Using the Circadian Rhythm for More Effective Blood Pressure Control

The Previous article, The Circadian Rhythm: Timing is Everything, mentioned that peripheral clocks in all organs follow the master clock in the brain. This article is about the circadian rhythm of the cardiovascular system and when anti-hypertensives should be used to maximize their effect.

The Cardiovascular System

The cardiovascular system or CVS is made of the heart and all the arterial system that carries blood to the whole body and the venous system that brings blood back to the heart. Cardiovascular disease or CVD affects not just the heart, but all the other organs supplied. Thus, CVD can lead to other diseases like strokes and kidney failure.

Circadian Changes in Blood Pressure

The blood pressure changes in a whole 24-hour cycle.

The sharpest rise of blood pressure is in the morning right before awakening. This may explain why sudden cardiac deaths, heart attacks, and strokes are higher in the morning.
Blood pressure cyclically lower or ‘dip’ at night. Non-dippers are people whose blood pressure does not dip. Because of the persistent rise of the blood pressure, non-dippers have a tendency to have to develop kidney failure that will ultimately need dialysis and have high cardiovascular mortality. Inverse dippers have blood pressures that rise instead of dip at night. Like non-dippers, inverse dippers also have higher cardiovascular mortality.

Sphygmomanometer

Circadian Rhythms and Heart Attacks

The higher blood pressure in the morning increases the work required from the heart to push the blood against a higher resistance. Greater work means more oxygen requirement for the heart muscles. If the coronary arteries have critical atherosclerosis, not enough blood may flow, and the heart muscles will not have enough oxygen. That situation can lead to angina and even a heart attack.
Certain substances that promote clotting are higher in the morning. Namely, plasminogen activator inhibitor-1 and GPIb and P-selectin. These substances facilitate an increased tendency for blood clot formation. Blood clots can block a coronary artery and lead to myocardial infarction.

Studies in Animals with Disrupted Circadian rhythms Showed:

Dilated cardiomyopathy, which decreases the pumping efficiency of the heart and leads to heart failure
Endothelial dysfunction where the blood vessels cannot do the necessary self-maintenance to preserve the integrity of the inner lining of the blood vessels and
Increased atherosclerosis because of impaired cholesterol metabolism.

Based on the knowledge about the cardiovascular circadian rhythm, a strategy can be implemented to make antihypertensive medications to be more effective.

Blood Pressure Control Using the Circadian Rhythm

Since hypertension is a significant risk factor for the development of cardiovascular diseases, it is essential to control blood pressure adequately. The rise of the blood pressure in the early morning before waking up can be addressed by taking the blood pressure medications at night.

The MAPEC Study (2) was designed to find out what is the best time to take anti-hypertensives. The study found out that:

Blood pressure medications, when taken at bedtime, resulted in lower blood pressure during sleep-time, reduced non-dipping, and better blood pressure control the next day. This is independent of the half-lives of the medications.
The subjects who were taking more than 1 BP-lowering medications at night were followed for 5.6 years. Those subjects had lower cardiovascular disease events that included heart attacks, ischemic strokes, and hemorrhagic strokes.
Another study (3) showed that the blood pressure is lower the next day if aspirin is taken at bedtime in pre-hypertensive patients.

Note: The MAPEC study was done in Spain. The Antihypertensive medications used by the patients were:

Angiotensin Receptor Blockers or ARBs (valsartan, telmisartan, and olmesartan)
Angiotensin-converting enzyme inhibitors or ACEIs (ramipril and spirapril)
Calcium channel blockers or CCBs (amlodipine and nifedipine)
beta-blocker nebivolol and a
water pill (torasemide).

Parting Message

Lack of sleep not only leads to hypertension but also contribute to the development of diabetes, immune problems, obesity, metabolic syndrome, and depression. Restful and adequate sleep is essential in preventing many common diseases. Talk to your physician before making any adjustments with your medications.

Don’t Get Sick.

References:

Chen, Lihong, and Guangrui Yang. “Recent advances in circadian rhythms in the cardiovascular system.” Frontiers in pharmacology vol. 6 71. 1 Apr. 2015, doi:10.3389/fphar.2015.00071
Hermida RC1, Ayala DE, Mojón A, Fernández JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010 Sep;27(8):1629-51. doi: 10.3109/07420528.2010.510230.
Ramón C. Hermida, Diana E. Ayala, Artemio Mojón, José R. Fernández, Ambulatory Blood Pressure Control With Bedtime Aspirin Administration in Subjects With Prehypertension, American Journal of Hypertension, Volume 22, Issue 8, August 2009, Pages 896–903, https://doi.org/10.1038/ajh.2009.83

Image Credit:

Sphygmomanometer Public Domain, https://commons.wikimedia.org/w/index.php?curid=307562

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