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Yang X, Lin L, Zhang Z, Chen X. Effects of catheter-based renal denervation on renin-aldosterone system, catecholamines, and electrolytes: A systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2022; 24:1537-1546. [PMID: 36321724 PMCID: PMC9731592 DOI: 10.1111/jch.14590] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/26/2022] [Accepted: 10/03/2022] [Indexed: 11/07/2022]
Abstract
In recent years, catheter-based renal denervation (RDN) has emerged as a promising instrumental therapy for hypertension. The interruption of sympathetic nervous system was regarded as a possible mechanism for RDN regulating blood pressure. While the results reflected by renin-angiotensin-aldosterone system (RAAS), catecholamines and electrolytes remained inconsistent and was never systematically assessed. Pubmed, Embase, and Web of Science were comprehensively searched from inception to September 5, 2021. Studies that evaluated the effects of RDN on RAAS, catecholamines, and electrolytes were identified. Primary outcomes were changes in RAAS hormones after RDN, and secondary outcomes involved changes in plasma norepinephrine, serum, and urinary sodium and potassium. Out of 6391 retrieved studies, 20 studies (two randomized controlled studies and 18 observational studies) involving 771 persons were eventually included. Plasma renin activity had a statistically significant reduction after RDN (0.24 ng/mL/h, 95% CI 0.04 to 0.44, P = .02). While no significant change was found regarding plasma aldosterone (1.53 ng/dL, 95% CI -0.61 to 3.67, P = .16), norepinephrine (0.42 nmol/L, 95% -0.51 to 1.35, P = 0.38), serum sodium and potassium (0.16 mmol/L, 95% CI -0.17 to 0.49, P = .34; -0.02 mmol/L, 95% CI -0.09 to 0.04, P = .48, respectively), and urinary sodium and potassium (3.95 mmol/24 h, 95% CI -29.36 to 37.26, P = .82; 10.22 mmol/24 h, 95% CI -12.11 to 32.54, P = .37, respectively). In conclusion, plasma renin activity significantly decreased after RDN, while no significant change was observed in plasma aldosterone, plasma norepinephrine, and serum and urinary electrolytes.
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Affiliation(s)
- Xiangyu Yang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Lede Lin
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhipeng Zhang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoping Chen
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
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Weber T, Wassertheurer S, Mayer CC, Hametner B, Danninger K, Townsend RR, Mahfoud F, Kario K, Fahy M, DeBruin V, Peterson N, Negoita M, Weber MA, Kandzari DE, Schmieder RE, Tsioufis KP, Binder RK, Böhm M. Twenty-Four-Hour Pulsatile Hemodynamics Predict Brachial Blood Pressure Response to Renal Denervation in the SPYRAL HTN-OFF MED Trial. Hypertension 2022; 79:1506-1514. [PMID: 35582957 PMCID: PMC9172874 DOI: 10.1161/hypertensionaha.121.18641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN.
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Affiliation(s)
- Thomas Weber
- Cardiology Department, Klinikum Wels-Grieskirchen, Austria (T.W., K.D., R.K.B.)
| | | | - Christopher C Mayer
- AIT - Austrian Institute of Technology, Vienna, Austria (S.W., C.C.M., B.H.)
| | - Bernhard Hametner
- AIT - Austrian Institute of Technology, Vienna, Austria (S.W., C.C.M., B.H.)
| | - Kathrin Danninger
- Cardiology Department, Klinikum Wels-Grieskirchen, Austria (T.W., K.D., R.K.B.)
| | - Raymond R Townsend
- Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.)
| | - Felix Mahfoud
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany (F.M., M.B.)
| | - Kazuomi Kario
- Jichi Medical University School of Medicine, Tochigi, Japan (K.K.)
| | - Martin Fahy
- Medtronic PLC, Santa Rosa, CA (M.F., V.D., N.P., M.N.)
| | | | | | | | | | | | - Roland E Schmieder
- Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich Alexander University Erlangen Nürnberg, Germany (R.E.S.)
| | - Konstantinos P Tsioufis
- 1st Cardiology Clinic, National and Kapodistrian University of Athens, Hippokration Hospital, Greece (K.P.T.)
| | - Ronald K Binder
- Cardiology Department, Klinikum Wels-Grieskirchen, Austria (T.W., K.D., R.K.B.)
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany (F.M., M.B.)
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3
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Sugimoto H, Hamaoka T, Murai H, Hirai T, Mukai Y, Kusayama T, Takashima S, Kato T, Takata S, Usui S, Sakata K, Kawashiri M, Takamura M. Relationships between muscle sympathetic nerve activity and novel indices of arterial stiffness using single oscillometric cuff in patients with hypertension. Physiol Rep 2022; 10:e15270. [PMID: 35587702 PMCID: PMC9118049 DOI: 10.14814/phy2.15270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 03/31/2022] [Indexed: 06/15/2023] Open
Abstract
The arterial velocity pulse index (AVI) and arterial pressure-volume index (API) have been proposed as new arterial stiffness indices that can be measured using an oscillometric cuff. Sympathetic nerve activity (SNA) contributes to arterial stiffness via increasing vascular smooth muscle tone. However, the associations between SNA and the AVI or API are not understood. The purpose of this study was to evaluate the relationships between muscle sympathetic nerve activity (MSNA) and the AVI or API in healthy individuals and patients with hypertension (HT). Forty healthy individuals (40.1 ± 15.2 years, 8 females) (healthy group) and 40 patients with HT (60.2 ± 13.6, 18 females) (HT group) were included in this study. The AVI, API, MSNA, beat-by-beat blood pressure, and heart rate were recorded simultaneously. The AVI and API were higher in the HT group than in the healthy group (AVI, 26.1 ± 7.6 vs. 16.5 ± 4.0, p < 0.001; API, 31.2 ± 8.6 vs. 25.5 ± 7.2, p = 0.002). MSNA in the HT group was also higher than in the healthy group (p < 0.001). MSNA was correlated with the AVI, but not with the API, in both the healthy group (R = 0.52, p = 0.001) and HT group (R = 0.57, p < 0.001). MSNA was independently correlated with the AVI in multivariate analysis (ß = 0.34, p = 0.001). In conclusion, AVI, obtained by a simple and less user-dependent method, was related to the MSNA in healthy individuals and patients with HT.
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Affiliation(s)
- Hiroyuki Sugimoto
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Takuto Hamaoka
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
- Penn State Heart and Vascular InstitutePennsylvania State University College of MedicineHersheyPennsylvaniaUSA
| | - Hisayoshi Murai
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
- Kanazawa Municipal HospitalKanazawaJapan
| | - Tadayuki Hirai
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Yusuke Mukai
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Takashi Kusayama
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Shinichiro Takashima
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Takeshi Kato
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | | | - Soichiro Usui
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Kenji Sakata
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Masa‐Aki Kawashiri
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
| | - Masayuki Takamura
- Department of Cardiovascular MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
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Pisano A, Iannone LF, Leo A, Russo E, Coppolino G, Bolignano D. Renal denervation for resistant hypertension. Cochrane Database Syst Rev 2021; 11:CD011499. [PMID: 34806762 PMCID: PMC8607757 DOI: 10.1002/14651858.cd011499.pub3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, in the last decade renal sympathetic ablation (renal denervation) has been proposed as a possible therapeutic alternative to treat this condition. OBJECTIVES We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile and kidney function, as well as the potential adverse events related to the procedure. SEARCH METHODS For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 3 November 2020: Cochrane Hypertension's Specialised Register, CENTRAL (2020, Issue 11), Ovid MEDLINE, and Ovid Embase. The World Health Organization International Clinical Trials Registry Platform (via CENTRAL) and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov were searched for ongoing trials. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed study risk of bias. We summarised treatment effects on available clinical outcomes and adverse events using random-effects meta-analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI). Certainty of evidence has been assessed using the GRADE approach. MAIN RESULTS We found 15 eligible studies (1416 participants). In four studies, renal denervation was compared to sham procedure; in the remaining studies, renal denervation was tested against standard or intensified antihypertensive therapy. Most studies had unclear or high risk of bias for allocation concealment and blinding. When compared to control, there was low-certainty evidence that renal denervation had little or no effect on the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (5 studies, 892 participants; RR 0.98, 95% CI 0.33 to 2.95), unstable angina (3 studies, 270 participants; RR 0.51, 95% CI 0.09 to 2.89) or hospitalisation (3 studies, 743 participants; RR 1.24, 95% CI 0.50 to 3.11). Based on moderate-certainty evidence, renal denervation may reduce 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (9 studies, 1045 participants; MD -5.29 mmHg, 95% CI -10.46 to -0.13), ABPM diastolic BP (8 studies, 1004 participants; MD -3.75 mmHg, 95% CI -7.10 to -0.39) and office diastolic BP (8 studies, 1049 participants; MD -4.61 mmHg, 95% CI -8.23 to -0.99). Conversely, this procedure had little or no effect on office systolic BP (10 studies, 1090 participants; MD -5.92 mmHg, 95% CI -12.94 to 1.10). Moderate-certainty evidence suggested that renal denervation may not reduce serum creatinine (5 studies, 721 participants, MD 0.03 mg/dL, 95% CI -0.06 to 0.13) and may not increase the estimated glomerular filtration rate (eGFR) or creatinine clearance (6 studies, 822 participants; MD -2.56 mL/min, 95% CI -7.53 to 2.42). AUTHORS' CONCLUSIONS: In patients with resistant hypertension, there is low-certainty evidence that renal denervation does not improve major cardiovascular outomes and renal function. Conversely, moderate-certainty evidence exists that it may improve 24h ABPM and diastolic office-measured BP. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardised procedural methods are necessary to clarify the utility of this procedure in this population.
