Insulin resistance is potentially associated with 24-h blood pressure variability related to blunted sympathetic reactivity in older adults with hypertension

Abstract Purpose Blood pressure variability (BPV) increases with aging and hypertension; however, the underlying mechanisms remain poorly understood. Aging-related insulin resistance is known to contribute to abnormalities in autonomic circulatory regulation. Although hypertension and autonomic dysfunction are closely linked, it remains unclear whether hypertension modifies the effects of insulin resistance on autonomic cardiovascular control and BPV. Since daily life is mostly spent upright, sympathetic responses to postural change may determine BPV. Therefore, we aimed to determine whether insulin resistance is associated with muscle sympathetic nerve activity (MSNA) responses to orthostatic stress in older adults with and without hypertension. Methods We studied 37 older adults without hypertension (normotension [NTN]) and 30 older patients with hypertension (HTN) without diabetes mellitus. Participants underwent 30° and 60° head-up tilt (HUT), whereby MSNA responses were assessed. In addition to 24-h BPV, fasting glucose, insulin, and homeostasis-model-assessment-estimated insulin resistance (HOMA-IR) were measured. Results HTN exhibited higher 24-h BPV. There were no significant group differences in MSNA responses to HUT or in fasting glucose, insulin, or HOMA-IR. Importantly, however, only in the HTN group, MSNA responses to HUT were negatively correlated with fasting glucose and HOMA-IR. In multivariable models adjusting for age, sex, and body mass index (BMI), fasting glucose remained an independent predictor of MSNA responsiveness. Furthermore, mediation analysis revealed indirect associations of fasting glucose and HOMA-IR with 24-h BPV in relation to attenuated MSNA responses to HUT. Conclusions In older adults with hypertension, insulin resistance may be associated with elevated BPV through blunted sympathetic responses to orthostatic stress.