health Risk Manag. 2014 Jul 21;10:435-50.

Clin Chim Acta. 2014 Aug 5;435:29-35. 

An Update on Troponin
December 28, 2014 11:02 AM by David Plaut

During a 12 month period, Villemain et al. analysed 102 patients. Final diagnosis was NSTEMI for 7.8% (n=8), unstable angina for 3.9% (n=4), cardiac but non-coronary artery disease for 8.8% (n=9), non-cardiac chest pain for 52% (n=53) and unknown for 27.5% (n=28). There was no statistical difference for copeptin values between patients with NSTEMI and others (respectively 5.5 pmol/L and 6.5 pmol/L. Only one patient with NSTEMI had a copeptin value above the cut-off of 95th percentile at admission.

The diagnosis of NSTEMI, in these patients showing suspected symptoms of ACS, was defined by a rise and/or fall of hs-cTnT with at least one value above the 99th percentile and with the following criteria: imaging evidence of new loss of viable myocardium or new regional wall motion abnormality or identification of an intracoronary thrombus by angiography.

Myeloperoxidase (MPO) levels from 266 patients revealed a sensitivity (Sens) of 82% and specificity (Spec) of 37% for major adverse cardiac events (MACE) compared with 61% Sens and 61% Spec for sensitive cTnI. In serial sensitive cTnI negative patients (n=218), MACE incidence was 6.4. (DP notes that these sens and spec may be misleading for as you know, lowering the spec raises the sen.  Which might change the interpretation.  See the table below.  I made this table to make the point.  Had another cut-off been chosen for one or the other tes, the sen and spec would have been nearly the same!)

              Test A

              Test B






































1.     Vasc Health Risk Manag. 2014 Jul 21;10:435-50

2.     BMJ Open. 2014 Mar 24;4(3):e004449

3.     Eur Heart J Acute Cardiovasc Care. 2013 Sep;2(3):203-10.

4.     Circ Cardiovasc Genet. 2012 Oct 1;5(5):561-8.

Cystatin C
December 16, 2014 10:42 AM by David Plaut

Recently, in one of the blogs, I discussed NGAL. In that blog, I mentioned cystatin C (CC). It occurred to me that all laboratories do not offer CC. Here, adapted from the September, 2013 issue of Am. J. of Kidney Disease, is a series of questions and answers about cystatin.

What if my lab cannot measure cystatin C?
The 2012 KDIGO guidelines will likely increase demand for CC, and we encourage clinicians to request CC from their clinical labs.

Is CC too expensive for routine measurement?
Because CC is automated, the labor costs are minimal and the primary costs are the reagents. This cost is less than or equivalent to the cost of several tests that nephrologists and cardiologists frequently order: troponin (~ $10), and B-type natriuretic peptide (~$15).

Which equation should we use?
The new CKD-EPI equations currently appear to be the best available GFR estimating equations using CC.

The choice of the combined creatinine-CC equation versus the CC alone equation depends upon the diagnostic strategy. If the goal is to choose the optimal GFR estimate for either screening or a specific clinical indication, then the combined eGFR(cr-cys) should be used. On the other hand, if CC is used as a secondary test based on the results of eGFRcr, then the eGFRcys should be used so that creatinine is not in both the screening and verification steps of a GFR estimating strategy. The approach in Sweden is to compare the eGFRcr and eGFRcys: if they are within 40% of one another, then their average is the best estimate; if the difference is >40%, then clinicians should choose the estimate least likely to be biased based on clinical characteristics.

Is it important to monitor changes in eGFR using CC?
Cystatin C may have advantages over creatinine for detecting acute changes in eGFR in the hospital setting for patients in intensive care; however, minimal difference was observed for patients undergoing cardiac surgery.50,51 Overall, we do not believe that routine use of cystatin C is warranted for monitoring acute changes in kidney function.


1.            Am J Kidney Dis. Sep 2013; 62(3): 595–603. This review article is available free. Just click on the reference itself.

