Felix Mahfoud1, Raymond R Townsend2, David E Kandzari3, Kazuomi Kario4, Roland E Schmieder5, Konstantinos Tsioufis6, Stuart Pocock7, Shukri David8, Kiritkumar Patel9, Anjani Rao9, Antony Walton10, Jason E Bloom10, Thomas Weber11, Markus Suppan11, Lucas Lauder12, Sidney A Cohen13, Pamela McKenna14, Martin Fahy14, Michael Böhm12, Michael A Weber15. 1. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany. Electronic address: Felix.Mahfoud@uks.eu. 2. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, Georgia, USA. 4. Department of Cardiovascular Medicine and Department of Sleep and Circadian Cardiology, Jichi Medical University School of Medicine, Tochigi, Japan. 5. Department of Nephrology and Hypertension, Universitätsklinikum Erlangen, Erlangen, Germany. 6. Department of Cardiology, University of Athens, Hippocratio Hospital, Athens, Greece. 7. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom. 8. Department of Cardiology, Providence Hospital, Southfield, Michigan, USA. 9. Department of Cardiology, Saint Joseph Mercy Oakland, Bloomfield Hills, Michigan, USA. 10. Department of Cardiology, The Alfred Hospital, Melbourne, Victoria, Australia. 11. Department of Cardiology, Klinikum Wels-Grieskirchen, Wels, Austria. 12. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany. 13. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Coronary and Renal Denervation Division, Medtronic PLC, Santa Rosa, California, USA. 14. Coronary and Renal Denervation Division, Medtronic PLC, Santa Rosa, California, USA. 15. Department of Medicine, SUNY Downstate College of Medicine, Brooklyn, New York, USA.
Abstract
BACKGROUND: The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. OBJECTIVES: The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. METHODS: Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. RESULTS: Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. CONCLUSIONS: Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749).
BACKGROUND: The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. OBJECTIVES: The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. METHODS: Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. RESULTS: Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. CONCLUSIONS: Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749).
Authors: Thomas Weber; Siegfried Wassertheurer; Christopher C Mayer; Bernhard Hametner; Kathrin Danninger; Raymond R Townsend; Felix Mahfoud; Kazuomi Kario; Martin Fahy; Vanessa DeBruin; Nicole Peterson; Manuela Negoita; Michael A Weber; David E Kandzari; Roland E Schmieder; Konstantinos P Tsioufis; Ronald K Binder; Michael Böhm Journal: Hypertension Date: 2022-05-18 Impact factor: 9.897
Authors: David E Kandzari; Felix Mahfoud; Michael A Weber; Raymond Townsend; Gianfranco Parati; Naomi D L Fisher; Melvin D Lobo; Michael Bloch; Michael Böhm; Andrew S P Sharp; Roland E Schmieder; Michel Azizi; Markus P Schlaich; Vasilios Papademetriou; Ajay J Kirtane; Joost Daemen; Atul Pathak; Christian Ukena; Philipp Lurz; Guido Grassi; Martin Myers; Aloke V Finn; Marie-Claude Morice; Roxana Mehran; Peter Jüni; Gregg W Stone; Mitchell W Krucoff; Paul K Whelton; Konstantinos Tsioufis; Donald E Cutlip; Ernest Spitzer Journal: Circulation Date: 2022-03-14 Impact factor: 29.690