Insulin Resistance and Blood Pressure Control on Cognitive Outcomes

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BACKGROUND: The influence of IR (insulin resistance) on the response of patients with hypertension to intensive systolic blood pressure treatment in terms of cognitive performance remains unclear, as does which circulating metabolites mediate this process. METHODS: This study comprised a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial). The SPRINT study enrolled 9361 participants aged ≥50 years with hypertension, of whom 7427 were analyzed. SPRINT participants were assigned to either intensive (<120 mm Hg) or standard systolic blood pressure treatment (<140 mm Hg). The primary cognitive outcome was probable dementia. Cox proportional hazards models, restricted cubic splines, and linear mixed models assessed the influence of systolic blood pressure control on cognitive functions and white matter hyperintensities across different triglyceride-glucose (TyG) levels. Mendelian randomization was used to estimate the mediation effect of circulating metabolites on the relationship between IR and cognitive outcomes. RESULTS: Among participants with elevated IR (TyG >9.07), intensive treatment was associated with a reduced risk of probable dementia and a slower progression of white matter hyperintensities. Our mediation analysis identified a potential pathway linking the TyG index to dementia via plasma glycosyl ceramide levels, accounting for ≈10.8% of the total effect. CONCLUSIONS: In patients with hypertension with TyG >9.07, lowering blood pressure to <120 mm Hg reduced dementia incidence more than standard control, hinting TyG modifies treatment effects, possibly via glycosyl ceramide. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

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