Metabolic score for insulin resistance and cancer mortality: Effect modification by hypertension in a nationwide cohort study

The metabolic score for insulin resistance (METS-IR) is associated with cardiovascular mortality, but its association with cancer-specific mortality remains unclear. This retrospective cohort study included 17,347 adults from the National Health and Nutrition Examination Survey 1999 to 2018. METS-IR was calculated based on fasting glucose, triglycerides and other indicators, with follow-up until December 31, 2019. Weighted Cox models and other analyses were performed. The results showed that each 1-unit increase in METS-IR was associated with a 3% higher risk of cancer-specific mortality ( P = .01), presenting an approximately linear dose–response relationship; METS-IR remained associated with cancer mortality risk when analyzed as a categorical variable. Subgroup analyses revealed a significant interaction between hypertension and METS-IR in relation to cancer mortality, and stratified analyses further indicated that hypertension status acted as an effect modifier of this association. Sensitivity analyses confirmed the robustness of these findings. Higher METS-IR was independently associated with increased risks of cancer mortality in the US population, with hypertension significantly amplifying this association.