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



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Hypertension is an important health problem because of its high prevalence and the consequence in terms of morbidity, mortality and health related costs. Periodic screening of blood pressure and, in most cases lifelong, treatment of hypertension prevents hypertension related morbidity and mortality such as stroke, dementia, myocardial infarction, congestive heart failure and renal failure. A recent study from the Framingham cohort has shown that persons with high normal blood pressure, also known as prehypertension, are at increased risk for cardiovascular complications, also after correction for standard cardiovascular risk factors. Moreover, prehypertensive persons have a 10% annual risk to progress to hypertension. Preventing or substantially delaying hypertension in these high risk patients by an early and temporary intervention is an interesting and probably cost-effective target for therapy. Recent studies in spontaneous hypertensive rats (SHR) have shown that it is possible to postpone the development of hypertension and hypertensive organ damage by early and temporary anti-hypertensive treatment with a renin-angiotensin system (RAS) blocker if started early in life. Whether this strategy is effective in humans is unknown. Increased intra-vascular resistance precedes the development of hypertension in humans and animals. The mode of action by which ACE inhibitors may prevent hypertension later in life may be caused by: 1. decreasing intra-renal resistance by inducing apoptosis of pericytes with subsequent increment of blood flow in the vasa recta of the kidney and 2. affecting renal medullar hemodynamics resulting in resetting the pressure-natriuresis curve. In a randomized, placebo-controlled trial we aim to demonstrate that brief temporary treatment with ACE inhibitors (for one year) compared to placebo is effective in reducing blood pressure levels at three years. We will examine whether this intervention leads to a reduction in hypertensive organ damage by measuring left ventricular mass, intima-media thickness of the carotid artery, and microalbuminuria. In additional analyses, we will try to identify subjects in whom the treatment effect was more pronounced through assessment of polymorphisms in the RAS and sodium chloride-channels known to be associated with hypertension.



Looptijd: 100 %
Looptijd: 100 %
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Verantwoordelijke organisatie:
Amsterdam UMC - locatie AMC