their consulting agreement with Gen- zyme and occasional consulting for. Sigma Diagnostics. References .... mez JA, Apple ES, Ladenson. JH, Jaffee. AS. 0 140.
Ltthrs implementation of Recommendations from the NCEP Working Group on Upoprotein Measurement
were being put into action. that implementing guidelines lem?
Congratulations
Group
for all their
to
Who says is a prob-
the
Working
efforts.
To the Editor: We were very pleased tion of the summary National
Cholesterol
to see the publicareports from the Education
Pro-
gram (NCEP) Working Group on Lipoprotein Measurement in Clinical Chemistry [1-3]. These summary reports represent a monumental effort on the part of the committees involved. The Working Group is to be commended. The work on these reports was largely completed by 1990. It is unfortunate that the National Institutes of Health (NIH) review process surrounding them has taken so long to reach conclusion. Many of us in the lipoprotein measurement field have been aware of the recommendations contained in the reports, and have been advocating them to the general clinical chemistry community, but have had only the preliminary summaries reported in the AACC Lipids and Lipoproteins Division newsletter to report [4, 5]. The NCEP Working Group determined that the combined variability derived from total and HDL cholesterol and triglyceride determinations would make it very difficult to derive LDL cholesterol measurements that would meet the recommended precision and bias limits if determinations continued to be obtained through calculations. They therefore recommended in the late 1980s that manufacturers begin developing methods for direct measurement of LDL cholesterol [1]. During the time that the NIH editorial and educational reviewers were commenting on the manuscripts, at least one method for direct measurement of LDL cholesterol was actually developed, clinically evaluated, cleared by the Food and Drug Administration, and brought to market. This test for measuring LDL cholesterol directly was developed by Genzyme Corp. (Cambridge, MA), and is now widely distributed by Sigma Diagnostics (St. Louis, MO). At present, we and others have published data comparing this method with the ultracentrifugation method [6-8]. These evaluations have shown that the method is capable of meeting the precision and accuracy guidelines of ±4% developed by the Working Group. So, before the guidelines were even published, the recommendations
contained
in those
guidelines
Editor’s note: The authors acknowledge their consulting agreement with Genzyme and occasional consulting for Sigma Diagnostics. References 1. Bachorik PS, Ross JW. National
Cholesterol
Education Program recommendations for measurement
of low-density
lipoprotein
cholesterol:
executive summary. Clin Chem 1995;41: 1414-20. 2. Stein EA, Myers GL. National Cholesterol Education Program recommendations for triglyceride measurement: executive summary. Clin Chem 1995;41:1421-6. 3. Wamick GR, Wood PD. National Cholesterol Education Program recommendations for measurement of high-density lipoprotein cholesterol: executive summary. Clin Chem 1995;41: 1427-33. 4. Bachorik PS. Development of NCEP guidelines for lipoprotein
and
triglyceride
measurement.
Fats of Life 1992;6(1):1. 5. Bachorik PS. Measurement of triglycerides and lipoproteins. Fats of Life 1992;6(4):9-10. 6. McNamara JR. Cole TG, Contois iH, Ferguson CA, Ordovas JM, Schaefer EJ. Immunoseparation method for measuring low-density lipoprotein cholesterol directly from serum evaluated. Clin Chem 1995;41:232-40. 7. Jialal I, llirany SV, Devaraj S. Sherwood TA. Comparison of an immunoprecipitation method for direct measurement of LDL-cholesterol with beta-quantification
(ultracentrifugation).
Am
Clin Pathol 1995;104:76-81. 8. Pisani T, Gebski CP, Leary El, Wamick GR, Ollington iF. Accurate direct determination of low-density
lipoprotein
cholesterol
using an im-
munoseparation reagent and enzymatic cholesterol assay. Arch Pathol Lab Med 1995;119: 1127-35.
Judith
R. McNamara* Ernst J. Schaefer Lipid Metab. Lab Human Nutr. Res. Center on Aging at Tufts Univ. 711 Washington St. Boston, MA 02111
USDA
*
Author
for correspondence.
