In the current study, a total of 547 patients with chronic stable CAD or acute coronary syndromes who successfully received PCI procedure from June 2014 to November 2017 in the Second Affiliated Hospital of Chongqing Medical University (Chongqing, China) was enrolled. All patients had at least one lesion with diameter stenosis (DS) greater than 50% in a blood vessel suitable for stent implantation (reference diameter between 2.25 and 4.00 mm). No restrictions for the number of lesions, number of treated vessels or stents implanted was set in current study. The primary criteria for exclusion were: pregnancy; allergy to contrast media, previous history of coronary artery bypass grafting (CABG), any planned surgery within 6 months of PCI (unless the patients will maintain dual antiplatelet therapy throughout the peri-operative period); or the participation in another trial before reaching the primary endpoint.

All patients received anticoagulation treatment as follows: clopidogrel 75 mg/day together with aspirin 100 mg/day, more than 24 h in advance before PCI procedure. During the primary PCI, unfractionated heparin (70–100 U/kg) was used for all patients. For patients with acute coronary syndromes requiring emergency PCI, Clopidogrel 600 mg loading dose and glycoprotein IIb/IIIa inhibitors were used. The selection of drug-eluting stents and adjunctive devices was at the operators’ own discretion. To deploy stents, high pressure balloon dilatation method was used to achieve optimal stent apposition. PCI was deemed angiographically successful if residual stenosis was less than 30% and the restoration of coronary TIMI (thrombolysis in myocardial infarction) 3 flow at the end stage of the procedure. Five out of 547 patients had coronary dissection, 28 out of 547 patients had side-branch occlusion, coronary perforation cases were rare and considered unsuccessful PCI, thus were not included in the study. All discharged patients were prescribed with clopidogrel 75 mg/day for at least 12 months together with lifelong aspirin at a dose of 100 mg/day. Patients were requested to return for a routine in-hospital follow-up at 1 month, 6 months and 12 months after discharge and additional telephonic follow-ups were performed for up to 2 years. Medical records were reviewed in addition to telephone follow-up of patients to confirm the occurrence of endpoints.

Two cardiologists adjudicated the angiographic features of each patient with very good agreement (kappa index = 0.81). In case discrepancies occur, a third cardiologist was invited to reach consensus. The SS for each patient was calculated by scoring all coronary lesions with a DS ≥ 50% in vessels ≥ 2.25 mm as has been instructed on the SYNTAX score website (www.​syntaxscore.​com). The demographic characteristics of each participating patient, together with their history of heart diseases, and related risk factors were collected and archived upon admission. The Age, Creatinine, and Ejection Fraction (ACEF) score was calculated by patients' left ventricular ejection fraction, age, and creatinine clearance [16]. The CSS was calculated by multiplying the modified ACEF score with SS (CSS = [SS] × [modified ACEF score]) according to previous publications [16].

The primary endpoint of this study included cardiac death, stroke, Myocardial infarction (MI) and any repeat revascularization (either PCI or CABG). The detailed definitions of each endpoints in current study were provided as below. All deaths were considered cardiogenic death unless a definite non-cardiogenic cause was recorded. Stroke was diagnosed by neurologists and was defined as a focal neurological deficit of vascular origin lasting for longer than 24 h. MI was defined according to definitions from Academic Research Consortium as the presence of new Q-waves of at least 0.4 s duration in ≥ 2 contiguous leads and elevation of cardiac enzyme. In those patients without pathologic Q-waves, MI was defined as the elevation of the creatine kinase level to > 2x of the upper limit of normal range, together with elevated level of creatine kinase MB or troponin I. Target-vessel revascularization or TLR was defined as an interventive procedure of either PCI or CABG for treatment of a stenosis within previous PCI treated vessel. Ischemia driven any repeat revascularization was defined by lumen stenosis ≥ 50% angiographically in the presence of ischemic symptoms, or stenosis ≥ 70% regardless of ischemic symptoms or signs. Stent thrombosis was defined as probable or definite, according to the recommendation of Academic Research Consortium.

