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Survival of the Fittest—Promoting Fitness Throughout the Life Span

Published:November 17, 2017DOI:https://doi.org/10.1016/j.mayocp.2017.10.006
      Considerable evidence during the past 3 decades has identified levels of cardiorespiratory fitness (CRF), generally determined by exercise treadmill or exercise bicycle testing, as a powerful risk factor for cardiovascular disease (CVD), as well as CVD and all-cause mortality.
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      In fact, in many studies, CRF is the most powerful risk factor, even more so than standard risk factors such as dyslipidemia, hypertension, glucose abnormalities including metabolic syndrome (MetSyn) and diabetes mellitus (DM), and smoking. In many studies, those with moderate and high levels of CRF but with potent CVD risk factors have lower CVD morbidity and mortality than do those without these risk factors but who have low levels of CRF. Although high levels of physical activity (PA) have also provided substantial protection against CVD and mortality,
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      • Lavie C.J.
      • Arena R.
      • Blair S.N.
      A call to increase physical activity across the globe in the 21st century.
      • Arena R.
      • Harrington R.A.
      • Després J.-P.
      A message from modern-day healthcare to physical activity and fitness: welcome home.
      most studies have found that CRF is a much more powerful predictor of risk than is PA.
      • Myers J.
      • McAuley P.
      • Lavie C.J.
      • Despres J.P.
      • Arena R.
      • Kokkinos P.
      Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.
      • DeFina L.F.
      • Haskell W.L.
      • Willis B.L.
      • et al.
      Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health?.
      Certainly, however, moderate to high levels of PA, especially PA that is high-intensity or increases heart rate,
      • Karlsen T.
      • Aamot I.L.
      • Haykowsky M.
      • Rognmo Ø.
      High intensity interval training for maximizing health outcomes.
      • Nes B.M.
      • Gutvik C.R.
      • Lavie C.J.
      • Nauman J.
      • Wisløff U.
      Personalized Activity Intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity.
      • Zisko N.
      • Skjerve K.N.
      • Tari A.R.
      • et al.
      Personal Activity Intelligence (PAI), sedentary behavior and cardiovascular risk factor clustering: the HUNT Study.
      are generally needed to increase levels of CRF, but there are also inherited and genetic non-PA components of CRF.
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      In the current issue of Mayo Clinic Proceedings, 2 articles highlight the importance of CRF on subsequent CVD and mortality risk.
      • Farrell S.W.
      • Finley C.E.
      • Barlow C.E.
      • et al.
      Moderate to high levels of cardiorespiratory fitness attenuate the effects of triglyceride to high-density lipoprotein cholesterol ratio on coronary heart disease mortality in men.
      • Castro-Piñero J.
      • Perez-Bey A.
      • Segura-Jiménez V.
      • et al.
      UP&DOWN Study Group
      Cardiorespiratory fitness cutoff points for early detection of present and future cardiovascular risk in children: a 2-year follow-up study.
      We believe that these articles add substantially to the existing literature on the importance of achieving moderate to high levels of CRF in both adults and children.
      Prior studies have reported that the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio, especially 3.5 or higher, is strongly related to insulin resistance, is a major factor in the MetSyn, and is a strong and independent predictor of coronary heart disease (CHD), CVD, and all-cause mortality.
      • Lavie C.J.
      • Milani R.V.
      • O'Keefe J.H.
      Dyslipidemia intervention in metabolic syndrome: emphasis on improving lipids and clinical event reduction.
      • Vega G.L.
      • Barlow C.E.
      • Grundy S.M.
      • Leonard D.
      • DeFina L.F.
      Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men.
      In the current issue of the Proceedings, Farrell et al
      • Farrell S.W.
      • Finley C.E.
      • Barlow C.E.
      • et al.
      Moderate to high levels of cardiorespiratory fitness attenuate the effects of triglyceride to high-density lipoprotein cholesterol ratio on coronary heart disease mortality in men.
      report their assessment of more than 40,000 men during a nearly 17-year follow-up to determine CHD mortality and whether CRF was protective against CHD mortality within various TG:HDL-C categories. As is widely accepted, CRF is known to be protective in many groups of high-risk patients, including those with obesity, hypertension, MetSyn, pre-DM, or type 2 DM and in patients at high risk due to psychological distress, who typically do better than do unfit individuals without these conditions.
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      • 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.
      • Lavie C.J.
      • Lee D.C.
      • Sui X.
      • et al.
      Effects of running on chronic diseases and cardiovascular and all-cause mortality.
      • Lavie C.J.
