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Response to Letter Regarding Article, Effect of Celecoxib on Cardiovascular Events and Blood Pressure in Two Trials for the Prevention of Colorectal Adenomas

Response to Letter Regarding Article, Effect of Celecoxib on Cardiovascular Events and Blood Pressure in Two Trials for the Prevention of Colorectal Adenomas
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  Correspondence Response to Letter Regarding Article, “Effect of Renal Sympathetic Denervation on GlucoseMetabolism in Patients With ResistantHypertension: A Pilot Study” We appreciate the comments of Dr Anyfanti and colleaguesregarding our recent article. 1 The authors are concerned about theinsulin sensitivity assessment methodology, which was based onhomeostasis model assessment-insulin resistance and on the Quali-tative Insulin Sensitivity Check Index instead of on the use of theeuglycemic clamp method. The glucose clamp approach is acceptedas the standard for directly determining metabolic insulin sensitivityin humans; however, several limitations have been discussed in theliterature. 2 We agree that the noninvasive measurements used in ourstudy might have limitations, which were discussed in the article, butthey also have several strengths. Homeostasis model assessment-insulin resistance and the Qualitative Insulin Sensitivity Check Indexwere shown to provide reasonable, reliable parameters for theevaluation of insulin resistance. 2 Both correlate to the results of hyperinsulinemic-euglycemic clamp in healthy subjects, obesity,diabetes mellitus, hypertension, and many other insulin-resistantstates (with correlation coefficients of    0.80), and are associatedwith sympathetic activity. 2,3 Our study was aimed to systematicallyevaluate the changes of glucose metabolism and insulin resistanceafter renal denervation in patients with resistant hypertension in areal-world setting. Therefore, we used noninvasive measures becausethey are more patient-focused and integrated. More recently, in-depth analyses of insulin sensitivity, as measured by the euglycemicclamp method, have been reported in 2 patients with polycysticovary syndrome who underwent renal denervation 4 and will beaddressed in an upcoming extension of our proof-on-principle study.Regardless of the specific methodology used to assess insulinsensitivity, we found significant improvements in glucose metabo-lism and diabetic control during oral glucose tolerance testing andsubstantial reductions in fasting insulin levels. However, despite theplausible concept of the underlying pathophysiology, 5 we totallyagree that the findings of our pilot study have to be proven in largerrandomized, controlled trials to investigate potential cardiovascular,renal, and retinal consequences. Disclosures Dr Sobotka is an employee of Ardian Inc. All authors receivedscientific support from Ardian Inc. Felix Mahfoud, MD Klinik fu¨r Innere Medizin III Universita¨tsklinikum des Saarlandes Homburg/Saar, Germany Markus Schlaich, MD  Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia Ingrid Kindermann, MDChristian Ukena, MDBodo Cremers, MD Klinik fu¨r Innere Medizin III Universita¨tsklinikum des Saarlandes Homburg/Saar, Germany Mathias C. Brandt, MDUta C. Hoppe, MD  Herzzentrum der Universita¨t zu Ko¨lnKlinik III fu¨r Innere MedizinKo¨ln, Germany Oliver Vonend, MDLars C. Rump, MD Klinik fu¨r NephrologieUniversita¨tskliniken Du¨sseldorf  Du¨sseldorf, Germany Paul A. Sobotka, MD The Ohio State UniversityColumbus, OH  Ardian, IncPalo Alto, CA Henry Krum, MBBS, PhD Centre of Cardiovascular Research and Education in Therapeutics Department of Epidemiology and Preventive Medicine Monash University Melbourne, VIC, Australia Murray Esler, MBBS, PhD, FRACP  Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia Michael Bo¨hm, MD Klinik fu¨r Innere Medizin III Universita¨tsklinikum des Saarlandes Homburg/Saar, Germany References 1. Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC,Hoppe UC, Vonend O, Rump LC, Sobotka PA, Krum H, Esler M, Bo¨hm M.Effect of renal sympathetic denervation on glucose metabolism in patientswith resistant hypertension: a pilot study.  Circulation . 2011;123:1940–1946.2. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches forassessing insulin sensitivity and resistance in vivo: advantages, limi-tations, and appropriate usage.  Am J Physiol Endocrinol Metab . 2008;294:E15–E26.3. Grassi G, Dell’Oro R, Facchini A, Quarti Trevano F, Bolla GB, Mancia G.Effect of central and peripheral body fat distribution on sympathetic andbaroreflex function in obese normotensives.  J Hypertens . 2004;22:2363–2369.4. Schlaich MP, Straznicky N, Grima M, Ika-Sari C, Dawood T, Mahfoud F,Lambert E, Chopra R, Socratous F, Hennebry S, Eikelis N, Bohm M, KrumH, Lambert G, Esler MD, Sobotka PA. Renal denervation: a potential newtreatment modality for polycystic ovary syndrome?  J Hypertens . 2011;29:991–996.5. Sobotka P, Mahfoud F, Schlaich M, Hoppe UC, Bo¨hm M, Krum H.Sympatho-renal axis in chronic disease  Clin Res Cardiol.  June 19, 2011. doi10.1007/s00392-011-0335-y. AccessedAugust 22, 2011. ( Circulation . 2011;124:e537.) © 2011 American Heart Association, Inc. Circulation  is available at DOI: 10.1161/CIRCULATIONAHA.111.055723 e537   by guest on May 17, 2016 Downloaded from   Esler and Michael BöhmMurrayC. Brandt, Uta C. Hoppe, Oliver Vonend, Lars C. Rump, Paul A. Sobotka, Henry Krum, Felix Mahfoud, Markus Schlaich, Ingrid Kindermann, Christian Ukena, Bodo Cremers, Mathias Glucose Metabolism in Patients With Resistant Hypertension: A Pilot Study''Response to Letter Regarding Article, ''Effect of Renal Sympathetic Denervation on Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2011 American Heart Association, Inc. All rights published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/CIRCULATIONAHA.111.0557232011;124:e537 Circulation. World Wide Web at: The online version of this article, along with updated information and services, is located on the is online at: Circulation Information about subscribing to Subscriptions: Information about reprints can be found online at: Reprints:  document. Permissions and Rights Question and Answer this process is available in theclick Request Permissions in the middle column of the Web page under Services. Further information aboutOffice. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Circulation in Requests for permissions to reproduce figures, tables, or portions of articles srcinally published Permissions:  by guest on May 17, 2016 Downloaded from 
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