December 9, 2014 10:45 AM by David Plaut

Recently, near my home in Texas, there was an Ebola scare when a case appeared quite unexpected until a little investigation discovered that the patient had been exposed on a recent trip. This suggested to me that a short blog on Ebola was in order. Ergo…

As of August 13, 2014, 2,127 patients across four West African countries have been infected with the Ebola virus over the past nine months. Among these patients, approximately 50 percent subsequently died from the disease. Ebola is transmitted only by patients who already present symptoms of the disease, and infection only occurs upon only direct contact with the blood or body fluids of an Ebola patient. Consequently, transmission of the outbreak can be contained through careful monitoring for fever among persons who have visited, or come into contact with persons from, the site of the outbreak. Thus, patients suspected of presenting symptoms characteristic of Ebola should be quarantined.

Here is where we are with regard to vaccines:

•             Successful EBOV vaccine candidates have been identified in preclinical studies

•             Gene-based EBOV vaccines are immunogenic in human clinical trials

•             An ideal EBOV vaccine will give rapid and durable immunity against multiple EBOV species


1.            BMC Medicine 2014, 12:196

2.            Neth J Med. 2014 Nov;72(9):442-8.

3.            J Venom Anim Toxins Incl Trop Dis. 2014 Oct 3;20(1):44

4.            BMC Med. 2014 Oct 10;12(1):196

Triage of Women with Minor Cervical Lesions
December 2, 2014 11:21 AM by David Plaut

Atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intra-epithelial lesions (LSIL) are minor lesions of the cervical epithelium detectable by cytological examination of cells collected from the surface of the cervix of a woman. Usually, women with ASCUS and LSIL do not have cervical (pre-) cancer. However, a substantial proportion of them do have underlying high-grade cervical intra-epithelial neoplasia (CIN, grade 2 or 3) and are at increased risk for developing cervical cancer. Therefore, accurate triage of women with ASCUS or LSIL is required to identify those who need further management.

Arbyn et al. studied two approaches to triage women with ASCUS or LSIL: 1) Repeating the cytological test, and 2) DNA testing for high-risk types of the human papillomavirus (hrHPV) -- the main causal factor of cervical cancer. They concluded that HPV-triage with HC2 for assay can be recommended because it has higher accuracy (significantly higher sensitivity, and similar specificity) than repeat cytology. When triaging women with LSIL, an HC2 test yields a significantly higher sensitivity, but a significantly lower specificity compared to a repeat cytology. Therefore, practice recommendations for management of women with LSIL should be balanced, taking local circumstances into account. (Keep in mind that it is possible that, by lowering the sensitivity, the specificity will increase, and thus it is possible that HC2 and cytology may be quite similar.)

It is the practice in some places that repeat cytology and HPV testing comprise delayed triage. Sorbye et al. compared HPV mRNA with HPV DNA to determine which was better for the HPV part. Their follow-up study of 311 women aged 25-69 years with ASC-US/LSIL index cytology indicated that, in triage of repeated ASC-US/LSIL, HPV mRNA testing is more specific and is more relevant in clinical use than an HPV DNA test.


1.            Cochrane Database Syst Rev. 2013 Mar 28;3:CD008054. HPV testing versus repeat

2.            PLoS One. 2014 Nov 18;9(11):e112934. HPV mRNA Is More Specific than HPV DNA

3.            Curr Pharm Des. 2013; 19(8):1401-5. HPV mRNA testing in triage of women with ASC-US cytology may reduce the time for CIN2+diagnosis compared with repeat cytology.

Has Neutrophil Gelatinase-Associated Lipocalin (NGAL) Made ‘The Big Time'?
November 24, 2014 11:17 AM by David Plaut

During the past few years a number of investigations of NGAL have demonstrated that this marker is a "useful biomarker in clinical nephrology which is helpful to diagnosis and evaluate the categories for CKD proposed by the KDIGO." In a recent study Xiang et al found that the concentration of the NGAL increased progressively with the increasing of risk categories (proposed by the revised CKD classification). The cutoff value of NGAL was calculated from stage 2 to stage 5. ROC analysis showed the AUC (serum NGAL > 0.8, urine NGAL > 0.7) and high specificity (sNGAL > 87%, uNGAL > 90%) on the cutoff value of NGAL.  Along the same lines, Shen et al noted five positive results in their study of NGAL: First, the serum NGAL levels of patients with stage 2-4 CKD were significantly increased compared with the control group. Second, there were positive correlations between NGAL and cystatin C levels and between NGAL and serum creatinine levels. Third, bounded by the progress of renal function, the area under the curve of serum NGAL was 0.87. A cut-off level of 246 ng/mL gave a sensitivity of 85% and a specificity of 82%. Fourth, Kaplan-Meier survival curve analysis showed that the serum NGAL level was closely related to the end-point of renal function in patients with CKD. Fifth, Cox multivariate regression analysis showed that the estimated glomerular filtration rate and blood NGAL are associated with progression of CKD.