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Affiliation(s)
- Anna Pisano
- Institute of Clinical Physiology, CNR - Italian National Council of Research, Reggio Calabria, Italy
| | | | - Antonio Leo
- Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Emilio Russo
- Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Giuseppe Coppolino
- Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Davide Bolignano
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
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Nardone M, Floras JS, Millar PJ. Sympathetic neural modulation of arterial stiffness in humans. Am J Physiol Heart Circ Physiol 2020; 319:H1338-H1346. [PMID: 33035441 DOI: 10.1152/ajpheart.00734.2020] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Elevated large-artery stiffness is recognized as an independent predictor of cardiovascular and all-cause mortality. The mechanisms responsible for such stiffening are incompletely understood. Several recent cross-sectional and acute experimental studies have examined whether sympathetic outflow, quantified by microneurographic measures of muscle sympathetic nerve activity (MSNA), can modulate large-artery stiffness in humans. A major methodological challenge of this research has been the capacity to evaluate the independent neural contribution without influencing the dynamic blood pressure dependence of arterial stiffness. The focus of this review is to summarize the evidence examining 1) the relationship between resting MSNA and large-artery stiffness, as determined by carotid-femoral pulse wave velocity or pulse wave reflection characteristics (i.e., augmentation index) in men and women; 2) the effects of acute sympathoexcitatory or sympathoinhibitory maneuvers on carotid-femoral pulse wave velocity and augmentation index; and 3) the influence of sustained increases or decreases in sympathetic neurotransmitter release or circulating catecholamines on large-artery stiffness. The present results highlight the growing evidence that the sympathetic nervous system is capable of modulating arterial stiffness independent of prevailing hemodynamics and vasomotor tone.
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Affiliation(s)
- Massimo Nardone
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - John S Floras
- University Health Network and Mount Sinai Hospital, Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | - Philip J Millar
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.,Toronto General Hospital Research Institute, Toronto, Ontario, Canada
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Ambulatory arterial stiffness index as a predictor of blood pressure response to renal denervation. J Hypertens 2019; 36:1414-1422. [PMID: 29465712 DOI: 10.1097/hjh.0000000000001682] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Renal denervation (RDN) can reduce blood pressure (BP) in patients with resistant hypertension, but less so in patients with isolated systolic hypertension. A possible explanation is that patients with stiffer arteries may have lesser neural contribution to their hypertension. METHOD We hypothesized that arterial stiffness predicts the response to RDN. From ambulatory BP monitoring (ABPM), ambulatory arterial stiffness index (AASI) was calculated as 1 - the regression slope of DBP versus SBP. RESULTS In 111 patients with resistant hypertension, RDN reduced office and 24-h SBP after 3, 6, and 12 months (by -11 ± 22, -11 ± 25, -14 ± 21 mmHg for office, and -4 ± 11, -5 ± 12, -5 ± 15 mmHg for 24-h SBP, respectively, P < 0.01). Patients with baseline AASI above the median (>0.51) showed no change in 24-h SBP at 6 months after RDN (-0.4 ± 12.3 mmHg, P > 0.05), whereas an AASI below 0.51was associated with a marked reduction (-9.3 ± 11.0 mmHg, P < 0.01). Across AASI quartiles, patients in the highest quartile (AASI ≥ 0.60) had lower muscle sympathetic nerve activity than the other three quartiles (39 ± 13 versus 49 ± 13 bursts/min, P = 0.035). The responder rate, defined as a 24-h SBP reduction of at least 5% was 58% in the lowest AASI quartile (<0.45) and 16% in the highest quartile (≥0.60). After adjustment for age, sex, BMI, office and 24-h SBP, an AASI less than 0.51predicted those who respond to RDN (odds ratio 3.46, P = 0.04). CONCLUSION We conclude that in patients with resistant hypertension, a lower AASI is an independent predictor of the BP response to RDN, possibly explained by a more pronounced neurogenic rather than biomechanical contribution to their BP elevation.
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Millar PJ, Notarius CF, Haruki N, Floras JS. Heart Failure-Specific Relationship Between Muscle Sympathetic Nerve Activity and Aortic Wave Reflection. J Card Fail 2019; 25:404-408. [PMID: 30862489 DOI: 10.1016/j.cardfail.2019.03.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 02/26/2019] [Accepted: 03/06/2019] [Indexed: 10/27/2022]
Abstract
BACKGROUND Reflected arterial waves contribute to left ventricular (LV) afterload. Heart failure patients with reduced ejection fraction (HFrEF) are afterload sensitive and sympathetically activated. We tested the hypothesis that HFrEF patients exhibit a positive relationship between sympathetic vasoconstrictor discharge and aortic wave reflection. METHODS Sixteen treated patients with HFrEF (61 ± 9 years of age, left ventricular ejection fraction 30 ± 7%, 3 women) and 16 similar-aged healthy control subjects (57 ± 7 years of age, 4 women) underwent noninvasive measurements of radial pulse waveforms (applanation tonometry) to calculate central blood pressures and aortic wave reflection characteristics: augmentation pressure (AP), augmentation index (AIx), and AIx corrected to a heart rate of 75 beats/min (AIx@75). Muscle sympathetic nerve activity (MSNA) burst frequency was recorded from the fibular nerve (microneurography). RESULTS HFrEF patients had higher AIx (26 ± 9 vs 17 ± 15%; P < .05) and MSNA burst frequency (48 ± 7 vs 39 ± 11 bursts/min; P < .05) and lower central diastolic pressure than control subjects (64 ± 8 vs 70 ± 9 mm Hg; P = 0.05). There were no between-group differences in heart rate, other measures of blood pressure (brachial and central; P > .05), AP (11 ± 5 vs 7 ± 8 mm Hg; P = 0.11), or AIx@75 (19 ± 9 vs 13 ± 11%,-P = 0.14). MSNA correlated positively with AP (r = 0.50; P < .05), AIx (r = 0.51; P < .05), and AIx@75 (r = 0.54; P < .05) in HFrEF patients but not in control subjects (r = 0.002-0.18; P > 0.49). CONCLUSIONS In patients with HFrEF, but not similarly aged healthy subjects, indices of aortic wave reflection correlate positively with MSNA. By increasing LV afterload, such neurovascular coupling could impair LV performance and worsen heart failure symptoms. Therapies that attenuate neurogenic vasoconstriction may benefit HFrEF patients by diminishing arterial wave reflection.
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Affiliation(s)
- Philip J Millar
- University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Catherine F Notarius
- University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Nobuhiko Haruki
- University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - John S Floras
- University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
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Clinical factors predicting blood pressure reduction after catheter-based renal denervation. ADVANCES IN INTERVENTIONAL CARDIOLOGY 2018; 14:270-275. [PMID: 30302103 PMCID: PMC6173095 DOI: 10.5114/aic.2018.78330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 06/04/2018] [Indexed: 11/19/2022] Open
Abstract
Introduction Renal denervation (RD) can lead to a significant and sustained decrease in mean values of arterial blood pressure (BP). However, there is still a subset of patients without a significant BP drop after RD (non-responders). Aim To compare characteristics of RD responders to RD non-responders and to identify the clinical predictors of BP reduction. Material and methods Thirty-one patients with diagnosed resistant hypertension underwent RD. Three years after RD the analysis of BP reduction was performed in regard to the baseline patient characteristics. Results After 3 years’ follow-up a 10% or more reduction of systolic baseline BP was observed in 74% of patients. Ten percent or more reduction of diastolic baseline BP was observed in 71% of patients. Among responders we observed the following risk factors: hypercholesterolemia in 70%, body mass index (BMI) > 30 kg/m2 in 55%, diabetes mellitus in 35%, current smoking in 5%. Comorbidity included coronary artery disease (CAD) in 30%, cardiomyopathy in 10%, chronic obstructive pulmonary disease (COPD) in 10%, renal insufficiency in 10%, and ventricular arrhythmia in 5%. Among non-responders we observed the following risk factors: hypercholesterolemia in 38%, diabetes mellitus type 2 in 38% and BMI > 30 kg/m2 in 86%. Comorbidity included CAD in 50% and cardiomyopathy in 13% of patients. Conclusions A 10% reduction of systolic baseline BP was observed in 74% of patients 3 years after renal denervation. Clinical factors like COPD, chronic kidney disease 3a, female sex and hypercholesterolemia increase the chances of effective reduction of BP.
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10
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Sata Y, Head GA, Esler MD, Schlaich MP. Reply. J Hypertens 2018; 36:1606-1607. [PMID: 29847455 DOI: 10.1097/hjh.0000000000001765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Yusuke Sata
- Neurovascular Hypertension and Kidney Disease Laboratory.,Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria
| | - Geoffrey A Head
- Neuropharmacology Laboratory, Baker Heart and Diabetes Institute
| | - Murray D Esler
- Neurovascular Hypertension and Kidney Disease Laboratory.,Department of Cardiovascular Medicine, Alfred Hospital
| | - Markus P Schlaich
- Neurovascular Hypertension and Kidney Disease Laboratory.,Department of Cardiovascular Medicine, Alfred Hospital.,Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria.,Royal Perth Hospital Unit, Dobney Hypertension Centre, School of Medicine, University of Western Australia, Perth, Western Australia, Australia
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11
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Völz S, Andersson B, Ljungman C, Gan LM, Rundqvist B, Svedlund S. Effect of renal denervation on coronary flow reserve in patients with resistant hypertension. Clin Physiol Funct Imaging 2018; 39:15-21. [PMID: 29761608 DOI: 10.1111/cpf.12523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/12/2018] [Indexed: 11/30/2022]
Abstract
Renal denervation (RDN) is a potential modality in the treatment of patients with resistant hypertension (RH) and has shown beneficial effect on a variety of cardiovascular surrogate markers. Coronary flow reserve, as assessed by transthoracic Doppler echocardiography (TDE-CFR) is impaired in patients with hypertension and is an independent predictor of cardiac morbidity. However, data on the effect of RDN on TDE-CFR are scarce. The main objective of this study was to assess the effect of RDN on TDE-CFR. Twenty-six consecutive patients with RH (9 female and 17 male; mean age 62 ± 8 years; mean number of antihypertensive drugs 4·2 ± 1·6) underwent bilateral RDN. CFR was assessed at baseline and 6 months after intervention. Mean flow velocity was measured in the left anterior descending artery by transthoracic Doppler echocardiography at baseline and during adenosine infusion (TDE-CFR). Systolic office blood pressure was reduced at follow-up (174 ± 24 versus 162 ± 27 mmHG; P = 0·01). Mean systolic ambulatory blood pressure decreased from 151 ± 21 to 147 ± 18 (P = 0·17). TDE-CFR remained unchanged 6 months after intervention (2·7 ± 0·6 versus 2·7 ± 0·7; P = 0·67). In conclusion, renal denervation was not associated with any changes in regard to coronary flow reserve at 6-month follow-up.