      • Menezes A.R.
      • De Schutter A.
      • Milani R.V.
      • Blumenthal J.A.
      Impact of cardiac rehabilitation and exercise training on psychological risk factors and subsequent prognosis in patients with cardiovascular disease.
      The findings of Farrell et al
      • Farrell S.W.
      • Finley C.E.
      • Barlow C.E.
      • et al.
      Moderate to high levels of cardiorespiratory fitness attenuate the effects of triglyceride to high-density lipoprotein cholesterol ratio on coronary heart disease mortality in men.
      support a clinically important concept that CVD risk increases progressively with increases in TG:HDL-C ratio, as they show in Table 3 in their article. However, when the interaction between CRF and TG:HDL-C ratio was considered, the risk was substantially lower for the moderately and highly fit individuals regardless of TG:HDL-C levels. For the high CRF group especially, the risk only became significantly higher (11%) than the reference group for those with a TG:HDL-C ratio of 2.4 to 3.9 and 93% for those with a TG:HDL-C ratio greater than 3.9. The risk for the low CRF group in the same TG:HDL-C categories was 3.07 and 4.26, respectively. These findings suggest that when CRF is not considered, the risk is overestimated for relatively fit individuals and underestimated for those with lower CRF levels. The current study does not provide the exercise level necessary to achieve the aforementioned favorable health outcomes. More than 20 years ago, however, in individuals of similar age (44±4 years), Kokkinos et al
      • Kokkinos P.F.
      • Holland J.C.
      • Narayan P.
      • Colleran J.A.
      • Dotson C.O.
      • Papademetriou V.
      Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men: a dose-response relationship.
      reported a dose-response association between miles run per week, TG, and HDL-C levels, with most significant changes occurring in those jogging between 7 and 14 miles per week. The metabolic equivalent (MET) level achieved by these individuals was approximately 11 to 15, very similar to the 11.1- and 14.0-MET levels reported in the current study for the moderately and highly fit individuals, respectively. Furthermore, for those jogging 7 to 14 miles per week, the TG:HDL-C ratio extrapolated from the study by Kokkinos et al was 2.0, similar to the ratio of the high CRF category in the current study. Collectively, these data support the following significant public health messages. First, CRF significantly modulates CVD risk associated with dyslipidemia. Second, accumulating 7 to 14 miles per week of moderate-intensity exercise, such as running,
      • Lavie C.J.
      • Lee D.C.
      • Sui X.
      • et al.
      Effects of running on chronic diseases and cardiovascular and all-cause mortality.
      • Lavie C.J.
      • Menezes A.R.
      • De Schutter A.
      • Milani R.V.
      • Blumenthal J.A.
      Impact of cardiac rehabilitation and exercise training on psychological risk factors and subsequent prognosis in patients with cardiovascular disease.
      • Kokkinos P.F.
      • Holland J.C.
      • Narayan P.
      • Colleran J.A.
      • Dotson C.O.
      • Papademetriou V.
      Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men: a dose-response relationship.
      can potentially lower the risk associated with increased TG:HDL-C levels as reported by the current study. Finally, CRF must be considered by health care professionals when CVD risk is assigned to patients.
      The study by Castro-Piñero et al
      • Castro-Piñero J.
      • Perez-Bey A.
      • Segura-Jiménez V.
      • et al.
      UP&DOWN Study Group
      Cardiorespiratory fitness cutoff points for early detection of present and future cardiovascular risk in children: a 2-year follow-up study.
      assessed 213 schoolchildren followed up for 2 years to examine the association of CRF at baseline and CVD risk, as well as its impact on their risk 2 years later. They found that CRF at baseline was inversely associated with individual CVD risk factors and CVD risk score at both baseline and at 2-year follow-up and that persistently low CRF or the decline in CRF at young ages is associated with later risk of CVD. Providing cutoff points of CRF in early life is critical to target children and adolescents at a high future CVD risk, potentially enabling special efforts at intervention to improve PA and exercise training, which could improve CRF. In fact, a recent scientific statement from the American Heart Association emphasized including CRF as a vital sign in modern health care.
      • Ross R.
      • Blair S.N.
      • Arena R.
      • et al.
      American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic HealthCouncil on Clinical CardiologyCouncil on Epidemiology and Prevention; Council on Cardiovascular and Stroke NursingCouncil on Functional Genomics and Translational BiologyStroke Council
      Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign; a scientific statement from the American Heart Association.
      These new findings in the Proceedings should be interpreted in relationship to the very recent and relevant meta-analysis that has provided cutoff points in young people with higher CVD risk.

