Advertisement

Exercise training in patients with pulmonary and systemic hypertension: A unique therapy for two different diseases

  • Massimo Leggio
    Correspondence
    Corresponding author at: Department of Medicine and Rehabilitation, Cardiac Rehabilitation Operative Unit, San Filippo Neri Hospital – Salus Infirmorum Clinic, Via della Lucchina 41, 00135 Rome, Italy.
    Affiliations
    Department of Medicine and Rehabilitation, Cardiac Rehabilitation Operative Unit, San Filippo Neri Hospital – Salus Infirmorum Clinic, Rome, Italy
    Search for articles by this author
  • Augusto Fusco
    Affiliations
    Physical Medicine and Neurorehabilitation Operative Unit, Salus Infirmorum Clinic, Rome, Italy
    Search for articles by this author
  • Giorgio Limongelli
    Affiliations
    Department of Medicine and Rehabilitation, Cardiac Rehabilitation Operative Unit, Santo Spirito Hospital – Villa Betania Clinic, Rome, Italy
    Search for articles by this author
  • Luca Sgorbini
    Affiliations
    Department of Medicine and Rehabilitation, Cardiac Rehabilitation Operative Unit, Santo Spirito Hospital – Villa Betania Clinic, Rome, Italy
    Search for articles by this author
Published:September 11, 2017DOI:https://doi.org/10.1016/j.ejim.2017.09.010

      Highlights

      • Pulmonary hypertension is a potentially life-threatening condition.
      • Systemic hypertension is one of the most important cardiovascular risk factors.
      • Exercise training in pulmonary hypertension patients has significant benefits.
      • Exercise training lowers blood pressure in individuals with systemic hypertension.
      • Physical activity is one of the most important modifiable factors of our lifestyle.

      Abstract

      Pulmonary hypertension is a potentially life-threatening condition. Given its evolving definition, the incidence and prevalence of the disease is difficult to define, but registries suggest an increased global awareness. The management of patients with pulmonary arterial hypertension is highly specialised and requires multi-disciplinary input from a range of healthcare professionals, including cardiologists, respiratory physicians, rheumatologists, rehabilitation physicians and cardio-pulmonary physiotherapists. Historically, exercise training in pulmonary hypertension has not been recommended because of safety concerns. However, an increasing number of studies have demonstrated the benefit of exercise training on exercise capacity, peak oxygen consumption and quality of life.
      Systemic hypertension is one of the most important risk factors for cardiovascular disease, and has been ranked as the leading cause for death and disability worldwide: therefore, adequate control of blood pressure is important for public health. Lowering of blood pressure and prevention of hypertension is in first instance preferable by lifestyle changes. These include weight loss, moderation of alcohol intake, a diet with increased fresh fruit and vegetables, reduced saturated fat, reduced salt intake, reduced stress, and, finally, increased physical activity. With regard to the latter, former guidelines predominantly recommended aerobic exercises such as walking, jogging, and cycling for lowering blood pressure.
      The main focus of this narrative overview paper is to briefly examine and summarize the benefit of exercise training in patients with pulmonary and systemic hypertension, suggest mechanisms by which exercise may improve symptoms and function and provide evidence-based recommendations regarding the frequency and intensity of exercise in these patients.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hoeper M.M.
        • Bogaard H.J.
        • Condliffe R.
        • Frantz R.
        • Khanna D.
        • Kurzyna M.
        • et al.
        Definitions and diagnosis of pulmonary hypertension.
        J Am Coll Cardiol. 2013; 62: D42-D50
        • Galiè N.
        • Humbert M.
        • Vachiery J.L.
        • Gibbs S.
        • Lang I.
        • Torbicki A.
        • et al.
        2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).
        Eur Heart J. 2016; 37: 67-119
        • Simonneau G.
        • Gatzoulis M.A.
        • Adatia I.
        • Celermajer D.
        • Denton C.
        • Ghofrani A.
        • et al.
        Updated clinical classification of pulmonary hypertension.
        J Am Coll Cardiol. 2013; 62: D34-D41
        • Strange G.
        • Playford D.
        • Stewart S.
        • Deague J.A.
        • Nelson H.
        • Kent A.
        • et al.
        Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort.
        Heart. 2012; 98: 1805-1811
        • Peacock A.J.
        • Murphy N.F.
        • McMurray J.J.
        • Caballero L.
