Heart-type fatty acid binding protein (H-FABP) in patients in an emergency department setting, suspected of acute coronary syndrome: Optimal cut-off point, diagnostic value and future opportunities in primary care

*Oral presentation at the annual research conference of the European Primary Care Cardiovascular Society (EPCCCS) in London, September 2013.

Figures & data

Figure 1. Study flow chart as executed in the emergency service of the hospital of Genk, Belgium. AMI, acute myocardial infarction; H-FABP, heart-type fatty acid binding protein.

Table 1. Outcome definitions as used by the expert panel.

Diagnosis	Definition as used by expert panel
AMI	Clinical presence of ACS with ECG-changes, hs-cTn results or results of imaging techniques supporting myocardial infarction. Exact cut-off values of hs-cTn were defined using the 99th percentile of the upper reference limit in a normal reference population, as is widely accepted (10,11). In all cases of AMI, distinction was made between STEMI and non-STEMI.
nSTEMI	A situation of complaints indicative for ACS combined with at least one measurement of hs-cTn above the 99th percentile and thereby a change between two measurements of at least 20%, without ST elevations on ECG recordings (21).
STEMI	Complaints indicative for ACS combined with ST elevations on ECG recordings (23).
Unstable angina	Clinical presence of ACS based on typical and recently developed or altered symptoms of myocardial ischemia without changes in ECG or hs-cTn indicative for AMI (21).
Stable angina	Angina pectoris occurring in a patient in predictable situations for months, without a recent change in severity or amount of exertion that is needed for angina pectoris to occur (22).
No coronary disorder	No coronary disorder was diagnosed when AMI, stable angina and unstable angina were excluded.

AMI, acute myocardial infarction; ACS, acute coronary syndrome; ECG, electrocardiogram; hs-cTn, high sensitivity cardiac specific troponin; STEMI, ST elevated myocardial infarction; nSTEMI, non-ST elevated myocardial infarction.

Table 2. Patient characteristics.

	All	AMI (%)	No AMI (%)
Number	202	111 (55)	91 (45)
Gender
Male	157	93 (59)	64 (41)
Female	45	18 (40)	27 (60)
Age group
> 65 years	84	43 (51)	41 (49)
≤ 65 years	118	68 (58)	50 (43)
Duration complaints at presentation
0–3 h	82	46 (56)	36 (44)
3–6 h	40	23 (58)	17 (43)
6–12 h	56	29 (52)	27 (48)
12–24 h	24	13 (54)	11 (46)
eGFR
≥ 30	193	108 (56)	85 (44)
< 30	9	3 (33)	6 (67)

AMI, acute myocardial infarction; eGFR, estimated glomerular filtration rate (using modification of diet in renal disease (MDRD)—formula.

Figure 2. Receiver operating characteristic (ROC) curve of high sensitivity troponin and H-FABP, optimal cut-off point for H-FABP using ACS as outcome. ACS, acute coronary syndrome; H-FABP, heart-type fatty acid binding protein; hs-cTnT high sensitivity cardiac specific troponin T; ROC curve, receiver operating characteristic curve.

Table 3. Sensitivity and specificity of H-FABP for ACS at different cut-off values between positive and negative. Sensitivity and specificity of H-FABP for ACS at different cut-off values are given for all patients presenting complaints with a duration of 0–24 h and for all patients presenting complaints with a duration of 3–24 h at presentation. NPV is estimated for a population representative for primary care (incidence of ACS = 22%). Sensitivity, specificity and NPV for hs-cTnT with a cut-off of 14 pg/ml are given for comparison.

Cut-off value	Interval onset complaints—presentation 0–24 h			Interval onset complaints—presentation (h) 3–24 (ng/ml)
	Specificity	Sensitivity	NPV	Specificity	Sensitivity	NPV
3.0	43.5	85.7	91.5	45.7	94.2	96.5
3.5	60.9	79.0	91.1	65.2	88.4	95.2
4.0	71.7	73.9	90.7	73.9	85.5	95.8
4.5	78.3	66.4	89.2	82.6	84.1	94.9
5.0	78.3	58.8	87.1	82.6	79.7	93.5
hs-cTnT	73.9	70.6	89.9	67.4	88.4	95.4

ACS, acute coronary syndrome; H-FABP, heart-type fatty acid binding protein; hs-cTnT, high sensitivity cardiac specific troponin T; NPV, negative predictive value.

