Coronary artery disease (CAD) is a major cause of death in the developed world. Unstable angina belongs to the spectrum of presentations known collectively as acute coronary syndrome and is defined as myocardial ischemia without significant myocardial necrosis [
Trimetazidine is a cytoprotective anti-ischemic agent that exerts its beneficial effects through several mechanisms that include inhibition of fatty acid oxidation, reduction in oxygen required for ATP production, and reduced intracellular accumulation of hydrogen ions, lactate, sodium ions, and calcium ions [
The study was approved by the Second Hospital of Tianjin Medical University Ethics Committee. All subjects provided written, informed consent for enrolment into this study. A total of 97 patients with unstable angina presenting to our hospital from July to December 2017 were recruited. The inclusion criteria were as follows: (i) patients diagnosed with unstable angina pectoris according to established guidelines [
Patients were randomly divided into trimetazidine group (
Peripheral venous blood (2 ml) was collected from all enrolled subjects immediately before PCI and at 6:00 AM the following morning after the procedure. The blood samples were subjected to centrifugation for 10 min at 2500 rpm/min. The sera supernatant separated was preserved at −80°C in a refrigerator. Detection of cTnI was performed using chemiluminescence immunoassay (Nanjing Jiancheng Biology Engineering Institute, Nanjing, China). CK-MB, h-FABP, and vWF were measured by ELISA (GBD, USA). NO was detected by the nitrate reductase method (Nanjing Jiancheng Biology Engineering Institute, Nanjing, China). All procedures were performed according to the protocols of the manufacturers.
Statistical analysis was performed using SPSS software (version 19.0; SPSS Inc., Chicago, IL, USA). Descriptive statistics for continuous variables were expressed as mean ± standard deviation (
In this study, a total of 97 patients (59 males and 38 females) with a mean age of 64.9 ± 10.8 years were included. Their baseline characteristics are shown in Table
Baseline characteristics of the control and trimetazidine groups.
Characteristics | Control group | Trimetazidine group |
|
---|---|---|---|
Cases ( |
49 | 48 | |
Age (years) | 64.22 ± 10.54 | 65.59 ± 12.07 | 0.399 |
Gender (male/female) | 31/18 | 27/21 | 0.766 |
Hypertension (yes/no) | 30/19 | 30/18 | 0.412 |
Diabetes (yes/no) | 11/38 | 8/40 | 0.195 |
Cerebral infarction (yes/no) | 4/45 | 8/40 | 0.240 |
Atrial fibrillation (yes/no) | 2/47 | 1/47 | 0.845 |
Smoking (yes/no) | 36/13 | 31/17 | 0.353 |
TC (mmol/L) | 5.09 ± 1.08 | 4.86 ± 1.07 | 0.525 |
TG (mmol/L) | 2.26 ± 1.92 | 1.78 ± 1.01 | 0.208 |
LDL-C (mmol/L) | 2.94 ± 0.89 | 2.78 ± 0.64 | 0.627 |
HDL-C (mmol/L) | 1.21 ± 0.38 | 1.12 ± 0.23 | 0.294 |
LVEF | 0.56 ± 6.32 | 0.55 ± 7.83 | 0.822 |
Arterial stenosis ( |
2.26 ± 0.81 | 2.46 ± 0.73 | 0.389 |
Stent ( |
1.54 ± 0.74 | 1.68 ± 0.82 | 0.130 |
Blood collection time after PCI ( |
16.70 ± 2.46 | 16.68 ± 3.42 | 0.543 |
TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction.
In the control group, the levels of myocardial injury, CK-MB (
CK-MB, cTnI, h-FABP, NO, and vWF in the control and trimetazidine groups.
Serum levels of CK-MB, cTnI, h-FABP, NO, and vWF in the control groups, expressed as
CK-MB (U/L) | cTnI (ng/mL) | h-FABP (ng/mL) | NO ( |
vWF (ng/ml) | |
---|---|---|---|---|---|
Pre-PCI | 11.25 ± 3.74 | 0.05 ± 0.18 | 0.84 ± 0.98 | 78.50 ± 3.75 | 2.18 ± 1.14 |
Post-PCI | 16.02 ± 11.01 | 0.47 ± 0.19 | 0.90 ± 1.04 | 54.31 ± 4.97 | 2.62 ± 1.30 |
|
0.043 |
0.000 |
0.333 | 0.000 |
0.005 |
PCI: percutaneous coronary intervention, CK-MB: creatine kinase-muscle/brain, cTnI: cardiac troponin I, h-FABP: heart-type fatty acid-binding protein, vWF: von Willebrand factor, and NO: nitric oxide.
