Hypertension Mediates the Association of Triglyceride–Glucose–Body Mass Index With Vascular Brain Injury in Older Adults: A Population-Based Magnetic Resonance Imaging Study

Abstract

BACKGROUND: Evidence has linked insulin resistance to hypertension, a major risk factor for vascular brain injury. We sought to explore the associations of the triglyceride–glucose–body mass index (TyG-BMI), a surrogate marker of insulin resistance, with magnetic resonance imaging markers for vascular brain injury in older people and the role of hypertension in their associations. METHODS: This population-based study included 1268 participants (age ≥60 years; 58.60% women) from the MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China) magnetic resonance imaging substudy. White matter hyperintensities (WMHs), enlarged perivascular spaces, cerebral microbleeds (CMBs), and lacunes were assessed on structural brain magnetic resonance imaging scans following the Standards for Reporting Vascular Changes on Neuroimaging 1 criteria. The TyG-BMI was calculated as ln(fasting triglyceride[mg/dL]×fasting glucose [mg/dL]/2)×BMI. Data were analyzed using the general linear, logistic, and mediation models controlling for multiple potential confounders. RESULTS: A higher TyG-BMI was significantly associated with greater volumes of total WMHs, periventricular WMHs, and deep WMHs (all P<0.05). After further adjustment for hypertension, the association remained statistically significant with deep WMH volume but was no longer significant with total and periventricular WMH volumes. The TyG-BMI was not significantly associated with enlarged perivascular spaces, lacunes, or cerebral microbleeds. Mediation analysis indicated that hypertension significantly mediated around 26% to 49% of the associations between TyG-BMI and WMH volumetric measures. The observed associations and mediation effects remained significant among participants free of diabetes or stroke. CONCLUSIONS: An increased insulin resistance, as indicated by high TyG-BMI, is associated with greater WMH volumes in older adults, even among those free of diabetes or stroke, and their associations are largely mediated by hypertension.