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Making the Case to Measure and Improve Cardiorespiratory Fitness in Routine Clinical Practice

  • Carl J. Lavie
    Correspondence
    Correspondence: Address to Carl J. Lavie, MD, John Ochsner Heart and Vascular Institute, 1514 Jefferson Hwy, New Orleans, LA 70121.
    Affiliations
    John Ochsner Heart and Vascular Institute, Ochsner Clinical School–The UQ School of Medicine, New Orleans, LA
    Healthy Living for Pandemic Event Protection (HL-PIVOT)
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  • Ross Arena
    Affiliations
    Department of Physical Therapy, College of Applied Health Sciences, University of Illinois Chicago, Chicago, IL
    Healthy Living for Pandemic Event Protection (HL-PIVOT)
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  • Leonard A. Kaminsky
    Affiliations
    Fisher Institute of Health and Well Being, Ball State University, Muncie, IN
    Healthy Living for Pandemic Event Protection (HL-PIVOT)
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      Substantial data have accumulated for decades demonstrating the protective effects of regular physical activity (PA), including exercise training, and cardiorespiratory fitness (CRF) on cardiovascular disease (CVD) morbidity and mortality as well as all-cause mortality.
      • Lavie C.J.
      • Ozemek C.
      • Carbone S.
      • Katzmarzyk P.T.
      • Blair S.N.
      Sedentary behavior, exercise, and cardiovascular health.
      In fact, PA and CRF may have stronger correlations with CVD prognosis than any of the traditional CVD risk factors.
      • Lavie C.J.
      • Ozemek C.
      • Carbone S.
      • Katzmarzyk P.T.
      • Blair S.N.
      Sedentary behavior, exercise, and cardiovascular health.
      In recent years, Mayo Clinic Proceedings has emphasized papers in the areas of PA and CRF,
      • Wittfeld K.
      • Jochem C.
      • Dorr M.
      • et al.
      Cardiorespiratory fitness is related to higher gray matter volume in temporal, frontal and cerebellar regions in the general population.
      • Petersen R.C.
      • Joyner M.J.
      • Jack Jr., C.R.
      Cardiorespiratory fitness and brain volumes.
      • Laukkanen J.A.
      • Kunutsor S.K.
      • Yates T.
      • et al.
      Prognostic relevance of cardiorespiratory fitness as assessed by submaximal exercise testing for all-cause mortality: a UK Biobank Prospective Study.
      • Lavie C.J.
      • Lee D.C.
      • Ortega F.B.
      UK Biobank contributes to aerobic and muscle fitness research.
      • Whelton S.P.
      • McAuley P.A.
      • Dardari Z.
      • et al.
      Fitness and mortality among persons 70 years and older across the spectrum of cardiovascular disease risk factor burden: the FIT project.
      • Kaminsky L.A.
      • Arena R.
      • Myers J.
      • et al.
      Updated reference standards for cardiorespiratory fitness measured with cardiopulmonary exercise testing: data from the Fitness Registry and the Importance of Exercise National Database (FRIEND).
      • Myers J.
      • Vainshelboim B.
      • Kamil-Rosenberg S.
      • Chan K.
      • Kokkinos P.
      Physical activity, cardiorespiratory fitness, and population-attributable risk.
      including publications that also incorporate adiposity, obesity, and the obesity paradox.
      • Sanchez-Lastra M.A.
      • Ding D.
      • Dalene K.E.
      • Ekelund U.
      • Tarp J.
      Physical activity and mortality across levels of adiposity: a prospective cohort study from the UK Biobank.
      • Rozanski A.
      • Gransar H.
      • Hayes S.W.
      • et al.
      Synergistic assessment of mortality risk according to body mass index and exercise ability and capacity in patients referred for radionuclide stress testing.
      • Allison T.G.
      Addressing the complex synergy between exercise capacity and BMI and its relationship to all-cause mortality.
      In this issue of Mayo Clinic Proceedings, Laukkanen et al
      • Laukkanen J.A.
      • Isiozor N.M.
      • Kunutsor S.K.
      Objectively assessed cardiorespiratory fitness and all-cause mortality risk: an updated meta-analysis of 37 cohort studies involving 2,258,029 million participants.
      performed one of the largest meta-analyses to date, reviewing data from 37 studies of nearly 2.3 million participants with the occurrence of close to 110,000 deaths. They demonstrated that every 1 metabolic equivalent increase in estimated CRF (eCRF) was associated with an 11% reduction in mortality. The top tertile of eCRF had a 45% lower mortality compared with the lowest tertile of eCRF. Finally, these associations were present regardless of year of publication, age, sex, follow-up duration, CRF assessment method, and risk of bias. The authors therefore justifiably suggested that guideline bodies should consider including CRF in standard risk panels for mortality risk assessment.
