Sex-based comparison of the blood pressure, haemodynamic and cardiac autonomic adaptations following isometric exercise training in sedentary adults: a randomised controlled trial

Objectives We aimed to explore sex-specific differences in resting blood pressure (BP) reduction and associated cardiovascular adaptations following isometric exercise training (IET).

Methods 100 sedentary adults with normal to high-normal systolic BP volunteered for the study. Participants either performed home-based lower-body IET in the form of a wall squat three times a week for 4 weeks (each session comprised 4×2 min bouts) or were allocated to the control group. Cardiovascular variables, including BP, cardiac output, total peripheral resistance, stroke volume and heart rate variability (HRV), were measured at rest preintervention and postintervention.

Results Following 4 weeks of IET, there were no significant differences in resting systolic BP and diastolic BP between females (122.1±6.9 and 80.0±8.3 mm Hg) and males (119.6±7.2 and 77.4±8.6 mm Hg). However, female participants had a greater cardiac autonomic response following training, evidenced by a lower low-frequency to high-frequency HRV ratio (F: 1.38±1.27 and M: 2.1±1.5, p=0.004) and decreased and elevated low-frequency normalised units (F: 50.3%±16.2% and M: 60.9%±16.9%, p=0.015) and high-frequency normalised units (F: 49.7%±16.2% and M: 39.1%±16.9%, p=0.015), respectively.

Conclusions While resting BP reductions were comparable between female and male participants, there was a greater autonomic response and a higher incidence of clinically important BP reductions in females, which could indicate a greater cardioprotective effect following IET. These findings highlight the importance of considering sex differences in the prescription and evaluation of exercise interventions for hypertension management.

​​1. Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Erratum: Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017 (The Lancet (2018) 392(10159) (1736–1788)(S0140673618322037)(10.1016/S0140-6736(18)32203-7)). Vol. 392, The Lancet. 2018.

​2. Saheera S, Krishnamurthy P. Cardiovascular Changes Associated with Hypertensive Heart Disease and Aging. Vol. 29, Cell Transplantation. 2020.

​3. Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. The Lancet. 2021;398(10304).

​4. Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 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). J Hypertens. 2023;41(12).

​5. Cornelissen VA, Smart NA. Exercise training for blood pressure: a systematic review and meta-analysis. Journal of the American Heart Association. 2013.

​6. 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;

​7. Inder JD, Carlson DJ, Dieberg G, Mcfarlane JR, Hess NCL, Smart NA. Isometric exercise training for blood pressure management: A systematic review and meta-analysis to optimize benefit. Hypertension Research. 2016;

​8. Smart NA, Way D, Carlson D, Millar P, McGowan C, Swaine I, et al. Effects of isometric resistance training on resting blood pressure: Individual participant data meta-Analysis. Journal of Hypertension. 2019.

​9. Bentley DC, Nguyen CH, Thomas SG. Resting blood pressure reductions following handgrip exercise training and the impact of age and sex: A systematic review and narrative synthesis. Systematic Reviews. 2018.

​10. World Health Organization. GLOBAL ACTION PLAN ON PHYSICAL ACTIVITY 2018-2030. GLOBAL ACTION PLAN ON PHYSICAL ACTIVITY 2018-2030. 2019.

​11. Faul F, Erdfelder E, Buchner A, Lang A georg. Statistical power analyses using G * Power 3 . 1 : Behav Res Methods. 2009;41(4).

​12. Taylor KA, Wiles JD, Coleman DA, Leeson P, Sharma R, O’Driscoll JM. Neurohumoral and ambulatory haemodynamic adaptations following isometric exercise training in unmedicated hypertensive patients. J Hypertens. 2019;

​13. Wiles JD, Goldring N, Coleman D. Home-based isometric exercise training induced reductions resting blood pressure. Eur J Appl Physiol. 2017;

​14. Fortin J, Habenbacher W, Gruellenberger R, Wach P, Skrabal F. Real-time monitor for hemodynamic beat-to-beat parameters and power spectra analysis of the biosignals. In 2002.

​15. Parati G, Ongaro G, Bilo G, Glavina F, Castiglioni P, Di Rienzo M, et al. Non-invasive beat-to-beat blood pressure monitoring: New developments. In: Blood Pressure Monitoring. 2003.