Table 4. Sensitivity and specificity of hs-cTnT and H-FABP. Sensitivity and specificity of hs-cTnT (cut-off 14 pg/mL) and H-FABP (cut-off 4 ng/mL) for AMI at different time intervals after onset of complaints.

Interval onset complaints—presentation (h)	0–3		3–6		6–12		12–24		0–24
	Sensitivity	Specificity	Sensitivity	Specificity	Sensitivity	Specificity	Sensitivity	Specificity	Sensitivity	Specificity
hs-cTnT	54.9	75.7	83.3	56.3	91.7	77.8	91.7	63.3	73.0	71.4
H-FABP	62.7	70.3	87.5	56.3	95.8	81.5	83.3	72.7	77.5	71.4
n	51	37	24	16	24	27	12	11	111	91

H-FABP, heart-type fatty acid binding protein; hs-cTnT, high sensitivity cardiac specific troponin T.

Table 5. Sensitivity of hs-cTnT and H-FABP. Sensitivity and median plasma concentrations (25th, 75th percentile) of hs-cTnT (cut-off 14 pg/ml) and H-FABP (cut-off 4 ng/ml) for STEMI, nSTEMI, all AMI (STEMI and nSTEMI), unstable angina and all ACS (AMI and unstable angina) at presentation, for all patients presenting complaints with a duration of 0–24 h and 3–24 h respectively.

Final diagnosis	STEMI		nSTEMI		AMI		Unstable angina		ACS
Interval onset complaints— presentation (h)	0–24	3–24	0–24	3–24	0–24	3–24	0–24	3–24	0–24	3–24
n	55	39	56	26	111	65	8	4	119	69
Sensitivity hs-cTnT	78.2	94.9	67.9	84.6	73.0	90.8	37.5	50.0	70.6	88.4
Sensitivity H-FABP	80.0	92.3	75.0	84.6	77.5	89.2	25.0	25.0	73.9	85.5
Median plasma concentration hs-cTnT (25th; 75th percentile)	129 (15;2140)	502 (49;3740)	24 (13;114)	88 (18;325)	45 (13;490)	194 (31;2140)	6 (3;15)	3 (3;15)	40 (13;325)	163 (31;1830)
Median plasma concentration H-FABP (25th; 75th percentile)	13.6 (4.3;24.9)	19.1 (10.0;25.6)	5.2 (3.9;11.3)	5.8 (4.2;11.7)	7.1 (4.1;18.4)	12.9 (5.4;21.6)	2.3 (2.2;3.5)	2.3 (2.3;3.1)	6.4 (3.9;18.1)	11.9 (4.9;21.2)

ACS, acute coronary syndrome; AMI, acute myocardial infarction; H-FABP, heart-type fatty acid binding protein; hs-cTnT, high sensitivity cardiac specific troponin T; nSTEMI, non-ST elevated myocardial infarction; STEMI, ST elevated myocardial infarction.

Table 6. Predictive values and likelihood ratios. PPV and NPV of hs-cTnT (cut-off 14 pg/ml) and H-FABP (cut-off 4 ng/ml) for AMI and ACS at time intervals of 0–24 h and 3–24 h after onset of complaints in a primary care setting with an incidence of AMI of 17% and ACS of 22%. PLR, NLR and OR of hs-cTnT (cut-off 14 pg/ml) and H-FABP (cut-off 4 ng/ml) for AMI and ACS at time intervals of 0–24 h and 3–24 h after onset of complaints.

	PPV		NPV		PLR		NLR		OR
Interval onset complaints—presentation (h)	0–24	3–24	0–24	3–24	0–24	3–24	0–24	3–24	0–24	3–24
hs-cTnT
AMI	34.3	39.5	92.8	97.3	2.55	2.94	0.38	0.13	6.75	22.0
ACS	42.9	47.6	89.9	94.8	2.66	3.22	0.40	0.16	6.65	20.2
H-FABP
AMI	35.7	40.1	93.9	97.1	2.71	3.27	0.32	0.15	8.60	22.1
ACS	42.9	48.6	90.8	94.8	2.67	3.36	0.36	0.20	7.41	17.2

ACS, acute coronary syndrome; AMI, acute myocardial infarction; H-FABP, heart-type fatty acid binding protein; hs-cTnT, high sensitivity cardiac specific troponin T; NLR, negative likelihood ratio; NPV, negative predictive value; OR, odds ratio; PLR, positive likelihood ratio; PPV, positive predictive value.

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