A brief history of circadian time in the heart

This review tracks the discovery of circadian biology in cardiovascular science, starting with early clinical observations of daily changes in heart rate, blood pressure, and cardiovascular events. These patterns suggested that time of day matters, but it was not until the past two decades that the mechanisms and knowledge translation of these rhythms were uncovered. We describe the heart's intrinsic circadian properties and importantly how this leads to regulation of cardiac gene and protein expression, neuroendocrine and vascular rhythms, metabolism, cellular electrophysiology, and cell signaling pathways. Next, we explore emerging themes, including the impact of circadian timing on ischemic injury, cardiac aging, and trends in circadian desynchrony, sex, and interorgan crosstalk. Building on these discoveries, circadian medicine is beginning to reshape clinical care including timing of surgery, chronotherapies, biomarkers, ICU design, novel molecular drugs targeting the circadian clock, the role of the microbiome and time restricted eating, the new field of rest, and the concept of One Health and applications to veterinary medicine. Looking ahead we address new frontiers such as epigenetics, gene editing, and spaceflight. Together, these advances offer a roadmap for how circadian rhythms can be harnessed to improve cardiovascular health and disease outcomes, supporting longer and healthier lives.