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INTRODUCTION
Acute Coronary Syndrome (ACS) refers to a group of clinical syndromes with acute myocardial ischemic events due to a sudden obstruction of the coronary blood flow. It is almost always associated with the rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery.
ACS generally is divided into ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). The occurrence of ACS is primarily due to plaque erosion or plaque rupture after coronary atherosclerosis, and can cause incomplete occlusion of blood vessels or secondary complete occlusive thrombosis, which ultimately leads to acute myocardial Ischemia1. ACS is easy to be missed in the clinical area due to the fact that its signs and symptoms usually begin abruptly. ACS progresses rapidly, which affects the survival time and quality of life of ACS patients 2,3. Therefore, an early diagnosis is very important for ACS.
Thrombosis is one of the leading causes of atherosclerotic plaque formation. The detection of thrombus markers can identify whether the patient is in the prethrombotic state, which is of particular significance to assess the risk of ACS. The thrombus precursor protein (TpP) is a marker, and the most direct evidence, of impending thrombosis 4. P-selectin (Ps) is a member of the selectin family of cell adhesion molecules, which plays a vital role in the initiation of inflammation, the mediation of leukocyte adhesion and aggregation on the endothelium, and the formation of thrombus 5. In this study, through the determination of the above two biomarkers in healthy individuals and patients with ACS or SA in our hospital, we comprehensively analyzed the differences in the levels of the two factors in each studied group and investigated the significance of combined detection of TpP and Ps in the early diagnosis of ACS.
MATERIALS AND METHODS
Subjects and study design
Sixty-four patients with ACS treated in the Shanghai Xinhua Hospital Chongming Branch, from October 2019 to October 2020, were randomly selected as the case groups (including 30 patients with unstable angina (UA) and 34 patients with acute myocardial infarction (AMI) (18 patients with NSTEMI, 16 patients with STEMI)). Thirty patients with stable angina (SA) and 32 healthy people corresponding to the case group in terms of gender, age, ethnicity, etc. were selected as the control groups. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Xinhua Hospital Chongming Branch. All subjects gave their informed consent for inclusion before participating in the study (on admission). After admission, patients in each group received a routine electrocardiogram (or dynamic electrocardiogram), and the grouping was determined after the measurement of myocardial enzymes. Patients receiving platelet therapy, or with an abnormal coagulation function (DIC, hemophilia, leukemia, abnormal coagulopathy caused by severe liver disease, vitamin K deficiency) were excluded.
Baseline data were collected, including gender, age, nationality, blood glucose, blood lipids, and myocardial enzyme indexes. All the candidates had 4 ml of fasting venous blood drawn at 8:00 in the morning after admission. The Ps tube was immediately centrifuged at 3,000 rpm for 10 minutes to collect serum. The TpP tube was added with sodium citrate for anticoagulation and centrifuged at 3,000 rpm for 10 minutes to collect plasma. The collected serum and plasma were stored at -70° for testing.
Biomarker assays
Serum P-selectin was determined using a kit provided by Wuhan USCN Business Co., Ltd., and plasma TpP was measured with a kit provided by Wuhan Cusabio Technology LLC. The model of the microplate reader was Shanghai Kehua st-360.
Statistical analyses
The data obtained from the experiment were analyzed by SPSS 22.0 statistical software. The measurement data were expressed by χ̄ ± SD. The comparison between means was made by the Student’s t-test (analysis of variance was used to compare more than two groups). The counting data was represented by the composition ratio, and comparison between groups was by the χ2 test. P<0.05 indicated that the difference was statistically significant.
RESULTS
Basic characteristics of the study participants
The details of demographic data of the 126 study participants are listed in Table 1. The results showed that there were no significant differences in age and sex among the groups.
Table 1 Basic information of patients.
| Index | ACS | Control Groups | p | ||||
|---|---|---|---|---|---|---|---|
| UA (n=30) | NSTEMI (n=18) | STEMI (n=16) | SA (n=30) | Healthy (n=32) | |||
| Age | 67.40±10.669 | 61.44±14.454 | 65.00±8.990 | 65.97±10.361 | 62.22±14.988 | NS | |
| Gender | Male (n/%) | 21/70 | 13/72 | 22/73 | 22/73 | 19/60 | NS |
| Female (n/%) | 9/30 | 5/28 | 8/27 | 8/27 | 19/60 | ||
ACS: Acute coronary syndrome; UA: unstable angina; NSTEMI: non-ST-segment elevation myocardial infarction; STEMI: ST-segment elevation myocardial infarction; SA: stable angina.
Comparison of results between Stable Angina patients and healthy people
The results in Table 2, show that there were no statistically significant differences in age, blood glucose concentration, blood lipid concentration or the serum Ps levels between stable angina patients and healthy people (P>0.05). The serum TpP level of patients with SA was higher than that of the healthy people (P<0.05).
Table 2 Comparison of results between Stable Angina patients and healthy people.
| Index | SA Group (30 cases) | Healthy Group (32 cases) | p |
|---|---|---|---|
| Age (years) | 65.97±10.361 | 62.22±14.988 | NS |
| Blood glucose (mmol/L) | 6.54±1.946 | 6.30±2.257 | NS |
| Blood lipid (mmol/L) | 1.69±1.544 | 1.60±1.069 | NS |
| Ps (ng/mL) | 45.74±28.427 | 58.12±36.322 | NS |
| TpP (ng/mL) | 4.27±1.932 | 2.73±1.159 | 0.001 |
SA: stable angina Ps: P-selectin TpP: Thrombus precursor protein.
