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2. Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries

Author

Rios, F, de Ciuceis, C, Georgiopoulos, G, Lazaridis, A, Nosalski, R, Pavlidis, G, Tual-Chalot, S, Agabiti-Rosei, C, Camargo, L, Dąbrowska, E, Quarti-Trevano, F, Hellmann, M, Masi, S, Lopreiato, M, Mavraganis, G, Mengozzi, A, Montezano, A, Stavropoulos, K, Winklewski, P, Wolf, J, Costantino, S, Doumas, M, Gkaliagkousi, E, Grassi, G, Guzik, T, Ikonomidis, I, Narkiewicz, K, Paneni, F, Rizzoni, D, Stamatelopoulos, K, Stellos, K, Taddei, S, Touyz, R, Virdis, A, Rios, Francisco J., de Ciuceis, Carolina, Georgiopoulos, Georgios, Lazaridis, Antonios, Nosalski, Ryszard, Pavlidis, George, Tual-Chalot, Simon, Agabiti-Rosei, Claudia, Camargo, Livia L., Dąbrowska, Edyta, Quarti-Trevano, Fosca, Hellmann, Marcin, Masi, Stefano, Lopreiato, Mariarosaria, Mavraganis, Georgios, Mengozzi, Alessandro, Montezano, Augusto C., Stavropoulos, Konstantinos, Winklewski, Pawel J., Wolf, Jacek, Costantino, Sarah, Doumas, Michael, Gkaliagkousi, Eugenia, Grassi, Guido, Guzik, Tomasz J., Ikonomidis, Ignatios, Narkiewicz, Krzysztof, Paneni, Francesco, Rizzoni, Damiano, Stamatelopoulos, Kimon, Stellos, Konstantinos, Taddei, Stefano, Touyz, Rhian M, Virdis, Agostino, Rios, F, de Ciuceis, C, Georgiopoulos, G, Lazaridis, A, Nosalski, R, Pavlidis, G, Tual-Chalot, S, Agabiti-Rosei, C, Camargo, L, Dąbrowska, E, Quarti-Trevano, F, Hellmann, M, Masi, S, Lopreiato, M, Mavraganis, G, Mengozzi, A, Montezano, A, Stavropoulos, K, Winklewski, P, Wolf, J, Costantino, S, Doumas, M, Gkaliagkousi, E, Grassi, G, Guzik, T, Ikonomidis, I, Narkiewicz, K, Paneni, F, Rizzoni, D, Stamatelopoulos, K, Stellos, K, Taddei, S, Touyz, R, Virdis, A, Rios, Francisco J., de Ciuceis, Carolina, Georgiopoulos, Georgios, Lazaridis, Antonios, Nosalski, Ryszard, Pavlidis, George, Tual-Chalot, Simon, Agabiti-Rosei, Claudia, Camargo, Livia L., Dąbrowska, Edyta, Quarti-Trevano, Fosca, Hellmann, Marcin, Masi, Stefano, Lopreiato, Mariarosaria, Mavraganis, Georgios, Mengozzi, Alessandro, Montezano, Augusto C., Stavropoulos, Konstantinos, Winklewski, Pawel J., Wolf, Jacek, Costantino, Sarah, Doumas, Michael, Gkaliagkousi, Eugenia, Grassi, Guido, Guzik, Tomasz J., Ikonomidis, Ignatios, Narkiewicz, Krzysztof, Paneni, Francesco, Rizzoni, Damiano, Stamatelopoulos, Kimon, Stellos, Konstantinos, Taddei, Stefano, Touyz, Rhian M, and Virdis, Agostino

Abstract

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease.

Published
2024

4. TIME to face the reality about evening dosing of antihypertensive drugs in hypertension

Author

Kjeldsen, S, Egan, B, Narkiewicz, K, Kreutz, R, Burnier, M, Oparil, S, Mancia, G, Kjeldsen S. E., Egan B. M., Narkiewicz K., Kreutz R., Burnier M., Oparil S., Mancia G., Kjeldsen, S, Egan, B, Narkiewicz, K, Kreutz, R, Burnier, M, Oparil, S, Mancia, G, Kjeldsen S. E., Egan B. M., Narkiewicz K., Kreutz R., Burnier M., Oparil S., and Mancia G.

Published
2023

5. Key questions regarding the SYMPLICITY HTN-3 trial

Author

Kjeldsen, S, Burnier, M, Narkiewicz, K, Kreutz, R, Mancia, G, Kjeldsen S. E., Burnier M., Narkiewicz K., Kreutz R., Mancia G., Kjeldsen, S, Burnier, M, Narkiewicz, K, Kreutz, R, Mancia, G, Kjeldsen S. E., Burnier M., Narkiewicz K., Kreutz R., and Mancia G.

Published
2023

6. Outcomes Following Radiofrequency Renal Denervation According to Antihypertensive Medications: Subgroup Analysis of the Global SYMPLICITY Registry DEFINE

Author

Mahfoud, F, Mancia, G, Schmieder, R, Ruilope, L, Narkiewicz, K, Schlaich, M, Williams, B, Ribichini, F, Weil, J, Almerri, K, Sharif, F, Lauder, L, Wanten, M, Fahy, M, Böhm, M, Mahfoud F., Mancia G., Schmieder R. E., Ruilope L., Narkiewicz K., Schlaich M., Williams B., Ribichini F., Weil J., Almerri K., Sharif F., Lauder L., Wanten M., Fahy M., Böhm M., Mahfoud, F, Mancia, G, Schmieder, R, Ruilope, L, Narkiewicz, K, Schlaich, M, Williams, B, Ribichini, F, Weil, J, Almerri, K, Sharif, F, Lauder, L, Wanten, M, Fahy, M, Böhm, M, Mahfoud F., Mancia G., Schmieder R. E., Ruilope L., Narkiewicz K., Schlaich M., Williams B., Ribichini F., Weil J., Almerri K., Sharif F., Lauder L., Wanten M., Fahy M., and Böhm M.

Abstract

Background: The Global SYMPLICITY Registry DEFINE (Denervation Findings in Real World) investigates radiofrequency renal denervation (RDN) in a broad range of patients with hypertension. We evaluated whether the number or type of antihypertensive medications were associated with increased long-term blood pressure (BP) reductions and cardiovascular outcomes following radiofrequency RDN. Methods: Patients underwent radiofrequency RDN and were categorized by baseline number (0-3 and ≥4) and different combinations of medication classes. BP changes were compared between groups through 36 months. Individual and composite major adverse cardiovascular events were analyzed. Results: Of 2746 evaluable patients, 18% were prescribed 0 to 3 and 82% prescribed ≥4 classes. At 36 months, office systolic BP significantly decreased (P<0.0001) by -19.0±28.3 and -16.2±28.6 mm Hg in the 0 to 3 and ≥4 class groups, respectively. Twenty-four-hour mean systolic BP significantly decreased (P<0.0001) by -10.7±19.7 and -8.9±20.5 mm Hg, respectively. BP reduction was similar between the medication subgroups. Antihypertensive medication classes decreased from 4.6±1.4 to 4.3±1.5 (P<0.0001). Most decreased (31%) or had no changes (47%) to the number of medications, while 22% increased. The number of baseline antihypertensive medication classes was inversely related to the change in prescribed classes at 36 months (P<0.001). Cardiovascular event rates were generally low. More patients in the ≥4 compared with 0 to 3 medication classes had myocardial infarction at 36 months (2.8% versus 0.3%; P=0.009). Conclusions: Radiofrequency RDN reduced BP safely through 36 months, independent of the number and type of baseline antihypertensive medication classes. More patients decreased than increased their number of medications. Radiofrequency RDN is a safe and effective adjunctive therapy regardless of antihypertensive medication regimen. Registration: URL: https://www. Clinicaltrials: gov; Uniqu