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Affiliation(s)
- Sebastian Völz
- Department of Cardiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
| | - Bert Andersson
- Department of Cardiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
| | - Charlotta Ljungman
- Department of Cardiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
| | - Li-Ming Gan
- Department of Cardiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.,CVMD IMED, Astra Zeneca, Mölndal, Sweden
| | - Bengt Rundqvist
- Department of Cardiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
| | - Sara Svedlund
- Department of Clinical Physiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
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12
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Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial. Clin Res Cardiol 2018. [PMID: 29520698 PMCID: PMC6060801 DOI: 10.1007/s00392-018-1229-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Renal sympathetic denervation (RDN) is under investigation as a treatment option in patients with resistant hypertension (RH). Determinants of arterial compliance may, however, help to predict the BP response to therapy. Aortic distensibility (AD) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR. This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes. We analyzed data of 65 patients with RH included in a multicenter trial. RDN was performed in all participants. A standardized CMR protocol was utilized at baseline and at 6-month follow-up. AD was determined as the change in cross-sectional aortic area per unit change in BP. Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg (p < 0.001) 6 months after RDN. Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm2 (p = 0.011). AD improved significantly by 33% from 1.52 ± 0.82 to 2.02 ± 0.93 × 10−3 mmHg−1 (p < 0.001). Increase of AD at follow-up was significantly more pronounced in younger patients (p = 0.005) and responders to RDN (p = 0.002). Patients with high-baseline AD were significantly younger (61.4 ± 10.1 vs. 67.1 ± 8.4 years, p = 0.022). However, there was no significant correlation of baseline AD to response to RDN. AD is improved after RDN across all age groups. Importantly, these improvements appear to be unrelated to observed BP changes, suggesting that RDN may have direct effects on the central vasculature.
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Nardone M, Incognito AV, Millar PJ. Evidence for Pressure-Independent Sympathetic Modulation of Central Pulse Wave Velocity. J Am Heart Assoc 2018; 7:JAHA.117.007971. [PMID: 29378730 PMCID: PMC5850264 DOI: 10.1161/jaha.117.007971] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Background Whether the sympathetic nervous system can directly alter central aortic stiffness remains controversial, mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure. Methods and Results To address this limitation, we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation. Blood pressure and carotid‐femoral aortic pulse wave velocity (cf‐PWV) were measured in 32 healthy participants (24±2 years; women: n=15) before and during 12‐minute applications of low‐level lower body negative pressure; −7 mm Hg) and lower body positive pressure; +7 mm Hg), applied in a random order. Fibular nerve microneurography was used to collect muscle sympathetic nerve activity (MSNA) in a subset (n=8) to confirm peripheral sympathetic responses. During lower body negative pressure, heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05); MSNA burst frequency (+15%; P=0.007), total MSNA (+44%; P=0.006), and cf‐PWV (∆+0.3±0.2 m/s; P<0.001) increased. In total, 28 (88%) of participants observed an increase in cf‐PWV greater than the baseline typical error of measurement. During lower body positive pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05), though blood pressure increased (P<0.05) and pulse pressure decreased (P=0.01); MSNA burst frequency (−4%; P=0.37), total MSNA (−7%; P=0.89), and cf‐PWV (∆0.0±0.2 m/s; P=0.68) were not statistically different. Conclusions These findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV in young participants independent of a change in distending or pulsatile blood pressure or heart rate.
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Affiliation(s)
- Massimo Nardone
- Department of Kinesiology, University of Guelph-Humber, Toronto, Ontario, Canada
| | - Anthony V Incognito
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Philip J Millar
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada .,Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, Canada
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Okamura K, Shirai K, Okuda T, Urata H. The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation. Intern Med 2018; 57:1-12. [PMID: 29033430 PMCID: PMC5799049 DOI: 10.2169/internalmedicine.9059-17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.
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Affiliation(s)
- Keisuke Okamura
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Japan
| | - Kazuyuki Shirai
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Japan
| | - Tetsu Okuda
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Japan
| | - Hidenori Urata
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Japan
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15
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Peters CD, Mathiassen ON, Vase H, Bech Nørgaard J, Christensen KL, Schroeder AP, Rickers HJVH, Opstrup UK, Poulsen PL, Langfeldt S, Andersen G, Hansen KW, Bøtker HE, Engholm M, Bertelsen JB, Pedersen EB, Kaltoft A, Buus NH. The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial). Blood Press 2017; 26:366-380. [PMID: 28830251 DOI: 10.1080/08037051.2017.1368368] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 08/13/2017] [Accepted: 08/14/2017] [Indexed: 10/19/2022]
Abstract
OBJECTIVES To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension. METHODS ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity FlexTM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor®-device. RESULTS Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN. CONCLUSIONS In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.
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Affiliation(s)
| | | | - Henrik Vase
- b Department of Cardiology , Aarhus University Hospital , Aarhus , Denmark
| | - Jesper Bech Nørgaard
- c University Clinic in Nephrology and Hypertension, Holstebro Hospital , Holstebro , Denmark
| | | | | | | | | | | | - Sten Langfeldt
- g Department of Radiology , Aarhus University Hospital , Skejby , Denmark
| | - Gratien Andersen
- g Department of Radiology , Aarhus University Hospital , Skejby , Denmark
| | | | - Hans Erik Bøtker
- a Department of Renal Medicine , Aarhus University Hospital , Aarhus , Denmark
| | - Morten Engholm
- b Department of Cardiology , Aarhus University Hospital , Aarhus , Denmark
| | | | | | - Anne Kaltoft
- b Department of Cardiology , Aarhus University Hospital , Aarhus , Denmark
| | - Niels Henrik Buus
- i Department of Nephrology , Aalborg University Hospital , Aalborg , Denmark
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Barber-Chamoux N, Esler MD. Predictive factors for successful renal denervation: should we use them in clinical trials? Eur J Clin Invest 2017; 47:860-867. [PMID: 28771706 DOI: 10.1111/eci.12792] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 07/29/2017] [Indexed: 01/01/2023]
Abstract
Renal denervation (RDN) is facing various challenges to its initial claimed value in hypertension treatment. Major concerns are the choice of the patients and the technical efficacy of the RDN. Different factors have been described as predicting the capacity of RDN to decrease blood pressure. These factors are related to the patients, the procedure and the tools to confirm successful neural ablation. Their use in future trials should help to improve RDN trials understanding and outcomes. This review summarizes the different predictive factors available and their potential benefits in patient selection and in procedure guidance.
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Affiliation(s)
- Nicolas Barber-Chamoux
- Cardiology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.,Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia
| | - Murray D Esler
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia.,Heart Centre, Alfred Hospital, Melbourne, Vic., Australia
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Musialowska D, Zbroch E, Koc-Zorawska E, Musialowski P, Malyszko J. Endocan Concentration in Patients With Primary Hypertension. Angiology 2017; 69:483-489. [DOI: 10.1177/0003319717736158] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammation and endothelial dysfunction may play an important role in the multifactorial pathogenesis of hypertension. Endocan is also thought to play a role in cell adhesion and inflammatory disorders. The aim of the study was to compare endocan concentrations in patients with primary hypertension and healthy volunteers. There were 104 patients with hypertension (study group) and 21 healthy volunteers (control group). The correlation between endocan, catecholamines, and blood pressure control in patients with primary hypertension and the control group was analyzed. The median endocan concentration in the study group (2.03 ng/mL) was significantly higher than in the control group (1.09 ng/mL, P = .0001). Endocan concentration was correlated positively with renalase ( r = .2, P = .047) and norepinephrine ( r = .25, P = .02). Negative correlation was observed between endocan and body mass index ( r = −.25, P = .016) and leukocyte count ( r = −.36, P = .0004). The present study reports higher plasma endocan concentration in patients with treated, well-controlled primary hypertension compared with healthy volunteers. The higher endocan concentration in the study group may reflect endothelial dysfunction in this population.
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Affiliation(s)
- Dominika Musialowska
- Second Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland
| | - Edyta Zbroch
- Second Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland
| | - Ewa Koc-Zorawska
- Second Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland
| | - Piotr Musialowski
- Second Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland
| | - Jolanta Malyszko
- Second Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland
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Hildreth CM, Boyd R, Kouchaki Z, Butlin M, Avolio AP, Pilowsky PM, Phillips JK. Increased arterial stiffness does not respond to renal denervation in an animal model of secondary hypertension. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2017; 2017:258-261. [PMID: 29059859 DOI: 10.1109/embc.2017.8036811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Renal denervation is a novel device based therapy promoted to reduce high blood pressure. We examined the impact of renal denervation on systolic blood pressure, renal function, and arterial stiffness in the Lewis Polycystic Kidney disease (LPK) rodent model of kidney disease. Animals were subjected to bilateral renal denervation or sham surgeries at age 6 and 12 weeks. Systolic blood pressure was monitored by tail-cuff plethysmography and renal function by urinalysis and creatinine clearance. At age 16 weeks, beat-to-beat aortic pulse wave velocity as a functional indicator of arterial stiffness was determined. Renal denervation produced an overall reduction in blood pressure in the LPK [(denervated 164±4 vs. sham-operated 180±6 mmHg, n = 6 per group, P=0.003)] and delayed, but did not prevent, the decline in renal function. Aortic pulse wave velocity was markedly elevated in the LPK compared with Lewis and was not altered by renal denervation in the LPK however a reduction was seen in the control Lewis animals. These results support the hypothesis that renal nerves contribute to secondary hypertension in conditions such as kidney disease.
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Schlaich MP. Renal Sympathetic Denervation: A Viable Option for Treating Resistant Hypertension. Am J Hypertens 2017; 30:847-856. [PMID: 28338871 DOI: 10.1093/ajh/hpx033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 02/12/2017] [Indexed: 01/20/2023] Open
Abstract
Accumulating evidence from mainly uncontrolled clinical studies with various types of ablation catheters have shown that renal denervation (RDN) can be applied safely and is effective in lowering blood pressure (BP) in patients with treatment-resistant hypertension. Sustained BP lowering has been documented up to 3 years. Furthermore, RDN has been associated with regression of target organ damage, such as left ventricular hypertrophy, arterial stiffness, and others. Several studies indicate potential benefit in other common clinical conditions associated with increased sympathetic tone including chronic kidney disease and heart failure. However, the recently published Symplicity HTN-3 study, the largest and most rigorously designed sham-controlled clinical trial, while confirming the safety of the procedure, failed to demonstrate a BP lowering effect beyond that of a sham procedure in patients with resistant hypertension. Efforts to unravel the reasons for the discrepant results from Symplicity HTN-3 have focused on a range of potential confounders including anatomical and procedural aspects. Indeed, data from post-hoc analyses indicate that sufficient RDN may not have been achieved in the majority of patients in Symplicity HTN-3. Furthermore, recent evidence from human postmortem and functional animal studies revealed new insights into the anatomical distribution of renal nerves and their accessibility by intravascular approaches. Initial results from recent clinical trials integrating these important findings indeed seem to confirm that RDN remains a viable option for the treatment of hypertension. Thorough further investigations will be key to determine the true potential of RDN in clinical conditions characterized by increased sympathetic drive.
