Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension

Objective Isometric wall squat training (IWST) is one of the most effective exercise modalities for lowering blood pressure. Among the physiological mechanisms contributing to this effect, the reduction in total peripheral resistance (TPR) is particularly relevant. There are differences in pathophys...

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Autores:
Quiceno Carmona, Maria Alexandra
Tipo de recurso:
Article of investigation
Fecha de publicación:
2025
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/47298
Acceso en línea:
https://hdl.handle.net/10495/47298
Palabra clave:
Hipertensión
Hypertension
Monitoreo ambulatorio de la presión arterial
Blood Pressure Monitoring, Ambulatory
Resistencia vascular
Vascular Resistance
Ejercicios isométricos
Isometric exercise
Sentadilla isométrica
https://id.nlm.nih.gov/mesh/D006973
https://id.nlm.nih.gov/mesh/D018660
https://id.nlm.nih.gov/mesh/D014655
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
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openAccess
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http://creativecommons.org/licenses/by-nc-sa/4.0/
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oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/47298
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.eng.fl_str_mv Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
dc.title.translated.none.fl_str_mv Efecto agudo de la sentadilla isométrica sobre el estado hemodinámico y autonómico según el sexo en pacientes con hipertensión
title Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
spellingShingle Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
Hipertensión
Hypertension
Monitoreo ambulatorio de la presión arterial
Blood Pressure Monitoring, Ambulatory
Resistencia vascular
Vascular Resistance
Ejercicios isométricos
Isometric exercise
Sentadilla isométrica
https://id.nlm.nih.gov/mesh/D006973
https://id.nlm.nih.gov/mesh/D018660
https://id.nlm.nih.gov/mesh/D014655
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
title_short Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
title_full Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
title_fullStr Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
title_full_unstemmed Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
title_sort Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertension
dc.creator.fl_str_mv Quiceno Carmona, Maria Alexandra
dc.contributor.advisor.none.fl_str_mv Gallo Villegas, Jaime Alberto
dc.contributor.author.none.fl_str_mv Quiceno Carmona, Maria Alexandra
dc.contributor.jury.none.fl_str_mv Velasquez Penagos, Jesus Arnulfo
Quintero Velasquez, Mario Andres
dc.subject.decs.none.fl_str_mv Hipertensión
Hypertension
Monitoreo ambulatorio de la presión arterial
Blood Pressure Monitoring, Ambulatory
Resistencia vascular
Vascular Resistance
topic Hipertensión
Hypertension
Monitoreo ambulatorio de la presión arterial
Blood Pressure Monitoring, Ambulatory
Resistencia vascular
Vascular Resistance
Ejercicios isométricos
Isometric exercise
Sentadilla isométrica
https://id.nlm.nih.gov/mesh/D006973
https://id.nlm.nih.gov/mesh/D018660
https://id.nlm.nih.gov/mesh/D014655
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
dc.subject.lem.none.fl_str_mv Ejercicios isométricos
Isometric exercise
dc.subject.proposal.spa.fl_str_mv Sentadilla isométrica
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D006973
https://id.nlm.nih.gov/mesh/D018660
https://id.nlm.nih.gov/mesh/D014655
dc.subject.ods.none.fl_str_mv ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
description Objective Isometric wall squat training (IWST) is one of the most effective exercise modalities for lowering blood pressure. Among the physiological mechanisms contributing to this effect, the reduction in total peripheral resistance (TPR) is particularly relevant. There are differences in pathophysiology between men and women in hypertension (HTN); it is unknown whether the effect of IWST is heterogeneous according to sex. This study aims to evaluate the acute hemodynamic and autonomic responses to IWST according to sex in patients with newly diagnosed HTN. Methods Quasi-experimental study that included patients with recently diagnosed HTN in whom the hemodynamic and autonomic response during a IWST session (4-repetition) was evaluated using impedance cardiography according to sex. The diagnosis of high blood pressure was confirmed by 24-hour ambulatory blood pressure monitoring. Results Among the patients included (n=74), the average age was 53.0  6.8 years; 56.7% (n=42) were men. Women showed a smaller increase in heart rate (HR) (–5.1; 95% CI: –9.3 to –0.8 bpm; p value = 0.019), and total peripheral resistance index (TPRI) (–299.6; 95% CI: –487.1 to –112.1 dyne·s·m²/cm⁵; p value = 0.002), less reduction in stroke volume index (SVI) (3.1; 95% CI: 0.8 to 5.4 mL/m2; p value = 0.009), and a greater increase in cardiac index (CI) (0.3; 95% CI: 0.03 to 0.5 L/min·m2; p value = 0.025) compared to men during the isometric squat repetitions. Likewise, during the recovery periods, women showed a greater reduction in HR (–6.0; 95% CI: –9.5 to –2.4 bpm; p value = 0.001) and TPRI (–181.0; 95% CI: –357.5 to –4.4 dyne·s·m²/cm⁵; p value = 0.045), a greater increase in SVI (3.0; 95% CI: 1.0 to 5.0 mL/m2; p value = 0.004), greater reduction in the sympathetic activity (LF/HF ratio) (–1.1; 95% CI: –2.2 to –0.05; p value = 0.041) and greater increase in spontaneous baroreflex sensitivity (SBS) (2.4; 95% CI: 0.5 to 4.2 ms/mmHg; p value = 0.011) compared to men. Notably, women showed a smaller increase in HR (–7.9; 95% CI: –12.4 to –3.3 bpm; p value = 0.001) following IWST, with no other between-sex differences observed post-session. Conclusion Individuals with newly diagnosed arterial HTN without anti-hypertensive pharmacological treatment present a heterogeneous hemodynamic and autonomic response during an IWST session according to sex. Women exhibit a smaller increase in TPR, greater increase in CI during the isometric squat, and greater reductions in TPR during recovery periods, accompanied by a better autonomic control, compared to men. These findings highlight the potential value of considering sex-specific mechanisms when prescribing isometric training as a non-pharmacological intervention for blood pressure control. Further studies are needed to evaluate chronic adaptations to this training modality.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-09-04T17:03:50Z
dc.date.issued.none.fl_str_mv 2025
dc.type.none.fl_str_mv Trabajo de grado - Especialización
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url https://hdl.handle.net/10495/47298
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.references.none.fl_str_mv Forouzanfar MH, Alexander L, Anderson HR, Bachman VF, Biryukov S, Brauer M, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(10010):2287-323.
Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224-60.
Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, et al. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017;317(2):165-82.
Zhou B, Perel P, Mensah GA, Ezzati M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol. 2021;18(11):785-802
Chapman N, Ching SM, Konradi AO, Nuyt AM, Khan T, Twumasi-Ankrah B, et al. Arterial Hypertension in Women: State of the Art and Knowledge Gaps. Hypertension. 2023;80(6):1140-9.
Safar ME, Smulyan H. Hypertension in women. Am J Hypertens. 2004;17(1):82-7.
Edwards JJ, Deenmamode AHP, Griffiths M, Arnold O, Cooper NJ, Wiles JD, et al. Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials. Br J Sports Med. 2023;57(20):1317-26.
Baffour-Awuah B, Pearson MJ, Dieberg G, Wiles JD, Smart NA. An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications. Clin Hypertens. 2023;29(1):9.
O'Driscoll JM, Edwards JJ, Coleman DA, Taylor KA, Sharma R, Wiles JD. One year of isometric exercise training for blood pressure management in men: a prospective randomized controlled study. J Hypertens. 2022;40(12):2406-12
World Medical A. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025;333(1):71-4.
O'Driscoll JM, Boucher C, Vilda M, Taylor KA, Wiles JD. Continuous cardiac autonomic and haemodynamic responses to isometric exercise in females. Eur J Appl Physiol. 2021;121(1):319-29.
Brown H PR. Applied mixed models in medicine. 3rd Edition ed: Willey; 2015
Joyner MJ, Wallin BG, Charkoudian N. Sex differences and blood pressure regulation in humans. Exp Physiol. 2016;101(3):349-55.
Taylor CE, Arnold AC, Fu Q, Shibao CA. Sex differences in cardiovascular autonomic control: introduction to the special issue. Clin Auton Res. 2020;30(5):365-7.
Jarvis SS, VanGundy TB, Galbreath MM, Shibata S, Okazaki K, Reelick MF, et al. Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans. Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R193-200.
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dc.publisher.program.none.fl_str_mv Especialización en Medicina Aplicada a la Actividad Física y al Deporte
dc.publisher.department.none.fl_str_mv Departamento de Fisiología y Bioquímica
dc.publisher.place.none.fl_str_mv Medellín, Colombia
dc.publisher.faculty.none.fl_str_mv Facultad de Medicina
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publisher.none.fl_str_mv Universidad de Antioquia
institution Universidad de Antioquia
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spelling Gallo Villegas, Jaime AlbertoQuiceno Carmona, Maria AlexandraVelasquez Penagos, Jesus ArnulfoQuintero Velasquez, Mario Andres2025-09-04T17:03:50Z2025https://hdl.handle.net/10495/47298Objective Isometric wall squat training (IWST) is one of the most effective exercise modalities for lowering blood pressure. Among the physiological mechanisms contributing to this effect, the reduction in total peripheral resistance (TPR) is particularly relevant. There are differences in pathophysiology between men and women in hypertension (HTN); it is unknown whether the effect of IWST is heterogeneous according to sex. This study aims to evaluate the acute hemodynamic and autonomic responses to IWST according to sex in patients with newly diagnosed HTN. Methods Quasi-experimental study that included patients with recently diagnosed HTN in whom the hemodynamic and autonomic response during a IWST session (4-repetition) was evaluated using impedance cardiography according to sex. The diagnosis of high blood pressure was confirmed by 24-hour ambulatory blood pressure monitoring. Results Among the patients included (n=74), the average age was 53.0  6.8 years; 56.7% (n=42) were men. Women showed a smaller increase in heart rate (HR) (–5.1; 95% CI: –9.3 to –0.8 bpm; p value = 0.019), and total peripheral resistance index (TPRI) (–299.6; 95% CI: –487.1 to –112.1 dyne·s·m²/cm⁵; p value = 0.002), less reduction in stroke volume index (SVI) (3.1; 95% CI: 0.8 to 5.4 mL/m2; p value = 0.009), and a greater increase in cardiac index (CI) (0.3; 95% CI: 0.03 to 0.5 L/min·m2; p value = 0.025) compared to men during the isometric squat repetitions. Likewise, during the recovery periods, women showed a greater reduction in HR (–6.0; 95% CI: –9.5 to –2.4 bpm; p value = 0.001) and TPRI (–181.0; 95% CI: –357.5 to –4.4 dyne·s·m²/cm⁵; p value = 0.045), a greater increase in SVI (3.0; 95% CI: 1.0 to 5.0 mL/m2; p value = 0.004), greater reduction in the