Published
2023

9. Cardiovascular Risk Reduction After Renal Denervation According to Time in Therapeutic Systolic Blood Pressure Range

Author

Mahfoud, F, Mancia, G, Schmieder, R, Ruilope, L, Narkiewicz, K, Schlaich, M, Williams, B, Ribichini, F, Weil, J, Kao, H, Rodriguez-Leor, O, Noory, E, Ong, T, Unterseeh, T, de Araujo Goncalves, P, Zirlik, A, Almerri, K, Sharif, F, Lauder, L, Wanten, M, Fahy, M, Bohm, M, Mahfoud F., Mancia G., Schmieder R. E., Ruilope L., Narkiewicz K., Schlaich M., Williams B., Ribichini F., Weil J., Kao H. -L., Rodriguez-Leor O., Noory E., Ong T. K., Unterseeh T., de Araujo Goncalves P., Zirlik A., Almerri K., Sharif F., Lauder L., Wanten M., Fahy M., Bohm M., Mahfoud, F, Mancia, G, Schmieder, R, Ruilope, L, Narkiewicz, K, Schlaich, M, Williams, B, Ribichini, F, Weil, J, Kao, H, Rodriguez-Leor, O, Noory, E, Ong, T, Unterseeh, T, de Araujo Goncalves, P, Zirlik, A, Almerri, K, Sharif, F, Lauder, L, Wanten, M, Fahy, M, Bohm, M, Mahfoud F., Mancia G., Schmieder R. E., Ruilope L., Narkiewicz K., Schlaich M., Williams B., Ribichini F., Weil J., Kao H. -L., Rodriguez-Leor O., Noory E., Ong T. K., Unterseeh T., de Araujo Goncalves P., Zirlik A., Almerri K., Sharif F., Lauder L., Wanten M., Fahy M., and Bohm M.

Abstract

Background: Renal denervation (RDN) has been shown to lower blood pressure (BP), but its effects on cardiovascular events have only been preliminarily evaluated. Time in therapeutic range (TTR) of BP is associated with cardiovascular events. Objectives: This study sought to assess the impact of catheter-based RDN on TTR and its association with cardiovascular outcomes in the GSR (Global SYMPLICITY Registry). Methods: Patients with uncontrolled hypertension were enrolled and treated with radiofrequency RDN. Office and ambulatory systolic blood pressure (OSBP and ASBP) were measured at 3, 6, 12, 24, and 36 months postprocedure and used to derive TTR. TTR through 6 months was assessed as a predictor of cardiovascular events from 6 to 36 months using a Cox proportional hazard regression model. Results: As of March 1, 2022, 3,077 patients were enrolled: 42.2% were female; mean age was 60.5 ± 12.2 years; baseline OSBP was 165.6 ± 24.8 mm Hg; and baseline ASBP was 154.3 ± 18.7 mm Hg. Patients were prescribed 4.9 ± 1.7 antihypertensive medications at baseline and 4.8 ± 1.9 at 36 months. At 36 months, mean changes were −16.7 ± 28.4 and −9.0 ± 20.2 mm Hg for OSBP and ASBP, respectively. TTR through 6 months was 30.6%. A 10% increase in TTR after RDN through 6 months was associated with significant risk reductions from 6 to 36 months of 15% for major adverse cardiovascular events (P < 0.001), 11% cardiovascular death (P = 0.010), 15% myocardial infarction (P = 0.023), and 23% stroke (P < 0.001). Conclusions: There were sustained BP reductions and higher TTR through 36 months after RDN. A 10% increase in TTR through 6 months was associated with significant risk reductions in major cardiovascular events from 6 to 36 months. (Global SYMPLICITY Registry [GSR] DEFINE; NCT01534299)

Published
2022

10. Renal denervation in patients with versus without chronic kidney disease: Results from the Global SYMPLICITY Registry with follow-up data of 3 years

Author

Ott, C, Mahfoud, F, Mancia, G, Narkiewicz, K, Ruilope, L, Fahy, M, Schlaich, M, Bohm, M, Schmieder, R, Ott C., Mahfoud F., Mancia G., Narkiewicz K., Ruilope L. M., Fahy M., Schlaich M. P., Bohm M., Schmieder R. E., Ott, C, Mahfoud, F, Mancia, G, Narkiewicz, K, Ruilope, L, Fahy, M, Schlaich, M, Bohm, M, Schmieder, R, Ott C., Mahfoud F., Mancia G., Narkiewicz K., Ruilope L. M., Fahy M., Schlaich M. P., Bohm M., and Schmieder R. E.

Abstract

Background: Activity of the sympathetic nervous system is increased in patients with hypertension and chronic kidney disease (CKD). Here we compare short-and long-term blood pressure (BP)-lowering effects of renal denervation (RDN) between hypertensive patients with or without CKD in the Global SYMPLICITY Registry. Methods: Office and 24-h ambulatory BP (ABP) were assessed at prespecified time points after RDN. The presence of CKD was defined according to the estimated glomerular filtration rate (eGFR) and enrolled patients were stratified based on the presence (n = 475, eGFR <60 mL/min/1.73 m2) or absence (n = 1505, eGFR ≥60mL/min/1.73 m2) of CKD. Results: Patients with CKD were older (P < 0.001) and were prescribed more antihypertensive medications (P < 0.001). eGFR decline per year was not significantly different between groups after the first year. Office and 24-h ABP were significantly reduced from baseline at all time points after RDN in both groups (all P < 0.001). After adjusting for baseline data, patients without CKD had a greater reduction in office systolic BP (-17.3 ± 28.3 versus-11.7 ± 29.9 mmHg; P = 0.009) but not diastolic BP at 36 months compared with those with CKD. Similar BP and eGFR results were found when the analysis was limited to patients with both baseline and 36-month BP data available. There was no difference in the safety profile of the RDN procedure between groups. Conclusions: After adjusting for baseline data, 24-h systolic and diastolic ABP reduction were similar in patients with and without CKD after RDN, whereas office systolic but not diastolic BP was reduced less in patients with CKD. We conclude that RDN is an effective antihypertensive treatment option in CKD patients.