      Ruiz JR, Cavero-Redondo I, Ortega FB, Welk GJ, Andersen LB, Martinez-Vizcaino V. Cardiorespiratory fitness cut points to avoid cardiovascular disease risk in children and adolescents: what level of fitness should raise a red flag? a systematic review and meta-analysis [published online ahead of print September 26, 2016]. Br J Sports Med. https://doi.org/10.1136/bjsports-2015-095903.

      As documented in this meta-analysis of 7 studies that included 9280 children and adolescents from 14 countries, CRF levels below 12 and 10 estimated METs (approximate peak oxygen consumption of 42 and 35 ml/kg per minute, respectively) for boys and girls, respectively, raise a “red flag” because these levels identify children and adolescents who may benefit from intensive primary and secondary CVD prevention.

      Ruiz JR, Cavero-Redondo I, Ortega FB, Welk GJ, Andersen LB, Martinez-Vizcaino V. Cardiorespiratory fitness cut points to avoid cardiovascular disease risk in children and adolescents: what level of fitness should raise a red flag? a systematic review and meta-analysis [published online ahead of print September 26, 2016]. Br J Sports Med. https://doi.org/10.1136/bjsports-2015-095903.

      This article in the Proceedings adds 2 important dimensions to the meta-analysis and the existing literature. First, Castro-Piñero et al
      • Castro-Piñero J.
      • Perez-Bey A.
      • Segura-Jiménez V.
      • et al.
      UP&DOWN Study Group
      Cardiorespiratory fitness cutoff points for early detection of present and future cardiovascular risk in children: a 2-year follow-up study.
      focused on young children (starting at 6 years), whereas most of the previous literature was derived from studies in older children or adolescents. Second, it adds the important longitudinal analysis regarding how changes in CRF at early ages relate to changes in CVD risk factors, whereas previous literature in this age group essentially involved cross-sectional studies.
      Particularly concerning is the lack of PA and exercise in the entire population, starting with schoolchildren, and the way that PA, exercise, and physical education programs have been reduced or even eliminated in many schools.
      • Hills A.P.
      • Dengel D.R.
      • Lubans D.R.
      Supporting public health priorities: recommendations for physical education and physical activity promotion in schools.
      Emphasis on PA is needed throughout the health care system and on a global basis,
      • Hills A.P.
      • Dengel D.R.
      • Lubans D.R.
      Supporting public health priorities: recommendations for physical education and physical activity promotion in schools.
      • Pratt M.
      • Perez L.G.
      • Goenka S.
      • et al.
      Can population levels of physical activity be increased? global evidence and experience.
      • Sallis R.
      • Franklin B.
      • Joy L.
      • Ross R.
      • Sabgir D.
      • Stone J.
      Strategies for promoting physical activity in clinical practice.
      and it is urgently needed in schools.
      • Hills A.P.
      • Dengel D.R.
      • Lubans D.R.
      Supporting public health priorities: recommendations for physical education and physical activity promotion in schools.
      Also concerning is the increase in obesity over recent decades, with almost 8% of adults in the United States considered morbidly obese or with class 3 obesity (body mass index [calculated as weight in kilograms divided by height in meters squared], ≥40 kg/m2).
      • Flegal K.M.
      • Kruszon-Moran D.
      • Carroll M.D.
      • Fryar C.D.
      • Ogden C.L.
      Trends in obesity among adults in the United States, 2005 to 2014.
      Even more alarming is the increase in childhood prevalence of overweight and obesity, which could be largely prevented by increasing PA together with a healthier diet.
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      • Lavie C.J.
      • De Schutter A.
      • Parto P.
      • et al.
      Obesity and prevalence of cardiovascular diseases and prognosis: the obesity paradox updated.
      • Ortega F.B.
      • Lavie C.J.
      • Blair S.N.
      Obesity and cardiovascular disease.
      However, when the authors of this editorial (now having a mean age of almost 60 years) were in their childhood, there were very few overweight children. What is particularly concerning is the relatively high current prevalence of overweight and obesity in children and adolescents, as this would culminate in an increased prevalence of obesity in adults in our society.
      However, a very recent pooled analysis of 1247 children aged 8 to 11 years from 3 projects found that CRF attenuated the adverse effects of severe/morbid obesity on cardiometabolic risk, including TG and HDL-C levels (as in the report by Farrell et al
      • Farrell S.W.
      • Finley C.E.
      • Barlow C.E.
      • et al.
      Moderate to high levels of cardiorespiratory fitness attenuate the effects of triglyceride to high-density lipoprotein cholesterol ratio on coronary heart disease mortality in men.
      ) and insulin resistance, with the largest effects noted in the most obese children.

