We developed a predictive risk score for saphenous vein graft SVG occlusion in patients with T2DM after CABG. We found that the model discrimination was good; in other words, the risk score was reliable in correctly classifying patients via risk stratification. However, the calibration was not ideal, which caused a modest underestimation of SVG occlusion for low risk patients, while demonstrating a relatively precise predictive performance for high risk patients. There are a total of 11 independent predictive factors in the scoring system that leads to calculation of a CABG patient’s personalized risk of developing late SVG occlusion. The risk score developed in this study could guide treatment strategy by focusing on the likelihood of late SVG occlusion in patients with T2DM after CABG with high-risk factors, such as hyperuricemia and the use of ACEI/ARB or CCB, which are not currently addressed in treatment recommendations. This risk score has significant implications for patients with T2DM after CABG, as those with higher risk scores should be managed with greater vigilance and intensive treatment to effectively mitigate cardiovascular risk factors.
CABG is one of the most effective revascularization strategies for CAD, especially for patients with T2DM and multivessel diseases, and has been shown to reduce mortality and improve quality of life (24). However, SVG occlusion has an adverse impact on the prognosis of patients and increases the economic burden of health care systems (9). Among all grafts, diabetes was associated with an increased risk of graft occlusion(25). SVG occlusion can be classified into two types: early and late. Early SVG occlusion is primarily attributed to a technical failure that results in graft thrombosis and hyperplasia as the SVG is arterialized. Late SVG occlusion is primarily due to generalized neointimal hyperplasia and atherosclerosis, which occurs over the injured endothelium (2), which was associated with diabetes progression. The risk factors associated with late SVG occlusion have been evaluated in some studies (10, 12, 14, 18, 26), but a widely accepted prediction model for late SVG occlusion in T2DM patients had not been previously developed. We have designed and validated a prediction model for late SVG occlusion in T2DM patients by using cohort data from a high-volume cardiac center. Previous studies have shown specific risk factors from patient-related, graft-related, and surgery-related perspectives. Female sex is an independent risk factor of SVG occlusion in early vein graft failure (11, 15, 17), possibly due to smaller target vessel diameter of female patients. Cardiovascular risk factors like smoking, dyslipidemia, and a history of PCI have also been identified as risk factors of late SVG occlusion (10, 18). Uric acid level had never been considered relevant to SVG occlusion, however, clinical practice experience and prior research indicate that hyperuricemia may lead to kidney injury (27), and chronic kidney disease has been reported as a risk factor for vein graft disease (12, 13). Off-pump surgery for CABG without cardioplegia has been associated with lower graft patency rates compared with on-pump surgery. Additionally, the coagulopathy and platelet dysfunction induced by cardiopulmonary bypass can affect SVG patency (26, 28). From the graft-related and surgery-related perspectives, any use of SVGs is independently associated with reduced survival after coronary artery bypass surgery (29), which is consistent with the risk factors we have derived. Most patients with diseases with multiple lesions have diffuse lesions, suggesting that the condition of the graft may be poor; these patients have a higher rate of late SVG occlusion. As for medications, the use of ACEI/ARB and CCB are both protective factors for SVG occlusion, which may be related to the dilation of blood vessels, antispasmodics, and increased graft diameter. Furthermore, the effects of antihypertensive medications may contribute to reduced risk of SVG hyperplasia, which has been demonstrated in a study on early SVG occlusion (30).
A variety of cardiac surgery risk prediction models have been established, including the Society of Thoracic Surgeons (STS) score (31), the American College of Cardiology/American Heart Association (ACC / AHA) score (32), the European EuroSCORE(European System for Cardiac Operative Risk Evaluation score) (33), and its modified version, the EuroSCORE II (34). These prediction models were primarily used for evaluating perioperative risk. For SVG occlusion, the SAFINOUS-CABG score (16) is a model for early SVG occlusion, with risk factors that include sex, diabetes, dyslipidemia, active smoking, and SVG number, which are mostly consist with the risk factors identified in our study. A study by Joseph et al. also found that female sex and diabetes are risk factors for graft occlusion (17). Moreno et al, Wezel et al, and Yazdani et al found that atherosclerosis and plaque rupture are the main causes of late vein graft failure. The formation of atheromatous plaques is promoted by predisposing factors for atherosclerosis (e.g., high blood pressure, diabetes, smoking), and damage to the vein wall is induced by highly proliferative smooth muscle cells and expression and secretion of pro-inflammatory cytokines (35–38). These findings are consistent with some of our results. Domanski et al. focused on prognostic factors for atherosclerosis progression in saphenous vein grafts, hypothesized that dyslipidemia, prior myocardial infarction, female sex and current smoker status were associated with acceleration of the atherosclerosis progression in saphenous vein grafts, thereby leading to late SVG occlusion (39).
Our study is the first large-scale comprehensive cohort–based development of a predictive model for late SVG occlusion in T2DM patients that could be used for risk stratification of CABG patients. The risk score system could inform clinical decision-making through calculation of individual risk for late SVG occlusion in T2DM patients. Assessment of the SVG risk score could improve surgical strategy and help in the development of personalized postoperative treatment plans. Proactive risk assessment and associated treatment may also be particularly cost-effective by reducing SVG occlusion and cardiovascular events in in T2DM patients after CABG.
We recognize that our study has limitations. First, this research is a retrospective investigation. Although we continuously enrolled patients with T2DM who underwent CABG, a small number of patients did not receive invasive angiography or CTA results during the follow-up time, which may result in selection bias. The time of postoperative invasive angiography or CTA depends on many factors. The most important factors are the patient's symptoms and the personal decision of the doctors providing outpatient services. Although this may affect the observation of the SVG occlusion, it is the best representation of the current context of clinical practice. There was also data missing from our database. Although we used MICE to impute missing values, bias is evitable. In addition, the absence of some variables, such as target vessel diameter, graft mean flow, and some surgical related items, leads to a risk of confounding. Also, microvascular disease, coronary atherosclerosis burden, progression and plaque composition, may need to be considered for a more refined risk stratification in these high-risk patients(40). Finally, our database was split into two groups randomly: one to develop a prediction model, and one to evaluate the predictive performance of the model. This design led to lack of power during model development (22, 41–43) and validation. Future validation studies carried out at different medical centers with different surgical strategies and external validation by other investigators would be welcome.