The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure – a prospective, randomized, controlled prevention trial of the German Hypertension League

Lüders, Stephan; Schrader, Joachim; Berger, Jürgen; Unger, Thomas; Zidek, Walter; Böhm, Michael; Middeke, Martin; Motz, W.; Lübcke, Cornelia; Gansz, Andrea; Brokamp, Ludmer; Schmieder, Roland E.; Trenkwalder, Peter; Haller, H.; Dominiak, Peter

doi:10.1097/hjh.0b013e3282ff8864

Cited by 192 publications

(120 citation statements)

References 18 publications

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“…49,50) In addition to this, if the results of our current study are applicable to humans, lifelong ARB treatment starting at an early age in subjects with a genetic predisposition to hypertension would be expected to prevent blood pressure elevation and the development of cardiovascular organ injury throughout life.…”

Section: Discussionmentioning

confidence: 99%

Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

et al. 2010

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SummaryMost previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year. Twelve SHR and 9 normotensive Wistar-Kyoto rats (WKY) were given normal tap water. Tail-cuff blood pressure was almost normalized by CS throughout 1 year (at 12-months: WKY 132 ± 3, SHR 229 ± 3, CS 137 ± 4 mmHg). After 1 year, cardiac ventricular weight (SHR +33%, CS -2% versus WKY) and aortic thickness (SHR +34%, CS +4% versus WKY) in the CStreated SHR rats were not different than those of WKY. Echocardiographic midwall fractional shortening (SHR -18%, CS -1% versus WKY) and left ventricular hydroxyproline content (SHR +47%, CS +11% versus WKY) were also improved by CS to the WKY level. With respect to kidney function, GFR (SHR -24%, CS +9% versus WKY) was preserved, proteinuria (SHR +312%, CS +12% versus WKY) was reduced, and the histological glomerular injury rate (SHR +186%, CS +6% versus WKY) was reduced by CS. These results suggest that long-term antihypertensive therapy with CS can completely prevent hypertensive cardiovascular and renal injuries in SHR. (Int Heart J 2010; 51: 359-364)

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Section: Discussionmentioning

confidence: 99%

Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

et al. 2010

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“…23 Hypertension was found to develop in 30.7% of the ramipril-treated patients compared with 42.9% of the controls, a relative risk reduction of 34.4%. These results suggested that treatment of prehypertensive patients with ACE inhibitor could prevent the development of hypertension in this population.…”

Section: Clinical Studies Of Hypertension Preventionmentioning

confidence: 99%

Prevention and regression of hypertension: role of renal microvascular protection

et al. 2009

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Hypertension is a disease which affects over 26.4% of the world adult population, therefore novel approaches to the prevention and treatment of this disease need to be examined. Previous studies from our and other laboratories have shown that treatment of spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats with a renin-angiotensin system (RAS) inhibitor during the 'critical period' in hypertension development results in prevention of the later development of hypertension. In humans, Julius et al. reported similar findings in the landmark TROPHY study. Recently, we reported that 'pulse' treatment of SHR with highdose angiotensin receptor blocker (ARB) is effective in causing sustained reduction of already established hypertension, even when the treatment was started after the 'critical period'. These results suggest the possibility that 'regression' of established hypertension may become feasible, and we have started a prospective, multicenter clinical study (STAR CAST study) to examine this possibility. In our animal studies, we found that treatment of rats during the 'critical period' with an ARB inhibits the development of renal arteriolar hypertrophy. Moreover, a high-dose angiotensin blocker caused a remarkable reversal of renal arteriolar hypertrophy in SHR, which was associated with changes in microvascular MMP expression. These results suggest that changes in the renal microvasculature may have an important role in the mechanisms of hypertension prevention and regression by ARB.

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“…Both lifestyle changes (20) and drug therapy (21)(22)(23) have been shown at least temporarily to slow the progression of prehypertension into hypertension. The trials, up until now, have likely been too late to stop the progress, because, at least in the spontaneously hypertensive rat (24), antihypertensive therapy must be given much earlier in the lifespan to prevent the future development of hypertension.…”

Section: Value Of Therapymentioning

confidence: 99%

Prehypertension

Kaplan¹

2009

Clinical Journal of the American Society of Nephrology

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The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure – a prospective, randomized, controlled prevention trial of the German Hypertension League

Cited by 192 publications

References 18 publications

Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

Prevention and regression of hypertension: role of renal microvascular protection

Prehypertension

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