Cardiovascular disease is the leading cause of death in many industrialized countries. Intensive effort has been made to understand the basic mechanisms. One field of investigation in recent years is the study of circadian rhythms. Increasing evidence has shown adverse effects of circadian disruption in the cardiovascular system. CRD Pharma CardioResync is the platform that is investigating time dependent effects for development improved drugs for cardiovascular diseases.

Day-night variations in blood pressure (BP) and heart rate (HR) are among the best known circadian rhythms of physiology. In humans, there is a 24-h variation in BP with a sharp rise before awakening, the highest BP value is around midmorning.

Many cardiovascular events, such as sudden cardiac death, myocardial infarction and stroke, display diurnal variations with an increased incidence in the morning.

These events, as well as kidney albuminuria and progression to end-stage renal diseases, are relatively common in patients whose blood pressure fails to decline during the night, so-called non-dippers. Inverse dippers—BP rises instead of decreases at night—showed even higher cardiovascular mortality.

Circadian rhythms in timing of onset and tolerance to myocardial infarction (MI) have been well established. It has been reported that the occurrence of MI is two to three times more frequent in the morning than at night.

In the early morning, the increased systolic BP and HR results in an increased energy and oxygen demand by the heart, while the vascular tone of the coronary artery rises in the morning, resulting in a decreased coronary blood flow and oxygen supply.

This mismatch between supply and demand elicits the high frequency of the onset of MI. In addition, plasminogen activator inhibitor-1 displayed a circadian pattern with high levels in the morning, which is coincident with the morning peak of thrombus formation and platelet aggregation.

Many cardiovascular disorders occur in a circadian manner. For example, acute myocardial infarction (AMI) and cerebral infarction most often occur in the early morning whereas subarachnoid hemorrhage and a subtype of atrial fibrillation are usually observed in the afternoon.

Acute Myocardial infarction and thrombotic events such as pulmonary embolism frequently occur in the early morning. As these disorders can be fatal, CRD Pharma is elucidating the mechanisms of circadian onset of cardiovascular disorders not only to help for a better understanding of their pathogenesis but also for establishing therapeutic strategies (CardioReSync Platform).

Resynchronization of the peripheral circadian clock with the environment or within each peripheral organ can become a potential target for establishing a novel preventive strategy or treatment for cardiovascular diseases.