Published
2022

11. Clinical event reductions in high-risk patients after renal denervation projected from the global SYMPLICITY registry

Author

Schmieder, R, Mahfoud, F, Mancia, G, Narkiewicz, K, Ruilope, L, Hutton, D, Cao, K, Hettrick, D, Fahy, M, Schlaich, M, Böhm, M, Pietzsch, J, Schmieder, RE, Hettrick, DA, Schlaich, MP, Pietzsch, JB, Schmieder, R, Mahfoud, F, Mancia, G, Narkiewicz, K, Ruilope, L, Hutton, D, Cao, K, Hettrick, D, Fahy, M, Schlaich, M, Böhm, M, Pietzsch, J, Schmieder, RE, Hettrick, DA, Schlaich, MP, and Pietzsch, JB

Abstract

Aims: Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach. Methods and results: The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N = 2651) were 166±25 and -14.8 ± 0.4 mmHg, respectively. Mean reductions in blood pressure ranged from -11.0 - 21.8 mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P < 0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses. Conclusion: Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.

Published
2023

14. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)

Author

Mancia, G, Kreutz, R, Brunström, M, Burnier, M, Grassi, G, Januszewicz, A, Muiesan, M, Tsioufis, K, Agabiti-Rosei, E, Algharably, E, Azizi, M, Benetos, A, Borghi, C, Hitij, J, Cifkova, R, Coca, A, Cornelissen, V, Cruickshank, J, Cunha, P, Danser, A, Pinho, R, Delles, C, Dominiczak, A, Dorobantu, M, Doumas, M, Fernández-Alfonso, M, Halimi, J, Járai, Z, Jelaković, B, Jordan, J, Kuznetsova, T, Laurent, S, Lovic, D, Lurbe, E, Mahfoud, F, Manolis, A, Miglinas, M, Narkiewicz, K, Niiranen, T, Palatini, P, Parati, G, Pathak, A, Persu, A, Polonia, J, Redon, J, Sarafidis, P, Schmieder, R, Spronck, B, Stabouli, S, Stergiou, G, Taddei, S, Thomopoulos, C, Tomaszewski, M, Van de Borne, P, Wanner, C, Weber, T, Williams, B, Zhang, Z, Kjeldsen, S, Mancia, Giuseppe, Kreutz, Reinhold, Brunström, Mattias, Burnier, Michel, Grassi, Guido, Januszewicz, Andrzej, Muiesan, Maria Lorenza, Tsioufis, Konstantinos, Agabiti-Rosei, Enrico, Algharably, Engi Abd Elhady, Azizi, Michel, Benetos, Athanase, Borghi, Claudio, Hitij, Jana Brguljan, Cifkova, Renata, Coca, Antonio, Cornelissen, Veronique, Cruickshank, J Kennedy, Cunha, Pedro G, Danser, A H Jan, Pinho, Rosa Maria de, Delles, Christian, Dominiczak, Anna F, Dorobantu, Maria, Doumas, Michalis, Fernández-Alfonso, María S, Halimi, Jean-Michel, Járai, Zoltán, Jelaković, Bojan, Jordan, Jens, Kuznetsova, Tatiana, Laurent, Stephane, Lovic, Dragan, Lurbe, Empar, Mahfoud, Felix, Manolis, Athanasios, Miglinas, Marius, Narkiewicz, Krzystof, Niiranen, Teemu, Palatini, Paolo, Parati, Gianfranco, Pathak, Atul, Persu, Alexandre, Polonia, Jorge, Redon, Josep, Sarafidis, Pantelis, Schmieder, Roland, Spronck, Bart, Stabouli, Stella, Stergiou, George, Taddei, Stefano, Thomopoulos, Costas, Tomaszewski, Maciej, Van de Borne, Philippe, Wanner, Christoph, Weber, Thomas, Williams, Bryan, Zhang, Zhen-Yu, Kjeldsen, Sverre E, Mancia, G, Kreutz, R, Brunström, M, Burnier, M, Grassi, G, Januszewicz, A, Muiesan, M, Tsioufis, K, Agabiti-Rosei, E, Algharably, E, Azizi, M, Benetos, A, Borghi, C, Hitij, J, Cifkova, R, Coca, A, Cornelissen, V, Cruickshank, J, Cunha, P, Danser, A, Pinho, R, Delles, C, Dominiczak, A, Dorobantu, M, Doumas, M, Fernández-Alfonso, M, Halimi, J, Járai, Z, Jelaković, B, Jordan, J, Kuznetsova, T, Laurent, S, Lovic, D, Lurbe, E, Mahfoud, F, Manolis, A, Miglinas, M, Narkiewicz, K, Niiranen, T, Palatini, P, Parati, G, Pathak, A, Persu, A, Polonia, J, Redon, J, Sarafidis, P, Schmieder, R, Spronck, B, Stabouli, S, Stergiou, G, Taddei, S, Thomopoulos, C, Tomaszewski, M, Van de Borne, P, Wanner, C, Weber, T, Williams, B, Zhang, Z, Kjeldsen, S, Mancia, Giuseppe, Kreutz, Reinhold, Brunström, Mattias, Burnier, Michel, Grassi, Guido, Januszewicz, Andrzej, Muiesan, Maria Lorenza, Tsioufis, Konstantinos, Agabiti-Rosei, Enrico, Algharably, Engi Abd Elhady, Azizi, Michel, Benetos, Athanase, Borghi, Claudio, Hitij, Jana Brguljan, Cifkova, Renata, Coca, Antonio, Cornelissen, Veronique, Cruickshank, J Kennedy, Cunha, Pedro G, Danser, A H Jan, Pinho, Rosa Maria de, Delles, Christian, Dominiczak, Anna F, Dorobantu, Maria, Doumas, Michalis, Fernández-Alfonso, María S, Halimi, Jean-Michel, Járai, Zoltán, Jelaković, Bojan, Jordan, Jens, Kuznetsova, Tatiana, Laurent, Stephane, Lovic, Dragan, Lurbe, Empar, Mahfoud, Felix, Manolis, Athanasios, Miglinas, Marius, Narkiewicz, Krzystof, Niiranen, Teemu, Palatini, Paolo, Parati, Gianfranco, Pathak, Atul, Persu, Alexandre, Polonia, Jorge, Redon, Josep, Sarafidis, Pantelis, Schmieder, Roland, Spronck, Bart, Stabouli, Stella, Stergiou, George, Taddei, Stefano, Thomopoulos, Costas, Tomaszewski, Maciej, Van de Borne, Philippe, Wanner, Christoph, Weber, Thomas, Williams, Bryan, Zhang, Zhen-Yu, and Kjeldsen, Sverre E

Abstract

Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

Published
2023

15. The Hypertension Excellence Centre programme of the European Society of Hypertension - current status, activities and reshaping for the future

Author

Weber, T, Doumas, M, Delles, C, Jelakovic, B, Viigimaa, M, Narkiewicz, K, Januszewicz, A, Kreutz, R, Grassi, G, Mancia, G, Weber, Thomas, Doumas, Michael, Delles, Christian, Jelakovic, Bojan, Viigimaa, Margus, Narkiewicz, Krzysztof, Januszewicz, Andrzej, Kreutz, Reinhold, Grassi, Guido, Mancia, Giuseppe, Weber, T, Doumas, M, Delles, C, Jelakovic, B, Viigimaa, M, Narkiewicz, K, Januszewicz, A, Kreutz, R, Grassi, G, Mancia, G, Weber, Thomas, Doumas, Michael, Delles, Christian, Jelakovic, Bojan, Viigimaa, Margus, Narkiewicz, Krzysztof, Januszewicz, Andrzej, Kreutz, Reinhold, Grassi, Guido, and Mancia, Giuseppe

Abstract

Purpose: To describe the history of the Excellence Centre (EC) programme of the European Society of Hypertension (ESH) since the beginning in 2006, its achievements, and its future developments. Materials and Methods: We list the number of ECs per country, the research projects performed so far, and the organisational steps needed to reshape the EC programme for the future. Results: In August 2023, the ESH EC programme includes 118 registered ECs in 21 European and 7 non-European countries. Updates about the formal steps for application, re-application, transfer of EC and retirement of EC heads are given. Conclusions: The EC programme of the ESH has been a success from the beginning. Further refinements will make it fit for the next decades.

