circadian rhythms

Optimizing Cardiovascular Care in Accordance with the Body’s Internal “Clock”

March 10, 2017

Key Takeaways

  • Timing medical therapy to the body’s circadian rhythms may play a key role in improving treatment outcomes among patients with heart failure, myocardial infarction, and hypertension.

The study of circadian rhythms as it relates to human health has expanded in recent years, with a large focus devoted to utilizing knowledge regarding the body’s “internal clock” for improving the treatment of cardiovascular-related therapies. The circadian rhythms are regulated by the suprachiasmatic nucleus, a “master clock” in the hypothalamus that responds to light and manages the expression of genes that are active at varying times throughout the day and night. Exposure to artificial light during the evenings, such as during shift work or sleep deprivation, can disrupt circadian rhythms and lead to the desynchronization of gene expression. This has been consistently linked to cardiovascular disease.1,2

The circadian rhythms represent a growing subject in medical education, with increasing attention being placed on its associations with cardiovascular health. Clinical trials, for instance, have shown that optimized medication therapy to circadian schedules can favorably impact patients with hypertension.3 Dr. Guangrui Yang of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania mentions that, after light disruption,

“…clocks in every organ will run their own speed.”

Therefore, the genes that regulate endothelial function, thrombus formation, and blood pressure may be at risk for impact if a patient is chronically exposed to excessive light when he/she should be asleep.

Chronotherapy, a term used to describe the circadian-wise timing of drug administration, is becoming an increasingly studied practice for improving treatment-related outcomes. An editorial by Kuehn BM in Circulation provides a brief overview of the importance of chronotherapy for cardiovascular treatment.4

Considering the fact that many medications used to treat high blood pressure and heart failure target circadian-controlled genes, the optimization of medication administration timing makes sense for improving efficacy. Rhythmic genes active at night, for example, may be key targets for chronotherapy. One study found that a short-acting ACE-inhibitor (captopril) administered at sleep time reduced heart enlargement and weight in mice with cardiac hypertrophy.5 This same administration upon waking in the morning provided no benefit, showing a clear advantage of therapy timing based on gene activity.

Patients recovering from an adverse cardiac event may also be affected by disruptions in circadian rhythms.

“Modern intensive care units and cardiac care units, which often have multi-bed rooms, lots of light, noisy machines, and frequent vitals checks were not designed to maintain patients’ normal circadian rhythms,”

says researcher Dr. Tami A. Martino of the University of Guelph in Canada and director of the Center for Cardiovascular Investigations. Martino’s mouse model featuring rodents with myocardial infarction examined the effects of normal day and night light vs altered lighting conditions on disease outcomes. Mice exposed to the altered lighting conditions, comprised of just a short-term disruption in the circadian cycles of the mice, was associated with greater infarct expansion and worse outcomes.6 This study, among many others, suggest the need for further research as well as physician education on the importance of optimizing therapy based on the circadian rhythms of their patients.

References:

  1. Portaluppi F, Tiseo R, Smolensky MH, et al. Circadian rhythms and cardiovascular health. Sleep Med Rev. 2012;16(2):151-166.
  2. Chen L, Yang G. Recent advances in circadian rhythms in cardiovascular system. Front Pharmacol. 2015;6:71.
  3. Hermida RC, Ayala DE, Calvo C. Optimal timing for antihypertensive dosing: focus on valsartan. Ther Clin Risk Manag. 2007;3(1):119-131.
  4. Kuehn BM. The Heart’s Circadian Rhythms Point to Potential Treatment Strategies. Circulation. 2016;134(23):1907-1908.
  5. Martino TA, Tata N, Simpson JA, et al. The primary benefits of angiotensin-converting enzyme inhibition on cardiac remodeling occur during sleep time in murine pressure overload hypertrophy. J Am Coll Cardiol. 2011;57(20):2020-2028.
  6. Alibhai FJ, Tsimakouridze EV, Chinnappareddy N, et al. Short-term disruption of diurnal rhythms after murine myocardial infarction adversely affects long-term myocardial structure and function. Circ Res. 2014;114(11):1713-1722.

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