Effects of low-dose aspirin taken at bedtime on hypertension

Aspirin is a potent vasoprotective drug, widely used in secondary prevention of cardiovascular events. Until recently, it was thought not have any influence on tension. However, in some recent studies, 100mg aspirin, administered at bedtime and not upon awakening, showed to decrease blood pressure significantly, although underlying mechanisms are unclear. Therefore, in this study we will examine through which mechanisms aspirin 100mg at bedtime could have supplementary benefit to patients with hypertension by reducing their tension.
We hypothesise that aspirin 100mg at bedtime decreases tension by nocturnally lessening increase of the renin-angiotensin-aldosterone system, enhancing NO bioavailability, lessening autonomous nervous system activity and inhibiting COX-1 dependent thromboxane A2 production. Our objectives are to examine effects of aspirin 100mg at bedtime on these mechanisms.
The trial will have a prospective, randomised, placebo controlled, double blind and crossover study design.
We will use 15 subjects with grade 1 essential hypertension (140/90-159/99 mmHg). Patients with more severe hypertension will be excluded, as well as them with secondary hypertension, personal history of cardiovascular events, diabetes mellitus, rheumatoid arthritis, vasoactive medication or any contraindication to use of aspirin.
After patient’s written informed consent and screening, subjects will be randomised between aspirin at awakening and at bedtime in two treatment periods of 2 weeks. They will also get a placebo for respectively evening and morning to achieve full blinding. Between treatment periods, there will be a washout period of 4 weeks.
Before both periods there will be a short visit of half an hour to our centre and after both periods there will be an admission for 24 hours to the research centre of general internal medicine. With regular intervals blood will be sampled, 24 hours urine will be collected, tension will be measured and also some other non-invasive experiments will be done.

We hypothesise that aspirin 100mg at bedtime decreases tension by nocturnally lessening increase of the renin-angiotensin-aldosterone system, enhancing NO bioavailability, lessening autonomous nervous system activity or inhibiting COX-1 dependent thromboxane A2 production. Our objectives are to examine effects of aspirin 100mg at bedtime on these mechanisms.

Before both 2-week periods there will be a short visit of half an hour to our centre and after both periods there will be an admission for 24 hours to the research centre of general internal medicine. With regular intervals blood will be sampled, 24 hours urine will be collected, tension will be measured and also some other non-invasive experiments will be done.

After patient’s written informed consent and screening, subjects will be randomised between 100 mg aspirin at awakening and at bedtime in two treatment periods of 2 weeks. They will also get a placebo for respectively evening and morning to achieve full blinding. Between treatment periods, there will be a washout period of 4 weeks.