        • Stewart S.
        An epidemiological study of pulmonary arterial hypertension.
        Eur Respir J. 2007; 30: 104-109
        • Archer S.L.
        • Weir E.K.
        • Wilkins M.R.
        Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies.
        Circulation. 2010; 121: 2045-2066
        • Galiè N.
        • Hoeper M.M.
        • Humbert M.
        • Torbicki A.
        • Vachiery J.L.
        • Barbera J.A.
        • et al.
        Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT).
        Eur Heart J. 2009; 30: 2493-2537
        • Barst R.J.
        • McGoon M.
        • Torbicki A.
        • Sitbon O.
        • Krowka M.J.
        • Olschewski H.
        • et al.
        Diagnosis and differential assessment of pulmonary arterial hypertension.
        J Am Coll Cardiol. 2004; 43: 40S-47S
        • Strange G.
        • Williams T.
        • Kermeen F.
        • Whyte K.
        • Keogh A.
        Pulmonary hypertension and breathlessness: is it a combination we can ignore?.
        Intern Med J. 2014; 44: 114-123
        • Gaine S.P.
        • Rubin L.J.
        Primary pulmonary hypertension.
        Lancet. 1998; 352: 719-725
        • Yuan P.
        • Yuan X.T.
        • Sun X.Y.
        • Pudasaini B.
        • Liu J.M.
        • Hu Q.H.
        Exercise training for pulmonary hypertension: a systematic review and meta-analysis.
        Int J Cardiol. 2015; 178: 142-146
        • Pandey A.
        • Garg S.
        • Khunger M.
        • Garg S.
        • Kumbhani D.J.
        • Chin K.M.
        • et al.
        Efficacy and safety of exercise training in chronic pulmonary hypertension: systematic review and meta-analysis.
        Circ Heart Fail. 2015; 8: 1032-1043
        • Buys R.
        • Avila A.
        • Cornelissen V.A.
        Exercise training improves physical fitness in patients with pulmonary arterial hypertension: a systematic review and meta-analysis of controlled trials.
        BMC Pulm Med. 2015; 15: 40
        • Babu A.S.
        • Padmakumar R.
        • Maiya A.G.
        • Mohapatra A.K.
        • Kamath R.L.
        Effects of exercise training on exercise capacity in pulmonary arterial hypertension: a systematic review of clinical trials.
        Heart Lung Circ. 2016; 25: 333-341
        • National Heart Institute
        Physical activity and cardiovascular health.
        JAMA. 1996; 273: 241-246
        • Tanaka H.
        • Dinenno F.A.
        • Monahan K.D.
        • Clevenger C.M.
        • DeSouza C.A.
        • Seals D.R.
        Aging, habitual exercise, and dynamic arterial compliance.
        Circulation. 2000; 102: 1270-1275
        • Kakiyama T.
        • Sugawa J.
        • Murakami H.
        • Maeda S.
        • Kuno S.
        • Matsuda M.
        Effects of short-term endurance training on aortic distensibility in young males.
        Med Sci Sports Exerc. 2005; 37: 267-271
        • Cameron J.D.
        • Dart M.D.
        Exercise training increase total systemic arterial compliance in humans.
        Am J Phys. 1994; 266: H693-H701
        • Kokkinos P.
        • Manolis A.
        • Pittaras A.
        • Doumas M.
        • Giannelou A.
        • Panagiotakos D.B.
        • et al.
        Exercise capacity and mortality in hypertensive men with and without additional risk factors.
        Hypertension. 2009; 53: 494-499
        • Myers J.
        • Prakash M.
        • Froelicher V.
        • Do D.
        • Partington S.
        • Atwood E.
        Exercise capacity and mortality among men referred for exercise testing.
        N Engl J Med. 2002; 346: 793-801
        • Boman K.
        • Gerdts E.
        • Wachtell K.
        • Dahlof B.
        • Nieminen M.S.
        • Olofsson M.
        • et al.
        Exercise and cardiovascular outcomes in hypertensive patients in relation to structure and function of left ventricular hypertrophy: the LIFE study.
        Eur J Cardiovasc Prev Rehabil. 2009; 16: 242-248
        • Guimarães G.V.
        • Ciolac E.G.
        • Carvalho V.O.
        • D'Avila V.M.
        • Bortolotto L.A.
        • Bocchi E.A.
        Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension.
        Hypertens Res. 2010; 33: 627-632
        • Leggio M.
