European Heart Journal Advance Access published online on August 5, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn363
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Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T
1 The Heart Centre, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, Northern Ireland, UK
2 Craigavon Cardiac Centre, Craigavon Area Hospital, Craigavon BT63 5QQ, Northern Ireland, UK
3 Nutrition and Metabolism Group, Centre for Clinical and Population Sciences, Queen's University Belfast, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK
Received 27 March 2008; revised 10 July 2008; accepted 17 July 2008.
* Corresponding author. Tel: +44 289 063 3714, Fax: +44 289 031 4169, Email: jennifer.adgey{at}belfasttrust.hscni.net
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Abstract |
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Aims: To evaluate the role of novel biomarkers in early detection of acute myocardial infarction (MI) in patients admitted with acute chest pain.
Methods and results: A prospective study of 664 patients presenting to two coronary care units with chest pain was conducted over 3 years from 2003. Patients were assessed on admission: clinical characteristics, ECG (electrocardiogram), renal function, cardiac troponin T (cTnT), heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, NT-pro-brain natriuretic peptide, D-dimer, hsCRP (high sensitivity C-reactive protein), myeloperoxidase, matrix metalloproteinase-9, pregnancy associated plasma protein-A, soluble CD40 ligand. A 
12 h cTnT sample was also obtained. MI was defined as cTnT 0.03 µg/L. In patients presenting <4 h of symptom onset, sensitivity of H-FABP for MI was significantly higher than admission cTnT (73 vs. 55%; P = 0.043). Specificity of H-FABP was 71%. None of the other biomarkers challenged cTnT. Combined use of H-FABP and cTnT (either one elevated initially) significantly improved the sensitivities of H-FABP or cTnT (85%; P 
0.004). This combined approach also improved the negative predictive value, negative likelihood ratio, and the risk ratio.
Conclusion: Assessment of H-FABP within the first 4 h of symptoms is superior to cTnT for detection of MI, and is a useful additional biomarker for patients with acute chest pain.
Key Words: Acute myocardial infarction • Diagnosis • Biomarkers
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Introduction |
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In those patients presenting with ischaemic-type chest pain the electrocardiogram (ECG) has only 50% sensitivity in the diagnosis of acute myocardial infarction (MI).1 In addition, cardiac troponin T (cTnT), as a marker of cell injury does not peak until
12 h after symptom onset.2 Thus, additional markers have been sought in order to improve the initial diagnosis and also to help risk stratification.
Therefore, we evaluated the utility of biomarkers sampled at the time of admission in the early diagnosis of acute MI in a prospective study of patients presenting within 24 h of onset of acute ischaemic-type chest pain. These included novel biomarkers of myocyte injury [heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB (GP-BB)], along with markers of neurohormonal activation [NT-pro-brain natriuretic peptide (NT-proBNP)], haemostatic activity (D-dimer), and vascular inflammation [high sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), pregnancy associated plasma protein-A (PAPP-A), and soluble CD40 ligand (sCD40L)]. Using the definition of MI as cTnT 0.03 µg/L the performance of these indicators were compared against cTnT.
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Methods |
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Study population and sample collection
From 1 August 2003 consecutive patients admitted to the cardiology department of the Royal Victoria Hospital, Belfast, with acute ischaemic-type chest pain of <24 h duration were eligible for enrolment in this prospective study. The cardiology department of Craigavon Area Hospital was added as an additional recruitment site from 1 January 2004. Enrolment was completed at the end of July 2006. Exclusion criteria were inability or unwillingness to give informed consent, age <18 years, interhospital transfer, and previous participation in the study. Admission sources at both sites included the mobile coronary care unit (MCCU); the Accident and Emergency department; and the rapid access chest pain clinic (RACPC).
A total of 664 patients were enrolled during the 3-year recruitment period (Figure 1). Patients were excluded if they were recruited following transfer from another hospital ward or from another hospital (n = 118) or if improper sample collection/timing made it impossible to establish or exclude the diagnosis of acute MI (n = 20). In addition, patients presenting 24 h from symptom onset were excluded (n = 52), and those from whom the initial blood sample had been taken after thrombolytic administration or in the presence of anticoagulant (n = 59). The remaining 415 patients were studied.
