Study population
This prospective clinical cohort study continuously enrolled stable angina or acute coronary syndrome patients who underwent DES implantation, and who were expected to undergo CAG repeated in clinical follow-up in the Department of Cardiology at the the second affiliated hospital of Jiaxing University from January 2012 to December 2017. The aim of the study was to determine whether patients with coronary artery disease who had risk factors including dyslipidaemia, elevated inflammatory factors, and high Gensini scores would be more likely to develop ISR, and to determine if the dynamic observation of the changes of comprehensive risk factors before and after PCI would be helpful for the early identification of ISR in patients with DM.
The inclusion criteria were: (1) patients older than 18 years; (2) patients who were diagnosed in accordance with the diagnostic criteria for coronary intervention therapy [13]; (3) patients with an initial stent treatment; (4) patients with a successful stent implantation, and residual stenosis that was less than 20%; (5) patients who experienced no serious complications during the operation and hospitalisation; and (6) long-term (at least one year) tolerance of dual antiplatelet drugs, and statin therapy after discharge.
The exclusion criteria were: (1) patients with a previous history of coronary stent treatment and coronary artery bypass grafting; (2) patients with a previous restenosis after coronary drug balloon therapy; (3) patients with a history of malignant tumour, abnormal liver and kidney function, or with infectious diseases or acute and chronic active inflammation; (4) patients who were allergic to aspirin, clopidogrel, statins, heparin and other drugs; and (5) patients who had a history of haemolytic diseases, rheumatism, and thyroid hormone abnormalities.
Because this was a prospective study, all subjects were required to sign an informed consent form. The study complied with the Declaration of Helsinki and was approved by the ethics committee of the second affiliated hospital of Jiaxing University.
Research plan
Grouping
According to the exposure factors for DM, all patients were assigned to the combined DM group or to the non-combined DM group. The patients’ baseline parameters included age, sex, the presence of risk factors related to CHD (DM, hypertension, dyslipidaemia, family history, and smoking), fasting blood glucose, thyroid function, blood electrolytes, blood lipid profile, left ventricular ejection score (LVEF), and cardiac ultrasound results were collected. Hypertension was defined as a history of systolic blood pressure (SBP)> 140 mmHg and / or diastolic blood pressure (DBP)> 90 mmHg. DM was defined by fasting blood glucose test results of at least 126 mg / dl and / or the use of insulin or other antidiabetic drugs.
Fasting venous blood was tested before PCI and before repeated CAG in follow-up. The specific indicators included: TC, TG, LDL-c, HDL-c, RPL-C (TC minus low-density lipoprotein and high-density lipoprotein), non-HDL-c (TC minus high-density lipoprotein), ApoA1, ApoB100, ApoE, uric acid (UC), creatinine (Ccr), blood calcium concentration, blood magnesium concentration, blood phosphorus concentration, homocysteine ( Hcy), Glycated haemoglobin A1c (HbA1c), C-reactive protein (CRP), white blood cell (WBC), neutrophil (N), lymphocyte (L), monocyte (M), red blood cell (RBC), haemoglobin (Hb), platelet value (PLT), RBC distribution width (RDW), and platelet distribution width (PDW).
Interventional treatment of coronary heart disease
Patients who underwent elective interventional therapy were administered aspirin 0.1 g, clopidogrel 75 mg, and atorvastatin 20 mg once a day 48 hours before surgery. Emergency intervention patients were administered aspirin 0.3 g, clopidogrel 600 mg and atorvastatin 40 mg once as a loading dose. We followed the standardised procedures for interventional treatment guidelines for stable CHD and unstable coronary heart disease [13]. The criteria for successful stent implantation included: complete stent expansion, residual stenosis <20%; no obvious damage to the proximal and distal vessels of the stent; and thrombolysis in myocardial infarction (TIMI) blood flow level 3. The PCI-related DES stent diameter, the length and balloon inflation pressure, and the postoperative standardised medical treatment were recorded.
The Gensini score was calculated based on the severity of coronary stenosis as shown by CAG as follows: 1% to 25% coronary stenosis was scored as one point, 26% to 50% stenosis was two points, 51% to 75% stenosis was four points, 76% to 90% was eight points, 91% to 99% was 19 points, and 100% complete occlusion was 32 points. The coefficients of the corresponding lesions and branch vessels were assessed as follows: 5 points for the left main trunk, 2.5 points for the anterior descending branch, 1.5 points for the middle segment, 1.5 points for the distal segment, 1 point for the first diagonal branch, 1 point for the second diagonal branch, 2.5 points for the proximal segment of the circumflex branch, 1 point for the distal segment, 1 point for the blunt margin branch, and 1 point each for the proximal segment of the right coronary artery, middle segment, distal segment, posterior descending branch, and posterior branch of the left ventricle. All the lesions were identified, then they were multiplied by the corresponding coefficient; the integrated score was the total Gensini score. The Gensini score (no-stent) was the total Gensini score minus the coronary with stent implantation Gensini score. The participants were assigned to the LDL-c achieved group or the LDL-c failure group according to whether LDL-c was decreased by more than 50% compared with baseline or was less than 1.80 mmol/L in the follow-up.
Clinical follow-up and CAG
After being discharged from the hospital, the patients were followed up by telephone or an outpatient clinic visit once a month to record the health status, medication use, and to inquire about the side effects and symptoms the patients have experienced. The end point was set as restenosis in the stent.
The CAG results were routinely reviewed 1 year after PCI in the enrolled population. If patients experienced clinical symptoms (typical angina symptoms, positive exercise plate test, acute coronary syndrome, among others), they could elect to undergo a repeat CAG. Two independent interventional physicians interpreted the CAG results. If the results were inconsistent, three or more interventional physicians provided a joint interpretation. CAG was performed with a digital subtraction angiography system (Allura Xper FD-20 X-ray system; Philips Medical, Netherlands). CAG ISR was determined as follows: re-angiography revealed that the stent or the surrounding segments of the stent (within 5 mm of the two sides of the stent) lumen diameter was narrowed by more than 50%. If <50% stenosis was observed, it was interpreted as non-ISR.
Statistical analysis
We used SPSS statistical software package, version 22.0 (IBM, New York, United States) to conduct the statistical analyses. The data distribution was analysed by a Kolmogorov-Smirnov test. When a normal distribution was met, the continuous variable data was expressed as a mean and standard deviation, and the non-normal data was expressed as a median (interquartile range). Continuous variables were tested using the independent Student test, Mann-Whitney U test or Wilcoxon rank sum test. The categorical variables were expressed as rates (%), and the chi-square test was used. Univariate and multivariate regression analysis was used to assess the association between the risk factors and ISR. The Receiver operating characteristic curve, (ROC) was used to determine the optimal cut-off value of the risk factors that could predict ISR. The Kaplan-Meier method was used to analyse the cumulative occurrence of ISR in the DM and non-DM groups, along with a log-rank calculation test. A two-sided P value <0.05 was determined to be statistically significant.