1.       Int J Clin Exp Pathol. 2014 Sep 15;7(10):7172-81

2.       Nephrology (Carlton). 2014 Mar;19(3):129-35

3.       Am J Kidney Dis. 2009 Dec;54(6):1012-24

Pre-analytical errors
November 4, 2014 11:48 AM by David Plaut

Pre-analytical errors remain the most common source of errors that a hospital laboratory must deal with. Specimen rejection is one of the pre-analytical errors. These while rare (0.2% Ref. 1), they have significant results – patient discomfort, delays in correct sample and a high rate of specimen or test discarded.

In a recent study Karcher and Lehman (1) found that the reason for most rejected specimens (92.4%) was inappropriate or inadequate specimen. The remaining 7.6% were rejected owing to improper labeling. Regarding specimens found to be improperly labeled, most (73.6%) were detected by laboratory review (“lab check”), 9.9% by feedback from caregiver, and 9.1% by delta check during the analytical phase.. Most rejected specimens (87.7%) were ultimately recollected, 1.1% were relabeled or corrected, and 11.2% were abandoned (neither recollected nor relabeled .)

Specimen rejection led to a (1) high rate of specimen recollection, (2) delay in result availability (median of 65 minutes), and (3) high rate of specimen/test abandonment. Relabeling of incorrectly labeled specimens was found to be of little benefit and was associated with a substantial percentage of subsequently mislabeled specimens.

Hemolyzed specimens continue to be a frequent occurrence in clinical laboratories. The prevalence can be as high as 3.3% of all of the routine samples, accounting for up to 40%-70% of all unsuitable specimens identified, nearly five times higher than other causes, such as insufficient, incorrect and clotted samples.


1.            Arch Pathol Lab Med. 2014 Aug;138(8):1003-8.

2.            Clin Chem Lab Med. 2008;46(6):764-72

Using correct SDs and Means together with TE and Tea
October 29, 2014 11:19 AM by David Plaut

I have seen data recently that indicate that some laboratories are not using their measured SDs (and sometimes means) for monitoring their QC. This can have two ramifications:

1) the QC will appear to be in control more often, saving time and trouble and

2) the analytical system may develop an error that could be missed by the incorrect SD (and mean).

This would lead to erroneous data being reported to the clinical staff. Which could lead to a missed diagnosis, an incorrect diagnosis, more laboratory tests, perhaps ‘scans’ or biopsies or worse. This is especially possible if the QC system does not use both the TE (total error = bias + 2*SD) AND the total error allowed (TEa, from for example CLIA or CAP) as a limit. In other words the TE must be less than the TEa for the QC system to be in control.

Here is an example of what I am saying. Suppose the SD for an analyte is 3.0 with a mean of 52 (and a peer mean of 50) and a TEa of 18%. The %TE is (52-50)*100/50 +2*6% =16%. Which is within the TEa. Suppose, however the laboratory sets the SD at 5. Without looking into the TEa the laboratory may go along reporting errors without being aware of that. It is obvious that setting the SD incorrectly is less likely if both TE and TEa are used to set the QC system. Using both will also help choose the best QC rule(s). Please use the measured mean and SD from YOUR QC data and check them when changing reagents and/or calibrators and choose QC rules based on both TE and TEa.

calibrators and choose QC rules based on both TE and TEa.