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cTnT was measured from an initial blood sample and a second sample obtained at least 12 h after admission. Levels of H-FABP, GP-BB, NT-proBNP, D-dimer, hsCRP, MPO, MMP-9, PAPP-A, and sCD40L were measured from the initial sample. Serum creatinine was also measured from the initial sample as chronic renal failure is known to affect the blood level of H-FABP.3 The glomerular filtration rate was then estimated (eGFR) depending on age, sex, and race. An eGFR<30 mL/min indicated severe renal impairment.
Laboratory analysis
Serum cTnT levels were measured immediately using the Elecsys Troponin T immunoassay (Roche Diagnostics, Switzerland). The lower detection limit was 0.01 µg/L. The upper reference limit (99th percentile) was <0.01 µg/L and the lowest concentration with a CV 10% was 0.03 µg/L (manufacturer's data). D-dimer was measured immediately for patients recruited at the Royal Victoria Hospital site, and after storage at –70°C for patients recruited at Craigavon Area Hospital. Plasma levels of D-dimer were quantified using an immunoturbidometric assay (STA-Liatest D-Di; Diagnostica Stago, France). The limit of detection for this assay was 0.01 µg/mL. For all other biomarkers, samples were stored at –70°C until analysis. Serum NT-proBNP was measured using the Elecsys proBNP immunoassay (Roche Diagnostics, Switzerland). The lower detection limit for this assay was 5 ng/L. Levels of cTnT, NT-proBNP, and D-dimer were all measured on high throughput automated analysers: Modular Analytics E170 (Roche Diagnostics, Switzerland) for cTnT and NT-proBNP; and STA (Diagnostica Stago, France) for D-dimer. All other biomarkers were measured in serum using commercially available immunoassays: hsCRP (Quantex CRP Ultra Sensitive kit; Biokit, Spain) with a limit of detection of 0.10 mg/L; MPO (BioCheck Myeloperoxidase Enzyme Immunoassay kit; BioCheck, USA) with a lower detection limit of 0.25 ng/mL; MMP-9 (DuoSet human MMP-9 ELISA kit; R&D Systems, USA) with a lower limit of detection of 156 ng/mL; PAPP-A (Demeditec PAPP-A Ultra Sensitive Enzyme Immunoassay kit; Demeditec Diagnostics, Germany) with a lower detection limit 0 ng/mL; sCD40L (DuoSet human CD40 Ligand ELISA kit; R&D Systems, USA) with a lower limit of detection of 39.1 pg/mL; H-FABP (Hycult Biotechnology Human H-FABP ELISA test kit; Hycult Biotechnology, The Netherlands) with a lower limit of detection of 1.2 ng/mL; and GP-BB (Diacordon GP-BB ELISA kit; Diagenics, USA) with a lower detection limit of 3.0 ng/mL.
Electrocardiogram analysis
The initial 12-lead ECG for each patient was assessed blindly. Presence or absence of the following ECG features were noted for each of the 12 leads: Q-waves with duration 0.03 s and amplitude 25% of the following R, ST-elevation (at the J-point) 1 mm, ST-elevation (at the J-point) 2 mm, ST-depression 0.5 mm 80 ms following the J-point, and T-inversion 1.0 mm at the nadir. Presence or absence of left bundle branch block (LBBB) was also recorded.
Final diagnosis
Acute myocardial infarction
Acute MI was diagnosed when either initial or 12 h cTnT was 0.03 µg/L, with or without ECG features of ischaemia/infarction, in the absence of any other cause for the chest pain. If this definition was met then classification was made into ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI). The diagnosis of STEMI required ST-segment elevation in at least two contiguous leads of the ECG or new onset of LBBB. ST-segment elevation was defined as 1 mm in leads I–III, aVL, aVF, V4, V5, and V6 and 2 mm in leads V1–V3. Categorization of patients as NSTEMI was by exclusion of STEMI.
Unstable angina
Unstable angina was diagnosed if the history and/or ECG changes were consistent with an acute coronary syndrome but the cTnT level 12 h after admission was <0.03 µg/L. Again there had to be no alternative clinical diagnosis to explain the chest pain. In addition, patients without a prior history of coronary artery disease had to have either significant ischaemic changes on the admission ECG (ST-segment depression 0.5 mm 80 ms after the J-point or T-wave inversion 1 mm at the nadir) or demonstrate evidence of coronary artery disease during the index hospital admission (significant ischaemic changes on a subsequent ECG, positive exercise stress test, inducible reperfusion defect on myocardial scintigraphy, or significant coronary artery disease in a coronary angiogram).
