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UK Biobank Contributes to Aerobic and Muscle Fitness Research

      Considerable evidence indicates a substantial lack of physical activity (PA) and exercise training (ET) and a very high prevalence of sedentary behavior throughout most of the world.
      • Lavie C.J.
      • Ozemek C.
      • Carbone S.
      • Katzmarzyk P.T.
      • Blair S.N.
      Sedentary behavior, exercise, and cardiovascular health.
      • Ozemek C.
      • Lavie C.J.
      • Rognmo Ø.
      Global physical activity levels: need for intervention.
      • Fletcher G.F.
      • Landolfo C.
      • Niebauer J.
      • Ozemek C.
      • Arena R.
      • Lavie C.J.
      Promoting physical activity and exercise: JACC Health Promotion Series.
      • Ozemek C.
      • Laddu D.R.
      • Lavie C.J.
      • et al.
      An update on the role of cardiorespiratory fitness, structured exercise and lifestyle physical activity in preventing cardiovascular disease and health risk.
      • Lavie C.J.
      • Ozemek C.
      • Kachur S.
      Promoting physical activity in primary and secondary prevention.
      This often leads to low levels of cardiorespiratory fitness (CRF), which is perhaps one of the strongest predictors of cardiovascular disease (CVD) as well as CVD and all-cause mortality.
      • Lavie C.J.
      • Ozemek C.
      • Carbone S.
      • Katzmarzyk P.T.
      • Blair S.N.
      Sedentary behavior, exercise, and cardiovascular health.
      ,
      • Fletcher G.F.
      • Landolfo C.
      • Niebauer J.
      • Ozemek C.
      • Arena R.
      • Lavie C.J.
      Promoting physical activity and exercise: JACC Health Promotion Series.
      ,
      • Ozemek C.
      • Laddu D.R.
      • Lavie C.J.
      • et al.
      An update on the role of cardiorespiratory fitness, structured exercise and lifestyle physical activity in preventing cardiovascular disease and health risk.
      ,
      • Kaminsky L.A.
      • Arena R.
      • Ellingsen Ø.
      • et al.
      Cardiorespiratory fitness and cardiovascular disease: the past, present, and future.
      ,
      • Imboden M.T.
      • Harber M.P.
      • Whaley M.H.
      • et al.
      The association between the change in directly measured cardiorespiratory fitness across time and mortality risk.
      In addition, recent evidence suggests that resistance exercise and muscular fitness also contribute to CVD risk factors,
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise, independent of and combined with aerobic exercise, with the incidence of metabolic syndrome.
      ,
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise with the incidence of hypercholesterolemia in men.
      including diabetes mellitus risk,
      • Wang Y.
      • Lee D.C.
      • Brellenthin A.G.
      • et al.
      Association of muscular strength and incidence of type 2 diabetes.
      and to CVD and all-cause mortality.
      • Liu Y.
      • Lee D.C.
      • Li Y.
      • et al.
      Associations of resistance exercise with cardiovascular disease morbidity and mortality.
      ,
      • Lavie C.J.
      • Kachur S.
      • Sui X.
      Impact of fitness and changes in fitness on lipids and survival.
      Indeed, many recent articles in Mayo Clinic Proceedings have emphasized the importance of PA/ET, CRF, and resistance exercise/muscular fitness for preventing CVD and improving survival.
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise, independent of and combined with aerobic exercise, with the incidence of metabolic syndrome.
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise with the incidence of hypercholesterolemia in men.
      • Wang Y.
      • Lee D.C.
      • Brellenthin A.G.
      • et al.
      Association of muscular strength and incidence of type 2 diabetes.
      ,
      • Sui X.
      • Howard V.J.
      • McDonnell M.N.
      • et al.
      Racial differences in the association between nonexercised estimated cardiorespiratory fitness and incident stroke.
      • Loprinzi P.D.
      Estimated cardiorespiratory fitness assessment as a patient vital sign.
      • Kieffer S.K.
      • Zisko N.
      • Coombes J.S.
      • Nauman J.
      • Wisløff U.
      Personal activity intelligence and mortality in patients with cardiovascular disease: the HUNT study.
