Jonathan Hicks

Introduction: Body processes have proven to follow a circadian clock¹, and incidence of cardiac events follows a diurnal pattern where most occur in the morning². Current beliefs follow that during the night, vascular tone, coagulability, oxygen demand, heart rate, and blood pressure are lower. In the morning, these reverse leading to higher incidence of cardiovascular events². Methods: Patients after onset of acute coronary syndrome were assessed for short sleep duration, obstructive sleep apnea, or overnight shift work and monitored for cardiovascular outcomes³. Patients with STEMI were divided based on time of onset and pathology (plaque rupture, plaque erosion, calcified plaque) searching for association between circadian rhythm and pathology⁴. Patients with T2DM were genotyped with PCR for single nucleotide polymorphisms in genes associated with circadian rhythm (ARNTL, CLOCK, and PER2) and analyzed for linkage to higher incidence of MI’s⁵. VEGF, SDF-1, and EPC were monitored in jet-lag model mice. Their femoral artery was ligated, and recovery was monitored⁶. Jet-lag, shift-work, and control mice were made using models for atherosclerotic development and compared⁷. Considering chronotherapy, participants taking antihypertensives took their medication in either morning or evening and monitored for adverse cardiovascular outcomes⁸. Other studies adjusted the time of day that patients would take acetylsalicylic acid and monitored blood pressure⁹, platelet inhibition and platelet turnover¹⁰, or platelet aggregation¹¹. Results: Short sleep duration, obstructive sleep apnea, and overnight shift work were associated with adverse cardiovascular outcomes, and having more than one of these risks showed an additive adverse effect³. The only pathology studied showing clear association with circadian rhythm was plaque rupture⁴. Certain ARNTL and CLOCK genes were associated with higher risk of MI⁵. In the jet-lag mice, the VEGF and EPC levels remained diminished, and reparative angiogenesis of the vascular injuries and blood perfusion recovery were inhibited⁶. The shift-work mice had almost a two-fold increase in atherosclerotic development⁷. Considering chronotherapy, antihypertensives led to diminished occurrences of cardiovascular events when taken in the evening⁸. Taking acetylsalicylic acid in the evening led to greater drop in blood pressure⁹, more platelet inhibition and platelet turnover¹⁰, and greater reduction in platelet aggregation¹¹. Conclusion: Both high-risk patients for cardiovascular events and mouse models show negative outcomes when subjected to disrupted circadian cycles. Chronotherapy of antihypertensives and acetylsalicylic acid showed positive results in cardiovascular risk reduction. When dealing with at-risk cardiovascular patients, it may be prudent to counsel on circadian sleep cycles and consider chronotherapy in their treatment.

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