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Affiliation(s)
- Markus P Schlaich
- Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia
- Cardiology Department, Royal Perth Hospital, Perth, Western Australia, Australia
- Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
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20
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Tsioufis C, Ziakas A, Dimitriadis K, Davlouros P, Marketou M, Kasiakogias A, Thomopoulos C, Petroglou D, Tsiachris D, Doumas M, Skalidis E, Karvounis C, Alexopoulos D, Vardas P, Kallikazaros I, Stefanadis C, Papademetriou V, Tousoulis D. Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry. Clin Res Cardiol 2017; 106:322-330. [PMID: 27957627 DOI: 10.1007/s00392-016-1056-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 11/22/2016] [Indexed: 12/28/2022]
Abstract
BACKGROUND/INTRODUCTION The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. METHODS In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m2; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. RESULTS Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 and -29/-12 mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9 mmHg, respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10-mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24-h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. CONCLUSIONS In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.
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Affiliation(s)
- C Tsioufis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece.
| | - A Ziakas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - K Dimitriadis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - P Davlouros
- Department of Cardiology, Patras University Hospital, Patras, Greece
| | - M Marketou
- Cardiology Department, Heraklion University Hospital, Crete, Greece
| | - A Kasiakogias
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - C Thomopoulos
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - D Petroglou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - D Tsiachris
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - M Doumas
- 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - E Skalidis
- Cardiology Department, Heraklion University Hospital, Crete, Greece
| | - C Karvounis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - D Alexopoulos
- Department of Cardiology, Attikon University Hospital, Athens, Greece
| | - P Vardas
- Cardiology Department, Heraklion University Hospital, Crete, Greece
| | - I Kallikazaros
- Cardiology Department, Hippokration Hospital, Athens, Greece
| | - C Stefanadis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - V Papademetriou
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - D Tousoulis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
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Coppolino G, Pisano A, Rivoli L, Bolignano D, Cochrane Hypertension Group. Renal denervation for resistant hypertension. Cochrane Database Syst Rev 2017; 2:CD011499. [PMID: 28220472 PMCID: PMC6464209 DOI: 10.1002/14651858.cd011499.pub2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications, or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, renal sympathetic ablation (renal denervation) has been recently proposed as a possible therapeutic alternative to treat this condition. OBJECTIVES We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile, and kidney function, as well as the potential adverse events related to the procedure. SEARCH METHODS We searched the following databases to 17 February 2016 using relevant search terms: the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed study risks of bias. We summarised treatment effects on available clinical outcomes and adverse events using random-effects meta-analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI). MAIN RESULTS We found 12 eligible studies (1149 participants). In four studies, renal denervation was compared to sham procedure; one study compared a proximal ablation to a complete renal artery denervation; in the remaining, renal denervation was tested against standard or intensified antihypertensive therapy.None of the included trials was designed to look at hard clinical end points as primary outcomes.When compared to control, there was low quality evidence that renal denervation did not reduce the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (4 studies, 823 participants; RR 1.15, 95% CI 0.36 to 3.72), or unstable angina (2 studies, 201 participants; RR 0.63, 95% CI 0.08 to 5.06), and moderate quality evidence that it had no effect on 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (5 studies, 797 participants; MD 0.28 mmHg, 95% CI -3.74 to 4.29), diastolic BP (4 studies, 756 participants; MD 0.93 mmHg, 95% CI -4.50 to 6.36), office measured systolic BP (6 studies, 886 participants; MD -4.08 mmHg, 95% CI -15.26 to 7.11), or diastolic BP (5 studies, 845 participants; MD -1.30 mmHg, 95% CI -7.30 to 4.69). Furthermore, low quality evidence suggested that this procedure produced no effect on either serum creatinine (3 studies, 736 participants, MD 0.01 mg/dL; 95% CI -0.12 to 0.14), estimated glomerular filtration rate (eGFR), or creatinine clearance (4 studies, 837 participants; MD -2.09 mL/min, 95% CI -8.12 to 3.95). Based on low-quality evidence, renal denervation significantly increased bradycardia episodes compared to control (3 studies, 220 participants; RR 6.63, 95% CI 1.19 to 36.84), while the risk of other adverse events was comparable or not assessable.Data were sparse or absent for all cause mortality, hospitalisation, fatal cardiovascular events, quality of life, atrial fibrillation episodes, left ventricular hypertrophy, sleep apnoea severity, need for renal replacement therapy, and metabolic profile.The quality of the evidence was low for cardiovascular outcomes and adverse events and moderate for lack of effect on blood pressure and renal function. AUTHORS' CONCLUSIONS In patients with resistant hypertension, there is low quality evidence that renal denervation does not change major cardiovascular events, and renal function. There was moderate quality evidence that it does not change blood pressure and and low quality evidence that it caused an increaseof bradycardia episodes. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardized procedural methods are necessary to clarify the utility of this procedure in this population.
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Affiliation(s)
- Giuseppe Coppolino
- "Pugliese‐Ciaccio" General HospitalNephrology and Dialysis UnitViale pio XCatanzaroCatanzaroItaly88100
| | - Anna Pisano
- CNR ‐ Italian National Council of ResearchInstitute of Clinical PhysiologyCNR‐IFC Via Vallone Petrara c/o Ospedali RiunitiReggio CalabriaItaly89100
| | - Laura Rivoli
- University "Magna Graecia"Department of Medical and Surgical Sciences, Nephrology and Dialysis UnitViale EuropaCatanzaroItaly88100
| | - Davide Bolignano
- CNR ‐ Italian National Council of ResearchInstitute of Clinical PhysiologyCNR‐IFC Via Vallone Petrara c/o Ospedali RiunitiReggio CalabriaItaly89100
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Low dose-eplerenone treatment decreases aortic stiffness in patients with resistant hypertension. J Clin Hypertens (Greenwich) 2017; 19:669-676. [DOI: 10.1111/jch.12986] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 12/13/2016] [Accepted: 12/25/2016] [Indexed: 11/26/2022]
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Zaldivia MTK, Rivera J, Hering D, Marusic P, Sata Y, Lim B, Eikelis N, Lee R, Lambert GW, Esler MD, Htun NM, Duval J, Hammond L, Eisenhardt SU, Flierl U, Schlaich MP, Peter K. Renal Denervation Reduces Monocyte Activation and Monocyte-Platelet Aggregate Formation: An Anti-Inflammatory Effect Relevant for Cardiovascular Risk. Hypertension 2016; 69:323-331. [PMID: 27956575 DOI: 10.1161/hypertensionaha.116.08373] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 09/17/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023]
Abstract
Overactivation of renal sympathetic nervous system and low-grade systemic inflammation are common features of hypertension. Renal denervation (RDN) reduces sympathetic activity in patients with resistant hypertension. However, its effect on systemic inflammation has not been examined. We prospectively investigated the effect of RDN on monocyte activation and inflammation in patients with uncontrolled hypertension scheduled for RDN. Ambulatory blood pressure, monocyte, and monocyte subset activation and inflammatory markers were assessed at baseline, 3 months, and 6 months after procedure in 42 patients. RDN significantly lowered blood pressure at 3 months (150.5±11.2/81.0±11.2 mm Hg to 144.7±11.8/77.9±11.0 mm Hg), which was sustained at 6 months (144.7±13.8/78.6±11.0 mm Hg). Activation status of monocytes significantly decreased at 3 months (P<0.01) and 6 months (P<0.01) after the procedure. In particular, classical monocyte activation was reduced at 6 months (P<0.05). Similarly, we observed a reduction of several inflammatory markers, including monocyte-platelet aggregates (3 months, P<0.01), plasma monocyte chemoattractant protein-1 levels (3 months, P<0.0001; 6 months, P<0.05), interleukin-1β (3 months, P<0.05; 6 months, P<0.05), tumor necrosis factor-α (3 months, P<0.01; 6 months, P<0.05), and interleukin-12 (3 months, P<0.01; 6 months, P<0.05). A positive correlation was observed between muscle sympathetic nerve activity and monocyte activation before and after the procedure. These results indicate that inhibition of sympathetic activity via RDN is associated with a reduction of monocyte activation and other inflammatory markers in hypertensive patients. These findings point to a direct interaction between the inflammatory and sympathetic nervous system, which is of central relevance for the understanding of beneficial cardiovascular effects of RDN.
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Affiliation(s)
- Maria T K Zaldivia
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Jennifer Rivera
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Dagmara Hering
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Petra Marusic
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Yusuke Sata
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Bock Lim
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Nina Eikelis
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Rebecca Lee
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Gavin W Lambert
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Murray D Esler
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Nay M Htun
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Jacqueline Duval
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Louise Hammond
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Steffen U Eisenhardt
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Ulrike Flierl
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Markus P Schlaich
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.)
| | - Karlheinz Peter
- From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
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Device Therapies for Resistant Hypertension. Clin Ther 2016; 38:2152-2158. [DOI: 10.1016/j.clinthera.2016.08.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Revised: 08/21/2016] [Accepted: 08/31/2016] [Indexed: 12/18/2022]
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Fengler K, Rommel KP, Okon T, Schuler G, Lurz P. Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success. World J Cardiol 2016; 8:436-46. [PMID: 27621771 PMCID: PMC4997524 DOI: 10.4330/wjc.v8.i8.436] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 06/21/2016] [Accepted: 07/14/2016] [Indexed: 02/06/2023] Open
Abstract
Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success.
