From light and activity to risk: circadian alignment as an emerging wearable biomarker

This editorial refers to ‘Accelerometer-measured circadian alignment predicts all-cause and cardiovascular mortality in middle-aged and older adults’, by J. Xie et al., https://doi.org/10.1093/eurjpc/zwaf445. Circadian rhythms orchestrate fundamental physiological processes, including sleep-wake cycles, hormonal secretion, and cardiovascular function. Disruption of these rhythms, whether through exposure to artificial light, irregular sleep patterns, or behavioural inconsistency, has been increasingly linked to adverse health outcomes.1 While millions of adults wear devices that track physical activity and sleep, synchrony between internal biological rhythms and the external 24-h light-dark cycle (i.e. circadian alignment) is rarely assessed in research and is not yet integrated into clinical practice. The study by Xie et al.,2 published in this issue of the European Journal of Preventive Cardiology, demonstrated that wearables can estimate circadian alignment using phasor metrics, which quantify the strength and regularity between daily light and activity patterns (phasor magnitude) and the timing offset between these patterns relative to the light-dark cycle (phasor angle). They report that circadian misalignment was independently associated with all-cause and cardiovascular mortality. This association may be particularly relevant in populations with chronic psychosocial stress, where disrupted rhythms could amplify vascular vulnerability. What distinguishes the phasor approach is the simultaneous integration of two dominant behavioural zeitgebers: light exposure and physical activity. Figure 1 illustrates conceptual profiles of circadian alignment vs. misalignment, highlighting how timing and regularity of light and activity relate to observed mortality risk. Traditional studies have examined these factors in isolation (e.g. shift work schedules, outdoor light exposure, or rest-activity patterns). However, Xie et al.2 advance a more physiologically integrated view of circadian function, highlighting that circadian health depends not merely on rhythms in each domain, but on their interactive alignment. Conceptual illustration of circadian alignment and misalignment. The left panel illustrates healthy circadian alignment, where activity and light exposure are synchronized with the natural light-dark cycle, a pattern associated with lower observed risk of all-cause and cardiovascular mortality. The right panel depicts misalignment scenarios identified in Xie et al.2: advanced timing (early activity before daylight), delayed timing (late-night activity), and low phasor magnitude (strength of light-activity synchronization), each linked to elevated mortality risk (hazard ratios shown). Practical strategies for supporting circadian alignment, such as maintaining a regular sleep-wake schedule, obtaining morning daylight exposure, and limiting bright light and late-night activity, are summarized in the lower left panel. These conceptual profiles highlight the potential for timing-aware behavioural interventions to complement traditional cardiovascular risk management. The study2 analysed 4814 US adults aged 45 and older from NHANES (2011–14), with 31 280 person-years of follow-up, 736 deaths, including 235 from cardiovascular diseases (CVD). Phasor magnitude reflects the strength and regularity of coupling between daily light and activity patterns (higher values indicate more consistent timing and stronger synchrony). A lower phasor magnitude (Q1 vs. Q4) was associated with a 70% higher risk of all-cause mortality. The phasor angle, representing the offset between activity and light, displayed a U-shaped pattern: both advanced (Q1) and delayed (Q4) timing carried a higher risk than typical timing (Q2; Q4 vs. Q2 HR 1.33, 95% CI 1.02–1.74). For cardiovascular mortality, advanced timing (Q1 vs. Q2) was associated with a higher risk (HR, 1.68; 95% CI, 1.09–2.60). Risk was lowest around a phasor magnitude of ∼0.4 (scale 0–1), indicating moderately strong consistency between daily activity and light exposure patterns. Optimal activity timing occurred approximately 1–2 h after sunrise on average, suggesting that individuals who were regularly active during morning daylight (rather than very early before sunrise or late at night) had the lowest risk of death from all causes, including CVD. These findings converge with emerging evidence linking circadian metrics with mortality.1 Indeed, recent studies using wearable accelerometry have demonstrated that blunted rest-activity rhythms,3 short sleep duration,4 severe circadian disruption clusters (i.e. misaligned activity patterns),5 and composite circadian syndrome risk factor scores6 are all associated with adverse CVD profiles and outcomes. What distinguishes the phasor approach is its integration of light and activity into a scalable framework measurable in free-living conditions, suggesting that population-level screening and monitoring are feasible. The U-shaped angle-mortality relationship reveals that circadian misalignment may involve distinct physiological pathways depending on the direction of deviation. Advanced alignment (i.e. activity substantially before light exposure) may blunt the cortisol awakening response and fragment restorative deep sleep, potentially triggering premature sympathetic activation before morning light synchronizes peripheral clocks.5 This mismatch is one hypothesized route to non-dipping BP, autonomic imbalance, and