Circadian rhythms in cardiovascular disease: a new perspective on inter-organ crosstalk

Cardiovascular diseases (CVDs) constitute a global health crisis, responsible for approximately 31% of all-cause mortality, and increasingly manifest as multisystem disorders involving cardio-cerebral, cardio-hepatic, and cardio-renal comorbidities, conceptualized as the cardiovascular-renal-hepatic-cerebral paradigm. This review synthesizes evidence demonstrating that circadian disruption (CD) serves as a pivotal underlying mechanism for these inter-organ interactions. The suprachiasmatic nucleus master clock synchronizes peripheral oscillators across organs, coordinating transcriptomic and physiological rhythms; however, misalignment due to sleep disorders, irregular meal timing, or shift work leads to internal desynchrony. This disruption propagates through shared pathways, including autonomic nervous system imbalance, hormonal fluctuations, metabolic dyshomeostasis, systemic inflammation, and gut microbiota dysbiosis. For instance, CD exacerbates morning surges in blood pressure and thrombosis risk in cardio-cerebral comorbidity, impairs lipid metabolism and insulin sensitivity in cardio-hepatic links, and dysregulates electrolyte handling and blood pressure in cardio-renal syndrome within the cardiovascular-kidney-metabolic framework. The review highlights the bidirectional nature of these relationships, where end-organ damage further perturbs circadian rhythms. Importantly, chronotherapeutic strategies, such as time-restricted eating to align nutrient intake with active phases or bedtime administration of antihypertensives, show promise in re-entraining circadian rhythms and mitigating multi-organ dysfunction. This chronobiological perspective underscores the need to integrate temporal dimensions into CVDs management, moving beyond organ-centric views to a network-based approach that targets circadian synchronization for personalized medicine.