​16. Fortin J, Haitchi G, Bojic A, Habenbacher W, Grüllenberger R, Heller A, et al. Validation and Verification of the Task Force® Monitor. FDA paper. 2001;

​17. Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: A quantitative probe of beat-to-beat cardiovascular control. Science (1979). 1981;

​18. Valipour A, Schneider F, Kössler W, Saliba S, Burghuber OC. Heart rate variability and spontaneous baroreflex sequences in supine healthy volunteers subjected to nasal positive airway pressure. J Appl Physiol. 2005;

​19. Canoy D, Nazarzadeh M, Copland E, Bidel Z, Rao S, Li Y, et al. How Much Lowering of Blood Pressure Is Required to Prevent Cardiovascular Disease in Patients With and Without Previous Cardiovascular Disease? Vol. 24, Current Cardiology Reports. 2022.

​20. Pagani M, Montano N, Porta A, Malliani A, Abboud FM, Birkett C, et al. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation. 1997;

​21. Kim HG, Cheon EJ, Bai DS, Lee YH, Koo BH. Stress and heart rate variability: A meta-analysis and review of the literature. Vol. 15, Psychiatry Investigation. 2018.

​22. Gerdts E, Sudano I, Brouwers S, Borghi C, Bruno RM, Ceconi C, et al. Sex differences in arterial hypertension. Vol. 43, European Heart Journal. 2022.

​23. Fisher JP, Adlan AM, Shantsila A, Secher JF, Sørensen H, Secher NH. Muscle metaboreflex and autonomic regulation of heart rate in humans. Journal of Physiology. 2013;591(15).

​24. Barbagallo M, Dominguez LJ, Licata G, Shan J, Bing L, Karpinski E, et al. Vascular effects of progesterone: Role of cellular calcium regulation. Hypertension. 2001;37(1).

​25. Aryan L, Younessi D, Zargari M, Banerjee S, Agopian J, Rahman S, et al. The role of estrogen receptors in cardiovascular disease. Vol. 21, International Journal of Molecular Sciences. 2020.

​26. Khalil RA. Sex hormones as potential modulators of vascular function in hypertension. Vol. 46, Hypertension. 2005.

​27. Xia Y, Krukoff TL. Estrogen induces nitric oxide production via activation of constitutive nitric oxide synthases in human neuroblastoma cells. Endocrinology. 2004;145(10).

​28. McEwen BS, Akama KT, Spencer-Segal JL, Milner TA, Waters EM. Estrogen effects on the brain: Actions beyond the hypothalamus via novel mechanisms. Behavioral Neuroscience. 2012;126(1).

​29. Machuki JO, Zhang HY, Harding SE, Sun H. Molecular pathways of oestrogen receptors and β-adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value. Vol. 222, Acta Physiologica. 2018.

​30. Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach J, Joyner MJ. Sex and ageing differences in resting arterial pressure regulation: The role of the β-adrenergic receptors. Journal of Physiology. 2011;589(21).

​31. Thayer JF, Lane RD. The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol. 2007;74(2).

​32. Kappus RM, Ranadive SM, Yan H, Lane-Cordova AD, Cook MD, Sun P, et al. Sex differences in autonomic function following maximal exercise. Biol Sex Differ. 2015;6(1).

​33. Teixeira AL, Ritti-Dias R, Antonino D, Bottaro M, Millar PJ, Vianna LC. Sex Differences in Cardiac Baroreflex Sensitivity after Isometric Handgrip Exercise. Med Sci Sports Exerc. 2018;50(4).

​34. Farah B, Germano-Soares A, Rodrigues S, Santos C, Barbosa S, Vianna L, et al. Acute and Chronic Effects of Isometric Handgrip Exercise on Cardiovascular Variables in Hypertensive Patients: A Systematic Review. Sports. 2017;

​35. Wright JT, Whelton PK, Johnson KC, Snyder JK, Reboussin DM, Cushman WC, et al. SPRINT Revisited: Updated Results and Implications. Vol. 78, Hypertension. 2021.

​36. Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: Updated systematic review and meta-analysis. The Lancet. 2016;387(10017).

​37. Wong GW, Boyda HN, Wright JM. Blood pressure lowering efficacy of beta-1 selective beta blockers for primary hypertension. Vol. 2016, Cochrane Database of Systematic Reviews. 2016.

​38. NICE. Hypertension in adults: Diagnosis and management. Vol. 49, Practice Nurse. 2019.

​39. Lea JWD, O’Driscoll JM, Wiles JD. The implementation of a home-based isometric wall squat intervention using ratings of perceived exertion to select and control exercise intensity: a pilot study in normotensive and pre-hypertensive adults. Eur J Appl Physiol. 2023;

​40. Teixeira AL, Ramos PS, Vianna LC, Ricardo DR. Heart rate variability across the menstrual cycle in young women taking oral contraceptives. Psychophysiology. 2015;52(11).

​41. Brahmbhatt Y, Gupta M, Hamrahian S. Hypertension in Premenopausal and Postmenopausal Women. Vol. 21, Current Hypertension Reports. 2019.