        • Mazza A.
        • Cruciani G.
        • Sgorbini L.
        • Pugliese M.
        • Bendini M.G.
        • et al.
        Effects of exercise training on systo–diastolic ventricular dysfunction in patients with hypertension: an echocardiographic study with tissue velocity and strain imaging evaluation.
        Hypertens Res. 2014; 37: 649-654
        • Caldarone E.
        • Lombardi M.
        • Severi P.
        • Leggio M.
        Ambient air pollution and hypertension: a relationship that strikes around the clock.
        Arch Clin Hypertens. 2016; 1: 044-045
        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        • Cushman W.C.
        • Green L.A.
        • Izzo Jr., J.L.
        • et al.
        Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood pressure.
        Hypertension. 2003; 42: 1206-1252
        • Mancia G.
        • De Backer G.
        • Dominiczak A.
        • Cifkova R.
        • Fagard R.
        • Germano G.
        • et al.
        2007 Guidelines for the Management of Arterial Hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
        J Hypertens. 2007; 25: 1105-1187
        • Fox B.D.
        • Kassirer M.
        • Weiss I.
        • Raviv Y.
        • Peled N.
        • Shitrit D.
        • et al.
        Ambulatory rehabilitation improves exercise capacity in patients with pulmonary hypertension.
        J Card Fail. 2011; 17: 196-200
        • Mereles D.
        • Ehlken N.
        • Kreuscher S.
        • Ghofrani S.
        • Hoeper M.M.
        • Halank M.
        • et al.
        Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension.
        Circulation. 2006; 114: 1482-1489
        • Singh S.J.
        • Puhan M.A.
        • Andrianopoulos V.
        • Hernandes N.A.
        • Mitchell K.E.
        • Hill C.J.
        • et al.
        An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease.
        Eur Respir J. 2014; 44: 1447-1478
        • Galiè N.
        • Manes A.
        • Negro L.
        • Palazzini M.
        • Bacchi-Reggiani M.L.
        • Branzi A.
        A meta-analysis of randomized controlled trials in pulmonary arterial hypertension.
        Eur Heart J. 2009; 30: 394-403
        • de Man F.S.
        • Handoko M.L.
        • Groepenhoff H.
        • van't Hul A.J.
        • Abbink J.
        • Koppers R.J.
        • et al.
        Effects of exercise training in patients with idiopathic pulmonary arterial hypertension.
        Eur Respir J. 2009; 34: 669-675
        • Martínez-Quintana E.
        • Miranda-Calderín G.
        • Ugarte-Lopetegui A.
        • Rodríguez-González F.
        Rehabilitation program in adult congenital heart disease patients with pulmonary hypertension.
        Congenit Heart Dis. 2010; 5: 44-50
        • Ihle F.
        • Weise S.
        • Waelde A.
        • Meis T.
        • Kneidinger N.
        • Schild C.
        • et al.
        An integrated outpatient training program for patients with pulmonary hypertension—the Munich Pilot Project.
        Int J Phys Med Rehabil. 2014; 21000204
        • Ehlken N.
        • Lichtblau M.
        • Klose H.
        • Weidenhammer J.
        • Fischer C.
        • Nechwatal R.
        • et al.
        Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial.
        Eur Heart J. 2016; 37: 35-44
        • Colombo R.
        • Siqueira R.
        • Becker C.U.
        • Fernandes T.G.
        • Pires K.M.
        • Valença S.S.
        • et al.
        Effects of exercise on monocrotaline-induced changes in right heart function and pulmonary artery remodeling in rats.
        Can J Physiol Pharmacol. 2013; 91: 38-44
        • Handoko M.L.
        • de Man F.S.
        • Happé C.M.
        • Schalij I.
        • Musters R.J.
        • Westerhof N.
        • et al.
        Opposite effects of training in rats with stable and progressive pulmonary hypertension.
        Circulation. 2009; 120: 42-49
        • Ley S.
        • Fink C.
        • Risse F.
        • Ehlken N.
        • Fischer C.
        • Ley-Zaporozhan J.
        • et al.
        Magnetic resonance imaging to assess the effect of exercise training on pulmonary perfusion and blood flow in patients with pulmonary hypertension.
        Eur Radiol. 2013; 23: 324-331
        • Mant J.
        • McManus R.J.
        Does it matter whether patients take their antihypertensive medication as prescribed? The complex relationship between adherence and blood pressure control.