Published
2023

16. The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Author

Mengozzi, A, de Ciuceis, C, Dell'Oro, R, Georgiopoulos, G, Lazaridis, A, Nosalski, R, Pavlidis, G, Tual-Chalot, S, Agabiti-Rosei, C, Anyfanti, P, Camargo, L, Dąbrowska, E, Quarti-Trevano, F, Hellmann, M, Masi, S, Mavraganis, G, Montezano, A, Rios, F, Winklewski, P, Wolf, J, Costantino, S, Gkaliagkousi, E, Grassi, G, Guzik, T, Ikonomidis, I, Narkiewicz, K, Paneni, F, Rizzoni, D, Stamatelopoulos, K, Stellos, K, Taddei, S, Touyz, R, Triantafyllou, A, Virdis, A, Mengozzi, Alessandro, de Ciuceis, Carolina, Dell'oro, Raffaella, Georgiopoulos, Georgios, Lazaridis, Antonios, Nosalski, Ryszard, Pavlidis, George, Tual-Chalot, Simon, Agabiti-Rosei, Claudia, Anyfanti, Panagiota, Camargo, Livia L, Dąbrowska, Edyta, Quarti-Trevano, Fosca, Hellmann, Marcin, Masi, Stefano, Mavraganis, Georgios, Montezano, Augusto C, Rios, Francesco J, Winklewski, Pawel J, Wolf, Jacek, Costantino, Sarah, Gkaliagkousi, Eugenia, Grassi, Guido, Guzik, Tomasz J, Ikonomidis, Ignatios, Narkiewicz, Krzysztof, Paneni, Francesco, Rizzoni, Damiano, Stamatelopoulos, Kimon, Stellos, Konstantinos, Taddei, Stefano, Touyz, Rhian M, Triantafyllou, Areti, Virdis, Agostino, Mengozzi, A, de Ciuceis, C, Dell'Oro, R, Georgiopoulos, G, Lazaridis, A, Nosalski, R, Pavlidis, G, Tual-Chalot, S, Agabiti-Rosei, C, Anyfanti, P, Camargo, L, Dąbrowska, E, Quarti-Trevano, F, Hellmann, M, Masi, S, Mavraganis, G, Montezano, A, Rios, F, Winklewski, P, Wolf, J, Costantino, S, Gkaliagkousi, E, Grassi, G, Guzik, T, Ikonomidis, I, Narkiewicz, K, Paneni, F, Rizzoni, D, Stamatelopoulos, K, Stellos, K, Taddei, S, Touyz, R, Triantafyllou, A, Virdis, A, Mengozzi, Alessandro, de Ciuceis, Carolina, Dell'oro, Raffaella, Georgiopoulos, Georgios, Lazaridis, Antonios, Nosalski, Ryszard, Pavlidis, George, Tual-Chalot, Simon, Agabiti-Rosei, Claudia, Anyfanti, Panagiota, Camargo, Livia L, Dąbrowska, Edyta, Quarti-Trevano, Fosca, Hellmann, Marcin, Masi, Stefano, Mavraganis, Georgios, Montezano, Augusto C, Rios, Francesco J, Winklewski, Pawel J, Wolf, Jacek, Costantino, Sarah, Gkaliagkousi, Eugenia, Grassi, Guido, Guzik, Tomasz J, Ikonomidis, Ignatios, Narkiewicz, Krzysztof, Paneni, Francesco, Rizzoni, Damiano, Stamatelopoulos, Kimon, Stellos, Konstantinos, Taddei, Stefano, Touyz, Rhian M, Triantafyllou, Areti, and Virdis, Agostino

Abstract

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

Published
2023

24. Missing Verification of Source Data in Hypertension Research: The HYGIA PROJECT in Perspective

Author

Brunstrom, M, Kjeldsen, S, Kreutz, R, Gjesdal, K, Narkiewicz, K, Burnier, M, Oparil, S, Mancia, G, Brunstrom M., Kjeldsen S. E., Kreutz R., Gjesdal K., Narkiewicz K., Burnier M., Oparil S., Mancia G., Brunstrom, M, Kjeldsen, S, Kreutz, R, Gjesdal, K, Narkiewicz, K, Burnier, M, Oparil, S, Mancia, G, Brunstrom M., Kjeldsen S. E., Kreutz R., Gjesdal K., Narkiewicz K., Burnier M., Oparil S., and Mancia G.

Published
2021

25. Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk: 2021 update

Author

Borghi, C, Domienik-Karlowicz, J, Tykarski, A, Widecka, K, Filipiak, K, Jaguszewski, M, Narkiewicz, K, Mancia, G, Borghi C., Domienik-Karlowicz J., Tykarski A., Widecka K., Filipiak K. J., Jaguszewski M. J., Narkiewicz K., Mancia G., Borghi, C, Domienik-Karlowicz, J, Tykarski, A, Widecka, K, Filipiak, K, Jaguszewski, M, Narkiewicz, K, Mancia, G, Borghi C., Domienik-Karlowicz J., Tykarski A., Widecka K., Filipiak K. J., Jaguszewski M. J., Narkiewicz K., and Mancia G.

Published
2021

29. Renal Denervation in High-Risk Patients With Hypertension

Author

Mahfoud, F, Mancia, G, Schmieder, R, Narkiewicz, K, Ruilope, L, Schlaich, M, Whitbourn, R, Zirlik, A, Zeller, T, Stawowy, P, Cohen, S, Fahy, M, Bohm, M, Mahfoud F., Mancia G., Schmieder R., Narkiewicz K., Ruilope L., Schlaich M., Whitbourn R., Zirlik A., Zeller T., Stawowy P., Cohen S. A., Fahy M., Bohm M., Mahfoud, F, Mancia, G, Schmieder, R, Narkiewicz, K, Ruilope, L, Schlaich, M, Whitbourn, R, Zirlik, A, Zeller, T, Stawowy, P, Cohen, S, Fahy, M, Bohm, M, Mahfoud F., Mancia G., Schmieder R., Narkiewicz K., Ruilope L., Schlaich M., Whitbourn R., Zirlik A., Zeller T., Stawowy P., Cohen S. A., Fahy M., and Bohm M.