Statistical analysis was performed using the Windows version of SPSS (ver. 19.0 SPSS, Inc, Chicago, IL, USA). All patients with calculated SS and CSS scores were included in the analysis. All continuous variables were in the form of mean and standard deviation (SD). All categorical variables were shown as counts and percentages. The Kolmogorov–Smirnov test was used for normality assessment of the SS and CSS distribution. All variables were stratified according to SS/CSS tertiles. The correlation between SS and CSS was assessed by Spearman’s test. Comparisons for continuous variables with a normal distribution were performed by one-way analysis of variance (ANOVA) and Chi-square test was used for all categorical variables. Time to event trends were demonstrated as Kaplan–Meier curve, and Log-rank test was used to assess the differences in survival among subgroups of patients.

The prognostic value of the SS and CSS was assessed by plotting the receiver-operator characteristic curves (ROCs), in which 0.50 indicates no discrimination and 1.0 indicates perfect discrimination. Areas-under-the-curves (AUCs) for SS and CSS were compared with the DeLong method using Windows version of MedCalc (ver. 11.6.0.0 MedCalc Software). Finally, to evaluate whether CSS is superior in the risk stratification comparing to SS, a net reclassification improvement analysis was performed.

To rule out potential confounders, univariable and multivariable Cox proportional hazard regression models was used to assess the relationship between SS/CSS and the incidence of primary endpoint. The variables were chosen according to their clinical significance. The following variables including sex, diabetes mellitus (DM), estimated glomerular filtration rate (eGFR), smoking, acute coronary syndrome (ACS), number of stents implanted, were tested on a per patient basis to determine suitability for inclusion in the multivariate model by univariate analysis.

Baseline clinical and risk factors of the study population, stratified according to SS tertile were presented in Table 1.

The SS was available for 547 patients (1314 lesions in total, with an average of 2.4 ± 1.4 lesions for each patient) enrolled in current study. Overall, the SS ranged from 1 to 47.5, with a mean of 14.90 ± 8.83 and a median of 13.00. The CSS ranged from 0.9 to 158.2, with a mean of 25.80 ± 15.23 and a median of 15.80. Expectedly, there was a strong correlation between the two scores (r = 0.713, p < 0.001). The distributions of the two scores within the study population were shown in Fig. 1. Both scores were not normally distributed (Kolmogorov–Smirnov test both p < 0.001) but skewed to the right. In this analysis, patients were categorized according to tertile of the SS and CSS as follows: SS_LOW ≤ 8 (n = 177), 8 < SS_MID < 18 (n = 177), 18 ≤ SS_HIGH (n = 193); CSS_LOW ≤ 10 (n = 180), 10 < CSS_MID ≤ 25 (n = 185), 25 < CSS_HIGH (n = 182), respectively.

The mean age was 66.82 ± 3.50 with 68.2% male predominance. There were 159 (29.1%) patients with diabetes mellitus, 68.3% patients with hypertension. Only 32 (5.9%) patients had myocardial infarction history. Of all enrolled patients, almost one in two patients (274/547, 50.1%) presented with ACS, among which, 151 presenting unstable angina, 87 presenting ST-Elevation Myocardial Infarction (STEMI), 36 presenting Non-ST-elevation myocardial infarction (NSTEMI).

The percentage of patients with 1-vessel, 2-vessel and 3-vessel lesion was 33.3%, 33.8% and 32.9%, respectively (Table 2). Complete revascularization was achieved in 265 (48.1%) patients, the percentage of patients underwent complete revascularization was 83.1% (147), 51.4% (91), 13.0% (25) in SS_LOW, in SS_MED and in SS_HIGH tertile, respectively (Table 2).

Only 36 (6.6%) patients had lesions involving the left main stem. 345 (63.1%) patients had right coronary artery DS > 50%. 441 (80.8%) patients had lesions located within the left anterior descending artery.

Baseline lesion and procedural characteristics were shown in Table 2. Markers which increase lesion complexity, such as the presence of bifurcation lesions, long lesions, calcification, and total occlusions were all significantly higher in the SS_HIGH tertile.

