ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT

Ceconi, Claudio; Fox, Kim; Remme, W. J.; Simoons, M. L.; Bertrand, M.; Parrinello, Giovanni; Kluft, C.; Blann, Andrew D.; Cokkinos, Dennis V.; Ferrari, Roberto

doi:10.1016/j.cardiores.2006.10.021

Cited by 155 publications

(73 citation statements)

References 33 publications

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“…53,54 In the PERTINENT study, perindopril also improved the endothelial function, and specifically decreased vWf levels. 55 This study extends this observation to demonstrate that ACE inhibition decreases acute endothelial injury during dialysis.…”

Section: Discussionsupporting

confidence: 67%

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Gamboa¹,

Pretorius²,

Todd-Tzanetos³

et al. 2012

Journal of the American Society of Nephrology

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Biomarkers of oxidative stress and inflammation predict cardiovascular events in maintenance hemodialysis patients. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) reduce cardiovascular mortality in the general population, but their benefit in maintenance hemodialysis patients is not fully explored. To test whether ACE inhibitors and ARBs differentially affect markers of oxidative stress, inflammation, and fibrinolysis during hemodialysis, we conducted a randomized, doubleblind, placebo-controlled 333 crossover study. We randomly assigned 15 participants undergoing hemodialysis to placebo, ramipril (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period of 3 weeks in between the treatments. On the morning of the seventh day of drug treatment, participants underwent serial blood sampling during hemodialysis. Neither ramipril nor valsartan affected BP during hemodialysis. Ramipril increased IL-1b concentrations (P=0.02) and decreased IL-10 concentrations (P=0.04) compared with placebo. Valsartan and ramipril both lowered IL-6 levels during dialysis (P,0.01 for each compared with placebo). Valsartan increased F 2 -isoprostane levels, and ramipril suggested a similar trend (P=0.09). Valsartan and ramipril both lowered D-dimer levels (P,0.01 for both), whereas only ramipril seemed to prevent a rise in vWf levels (P=0.04). In summary, during hemodialysis, valsartan induces a greater anti-inflammatory effect compared with ramipril, although ramipril seems to prevent dialysis-induced endothelial dysfunction as measured by levels of vWf. A prospective clinical trial is necessary to determine whether ACE inhibitors and ARBs also differ with respect to their effects on cardiovascular mortality in this population. 23: 334-342, 201223: 334-342, . doi: 10.1681 In ESRD patients, cardiovascular death accounts for .50% of overall mortality and the risk of cardiovascular death is 30 times higher than in the general population. 1,2 Moreover, patients undergoing maintenance hemodialysis (MHD) have a 5-year survival rate of 10% after acute myocardial infarction. 3 Traditional risk factors, as used in Framingham risk scoring, only explain half of the excessive cardiovascular mortality observed in ESRD patients, 4 and it is thought that other factors contribute to the high cardiovascular mortality among ESRD patients. J Am Soc NephrolIncreased oxidative stress and inflammation may contribute to accelerated atherosclerosis and cardiovascular events in patients with MHD. 5,6 Markers of oxidative stress, such as F 2 -isoprostanes, are increased in MHD patients. 7,8 Inflammatory markers, particularly IL-1, IL 6, and TNFa, are also elevated in MHD patients and are associated with

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Section: Discussionsupporting

confidence: 67%

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Gamboa¹,

Pretorius²,

Todd-Tzanetos³

et al. 2012

Journal of the American Society of Nephrology

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“…In a subanalysis of the recent EUROPA study (examining the beneficial effects of ACE-inhibition in patients with stable coronary artery disease), perindopril appeared to increase expression and activity of eNOS by 19% and 27% respectively, as well as a significant reduction in plasma levels of angiotensin II, tumour necrosis factor-α and an increase in bradykinin, nitrate and nitrite 82 .…”

Section: The Renin-angiotensin-aldosterone Systemmentioning

confidence: 98%

Endothelial dysfunction in human essential hypertension

Mordi

Delles

et al. 2016

Journal of Hypertension

125

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Abstract:Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. It is increasingly recognised that this is related to hypertension, although whether it predates hypertension or is a consequence of it is still unknown. In this review we explore the mechanisms of endothelial dysfunction in hypertension, its prognostic significance and methods of pharmacological reversal. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation CONDENSED ABSTRACTEndothelial dysfunction is prevalent in hypertension and has a recognised association with the condition. In this article we review the pathophysiology of endothelial dysfunction in human hypertension, its prognostic significance and methods of pharmacological reversal. We appreciate the opportunity to revise this manuscript again and particularly would like to thank Reviewer whose constructive criticism has certainly improved the manuscript. We have addressed the minor comments suggested as attached to this letter.We are extremely grateful once again to the reviewers and the editors for their detailed critique which has undoubtedly improved the quality of the manuscript.We thank you once again for the opportunity to resubmit our manuscript and look forward to your decision. Yours sincerely Dr Ify Mordi Submission letterReviewer #2:I thank you the author for their last revision: the paper improved quite a lot! Just few points should be still addressed:We thank the reviewer for their positive appraisal of our revised manuscript -we agree that the comments provided have substantially improved the review. We agree with the reviewer that this sentence is out of place. Given the length of the review and the fact that this is covered elsewhere we have now deleted the sentence.-Please move the description of micromyography to the invasive methods as tissue biopsies are necessary.We thank the reviewer for pointing out this error. We have now moved the description of myography to the invasive methods section (page 5). We have no conflict of interest. Endothelial Dysfunction in Human Essential Hypertension Manuscript 2 ABSTRACTAlthough the endothelium has a number of important functions, the term endothelial

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“…14 The Perindopril Dysfunction and Neurohormonal Activation Trail, a substudy of the EUROPA trial, has shown that perindopril reduces the rate of endothelial apoptosis. 15 Increased myocyte apoptosis is an important biological component of remodeling, particularly in elderly patients. All of these hypotheses are being explored in predefined sub-studies of PREAMI.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Cardiac Regeneration by ACE Inhibition Following Donor Heart Myocardial Infarction After Heterotopic Transplantation in Tg Mice

Matsushima

Nakamura

Umemoto

et al. 2008

Circ J

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ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT

Abstract: Abnormal endothelial function occurs in patients with coronary artery disease, and this can be counteracted by angiotensin-converting enzyme inhibition with perindopril. These effects could contribute, at least in part, to explaining the results of the main EUROPA Study.

Cited by 155 publications

References 33 publications

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Endothelial dysfunction in human essential hypertension

Regulation of Cardiac Regeneration by ACE Inhibition Following Donor Heart Myocardial Infarction After Heterotopic Transplantation in Tg Mice

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