Abstract

Background: Renal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN. Objectives: The purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations. Methods: BP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age <65 years, with versus without isolated systolic hypertension, with versus without atrial fibrillation, and with versus without diabetes mellitus. Baseline cardiovascular risk was estimated using the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerosis cardiovascular disease (ASCVD) risk score. Results: Reduction in 24-h systolic BP at 3 years was −8.9 ± 20.1 mm Hg for the overall cohort, and for high-risk subgroups, BP reduction was −10.4 ± 21.0 mm Hg for resistant hypertension, −8.7 ± 17.4 mm Hg in patients age ≥65 years, −10.2 ± 17.9 mm Hg in patients with diabetes, −8.6 ± 18.7 mm Hg in isolated systolic hypertension, −10.1 ± 20.3 mm Hg in chronic kidney disease, and −10.0 ± 19.1 mm Hg in atrial fibrillation (p < 0.0001 compared with baseline for all). BP reduction in patients with measurements at 6, 12, 24, and 36 months showed similar reductions in office and 24-h BP for patients with varying baseline ASCVD risk scores, which was sustained to 3 years. Adverse event rates at 3 years were higher for patients with higher baseline CV risk. Conclusions: B

Published
2020

30. Update of the position paper on arterial hypertension and erectile dysfunction

Author

Viigimaa, M, Vlachopoulos, C, Doumas, M, Wolf, J, Imprialos, K, Terentes-Printzios, D, Ioakeimidis, N, Kotsar, A, Kiitam, U, Stavropoulos, K, Narkiewicz, K, Manolis, A, Jelakovic, B, Lovic, D, Kreutz, R, Tsioufis, K, Mancia, G, Viigimaa M., Vlachopoulos C., Doumas M., Wolf J., Imprialos K., Terentes-Printzios D., Ioakeimidis N., Kotsar A., Kiitam U., Stavropoulos K., Narkiewicz K., Manolis A., Jelakovic B., Lovic D., Kreutz R., Tsioufis K., Mancia G., Viigimaa, M, Vlachopoulos, C, Doumas, M, Wolf, J, Imprialos, K, Terentes-Printzios, D, Ioakeimidis, N, Kotsar, A, Kiitam, U, Stavropoulos, K, Narkiewicz, K, Manolis, A, Jelakovic, B, Lovic, D, Kreutz, R, Tsioufis, K, Mancia, G, Viigimaa M., Vlachopoulos C., Doumas M., Wolf J., Imprialos K., Terentes-Printzios D., Ioakeimidis N., Kotsar A., Kiitam U., Stavropoulos K., Narkiewicz K., Manolis A., Jelakovic B., Lovic D., Kreutz R., Tsioufis K., and Mancia G.

Abstract

Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensi

Published
2020

31. Circadian variations in blood pressure and their implications for the administration of antihypertensive drugs: Is dosing in the evening better than in the morning?

Author

Burnier, M, Kreutz, R, Narkiewicz, K, Kjeldsen, S, Oparil, S, Mancia, G, Burnier M., Kreutz R., Narkiewicz K., Kjeldsen S., Oparil S., Mancia G., Burnier, M, Kreutz, R, Narkiewicz, K, Kjeldsen, S, Oparil, S, Mancia, G, Burnier M., Kreutz R., Narkiewicz K., Kjeldsen S., Oparil S., and Mancia G.

Abstract

Blood pressure (BP) follows a circadian rhythm with a physiological decrease during the night. Studies have demonstrated that nocturnal BP as well as its dipping pattern during night-time have a significant prognostic importance for mortality and the occurrence of cardiovascular events. Therefore, hypertension management guidelines recommend to ascertain that patients treated for hypertension have well controlled BP values around the clock. To improve hypertension control during the night and eventually further reduce cardiovascular events, it has been proposed by some to prescribe at least one antihypertensive medication at bedtime. In this review, we have examined the data which could support the benefits of prescribing BP-lowering drugs at bedtime. Our conclusion is that there is no convincing evidence that the administration of BP-lowering drugs in the evening provides any significant advantage in terms of quality of BP control, prevention of target organ damage or reduction of cardiovascular events. Before changing practice for unproven benefits, it would be wise to wait for the results of the ongoing trials that are addressing this issue.

Published
2020

33. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial

Author

Schlaich, M.P., Bellet, M., Weber, Manuel, Danaietash, P., Bakris, G.L., Flack, J.M., Dreier, R.F., Sassi-Sayadi, M., Haskell, L.P., Deinum, J., Narkiewicz, K., Wang, J.G., Schlaich, M.P., Bellet, M., Weber, Manuel, Danaietash, P., Bakris, G.L., Flack, J.M., Dreier, R.F., Sassi-Sayadi, M., Haskell, L.P., Deinum, J., Narkiewicz, K., and Wang, J.G.

Abstract

Item does not contain fulltext, BACKGROUND: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. METHODS: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. FINDINGS: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square m