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Affiliation(s)
- Karl Fengler
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Karl Philipp Rommel
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Thomas Okon
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Gerhard Schuler
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Philipp Lurz
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
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Qi XY, Cheng B, Li YL, Wang YF. Renal denervation, adjusted drugs, or combined therapy for resistant hypertension: A meta-regression. Medicine (Baltimore) 2016; 95:e3939. [PMID: 27472671 PMCID: PMC5265808 DOI: 10.1097/md.0000000000003939] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The objective of this study is to systematically evaluate the efficacy of renal denervation (RD), adjusted drugs, or combined therapy for resistant hypertension (RH) through a systematic review and meta-analysis of controlled studies.Publications were comprehensively searched. Studies that investigated the effects of RD and/or adjusted drugs in lowering blood pressure (BP) were included. After quality assessment and data extraction, subgroup analyzes were first performed according to blinding method. Meta-regression and inverted funnel plots were also conducted.A total of 13 studies containing 1604 RH patients were included. Compared with control, the meta-analysis showed that RD significantly reduced office-based BP and ambulatory BP in 6 months in the unblinded studies, while no significant difference was found in the blinded studies. Meta-regression demonstrated the significant influence of blinding method on BP reduction, and further analysis revealed a significant BP reduction compared with baseline even in the control arm of blinded studies. RD had similar effects compared with adjusted drugs, and combined therapy seemed to further reduce the level of BP.The efficacy of RD was different between blinded and unblinded studies, and our data revealed a significant BP-lowering effect in the control arm of blinded studies, which was helpful to explain this finding. Furthermore, RD seemed to be equivalent to adjusted drugs, and also we suggested a potential advantage of combined therapy of RD and adjusted drugs compared with monotherapy for RH. However, more studies are warranted to better address the issue.
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Affiliation(s)
- Xiao-Yu Qi
- Department of Internal Medicine-Cardiovascular, Daqing Oilfield General Hospital, Daqing, China
| | - Bin Cheng
- Department of Pharmacy, Daqing Oilfield General Hospital, Daqing, China
| | - Ying-Li Li
- School of Nursing, Daqing Campus Harbin Medical University, Daqing, China
| | - Yue-Feng Wang
- School of Nursing, Daqing Campus Harbin Medical University, Daqing, China
- Correspondence: Yue-Feng Wang, School of Nursing, Daqing Campus Harbin Medical University, No. 39, Xinyang Road, Gaoxin District, Daqing City 163319, Heilongjiang Province, China (e-mail: )
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Silva JD, Costa M, Gersh BJ, Gonçalves L. Renal denervation in the era of HTN-3. Comprehensive review and glimpse into the future. ACTA ACUST UNITED AC 2016; 10:656-70. [PMID: 27319336 DOI: 10.1016/j.jash.2016.05.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Revised: 05/16/2016] [Accepted: 05/24/2016] [Indexed: 12/17/2022]
Abstract
The pathophysiological role of sympathetic overactivity in conditions such as hypertension has been well documented. Catheter-based renal denervation (RDN) is a minimally invasive percutaneous procedure which aims to disrupt sympathetic nerve afferent and efferent activity through the application of radiofrequency energy directly within the renal artery wall. This technique has emerged as a very promising treatment with dramatic effects on refractory hypertension but also in other conditions in which a sympathetic influence is present. Several studies have evaluated the safety and efficacy of this procedure, presently surrounded by controversy since the recent outcome of Symplicity HTN-3, the first randomized, sham-control trial, which failed to confirm RDN previous reported benefits on BP and cardiovascular risk lowering. Consequently, although some centers halted their RDN programs, research continues and both the concept of denervation and treatment strategies are being redefined to identify patients who can drive the most benefit from this technology. In the United States, the Food and Drug Administration (FDA) has appropriately mandated that RDN remains an investigative procedure and a new generation of sham-controlled trials are ongoing and aimed to assess not only its efficacy against pharmacotherapy but also trials in drug free patients with the objective of demonstrating once and for all whether the procedure actually does lower BP in comparison to a placebo arm. In this article, we present an overview of the sympathetic nervous system and its role in hypertension, examine the current data on RDN, and share some insights and future expectations.
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Affiliation(s)
- Joana Delgado Silva
- Faculty of Medicine, University of Coimbra, Portugal; Department of Cardiology, Coimbra's Hospital and University Centre, General Hospital, Coimbra, Portugal.
| | - Marco Costa
- Department of Cardiology, Coimbra's Hospital and University Centre, General Hospital, Coimbra, Portugal
| | - Bernard J Gersh
- Division of Cardiovascular Diseases, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Lino Gonçalves
- Faculty of Medicine, University of Coimbra, Portugal; Department of Cardiology, Coimbra's Hospital and University Centre, General Hospital, Coimbra, Portugal
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28
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Hering D, Schlaich M. The Role of Central Nervous System Mechanisms in Resistant Hypertension. Curr Hypertens Rep 2016; 17:58. [PMID: 26070453 DOI: 10.1007/s11906-015-0570-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Arterial hypertension remains a primary global health problem with significant impact on cardiovascular morbidity and mortality. The low rate of hypertension control and failure to achieve target blood pressure levels particularly among high-risk patients with resistant hypertension has triggered renewed interest in unravelling the underlying mechanisms to implement therapeutic approaches for better patient management. Here, we summarize the crucial role of neurogenic mechanisms in drug-resistant hypertension, with a specific focus on central control of blood pressure, the factors involved in central integration of afferent signalling to increase sympathetic drive in resistant hypertension, and briefly review recently introduced interventional strategies distinctively targeting sympathetic activation.
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Affiliation(s)
- Dagmara Hering
- School of Medicine and Pharmacology - Royal Perth Hospital Unit, The University of Western Australia, Level 3 MRF Building, Rear 50 Murray Street, Perth, WA, 6000 MDBP: M570, Australia,
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Howard JP, Shun-Shin MJ, Hartley A, Bhatt DL, Krum H, Francis DP. Quantifying the 3 Biases That Lead to Unintentional Overestimation of the Blood Pressure-Lowering Effect of Renal Denervation. Circ Cardiovasc Qual Outcomes 2016; 9:14-22. [PMID: 26758193 DOI: 10.1161/circoutcomes.115.002533] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Accepted: 12/07/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Studies of renal denervation report disparate results. Meta-analysis by trial design may allow quantitative estimation of sources and magnitude of biases in denervation studies. METHODS AND RESULTS One hundred forty nonrandomized, 6 randomized open-label, and 2 randomized blinded studies were analyzed for 2 outcomes: (1) blood pressure changes for nonrandomized, open-label randomized, and blinded studies; and (2) quantification of 3 biases potentially contributing to apparent antihypertensive effects: (a) regression to the mean, (b) asymmetrical data handling, and (c) true blood pressure drops caused by something other than the tested therapy (confounding). Nonrandomized studies and open-label randomized trials reported large reductions in office blood pressure of 23.6 mm Hg (95% confidence interval [CI], 22.0 to 25.3) and 29.1 mm Hg (95% CI, 25.2 to 33.1 mm Hg), respectively. They reported smaller reductions in ambulatory blood pressures (11.2 mm Hg; 95% CI, 10.0 to 12.4). The blinded trials found no significant reduction in blood pressure (2.9 mm Hg; 95% CI, -0.4 to 6.3). Analyses of these data indicate the magnitude of the 3 potential sources of bias to be regression to the mean, -1.01 mm Hg (95% CI, 4.24 to -6.27); asymmetrical data handling, -10.8 mm Hg (95% CI, -8.77 to -12.87); and confounding, -8.3 mm Hg (95% CI, -4.73 to -11.83). CONCLUSIONS Increasingly bias-resistant trial designs report effect sizes of decreasing magnitude. This disparity may be caused by asymmetrical data handling and confounding (eg, increased drug adherence). If these differences are caused by trial design and not by some other differences in patients or procedures, which happen to match the trial design, then randomization alone is not enough: blinding is also needed. This has broad implications across trials of medications and devices.
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Affiliation(s)
- James P Howard
- From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom (J.P.H., M.J.S.-S., A.H., D.P.F.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (H.K.).
| | - Matthew J Shun-Shin
- From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom (J.P.H., M.J.S.-S., A.H., D.P.F.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (H.K.)
| | - Adam Hartley
- From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom (J.P.H., M.J.S.-S., A.H., D.P.F.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (H.K.)
| | - Deepak L Bhatt
- From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom (J.P.H., M.J.S.-S., A.H., D.P.F.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (H.K.)
| | - Henry Krum
- From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom (J.P.H., M.J.S.-S., A.H., D.P.F.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (H.K.)
| | - Darrel P Francis
- From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom (J.P.H., M.J.S.-S., A.H., D.P.F.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (H.K.)
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Hering D, Kara T, Kucharska W, Somers VK, Narkiewicz K. Longitudinal tracking of muscle sympathetic nerve activity and its relationship with blood pressure in subjects with prehypertension. Blood Press 2015; 25:184-92. [PMID: 26654200 DOI: 10.3109/08037051.2015.1121708] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Prehypertension is associated with increased cardiovascular events. While the "tracking phenomenon" is an important longitudinal characteristic of blood pressure (BP), changes in muscle sympathetic nerve activity (MSNA) over time remain unclear. This study tested the hypothesis that MSNA tracking contributes to BP trends in prehypertension. BP and MSNA were assessed in 13 prehypertensive males at rest, during hand grip and mental stressors at baseline and after 8 years. Baseline office BP averaged 127 ± 2/81 ± 2 mmHg and MSNA 24 ± 4 bursts/min. BP increased by 7 ± 2/5 ± 2 mmHg (P < 0.01) and MSNA by 11 ± 2 bursts/min (P < 0.001) at follow-up. SBP and DBP were interrelated at baseline (r = 0.65, P = 0.02) and at follow-up (r = 0.78, P = 0.002). MSNA tracking (r = 0.82; P < 0.001) was similar to BP. MSNA was strongly related to DBP at baseline (r = 0.73; P < 0.01) and follow-up (r = 0.64; P = 0.01), more so than SBP. BMI increased (P < 0.001) at follow-up but was unrelated to BP or MSNA. Despite comparable pressor and cardiac increases to handgrip and mental stressors, sympathetic responses were blunted, more pronounced to isometric test (P < 0.006) at follow-up. In conclusion, the trend in MSNA corresponds with BP changes over time suggesting that tonic sympathetic activation may contribute to time-related increase in resting BP and the development of sustained hypertension in prehypertension.