Non-ischaemic chest pain
Non-ischaemic chest pain was diagnosed when acute MI and unstable angina were excluded.
Statistical analysis
Sample size for this study was calculated prospectively on the basis of obtaining estimates of sensitivity and specificity with adequate precision. Assuming 50% of patients enrolled were diagnosed with acute MI, 400 patients were required to produce 95% confidence intervals (CIs) no wider than ± 5% for an assumed sensitivity or specificity of 85%. All data analyses were performed using the SPSS v 11 statistical package. Baseline characteristics were assessed with the Student's t-test (parametric) and Mann–Whitney U test (non-parametric) for continuous variables, and the 
2 test for categorical variables, with two-tailed P-values < 0.05 taken as significant. The Mann–Whitney U test was used to compare biomarker levels between two independent groups (e.g. patients with and without acute MI). Receiver operating characteristic (ROC) curves were generated for each biomarker to assess their performance as early indicators of acute MI. McNemar's test was used to compare sensitivities and specificities. Logistic regression modelling was used to establish the predictive relationship between biomarker elevation and the diagnosis of acute MI. Variables assessed for inclusion in the model were clinical (age, gender, smoking status, hypertension, hyperlipidaemia, diabetes mellitus, family history of ischaemic heart disease, previous MI, previous percutaneous coronary intervention, previous coronary artery bypass graft surgery, current aspirin use, and severe renal impairment), ECG (ST-elevation, ST-depression, Q-waves, T-wave inversion and LBBB on the initial ECG) and biomarker (initial cTnT, H-FABP, GP-BB, NT-proBNP, D-dimer, hsCRP, MPO, MMP-9, PAPP-A, and sCD40L). Forward stepwise selection of variables was performed, refusing entry to variables with P 0.05. The Hosmer and Lemeshow goodness-of-fit test was performed. The linearity assumption was assessed and satisfied for all continuous variables in the model by division into quintiles.
This study complies with the Declaration of Helsinki. The Research Ethics Committee of Queen's University Belfast granted ethical approval for this research prior to commencement. All patients gave informed consent at the time of enrolment.
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Factors influencing early presentation
Patients admitted with an acute MI were older, less likely to be taking chronic aspirin therapy, more likely to have hypertension, less likely to have a family history of ischaemic heart disease, and less likely to have had a prior MI or revascularization procedure when compared with those with no acute MI (Table 1). Median time from pain onset to initial blood sampling for the total population was 5.3 h [interquartile range (IQR) 2.7–8.9 h] (Table 1). The final diagnosis was STEMI in 73 (18%), NSTEMI in 125 (30%), unstable angina in 124 (30%), and non-ischaemic chest pain in 93 (22%) (Table 2). Patients were admitted from the Accident and Emergency department (n = 250, 60%), the MCCU (n = 139, 34%), and from the RACPC (n = 26, 6%) (Table 2).
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Of the 415 patients, 156 (38%) were admitted within 4 h from symptom onset (Table 2). These patients were not significantly different in terms of mean age and past history when compared with patients presenting
4 h from symptom onset, but were more likely to be male and to have a negative initial cTnT. They were no more likely to have severe renal impairment and were no more likely to have an acute MI than patients presenting later. However when the acute MI subgroups were examined separately, a significantly higher proportion of patients had a diagnosis of STEMI compared with patients presenting 4 h from symptom onset. There was no significant difference for patients with NSTEMI. The median time from symptom onset to admission was shortest for patients admitted via the MCCU (median 2.9 h; IQR 2.0–5.5 h) and longest for those admitted via Accident and Emergency (median 6.5 h; IQR 4.3–10.1 h); P < 0.001.
Cardiac biomarkers
None of the biomarkers in this study were normally distributed. Table 3 compares the median of each biomarker (and the IQR) between patients with and without a diagnosis of acute MI. Median levels of H-FABP, GP-BB, NT-proBNP, D-dimer, hsCRP, MMP-9, and PAPP-A are all significantly higher in patients with acute MI compared with those without acute MI. There was no significant difference for the median levels of MPO and sCD40L. For each biomarker the completeness of the data are listed: H-FABP, 95.2%; GP-BB, 95.9%; NT-proBNP, 98.6%; D-dimer, 91.8%; hsCRP, 94.7%; MPO, 90.6%; MMP-9, 95.7%; PAPP-A, 98.6%; sCD40L, 94.5%.
