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Alan H.B. Wu, et al. Creation of a Universal Sample Bank for Determining the 99th Percentile for Cardiac Troponin Assays. J Appl Lab Med 2017;1:711-19.
Dr. Alan Wu is Professor of Laboratory Medicine at the University of California, San Francisco and co-core laboratory chief at Zuckerberg San Francisco General Hospital.
Hello, and welcome to this edition of “JALM Talk” from The Journal of Applied Laboratory Medicine, a publication of the American Association for Clinical Chemistry. I’m your host, Randye Kaye.
Cardiac troponins T and I are the preferred biomarkers for detection of myocardial injury. However, they are also elevated in a number of other chronic diseases, such as kidney disease, diabetes, and vascular disease. In order to diagnose acute myocardial infarction, AMI, professional organizations including cardiology, emergency medicine, and laboratory medicine practitioners agree that laboratories should use elevations in troponin above the 99th percentile of a healthy population as the cutoff concentration. However, this 99th percentile cutoff is assay- and sample population- dependent and is therefore inconsistent between assays.
An initiative funded by a research grant from the American Association for Clinical Chemistry, and it was carried out by the Biomarkers of Acute Cardiovascular Disease Division. This led to an article published in the May 2017 issue of JALM. It’s entitled “Creation of a Universal Sample Bank for Determining the 99th Percentile for Cardiac Troponin Assays.” This article aimed to help streamline the determination of the 99th percentile for troponin assay manufacturers. The first author of this article is Dr. Alan Wu, Professor of Laboratory Medicine at the University of California, San Francisco and co-core laboratory chief at Zuckerberg San Francisco General Hospital. He’s our guest for today’s podcast. Welcome, Dr. Wu.
Thank you, Randye.
So my first question is, let’s just ask, why did the AACC create this sample bank?
Well, there are a number of manufacturers of troponin I assays and the bad thing is that none of them are standardized to each other. So when you get a result from one assay, you have to compare it against either the manufacturer’s stated 99th percentile cutoff, or the hospital
has to establish their own. While that’s okay when you’re
just looking at one assay at one institution, when you want
to try to compare results against another institution, or if
you want to compare how one assay is rated against
another, then we felt that it was necessary to establish the
99th percentile on a single population, because who you
select as being “normal” will determine the actual 99th
All right. So what did you do next?
So we submitted a proposal to the AACC to fund a project
whereby we would enroll apparently healthy subjects
attending the AACC Annual Meeting that was held in 2015 in
Atlanta, Georgia. So we got a grant. It was approved by
the AACC Board of Directors, and we spent many months
planning a blood collection protocol. It was done in
conjunction with the AACC Meetings Management Group.
Great! So how many people signed up to participate?
On the week of the AACC meeting, we had over 800
individuals who participated in the program. They were
each given a gift card for participating at the AACC
bookstore. They were also asked to fill out a case report
form which told us who they were and whether or not they
had any comorbidities that might affect the 99th percentile
Great! Is there anything else I should know about how they
were processed through this procedure?
That’s a great question. What we had were a number of
phlebotomists that we had on hand. We also had
processors. Once an individual had consented to participate
in the study, blood was collected. They were centrifuged
onsite, aliquoted into small freezer vials, about 250
microliters into each and about 100 different aliquots were
stored, aliquots that were collected in blood that were
preserved with either EDTA, heparin, or no preservatives, in
which case, we froze serum samples.
Okay. So now you’ve got all these samples, so what are
you going to do with the samples?
So these samples then were put into boxed sets, whereby
all of the sets would contain at least one sample from each
individual. We also did some screening tests to rule
diseases that we knew were going to affect the troponin
values. So we ran NT-proBNP which is a marker of left
ventricular dysfunction. We measured hemoglobin A1c to
determine if there was any diabetes or pre-diabetes or uncontrolled glucose. And we also ran a creatinine and from
that calculated the eGFR, the estimated glomerular filtration
rate, to determine whether or not any of these individuals
had any renal insufficiency.Randye Kaye:
And so there’s testing for troponin. Now, what’s going to be
the impact of that testing?
So these individual boxed sets then were made available to
different companies who purchased them and are running
troponins now. In addition, the Biomarkers of Acute
Cardiovascular Disease Division of the AACC has also
obtained boxed sets and are running troponin independently
of the manufacturers to determine the 99th percentile in our
Terrific! So, if there’s another researcher or manufacturer
that would like to purchase a set, is there a way that they
can do that?
Yes. So the sets were originally designed for measuring the
99th percentile of troponin. But we have enough leftover
samples that we haven’t sold that now are going to be made
available to other manufacturers or researchers who are
interested in determining the normal range for other clinical
chemistry analytes. They would be made available for sale
in the same manner.
And who would they contact to purchase one, if they wanted
So they should contact the AACC office, Stephanie Kleinman
or Loretta Doan. These individuals are going to be the
custodians of the sample bank, and communications
through them directly would allow anybody to make a
All right. Thank you! Just last question, is there anything
else you’d like to say or add to what you’ve already shared
with us that you haven’t had a chance to say?
Well, the publication in The Journal of Applied Laboratory
Medicine details the methodology that we used, the
screening data that we imposed, and the final number of
subjects which is a smaller subset of individuals than the
total amount. We took out people with some of these
comorbidities, but if you are interested in purchasing this
set, you can then determine if you want to exclude these
individuals. If not, because you may not need to be
concerned about renal function, then the entire set can be
All right. Very interesting! Thank you so much for joining
us today, Dr. Wu.
That was Dr. Alan Wu from the University of California, San
Francisco, talking about the JALM article, “Creation of a
Universal Sample Bank for Determining the 99th Percentile
for Cardiac Troponin Assays” for this podcast. Thanks for
tuning in for “JALM Talk.” See you next time and don’t
forget to submit something for us to talk about.