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Affiliation(s)
- Dagmara Hering
- a Department of Hypertension and Diabetology , Medical University of Gdansk , Gdansk , Poland ;,b International Clinical Research Center, Department of Cardiovascular Diseases , St. Anne's University Hospital Brno , Brno , Czech Republic
| | - Tomas Kara
- b International Clinical Research Center, Department of Cardiovascular Diseases , St. Anne's University Hospital Brno , Brno , Czech Republic ;,c Divisions of Cardiovascular Disease and Hypertension , Mayo Clinic , Rochester , MN , USA
| | - Wiesława Kucharska
- a Department of Hypertension and Diabetology , Medical University of Gdansk , Gdansk , Poland
| | - Virend K Somers
- c Divisions of Cardiovascular Disease and Hypertension , Mayo Clinic , Rochester , MN , USA
| | - Krzysztof Narkiewicz
- a Department of Hypertension and Diabetology , Medical University of Gdansk , Gdansk , Poland ;,b International Clinical Research Center, Department of Cardiovascular Diseases , St. Anne's University Hospital Brno , Brno , Czech Republic ;,c Divisions of Cardiovascular Disease and Hypertension , Mayo Clinic , Rochester , MN , USA
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Patel HC, Hayward C, Vassiliou V, Patel K, Howard JP, Di Mario C. Renal denervation for the management of resistant hypertension. Integr Blood Press Control 2015; 8:57-69. [PMID: 26672761 PMCID: PMC4675644 DOI: 10.2147/ibpc.s65632] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.
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Affiliation(s)
- Hitesh C Patel
- NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
| | - Carl Hayward
- NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
| | - Vassilis Vassiliou
- NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
| | - Ketna Patel
- Department of Cardiology, Royal Free Hospital, London, UK
| | - James P Howard
- National Heart and Lung Institute, Imperial College, London, UK
| | - Carlo Di Mario
- NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
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Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension. Int J Cardiol 2015; 202:388-93. [PMID: 26432488 DOI: 10.1016/j.ijcard.2015.09.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 06/20/2015] [Accepted: 09/15/2015] [Indexed: 11/21/2022]
Abstract
BACKGROUND Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. METHODS We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. RESULTS RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (P<0.001) but not in groups 2 and 3. Similarly, a significant reduction in resting baseline MSNA was only observed in group 1 (P<0.05). There was no deterioration in kidney function in any group. CONCLUSION While RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences.
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Lambert EA, Straznicky NE, Dixon JB, Lambert GW. Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity? Am J Physiol Heart Circ Physiol 2015; 309:H244-58. [DOI: 10.1152/ajpheart.00096.2015] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 05/11/2015] [Indexed: 02/03/2023]
Abstract
The sympathetic nervous system (SNS) plays a key role in both cardiovascular and metabolic regulation; hence, disturbances in SNS regulation are likely to impact on both cardiovascular and metabolic health. With excess adiposity, in particular when visceral fat accumulation is present, sympathetic activation commonly occurs. Experimental investigations have shown that adipose tissue releases a large number of adipokines, cytokines, and bioactive mediators capable of stimulating the SNS. Activation of the SNS and its interaction with adipose tissue may lead to the development of hypertension and end-organ damage including vascular, cardiac, and renal impairment and in addition lead to metabolic abnormalities, especially insulin resistance. Lifestyle changes such as weight loss and exercise programs considerably improve the cardiovascular and metabolic profile of subjects with obesity and decrease their cardiovascular risk, but unfortunately weight loss is often difficult to achieve and sustain. Pharmacological and device-based approaches to directly or indirectly target the activation of the SNS may offer some benefit in reducing the cardiometabolic consequences of obesity. Preliminary evidence is encouraging, but more trials are needed to investigate whether sympathetic inhibition could be used in obesity to reverse or prevent cardiometabolic disease development. The purpose of this review article is to highlight the current knowledge of the role that SNS plays in obesity and its associated metabolic disorders and to review the potential benefits of sympathoinhibition on metabolic and cardiovascular functions.
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Affiliation(s)
- Elisabeth A. Lambert
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Physiology, Monash University, Clayton, Australia
| | - Nora E. Straznicky
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
| | - John B. Dixon
- Clinical Obesity Research Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and
| | - Gavin W. Lambert
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia
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Tuohy ST, Kyvelou SMG, Gleeson PJ, Daniels FB, Ryan LA, Lappin DW, O'Donnell MJ, Sharif F. The effect of renal sympathetic denervation on nocturnal dipping in patients with resistant hypertension; observational data from a tertiary referral centre in the Republic of Ireland. Ir J Med Sci 2015; 185:635-641. [PMID: 26089291 DOI: 10.1007/s11845-015-1324-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 05/30/2015] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Renal sympathetic denervation (RSD) is an emerging device based treatment for patients with resistant hypertension. Nocturnal dipping (ND) is defined as a decrease in BP of 10-20 % during sleep, and has been shown to be protective against cardiovascular disease. This study examined the effect of RSD on the 24 h BP profile of patients with resistant hypertension. METHODS AND RESULTS The first 23 consecutive patients with resistant hypertension scheduled for renal denervation in a single centre were included. 24 h ambulatory blood pressure monitors (ABPM) were given to patients pre-procedure and 9 months post-procedure. RSD led to a statistically non-significant reduction in overall 24 h ABPM BP (150/85 ± 12/9 vs. 143/84 ± 15/11 mmHg; P > 0.05) despite a reduction in the number of antihypertensive medications (4.9 ± 1.2 vs. 4.3 ± 1.2; P = 0.001). There were improvements in systolic ND 1.7 ± 8 vs. 5.2 ± 8 %; P < 0.05), diastolic ND (5.2 ± 8 vs. 10.2 ± 9 %; P < 0.05) and mean arterial pressure (MAP) ND (4.2 ± 8 vs. 8.0 ± 8 %; P < 0.05). Non-significant changes in ND status were observed in systolic (17 vs. 43 % of participants; P > 0.05), diastolic (30 vs. 43 % of participants; P > 0.05) and MAP (22 vs. 39 % of participants; P > 0.05) measurements. CONCLUSIONS These data suggest that RSD may lead to an improvement in nocturnal dipping in selected patients with resistant hypertension. This may have cardiovascular benefits even if reduction in BP is not achieved with RSD.
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Affiliation(s)
- S T Tuohy
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland.
| | - S-M G Kyvelou
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland
| | - P J Gleeson
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland
| | - F B Daniels
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland
| | - L A Ryan
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland
| | - D W Lappin
- Department of Nephrology, Galway University Hospital, Galway, Republic of Ireland
| | - M J O'Donnell
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland.,Clinical Research Facility, National University of Ireland, Galway, Republic of Ireland
| | - F Sharif
- Department of Cardiology, Galway University Hospital, Galway, Republic of Ireland.,Clinical Research Facility, National University of Ireland, Galway, Republic of Ireland
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Tanındı A, Erkan AF, Alhan A, Töre HF. Arterial stiffness and central arterial wave reflection are associated with serum uric acid, total bilirubin, and neutrophil-to-lymphocyte ratio in patients with coronary artery disease. Anatol J Cardiol 2015; 15:396-403. [PMID: 25430407 PMCID: PMC5779177 DOI: 10.5152/akd.2014.5447] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2014] [Indexed: 01/12/2023] Open
Abstract
OBJECTIVE Total bilirubin (TB) was recently recognized as an endogenous anti-inflammatory and anti-oxidant molecule. Uric acid (UA) takes part in cardiovascular diseases by inducing oxidative stress, inflammation, and endothelial dysfunction. We assessed the relationship between serum TB levels, serum UA levels, and inflammatory status assessed by neutrophil-to-lymphocyte ratio (N/L) and arterial stiffness and arterial wave reflection in patients with a clinical diagnosis of coronary artery disease (CAD). METHODS We included 145 consecutive patients admitted with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood samples were drawn at admission for complete blood count and biochemistry. Non-invasive pulse waveform analysis for the determination of augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) measurements were performed with the commercially available SphygmoCor system. RESULTS When patients were divided into tertiles of PWV and AIx, median N/L and median serum UA levels were the highest and mean TB levels were the lowest in the third tertile (p<0.001 for all). AIx and PWV were positively associated with serum UA and N/L and negatively associated with serum TB levels (p<0.001 for all). After adjustments for age, gender, heart rate, systolic blood pressure, and presence of diabetes, significant correlations persisted for N/L, UA, and TB in ACS patients (p<0.05). In the SAP group, TB was significantly negatively correlated with AIx and PWV, and UA was significantly positively correlated with PWV (p<0.05). CONCLUSION N/L ratio and serum UA and TB levels might be used to risk-stratify patients with respect to arterial stiffness in CAD patients, especially in the presence of ACS.
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Affiliation(s)
- Aslı Tanındı
- Department of Cardiology, Faculty of Medicine, Ufuk University; Ankara-Turkey.
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McArdle MJ, deGoma EM, Cohen DL, Townsend RR, Wilensky RL, Giri J. Beyond blood pressure: percutaneous renal denervation for the management of sympathetic hyperactivity and associated disease states. J Am Heart Assoc 2015; 4:e001415. [PMID: 25801757 PMCID: PMC4392429 DOI: 10.1161/jaha.114.001415] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Michael J McArdle
- Department of Internal Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (M.J.M.A.)
| | - Emil M deGoma
- Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (E.M.G., R.L.W., J.G.)
| | - Debbie L Cohen
- Division of Renal, Electrolyte, and Hypertension, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (D.L.C., R.R.T.)
| | - Raymond R Townsend
- Division of Renal, Electrolyte, and Hypertension, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (D.L.C., R.R.T.)
| | - Robert L Wilensky
- Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (E.M.G., R.L.W., J.G.)
| | - Jay Giri
- Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (E.M.G., R.L.W., J.G.)
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Böhm M, Mahfoud F, Ukena C, Hoppe UC, Narkiewicz K, Negoita M, Ruilope L, Schlaich MP, Schmieder RE, Whitbourn R, Williams B, Zeymer U, Zirlik A, Mancia G. First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension. Hypertension 2015; 65:766-74. [PMID: 25691618 DOI: 10.1161/hypertensionaha.114.05010] [Citation(s) in RCA: 145] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
UNLABELLED This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were -11.6±25.3 and -6.6±18.0 mm Hg for all patients (P<0.001 for both) and -20.3±22.8 and -8.9±16.9 mm Hg for those with severe hypertension (P<0.001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis >70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT01534299.
