Feasibility of Treating Prehypertension with an Angiotensin-Receptor Blocker

Julius, Stevo; Nesbitt, Shawna D.; Egan, Brent M.; Weber, Michael A.; Michelson, Eric L.; Kaciroti, Niko; Black, Henry R.; Grimm, Richard H.; Messerli, Franz H.; Oparil, Suzanne; Schork, M. Anthony

doi:10.1056/nejmoa060838

Cited by 827 publications

(544 citation statements)

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“…The results demonstrated a reduced frequency with which stage I hypertension occurred in the ARB-treated patients. 66 Circulating Biochemical Markers of Vascular Inflammation Angiotensin II has been identified in studies of tissues and experimental animals as a proinflammatory molecule that stimulates the formation of reactive oxygen species, resulting in the upregulation of inflammatory mediators such as the transcription factor NF-jB and increased formation of chemokines, C-reactive protein (CRP), and adhesion molecules and activation of T lymphocytes that contribute to both BP elevation and atherosclerosis. 2,3,67 An increase in circulating markers of inflammation have been documented in patients with hypertension, obesity, and diabetes, and one of these agents, CRP, has been reported to independently predict CV risk.…”

Section: Prevention Of Hypertensionmentioning

confidence: 99%

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

Taylor

Siragy

Nesbitt

2011

The Journal of Clinical Hypertension

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Key Points and Practical Recommendations• The angiotensin receptor blockers are highly effective antihypertensive agents that are also particularly well tolerated.• There are no major differences in efficacy or other clinical characteristics among older drugs in this class, although some of the newer agents may more effectively reduce blood pressure than older agents.• Major randomized clinical trials have demonstrated that angiotensin receptor blockers provide significant outcomes benefits in conditions such as diabetic nephropathy, chronic heart failure or heart failure following myocardial infarction, hypertension with left ventricular hypertrophy and in patients whose histories of previous events or complicated diabetes puts them at high cardiovascular risk.• In treating hypertension, angiotensin receptor blockers can be used as first-line therapy or added at later stages of treatment titration.• These drugs are very effective in combination with thiazide diuretics or calcium channel blockers and there are several single-pill, fixed-dose combinations of angiotensin receptor blockers with hydrochlorothiazide, amlodipine, or aliskiren. These combinations can be given as initial therapy (where appropriate) or later in the course of treatment. Three-drug combinations (angiotensin receptor blocker plus amlodipine plus hydrochlorothiazide and angiotensin receptor blocker plus aliskiren plus hydrochlorothiazide) are also available. J Clin Hypertens (Greenwich). 2011;13:677-686. Ó2011 Wiley Periodicals, Inc.The renin-angiotensin-aldosterone system (RAAS) plays an important role in protecting vertebrates against cardiovascular collapse due to hypotension and volume loss in the event of traumatic injury that involves blood loss. In certain humans, however, inappropriate or exaggerated activity of the RAAS contributes to the development of hypertension and the initiation of a molecular cascade in tissues with consequent injury to critical organs such as the brain, kidneys, heart, and blood vessels. 1-3 As understanding of the pathologic role of the RAAS in hypertensive vascular disease has unfolded during the past century, so has the interest in developing drugs that could interdict specific components of the RAAS. The first of the RAAS-blocking drugs to become commercially available were the aldosterone antagonists in the 1970s, followed by the angiotensin-converting enzyme (ACE) inhibitors in the 1980s and the angiotensin II receptor blockers (ARBs) in the 1990s. Unlike ACE inhibitors that inhibit the conversion of angiotensin I to II, ARBs bind to the angiotensin II AT 1 receptor, thereby inhibiting the cellular actions of angiotension II mediated by the receptor in which the tissue is located. During the past 20 years, studies in the laboratory and clinic have documented that ARBs, either alone or in combination with drugs of other classes, reduce blood pressure (BP) in hypertensive animals and humans; reduce rates of myocardial infarction (MI), stroke, and progression of renal impairment; and positively impact oth...

