Background: The precise pathways connecting insulin resistance (IR) to atherosclerotic cardiovascular disease (ASCVD) remain undefined. The present study aimed to examine the mediating role of arterial stiffness in the association between IR and ASCVD, providing epidemiology insights into the potential mechanisms driving IR to incident ASCVD.
Methods: A total of 59,777 participants from the Kailuan Study Arterial Stiffness Subcohort who were free of ASCVD at baseline were enrolled in the present study. Arterial stiffness was assessed using baPWV and IR was assessed by triglyceride glucose index (TyG) or metabolic score for insulin resistance (METS-IR). Mediation analysis was adopted to explore the mediating effects of baPWV on the associations between IR and ASCVD and its subtypes.
Results: Over a median follow-up of 5.97 years, a total of 2073 cases of ASCVD were identified, with 478 cases of coronary heart disease (CHD) and 1636 cases of ischemic stroke. Mediation analyses revealed that 11.1% of the total association (HR 1.23; 95% CI 1.17 to 1.30) between the TyG index and ASCVD was mediated through baPWV. Specifically, 6.58% and 14.0% of the total associations of the TyG index with CHD and ischemic stroke, respectively, were mediated through baPWV. Similar patterns were observed for METS-IR. These results remained consistent when assessed through causal mediation analysis, time-lagged mediation analysis, and various sensitivity analyses.
Conclusions: The association between IR indices and ASCVD was found to be partly mediated by baPWV, indicating a pathway connecting IR to ASCVD outcomes and the potential for interventions targeting arterial stiffness for ASCVD prevention.
Keywords: Arterial stiffness; Atherosclerotic cardiovascular disease; Cohort study; Insulin resistance; Mediator.
Insulin resistance (IR) is a known risk factor for atherosclerotic cardiovascular disease (ASCVD) and closely linked to arterial stiffness. This study aimed to investigate whether arterial stiffness, measured by the brachial-ankle pulse wave velocity (baPWV), explains the connection between IR and ASCVD. Among the Chinese general population, both IR indices (triglyceride glucose index [TyG] or metabolic score for insulin resistance [METS-IR]) and baPWV were significantly associated with incident ASCVD. Arterial stiffness partly mediated the relationship between IR and ASCVD. Specifically, 11.1% of the association between IR (measured by the TyG) and ASCVD was explained by baPWV, with stronger mediation for ischemic stroke (14%) and weaker mediation for coronary heart disease (6.58%). A similar pattern was found when using METS-IR to assess IR.
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