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Affiliation(s)
- Michael Böhm
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.).
| | - Felix Mahfoud
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Christian Ukena
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Uta C Hoppe
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Krzysztof Narkiewicz
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Manuela Negoita
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Luis Ruilope
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Markus P Schlaich
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Roland E Schmieder
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Robert Whitbourn
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Bryan Williams
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Uwe Zeymer
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Andreas Zirlik
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
| | - Giuseppe Mancia
- From the Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany (M.B., F.M, C.U.); Department of Internal Medicine II, Paracelsus University Salzburg, Salzburg, Austria (U.C.H.);Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); Global Clinical Research, Coronary and Structural Heart Disease Management, Medtronic Inc, Santa Rosa, CA (M.N.); Institute of Research & Hypertension Unit, Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain (L.R.); School of Medicine and Pharmacology-Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia (M.P.S.); Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany (R.E.S.); Cardiovascular Research Centre, Interventional Cardiology, St. Vincent's Hospital, Melbourne, Australia (R.W.); Institute of Cardiovascular Sciences, University College London (UCL), National Institute for Health Research UCL Hospitals Biomedical Research Centre, London, United Kingdom (B.W.); Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany (U.Z.); Department of Cardiology and Angiology I, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Freiburg, Germany (A.Z.); and IRCCS Istituto Auxologico Italiano, Center of Epidemiology and Clinical Trials, University of Milano-Bicocca, Milan, Italy (G.M.)
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Park J, Liao P, Sher S, Lyles RH, Deveaux DD, Quyyumi AA. Tetrahydrobiopterin lowers muscle sympathetic nerve activity and improves augmentation index in patients with chronic kidney disease. Am J Physiol Regul Integr Comp Physiol 2015; 308:R208-18. [PMID: 25477424 PMCID: PMC4313073 DOI: 10.1152/ajpregu.00409.2014] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 12/01/2014] [Indexed: 11/22/2022]
Abstract
Chronic kidney disease (CKD) is characterized by overactivation of the sympathetic nervous system (SNS) that contributes to cardiovascular risk. Decreased nitric oxide (NO) bioavailability is a major factor contributing to SNS overactivity in CKD, since reduced neuronal NO leads to increased central SNS activity. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase that increases NO bioavailability in experimental models of CKD. We conducted a randomized, double-blinded, placebo-controlled trial testing the benefits of oral sapropterin dihydrochloride (6R-BH4, a synthetic form of BH4) in CKD. 36 patients with CKD and hypertension were randomized to 12 wk of 1) 200 mg 6R-BH4 twice daily + 1 mg folic acid once daily; vs. 2) placebo + folic acid. The primary endpoint was a change in resting muscle sympathetic nerve activity (MSNA). Secondary endpoints included arterial stiffness using pulse wave velocity (PWV) and augmentation index (AIx), endothelial function using brachial artery flow-mediated dilation and endothelial progenitor cells, endothelium-independent vasodilatation (EID), microalbuminuria, and blood pressure. We observed a significant reduction in MSNA after 12 wk of 6R-BH4 (-7.5 ± 2.1 bursts/min vs. +3.2 ± 1.3 bursts/min; P = 0.003). We also observed a significant improvement in AIx (by -5.8 ± 2.0% vs. +1.8 ± 1.7 in the placebo group, P = 0.007). EID increased significantly (by +2.0 ± 0.59%; P = 0.004) in the 6R-BH4 group, but there was no change in endothelial function. There was a trend toward a reduction in diastolic blood pressure by -4 ± 3 mmHg at 12 wk with 6R-BH4 (P = 0.055). 6R-BH4 treatment may have beneficial effects on SNS activity and central pulse wave reflections in hypertensive patients with CKD.
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Affiliation(s)
- Jeanie Park
- Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Research Service Line, Department of Veterans Affairs Medical Center, Decatur, Georgia;
| | - Peizhou Liao
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia; and
| | - Salman Sher
- Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Robert H Lyles
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia; and
| | - Don D Deveaux
- Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Research Service Line, Department of Veterans Affairs Medical Center, Decatur, Georgia
| | - Arshed A Quyyumi
- Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
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Tzafriri AR, Mahfoud F, Keating JH, Markham PM, Spognardi A, Wong G, Fuimaono K, Böhm M, Edelman ER. Innervation patterns may limit response to endovascular renal denervation. J Am Coll Cardiol 2015; 64:1079-87. [PMID: 25212640 DOI: 10.1016/j.jacc.2014.07.937] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Revised: 07/01/2014] [Accepted: 07/07/2014] [Indexed: 01/03/2023]
Abstract
BACKGROUND Renal denervation is a new interventional approach to treat hypertension with variable results. OBJECTIVES The purpose of this study was to correlate response to endovascular radiofrequency ablation of renal arteries with nerve and ganglia distributions. We examined how renal neural network anatomy affected treatment efficacy. METHODS A multielectrode radiofrequency catheter (15 W/60 s) treated 8 renal arteries (group 1). Arteries and kidneys were harvested 7 days post-treatment. Renal norepinephrine (NEPI) levels were correlated with ablation zone geometries and neural injury. Nerve and ganglion distributions and sizes were quantified at discrete distances from the aorta and were compared with 16 control arteries (group 2). RESULTS Nerve and ganglia distributions varied with distance from the aorta (p < 0.001). A total of 75% of nerves fell within a circumferential area of 9.3, 6.3, and 3.4 mm of the lumen and 0.3, 3.0, and 6.0 mm from the aorta. Efficacy (NEPI 37 ng/g) was observed in only 1 of 8 treated arteries where ablation involved all 4 quadrants, reached a depth of 9.1 mm, and affected 50% of nerves. In 7 treated arteries, NEPI levels remained at baseline values (620 to 991 ng/g), ≤20% of the nerves were affected, and the ablation areas were smaller (16.2 ± 10.9 mm(2)) and present in only 1 to 2 quadrants at maximal depths of 3.8 ± 2.7 mm. CONCLUSIONS Renal denervation procedures that do not account for asymmetries in renal periarterial nerve and ganglia distribution may miss targets and fall below the critical threshold for effect. This phenomenon is most acute in the ostium but holds throughout the renal artery, which requires further definition.
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Affiliation(s)
| | - Felix Mahfoud
- Klinik für Innere Medizin III, Kardiologie, Angiologie, und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | | | | | | | - Gee Wong
- CBSET Inc., Lexington, Massachusetts
| | | | - Michael Böhm
- Klinik für Innere Medizin III, Kardiologie, Angiologie, und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Elazer R Edelman
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Azizi M. [New invasive therapies for management of resistant hypertension]. Biol Aujourdhui 2014; 208:211-6. [PMID: 25474002 DOI: 10.1051/jbio/2014012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Indexed: 11/15/2022]
Abstract
The failure of pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments. New catheter systems using radiofrequency or ultrasound energy have been developed, allowing a percutaneous endovascular approach to renal denervation for patients with resistant hypertension. To date, this technique has been evaluated only in a few open-label trials including small numbers and the available evidence suggests a favorable blood pressure-lowering effect in the short-term and a low incidence of immediate complications. All studies published to date have several limitations due to their open-label design. Carotid baroreceptor stimulation requires surgical implantation of electrodes connected to a stimulator. Preliminary results show a positive effect on blood pressure with a complication rate similar to the implantation of a pacemaker. In this context, there are arguments against an uncontrolled use of these procedures in routine practice: an unknown benefit/risk ratio, a variable blood pressure response, absence of cost-effectiveness evaluation. The indications of these procedures should follow the 2013 European Society of Hypertension guidelines. A strict follow-up of patients remains necessary at best by including them in clinical trials or international registries.
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Affiliation(s)
- Michel Azizi
- Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité d'Hypertension Artérielle, 20 rue Leblanc, 75015 Paris, France - Université Paris-Descartes, Faculté de Médecine, 15 rue de l'École de Médecine, 75006 Paris, France - INSERM, CIC HEGP 1418, 20 rue Leblanc, 75015 Paris, France
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Abstract
Hypertension has wide (30-45 %) prevalence in the general population and is related to important increases in overall cardiovascular morbidity and mortality. Despite lifestyle modifications and optimal medical therapy (three drugs, one being diuretic), about 5-20 % of hypertensives are affected by resistant hypertension. Chronic high blood pressure has adverse effects on the heart and other organs such as the kidneys and vasculature. Renal sympathetic denervation and baroreceptor stimulation are invasive approaches initially investigated to treat resistant hypertension. Their pleiotropic effects appear promising in cardiovascular remodeling, heart failure and arrhythmias and could potentially affect cardiovascular morbidity and mortality.
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Ewen S, Ukena C, Linz D, Kindermann I, Cremers B, Laufs U, Wagenpfeil S, Schmieder RE, Böhm M, Mahfoud F. Reduced effect of percutaneous renal denervation on blood pressure in patients with isolated systolic hypertension. Hypertension 2014; 65:193-9. [PMID: 25331843 DOI: 10.1161/hypertensionaha.114.04336] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Renal denervation can reduce blood pressure in certain patients with resistant hypertension. The effect in patients with isolated systolic hypertension (ISH, ≥140/<90 mm Hg) is unknown. This study investigated the effects of renal denervation in 126 patients divided into 63 patients with ISH and 63 patients with combined hypertension (CH, ≥140/≥90 mm Hg) defined as baseline office systolic blood pressure (SBP) ≥140 mm Hg despite treatment with ≥3 antihypertensive agents. Renal denervation significantly reduced office SBP and diastolic blood pressure (DBP) at 3, 6, and 12 months by 17/18/17 and 5/4/4 mm Hg in ISH and by 28/27/30 and 13/16/18 mm Hg in CH, respectively. The reduction in SBP and DBP in ISH was lower compared with patients with CH at all observed time points (P<0.05 for SBP/DBP intergroup comparison). The nonresponder rate (change in office SBP <10 mm Hg) after 6 months was 37% in ISH and 21% in CH (P<0.001). Mean 24-hour ambulatory SBP and DBP after 3, 6, and 12 months were significantly reduced by 10/13/15 and 6/6/9 mm Hg in CH, respectively. In patients with ISH the reduction in systolic ambulatory blood pressure was 4/8/7 mm Hg (P=0.032/P<0.001/P=0.009) and 3/4/2 mm Hg (P=0.08/P<0.001/P=0.130) in diastolic ambulatory blood pressure after 3, 6, and 12 months, respectively. The ambulatory blood pressure reduction was significantly lower after 3 and 12 months in SBP and after 12 months in ambulatory DBP, respectively. In conclusion, renal denervation reduces office and ambulatory blood pressure in patients with ISH. However, this reduction is less pronounced compared with patients with CH.