        J Hum Hypertens. 2006; 20: 551-553
        • Halm J.
        • Amoako E.
        Physical activity recommendation for hypertension management: does healthcare providers' advice make a difference?.
        Ethn Dis. 2008; 18: 278-282
        • Vatten L.J.
        • Nilsen T.I.
        • Holmen J.
        Combined effect of blood pressure and physical activity on cardiovascular mortality.
        J Hypertens. 2006; 24: 1939-1946
        • Burke V.
        • Beilin L.J.
        • Cutt H.E.
        • Mansour J.
        • Williams A.
        • Mori T.A.
        A lifestyle programme for treated-hypertensives-improved-health-related behaviours and cardiovascular risk factors, a randomized control trial.
        J Clin Epidemiol. 2007; 60: 133-141
        • Cox K.K.
        Exercise and blood pressure: applying findings from the laboratory to the community settings.
        Clin Exp Pharmacol Physiol. 2006; 33: 868-871
        • Cornelissen V.A.
        • Fagard R.H.
        Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors.
        Hypertension. 2005; 46: 667-675
        • Pescatello L.S.
        • Franklin B.A.
        • Fagard R.
        • Farquhar W.B.
        • Kelley G.A.
        • Ray C.A.
        American College of Sports Medicine position stand. Exercise and hypertension.
        Med Sci Sports Exerc. 2004; 36: 533-553
        • Graham I.
        • Atar D.
        • Borch-Johnsen K.
        • Boysen G.
        • Burell G.
        • Cifkova R.
        • et al.
        European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
        Eur J Cardiovasc Prev Rehabil. 2007; 14: S1-S113
        • Kokkinos P.F.
        • Giannelou A.
        • Manolis Pittaras A.
        Physical activity in the prevention and management of high blood pressure.
        Hell J Cardiol. 2009; 50: 52-59
        • Williams M.A.
        • Haskell W.L.
        • Ades P.A.
        • Amsterdam E.A.
        • Bittner V.
        • Franklin B.A.
        • et al.
        Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity and Metabolism.
        Circulation. 2007; 116: 572-584
        • Braith R.W.
        • Stewart K.J.
        Resistance exercise training: its role in the prevention of cardiovascular disease.
        Circulation. 2006; 113: 2642-2650
        • Appel L.J.
        Lifestyle modification as a means to prevent and treat high blood pressure.
        J Am Soc Nephrol. 2003; 14: S99-S102
        • Cornelissen V.A.
        • Fagard R.H.
        • Coeckelberghs E.
        • Vanhees L.
        Impact of resistance training on blood pressure and other cardiovascular risk factors. A meta-analysis of randomized, controlled trials.
        Hypertension. 2011; 58: 950-958
        • Lewington S.
        • Clarke R.
        • Qizilbash N.
        • Peto R.
        • Collins R.
        Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.
        Prospective Studies Collaboration Lancet. 2002; 360: 1903-1913
        • Stamler R.
        Implications of the INTERSALT study.
        Hypertension. 1991; 17 (I-16 – I-20)
        • Whelton P.K.
        • He J.
        • Appel L.J.
        • Cutler J.A.
        • Havas S.
        • Kotchen T.A.
        • et al.
        Primary prevention of hypertension: clinical and public health advisory from the National High Blood Pressure Education Program.
        JAMA. 2002; 288: 1882-1888
        • Kodama S.
        • Saito K.
        • Tanaka S.
        • Maki M.
        • Yachi Y.
        • Asumi M.
        • et al.
        Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women.
        JAMA. 2009; 301: 2024-2035
        • Dengel D.R.
        • Hagberg J.M.
        • Pratley R.E.
        • Rogus E.M.
        • Golberg A.P.
        Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men.
        Metabolism. 1998; 47: 1075-1082
        • Douglas J.G.
        • Bakris G.L.
        • Epstein M.
        • Ferdinand K.C.
        • Ferrario C.
        • Flack J.M.
        • et al.
        Hypertension in African Americans working group of the International Society on Hypertension in Blacks. Management of high blood pressure in Americans. Consensus statement of the Hypertension in Africans and Americans Working group of the International Society on Hypertension in Blacks.
        Arch Intern Med. 2003; 163: 525-541
        • Hagberg J.M.
        • Park J.J.
        • Brown M.D.
        The role of exercise training in the treatment of hypertension: an update.