Prognostic Value of Cardiac Troponin I in Patients with Chest Pain To the Editor: Cardiac troponins T (cTnT) and I (cTnI) are structural proteins of the thin filament. High concentrations of these proteins in blood are indicative of acute myocardial infarction (AM!) and minor
myocardial injury [1, 2]. Previous studies showed that analysis for serum cTnT had prognostic value in non-AMI patients with cardiac disease. Hamm et al. [3] showed that, of 33 unstable angina patients who had above-cutoff values for cTnT, 30% had AM! during their hospitalization, in contrast to only 2% of those who had normal cTnT values. In a meta-analysis combining data from five published studies (392 subjects overall), patients with an abnormal cTnT had an 11-fold higher risk for development of AMI or cardiac death within 6 months than those with normal values 141. Recently, studies with larger numbers of subjects showed that the degree of cardiac risk was linked to the degree of cTnT increase [5]. Biochemical risk assessments might be used to determine which cardiac patient should be more aggressively treated by angioplasty or coronary artery bypass graft surgery. Although cTnI appears to exhibit release patterns very similar to that of cTnT in blood of AM! patients, only two abstracts have been published on the use of cTnI for risk stratification [6, 7]. We evaluated a creatine kinase (CK)MB mass assay and a premarket cTnI assay to determine whether these markers could also be used for risk stratification of patients with coronary artery disease. A total of 218 blood samples were collected from 74 consecutively admitted non-AM! patients with chest pain, at admission and daily for as many as 3 days; patients with AMI were excluded from the study. The study period was from June 1 toJuly 15, 1995. The protocol was reviewed and approved by the Institutional Review Board at Hartford Hospital. The mean and median length of stay for these non-AMI patients was 7.5 and 5 days, respectively (range 2-34 days). A diagnosis of AM! was ruled out by attending physicians on the basis of clinical history, electrocardiogram, and enzymes, including total CK and CK-MB; the cTnI assay results were not made known to these physicians. Outcomes for cardiac death and nonfatal AM! at 3 months after discharge were available for 65 of these 74 patients. Blood was collected into evacuated heparin-containing green-top tubes. Within 48 h of collection, plasma was assayed for CK-MB and cTnI with the Opus Plus Immunoassay Analyzer (Behring Diagnostics, Westwood, MA).
Clinical Chemistry
42, No.
4, 1996
651
Letters
Table 1. Odds ratios for a poor outcome from CK-MB and cTnl values in non-AMI patients with chest pain. Cutoff conc, CK-MB 3.0 3.5
zg/L
Odds ratIo (95% CI)
elevated cardiac troponin I in unstable angina [Abstract]. Circulation 1995;92(Suppl l):598. 8. Wu AHB, Feng YJ, Contois JH, Pervaiz S. Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction. Ann Clin Lab Sci 1996;26:in
press.
3.1 (0.88-15.9)
3.20
0.735
9. Adams JE, Bodor GS, Davaila-Roman VG, Delmez JA, Apple ES, Ladenson JH, Jaffee AS.
3.1 (0.88-15.9)
3.20
0.735
4.0
6.5 (1.46-29.1)
6.04
0 140
4.5 5.0 cTnl 1.00
4.2 (0.94-18.6)
3.51
0.061
5.6 (1.21-26.0)
4.84
0.278
4.1 (0.97-17.7)
3.66
0.0557
1.25 1.50
4.6 (1.06-19.8) 7.5 (1.65-34.0)
4.17
0.0412
6.81
U.UU
Katus HA, Hailer C, Muller-Bardorff M, Scheffold I, Remppis A, Hafner G, et al. Cardiac troponin I in end-stage renal disease patients
1.60
8.8 (1.90-40.6)
7.67
0.0056
undergoing
2.00 2.25 2.50
4.2 (0.82-21.1)
2.97
0 085
5.1 (0.97-26.9)
3.69
0.055
wasser
2.9 (0.47-17.8)
1.33
2.91
Response
Cardiac troponin ity for cardiac 88:101-6.
10. Wu AHB, Abbas
SA, Green S. Pearsall P. Dhakam 5, Azar R, et al. The prognostic value of cardiac troponin I in patients with unstable angina. Am J Cardiol 1995:76:970-2.
11.
if results
creased
We
in
are
indeed
falsely
Behring
Diagnostics,
CIin
of
acute
myocardial
infarction.
Clin
Chem 1993:39:972-9. 2. Wu AHB, Valdes R Jr. Apple FS, Gornet 1, Stone MA, Mayfield-Stokes 5, et al. Cardiac troponin-T immunoassay for diagnosis of acute myocardial infarction and detection of minor myocardial injury. Clin Cheni 1994:40:900-7. 3. Hamm CW, Ravkilde i, Gerhardt W, i#{248}rgensen P, Peheim E, Ljungdahi L. The prognostic value of serum troponin T in unstable angina. N Engi
Med 1992:327:146-50.
