Association of Triglyceride-Glucose Index and Its Derivatives With Incidence and Cause-Specific Mortality of Cardiovascular and Cerebrovascular Diseases Among Cancer Survivors

Background The risk and specific mortality of cardiovascular and cerebrovascular diseases (CCVD) would greatly increase among cancer survivors, with prevalent cardiovascular risk scores for regular populations showing poor performance. We aim to evaluate four insulin resistance (IR) indices—the triglyceride-glucose (TyG) index and its derivatives (TyG-BMI, TyG-WC, TyG-WHtR)—for their association with CCVD outcomes in cancer survivors. Methods This prospective cohort study is based on data from the UK Biobank. Fasting glucose, triglycerides, and anthropometric measures were used to calculate IR indices. Primary outcomes were CCVD incidence (composite of cardiovascular disease [CVD], stroke, and heart failure) and CCVD-specific mortality. Cox regression models adjusted for demographics, lifestyle, and comorbidities assessed hazard ratios (HRs) by index quartiles (Q1–Q4). Sensitivity and subgroup analyses were used to evaluate robustness and effect modification. Results Among cancer survivors, higher IR indices correlated with higher CCVD incidence and specific mortality (p-trend < 0.001). For CCVD incidence, TyG-WC showed the strongest association (Q4 HR = 1.51 (1.33, 1.71), p < 0.001), while TyG-WHtR best predicted CCVD mortality (Q4 HR = 3.17, 1.72–5.85). CVD-specific mortality risk was highest with TyG-WHtR (5.89-fold increase per 3-unit increment, p < 0.001). Heart failure risk rose significantly in Q4 for obesity-adjusted indices (e.g., TyG-WC HR = 3.17 (1.72, 5.85), p < 0.001), but no associations emerged for stroke outcomes. Subgroup analyses revealed stronger CCVD risk prediction in female patients, nondiabetics, and alcohol consumers (interaction p < 0.05). Sensitivity analyses confirmed the robustness of the results after excluding early events. Conclusion Except for the TyG index, the IR indices showed a close association with CCVD incidence and specific mortality among cancer survivors. The relation of TyG-WHtR was stronger than that of TyG-BMI and TyG-WC in CCVD, CVD, and heart failure, and this association could further increase in specific subgroups. Trial registration The ethical approval for the UK Biobank research was granted by the North West Multicenter Research Ethical Committee. This current study was specifically approved by the UK Biobank under application number 332912.