Encouraging Immune Therapy for Certain Cancers
October 15, 2014 10:40 AM by David Plaut

Upon emerging from the thymus, naive T cells circulate in the blood through lymph nodes and seek foreign (“nonself”) antigens. T cells can recognize not only pathogen-associated antigens, but also abnormally expressed self-proteins—indicating mutated or transformed tumorigenic cells -- as “nonself.” If T cells encounter their specific antigen in the context of appropriate co-stimulatory molecules, the cells become activated and upregulate activation and homing molecules. These T cells, termed effector T cells, are able to enter inflamed tissues in search of infected or cancerous cells. Among other functions, effector T cells can produce inflammatory cytokines and/or cytolytic granules, leading to apoptosis or necrosis of infected or tumor cells. The use of immunotherapy to unlock the immune system’s ability to eradicate cancer cells is an exciting new avenue for treatment of solid tumors -- even in an extremely aggressive disease with poor prognosis, such as advanced lung cancer -- but the exact clinical applications are still not clear.

In lung cancer therapy, the emergence of targeted agents with mechanisms of action based on driver mutations have introduced a set of standard predictive biomarkers to aid in clinical decision making. Immune checkpoint blockade, however, is designed to act on a complex and intact immunological pathway rather than individual mutations or antigens. As such, identification of a predictive biomarker has proven challenging. Answers as to whether biomarkers such as PD-L1 can predict tumor responsiveness to agents targeting this pathway have been equivocal so far.

In summary, the goal of immunotherapy is to prolong survival and quality of life for patients with lung cancer by stimulating the patient’s own immune system to combat cancer. This new treatment approach is still earl and more data from mechanistic and clinical studies are needed on strategies to optimize the clinical impact of these therapies.


1. Clinical Pharmacology & Therapeutics (2014); 96 2, 214–223. doi:10.1038/clpt.2014.74

2. http://news.bms.com/press-release/phase-3-first-line-melanoma-study-nivolumab-investigational-pd-1-checkpoint-inhibitor-

3. http://www.uptodate.com/contents/immunotherapy-of-advanced-melanoma-with-immune-checkpoint-inhibition

4. Groopman, J, The T-cell Army, The New Yorker, April 23, 2012.

5. https://www.google.com/search?q=william+coley&oq=william+coley&aqs=chrome..69i57j0l5.14083j0j4&sourceid=chrome&es_sm=0&ie=UTF-8

An Interesting AML Study
October 8, 2014 1:31 PM by David Plaut

In mid-2013, William Kuhens was diagnosed with myelogenous leukemia (AML). The only treatment for him was experimental. He was assigned in a Phase 1 trial with little hope -- for these studies are usually used only to investigate what dose could be handled and what the side effects were, not to send the cancer into remission. There were 10 patients in this trial of a new drug, AG-221, which targeted a mutated gene that affected an enzyme – isocitrate dehydrogenase (IDH-2). Of these first 10 subjects, three died from AML before the drug could even be evaluated, but the data on six of the remaining seven was striking – five went into complete remission and one was in partial remission. Nothing like that was even imagined. As of the middle of September, Kuhens is in remission. The only side effect is that he can no long eat mayonnaise – it doesn’t taste good. In June this year, another study of 35 other patients was reported. Fourteen patients improved – nine went into complete remission; 10 died before the drug could begin to work.

An interesting aspect of this drug -- and another like it, AG-120 -- is that rather than destroy the cancer cells, these two turn the cancerous cells around so that, rather than stay immature, and given only to reproducing and continue to mature and act ‘normal.’ Only about 25 percent of AML patients have the mutated gene and thus are not candidates for these drugs, but the function of the mutant genes will lead to looking for similar defects which may be targets for similar treatment -- a new avenue to try.


1.            Chaturvedi A, Araujo Cruz MM, Jyotsana N, et al. Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML. Blood2013;122(16):2877-2887

2.            Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med2009;360(8):765-773.

3.            Abbas S, Lugthart S, Kavelaars FG, et al. Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value. Blood 2010;116(12):2122-2126. FREE Full Text

Reporting Hemoglobin A1c – SI or per cent?
September 30, 2014 9:59 AM by David Plaut

There was a point-counterpoint “debate” in a recent issue of Clinical Lab News. Arguing for reporting A1c as SI was Ian Young from Ireland; for keeping A1c as percentage -- at least in the United States -- was David Sacks from the NIH in Bethesda, MD.

