Angiology: Open Access
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Importance of Heart-Type Fatty Acid-Binding Protein Combined with Creatinine Kinase and Homocysteine in Determining the Severity of Acute Poisoning

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Introduction

Acute poisoning is a common disease in Emergency Medicine (ED) which usually secondary results in destruction of multiple organs and system especially myocardial damage [1]. Although it does not represent the largest group of disease, such as stroke, heart attacks and infections, but in China acute poisoning is responsible for about 10.7% of all causes of death. It mainly includes the following categories: Intoxication with carbon monoxide (CO), intoxication with medical drugs, and intoxication with chemical products and pesticide.

Heart-type Fatty Acid-Binding Protein (H-FABP) is a soluble small molecule protein composed of 133 amino acid residues, mainly distributed in the heart, skeletal muscle, kidney, brain and other tissues [2,3]. It plays a role in intracellular fatty acid transport [4]. This protein has been recently used as a new marker since it released into the blood when myocardial cell destruction. In the acute poisoning patients, an increase in cardiac biochemical indicators like e.g. Creatinine Kinase (CK), Creatinine Kinase MB (CK-MB), myoglobin changes have been reported [5,6]. Homocysteine (Hcy) is an oxidant that causes oxidative stress in the body [7,8]. It has been reported that the role of oxidative stress as a major pathogenetic factor in some exogenous intoxication [9,10].

In recent years, serum H-FABP is more specific than myoglobin and it can be identified earlier than CK-MB and troponins in acute coronary syndromes [11,12]. Meanwhile, H-FABP combined with other biochemical indicators have been widely used in the detection of myocardial damage caused by different diseases [13]. However, studies specially focused on the significance diagnosis of H-FABP combined with CK and Hcy in the acute poisoning are limited. Herein, we monitor the difference of H-FABP, CK and Hcy in different type of the acute poisoning patients. Our specific objective is to assess the value of the three biomarkers in the diagnosis of moderate and severe acute poisoning.

Materials and Methods

The study followed the STROBE guidelines and was approved by the Ethical Committee of the Xi’an Central Hospital (2021-2020). The study was conducted as an observational study. Participating subjects read and signed the informed consent prior to enrolling in the study. This study was conducted on 224 cases of clinically diagnosed acute poisoning including carbon monoxide (CO), alcohol, pesticide and drug in the Department of Occupational Medicine of Xi’an Central Hospital between July 2017 and September 2020. Fifty healthy sex and age matched people were included in the control group. The sample size of our study was calculated after conducting a statistical analysis.

Distribution

• By gender: 102 women and 122 men

• By age: From 18 to 76 years old, the mean age of subjects was 50.4 ± 9.7 years

Blood samples were collected at the time of admission and the H-FABP, CK, Hcy of serum were tested at the time point. Laboratory tests were performed at the Clinical Laboratory of Department of Occupational Medicine of Xi’an Central Hospital.

Statistical analysis

Statistical analysis was performed using SPSS19.0 software (SPSS, Chicago, USA). All data were expressed as mean ± Standard Deviation (SD). All the data were normally distributed. The results of the parameters (H-FABP, CK, Hcy) were compared using the One-Way Analysis of Variance (ANOVA) among the groups. The Receiver Operating Characteristic (ROC)-curve analysis was conducted to evaluate the consequence of the index we established. The P-value<0.05 was considered significant.

Results and Discussion

Analysis of data from monitoring serum biomarkers traceability showed that in all four observed groups, the average H-FABP, CK and Hcy levels were significantly higher than those of the control group (p<0.05). The H-FABP of CO and drug groups were higher than the other two groups (p<0.05). The CK of CO group was highest and that of drug and alcohol groups were higher than pesticide group (p<0.05). The Hcy of alcohol group was highest and that of CO group was higher than pesticide and drug groups (p<0.05) (Table 1).

Table 1: Serum level of H-FABP, CK and Hcy in the groups.

To assess the dependence between the type of toxic substance and the severity of poisoning, we used cross tabulation on these categories. We found the expression of H-FABP had a statistically significant correlation between the moderate and severe of all types of poisoning (p ≤ 0.01) (Table 2). The expression of CK had a statistically significant correlation between the moderate and severe of all types of poisoning (p<0.01) expect alcohol group (p=0.318) (Table 3). The expression of Hcy were significant correlation between the moderate and severe of alcohol and drug poisoning (P<0.01) while no difference was found in the CO and pesticide poisoning (Table 4).

Table 2: H-FABP (ng/ml) of toxic substance and severity of acute poisoning.

Table 3: CK (u/l) of toxic substance and severity of acute poisoning.

Table 4: Hcy (umol/l) of toxic substance and severity of acute poisoning.