      Nyström CD, Henriksson P, Martínez-Vizcaíno V, et al. Does cardiorespiratory fitness attenuate the adverse effects of severe/morbid obesity on cardiometabolic risk and insulin resistance in children? a pooled analysis [published online ahead of print September 22, 2017]. Diabetes Care. https://doi.org/10.2337/dc17-1334.

      Therefore, besides reducing the risk of obesity in the first place, PA and exercise training that improve CRF may also play an important role in lowering the risk of cardiometabolic disease and MetSyn in obese children, as it does in adults.
      In conclusion, greater attention should be focused on increasing PA and exercise training, such that levels of CRF are improved and, most importantly, low levels of CRF are prevented in schoolchildren, adolescents, and adults. It has been said that low PA may be the greatest threat to the health of the population in the 21st century.
      • Lavie C.J.
      • Arena R.
      • Blair S.N.
      A call to increase physical activity across the globe in the 21st century.
      Reversing this trend is an urgently needed, cost-effective strategy
      • Carlson S.A.
      • Fulton J.E.
      • Pratt M.
      • Yang Z.
      • Adams E.K.
      Inadequate physical activity and health care expenditures in the United States.
      that would provide incalculable benefit to the health of the US population and that of other countries.

      References

        • Lavie C.J.
        • Arena R.
        • Swift D.L.
        • et al.
        Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
        Circ Res. 2015; 117: 207-219
        • Lavie C.J.
        • Arena R.
        • Blair S.N.
        A call to increase physical activity across the globe in the 21st century.
        Future Cardiol. 2016; 12: 605-607
        • Arena R.
        • Harrington R.A.
        • Després J.-P.
        A message from modern-day healthcare to physical activity and fitness: welcome home.
        Prog Cardiovasc Dis. 2015; 57: 293-295
        • Myers J.
        • McAuley P.
        • Lavie C.J.
        • Despres J.P.
        • Arena R.
        • Kokkinos P.
        Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.
        Prog Cardiovasc Dis. 2015; 57: 306-314
        • DeFina L.F.
        • Haskell W.L.
        • Willis B.L.
        • et al.
        Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health?.
        Prog Cardiovasc Dis. 2015; 57: 324-329
        • Karlsen T.
        • Aamot I.L.
        • Haykowsky M.
        • Rognmo Ø.
        High intensity interval training for maximizing health outcomes.
        Prog Cardiovasc Dis. 2017; 60: 67-77
        • Nes B.M.
        • Gutvik C.R.
        • Lavie C.J.
        • Nauman J.
        • Wisløff U.
        Personalized Activity Intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity.
        Am J Med. 2017; 130: 328-336
        • Zisko N.
        • Skjerve K.N.
        • Tari A.R.
        • et al.
        Personal Activity Intelligence (PAI), sedentary behavior and cardiovascular risk factor clustering: the HUNT Study.
        Prog Cardiovasc Dis. 2017; 60: 89-95
        • Farrell S.W.
        • Finley C.E.
        • Barlow C.E.
        • et al.
        Moderate to high levels of cardiorespiratory fitness attenuate the effects of triglyceride to high-density lipoprotein cholesterol ratio on coronary heart disease mortality in men.
        Mayo Clin Proc. 2017; 92: 1763-1771
