Table 4.

Conflicting findings in human versus animals in the context of circadian studies.

Conflicting Finding	Human Studies	Animal Studies	Ref.
Sex-specific CVD risk from circadian disruption	Daylight saving time shifts increase MI risk, with higher risk in women in spring and men in fall; confounding factors like sleep and chronotype not controlled.	Rodent studies show greater circadian-dependent MI mortality in males; controlled genetic/environmental manipulations reveal direct sex-specific effects.	(Young, 2023; Rabinovich-Nikitin et al., 2019)
Mechanisms of circadian influence	Mechanisms linking circadian disruption to CVD remain cryptic, with multiple confounders (sleep deprivation, hormonal changes, inflammation).	Genetic ablation of clock genes (e.g., CLOCK/BMAL1) in mice leads to cardiomyopathy, arrhythmias, and altered metabolism, directly linking clock disruption to pathology.	(Young, 2023), (Eckle et al., 2024), (Rabinovich-Nikitin et al., 2019)
Role of central vs. peripheral clocks	Human studies often cannot distinguish effects of central (brain) vs. peripheral (heart) clocks due to complexity of environmental cues.	Animal models can isolate central and peripheral clock contributions; disruption in specific tissues (e.g., cardiomyocytes) demonstrates distinct roles in cardiac rhythms and disease.	(Young, 2023; Rabinovich-Nikitin et al., 2019; Hayter et al., 2021)
Impact of environmental circadian misalignment	Shift work, daylight saving, and Intensive Care Unit (ICU) environments linked to increased CVD risk, but with variable and sometimes contradictory findings due to uncontrolled variables.	Controlled circadian misalignment (e.g., jet lag simulation) in animals consistently increases CVD risk and inflammatory responses, independent of sleep loss.	(Rabinovich-Nikitin et al., 2019), (Morris et al., 2016)
Chronotherapy and biomarker rhythms	Human biomarker studies show circadian variation, but clinical translation for optimized therapy timing remains inconsistent.	Animal studies demonstrate robust circadian regulation of cardiac gene/protein expression and response to therapy, supporting chronotherapy strategies.	(Young, 2023; Rabinovich-Nikitin et al., 2019; Scheer et al., 2010)