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Receiver operating characteristic curves
The area under the ROC curve (c-statistic) is highest for initial cTnT (0.88). Of the investigational markers, the best performance was seen with H-FABP (0.74), GP-BB (0.61), NT-proBNP (0.68), and D-dimer (0.62) (Table 4). For patients admitted within 4 h of symptom onset the c-statistic for initial cTnT is seen to fall (0.78), while for H-FABP it rises (0.77) (Table 4). For this group of patients, the c-statistic for H-FABP is comparable with that of initial cTnT, but the diagnostic performance of NT-proBNP deteriorated (c-statistic 0.57).
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The investigational biomarkers most likely to assist with early detection of acute MI are therefore H-FABP, GP-BB, and D-dimer. Previously published decision limits (H-FABP,
5 ng/mL; GP-BB, 7 ng/mL; D-dimer, 0.5 µg/mL)4–6 were then used so that marker concentrations could be dichotomized.
Comparing sensitivities with initial cardiac troponin T
Sensitivities of these biomarkers were compared with that of initial cTnT for the diagnosis of acute MI (Figure 2). The sensitivity of cTnT at the time of admission was best for patients who presented 12 h after symptom onset. Conversely, the sensitivity is lowest when patients presented within 4 h. Sensitivity of H-FABP for acute MI (5 ng/mL) was superior to cTnT for patients admitted within 4 h of symptom onset. For patients who were admitted 4 h or more following symptom onset there was no significant difference between the sensitivities of H-FABP and cTnT. For patients who presented within 4 h of chest pain there was no significant improvement of GP-BB and D-dimer over the sensitivity of cTnT (Figure 2). For patients who presented later than this, the sensitivity of cTnT was significantly better than the sensitivity of D-dimer.
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Combining cTnT and H-FABP (either elevated) provided a significant improvement in sensitivity for patients presenting within 4 and 12 h of symptom onset (Figure 3). For patients presenting
12 h from the onset of chest pain the sensitivity of either marker positive was 100%. Adding GP-BB or D-dimer to cTnT did not result in a statistically significant increase in sensitivity.
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Although the sensitivity of H-FABP was significantly higher than cTnT only in patients who presented within 4 h of symptom onset, the specificity of H-FABP was significantly lower than cTnT (P < 0.001 overall; Table 5). The combined use of H-FABP and cTnT (either one elevated) significantly improved the sensitivity of H-FABP or cTnT. This was true for the entire patient group as well as for the two subgroups (<4 h,
4 h). In addition to improving sensitivities, using the combination approach consistently improved the negative predictive value, negative likelihood ratio, and the risk ratio (Table 5).
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Furthermore, when the 73 patients with STEMI were excluded from analysis the sensitivity of either cTnT or H-FABP elevated [86% (95% CI 72–94)] was significantly higher than the sensitivity of cTnT alone [65% (95% CI 50–78)] for patients admitted <4 h from pain onset; P = 0.016. This is achieved with a specificity of 69% (95% CI 58–79) and a negative predictive value of 91% (95% CI 81–96). For patients admitted
4 h from pain onset the sensitivity of either marker elevated [98% (95% CI 91–99)] was again superior to cTnT alone [91% (95% CI 83–95); P = 0.031]. The specificity of the combination approach for this subgroup was 55% (95% CI 47–64) and the negative predictive value was 97% (95% CI 91–99).
Logistic regression analysis
A forward stepwise logistic regression model which included the natural logarithmic transformations of initial cTnT, H-FABP, GP-BB, NT-proBNP, D-dimer, hsCRP, MPO, MMP-9, PAPP-A, and sCD40L was performed. After inclusion of all ECG variables in the model and adjustment for age, gender, risk factors, and impaired renal function (eGFR < 30 mL/min) the only novel biomarker to demonstrate significant independent predictive value for diagnosis of acute MI was H-FABP. A model which contained elevated H-FABP and elevated initial cTnT as categorical variables confirmed elevated H-FABP as a significant independent predictor of acute MI with an adjusted odds ratio of 2.1 (95% CI 1.1–3.9; P = 0.026). This model contained four variables: elevated initial cTnT, elevated H-FABP, ST-elevation on the initial ECG, and ST-depression on the initial ECG. The c-statistic for this model was 0.92 (95% CI 0.89–0.95); P < 0.001. The Hosmer and Lemeshow goodness-of-fit test was performed: P = 0.294.