In SS_HIGH tertile, the mean number of significant lesions for each patient was 3.3, received 3.0 stents with an average total stented length of 64.3 mm with the mean maximal air pressure 14.8 for stent deployment; all of which were significantly higher. Moreover, post-procedure in hospital stay was also significantly longer in the SS_HIGH tertile.

Clinical outcomes across SS tertiles were shown in Table 3, the rate of MACCE, Target lesion failure (TLF, including cardiac death, target-vessel driven myocardial infarction, ischemia-driven target lesion revascularization), cardiac death, MI and any repeat revascularization were significant higher in the SS_HIGH tertile. During the follow-up period, 17 patients died. The rates of all-cause death in three group were 1.7% in SS_LOW tertile, 3.4% in SS_MED tertile and 4.1% in SS_HIGH tertile. Three patients died of definite non-cardiogenic cause (one died of traffic accident, one died of pulmonary carcinoma and another died of cerebral hemorrhage) were categorized into SS_LOW tertile.

Clinical outcomes stratified CSS tertile were shown in Table 4. Comparing with those stratified by SS, CSS yielded similar results when comparing between the high and low risk group. However, in contrast to the SS analysis, there was significant difference in event rates for all-cause death between high and low CSS tertile.

As shown in Fig. 2A, the MACCE-free survival was significantly lower in SS_HIGH compared with SS_LOW (86.5% vs. 100%, p < 0.0001), such trend was also observed for survival rates of endpoints TLF (94.3% vs. 100%, p = 0.03) and cardiac death/MI (94.3% vs. 100%, p = 0.02). However, no trends were observed among the free survival rate of all-cause death (98.3% in the low, 96.6% in the median, 95.9% in the high, p = 0.377).

Clinical outcomes across by CSS tertile were shown in Fig. 2B. Survival curve of all-cause death was significantly higher in CSS_HIGH compare with CSS_LOW (Fig. 2B). The survival rate of MACCE, TLF and cardiac death/MI were also significantly higher in CSS_HIGH compared with CSS_LOW tertile, similar to results from SS tertile.

The receiver operating characteristic (ROC) curves for MACCE, TLF, all-cause death and cardiac death/MI during 2-year follow-up were shown in Fig. 3A–D. In this analysis, the areas under the curves (AUC) of both scores were significantly (both p < 0.001) higher than the area of diagnostic indifference. However, we found the AUC is not larger for CSS MACCE (AUC SS, 0.78; AUC CSS, 0.75), TLF (AUC SS, 0.77; AUC CSS, 0.72) and cardiac death/MI (AUC SS, 0.80; AUC CSS, 0.70). The AUC for all-cause death by CSS was slightly larger comparing to SS but not significant (AUC SS, 0.64; AUC CSS, 0.71; p = 0.23) (Fig. 3C). The optimal cut-points were selected using the common method of Youden index method. Optimal cut-points were calculated as 21.00 for SS and 45.35 for CSS. We calculated the Youden index, positive and negative prediction values. Youden index is 0.38 and 0.46 for SS and CSS, respectively. Positive/negative prediction value is 20.62%/96.00% for SS and 23.47%/96.65% for CSS. These results suggested comparable prediction ability comparing SS and CSS in our study population.

The results of COX multivariable analysis were shown in Table 5. After adjust confounding factors including age, sex, DM, presentation with ACS, number stent implanted, the SS remained as an independent predictor for MACCE [1.101 (1.070–1.134), p < 0.0001]. The CSS remained as an independent predictor for all-cause death at 2-year follow up [1.012 (1.000–1.024), p < 0.05].

When reclassifying patients with MACCE from SS tertiles into CSS tertiles, 4/10 (40.0%) patients with events were moved to higher risk categories (upward) and 6/10 (60.0%) to lower risk categories (downward) with a net difference of 20.0%. In patients without MACCE, 92/537 (17.1%) were moved downward and 77/537 (14.3%) upward, with a net difference of 2.8%, as shown in Table 6 and Fig. 4.