      These results by Laukkanen et al
      • Laukkanen J.A.
      • Isiozor N.M.
      • Kunutsor S.K.
      Objectively assessed cardiorespiratory fitness and all-cause mortality risk: an updated meta-analysis of 37 cohort studies involving 2,258,029 million participants.
      as well as the considerable body of evidence supporting the importance of CRF for assessment of mortality risk add to the classic study by Kodama et al
      • Kodama S.
      • Saito K.
      • Tanaka S.
      • et al.
      Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis.
      published more than a decade ago and updated by Harber et al in 2017.
      • Harber M.P.
      • Kaminsky L.A.
      • Arena R.
      • et al.
      Impact of cardiorespiratory fitness on all-cause and disease-specific mortality: advances since 2009.
      The study by Laukkanen et al
      • Laukkanen J.A.
      • Isiozor N.M.
      • Kunutsor S.K.
      Objectively assessed cardiorespiratory fitness and all-cause mortality risk: an updated meta-analysis of 37 cohort studies involving 2,258,029 million participants.
      confirms the importance of objectively measured CRF with cardiopulmonary stress testing (CPX) or eCRF from submaximal and maximal exercise tests (ie, blood pressure, electrocardiography, and subjective scale monitoring) without CPX. Although better than nonexercise eCRF, there still is some error associated with maximal exercise testing compared with precise assessment of CRF by ventilatory expired gas analysis (ie, CPX).
      • Peterman J.E.
      • Harber M.P.
      • Imboden M.T.
      • et al.
      Accuracy of nonexercise prediction equations for assessing longitudinal changes to cardiorespiratory fitness in apparently healthy adults: BALL ST Cohort.
      When using eCRF to categorize participants into tertiles, submaximal exercise equations correctly classified an average of only 51% (range, 37% to 58%) and maximal exercise equations correctly classified an average of only 59% (range, 43% to 46%).
      • Peterman J.E.
      • Harber M.P.
      • Imboden M.T.
      • et al.
      Accuracy of exercise-based equations for estimating cardiorespiratory fitness.
      In addition, Laukkanen et al
      • Laukkanen J.A.
      • Isiozor N.M.
      • Kunutsor S.K.
      Objectively assessed cardiorespiratory fitness and all-cause mortality risk: an updated meta-analysis of 37 cohort studies involving 2,258,029 million participants.
      use the “old” dogma that “a major reason why CRF is not employed in routine clinical practice is because the use of CPX for defining CRF involves skills, equipment, and relatively high costs compared to the assessment of other risk factors such as blood pressure, blood lipid levels and smoking status.”
      • Kodama S.
      • Saito K.
      • Tanaka S.
      • et al.
      Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis.
      However, as Kaminsky et al
      • Kaminsky L.A.
      • Arena R.
      • Ellingsen Ø.
      • et al.
      Cardiorespiratory fitness and cardiovascular disease: the past, present, and future.
      recently pointed out, “with rapid technological advancements, commercial metabolic exercise testing units that are compact, easy to use, provide breath-by-breath analysis in real time and can include built in electrocardiogram equipment are now readily available at competitive prices. Coupled with the wealth of clinically meaningful cardiopulmonary data that can be acquired by these units, the implementation of CPX in hospitals is now more feasible and should be pursued.”
      • Kaminsky L.A.
      • Arena R.
      • Ellingsen Ø.
      • et al.
      Cardiorespiratory fitness and cardiovascular disease: the past, present, and future.
      Therefore, as recently reviewed in Mayo Clinic Proceedings, the “gold standard” CRF assessment with CPX should be more commonly used in routine clinical practice.
      • Kaminsky L.A.
      • Arena R.
      • Myers J.
      • et al.
      Updated reference standards for cardiorespiratory fitness measured with cardiopulmonary exercise testing: data from the Fitness Registry and the Importance of Exercise National Database (FRIEND).
      Nevertheless, clearly most stress tests in the United States and worldwide do not include CPX but rather CRF being assessed by speed and incline on the treadmill or by workload on a cycle ergometry test; most studies during the past 3 decades have used this method to assess and define CRF. As Kodama et al
      • Kodama S.
      • Saito K.
      • Tanaka S.