        Sports Med. 2000; 30: 193-206
        • Kinoshita A.
        • Urata H.
        • Tanabe Y.
        • Ikeda M.
        • Tanaka H.
        • Shindo M.
        • et al.
        What types of hypertensives respond better to mild exercise therapy?.
        J Hypertens Suppl. 1988; 6: S631-S633
        • Ades P.A.
        • Gunther P.G.
        • Meyer W.L.
        • Gibson T.C.
        • Maddalena J.
        • Orfeo T.
        Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol).
        Am J Cardiol. 1990; 66: 591-596
        • Nami R.
        • Mondillo S.
        • Agricola E.
        • Lenti S.
        • Ferro G.
        • Nami N.
        • et al.
        Aerobic exercise training fails to reduce blood pressure in nondipper-type hypertension.
        Am J Hypertens. 2000; 13: 593-600
        • Westhoff T.H.
        • Schmidt S.
        • Gross V.
        • Joppke M.
        • Zidek W.
        • van der Giet M.
        • et al.
        The cardiovascular effects of upper-limb aerobic exercise in hypertensive patients.
        J Hypertens. 2008; 26: 1336-1342
        • Martin 3rd, W.H.
        • Montgomery J.
        • Snell P.G.
        • Corbett J.R.
        • Sokolov J.J.
        • Buckey J.C.
        • et al.
        Cardiovascular adaptations to intense swim training in sedentary middle-aged men and women.
        Circulation. 1987; 75: 323-330
        • Thompson P.D.
        Exercise and sport cardiology.
        Vol. 404. McGraw-Hill, New York2001
        • Stewart K.J.
        Exercise guidance in hypertension.
        Phys Sportsmed. 2000; 28: 81-82
        • Laterza M.C.
        • de Matos L.D.
        • Trombetta I.C.
        • Braga A.M.
        • Roveda F.
        • Alves M.J.
        • et al.
        Exercise training restores baroreflex sensitivity in never-treated hypertensive patients.
        Hypertension. 2007; 49: 1298-1306
        • Zanesco A.
        • Antunes E.
        Effects of exercise training on the cardiovascular system: pharmacological approaches.
        Pharmacol Ther. 2007; 114: 307-317
        • Fagard R.
        • Cornelissen V.A.
        Physical activity, exercise, fitness and blood pressure.
        in: Battagay E.J. GYH Lip Bakris G.L. Hypertension: principles and practice. Taylor & Francis Group: Boca Raton, USA2005
        • Brown M.D.
        • Dengel D.R.
        • Hogikyan R.V.
        • Supiano M.A.
        Sympathetic activity and the heterogenous blood pressure response to exercise training in hypertensives.
        J Appl Physiol. 1985; 2002: 1434-1442
        • Lombardi M.
        • Severi P.
        • Mazza A.
        • Bendini M.G.
        • Caldarone E.
        • Armeni M.
        • et al.
        Sex differences in hypertension: a question worth asking?.
        Heighpubs J Clin Hypertens. 2017; 1: 001-005
        • Caldarone E.
        • Severi P.
        • Lombardi M.
        • D'Emidio S.
        • Mazza A.
        • Bendini M.G.
        • et al.
        Hypertensive response to exercise and exercise training in hypertension: odd couple no more.
        Clin Hypertens. 2017; 23: 11
        • Severi P.
        • D'Emidio S.
        • Armeni M.
        • Bravi V.
        • Leggio M.
        Exercise training and hypertension: ready for prime-time?.
        Sports Med Rehabil J. 2017; 2: 1011
        • Leggio M.
        • Cruciani G.
        • Sgorbini L.
        • Mazza A.
        • Bendini M.G.
        • Pugliese M.
        • et al.
        Obesity-related adjunctive systo-diastolic ventricular dysfunction in patients with hypertension: echocardiographic assessment with tissue Doppler velocity and strain imaging.
        Hypertens Res. 2011; 34: 468-473
        • Grünig E.
        • Ehlken N.
        • Ghofrani A.
        • Staehler G.
        • Meyer F.J.
        • Juenger J.
        • et al.
        Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension.
        Respiration. 2011; 81: 394-401
        • Grünig E.
        • Lichtblau M.
        • Ehlken N.
        • Ghofrani H.A.
        • Reichenberger F.
        • Staehler G.
        • et al.