To validate our model we divided our data set randomly into a training set and validation set. A new model based on the training set but using only these four variables was estimated. Those estimates were then used to predict the validation set. Three of the variables were significant in the training set (elevated initial cTnT, elevated H-FABP, and ST-depression on the initial ECG). This model had a c-statistic of 0.89 (95% CI 0.84–0.93; P < 0.001) for the training set and of 0.93 (95% CI 0.89–0.96; P < 0.001) for the validation set.
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Discussion |
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Early diagnosis of acute MI facilitates rapid and appropriate triage of patients within the Accident and Emergency department, helping to prevent inadvertent discharge of patients with acute MI. It also avoids delay in administering treatment for acute MI, and reduces the possibility of patients without acute MI given treatments from which they will not benefit, and which have the potential to cause significant harm. The 12-lead ECG is an important tool for early detection of acute MI, but it has significant limitations, e.g. LBBB or a permanent pacemaker, etc. may make interpretation impossible. Another significant factor is that interpretation of the 12-lead ECG is dependent on the experience of the physician.7
Acute MI is diagnosed if there is biochemical evidence of cardiac myocyte necrosis in the appropriate clinical setting.8 Cardiac troponins have assumed an important role in modern cardiology practice, both in diagnosis of acute MI and in risk stratification of patients with acute chest pain. A major drawback with cardiac troponins is that they are released relatively slowly from damaged myocytes.2 This study confirms the limitation of sampling cTnT at the time of admission for patients presenting with acute ischaemic-type chest pain. The sensitivity of initial cTnT for acute MI was 75% (95% CI 69–81). The sensitivity of initial cTnT was at its lowest for patients who presented within 4 h of symptom onset [55% (95% CI 44–66)]. It increased with increasing time from symptom onset to admission, with a sensitivity of 97% (95% CI 83–99) for patients who presented 12 h. This still leaves a false negative rate of 3% for the initial cTnT in this group of patients (i.e. second cTnT sampled 12 h or later from admission becoming positive).
This study has demonstrated that, of all the investigational biomarkers, H-FABP has a potential role in the early diagnosis of acute MI. There has been interest in H-FABP as a biochemical marker of myocardial injury since it was demonstrated to be released from injured myocardium in 1988.9 The release characteristics of H-FABP after acute MI show that a rise is detectable as early as 1.5 h after symptom onset, a peak level is reached after 4–6 h and, due to rapid renal clearance, the level returns to baseline within 20 h.10 Several studies reporting the usefulness of H-FABP as an early marker of acute MI pre-dated the widespread use of cardiac troponins and used the World Health Organization definition.11–13 Data for the diagnostic performance of admission H-FABP using the modern definition of acute MI are limited. H-FABP is present at high concentration within cardiac myocytes, and at lower concentration in other tissues such as skeletal muscle, kidney, specific parts of the brain, lactating mammary glands, and placenta.14 Early assays used antibodies which had high degrees of cross-reactivity with other FABP types. This may have hampered their clinical utility. More modern assays rely on monoclonal antibodies that have no cross-reactivity.15 The normal ranges reported for H-FABP are dependent on the assay used. The normal basal level of H-FABP within the plasma most likely relates to the continuous release from damaged skeletal muscle. In patients with renal insufficiency the level of H-FABP may be markedly raised, making interpretation problematic.3
Our study has demonstrated that measurement of H-FABP in patients with acute ischaemic-type chest pain at the time of admission is useful and complements the measurement of cTnT. The sensitivity of H-FABP is superior to initial cTnT for those seen within 4 h, but the specificity of H-FABP for acute MI was poor [71% (95% CI 60–80)]. The specificity of H-FABP for acute MI reported in previous studies varies from 49 to 86%.11–13,16 The most recent of these is by Mad et al.,16 who evaluated a qualitative point-of-care test for H-FABP and recruited patients at the time of presentation to an Accident and Emergency department. They quoted an overall sensitivity of 69% and specificity of 74%.
