Development and Validation of a Predictive Model Based on Serum Silent Information Regulator 6 Levels in Chinese Older Adult Patients: Cross-Sectional Descriptive Study.

Abstract

Background: Serum levels of silent information regulator 6 (SIRT6), a key biomarker of aging, were identified as a predictor of coronary artery disease (CAD), but whether SIRT6 can distinguish severity of coronary artery lesions in older adult patients is unknown.

Objectives: This study developed a nomogram to demonstrate the functionality of SIRT6 in assessing severity of coronary artery atherosclerosis.

Methods: Patients aged 60 years and older with angina pectoris were screened for this single-center clinical study between October 1, 2022, and March 31, 2023. Serum specimens of eligible patients were collected for SIRT6 detection by enzyme-linked immunosorbent assay. Clinical data and putative predictors, including 29 physiological characteristics, biochemical parameters, carotid artery ultrasonographic results, and complete coronary angiography findings, were evaluated, with CAD diagnosis as the primary outcome. The nomogram was derived from the Extreme Gradient Boosting (XGBoost) model, with logistic regression for variable selection. Model performance was assessed by examining discrimination, calibration, and clinical use separately. A 10-fold cross-validation technique was used to compare all models. The models' performance was further evaluated on the internal validation set to ensure that the obtained results were not due to overoptimization.

Results: Eligible patients (n=222) were divided into 2 cohorts: the development cohort (n=178) and the validation cohort (n=44). Serum SIRT6 levels were identified as both an independent risk factor and a predictor for CAD in older adults. The area under the receiver operating characteristic curve (AUROC) was 0.725 (95% CI 0.653-0.797). The optimal cutoff value of SIRT6 for predicting CAD was 546.384 pg/mL. Predictors included in this nomogram were serum SIRT6 levels, triglyceride glucose (TyG) index, and apolipoprotein B. The model achieved an AUROC of 0.956 (95% CI 0.928-0.983) in the development cohort. Similarly, in the internal validation cohort, the AUROC was 0.913 (95% CI 0.828-0.999). All models demonstrated satisfactory calibration, with predicted outcomes closely aligning with actual results.

Conclusions: SIRT6 shows promise in predicting CAD, with enhanced predictive abilities when combined with the TyG index. In clinical settings, monitoring fluctuations in SIRT6 and TyG may offer valuable insights for early CAD detection. The nomogram for CAD outcome prediction in older adult patients with angina pectoris may aid in clinical trial design and personalized clinical decision-making, particularly in institutions where SIRT6 is being explored as a biomarker for aging or cardiovascular health.