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Section: Prevention Of Hypertensionmentioning

confidence: 99%

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

Taylor

Siragy

Nesbitt

2011

The Journal of Clinical Hypertension

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“…Interestingly, the Trial of Preventing Hypertension Study showed that the treatment of prehypertensive patients with the AT 1 receptor blocker (ARB) candesartan for 2 years significantly delayed the progression from pre-hypertension to stage 1 hypertension during the following 2 years. 5 This finding suggests long-lasting effects of transitory activation of the AT 1 receptor in the development of hypertension. The results of the Trial of Preventing Hypertension Study bear certain similarities to those of a study by Holman et al 6 (United Kingdom Prospective Diabetes Study), indicating the so-called 'legacy effect' .…”

Section: Introductionmentioning

confidence: 93%

Angiotensin II receptor activation in youth triggers persistent insulin resistance and hypertension—a legacy effect?

et al. 2011

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Although the involvement of angiotensin II (Ang II) in insulin resistance and hypertension has been established, the temporal relationships between Ang II receptor activation and changes in insulin sensitivity and blood pressure are not clear. To better understand this issue, we infused rats with Ang II (200 ng kg À1 min À1 ) or vehicle for 4 weeks and assessed the residual effects after the discontinuation of the infusion on blood pressure, insulin sensitivity and tissue parameters of inflammation. Four weeks after the discontinuation of the Ang II infusion, the blood pressure was higher by 12.8 mm Hg, and insulin sensitivity as determined by a euglycemic hyperinsulinemic glucose clamp was reduced (glucose infusion rate: 11.1 ± 0.7 vs. 17.6±0.5 mg kg À1 min À1 ) in the Ang II-treated group compared with controls. The persistent hypertension and insulin resistance were associated with greater than two-fold increases in macrophage chemoattractant protein-1, tumor necrosis factor-a and thiobarbituric acid-reactive substrates in the soleus muscle. Furthermore, total and activated forms of Rac-1, a regulatory subunit of the NADPH oxidase complex, were increased by 144 ± 14% and 277 ± 82%, respectively, in the skeletal muscle of Ang II-treated rats. These residual effects after Ang II infusion were all attenuated by the co-administration of tempol, a free radical scavenger, or candesartan with Ang II. The effects of candesartan were not mimicked by hydralazine at an equidepressant dose. These findings suggest that Ang II receptor activation in youth triggers the upregulation of inflammatory cytokines and the production of reactive oxygen species, thereby inducing later insulin resistance and hypertension. INTRODUCTIONEvidence from patients and animal models has indicated that the angiotensin II (Ang II) type 1 receptor (AT 1 receptor) has a major role in the development of insulin resistance and hypertension. 1-4 However, the relationship between timing of the AT 1 receptor activation and the development (and persistence) of changes in insulin sensitivity and blood pressure has not been fully elucidated. Interestingly, the Trial of Preventing Hypertension Study showed that the treatment of prehypertensive patients with the AT 1 receptor blocker (ARB) candesartan for 2 years significantly delayed the progression from pre-hypertension to stage 1 hypertension during the following 2 years. 5 This finding suggests long-lasting effects of transitory activation of the AT 1 receptor in the development of hypertension. The results of the Trial of Preventing Hypertension Study bear certain similarities to those of a study by Holman et al. 6 (United Kingdom Prospective Diabetes Study), indicating the so-called 'legacy effect' . These authors found that the reduction of microvascular events continued for 10 years, in spite of the loss of differences in glycemic control after 10 years of intensive glycemic control had been discontinued. Furthermore, such 'legacy

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“…Furthermore, their range of clinical use has recently been expanded as a result of proven protective effects against renal deterioration in diabetic nephropathy and their favourable metabolic effects, including the delay or prevention of diabetes 29 and possibly hypertension. 30 These two classes of drugs do affect renin-angiotensin cascade at different levels, which lead to different patterns of renin and angiotensin effect that may potentially translate in different clinical consequences. However, whether or not the two classes differ clinically is still open to debate.…”

Section: Angiotensin II Receptor Blockers Versus Ace Inhibitors On Hamentioning

confidence: 99%