Comparison within case groups
In the case groups, there was no significant difference in the baseline data between patients with UA, STEMI and NSTEMI (P> 0.05). The serum levels of Ps and TpP of patients with NSTEMI and STEMI were higher than those of patients with UA (P<0.05). See Table 3.
Table 3 Comparison of the results of UA, NSTEMI and STEMI within the case group.
| Index | UA (30 cases) | NSTEMI (18 cases) | STEMI (16 cases) | p | ||
|---|---|---|---|---|---|---|
| (a and c1) | (a and c2) | (c1 and c2) | ||||
| Blood glucose (mmol/L) | 6.57±2.253 | 8.52±4.150 | 7.09±2.041 | NS | NS | NS |
| Blood lipids (mmol/L) | 1.81±1.504 | 1.91±1.198 | 1.99±1.168 | NS | NS | NS |
| Ps (ng/mL) | 39.09±12.139 | 87.40±37.413 | 93.39±39.000 | <0.001 | <0.0010 | NS |
| TpP (ng/mL) | 6.03±2.033 | 9.82±3.659 | 10.93±3.725 | 0.001 | 0.001 | NS |
UA: unstable angina NSTEMI: non-ST-segment elevation myocardial infarction; STEMI: ST-segment elevation myocardial infarction Ps: P-selectin TpP: Thrombus precursor protein.
Comparison of results between case and control groups
The demographics, clinical, and laboratory data (age, gender, blood glucose, blood lipids, etc.) between case groups and control groups had no significant difference (P> 0.05). The Ps and TpP levels of case groups were significantly higher than those of control groups (P<0.05). See Table 4.
Table 4 Comparison of results between case and control groups.
| Index | Case | Control | p |
|---|---|---|---|
| Age (years) | 65.23±11.396 | 64.03±12.990 | 0.581 |
| Blood glucose (mmol/L) | 7.20±2.886 | 6.41±2.103 | 0.090 |
| Blood lipids (mmol/L) | 1.89±1.326 | 1.64±1.318 | 0.319 |
| Ps (ng/mL) | 66.25±38.39 | 52.13±33.07 | 0.029 |
| TpP (ng/mL) | 8.32±3.69 | 3.47±1.746 | <0.001 |
Ps: P-selectin TpP: Thrombus precursor protein.
DISCUSSION
Many studies have confirmed that ACS is caused by unstable plaque, surface rupture, and breakage in the coronary arteries, which cause bleeding and thrombosis, leading to partial or complete occlusion of the coronary arteries. Platelet adhesion, activation, aggregation, and thrombosis are central to its pathogenesis 6. Through the detection of related factors involved in thrombosis, the early recognition of ACS can be improved.
TpP is a high molecular weight soluble fibrin polymer, formed by the polymerization of fibrin monomers produced by the action of thrombin on fibrinogen and is the direct precursor of insoluble fibrin. Studies have confirmed that when the TpP level rises, it means that the thrombus has started, and the fibrin monomer has begun to polymerize, which can be used as a predictor of thrombosis 7. Because of the specific antigenic determinants on the structure, this antigenic determinant does not exist on fibrinogen and fibrin degradation products. It may be more clinically significant than other indicators for diagnosing various thrombotic diseases 8.
Ps is a member of the selectin family of adhesion molecules. It plays a vital role in the process from leukocyte recruitment to plaque rupture. Related experiments have shown that Ps expression in platelets near the ruptured plaque was significantly increased, and there were a large number of mononuclear macrophages and T lymphocytes around it 9. Many studies have also confirmed that the level of Ps can be used to determine the incidence and severity of coronary heart disease 10,11.
The levels of the two indicators in the case group, were generally higher than those of healthy individuals and SA patients, which were similar to the results of Atalar 12 and Kayikcioglu et al. 13. In addition, this study found that the levels of Ps and TpP in patients with acute myocardial infarction were significantly higher than those in patients with unstable angina. This indicated that there is a significant correlation between the changes in the levels of the two and AMI, but there is little difference between petients with STEMI and NSTEMI. There was no significant difference between healthy people and SA patients. Ps and TpP may play a role in early detection of ACS, but they cannot distinguish between NSTEMI and STEMI.
The concentration of TpP in plasma reflects the activity of thrombin in circulation. The increase of TpP indicates that the fibrin monomer has polymerized, which indicates that the thrombus is about to form (and is an indicator of thrombus activity this is a repetition). Stimulated by hypoxia, free radicals, and thrombin, the expression of Ps increases, which mediates the adhesion of leukocytes and endothelial cells and plays a central role in thrombosis 14,15. Therefore, in patients with ACS caused by thrombosis, the expression levels of TpP and Ps may be significantly up-regulated. TpP is of great significance not only for the early diagnosis but also for the severity and prognosis of ACS 16. Thus, TpP cannot only be used for the diagnosis but also for the classification of ACS in the future.
In summary, through the detection of molecular markers of the prethrombotic state, the early diagnosis of ACS can be achieved. It provides crucial guidance for further decisions on treatment options in clinical work, reduces the risk of premature death, improves the survival rate of patients, and brings greater benefits to the clinical response in the occurrence of acute cardiovascular events.
