Study patients
The present study is a retrospective cohort study of 2701 coronary artery disease (CAD) patients with Type 2 diabetes mellitus (T2DM) who underwent successful coronary second-generation drug-eluting stents (G2-DESs) implantation at Beijing Anzhen Hospital (Beijing, China) from January 2013 to December 2014 and were followed up by angiography. Patients who died in the hospital after baseline PCI or without sufficient clinical and angiographic data at baseline and follow up were excluded. Of these patients, 2312 patients who met the inclusion and exclusion criteria were analysed in the present study. Multivariate Cox’s proportional hazards regression modelling showed that RLP-C was an independent risk factor for ISR. According to the receiver operating characteristic (ROC), the optimal cutoff point of the RLP-C was identified, and the patients were divided into the following 2 groups: low RLP-C group (n = 1072) and high RLP-C group (n = 1240). Propensity score matching analysis was performed in the two groups with a proportion of 1:1, including baseline data (age, gender, BMI, duration of diabetes mellitus, symptom-driven hospitalization and SYNTAX score). Finally, 762 pairs of DM patients were successfully matched. Log-rank tests were used to compare Kaplan–Meier curves for overall follow-up to assess ISR between the two groups.
Stent implantation
All enrolled patients received G2-DESs implantations in the catheterization centre. The type of G2-DESs included zotarolimus-eluting stents (Endeavor and Endeavor Resolute; Medtronic Vascular, USA), domestic sirolimus-eluting stents (Firebird2; MicroPort Medical, China), everolimus-eluting stents (Xience V and Xience Prime; Abbott Vascular, USA, Promus and Promus Element; Boston Scientific, USA). Stent implantation was performed according to current practice guidelines, and stents were selected by experienced interventional cardiologists. During the procedure, patients received a bolus of 100 IU/kg heparin with a repeated bolus of 2000 IU heparin to maintain the activated clotting time of ≥ 300 s. All patients received aspirin (100 mg/day was administered) and clopidogrel (300 mg loading dose followed by 75 mg/day for at least 12 months). When ISR was diagnosed, patients were treated with re-DES implantation. Procedural success was defined as follows: reduction of stenosis to less than 10% residual narrowing; thrombolysis in myocardial infarction (TIMI) flow grade III; improvement in ischaemic symptoms; and no major procedure related complications [7].
Data collection
A standard case report form (CRF) was used to collect patients’ demographic and clinical characteristics, including age, gender, smoking, drinking, CAD risk factors, family history, life style, medical history and coronary angiographic information at baseline PCI and follow-up angiography. During a physical examination, anthropometric indices, such as weight, height and blood pressure (BP), were measured. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in metres.
Coronary angiogram data, such as minimal stent diameter, average stent length and stenosis percent, were also recorded by two experienced investigators at baseline and follow-up for coronary angiography analysis.
Laboratory analysis
Venous blood samples were collected after an overnight fast for testing lipid profiles, HbA1c, fasting blood glucose (FBG), high-sensitivity C-reactive protein (hs-CRP) and uric acid (UA) levels using standard laboratory methods at baseline PCI and follow-up angiography.
The HbA1c was tested using ion exchange high-performance liquid chromatograph (HPLC) method. Blood samples for lipid profiles were collected from patients taking statin for more than 2 weeks. The total cholesterol (TC), TG, FBG and UA levels were determined according to enzymatic methods. LDL-C and high-density lipoprotein cholesterol (HDL-C) levels were measured by homogeneous assays. RLP-C levels were calculated as TC minus LDL-C and HDL-C according to the recommendation of dyslipidaemia guidelines [10, 11].
Disease definitions
The primary end point of the present study was the occurrence of ISR. ISR was defined as a diameter stenosis of ≥ 50% occurring in the segment inside the stent, 5 mm proximal to the stent or 5 mm distal to the stent at follow-up angiography [12]. The target lesion was considered as the most severe narrowing vessel identified by angiographic appearance with electrocardiograph (ECG) changes. Multivessel disease (MVD) was defined as a diameter stenosis of ≥ 50% occurring in 2 or more vessels.
Diabetes mellitus was defined as either a previous diagnosis of DM (treated with diet, oral agents or insulin) or a new diagnosis of DM (FBG ≥ 7.0 mmol/L on 2 occasions during hospitalization) [13]. Hypertension was defined by systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg and/or the use of antihypertensive treatment in the past 2 weeks [14]. The severity of coronary artery lesions was quantified by the synergy between PCI with taxus and cardiac surgery (SYNTAX) score, which was calculated using the online calculator for SYNTAX score.
Statistical analysis
Continuous variables were expressed as the mean (\( {\bar{\text{X}}} \)) ± standard deviation (SD) in the case of normal distribution, and differences between two groups were determined by two-sided t-test. Data were expressed as medians (interquartile ranges, P25, and P75) in the case of skewed distribution and compared between two groups using the Mann–Whitney test. Categorical variables were presented as counts (percentages) and compared by Chi square test.
Univariate Cox’s proportional hazards regression modelling was performed to identify determinants of ISR in diabetic patients. Baseline variables were selected if they had either a clinically plausible relation with the ISR or appeared to be imbalanced between ISR and non-ISR patients with a P-value less than 0.2. The potential variables were entered into multivariate Cox’s proportional hazards regression modelling using the stepwise method (entry, 0.05; removal, 0.05) to determine their independent risk associated with ISR in diabetes. The hazard ratio (HR) and 95% confidence intervals (95% CIs) were calculated to estimate the adjusted risk of ISR in diabetic patients. The predictive value of the Cox’s regression model was evaluated using the area under the receiver operating characteristics curve (AUC).
According to the ROC, the optimal cutoff point of the RLP-C was identified, and patients were divided into 2 groups. Propensity score matching analysis was performed in the two groups with a proportion of 1:1. Log-rank tests were used to compare Kaplan–Meier curves for overall follow-up to assess ISR between the two groups.
Statistical analyses were performed using SPSS software for Windows (version 24.0, SPSS Inc., Chicago, Illinois, USA). A two-sided probability value of < 0.05 was considered statistically significant in all analyses.