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Affiliation(s)
- Sebastian Ewen
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.).
| | - Christian Ukena
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Dominik Linz
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Ingrid Kindermann
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Bodo Cremers
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Ulrich Laufs
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Stefan Wagenpfeil
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Roland E Schmieder
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Michael Böhm
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.)
| | - Felix Mahfoud
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (S.E., C.U., D.L., I.K., B.C., U.L., M.B., F.M.) and Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (S.W.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; and Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany (R.E.S.).
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Kujawa-Szewieczek A, Kolonko A, Chudek J, Więcek A. No effect of pretransplantation bilateral nephrectomy on the resistive indices measured in the kidney allograft. Transplant Proc 2014; 46:2602-2605. [PMID: 25380876 DOI: 10.1016/j.transproceed.2014.08.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND The cirrhotic kidney is the cause of sympathetic nervous system and the renin-angiotensin system activation leading to increased vascular resistance and arterial hypertension. The impact of unilateral or bilateral nephrectomy (UN or BN) performed before kidney transplantation on kidney graft intrarenal resistance has not been assessed yet. The aim of this study is to assess the intrarenal resistance parameters measured by Doppler ultrasound in the transplanted kidney in either nephrectomized or non-nephrectomized kidney transplant recipients. METHODS Among 686 consecutive successful first cadaveric kidney graft recipients transplanted from 1998 to 2012, we identified 43 patients who underwent BN and 49 patients who underwent UN. Patients with acute rejection episodes within an early post-transplantation period were excluded. We have analyzed both pulsatility (PI) and resistance (RI) indices measured within the kidney graft before discharge from the hospital. RESULTS The prevalence of hypertension in the follow-up period after transplantation was significantly lower in the BN group (65.1% versus 81.0% in other groups). Neither BN nor UN influenced the PI or RI values. The mean PI and RI values were 1.50 (1.38-1.61) and 0.75 (0.73-0.78) in BN, 1.48 (1.37-1.58) and 0.76 (0.73-0.79) in UN, and 1.47 (1.43-1.50) and 0.74 (0.73-0.75) in non-nephrectomized patients, respectively. The results of multivariate analysis confirmed the lack of influence of nephrectomy on kidney graft resistive indices. CONCLUSION BN before transplantation resulted in lower frequency of hypertension, but it did not affect the intrarenal vascular resistance measured in the kidney graft.
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Affiliation(s)
- A Kujawa-Szewieczek
- Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland
| | - A Kolonko
- Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland
| | - J Chudek
- Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland; Department of Pathophysiology, Medical University of Silesia, Katowice, Poland
| | - A Więcek
- Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland.
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Böhm M, Linz D, Ukena C, Esler M, Mahfoud F. Renal Denervation for the Treatment of Cardiovascular High Risk-Hypertension or Beyond? Circ Res 2014; 115:400-9. [DOI: 10.1161/circresaha.115.302522] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Michael Böhm
- From the Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (M.B., D.L., C.U., F.M.); and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.E.)
| | - Dominik Linz
- From the Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (M.B., D.L., C.U., F.M.); and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.E.)
| | - Christian Ukena
- From the Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (M.B., D.L., C.U., F.M.); and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.E.)
| | - Murray Esler
- From the Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (M.B., D.L., C.U., F.M.); and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.E.)
| | - Felix Mahfoud
- From the Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (M.B., D.L., C.U., F.M.); and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.E.)
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45
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Hypertensive subjects with type-2 diabetes, the sympathetic nervous system, and treatment implications. Int J Cardiol 2014; 174:702-9. [DOI: 10.1016/j.ijcard.2014.04.204] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 04/19/2014] [Accepted: 04/19/2014] [Indexed: 11/19/2022]
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46
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Salusin-β in rostral ventrolateral medulla increases sympathetic outflow and blood pressure via superoxide anions in hypertensive rats. J Hypertens 2014; 32:1059-67; discussion 1067. [DOI: 10.1097/hjh.0000000000000143] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Hering D, Marusic P, Walton AS, Lambert EA, Krum H, Narkiewicz K, Lambert GW, Esler MD, Schlaich MP. Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension. Hypertension 2014; 64:118-24. [PMID: 24732891 DOI: 10.1161/hypertensionaha.113.03098] [Citation(s) in RCA: 113] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Renal denervation (RDN) reduces muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in resistant hypertension. Although a persistent BP-lowering effect has been demonstrated, the long-term effect on MSNA remains elusive. We investigated whether RDN influences MSNA over time. Office BP and MSNA were obtained at baseline, 3, 6, and 12 months after RDN in 35 patients with resistant hypertension. Office BP averaged 166±22/88±19 mm Hg, despite the use of an average of 4.8±2.1 antihypertensive drugs. Baseline MSNA was 51±11 bursts/min ≈2- to 3-fold higher than the level observed in healthy controls. Mean office systolic and diastolic BP significantly decreased by -12.6±18.3/-6.5±9.2, -16.1±25.6/-8.6±12.9, and -21.2±29.1/-11.1±12.9 mm Hg (P<0.001 for both systolic BP and diastolic BP) with RDN at 3-, 6-, and 12-month follow-up, respectively. MSNA was reduced by -8±12, -6±12, and -6±11 bursts/min (P<0.01) at 3-, 6-, and 12-month follow-up. The reduction in MSNA was maintained, despite a progressive fall in BP over time. No such changes were observed in 7 control subjects at 6-month follow-up. These findings confirm previous reports on the favorable effects of RDN on elevated BP and demonstrate sustained reduction of central sympathetic outflow ≤1-year follow-up in patients with resistant hypertension and high baseline MSNA. These observations are compatible with the hypothesis of a substantial contribution of afferent renal nerve signaling to increased BP in resistant hypertension and argue against a relevant reinnervation at 1 year after procedure.
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Affiliation(s)
- Dagmara Hering
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Petra Marusic
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Antony S Walton
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Elisabeth A Lambert
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Henry Krum
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Krzysztof Narkiewicz
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Gavin W Lambert
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Murray D Esler
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia
| | - Markus P Schlaich
- From the Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (D.H., P.M., E.A.L., G.W.L., M.D.E., M.P.S.); Department of Hypertension and Diabetology, Medical University of Gdansk, Gdańsk, Poland (D.H., K.N.); Heart Centre Alfred Hospital, Melbourne, Australia (A.S.W., H.K., M.D.E., M.P.S.); and Department of Physiology, Faculty of Medicine, Nursing and Health Sciences (E.A.L., G.W.L., M.P.S.) and Department of Epidemiology and Preventive Medicine (H.K.), Monash University, Melbourne, Australia.
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Schlaich MP, Esler MD, Fink GD, Osborn JW, Euler DE. Targeting the Sympathetic Nervous System. Hypertension 2014; 63:426-32. [DOI: 10.1161/hypertensionaha.113.02144] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Markus P. Schlaich
- From the Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.P.S, M.D.E.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing (G.D.F); Department of Integrative Biology and Physiology, Lillehei Heart Institute, University of Minnesota, Minneapolis (J.W.O.); and Medtronic, Vascular, Santa Rosa, CA (D.E.E.)
| | - Murray D. Esler
- From the Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.P.S, M.D.E.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing (G.D.F); Department of Integrative Biology and Physiology, Lillehei Heart Institute, University of Minnesota, Minneapolis (J.W.O.); and Medtronic, Vascular, Santa Rosa, CA (D.E.E.)
| | - Greg D. Fink
- From the Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.P.S, M.D.E.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing (G.D.F); Department of Integrative Biology and Physiology, Lillehei Heart Institute, University of Minnesota, Minneapolis (J.W.O.); and Medtronic, Vascular, Santa Rosa, CA (D.E.E.)
| | - John W. Osborn
- From the Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.P.S, M.D.E.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing (G.D.F); Department of Integrative Biology and Physiology, Lillehei Heart Institute, University of Minnesota, Minneapolis (J.W.O.); and Medtronic, Vascular, Santa Rosa, CA (D.E.E.)
| | - David E. Euler
- From the Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.P.S, M.D.E.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing (G.D.F); Department of Integrative Biology and Physiology, Lillehei Heart Institute, University of Minnesota, Minneapolis (J.W.O.); and Medtronic, Vascular, Santa Rosa, CA (D.E.E.)
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49
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Affiliation(s)
- Edward J Johns
- Department of Physiology, University College Cork, Cork, Republic of Ireland.
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50
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Bellinazzi VR, Sposito AC, Schreiber R, Mill JG, Krieger JE, Pereira AC, Nadruz W. Response to cold pressor test predicts long-term changes in pulse wave velocity in men. Am J Hypertens 2014; 27:157-61. [PMID: 24222667 DOI: 10.1093/ajh/hpt213] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Aortic stiffness is associated with increased cardiovascular mortality. However, the determinants of aortic stiffness progression are not fully established. This study evaluated the predictive value of blood pressure (BP) response to cold pressor test (CPT) in the progression of carotid-femoral pulse wave velocity (PWV) in men and women. METHODS A total of 408 individuals (165 men, 243 women) from Vitoria, Brazil, underwent BP evaluation, clinical and laboratorial investigations, and CPT and PWV assessment. Five years later, the studied individuals were re-evaluated, except for the CPT. RESULTS In men, 5-year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with BP response to CPT (P < 0.05) and 5-year BP change (P < 0.05). In women, 5-year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with age (P < 0.01), glycemia (P < 0.05) and 5-year BP change (P < 0.05) but not with BP response to CPT. Further linear regression analysis showed that 5-year PWV change was associated with baseline PWV, systolic BP response to CPT, and 5-year systolic BP change in men and with baseline PWV, age, glycemia, and 5-year systolic BP change in women. CONCLUSIONS BP response to CPT was a predictor of PWV progression in men after 5 years of follow-up. These findings provide further insights into the pathophysiologic mechanisms of arterial stiffness, suggesting that elevated sympathetic reactivity may be a predisposing factor for future increases in aortic stiffness, at least in men.
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