        Safety and efficacy of exercise training in various forms of pulmonary hypertension.
        Eur Respir J. 2012; 40: 84-92
        • Holland A.E.
        • Wadell K.
        • Spruit M.A.
        How to adapt the pulmonary rehabilitation programme to patients with chronic respiratory disease other than COPD.
        Eur Respir Rev. 2013; 22: 577-586
        • Swain D.P.
        • Franklin B.A.
        Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise.
        Am J Cardiol. 2006; 97: 141-147
        • Wisløff U.
        • Støylen A.
        • Loennechen J.P.
        • Bruvold M.
        • Rognmo Ø.
        • Haram P.M.
        • et al.
        Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study.
        Circulation. 2007; 115: 3086-3094
        • Rognmo Ø1.
        • Hetland E.
        • Helgerud J.
        • Hoff J.
        • Slørdahl S.A.
        High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease.
        Eur J Cardiovasc Prev Rehabil. 2004; 11: 216-222
        • Wenger H.A.
        • Bell G.J.
        The interactions of intensity, frequency and duration of exercise training in altering cardiorespiratory fitness.
        Sports Med. 1986; 3: 346-356
        • Tjønna A.E1.
        • Lee S.J.
        • Rognmo Ø.
        • Stølen TO
        • Bye A.
        • Haram P.M.
        • et al.
        Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study.
        Circulation. 2008; 118: 346-354
        • Cornelissen V.A.
        • Verheyden B.
        • Aubert A.E.
        • Fagard R.H.
        Effects of aerobic training intensity on resting, exercise and post-exercise blood pressure, heart rate and heart-rate variability.
        J Hum Hypertens. 2010; 24: 175-182
        • Haskell W.L.
        • Lee I.M.
        • Pate R.R.
        • Powell K.E.
        • Blair S.N.
        • Franklin B.A.
        • et al.
        Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association.
        Circulation. 2007; 116: 1081-1093
        • Corneliessen V.A.
        • Arnout J.
        • Holvoet P.
        • Fagard R.H.
        Influence of exercise at lower and higher intensity on blood pressure and cardiovascular risk factors at older age.
        J Hypertens. 2009; 27: 753-762
        • Roger M.W.
        • Probst M.M.
        • Gruber J.J.
        • Berger R.
        • Boone Jr., J.B.
        Differential effects of exercise training intensity on blood pressure and cardiovascular responses to stress in borderline hypertensive humans.
        J Hypertens. 1996; 14: 1369-1375
        • Tashiro E1.
        • Miura S.
        • Koga M.
        • Sasaguri M.
        • Ideishi M.
        • Ikeda M.
        • et al.
        Crossover comparison between the depressor effects of low and high work-rate exercise in mild hypertension.
        Clin Exp Pharmacol Physiol. 1993; 20: 689-696
        • Fagard R.H.
        Exercise characteristics and the blood pressure responses to dynamic physical training.
        Med Sci Sports Exerc. 2001; 33: S484-S492
        • Kokkinos P.
        • Pittaras A.
        • Manolis A.
        • Panagiotakos D.
        • Narayan P.
        • Manjoros D.
        • et al.
        Exercise capacity and 24-h blood pressure in prehypertensive men and women.
        Am J Hypertens. 2006; 19: 251-258
        • Molmen-Hansen H.E.
        • Stolen T.
        • Tjonna A.E.
        • Aamot I.L.
        • Ekeberg I.S.
        • Tyldum G.A.
        • et al.
        Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients.
        Eur J Prev Cardiol. 2012; 19: 151-160
        • Wasfy M.M.
        • Baggish A.L.
        Exercise dose in clinical practice.
        Circulation. 2016; 133: 2297-2313
        • Thompson P.D.
        • Funk E.J.
        • Carleton R.A.
        • Sturner W.Q.
        Incidence of death during jogging in Rhode Island from 1975 through 1980.
        JAMA. 1982; 247: 2535-2538
        • Siscovick D.S.
        • Weiss N.S.
        • Fletcher R.H.
        • Lasky T.
        The incidence of primary cardiac arrest during vigorous exercise.
        N Engl J Med. 1984; 311: 874-877
        • Vina J.
        • Sanchis-Gomar F.
        • Martinez-Bello V.
        • Gomez-Cabrera M.C.
        Exercise acts as a drug; the pharmacological benefits of exercise.
        Br J Pharmacol. 2012; 167: 1-12