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Insulin Resistance and Blood Pressure Control on Cognitive Outcomes
Chenyu Fan1, Xuan Wang2,3, Liyuan Tao4
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, National Health Commission Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (C.F., L.J., Q.S., H.W., Y.S., T.C., Y.X., J.W., M.X.).
Intensive blood pressure treatment benefits hypertensive patients with insulin resistance, reducing dementia risk. This effect may be mediated by plasma glycosyl ceramide levels.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Metabolic Disorders
Background:
- The impact of insulin resistance (IR) on cognitive outcomes in hypertensive patients undergoing intensive blood pressure treatment is not fully understood.
- The specific circulating metabolites mediating this relationship require identification.
Purpose of the Study:
- To investigate how insulin resistance influences the cognitive response to intensive systolic blood pressure treatment in hypertensive individuals.
- To identify potential circulating metabolite mediators in the relationship between IR and cognitive decline.
Main Methods:
- Post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) involving 7427 hypertensive participants.
- Assessment of cognitive outcomes (probable dementia) and white matter hyperintensities using Cox models and mixed models across different triglyceride-glucose (TyG) levels.
- Mendelian randomization analysis to explore mediation effects of circulating metabolites.
Main Results:
- Intensive treatment (<120 mm Hg) significantly reduced dementia risk and slowed white matter hyperintensity progression in participants with elevated IR (TyG >9.07).
- Mediation analysis revealed a pathway where the TyG index influences dementia risk via plasma glycosyl ceramide levels, explaining approximately 10.8% of the effect.
Conclusions:
- In hypertensive patients with elevated IR, intensive blood pressure control (<120 mm Hg) offers greater cognitive benefits than standard control.
- The triglyceride-glucose (TyG) index appears to modify treatment effects on cognitive decline, potentially through glycosyl ceramide mediation.
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