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Application value of hypersensitive C-reactive protein, lactic acid and myoglobin in the combined detection of myocarditis

Application value of hypersensitive C-reactive protein (hs-CRP), blood lactic acid (LAC) and myoglobin (Mb) in the combined detection of myocarditis was explored. A total of 107 patients with suspected myocarditis treated in The Second Nanning People's Hospital from January 2015 to December 2017 were retrospectively analyzed, of whom 81 patients diagnosed with myocarditis were enrolled into the research group, and 26 non-myocarditis individuals were enrolled into the control group. Fasting venous blood was drawn from all patients to detect the hs-CRP, LAC and Mb, and their levels were compared and analyzed between the two groups. Moreover, the coincidence rate, sensitivity and specificity of single detection and combined detection by hs-CRP, LAC and Mb in the diagnosis of myocarditis were compared and analyzed. There were no significant differences in the sex, age, smoking status, alcohol consumption, chest distress, palpitation, angina and dyspnea between the two groups (P>0.05), proving that patients in both groups were comparable. The levels of hs-CRP, LAC and Mb in the research group were significantly higher than those in the control group, displaying statistically significant differences (P<0.05). According to the receiver operating characteristic (ROC) curve, the area under the curve (AUC), coincidence rate, sensitivity and specificity in the diagnosis of myocarditis, respectively, were 0.610 (95% CI: 0.495–0.725), 58.88, 51.85 and 80.77% for hs-CRP, 0.657 (95% CI: 0.551–0.763), 58.88, 54.32 and 73.08% for LAC, 0.747 (95% CI: 0.651–0.843), 69.16, 64.20 and 84.62% for Mb, and 0.773 (95% CI: 0.680–0.867), 76.64, 79.01 and 69.23% for combined detection. Hs-CRP, LAC and Mb are highly expressed in the serum of patients with myocarditis, and their combined detection has guiding significance for the prevention and treatment of myocarditis.


Introduction
Myocarditis is a severe myocardial injury, and the dysfunction of cardiac electrical pathway caused by myocarditis is also one of the major causes of sudden death in young adults (1). In the early stage of the disease, patients only suffer from chest distress and palpitation, so it is often ignored by them. Besides, the diagnosis of non-specific symptoms is difficult, so the optimal treatment opportunity is often missed (2). Currently, the pathogenesis of myocarditis remains unclear in clinic. Myocarditis can be caused by a variety of factors, and it is characterized by acute onset, rapid progression, and even death in severe cases. Therefore, the early diagnosis of myocarditis plays a key role in clinical treatment and prevention (3).
It is very difficult to diagnose myocarditis, and the optimal means of diagnosing the type of myocarditis and determining its cause is an endomyocardial pathological biopsy. However, there is psychological repellence in patients due to the invasive examination and complications (4). C-reactive protein (CRP) is the most commonly-used acute-phase response index in clinic, which is involved in multiple stress responses and serves as an important index for the diagnosis of cardiovascular and cerebrovascular diseases (5). Hypersensitive CRP (hs-CRP) is not affected by diet, time and corticosteroid therapy, which can reflect the severity of cardiovascular and cerebrovascular injury in patients more quickly and effectively (6). Blood lactic acid (LAC) is a product of anaerobic glycolysis closely related to the metabolism and movement, which cannot only detect whether there are disorders in the respiratory system and circulatory system in human body, but also reflect the severity of disease (7). Myoglobin (Mb) is a kind of protein for cell storage and oxygen distribution in mammals, and serves as an important index for myocardial and skeletal muscle injury (8). However, hs-CRP and Mb are non-specific diagnostic indexes, so the single detection has no high diagnostic value in myocarditis. The combined detection can provide more complete indexes for clinicians and high reference value in the diagnosis of myocarditis, so it can be used as an effective means for the early diagnosis and determination of risk factors for prognosis of patients with myocarditis (9). At present, there are few studies on the diagnosis of myocarditis via combined detection of hs-CRP, LAC and Mb. In this study, the expression levels of hs-CRP, LAC and Mb in patients with myocarditis were studied, and the coincidence rate, sensitivity and specificity of single detection and combined detection of hs-CRP, LAC and Mb in the diagnosis of myocarditis were analyzed, so as to determine whether the single detection and combined detection of hs-CRP, LAC and Mb can be used as diagnostic methods for myocarditis, and provide efficient and reliable references for the clinical treatment of patients with myocarditis in the future.