      • Franklin B.A.
      • Kaminsky L.A.
      • Kokkinos P.
      Quantitating the dose of physical activity in secondary prevention: relation of exercise intensity to survival.
      • de Lannoy L.
      • Sui X.
      • Lavie C.J.
      • Blair S.N.
      • Ross R.
      Change in submaximal cardiorespiratory fitness and all-cause mortality.
      • Schnohr P.
      • O’Keefe J.H.
      • Holtermann A.
      • et al.
      Various leisure-time physical activities associated with widely divergent life expectancies: the Copenhagen City Heart Study.
      • McAuley P.A.
      • Keteyian S.J.
      • Brawner C.A.
      • et al.
      Exercise capacity and the obesity paradox in heart failure: the FIT (Henry Ford Exercise Testing) Project.
      • Pandey A.
      • Patel K.V.
      • Lavie C.J.
      Obesity, central adiposity, and fitness: understanding the obesity paradox in the context of other cardiometabolic parameters.
      • Kokkinos P.
      • Myers J.
      • Franklin B.
      • Narayan P.
      • Lavie C.J.
      • Faselis C.
      Cardiorespiratory fitness and health outcomes: a call to standardize fitness categories.
      • Zaccardi F.
      • Davies M.
      • Khunti K.
      Comparative relevance of physical fitness and adiposity on life expectancy: a UK Biobank Observational Study.
      • Rao S.
      • Pandey A.
      • Garg S.
      • et al.
      Effect of exercise and pharmacological interventions on visceral adiposity: a systematic review and meta-analysis of long-term randomized controlled trials.
      • Ruiz J.R.
      • Lavie C.J.
      • Ortega F.B.
      Exercise versus pharmacological interventions for reducing visceral adiposity and improving health outcomes.
      • Imboden M.T.
      • Harber M.P.
      • Whaley M.H.
      • et al.
      The influence of change in cardiorespiratory fitness with short-term exercise training on mortality risk from the Ball State Adult Fitness Longitudinal Lifestyle Study.
      • Myers J.
      • Doom R.
      • King R.
      • et al.
      Association between cardiorespiratory fitness and health care costs: the Veterans Exercise Testing Study.
      • Wang Y.
      • Chen S.
      • Zhang J.
      • et al.
      Nonexercise estimated cardiorespiratory fitness and all-cancer mortality: the NHANES III Study.
      In this Issue of Mayo Clinic Proceedings, two major studies from the UK Biobank contribute significantly to the evidence regarding the importance of PA, CRF, and muscular fitness. Laukkanen et al
      • 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.
      assessed CRF using 6-minute submaximal cycle tests in nearly 59,000 participants aged 40 to 69 years who were followed for a median of 5.8 years, and they analyzed 936 deaths. Not only was CRF, estimated as metabolic equivalents, strongly associated with survival, as is typically the case in almost all studies, but the data also demonstrated that the addition of CRF to established CVD risk factors strongly augmented the prediction of 5-year survival, with an even more pronounced effect in older individuals, smokers, and men.
      Certainly, numerous studies, including many referenced previously herein, show the powerful impact of CRF in predicting risk. Although the gold standard assessment of CRF is cardiopulmonary exercise testing and using gas exchange to measure peak oxygen consumption,
      • Bakker E.A.
      • Lee D.C.
      • Sui X.
      • et al.
      Association of resistance exercise, independent of and combined with aerobic exercise, with the incidence of metabolic syndrome.
      ,
      • Zaccardi F.
      • Davies M.
      • Khunti K.
      Comparative relevance of physical fitness and adiposity on life expectancy: a UK Biobank Observational Study.
      ,
      • Imboden M.T.
      • Harber M.P.
      • Whaley M.H.
      • et al.
      The influence of change in cardiorespiratory fitness with short-term exercise training on mortality risk from the Ball State Adult Fitness Longitudinal Lifestyle Study.
      many clinicians do not have easy access to such testing, and neither do they have the equipment and personnel to monitor these tests, not to mention the moderate expense of this testing. Less expensive yet reliable and readily available tests for CRF include modalities such as the 6-Minute Walk Test, walking distance, and shuttle tests. The unique aspect of the present UK Biobank study was using a submaximal 6-minute bicycle test in a very large cohort to assess CRF and mortality combined with established CVD risk factors.