      • et al.
      Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis.
      and Harber et al
      • Harber M.P.
      • Kaminsky L.A.
      • Arena R.
      • et al.
      Impact of cardiorespiratory fitness on all-cause and disease-specific mortality: advances since 2009.
      previously demonstrated and Laukkanen et al
      • Laukkanen J.A.
      • Isiozor N.M.
      • Kunutsor S.K.
      Objectively assessed cardiorespiratory fitness and all-cause mortality risk: an updated meta-analysis of 37 cohort studies involving 2,258,029 million participants.
      reinforce now, eCRF strongly correlates with survival. In addition, besides eCRF being strongly related with CVD and CVD morbidity and mortality, it is also highly associated with healthy vascular aging,
      • Fleenor B.S.
      • Carlini N.A.
      • Kaminsky L.A.
      • et al.
      Healthy vascular aging is associated with higher cardiorespiratory fitness.
      inflammation, and respiratory diseases, such as chronic obstructive pulmonary disease and pneumonia.
      • Kunutsor S.K.
      • Jae S.Y.
      • Mäkikallio T.H.
      • Laukkanen J.A.
      Cardiorespiratory fitness, inflammation, and risk of chronic obstructive pulmonary disease in middle-age men: a cohort study.
      ,
      • Jae S.Y.
      • Heffernan K.S.
      • Kurl S.
      • et al.
      Cardiorespiratory fitness, inflammation, and the incident risk of pneumonia.
      Although genetics certainly play a role in CRF,
      • Lavie C.J.
      • Ozemek C.
      • Carbone S.
      • Katzmarzyk P.T.
      • Blair S.N.
      Sedentary behavior, exercise, and cardiovascular health.
      changes in CRF are heavily affected by an individual’s regular PA and exercise training habits. These data reinforce not only the importance of measuring or estimating CRF but also that clinicians across a wide range of disciplines throughout the health care system need to promote regular PA and exercise training, especially that which increases levels of CRF, throughout their daily patient encounters.
      With the past 2 years being dominated by the coronavirus disease 2019 (COVID-19) pandemic, healthy lifestyle, including PA and CRF, may be even more important than ever.
      • Arena R.
      • Lavie C.J.
      HL-PIVOT Network
      The global path forward: Healthy Living for Pandemic Event Protection (HL-PIVOT).
      • Hall G.
      • Laddu D.R.
      • Phillips S.A.
      • Lavie C.J.
      • Arena R.
      A tale of two pandemics: how will COVID-19 and global trends in physical inactivity and sedentary behavior affect one another?.
      • Laddu D.R.
      • Lavie C.J.
      • Phillips S.A.
      • Arena A.
      Physical activity for immunity protection: inoculating populations with healthy living medicine in preparation for the next pandemic.
      Mayo Clinic Proceedings appears to have had the first major publication demonstrating that CRF strongly affected prognosis during infections with COVID-19,
      • Brawner C.A.
      • Ehrman J.K.
      • Bole S.
      • et al.
      Inverse relationship of maximal exercise capacity to hospitalization secondary to coronavirus disease 2019.
      • Lavie C.J.
      • Sanchis-Gomar F.
      • Arena R.
      Fit is it in COVID-19, future pandemics and overall healthy living.
      • Kerrigan D.J.
      • Brawner C.A.
      • Ehrman J.K.
      • Keteyian S.
      Cardiorespiratory fitness attenuates the impact of risk factors associated with COVID-19 hospitalization.
      • Lavie C.J.
      • Sanchis-Gomar F.
      • Arena R.
      In reply: cardiorespiratory fitness attenuates the impact of risk factors associated with COVID-19 hospitalization.
      and subsequent to this, Sallis et al
      • Sallis R.
      • Young D.R.
      • Tartof S.Y.
      • et al.
      Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients.
      using data from Kaiser Permanente demonstrated the powerful impact of PA, the main correlate of CRF, with COVID-19 prognosis. This major paper by Laukkanen et al
      • Laukkanen J.A.
      • Isiozor N.M.
      • Kunutsor S.K.
      Objectively assessed cardiorespiratory fitness and all-cause mortality risk: an updated meta-analysis of 37 cohort studies involving 2,258,029 million participants.
      should further facilitate and reinforce efforts to promote the routine assessment and improvement, when necessary, of CRF on a population level. Healthy living medicine, of which optimization of CRF and PA promotion are central components, should be a priority for every individual’s plan of care.

      Potential Competing Interests

      The authors report no competing interests.

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