Effects of low-dose aspirin taken at bedtime on pathophysiologic mechanisms underlying hypertension in subjects with grade 1 essential hypertension: the Aspirin In Reduction of Tension (ASPIRETENSION) study

Cardiovascular events are the leading cause of mortality and morbidity at
present. One of the most important risk factors is hypertension and unless the
existence of many antihypertensive agents, lots of patients maintain an
uncontrolled tension.
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.

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.

Totally, the study will have a duration of 8 weeks. Patients will take pills
for 4 weeks. The most important burden consists of two admissions of 24 hours
to our research center.
Risks are very low. Mostly described adverse effects of aspirin are formed by a
somewhat higher risk for bleeding, particularly in the gastrointestinal tract,
but our dosage and length of intervention minimalise this risk. Patients with a
history of gastrointestinal ulcus or bleeding will be excuded from
participation, as will patients with asthma, because aspirin could provoke
excacerbations of this disease.