Young posited that the use of percent gave values that were quite similar to the SI units (mmol/L) for glucose and are confusing to both patients and physicians. He pushed for using SI units for A1c. We will assume that the total hemoglobin A would remain in SI as it now is. Thus, it seems that two values would be necessary for A1c – the A1c and Hgb A. Although this was not mentioned by Dr. Young, to me, this would not be an answer for it is the relative amount of A1c that is of interest – not the absolute amount. IF only the amount of A1c were reported (without the Hgb A), how would a patient of a physician know whether that individual was in glucose control? I am certain that physicians can explain the A1c as a percent to a patient who can remember that 6 percent is good and 6.5 is not so good. And there are the H and L and “interpretative comments” to help the patient if the clinician does not explain it. I vote for percent around the world.

I recently read that the journal Science sent out an article under a pseudonym and an imaginary address to several hundred journals asking that the article be published. The article had not basis in fact and had a few patently false statements. Curiously(?), nearly half of the journals accepted the article. Science withdrew the article from those who accepted it. One must wonder how often such articles, often unwittingly, are submitted and printed.

Hemoglobin A1c in Non-diabetic Patients.
September 24, 2014 10:28 AM by David Plaut

We all know that hemoglobin A1c (A1c) is a good marker for the amount of glucose in the blood stream and that a level of 6.0 percent is considered “normal.” As Oscar Wilde had one of his characters in the Importance of Being Earnest say, “Life is rarely pure and never simple.” I am sure we would all agree with this. There was an article in the July issue of the Mayo Clinic Proceedings that discussed a group of 1141 ‘non-diabetic’ patients who underwent coronary angiography. The patients were divided into four subgroups based on their A1c levels (<5.5%, 5.5-5.7%, 5.8-6.1% and >6.1%). The study found that patients with higher A1c levels “tended to be older, over weight and hypertensive.” They also had higher blood glucose levels and low GFR rates. The study concluded that “the A1c level has a linear incremental association with CAD in non-diabetic individuals. The A1c level is also independently correlated with disease severity and higher SYNTAX scores (an angiographic grading tool to determine the complexity of coronary artery disease). Thus, A1c measurement could be used to improve cardiovascular risk assessment in non-diabetic individuals.” This seems to cast some doubt about whether a 6 percent level of A1c is “normal.”


1.            Hemoglobin A1c in non-diabetic patients: an independent predictor of coronary artery disease and its severity. Mayo Clin Proc. 2014 Jul;89(7):908-16.  Garg N, Moorthy N, Kapoor A,

2.            Comparison of glycemic variability and glycated hemoglobin as risk factors of coronary artery disease in patients with undiagnosed diabetes. Chin MedJ (Engl). 2012 Jan;125(1):38-43. 1, Su G, Li Z, et al.

3.            Glucose intolerance, as reflected by hemoglobin A1c level, is associated with the incidence and severity of transplant coronary arteryMi SH disease.[J Am Coll Cardiol. 2004] J Am Coll Cardiol. 2004 Mar 17;43(6):1034-4 Kato T, Chan MC, Gao SZ, et al.

A Change in QC Rules?
September 17, 2014 10:22 AM by David Plaut

In 1974, the College of American Pathologists (CAP) proposed an algorithm for accepting/rejecting analytical runs using 2 controls. The algorithm used 3 rules to reject a run – 1 3SD,* 2 2SDw and 2 2SDa. In 1981, Westgard et al. (JOW) proposed an expanded set of rules. Both groups were clear on the idea that a single value beyond the 2 SD limits was not a reject signal.

In the past 40 years, improvements in instruments, reagents and calibrators have resulted in a significant improvement of precision. This improvement suggests that QC monitoring systems should review rules based on the SDs from current data, not based on data from 30-plus years ago. Do we use 30 year old instruments? Or computers? Or phones?

At the AACC meeting in July, 2014, I presented a poster looking at the changes in precision since 1988. Surveys from 1988 and 2012 were studied. We used %CV to correct for the variation in means from one survey to another. Our survey of 35 analytes from chemistry, hematology and hemostasis indicated a decrease of 40 percent (average; range 24-77) in CVs.

The table shows representative changes in SDs measured as %CV and the change over time.

1988 2012   %Change

Analyte Method Mean %CV Mean %CV

Hemoglobin Coulter 2.9 1.7 41

WBC Coulter 3.8 2.7 24

Cholesterol Abbott 2.9 1.0 66

AST Roche 8.4 5.2 33

Ca Baker 4.9 1.3 77

Prothrombin time    * 6.4 2.8 56

APTT Stago 10.4 2.9 78

*In 1988 most laboratories user a manual method.


