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Letters |
Departments of,
1
Physiology,
2
Biochemistry,,
3
Medical Informatics, and,
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Cardiovascular Research, Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands
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Department of Clinical Chemistry, University of Liège, CHU B35, Domaine Universitaire du Sart Tilman, B-4000 Liège, Belgium
a Author for correspondence. Fax 31-43-367 1028; e-mail maurice.pelsers{at}fys.unimaas.nl
To the Editor:
Fatty acid-binding protein (FABP), like myoglobin (Mb), increases significantly within ~3 h after onset of symptoms of acute myocardial infarction (AMI) and returns to health-related values within 12 to 24 h (1). For the early assessment or exclusion of AMI, FABP performs better than Mb (2)(3). Although FABP, like Mb, is also found in skeletal muscle, the distinct ratio of the contents of Mb over FABP in heart (ratio, 4–5) and skeletal muscle (ratio, 20–70) allows the discrimination between myocardial and skeletal muscle injury (4).
For the assessment of clinical reference values, it is important to know the possible influence of biological variations such as age, sex, and day-to-day and within-day fluctuations (5); however, for FABP such data are lacking. The aim of the present study was to establish these parameters for FABP first in a large group of volunteers of different ages. Mb was also measured to delineate possible effects of age and sex on the ratio of the plasma concentrations of Mb over FABP. We also studied day-to-day and within-day biologic variation (within-person) for both FABP and Mb concentrations in another group of volunteers.
For the first substudy, plasma samples were taken from 312 donors (110 women and 202 men; ages, 21–70 years) visiting the blood bank of Liège, Belgium. EDTA was added to samples to prevent clotting. For the study of within-person biologic variation, blood samples were obtained from young and apparently healthy volunteers (six men and six women; ages, 19–27 years) recruited from the student population of Maastricht University. Samples were obtained at the following time points: on day 1, at 0930, 1100, 1400, 1700, 2000, and 2300; on day 2, at 0300, 0700, 0930; and on days 8, 15, 22, 29, and 57 at 0930. Citrate was added to prevent clotting, and samples were immediately aliquoted and frozen at -80 °C until use. The study was approved by the medical ethics committee of the Academic Hospital Maastricht, and all subjects gave informed consent. FABP was measured with a sensitive noncompetitive sandwich-type ELISA (6), using recombinant human (heart-type) FABP as the calibrator (7). Mb was measured with a turbidimetric immunoassay (Unimate 3 Myo; Roche Diagnostic Systems) on a Cobas Mira plus analyzer (Roche). The inter- and intraassay analytical imprecision (CV) was <10% for FABP (6) and <6% for Mb (Unimate 3 performance data; Roche). Both assays showed no interference from either citrate or EDTA (data not shown). BMDP Statistical software was used for statistical analysis. All data are presented as medians, with 25 and 75 percentiles in parentheses. Samples with values below the detection limit of 0.3 µg/L FABP or 7.5 µg/L Mb were assigned the detection limit.
The median plasma concentrations of FABP and Mb in the first substudy
(n = 312) were 1.5 µg/L (25–75 percentiles, 1.1–2.1 µg/L)
and 27 µg/L (25–75 percentiles, 20–36 µg/L), respectively. The
median ratio of the plasma concentrations of Mb over FABP was 19
(25–75 percentiles, 13–24). Plasma concentrations of both
cardiac markers showed a sex dependency. Plasma FABP
(P <0.005; Mann–Whitney test) and Mb (P
<0.0001) values were lower in women than in men (Fig. 1
). The ratio of Mb over FABP showed no significant difference
between sexes.
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Both cardiac markers also showed an increase in the health-related
plasma concentration during aging (Fig. 1
). The effect of aging was
more prominent in the plasma concentration of FABP (P
<0.0001; regression analysis) than Mb (P <0.01). As a
result, the ratio of Mb over FABP was also age-dependent (P
<0.001).
The day-to-day variation in plasma concentrations of FABP and Mb, expressed as mean CV (within-person) of seven time points (days 1, 2, 8, 15, 22, 29, and 57) of all 12 subjects and calculated as CV2 within-person = CV2 total - CV2 analytical imprecision (5) was 14% for FABP and 18% for Mb. For analysis of within-day variation of FABP and Mb, three time blocks were used: daytime as the most active period (0930–1700), evening as a more relaxed period (1700–0100), and night as the resting period (0100–0930). For plasma FABP, a significant increase was seen (P <0.005; BMDP Statistical Software, program 2V) from daytime (0.8 µg/L) to evening (0.9 µg/L) to night (1.1 µg/L). For Mb, a similar trend was found from daytime (20.9 µg/L) to evening (22.6 µg/L) to night (23.1 µg/L); however, this did not reach statistical significance. The overall values for men [FABP, 1.2 µg/L (0.6–1.6 µg/L); Mb, 25 µg/L (22–29 µg/L)] and women [FABP, 0.7 µg/L (0.4–1.2 µg/L); Mb, 20 µg/L (15–22 µg/L)] confirm the data of the first substudy (age group, 21–30 years).
The measured median plasma FABP (1.5 µg/L) and Mb (27 µg/L) concentrations of healthy subjects are similar to previously published values of 1.6 µg/L for FABP and 33 µg/L for Mb (1)(6), as are the differences in Mb plasma values between men and women (8)(9). The observed increases of the FABP and Mb plasma concentrations with age, especially after 50 years, are most likely explained by the decrease in renal function in elderly people, which in the case of Mb may be partly counterbalanced by diminishing skeletal muscle mass, especially in men (10). Both cardiac markers show differences between men and women, which might be explained by the fact that men have a relatively larger muscle mass than women.
The within-day variations found for FABP may be related to the reported increased glomerular filtration rate during the day (11); however, this explanation is not confirmed by a significant within-day variation of Mb. A limitation of this substudy is that observations were made for subjects 19–27 years of age, whereas most acute coronary syndromes appear in older persons.
In conclusion, this study shows that when using FABP and (or) Mb as plasma markers for the diagnosis of AMI, the time of day is of minor relevance; age and sex, however, are more important because these will influence the upper reference concentrations of both these markers. In addition, caution should be taken when using the Mb over FABP ratio to discriminate cardiac from skeletal muscle injury, especially for patients >50 years of age.
We thank N. Drees, Roche Diagnostic Systems, for stimulating discussions and for providing the Mb assays.
References
The following articles in journals at HighWire Press have cited this article:
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  M. Puls, C. Dellas, M. Lankeit, M. Olschewski, L. Binder, A. Geibel, C. Reiner, K. Schafer, G. Hasenfuss, and S. Konstantinides Heart-type fatty acid-binding protein permits early risk stratification of pulmonary embolism Eur. Heart J., January 2, 2007; 28(2): 224 - 229. [Abstract] [Full Text] [PDF]
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 H. M.E. Azzazy, M. M.A.L. Pelsers, and R. H. Christenson Unbound Free Fatty Acids and Heart-Type Fatty Acid-Binding Protein: Diagnostic Assays and Clinical Applications Clin. Chem., January 1, 2006; 52(1): 19 - 29. [Abstract] [Full Text] [PDF]
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M. M.A.L. Pelsers, T. Hanhoff, D. Van der Voort, B. Arts, M. Peters, R. Ponds, A. Honig, W. Rudzinski, F. Spener, J. R. de Kruijk, et al. Brain- and Heart-Type Fatty Acid-Binding Proteins in the Brain: Tissue Distribution and Clinical Utility Clin. Chem., September 1, 2004; 50(9): 1568 - 1575. [Abstract] [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) and women (
) of
different age groups.