sympathetic activity (LF/HF ratio) (–1.1; 95% CI: –2.2 to –0.05; p value = 0.041) and greater increase in spontaneous baroreflex sensitivity (SBS) (2.4; 95% CI: 0.5 to 4.2 ms/mmHg; p value = 0.011) compared to men. Notably, women showed a smaller increase in HR (–7.9; 95% CI: –12.4 to –3.3 bpm; p value = 0.001) following IWST, with no other between-sex differences observed post-session. Conclusion Individuals with newly diagnosed arterial HTN without anti-hypertensive pharmacological treatment present a heterogeneous hemodynamic and autonomic response during an IWST session according to sex. Women exhibit a smaller increase in TPR, greater increase in CI during the isometric squat, and greater reductions in TPR during recovery periods, accompanied by a better autonomic control, compared to men. These findings highlight the potential value of considering sex-specific mechanisms when prescribing isometric training as a non-pharmacological intervention for blood pressure control. Further studies are needed to evaluate chronic adaptations to this training modality.EspecializaciónEspecialista en Medicina Aplicada a la Actividad Física y al Deporte33 páginasapplication/pdfapplication/vnd.ms-excelengUniversidad de AntioquiaEspecialización en Medicina Aplicada a la Actividad Física y al DeporteDepartamento de Fisiología y BioquímicaMedellín, ColombiaFacultad de MedicinaCampus Medellín - Ciudad Universitariahttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Acute effect of isometric wall squat on hemodynamic and autonomic status according to sex in patients with hypertensionEfecto agudo de la sentadilla isométrica sobre el estado hemodinámico y autonómico según el sexo en pacientes con hipertensiónTrabajo de grado - Especializaciónhttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/resource_type/c_93fchttp://purl.org/redcol/resource_type/ARTTexthttp://purl.org/coar/version/c_b1a7d7d4d402bcceinfo:eu-repo/semantics/reportinfo:eu-repo/semantics/draftForouzanfar MH, Alexander L, Anderson HR, Bachman VF, Biryukov S, Brauer M, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(10010):2287-323.Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224-60.Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, et al. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017;317(2):165-82.Zhou B, Perel P, Mensah GA, Ezzati M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol. 2021;18(11):785-802Chapman N, Ching SM, Konradi AO, Nuyt AM, Khan T, Twumasi-Ankrah B, et al. Arterial Hypertension in Women: State of the Art and Knowledge Gaps. Hypertension. 2023;80(6):1140-9.Safar ME, Smulyan H. Hypertension in women. Am J Hypertens. 2004;17(1):82-7.Edwards JJ, Deenmamode AHP, Griffiths M, Arnold O, Cooper NJ, Wiles JD, et al. Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials. Br J Sports Med. 2023;57(20):1317-26.Baffour-Awuah B, Pearson MJ, Dieberg G, Wiles JD, Smart NA. An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications. Clin Hypertens. 2023;29(1):9.O'Driscoll JM, Edwards JJ, Coleman DA, Taylor KA, Sharma R, Wiles JD. One year of isometric exercise training for blood pressure management in men: a prospective randomized controlled study. J Hypertens. 2022;40(12):2406-12World Medical A. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025;333(1):71-4.O'Driscoll JM, Boucher C, Vilda M, Taylor KA, Wiles JD. Continuous cardiac autonomic and haemodynamic responses to isometric exercise in females. Eur J Appl Physiol. 2021;121(1):319-29.Brown H PR. Applied mixed models in medicine. 3rd Edition ed: Willey; 2015Joyner MJ, Wallin BG, Charkoudian N. Sex differences and blood pressure regulation in humans. Exp Physiol. 2016;101(3):349-55.Taylor CE, Arnold AC, Fu Q, Shibao CA. Sex differences in cardiovascular autonomic control: introduction to the special issue. Clin Auton Res. 2020;30(5):365-7.Jarvis SS, VanGundy TB, Galbreath MM, Shibata S, Okazaki K, Reelick MF, et al. Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans. Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R193-200.HipertensiónHypertensionMonitoreo ambulatorio de la presión arterialBlood Pressure Monitoring, AmbulatoryResistencia vascularVascular ResistanceEjercicios isométricosIsometric exerciseSentadilla isométricahttps://id.nlm.nih.gov/mesh/D006973https://id.nlm.nih.gov/mesh/D018660https://id.nlm.nih.gov/mesh/D014655ODS 3: Salud y bienestar. 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