4. Wu AHB, Lane Pi. Meta-analysis in clinical chemistry: validation of cardiac troponin I as a marker for ischemic heart diseases. Clin Chem
1995:41:1228-33. 5. Lindahl B, Toss H, Venge P, Wallentin
L. Troponm T is an independent prognostic marker for subsequent cardiac events in patients with unstable coronary artery disease [Abstract]. Circulation 1995;92(Suppl l):663. 6. Antman EM, Tanasijevic Mi, Cannon CP, Schactman M, McCabe CH, Fischer G, et al. Cardiac troponin I on admission predicts death
by 42 days in unstable
angina and improved
survival with an early invasive strategy: from TIMI Ill B [Abstract]. Circulation
results 1995;
92(Suppl1):663. 7. Galvani M, Ottani
Letter.
P, et
Chem
al.
1995;
I in renal disease
F, Ladenson JH, Fermi D, Destro A, Baccos 0, et al. Adverse influence of
[Letter].
Clin Chem
1995:41:1671-2.
Alan H.B. Wu* Yue Jin Feng John H. Contois Dept.ofPatholand Lab Med. Rabih Azar David Waters Dept. of Med., Cardiol. Div. Hartford Hospital Hartford, CT 06102
West-
References 1. Larue C, Caizolari C, Bertinchant i-P. Leclercq F, Grolleau R, Pau B. Cardiac-specific immunoenzymometric assay of troponin I in the early
I
W, Cummins
to
in-
wood, MA, for loan of equipment, gifts of reagents, and financial assistance to conduct this study.
phase
hemodialysis
I, Ehrenthal
these patients.
thank
maintenance
41:1202-3. 13. CollinsonP0, Stubbs PJ,RosalkiSB. Cardiac
to those in our previous study of cTnT [10]. Whether or not cTn! is equal to or better than cTnT remains to be determined. The specificity of cTnT has been debated, particularly in patients with chronic renal failure [11-13]; use of cTnT for risk stratification would be less useful
chronic
[Letter]. Clin Chem 1995;41:1201-2. 12. Hafner G, Thome-Kromer B, Schaube J, Kupfer-
troponin The CK-MB cutoff concentration for AMI diagnosis was 5.0 j.tg/L. For the premarket cTn! assay, we previously determined a normal range of 0-0.5 tg/L from 150 healthy individuals, and a cutoff value of 2.5 gfL for AMI diagnosis [8]. Logistic regression analysis was performed with a PC-based statistical package (Version 4.0; Crunch Software, Oakland, CA). During the study period, 9 patients had adverse outcomes. There were 3 AMIs during hospitalization and 3 after discharge, and there were 4 cardiac deaths overall. Different cutoff concentrations for CK-MB and cTn! were considered in determining what values produced the best discrimination between good and poor outcomes. Table 1 lists the odds ratios and 95% confidence intervals (CI) for the prediction of shortterm risk. Cutoff values of 4.0 j.tg/L for CK-MB and 1.6 pgfL for cTn! produced results with the highest odds ratios: 6.5 (95% Cl, 1.5-29) and 8.8 (1.9-41), respectively. The results obtained with these lower cutoff concentrations were more predictive than those based on the preestablished AM! cutoff values of 5.0 and 2.5 .tg/L, respectively. These odds ratios show that poor outcome was significantly more frequent in the high-cTnI group than in the lowcTnI group. Although also prognostic in this study, the utility of CK-MB for risk stratification remains questionable, given the conflicting results of previous studies [4]. cTnI may have more promise because it has higher specificity for heart damage than does CK-MB [9]. Odds ratios for cTnI in this study were similar
I. A marker with high specificinjury. Circulation 1993;
*
Author for correspondence.
Choice of Materials for Long-Term Quality Control of Blood Folate Assays
To the Editor: As a national reference laboratory in the nutritional anemias, we report >12 000 diagnostic blood folate estimations annually. The accuracy and long-term reproducibility of our folate microbiological assays are thus important, and care is taken to ensure both the quality and stability of our in-house control materials for the assay. We recently compared the long-term performances of these inhouse human blood controls and of those from a commercial source. Commercially available lyophilized human blood controls (Lyphochek Whole Blood Controls, lot 28200; ECS Division, Bio-Rad Labs., Anaheim, CA) reportedly performed 2-year evaluation [1].
trols,
which
were
well
during
These two conreconstituted, diluted
a