•             The changes in analytical precision strongly suggest that QC rules be reevaluated. We "translated" the SD of the year 2012 into a new set of rules to detect both systematic and increased random errors. Our translations indicate that based on a 40 percent decrease the following rules would work very effectively: 1 4 SD, 2 3 SD, and R 5 SD. If you are squeamish about the 1 4 SD rule, use either 1 3 SD or at least 1 2.5 SD

•             The changes in the rules will yield essentially 0% false rejects and an error detection of nearly 100%

•             As before each analyte should be assessed to determine the proper rule(s).

Hops and Sleeping
September 10, 2014 12:36 PM by David Plaut

I ran across an article recently that I thought you, like me, would find it interesting. The title of the article is “Effect of non-alcoholic beer on Subjective Sleep  in  university stressed population.” Of course, you easily relate to the word “stressed.” Who working in a laboratory isn’t stressed? The other part of the title was the idea of “non-alcoholic beer.” You may, as did I, say how can that be? What is beer if not alcoholic? But is does exist – if only to get the hops into your system. It turns out that beer is the only beverage that contains hops, and hops is known to have a sedative effect.

Here is the result of this study and another one carried out on nurses. There is a sleep quality index from Pittsburgh that measures the quality of your sleep and uses the 30 students as their own control for the first week of three. During the last two weeks, the students were asked to drink the NAB at dinner and then fill out the survey. The overall rating improved significantly (“p<0.05”), as was the sleep latency also a level of significance of “<0.05.” As I mentioned, another study measured other aspects of sleep and found the same high level of significance. 

It turns out that there are quite a number of non-alcoholic beers, although they can contain as much as 1.0% (but usually 0.5%) alcohol.


1. Acta Physiol Hung. 2014 Sep;101(3):353-61..Effect of non-alcoholic beer on Subjective Sleep Quality in a university stressed population. Franco L, Bravo R, Galán C, et al.

2. PLoS One. 2012;7(7):e37290. The sedative effect of non-alcoholic beer in healthy female nurses. Franco L  Sánchez C, Bravo R, et al.

Troponin: An update
September 4, 2014 1:18 PM by David Plaut

I have been working with troponin since it came to this country several years ago. Most of my experience has been with troponin I (cTnI). When cTnI first was released to the laboratories the cut-off was set at 0.4. Then it dropped to 0.2 and now it has been lowered by some laboratories even further. These newer variations have pros and cons as you have seen. For example, there are reports of measurable cTn following a marathon.

"The increase in early diagnostic sensitivity of hs-cTn assays for ACS comes at the cost of a reduced ACS specificity, because more patients with other causes of acute or chronic myocardial injury without overt myocardial ischemia are detected than with previous cTn assays." 

These newer assays detect low levels of cTn in apparently healthy people. "In addition, the sensitive assays detect more cTn positive patients who do not have a final diagnosis of ACS. It is unknown if such mild elevations in cTn detected by sensitive assays are of clinical concern. What is certain is that AMI remains a clinical not a biochemical diagnosis and interpretation of cTn concentrations should be made according to the clinical context." It has been demonstrated that the newer assays are better able (using the area under the ROC curve) to identify AMI in patients with existing CAD compared to the ‘standard' cTn.

A diagnostic accuracy study of patients presenting to the emergency department (ED) with symptoms of ACS was performed. Troponin was measured at 0, 2 and 6h post-presentation. AMI was made by 2 cardiologists and incorporated the 0 and 6h troponin values measured by a sensitive troponin assay. There was no significant difference in the diagnostic accuracy of early versus late biomarker strategies when used with the current risk stratification processes. Incorporation of a significant delta did not improve the stratification at 2h post-presentation."


1. Mair J., World J Cardiol. 2014 Apr 26;6(4):175-82.

2. Gaze DC., Curr Med Chem. 2011;18(23):3442-5. Curr Med Chem. 2011;18(23):3442-5.

3. Reiter M, Twerenbold R, Reichlin T, et al. Eur Heart J. 2012 Apr;33(8):988-97.

4. Cullen L, Greenslade J, Than M et al., Heart Lung Circ. 2014 May;23(5):428-34.



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