Incremental prognostic value of insulin resistance surrogate indices for stroke outcomes in minor ischaemic stroke or transient ischaemic attack

Background Insulin resistance is an established predictor of stroke outcomes, yet the predictive performance and incremental prognostic value of various insulin resistance surrogate indices remain systematically unevaluated. We aimed to examine whether these indices could improve outcome prediction among patients with minor ischaemic stroke or transient ischaemic attack (TIA).Methods We included Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) participants with minor ischaemic stroke or TIA carrying CYP2C19 loss-of-function alleles. They were recruited from 202 hospitals across China between September 2019 and March 2021 in a randomised, double-blind, double-dummy, placebo-controlled trial. Stroke recurrence within 1 year was assessed as the primary outcome, with disability and all-cause mortality evaluated as additional outcomes. Associations of the five insulin resistance surrogate indices with clinical outcomes were examined using multivariable models. Incremental prognostic value was quantified using change in C-index (delta C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI).Results Among 4235 included patients, 405 (9.6%) experienced stroke recurrence within 1 year. After adjusting for potential confounders, triglyceride-glucose (TyG), TyG-Chinese visceral adiposity index (TyG-CVAI), cholesterol, high-density lipoprotein, and glucose (CHG) and C-reactive protein-triglyceride-glucose index (CTI) were positively associated with stroke recurrence, whereas estimated glucose disposal rate exhibited an inverse association. All indices provided modest incremental prognostic value, and CTI demonstrated relatively stable performance across multiple clinical subgroups. When CTI was incorporated into the reference model, the C-index increased by 0.013 (95% CI 0.002 to 0.029). The NRI was 0.121 (95% CI 0.057 to 0.171; p<0.001) and the IDI was 0.004 (95% CI 0.001 to 0.010; p<0.001). Incorporating CTI into established prognostic models resulted in a C-index increase of 0.017 (95% CI 0.002 to 0.041) for the Essen Stroke Risk Score (ESRS) and 0.019 (95% CI 0.002 to 0.042) for the Stroke Prognostic Instrument I (SPI-I).Conclusion Multiple insulin resistance surrogate indices independently predict 1-year stroke recurrence and provide modest incremental prognostic value.