Circadian impairment of postural blood pressure control: A hidden risk factor for night‐time falls in older adults?

The ability to maintain blood pressure (BP) upon standing is critical to cerebral perfusion and prevention of syncope and falls, particularly in older adults. Approximately 27% of people over 60 experience falls each year (Salari et al., 2022) and multiple factors influence fall risk, including mechanical disturbance, disturbed vision (e.g. distraction or dim light conditions) and orthostatic hypotension. Falls often happen at night with devastating consequences for mortality, as evidenced by a doubling of the odds of death if the fall occurs at night (McMahon et al., 2012). Orthostatic hypotension, defined by impaired BP recovery after standing, is a strong predictor of both future falls and all-cause mortality (Lagro et al., 2014). Despite these clinical implications, the circadian modulation of BP responses to postural change in older adults remains poorly understood. Previous studies have demonstrated that circadian processes lower BP responses to passive tilt in younger adults, especially during the biological night (Hu et al., 2011). Whether these endogenous mechanisms extend to active standing, and whether they contribute to the greater vulnerability of older adults, has remained an open question. In a recently published study in The Journal of Physiology, Thosar and Shea directly addressed this knowledge gap by examining circadian influences on BP responses to active standing in middle-aged and older adults (Thosar & Shea, 2025). Thosar and Shea (2025) recruited 25 rigorously screened healthy participants (19 middle-aged, aged 40–59 years; six older, aged 60–70 years) for a previously published study (NCT02202811) investigating circadian variation in vascular function in middle-aged adults in a highly controlled 5-day forced desynchrony protocol under dim light conditions. In this recent publication, the authors used additional data from that experiment to investigate the role of the endogenous circadian system in BP regulation upon standing in a secondary analysis. Forced desynchrony as an experimental design is considered the gold standard for isolating circadian from behavioural and environmental influences, as it distributes sleep, meals and activity evenly across the 24 h day. During each waking episode, participants underwent an active standing challenge following 24 min of supine rest after waking, with BP and heart rate measured at the end of the supine resting period and at 1 and 3 min post-standing. The main finding of this study was that older adults exhibited significantly impaired systolic BP responses at both 1 min (−12 mmHg, P = 0.014) and 3 min (−11 mmHg, P = 0.03) post-standing compared with midlife adults. Diastolic BP was also reduced at 3 min (−6 mmHg, P = 0.013). Crucially, these impairments were most pronounced during the biological night (10:30 PM–06:30 AM), when five of six older adults showed an abnormal systolic BP drop at 1 min of standing, compared with only a quarter of middle-aged participants. Interestingly, heart rate responses to standing were similar across groups and circadian phases, suggesting that the impairment was not due to central autonomic drive but likely due to peripheral vasoconstriction, as the authors note. A schematic summary of the main findings of this study is shown in Figure 1. The study's major strength lies in its use of the forced desynchrony protocol, which elegantly eliminates environmental and behavioural confounds such as sleep, food intake or physical activity that typically complicate the assessment of circadian effects. The development of forced desynchrony was a major milestone in the history of circadian research. Until its establishment as an experimental approach, it remained impossible to disentangle whether an observed physiological rhythm was due to diurnal changes in the zeitgeber (from German: time-giver) input, i.e. behavioural and environmental changes over the day, versus endogenously circadian, meaning the observed 24 h rhythm persists in the absence of zeitgeber input and hence has to originate from within the organism. By setting light exposure to constantly dim levels throughout 24 h and evenly dispersing other zeitgebers in a highly standardised and regularly recurring manner, the impacts of sleep and wake, rest and activity, as well as food intake and fasting, are controlled so that the physiological rhythms that remain in this setting can no longer be directed by zeitgebers directly but must be maintained by an internal time keeping system at least somewhat independent of the zeitgebers. By combining this design with careful participant screening and standardised postural testing, the authors were able to demonstrate a clear circadian impairment of BP recovery upon standing at night in older compared with middle-aged adults. The findings have important clinical relevance. They provide a mechanistic explanation for the high prevalence of night-time falls in older adults and suggest that circadian biology should be explicitly considered in fall-prevention