Binary logistic regression was used to evaluate the effect of HFABP, CK and Hcy on the diagnosis of the severity of acute poisoning. ROC curves depicted the discriminative value of our established evaluating system. The AUC was highest for combination group (H-FABP, CK and Hcy) (0.91) among all biomarkers (H-FABP 0.854, CK 0.833, Hcy 0.735). According to the ROC curves, we found that the optimal cutoff values were 4.08 ng/mL for H-FABP, 294.5 u/l for CK, 14.245 ng/mL for Hcy. Above their cutoffs, combination group had high sensitivities and specificities (81.4% and 90.0%, respectively). Meanwhile, combination group of the cutoff values could improve diagnostic performances of severity of acute poisoning (Table 5).

Table 5: Performance parameters for predictors of severity of acute poisoning.

Acute poisoning is defined as an acute exposure (less than 24 hours) to a toxic substance and characterized by extensive damage to organs, including chemical pulmonary edema, bone damage, heart failure, toxic encephalopathy, liver disease, and even death. It is one of the most frequent causes of visits to the ED. The annual rate of ED visits associated with poisoning varies widely across the world, and ranges from 0.1% to 0.7% [14]. Common symptoms due to intoxication include headaches, nausea, vomiting, slumber, and weakness, which may lead to neurological symptoms varying from confusion to coma. Sometimes the poison is unknown when a patient is found comatose with an unknown history. Thus, early identification of findings of type and severity of poisoning is highly important. In the various types of intoxication, CO poisoning is a type of intoxication with serious mortality particularly during winter months, alcohol poisoning mostly occurs in young adults, pesticide poisoning is the most common in most regions of China, while therapeutic drug poisoning is the main type of intoxication in developed regions or cities, such as Shanghai [15-18]. Therefore, poisoned patients were divided into the following categories in our study: CO, alcohol, pesticide and drug.

Erenler, et al. [19] showed that H-FABP might be a promising biomarker in evaluation of clinical severity in acute CO poisoning. Kim, et al. [20] considered higher CK-MB could be a screening tool for CO poisoning. Tufkova, et al. [21] showed that monitoring the serum level of Hcy could be a reliable marker in alcohol poisoning. But previous researches have been limited to a single biomarker or a single type of poisoning.

In our study, we monitored three biomarkers and H-FABP, CK and Hcy were significantly increased in all four poisoning groups than control group. Furthermore, we assessed the dependence between the type of toxic substance and the severity of poisoning. We found H-FABP and CK was significantly increased in severe patients than moderate patients in CO and pesticide poisoning. H-FABP and Hcy was significantly increased in severe patients than moderate patients in alcohol poisoning, while CK had no difference. H-FABP, CK and Hcy were significantly increased in severe patients than moderate patients in drug poisoning. The reasons of different expression of biomarkers in different types of poisoning maybe as follows: HFABP is a cytosolic protein found in large amounts in the myocardium and also found in the neuronal cell [22]. It plays a role in intracellular transport of fatty acid and would be released very early from damaged cells into the circulation. So it is the most sensitive biomarker in all types of poisoning patients. The results of previous study showed that serum CK activity was increased in imazalil and cypermethrin treated groups [23]. It is consistent with our study in pesticide poisoning. Alcohol mainly causes liver damage, while CK is mainly distributed in myocardium and skeletal muscle but the least in liver. Hcy as an oxidant is mainly associated with the systematic alcohol dependence [9,24]. Study on Hcy suggested that there was no difference between moderate and severe medications poisoning [21]. However, the present results showed an increasing Hcy in severe drug poisoning. It maybe because most of the drug poisoning were composed of anti-psychotic and anti-depressant drugs in our study. A number studies on Hcy showed that elevations of serum Hcy was identified as the harmful cause of the cardiovascular and nervous system [25,26].

Conclusion

In summary, serum H-FABP, CK, and Hcy are closely related to acute poisoning. H-FABP combined with CK and Hcy in determining the type and the severity of acute poisoning has an important value. This result implies that the expression of Hcy depends on the type of toxic drug. In assessing the kind and degree of acute poisoning, H-FABP has significant usefulness in combination with CK and Hcy. Meanwhile, we established the system to evaluate moderate and severe poisoning, the result showed H-FABP combined with CK and Hcy could improve the severity diagnostic performances.

Declarations

Author’s contributions

Yanli Wang and Xikai Wang conceived and designed the study. Xikai Wang and Jingjing Ma performed the study, collected and assembled the data. Yanli Wang performed the data analysis and interpretation. Xikai Wang and Yanli Wang wrote the manuscript. All authors read and approved the manuscript.

Funding

This work was supported by the Key research and development project in Shaanxi province (grant number: 2021SF-473).

Competing interests

The authors declare that there are no competing interests in this study.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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