Published
2022

39. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial

Author

Schlaich, M, Bellet, M, Weber, M, Danaietash, P, Bakris, G, Flack, J, Dreier, R, Sassi-Sayadi, M, Haskell, L, Narkiewicz, K, Wang, J, Reid, C, Katz, I, Ajani, A, Biswas, S, Esler, M, Elder, G, Roger, S, Colquhoun, D, Mooney, J, De Backer, T, Persu, A, Chaumont, M, Krzesinski, J, Vanabsche, T, Girard, G, Pliamm, L, Schiffrin, E, Merali, F, Dresser, G, Vallee, M, Jolly, S, Chow, S, Mu, J, Yu, J, Yuan, H, Feng, Y, Zhang, X, Xie, J, Lin, L, Soucek, M, Widimsky, J, Cifkova, R, Vaclavik, J, Ullrych, M, Lukac, M, Rychlik, I, Guldager Lauridsen, T, Kantola, I, Taurio, J, Ukkola, O, Ormezzano, O, Gosse, P, Azizi, M, Courand, P, Delsart, P, Tartiere, J, Mahfoud, F, Schmieder, R, Stegbauer, J, Lurz, P, Koziolek, M, Ott, C, Toursarkissian, N, Tsioufis, K, Kyfnidis, K, Manolis, A, Patsilinakos, S, Zebekakis, P, Karavidas, A, Denes, P, Bezzegh, K, Zsom, M, Kovacs, L, Sharabi, Y, Elias, M, Sukholutsky, I, Yosefy, C, Kenis, I, Atar, S, Volpe, M, Lorenza, M, Taddei, S, Grassi, G, Veglio, F, Son, J, Kim, J, Park, J, Lee, C, Lee, H, Raugaliene, R, Marcinkeviciene, J, Kavaliauskiene, R, Deinum, J, Kroon, A, van den Born, B, Januszewicz, A, Tykarski, A, Walczewska, J, Gaciong, Z, Wiecek, A, Chrostowska, M, Kleinrok, A, Krekora, J, Kania, G, Podrazka-Szczepaniak, A, Golawski, C, Podziewski, M, Kaczmarek, B, Skoczylas, G, Wilkolaski, A, Wozniak, I, Janik-Palazzolo, M, Rewerska, B, Konradi, A, Shvarts, Y, Pecherina, T, Nikolaev, K, Liudmila, G, Orlikova, O, Mordovin, V, Petrochenkova, N, Kamalov, G, Kosmacheva, E, Tyrenko, V, Gorbunov, V, Obrezan, A, Supryadkina, T, Ler, I, Kotenko, O, Kuzin, A, Martinez, F, Redon, J, Oliveras, A, Beltran Romero, L, Shatylo, V, Rudenko, L, Bazylevych, A, Rudyk, Y, Karpenko, O, Stanislavchuk, M, Tseluyko, V, Kushnir, M, Asanov, E, Sirenko, Y, Yagensky, A, Collier, D, Gupta, P, Webb, D, Macleod, M, Mclay, J, Peace, A, Arora, S, Buchanan, P, Harris, R, Degarmo, R, Guillen, M, Karns, A, Neutel, J, Paliwal, Y, Pettis, K, Toth, P, Wayne, J, Butcher, B, Diller, P, Oparil, S, Calhoun, D, Brautigam, D, Goldman, J, Rashidi, A, Aslam, N, Haley, W, Andrawis, N, Lang, B, Miller, R, Powell, J, Dewhurst, R, Pritchard, J, Khanna, D, Tang, D, Gabra, N, Jones, C, Scott, C, Luna, B, Mussaji, M, Bhagwat, R, Bauer, M, Mcginty, J, Nambiar, R, Sangrigoli, R, Ross Davis, W, Eaves, W, Mcgrew, F, Awad, A, Bolster, E, Scott, D, Kalirao, P, Dabel, P, Calhoun, W, Gouge, S, Warren, M, Lawrence, M, Jamal, A, El-Shahawy, M, Mercado, C, Kumar, J, Velasquez-Mieyer, P, Busch, R, Lewis, T, Rich, L, Schlaich, Markus P, Bellet, Marc, Weber, Michael A, Danaietash, Parisa, Bakris, George L, Flack, John M, Dreier, Roland F, Sassi-Sayadi, Mouna, Haskell, Lloyd P, Narkiewicz, Krzysztof, Wang, Ji-Guang, Reid, Christopher, Schlaich, Markus, Katz, Ivor, Ajani, Andrew, Biswas, Sinjini, Esler, Murray, Elder, Grahame, Roger, Simon, Colquhoun, David, Mooney, John, De Backer, Tine, Persu, Alexandre, Chaumont, Martin, Krzesinski, Jean-Marie, Vanabsche, Thomas, Girard, Ginette, Pliamm, Lew, Schiffrin, Ernesto, Merali, Fatima, Dresser, George, Vallee, Michel, Jolly, Shivinder, Chow, Stephen, Wang, Jiguang, Mu, Jianjun, Yu, Jing, Yuan, Hong, Feng, Yingqing, Zhang, Xin, Xie, Jianhong, Lin, Ling, Soucek, Miroslav, Widimsky, Jiri, Cifkova, Renata, Vaclavik, Jan, Ullrych, Martin, Lukac, Martin, Rychlik, Ivan, Guldager Lauridsen, Thomas, Kantola, Ilkka, Taurio, Jyrki, Ukkola, Olavi, Ormezzano, Olivier, Gosse, Philippe, Azizi, Michel, Courand, Pierre-Yves, Delsart, Pascal, Tartiere, Jean Michel, Mahfoud, Felix, Schmieder, Roland, Stegbauer, Johannes, Lurz, Philipp, Koziolek, Michael, Ott, Christian, Toursarkissian, Nicole, Tsioufis, Konstantinos, Kyfnidis, Konstantinos, Manolis, Athanasios, Patsilinakos, Sotirios, Zebekakis, Pantelis, Karavidas, Apostolos, Denes, Pall, Bezzegh, Katalin, Zsom, Marianna, Kovacs, Laszlo, Sharabi, Yehonatan, Elias, Mazen, Sukholutsky, Ivetta, Yosefy, Chaim, Kenis, Irina, Atar, Shaul, Volpe, Massimo, Lorenza, Muiesan Maria, Taddei, Stefano, Grassi, Guido, Veglio, Franco, Son, Jung Woo, Kim, Jang-Young, Park, Joong-Il, Lee, Chang Hoon, Lee, Hae-Young, Raugaliene, Rasa, Marcinkeviciene, Jolanta Elena, Kavaliauskiene, Roma, Deinum, Jaap, Kroon, Abraham, van den Born, Bert-Jan, Januszewicz, Andrzej, Tykarski, Andrzej, Walczewska, Jolanta, Gaciong, Zbigniew, Wiecek, Andrzej, Chrostowska, Marzena, Kleinrok, Andrzej, Krekora, Jan, Kania, Grzegorz, Podrazka-Szczepaniak, Anna, Golawski, Cezary, Podziewski, Maciej, Kaczmarek, Barbara, Skoczylas, Grzegorz, Wilkolaski, Andrzej, Wozniak, Iwona, Janik-Palazzolo, Marzena, Rewerska, Barbara, Konradi, Alexandra, Shvarts, Yuriy, Pecherina, Tamara, Nikolaev, Konstantin, Liudmila, Gapon, Orlikova, Olga, Mordovin, Viktor, Petrochenkova, Natalia, Kamalov, Gadel, Kosmacheva, Elena, Tyrenko, Vadim, Gorbunov, Vladimir, Obrezan, Andrey, Supryadkina, Tatiana, Ler, Irina, Kotenko, Oleg, Kuzin, Anatoly, Martinez, Fernando, Redon, Josep, Oliveras, Anna, Beltran Romero, Luis, Shatylo, Valerii, Rudenko, Leonid, Bazylevych, Andriiy, Rudyk, Yurii, Karpenko, Oleksandr, Stanislavchuk, Mykola, Tseluyko, Vira, Kushnir, Mykola, Asanov, Ervin, Sirenko, Yuriy, Yagensky, Andriy, Collier, David, Gupta, Pankaj, Webb, David, MacLeod, Mary, McLay, James, Peace, Aaron, Arora, Samir, Buchanan, Patricia, Harris, Robert, Degarmo, Ronald, Guillen, Mario, Karns, Adam, Neutel, Joel, Paliwal, Yogesh, Pettis, Karlton, Toth, Phillip D., Wayne, Jeffrey M., Butcher, Bain, Diller, Phillip M., Oparil, Suzanne, Calhoun, David, Brautigam, Donald, Flack, John, Goldman, Jesse M., Rashidi, Arash, Aslam, Nabeel, Haley, William, Andrawis, Nabil, Lang, Brian, Miller, Randy, Powell, James, Dewhurst, Robert, Pritchard, James, Khanna, Dinesh, Tang, Dennis, Gabra, Nashwa, Park, Jean, Jones, Conigliaro, Scott, Cranford, Luna, Blanca, Mussaji, Murtaza, Bhagwat, Ravi, Bauer, Michael, McGinty, John, Nambiar, Rajesh, Sangrigoli, Renee, Ross Davis, William, Eaves, William, McGrew, Frank, Awad, Ahmed, Bolster, Eric, Scott, David, Kalirao, Paramjit, Dabel, Pascal, Calhoun, Wesley, Gouge, Steven, Warren, Mark, Lawrence, Mary