The reason for the relatively poor specificity of H-FABP in the current study may relate to a number of factors. First, H-FABP is present, albeit at lower concentrations, in skeletal muscle. In this study no data were collected on recent physical exercise, recent injury or non-cardiac surgery, or recent intramuscular injections. Secondly, H-FABP may be released from ischaemic myocardium as well as infarcted myocardium. In this study, however, the median level of H-FABP was not significantly elevated in patients diagnosed with unstable angina compared with patients diagnosed with non-ischaemic chest pain. Thirdly, in this study the median H-FABP level for patients with severe renal dysfunction (defined as eGFR < 30 mL/min) is significantly higher than for patients without renal dysfunction (P < 0.001). Although only 5% of the study population had a eGFR < 30 mL/min, substantially more (18%) had a milder degree of renal impairment (eGFR 30 to <60 mL/min) which could interfere with H-FABP levels given that H-FABP is renally excreted. If all patients with eGFR < 60 mL/min (n = 94) were excluded from analysis the specificity of H-FABP rose from 61% (95% CI 55–68) to 66% (95% CI 59–73) (overall); 71% (95% CI 60–80) to 76% (95% CI 64–85) (<4 h); and 56% (95% CI 48–64) to 61% (95% CI 51–69) (4 h).
The results of this trial would support the use of H-FABP, measured in combination with cTnT at the time of admission, to improve upon early detection of acute MI. This combined approach (either marker elevated) significantly improved sensitivity for acute MI of patients admitted within 12 h of symptom onset. For patients presenting 12 h after the onset of pain the increase in sensitivity achieved by combining the markers does not reach statistical significance. However, for these patients the sensitivity becomes 100% (95% CI 88–100). With this combination approach there is also a useful improvement in other parameters of diagnostic performance, particularly negative predictive value and negative likelihood ratio, and risk ratio indicating a role for H-FABP in rule-out acute MI in patients presenting with acute chest pain.
The clinical advantage of this combined approach can be illustrated by determining the effect on a group of 1000 patients with acute MI admitted with chest pain duration <4 h. If only cTnT is assessed at admission, 450 patients would have a delay in diagnosis. If the combination approach is used only 150 patients would have a delay. The disadvantage can be appreciated by considering a group of 1000 patients without acute MI but with acute chest pain of <4 h duration. Assessing cTnT alone will mean that 50 patients will be incorrectly diagnosed with acute MI. This will rise to 310 patients if the combination approach is used.
This study was designed as a proof of concept study of investigational biomarkers, with the exception of D-dimer, analysed in batches after a period of storage of serum at –70°C. To be clinically useful for early diagnosis of acute MI a rapid turnaround or point of care assay would be required.
Limitations
A limitation with this study is that recruitment took place at the time of admission. The reason for this design was that both recruitment sites operate a MCCU service which admits patients directly to the cardiology unit. This is reflected in the relatively high incidence of acute MI (48%). As a consequence, the results presented may not necessarily be applicable to lower risk populations, such as all patients with chest pain presenting to the Accident and Emergency department. Another limitation is that this study only assessed the potential benefit from a single measurement of each biomarker at the time of admission. Sequential measurements were not investigated. Myoglobin was not measured for comparison purposes. Unlike myoglobin, the concentration of H-FABP in cardiac muscle is higher than in skeletal muscle.10 This may mean that H-FABP is potentially more suitable as an early marker of myocyte injury than myoglobin. However, this study was designed with cTnT as the only comparator. Given the central role of cTnT in the assessment of patients with acute ischaemic chest pain, the priority was to determine if measuring other markers added significant information.
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Conclusions |
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Measuring H-FABP in addition to cTnT at the time of admission with acute ischaemic chest pain will assist in the early diagnosis of acute MI. For patients presenting within 4 h of symptom onset the sensitivity of H-FABP is significantly higher than cTnT. Using a combined approach improves sensitivity further for these patients. There is also a favourable increase in negative predictive value when H-FABP is measured with cTnT at the time of admission suggesting that H-FABP also has a valuable role in rule-out of acute MI. However, the specificity of H-FABP, either alone or in combination with cTnT, for acute MI is poor [71% (95% CI 60–80), 69% (95% CI 58–79)].
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Funding |
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Research Fellowship Royal Victoria Hospital; The Heart Trust Fund (Royal Victoria Hospital); Northern Ireland Chest, Heart, and Stroke Association (200312); Merck Sharp and Doehme.
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Acknowledgements |
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We are grateful to Mike Stevenson from Queen's University Belfast for his assistance with the statistical analyses performed for this research.
Conflict of interest: none declared.
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References |
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