The Prognostic Significance of the Metabolic Score for Insulin Resistance and Subclinical Myocardial Injury for Cardiovascular Mortality in the General Population

<b>Background/Objectives</b>: The Metabolic Score for Insulin Resistance (METS-IR), a non-insulin-based index of insulin resistance (IR), and subclinical myocardial injury (SCMI), identified by electrocardiogram (ECG), are each associated with cardiovascular disease (CVD). However, their joint impact on mortality remains unclear. We examined the association of the METS-IR with SCMI and evaluated the individual and combined associations of SCMI and IR with cardiovascular mortality. <b>Methods</b>: We analyzed adults without baseline CVD from the Third National Health and Nutrition Examination Survey (1988-1994) with mortality follow-up through 31 December 2019. The METS-IR was calculated from fasting glucose, triglycerides, high-density lipoprotein cholesterol, and body mass index and categorized as low (<75th percentile) or high (≥75th percentile). SCMI was defined as a cardiac infarction injury score ≥ 10 on ECG. Multivariable logistic regression assessed associations between the METS-IR and SCMI, and Cox regression estimated cardiovascular mortality risk across SCMI-IR combinations. <b>Results</b>: Among 6079 participants, 14.1% had SCMI. Higher METS-IR values were associated with greater SCMI odds (OR (95% CI): 1.58 (1.31-1.90)). Over a median of 18.8 years, 563 (9.1%) cardiovascular deaths occurred. Both SCMI and high IR were individually associated with increased cardiovascular mortality ((HR (95% CI): 1.41 (1.19-1.69) and 1.32 (1.09-1.59), respectively). Participants with both SCMI and high IR had the highest risk (HR 1.92; 95% CI 1.49-2.50) compared with those with neither condition. <b>Conclusions</b>: In adults without prior CVD, the METS-IR was positively associated with SCMI. The coexistence of SCMI and high IR identified a subgroup at nearly twofold higher risk of cardiovascular mortality, supporting the combined use of ECG-based injury markers and metabolic indices for cardiovascular risk stratification.