worse cardiometabolic burden. Moreover, late-night activity is associated with sustained elevations in inflammatory markers and a misalignment between metabolic rhythms and behavioural energy demands.7 In addition, the heightened mortality risk associated with delayed circadian timing in women (Q4 vs. Q2: HR 1.94 in females; HR 0.87 in males) may reflect oestrogen-mediated amplification of circadian gene expression, highlighting the sex-specific complexity of the underlying mechanisms.8 Optimal phasor values (magnitude ≥ 0.40–0.41; angle ∼1.21–1.70 h) suggest potential targets that require external device-agnostic validation for cardiovascular health, enabling a transition from population-level risk identification to individual phenotyping. Consider three individuals with otherwise identical traditional cardiovascular risk profiles: a sedentary worker with weak light-activity synchronization (low magnitude), a worker who must wake up and get to work well before sunrise (negative angle), and a night owl with delayed alignment (high positive angle). Current risk calculators treat these individuals equivalently; however, their phasor profiles reveal distinct circadian vulnerabilities that require different interventions. Furthermore, sex-specific signals may warrant sex-stratified targets if replicated across cohorts and devices. Clinical implications extend beyond risk assessment to the development of phenotype-specific strategies, although evidence from interventions remains limited.9 Individuals with low phasor magnitude may benefit from strengthening circadian cues through consistent sleep-wake routines, aligning daytime physical activity with natural light exposure, and maximizing exposure to natural daylight while minimizing artificial light at night. As shown in Figure 1, patterns aligned with the natural light-dark cycle are associated with lower observed risk, whereas advanced or delayed timing and irregular routines confer higher risk. For advanced timing, aligning activity with morning bright light, preferably outdoors when feasible, may mitigate early, dim-light activity patterns. Individuals demonstrating delayed timing may benefit from shifting their activity earlier in the day and limiting evening light, particularly from blue-enriched screens. For shift workers, targeting bright light during work periods combined with darkness during rest can enhance regularity and stabilize the phasor magnitude, even if not fully normalized.10 Finally, integrating phasor metrics into commercial wearable platforms could enable real-time monitoring and tailored feedback; however, randomized trials are needed to determine whether phasor-guided interventions improve sleep regularity, blood pressure patterns, or cardiovascular outcomes. Several limitations warrant emphasis. Single-time point assessment cannot distinguish between chronic misalignment and acute disruption, nor can it determine whether intra-individual variability predicts outcomes. Longitudinal studies tracking phasor trajectories would clarify whether progressive misalignment, fluctuating instability, or sudden disruptions drive mortality risk. Accelerometer-derived light measurements cannot distinguish natural from artificial sources, which is critical given their differential circadian effects. A phase-advanced individual might awaken to dim indoor light rather than bright outdoor illumination, while phase-delayed subjects could experience light pollution rather than intentional evening activities. Studies incorporating spectral light analysis, chronotype assessment, and circadian biomarkers, alongside phasor metrics, could clarify the mechanistic pathways. The absence of shift work and detailed occupational data represents a significant gap. Future investigations should determine whether phasor metrics predict mortality independently of work-schedule-induced disruption. Additionally, the heterogeneity in individual responses to circadian misalignment (why some individuals with severely disrupted phasor metrics avoid adverse outcomes while others with modest misalignment experience elevated mortality) requires systematic investigation to refine risk prediction and guide precision interventions. Xie et al.2 provide evidence that circadian alignment, quantified from wearable-derived phasor metrics, is independently associated with total and cardiovascular mortality. By integrating light exposure with physical activity, the dual-zeitgeber framework captures physiology that single-domain measures overlook. These emerging digital biomarkers shift the field from population-level associations to phenotype-specific targets, supporting the development of timing-aware interventions to improve health outcomes. In the next arc of preventive cardiology, timing becomes a target. As wearables shift from counting steps to synchronizing clocks, circadian alignment emerges as a wearable, modifiable, digital biomarker with the potential to inform actionable clinical guidance as validation progresses. Zachary T. Martin (Conceptualization [lead], Writing—original draft [lead]), Abdulkareem B. Murtala (Conceptualization [supporting], Writing—review & editing [supporting]), and Jose R. Medina-Inojosa (Conceptualization [lead], Supervision [lead], Writing—review & editing [lead]) Z.T.M. and J.R.M.-I. were supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) T32 Training Grant HL130025. J.R.M.-I. is supported by National Institutes of Health/NHLBI F32HL182343. No new data were generated or analysed in support of this editorial.