Key result
Transient cardiac output drops upon standing are linked to CVD, frailty, and cognitive decline.
Why the study?
While orthostatic blood pressure responses have been extensively studied, the role, physiological determinants, and clinical relevance of orthostatic cardiac output responses remained unclear.
Does a transient fall in cardiac output upon standing associate with cardiovascular disease, mobility reduction, and cognitive alterations in adults?
Cohort (n=6,099)
Yes
Does a transient fall in cardiac output upon standing associate with cardiovascular disease, mobility reduction, and cognitive alterations in adults?
A transient fall in cardiac output upon standing is a newly identified autonomic phenotype associated with cardiovascular disease, frailty, cognitive decline, and increased fall risk in older adults.
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.
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Xie et al. (2025) conducted a cohort in Orthostatic haemodynamic response (n=6,099). Initial orthostatic cardiac output fall (COF) vs. Initial orthostatic cardiac output rise (COR) was evaluated on Falls among subjects on negatively chronotropic drugs (OR 1.82, 95% CI 1.18-2.80). An initial orthostatic cardiac output fall upon standing was associated with increased odds of falls among older adults on negatively chronotropic drugs (OR 1.82; 95% CI 1.18-2.80).
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