Peripheral autonomic dysregulation in response to standing: a new form associated with cardiovascular disease, mobility reduction, and cognitive alterations.

BACKGROUND AND AIMS: Cardiovascular responses to standing are essential for maintaining cerebrovascular blood flow. While orthostatic blood pressure (BP) responses have been studied extensively, the role of cardiac output (CO) remains unclear. This study aimed to investigate patterns of orthostatic CO responses, their physiological determinants, and clinical relevance.

METHODS

Real-time haemodynamic responses to active standing were recorded in two prospective cohorts: 3074 young (Melbourne) and 3025 older (Ireland) adults. In the young, five subgroups assessed phenotype reproducibility (same-day and two-week retests), responses to vasodilation (sublingual glyceryl trinitrate, GTN) or sympathetic activation (SA; handgrip with phenylephrine), and associations with urinary electrolyte excretion. In older adults, CO patterns were related to clinical characteristics and outcomes.

RESULTS

A reproducible dichotomy in the initial orthostatic CO response was identified: either a transient rise (COR: 66% young, 78% older) or fall (COF: 34% young, 22% older). COF subjects had less heart rate increase and greater transient reductions in stroke volume and BP upon standing, despite an increased sympathetic response. GTN exaggerated COF, whereas SA mitigated it. In older adults, COF was more prevalent with cardiovascular disease, higher body mass index, smoking, diabetes, or antihypertensive use. After adjustment, COF remained associated with slower gait, frailty, and diminished cognitive function (all P < .001). Among subjects on negatively chronotropic drugs (n = 487), falls were more frequent in COF (odds ratio 1.82, 95% confidence interval 1.18-2.80).

CONCLUSIONS

These findings reveal a novel variant of the autonomic cardiovascular response to standing, with important clinical implications for functional decline in older adults.