Katherine, Jamal, Aamir, El-Shahawy, Mohamed, Mercado, Carlos, Kumar, Jayant, Velasquez-Mieyer, Pedro, Busch, Robert, Lewis, Todd, Rich, Lisa, Schlaich, M, Bellet, M, Weber, M, Danaietash, P, Bakris, G, Flack, J, Dreier, R, Sassi-Sayadi, M, Haskell, L, Narkiewicz, K, Wang, J, Reid, C, Katz, I, Ajani, A, Biswas, S, Esler, M, Elder, G, Roger, S, Colquhoun, D, Mooney, J, De Backer, T, Persu, A, Chaumont, M, Krzesinski, J, Vanabsche, T, Girard, G, Pliamm, L, Schiffrin, E, Merali, F, Dresser, G, Vallee, M, Jolly, S, Chow, S, Mu, J, Yu, J, Yuan, H, Feng, Y, Zhang, X, Xie, J, Lin, L, Soucek, M, Widimsky, J, Cifkova, R, Vaclavik, J, Ullrych, M, Lukac, M, Rychlik, I, Guldager Lauridsen, T, Kantola, I, Taurio, J, Ukkola, O, Ormezzano, O, Gosse, P, Azizi, M, Courand, P, Delsart, P, Tartiere, J, Mahfoud, F, Schmieder, R, Stegbauer, J, Lurz, P, Koziolek, M, Ott, C, Toursarkissian, N, Tsioufis, K, Kyfnidis, K, Manolis, A, Patsilinakos, S, Zebekakis, P, Karavidas, A, Denes, P, Bezzegh, K, Zsom, M, Kovacs, L, Sharabi, Y, Elias, M, Sukholutsky, I, Yosefy, C, Kenis, I, Atar, S, Volpe, M, Lorenza, M, Taddei, S, Grassi, G, Veglio, F, Son, J, Kim, J, Park, J, Lee, C, Lee, H, Raugaliene, R, Marcinkeviciene, J, Kavaliauskiene, R, Deinum, J, Kroon, A, van den Born, B, Januszewicz, A, Tykarski, A, Walczewska, J, Gaciong, Z, Wiecek, A, Chrostowska, M, Kleinrok, A, Krekora, J, Kania, G, Podrazka-Szczepaniak, A, Golawski, C, Podziewski, M, Kaczmarek, B, Skoczylas, G, Wilkolaski, A, Wozniak, I, Janik-Palazzolo, M, Rewerska, B, Konradi, A, Shvarts, Y, Pecherina, T, Nikolaev, K, Liudmila, G, Orlikova, O, Mordovin, V, Petrochenkova, N, Kamalov, G, Kosmacheva, E, Tyrenko, V, Gorbunov, V, Obrezan, A, Supryadkina, T, Ler, I, Kotenko, O, Kuzin, A, Martinez, F, Redon, J, Oliveras, A, Beltran Romero, L, Shatylo, V, Rudenko, L, Bazylevych, A, Rudyk, Y, Karpenko, O, Stanislavchuk, M, Tseluyko, V, Kushnir, M, Asanov, E, Sirenko, Y, Yagensky, A, Collier, D, Gupta, P, Webb, D, Macleod, M, Mclay, J, Peace, A, Arora, S, Buchanan, P, Harris, R, Degarmo, R, Guillen, M, Karns, A, Neutel, J, Paliwal, Y, Pettis, K, Toth, P, Wayne, J, Butcher, B, Diller, P, Oparil, S, Calhoun, D, Brautigam, D, Goldman, J, Rashidi, A, Aslam, N, Haley, W, Andrawis, N, Lang, B, Miller, R, Powell, J, Dewhurst, R, Pritchard, J, Khanna, D, Tang, D, Gabra, N, Jones, C, Scott, C, Luna, B, Mussaji, M, Bhagwat, R, Bauer, M, Mcginty, J, Nambiar, R, Sangrigoli, R, Ross Davis, W, Eaves, W, Mcgrew, F, Awad, A, Bolster, E, Scott, D, Kalirao, P, Dabel, P, Calhoun, W, Gouge, S, Warren, M, Lawrence, M, Jamal, A, El-Shahawy, M, Mercado, C, Kumar, J, Velasquez-Mieyer, P, Busch, R, Lewis, T, Rich, L, Schlaich, Markus P, Bellet, Marc, Weber, Michael A, Danaietash, Parisa, Bakris, George L, Flack, John M, Dreier, Roland F, Sassi-Sayadi, Mouna, Haskell, Lloyd P, Narkiewicz, Krzysztof, Wang, Ji-Guang, Reid, Christopher, Schlaich, Markus, Katz, Ivor, Ajani, Andrew, Biswas, Sinjini, Esler, Murray, Elder, Grahame, Roger, Simon, Colquhoun, David, Mooney, John, De Backer, Tine, Persu, Alexandre, Chaumont, Martin, Krzesinski, Jean-Marie, Vanabsche, Thomas, Girard, Ginette, Pliamm, Lew, Schiffrin, Ernesto, Merali, Fatima, Dresser, George, Vallee, Michel, Jolly, Shivinder, Chow, Stephen, Wang, Jiguang, Mu, Jianjun, Yu, Jing, Yuan, Hong, Feng, Yingqing, Zhang, Xin, Xie, Jianhong, Lin, Ling, Soucek, Miroslav, Widimsky, Jiri, Cifkova, Renata, Vaclavik, Jan, Ullrych, Martin, Lukac, Martin, Rychlik, Ivan, Guldager Lauridsen, Thomas, Kantola, Ilkka, Taurio, Jyrki, Ukkola, Olavi, Ormezzano, Olivier, Gosse, Philippe, Azizi, Michel, Courand, Pierre-Yves, Delsart, Pascal, Tartiere, Jean Michel, Mahfoud, Felix, Schmieder, Roland, Stegbauer, Johannes, Lurz, Philipp, Koziolek, Michael, Ott, Christian, Toursarkissian, Nicole, Tsioufis, Konstantinos, Kyfnidis, Konstantinos, Manolis, Athanasios, Patsilinakos, Sotirios, Zebekakis, Pantelis, Karavidas, Apostolos, Denes, Pall, Bezzegh, Katalin, Zsom, Marianna, Kovacs, Laszlo, Sharabi, Yehonatan, Elias, Mazen, Sukholutsky, Ivetta, Yosefy, Chaim, Kenis, Irina, Atar, Shaul, Volpe, Massimo, Lorenza, Muiesan Maria, Taddei, Stefano, Grassi, Guido, Veglio, Franco, Son, Jung Woo, Kim, Jang-Young, Park, Joong-Il, Lee, Chang Hoon, Lee, Hae-Young, Raugaliene, Rasa, Marcinkeviciene, Jolanta Elena, Kavaliauskiene, Roma, Deinum, Jaap, Kroon, Abraham, van den Born, Bert-Jan, Januszewicz, Andrzej, Tykarski, Andrzej, Walczewska, Jolanta, Gaciong, Zbigniew, Wiecek, Andrzej, Chrostowska, Marzena, Kleinrok, Andrzej, Krekora, Jan, Kania, Grzegorz, Podrazka-Szczepaniak, Anna, Golawski, Cezary, Podziewski, Maciej, Kaczmarek, Barbara, Skoczylas, Grzegorz, Wilkolaski, Andrzej, Wozniak, Iwona, Janik-Palazzolo, Marzena, Rewerska, Barbara, Konradi, Alexandra, Shvarts, Yuriy, Pecherina, Tamara, Nikolaev, Konstantin, Liudmila, Gapon, Orlikova, Olga, Mordovin, Viktor, Petrochenkova, Natalia, Kamalov, Gadel, Kosmacheva, Elena, Tyrenko, Vadim, Gorbunov, Vladimir, Obrezan, Andrey, Supryadkina, Tatiana, Ler, Irina, Kotenko, Oleg, Kuzin, Anatoly, Martinez, Fernando, Redon, Josep, Oliveras, Anna, Beltran Romero, Luis, Shatylo, Valerii, Rudenko, Leonid, Bazylevych, Andriiy, Rudyk, Yurii, Karpenko, Oleksandr, Stanislavchuk, Mykola, Tseluyko, Vira, Kushnir, Mykola, Asanov, Ervin, Sirenko, Yuriy, Yagensky, Andriy, Collier, David, Gupta, Pankaj, Webb, David, MacLeod, Mary, McLay, James, Peace, Aaron, Arora, Samir, Buchanan, Patricia, Harris, Robert, Degarmo, Ronald, Guillen, Mario, Karns, Adam, Neutel, Joel, Paliwal, Yogesh, Pettis, Karlton, Toth, Phillip D., Wayne, Jeffrey M., Butcher, Bain, Diller, Phillip M., Oparil, Suzanne, Calhoun, David, Brautigam, Donald, Flack, John, Goldman, Jesse M., Rashidi, Arash, Aslam, Nabeel, Haley, William, Andrawis, Nabil, Lang, Brian, Miller, Randy, Powell, James, Dewhurst, Robert, Pritchard, James, Khanna, Dinesh, Tang, Dennis, Gabra, Nashwa, Park, Jean, Jones, Conigliaro, Scott, Cranford, Luna, Blanca, Mussaji, Murtaza, Bhagwat, Ravi, Bauer, Michael, McGinty, John, Nambiar, Rajesh, Sangrigoli, Renee, Ross Davis, William, Eaves, William, McGrew, Frank, Awad, Ahmed, Bolster, Eric, Scott, David, Kalirao, Paramjit, Dabel, Pascal, Calhoun, Wesley, Gouge, Steven, Warren, Mark, Lawrence, Mary Katherine, Jamal, Aamir, El-Shahawy, Mohamed, Mercado, Carlos, Kumar, Jayant, Velasquez-Mieyer, Pedro, Busch, Robert, Lewis, Todd, and Rich, Lisa