      • 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.
      We recently reported the potential for submaximal CRF assessed by a 5-minute treadmill test to measure estimated metabolic equivalents and to predict mortality in 6106 men and women from the Aerobics Center Longitudinal Study and the ability of changes in submaximal CRF to predict survival.
      • de Lannoy L.
      • Sui X.
      • Lavie C.J.
      • Blair S.N.
      • Ross R.
      Change in submaximal cardiorespiratory fitness and all-cause mortality.
      Also in this Issue of Mayo Clinic Proceedings, Welsh et al
      • Welsh C.E.
      • Celis-Morales C.A.
      • Ho F.K.
      • et al.
      Grip strength and walking pace and CVD risk prediction in 406,834 UK Biobank participants.
      assessed more than 400,000 UK Biobank participants without baseline CVD and assessed the associations of grip strength and self-reported walking pace and CVD risk factors on major CVD outcomes during median follow-up of 8.9 years. Assessing 7274 major CVD events and 1955 fatal events, both grip strength and self-reported walking pace were associated with major CVD outcomes even after adjusting for major baseline CVD risk factors. In addition, grip strength and self-reported walking pace added to the baseline risk factors for predicting prognosis. A previous study from the UK Biobank by Yates et al
      • Yates T.
      • Zaccardi F.
      • Dhalwani N.N.
      • et al.
      Association of walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality: a UK Biobank observational study.
      also showed the value of walking pace and handgrip strength on CVD mortality. However, the present study adds to this knowledge about the improved CVD risk prediction by adding these parameters to the existing risk score.
      Certainly, usual walking pace is considered as a health risk factor, but probably more so in older adults than younger ones. For example, gait speed is often used as one of the diagnostic criteria for sarcopenia in older adults, which is strongly associated with physical function and various health outcomes, including CVD mortality. In the current UK Biobank study,
      • Welsh C.E.
      • Celis-Morales C.A.
      • Ho F.K.
      • et al.
      Grip strength and walking pace and CVD risk prediction in 406,834 UK Biobank participants.
      the age range was quite wide (37-73 years), and it seems likely that the effect could be much higher in the older than in the younger cohort. Although the authors adjusted for age in their models, it is still possible that age group–stratified analyses would not completely remove the strong possible influence of age on walking pace. Also, they estimated walking pace as opposed to precisely measuring it, and they assessed self-reported walking pace and not walking volume. A recent study by Lee et al
      • Lee I.M.
      • Shiroma E.J.
      • Kamada M.
      • Bassett D.R.
      • Matthews C.E.
      • Buring J.E.
      Association of step volume and intensity with all-cause mortality in older women.
      of more than 18,000 women in the Women’s Health Study found that the association of walking intensities or cadence with all-cause mortality were largely attenuated or no longer significant after further adjustment for walking amount measured as steps per day, whereas mortality rate progressively decreases with more steps per day even after adjusting for intensity. Finally, although Welsh et al
      • Welsh C.E.
      • Celis-Morales C.A.
      • Ho F.K.
      • et al.
      Grip strength and walking pace and CVD risk prediction in 406,834 UK Biobank participants.
      showed large improvements in the C-index when both grip strength and self-reported walking pace were included in their models, if one looks closely at their Figures 2 and 3, there seems to be little difference when walking pace and grip strength are compared with walking pace alone, suggesting that self-reported walking pace is even more important than grip strength for predicting CVD outcomes. Although their walking pace was estimated and not measured, this very simple parameter was a potent predictor of prognosis.
      Based on the constellation of findings, considerable efforts are needed to increase both aerobic PA/ET to increase walking pace and CRF and resistance exercise to increase muscular strength. Quoting the famous Walt Disney, “The way to get started is to quit talking and start doing,” as certainly we need to do a better job promoting PA and ET (aerobic and resistance) throughout the health care system, schools, the workplace, and society for the primary and secondary prevention of CVD. The long-term health of our populations will depend on the success of these efforts.

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