Prognostic Value of the Cardiac Form of Fatty Acid-Binding Protein in Patients with Acute Coronary Syndrome without ST-Segment Elevation on ECG

The dissertation is devoted to the investigation of the prognostic value of measuring the cardiac form of fatty acid-binding protein (h-FABP) in patients with acute coronary syndrome without ST-segment elevation on ECG (NSTE-ACS) hospitalised in the early hours after symptom onset. The study examines the limitations of existing biochemical markers of myocardial necrosis, in particular cardiac troponins and CK-MB, which are associated with the late rise of their blood levels and insufficient sensitivity during the first hours of the disease. A comparative assessment is made of the diagnostic and prognostic value of h-FABP, cTnI and CK-MB with respect to long-term adverse events, as well as in specific patient subgroups—those hospitalised within the first 3 hours, with non-diagnostic ECG, elevated creatinine and a history of diabetes mellitus. Based on the results, a scoring system is proposed for the early identification of patients at high risk of adverse events.

RELEVANCE OF THE STUDY

The contemporary approach to the management of patients with acute coronary syndrome without ST-segment elevation on ECG (NSTE-ACS) presupposes the obligatory stratification of patients according to the risk of serious complications and adverse events. Identification of a high-risk group allows a more aggressive treatment strategy to be applied to such patients, for example, initiation of heparin therapy and/or early invasive intervention.

The determination of biochemical markers of myocardial necrosis occupies a central place in the assessment of the risk of death and myocardial infarction (MI) in patients with NSTE-ACS.

At present, measurement of cardiac troponin T or I (cTnT or cTnI) levels is considered the "gold standard" both for the diagnosis of MI and for risk stratification in patients with NSTE-ACS.

However, cardiac troponins, as markers of myocardial necrosis, have a number of limitations that complicate the interpretation of their results. Troponins are released into the blood from damaged cardiomyocytes only 4–6 hours after the onset of myocardial ischaemia; therefore, measurement of troponin levels in the very first hours of the disease is poorly informative and repeat testing 8–12 hours later is required.

In addition to cardiac troponins, other biochemical markers of myocardial necrosis are widely used in clinical practice, but they too have significant limitations. For example, measurement of the MB fraction of creatine kinase (CK-MB) in the first hours after the onset of NSTE-ACS may be uninformative because of its relatively late release into the blood (approximately 6 hours after symptom onset). Moreover, in terms of sensitivity for myocardial necrosis and for prognostic purposes, CK-MB measurement is markedly inferior to cardiac troponins.

In NSTE-ACS, blood myoglobin levels rise very early; however, its use in clinical practice is limited by its very low specificity for myocardial necrosis.

Thus, early diagnosis and risk stratification in patients with NSTE-ACS remains an important and unresolved clinical problem.

Relatively recently, fatty acid-binding protein (FABP) has been proposed as an early biomarker of myocardial necrosis. The cardiac form of this protein (h-FABP) has a low molecular weight (approximately 15 kDa) and is located predominantly in the cytosol of cardiomyocytes in a free form. Because of these features, when cardiomyocytes are damaged, h-FABP is released into the bloodstream within the first hours after the onset of myocardial ischaemia and can be detected.

By analogy with cardiac troponins, elevation of which in NSTE-ACS not only identifies MI but also determines prognosis, it may be assumed that h-FABP also has not only diagnostic but also prognostic value with respect to MI (the former having already been demonstrated in several studies). However, the association between early measurement of h-FABP and the risk of adverse events in patients with NSTE-ACS has been very little studied, particularly with regard to long-term prognosis. Moreover, there are no data on the comparison of the long-term prognostic value of h-FABP measurement with that of cTnI and other biomarkers of myocardial necrosis in patients hospitalised early with NSTE-ACS.

AIM OF THE STUDY

To investigate the prognostic value of measuring h-FABP levels in patients with NSTE-ACS hospitalised within the first 12 hours after symptom onset.

OBJECTIVES OF THE STUDY

A. To evaluate the association between h-FABP levels in patients with NSTE-ACS and the development of serious adverse events during hospitalisation as well as at 6 and 12 months after inclusion.

B. To compare the prognostic value of h-FABP measurement with that of well-established and recommended markers of myocardial necrosis (cTnI and CK-MB) in patients with NSTE-ACS.

C. To evaluate the prognostic value of h-FABP measurement in various subgroups of patients with NSTE-ACS: those hospitalised within the first 3 hours after symptom onset, with non-diagnostic ECG, with elevated creatinine levels, and with diabetes mellitus in their history. To compare the prognostic value of h-FABP, cTnI and CK-MB in these subgroups.

D. To evaluate the diagnostic value of h-FABP measurement in patients with NSTE-ACS (to confirm the reproducibility of the study results).

SCIENTIFIC NOVELTY

A. For the first time, the prognostic value of early measurement of h-FABP levels in patients with NSTE-ACS has been evaluated with respect to the development of long-term adverse events (at 6 and 12 months).

B. For the first time, the prognostic values of h-FABP, cTnI and CK-MB have been compared in patients with NSTE-ACS.

C. For the first time, the optimal time after symptom onset of NSTE-ACS for measuring h-FABP in order to identify patients with an adverse prognosis has been determined (6 hours after symptom onset).

D. For the first time, an attempt has been made to assess the prognostic value of h-FABP measurement in individual patient groups (with non-diagnostic ECG, with diabetes mellitus, and with elevated creatinine levels).

E. The available information on the diagnostic value of h-FABP for myocardial necrosis has been supplemented.

PRACTICAL SIGNIFICANCE

A. The data obtained from the study of the prognostic value of early h-FABP measurement in patients with NSTE-ACS may serve as a basis for using h-FABP as a biomarker of long-term adverse prognosis following NSTE-ACS.

B. The advantage of h-FABP over cTnI as a marker of adverse long-term prognosis, demonstrated in the study, may provide a rationale for using h-FABP measurement in broad clinical practice alongside cardiac troponins but at earlier time points.

C. The scoring system developed on the basis of the study results for the early identification of patients at high risk of adverse events can be applied in clinical practice for more accurate risk stratification in patients with NSTE-ACS.

THEORETICAL SIGNIFICANCE

The results of this study may serve as a theoretical foundation for further, more detailed investigation of the prognostic value of h-FABP in NSTE-ACS. An example of such research would be a study in which h-FABP levels directly influence the choice of treatment strategy.