The Prognostic Value of Insulin Resistance Indices for Major Adverse Cardiovascular Events in Young and Middle‐Aged Patients With Hypertension

Young and middle-aged adults with hypertension develop the disease earlier and accrue longer exposure to elevated blood pressure, conferring higher lifetime cardiovascular risk. However, reliable markers predicting long-term major adverse cardiovascular events (MACEs) in this group remain unclear. Insulin resistance (IR) is crucial to hypertensive pathophysiology, but direct measurement is impractical. We evaluated the prognostic value of three laboratory-derived IR indices, the triglyceride-glucose (TyG) index, the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C), and the metabolic score for IR (METS-IR), in predicting MACEs. In this retrospective cohort of 4861 patients aged 18-65 years with primary hypertension, baseline indices were calculated and classified into tertiles. Patients were followed for a median of 73 months, during which 372 MACEs occurred. Multivariable Cox regression showed that higher TyG, TG/HDL-C, and METS-IR were independently associated with increased MACEs risk. In fully adjusted models, each standard deviation increase in METS-IR conferred a 55.7% higher risk (HR = 1.557, 95% CI: 1.154-2.101, p < 0.01), and patients in the highest tertile had more than double the risk vs. the lowest. METS-IR showed superior discrimination (AUC = 0.803, 95% CI: 0.774-0.886) and significant net reclassification improvement (NRI = 0.147, 95% CI: 0.073-0.239, p = 0.001) and integrated discrimination improvement (IDI = 0.006, 95% CI: 0.002-0.010, p = 0.002), whereas TyG showed borderline benefit and TG/HDL-C offered no incremental value. These findings highlight METS-IR as a pragmatic predictor of long-term cardiovascular risk in younger hypertensive patients, supporting its integration into clinical risk stratification.