strategies, including the timing of BP medication. Moreover, the study extends prior work on passive tilt responses in young adults (Hu et al., 2011) to a more ecologically relevant behaviour (i.e. active standing) in a vulnerable population. Despite its strengths, the study has several limitations. The most significant is the small sample size of older adults (n = 6) and skewed sex distribution with only one older female, which, together with the inclusion of healthy adults without medication requirements, limits the generalisability of the findings. Although the effect sizes appear large and consistent, replication in larger, more heterogenous cohorts is needed. This is particularly important considering that these results are a secondary analysis of a previous study that was not powered to determine age-related circadian differences in BP reactivity upon standing. Secondly, the study did not measure autonomic or vascular mechanisms directly. The interpretation that impaired peripheral vasoconstriction underlies the observed BP responses is plausible but speculative and remains to be supported by data in future studies. Direct measures of autonomic balance (e.g. using heart rate variability), vascular resistance, baroreflex sensitivity and particularly measuring the circadian variation of all three would help to clarify underlying mechanisms. Thirdly, while the results strongly implicate circadian regulation in impaired BP responsiveness, the study did not examine actual fall outcomes. Thus, the translation from laboratory impairment to clinical fall risk remains inferential. Nonetheless, prior evidence linking impaired orthostatic BP recovery to falls and mortality strengthens the authors’ conclusions (Lagro et al., 2014). These findings highlight an underappreciated role of the circadian system in exacerbating orthostatic intolerance in older adults at night. Clinically, this may explain why night-time bathroom visits are particularly hazardous with regard to fall risk in this older population. The work suggests potential chronotherapeutic strategies, such as adjusting the timing of antihypertensive medications, the use of compression garments during night-time hours, or environmental modifications to reduce the fall risk linked to orthostatic imbalance (e.g. bedside commodes to hold onto and movement-responsive night-time lighting). Such strategies may be particularly beneficial for individuals with conditions that increase the risk of falls (e.g. vascular disease, arthritis or diabetes), as well as for older adults taking medications known to heighten fall risk, such as benzodiazepines, sedatives or diuretics. Beyond immediate clinical translation, this study also underscores the importance of considering circadian physiology when evaluating cardiovascular function. Importantly, a single, static daytime assessment of orthostatic BP may underestimate risk in older adults who are most vulnerable to falls and at higher odds of death after falling at night (McMahon et al., 2012). Further, conducting 24 h ambulatory BP monitoring may hence prove useful in this population to identify individuals at risk of night falls. Future research should expand these observations by including larger, more diverse cohorts, incorporating mechanistic measures of circadian variation in vascular resistance, autonomic and baroreflex function, and directly tracking falls or presyncopal events in real-world settings. In conclusion, Thosar and Shea (2025) provide intriguing evidence that the endogenous circadian system impairs night-time BP responses to standing in older adults, which warrants further investigation. By revealing a time-of-day-dependent vulnerability in postural cardiovascular control, this work advances our understanding of fall risk and highlights the need for future synergies between chronobiological research and treatment, as well as prevention approaches. Although further research is needed to clarify mechanisms and clinical outcomes, this study represents an important step towards integrating chronobiology into cardiovascular physiology and fall-prevention strategies. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. The authors declare no competing interests. J.-F.H. and D.D. worked on the conception and design of the work. All authors worked on the analysis and interpretation of the work, drafted the work and revised it critically for important intellectual content. All authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. Ministry of Culture and Science of the State of Northrhine Westphalia: Jan-Frieder Harmsen, PB22-062. Jan-Frieder Harmsen is funded by the project ‘Profilbildung Built and Lived Environment’ (PB22-062). The project ‘Profilbildung Built and Lived Environment’ is receiving funding from the programme ‘Profilbildung 2022’, an initiative of the Ministry of Culture and Science of the State of North Rhine-Westphalia. The sole responsibility for the content of this publication lies with the authors. The authors would like to acknowledge Dr Christopher McCrum for his input on the physiological relevance of the discussed findings on fall risk.