Effects of Temporary Inhibition of the Renin-Angiotensin System on future blood pressure and hypertensive organ damage in young prehypertensive adults * TIResiAS

Blood pressure is linearly related with cardiovascular risk.. A recent
population based survey showed that 30% of persons with high normal blood
pressure (BP 130-140/85-90 mmHg) developed hypertension during 3 years
follow-up. This was also accompanied by an increase in cardiovascular
complications. Prevention or delaying hypertension by an early and temporary
intervention in these high risk individuals is an interesting and probably cost
effective therapeutic strategy. Recent experiments in spontaneous hypertensive
rats (SHR) have shown that early and temporary inhibition of the
renin-angiotensin system (RAS) results in a long term anti-hypertensive effect,
also after cessation of treatment and prevents hypertensive organ damage.
Possibly this is the case for humans. The hypothesis that temporary treatment
of prehypertensive persons results in future blood pressure reduction in humans
is currently being tested in a multi-centre trial elsewhere. The design of this
study poses several limitations. These issues will be overcome in the TIResiAS
study.

To test the hypothesis whether treatment with an ACE inhibitor in young
prehypertensive adults reduces blood pressure 2 years after cessation of active
treatment and to determine whether this treatment can reduce left ventricular
mass and microalbuminuria.

Multi-centre double blind randomized placebo controlled trial.

Individuals are randomized to receive either lisinopril 10mg daily for three
weeks followed by lisinopril 20mg daily or matched placebo for a period of one
year. This is followed by two years of regular blood pressure monitoring.

Study burden: 4 visits of 3 hours, 16 visits of 15-30 minutes, 4 times 24 hours
ambulatory blood pressure monitoring and 24 hours urine collection. The total
study takes 3 years of which 1 year of daily medication intake. ACE inhibitors
are save and effective antihypertensive drugs, side effect include a
non-productive cough (estimated prevalence 5-10%), deterioration of renal
function, hyperkalemia, (orthostatic) hypotension and angioedema (prevalence
<0.4 %). All side effects will be closely monitored, stop criteria have been
clearly defined in the study. Lisinopril may cause damage to the unborn fetus
in the 2nd
and 3rd trimester of pregancy. At the start of the study pregnancy will be
excluded by a pregnancy test. Women participating in this study will be advised
to use reliable contraceptives during the active treatment period and advised
to contact the study doctor in case the menstrual period is more than 2 weeks
overdue for a pregnancy test. If study participants develop hypertension (BP
>140/90 mmHg) antihypertensive therapy will be instituted according to
standardized protocols, following present guidelines.