Patients and methods
Data of patients. A total of 107 patients with suspected myocarditis treated in the Second Nanning People's Hospital (Nanning, China) from January 2015 to December 2017 were selected, of whom 81 patients diagnosed with myocarditis were enrolled into the research group, and 26 non-myocarditis individuals were enrolled into the control group. In the research group, there were 37 females and 44 males aged 22-64 years with an average of 37.91±4.72 years. In the control group, there were 11 females and 15 males aged 19-63 years with an average of 41.17±4.38 years. Inclusion criteria were: patients diagnosed with suspected myocarditis via electrocardiography, echocardiography and X-ray examination, patients with complete data, patients aged >18 years, and patients who did not receive relevant treatments before admission. Exclusion criteria were: patients with other basic heart disease, pregnant or lactating patients, patients with other severe diseases or tumors, patients who were unwilling to undergo endomyocardial biopsy to diagnose myocarditis, or patients with communication or cognitive disorders.
This study was approved by the Ethics Committee of The Second Nanning People's Hospital. All the patients and their families signed an informed consent and cooperated with medical workers in relevant diagnoses and treatments. Diagnostic criteria. According to relevant literature (9), the criteria in single detection in the diagnosis of myocarditis are as follows: hs-CRP >10 mg/l, LAC >100 mg/l, and Mb>80 µg/l. The criteria in combined detection in the diagnosis of myocarditis are as follows: hs-CRP, LAC and Mb levels are higher than the threshold value.
Statistical analysis. SPSS 18.1 (Beijing ND Times Technology Co., Ltd.) software system was used for the statistical analysis. The basic enumeration data of patients were expressed as percentage (%), and Chi-square test was adopted. The expression levels of hs-CRP, LAC and Mb were expressed as mean ± standard deviation, and t-test was used for the difference between the two groups. P<0.05 was considered to indicate a statistically significant difference.

Comparison of clinical data of patients.
To make the experimental results accurate and reliable, the sex, age, smoking status, alcohol consumption, chest distress, palpitation, angina and dyspnea were compared between the two groups, and it was found that there were no significant differences (P>0.05), proving that patients in both groups were comparable. The basic data of patients are shown in Table Ⅰ.    (Table Ⅶ and Fig. 1).