Abstract

Background: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. Methods: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. Findings: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square m

Published
2022

47. Acute Effects of Electronic and Tobacco Cigarette Smoking on Sympathetic Nerve Activity and Blood Pressure in Humans

Author

Dimitriadis, K. Narkiewicz, K. Leontsinis, I. Konstantinidis, D. Mihas, C. Andrikou, I. Thomopoulos, C. Tousoulis, D. Tsioufis, K.

Abstract

Introduction: Acute tobacco cigarette (TC) smoking increases blood pressure and sympathetic nerve activity, whereas there are scarce data on the impact of electronic cigarette (EC) smok-ing. We assessed the acute effects of TC, EC and sham smoking on blood pressure, heart rate and sympathetic nervous system. Methods: We studied 12 normotensive male habitual smokers (mean age 33 years) free of cardiovascular disease. The study design was randomized and sham controlled with three experimental sessions (sham smoking, TC smoking and EC smoking). After baseline measurements at rest, the subjects were then asked to smoke (puffing habits left uncontrolled) two TC cigarettes containing 1.1 mg nicotine, EC smoking or simulated smoking with a drinking straw with a filter (sham smoking), in line with previous methodology. Results: EC smoking at 5 and 30 min compared to baseline was accompanied by the augmentation of mean arterial pressure (MAP) and heart rate (p < 0.001 for all). The muscle sympathetic nerve activity (MSNA) decrease was significant during both TC and EC sessions (p < 0.001 for both comparisons) and was similar between them (−25.1% ± 9.8% vs. −34.4% ± 8.3%, respectively, p = 0.018). Both MSNA decreases were significantly higher (p < 0.001 for both comparisons) than that elicited by sham smoking (−4.4% ± 4.8%). Skin sympathetic nerve activity increase was significant in both TC and EC groups (p < 0.001 for both comparisons) and similar between them (73.4% ± 17.9% and 71.9% ± 7%, respectively, p = 0.829). Conclusion: The unfavorable responses of sympathetic and arterial pressure to EC smoking are similar to those elicited by TC in healthy habitual smokers. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2022

49. Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry

Author

Mahfoud, F, Bohm, M, Schmieder, R, Narkiewicz, K, Ewen, S, Ruilope, L, Schlaich, M, Williams, B, Fahy, M, Mancia, G, Mahfoud F., Bohm M., Schmieder R., Narkiewicz K., Ewen S., Ruilope L., Schlaich M., Williams B., Fahy M., Mancia G., Mahfoud, F, Bohm, M, Schmieder, R, Narkiewicz, K, Ewen, S, Ruilope, L, Schlaich, M, Williams, B, Fahy, M, Mancia, G, Mahfoud F., Bohm M., Schmieder R., Narkiewicz K., Ewen S., Ruilope L., Schlaich M., Williams B., Fahy M., and Mancia G.

Abstract

Aims: Several studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function. Methods and results: The Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (-16.5 ± 28.6 mmHg, P < 0.001) and 24-h ambulatory SBP (-8.0 ± 20.0 mmHg; P < 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m2; baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR <60 mL/min/1.73 m2; baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure. Conclusion: Long-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.

Published
2019

50. Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk

Author

Borghi, C, Tykarski, A, Widecka, K, Filipiak, K, Domienik-Karlowicz, J, Kostka-Jeziorny, K, Varga, A, Jaguszewski, M, Narkiewicz, K, Mancia, G, Borghi C., Tykarski A., Widecka K., Filipiak K. J., Domienik-Karlowicz J., Kostka-Jeziorny K., Varga A., Jaguszewski M., Narkiewicz K., Mancia G., Borghi, C, Tykarski, A, Widecka, K, Filipiak, K, Domienik-Karlowicz, J, Kostka-Jeziorny, K, Varga, A, Jaguszewski, M, Narkiewicz, K, Mancia, G, Borghi C., Tykarski A., Widecka K., Filipiak K. J., Domienik-Karlowicz J., Kostka-Jeziorny K., Varga A., Jaguszewski M., Narkiewicz K., and Mancia G.

Published
2019

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