Cardiovascular disease (CVD) and chronic renal insufficiency (CRI) are global public health concerns [1]. Earlier research has indicated an increasing prevalence of concomitant CVD with worsening renal function [2]. Patients with CRI have a lower success rate, higher risk of complications, and worse clinical results in comparison with normal renal function patients while receiving percutaneous coronary intervention (PCI) [3]. Therefore, identifying high-risk CRI patients and undertaking early warning and intervention measures could enhance the clinical results following PCI. The SYNTAX score (SS) is recognized as a vital tool for guiding decisions between coronary artery bypass grafting (CABG) and PCI [4, 5, 6]. It has been demonstrated that the SS’s utility in objectively selecting the most appropriate revascularization technique can be further enhanced by the inclusion of clinical factors [7]. The clinical SYNTAX score (CSS), calculated by multiplying the SS with the modified age, creatinine, and left ventricular ejection fraction (ACEF) score (ACEF${}_{\text{CrCl}}$ Score: age/ejection fraction + 1 for each 10 mL the creatinine clearance 60 mL/min per 1.73 m${}^2$), has been validated for accurately predicting long-term adverse event risks in patients undergoing PCI [8, 9]. However, no study has yet investigated the predictive ability of the CSS for long-term clinical outcomes in patients with complex CAD and CRI following PCI.

This research verified the prognostic significance of CSS in patients with left main and/or three-vessel CAD and CRI undergoing PCI. The primary finding of the current research was as follows: following PCI with left main and/or three-vessel CAD and CRI patients, the CSS exhibited superior predictive performance compared to the SS in relation to ACM and CM. Additionally, the CSS served as an independent predictor of long-term ACM, CM, MI, stroke, unplanned revascularization, and MACCE.

Chronic kidney disease (CKD) is a considerable concern of public health worldwide [14]. It is believed to have a prevalence of 14% in the United States [15]. Over the period of 1990 to 2016, the global incidence, prevalence, deaths, and DALYs related to CKD have increased by 89%, 87%, 98%, and 62%, respectively [14]. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the Chronic Renal Insufficiency Cohort (CRIC) study, a multicentric prospective cohort research [16]. It has been revealed that CRI was significantly associated with left ventricular hypertrophy, heart failure [17], vascular stiffness, coronary artery calcification [18, 19], and adverse cardiovascular events [20]. Furthermore, prior investigations have revealed that CRI is associated with lower surgical success rates, more severe complications, increased risk of restenosis, recurrent MI, and stent thrombosis [3].

Within daily clinical practice, the stratification of risk and risk-benefit assessment following PCI hold immense importance. The SS, derived from the complexity and severity of CAD, has been demonstrated to be a valuable tool for stratifying complex CAD patients to assist in decisions of revascularization [4, 5]. Additional studies have substantiated its ability to predict clinical results following PCI in diverse clinical settings [21, 22]. However, SS’s prognostic significance was questioned for its accuracy and specificity, owing to its lack of incorporation of clinical characteristics that influence clinical outcomes [9]. The ROC analysis in the current research indicated a modest predictive value of SS for median 3-year ACM and CM. In addition, the C-statistics for ACM and CM were 0.597 and 0.592, respectively, and these values were insufficient to serve as a reference for clinical practice.

Earlier research has highlighted that scoring systems which incorporate anatomic and clinical variables are superior to angiographic SS [23]. The ACEF score, established with only age, LVEF, and serum creatinine values, has validated its comparability to complex scores, like the European System for Cardiac Operative Risk Evaluation (EUROSCORE) which included 17 clinical variables [24]. The CSS, incorporating both anatomical features and clinical variables (as with the ACEF${}_{\text{CrCL}}$ score), has been proven to be a convenient and straightforward predictive tool for predicting clinical results [8, 9]. The incremental prognostic value of the CSS was initially unveiled in the ARTS-II study involving 512 patients, as observed by Garg et al. [8]. The C-statistics for the CSS, SS, and ACEF${}_{\text{CrCL}}$ scores for 5-year MACCE were 0.62, 0.59, and 0.57, and were 0.69, 0.62, and 0.65, respectively, for 5-year mortality. The prognosis predictive ability of CSS for clinical outcomes for a long time in patients enduring PCI was confirmed by Girasis and his colleagues. The respective AUCs for SS and CSS for 5-year major adverse cardiac events (MACE) were 0.61 and 0.62, for 5-year ACM were 0.58 and 0.66, and for 5-year CM were 0.63 and 0.72 [9]. Capodanno et al. [25] demonstrated that CSS exhibited a superior discriminatory ability in assessing the risk of CM in patients with left main CAD post PCI, when compared against SS and EuroSCORE. For a 2-year CM, the CSS was demonstrated to have a satisfactory predictive capacity (AUC: 0.762). Recently, He et al. [26] validated the predictive value of CSS in acute coronary syndrome patients following PCI on 2-year clinical results. They revealed that CSS had a significantly superior performance for 2-year CM (AUC: 0.74 vs. 0.62, p 0.001) but not for MACE (AUC: 0.60 vs. 0.59, p = 0.290) compared with baseline SS.

This study marks the first validation of CSS’s predictive significance in terms of median 3-year outcomes for patients with complex CAD and CRI following PCI. As per the findings of this research, CSS exhibited superior accuracy in predicting ACM (AUC: 0.666 vs. 0.597, p = 0.018) and CM (AUC: 0.668 vs. 0.592, p = 0.035) in comparison to SS. The performance of CSS for predicting ACM resembled the results obtained by Garg and Girasis [8]. However, the predictive ability of CSS for CM was notably lower compared with the studies conducted by Capodanno et al. [25] and He et al. [26] (AUC: 0.668 vs. 0.762 or 0.740). A possible explanation for this difference could be the fact that the population and follow-up timing in these studies were different.

The current research has several limitations. First, owing to the post-hoc nature of the analysis, the findings should only be used to form hypotheses. Second, patients with prior PCI or CABG, prior MI, and a previous history of undergoing other cardiac surgery and malignant tumors were excluded from this research. Therefore, a selection bias might be present. Third, in this research, the fractional flow reserve (FFR) to determine the functional significance of coronary artery lesions was not used, as recommended by international guidelines in clinical practice [6]. Finally, this was a single-center, real-world study. To effectively understand individual performance with diverse risk models, further prospective, multicenter, and large-sample clinical studies should be conducted

The CSS significantly improved risk stratification for median 3-year ACM and CM in comparison with SS. Hence, this allowed for an individualized risk assessment in complex CAD and CRI patients following PCI.

The authors are committed to providing raw data supporting the conclusions of this study. The detailed data related to the findings of this study are available from the corresponding author upon reasonable request.

LQY and MYL designed the research study. MYL, XL, MJ performed the research. YML, ZPL, SCL, YM and XFC analyzed the data. LQY, MYL, XL, MJ, YML, ZPL, SCL, YM and XFC been involved in drafting the manuscript or reviewing it critically for important intellectual content; All authors read and approved the final manuscript. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. The manuscript’s submission was approved by all authors who contributed to it.

Cangzhou Central Hospital’s Ethics Committee, Hebei Medical University granted its approval to the research procedure. In all cases, written informed permission could be effectively provided. The ethics approval number is 2017-006-01.

We are grateful to all of the volunteers whose contributions made this research possible.

Natural Science Foundation of Hebei Province, China (H2021110008) and Hebei Provence Key Research Projects (172777163) provided funding for this research.

The authors declare no conflict of interest.