Serum levels of CK-MB, cTnI, h-FABP, NO, and vWF in the trimetazidine groups, expressed as
CK-MB (U/L) | cTnI (ng/mL) | h-FABP (ng/mL) | NO ( |
vWF (ng/ml) | |
---|---|---|---|---|---|
Pre-PCI | 13.45 ± 3.06 | 0.16 ± 0.37 | 1.09 ± 0.97 | 60.53 ± 6.87 | 2.43 ± 0.58 |
Post-PCI | 13.68 ± 8.87 | 0.22 ± 0.14 | 1.13 ± 1.21 | 60.46 ± 9.19 | 2.62 ± 0.54 |
|
0.113 | 0.051 | 0.284 | 0.905 | 0.143 |
PCI: percutaneous coronary intervention, CK-MB: creatine kinase-muscle/brain, cTnI: cardiac troponin I, h-FABP: heart-type fatty acid-binding protein, vWF: von Willebrand factor, and NO: nitric oxide.
Levels of h-FABP at different time points for the control group. 1, pre-PCI right time; 2, 3 h post-PCI; 3, 6 h post-PCI; 4, >10 h post-PCI;
Next, the changes in the levels of the above markers between the control and trimetazidine groups were compared (Table
Changes in CK-MB, cTnI, h-FABP, NO, and vWF levels before and after PCI in the control and trimetazidine groups, expressed as
ΔCK-MB (U/L) | ΔcTnI (ng/mL) | Δh-FABP (ng/mL) | ΔNO ( |
ΔvWF (ng/ml) | |
---|---|---|---|---|---|
Control group | 4.77 ± 13.73 | 0.42 ± 0.78 | 0.06 ± 0.37 | 24.19 ± 5.85 | 0.43 ± 0.72 |
Trimetazidine group | 0.23 ± 2.60 | 0.06 ± 0.37 | 0.04 ± 1.31 | 0.07 ± 7.90 | 0.19 ± 0.13 |
|
0.016 |
0.035 |
0.640 | 0.010 |
0.002 |
ΔCK-MB: change in creatine kinase-muscle/brain, ΔcTnI: change in cardiac troponin I, Δh-FABP: change in heart-type fatty acid-binding protein, ΔNO: change in nitric oxide, and ΔvWF: change in von Willebrand factor.
Difference in the levels of CK-MB, cTnI, h-FABP, NO, and vWF between pre- and post-PCI in the control and trimetazidine groups. C, control group; T, trimetazidine group; ΔCK-MB, the ascended levels of CK-MB; ΔcTnI, the ascended levels of cTnI; Δh-FABP, the ascended levels of h-FABP; ΔNO, the descended levels of NO; ΔvWF, the ascended levels of vWF;
The main findings of this clinical study are that in patients with unstable angina, trimetazidine treatment prevented the increase in CK-MB, cTnI, and vWF and the decrease in NO induced by PCI but did not significantly affect the levels of h-FABP.
ACS is a major cause of increased mortality in patients with CAD [
CK-MB and cTnI are established markers of myocardial injury, released by cardiomyocytes in response to damage. h-FABP is a low-molecular-weight protein (14.5 kDa) comprised of 132-amino acid residues found in cardiomyocytes [
Moreover, vWF is stored in and secreted from the Weibel–Palade bodies (WPBs) of endothelial cells [
Previous studies showed that trimetazidine improves endothelial dysfunction and myocardial injury in patients with ischemic heart disease or chronic heart failure [
In this prospective, observational study, our results indicated the obvious advantages of additional use of trimetazidine before PCI, in line with data from a recently published study [
Several limitations should be noted. Firstly, this study included a relatively small sample assessing changes in myocardial and endothelial injury markers over a short period of time. Further prospective studies are needed to explore the potential beneficial effects of trimetazidine over a longer timescale. Secondly, endothelial and myocardial damage was assessed using established biomarkers. Additional basic science studies are needed to better elucidate the underlying molecular mechanisms through which trimetazidine exerts its actions. Thirdly, given the benefit of statin pretreatment for patients with stable angina and acute coronary syndrome undergoing PCI [
The endothelial and myocardial damage caused by PCI in patients with unstable angina can be prevented by perioperative use of trimetazidine.
The data used to support the finding of this study are included within the tables of the article.
The authors declare that they have no conflicts of interest.
This study was funded by the Tianjin Natural Science Foundation (Grant no. 18JCQNJC11200). The authors thank all the patients, their families, and the institutions involved in this study.