Discussion
Myocarditis can cause severe hemodynamic damage. The proportion of myocarditis is up to 13% in the cause of sudden death in adolescents, and its global incidence rate is 18.27/100,000 and prevalence rate is 21.83/100,000 (10). Pathogenesis of myocarditis has been studied by a large number of scholars, but its clinical manifestations are non-specific and diverse, and dependent on the range and severity of lesion due to the different etiology, and there may even be no clinical symptoms, making it one of the most challenging cardiovascular diseases (11). Moreover, it is hard to conduct multi-center large-scale experiments due to the limited incidence rate, so myocarditis is a major challenge in the medical field (12). In this study, a total of 107 patients with suspected myocarditis were retrospectively analyzed, including 81 patients pathologically diagnosed with myocarditis and 26 non-myocarditis patients. The levels of hs-CRP, LAC and Mb were compared and analyzed between the two groups of patients, and the coincidence rate, sensitivity and specificity of single detection and combined detection by hs-CRP, LAC and Mb in the diagnosis of myocarditis were also compared. The expression level of hs-CRP in the research group was significantly higher than that in the control group (10.79±1.63 mg/l vs. 9.67±1.22 mg/l), and there was a statistically significant difference. There were 47 cases of myocarditis diagnosed in the single detection by hs-CRP, and 42 cases were correctly diagnosed. According to the ROC curve, AUC, coincidence rate, sensitivity and specificity in the diagnosis of myocarditis, respectively, were 0.610 (95% CI: 0.495-0.725), 58.88, 51.85 and 80.77% for hs-CRP. hs-CRP is an acute-phase reactive protein synthesized by the liver, and the changes in its expression level can rapidly reflect the subtle changes in the circulatory system. Besides, it is less affected by anti-inflammatory and hormone drugs, which can reflect the severity of cardiovascular injury more sensitively (13). However, hs-CRP is increased in acute myocardial infarction and stress response, so it is not a specific diagnostic index (14).
Gölbasi et al (15) reported that the level of hs-CRP in patients with acute myocarditis is increased, and the ST-T changes in more than 2 out of 4 leads (EKGI, II, aVF and V5) indicate the increased risk of myocarditis. The expression level of LAC in the research group was significantly higher than that in the control group (106.24±14.08 mg/l vs. 98.15±11.43 mg/l), and there was a statistically significant difference. There were 51 cases of myocarditis diagnosed in a single detection of LAC, and 44 cases were correctly diagnosed. According to the ROC curve, AUC, coincidence rate as well as sensitivity and specificity in the diagnosis of myocarditis, respectively, were 0.657 (95% CI: 0.551-0.763), 58.88, 54.32 and 73.08% for LAC. In patients with myocarditis, a large number of catecholamines are secreted due to the stimulation of inflammatory factors, thus leading to the increased level of fasting blood glucose. Then the high-level fasting blood glucose promotes anaerobic glycolysis, and a large amount of LAC is produced in the body. The increase in LAC in patients can suggest disorders in the respiratory or circulatory system. However, LAC can be easily affected by blood glucose, so it is not specific in the diagnosis of myocarditis (16). The expression level of Mb in the research group was obviously higher than that in the control group (82.31±7.15 µg/l vs. 77.87±5.54 mg/l), and the difference was statistically significant. There were 56 cases of myocarditis diagnosed in the single detection of Mb, and 52 cases were correctly diagnosed. According to the ROC curve, AUC, coincidence rate as well as sensitivity and specificity in the diagnosis of  (17). As a small-molecule protein containing heme, Mb can display the tissue hypoperfusion and oxygenation dysfunction, so its level increases in the case of shortness of breath or chest pain in patients with myocarditis (18). Related studies (19) have demonstrated that if patients suffer from severe myocardial damage or ventricular systolic dysfunction, the level of Mb is increased, which has a significantly positive correlation with the degree of degeneration or necrosis of myocardial cells. The above research results are similar to this study, proving these findings. There were 72 cases of myocarditis diagnosed in the combined detection, and 64 cases were correctly diagnosed. According to the ROC curve, AUC, coincidence rate as well as sensitivity and specificity in the diagnosis of myocarditis, respectively, were 0.773 (95% CI: 0.680-0.867), 76.64, 79.01 and 69.23% for combined detection. hs-CRP, LAC and Mb are commonly-used indexes reflecting the myocardial damage of patients, as well as reference indexes in the diagnosis of myocarditis (20). According to literature (21), the peaks of hs-CRP, LAC and Mb indicate severe myocardial damage. Berg et al (22) conducted a 5-year follow-up study on child patients with myocarditis, and found that hs-CRP, LAC and Mb are risk factors for prognosis of patients. These research results can prove the conclusion in this study that the combined detection has high value in the diagnosis of myocarditis.
In this experiment, the sample size was small due to the limited medical resources in the hospital, so the results may have certain contingency. Therefore, further studies are needed for confirmation.
In conclusion, hs-CRP, LAC and Mb are highly expressed in the serum of patients with myocarditis, and their combined detection has guiding significance for the prevention and treatment of myocarditis.