        • Castro-Piñero J.
        • Perez-Bey A.
        • Segura-Jiménez V.
        • et al.
        • UP&DOWN Study Group
        Cardiorespiratory fitness cutoff points for early detection of present and future cardiovascular risk in children: a 2-year follow-up study.
        Mayo Clin Proc. 2017; 92: 1753-1762
        • Lavie C.J.
        • Milani R.V.
        • O'Keefe J.H.
        Dyslipidemia intervention in metabolic syndrome: emphasis on improving lipids and clinical event reduction.
        Am J Med Sci. 2011; 341: 388-393
        • Vega G.L.
        • Barlow C.E.
        • Grundy S.M.
        • Leonard D.
        • DeFina L.F.
        Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men.
        J Investig Med. 2014; 62: 345-349
        • 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.
        JAMA. 2009; 301: 2024-2035
        • Lavie C.J.
        • Lee D.C.
        • Sui X.
        • et al.
        Effects of running on chronic diseases and cardiovascular and all-cause mortality.
        Mayo Clin Proc. 2015; 90: 1541-1552
        • Lavie C.J.
        • Menezes A.R.
        • De Schutter A.
        • Milani R.V.
        • Blumenthal J.A.
        Impact of cardiac rehabilitation and exercise training on psychological risk factors and subsequent prognosis in patients with cardiovascular disease.
        Can J Cardiol. 2016; 32: S365-S373
        • Kokkinos P.F.
        • Holland J.C.
        • Narayan P.
        • Colleran J.A.
        • Dotson C.O.
        • Papademetriou V.
        Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men: a dose-response relationship.
        Arch Intern Med. 1995; 155: 415-420
        • Ross R.
        • Blair S.N.
        • Arena R.
        • et al.
        • American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic Health
        • Council on Clinical Cardiology
        • Council on Epidemiology and Prevention; Council on Cardiovascular and Stroke Nursing
        • Council on Functional Genomics and Translational Biology
        • Stroke Council
        Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign; a scientific statement from the American Heart Association.
        Circulation. 2016; 134: e653-e699
      1. Ruiz JR, Cavero-Redondo I, Ortega FB, Welk GJ, Andersen LB, Martinez-Vizcaino V. Cardiorespiratory fitness cut points to avoid cardiovascular disease risk in children and adolescents: what level of fitness should raise a red flag? a systematic review and meta-analysis [published online ahead of print September 26, 2016]. Br J Sports Med. https://doi.org/10.1136/bjsports-2015-095903.

        • Hills A.P.
        • Dengel D.R.
        • Lubans D.R.
        Supporting public health priorities: recommendations for physical education and physical activity promotion in schools.
        Prog Cardiovasc Dis. 2015; 57: 368-374
        • Pratt M.
        • Perez L.G.
        • Goenka S.
        • et al.
        Can population levels of physical activity be increased? global evidence and experience.
        Prog Cardiovasc Dis. 2015; 57: 356-367
        • Sallis R.
        • Franklin B.
        • Joy L.
        • Ross R.
        • Sabgir D.
        • Stone J.
        Strategies for promoting physical activity in clinical practice.
        Prog Cardiovasc Dis. 2015; 57: 375-386
        • Flegal K.M.
        • Kruszon-Moran D.
        • Carroll M.D.
        • Fryar C.D.
        • Ogden C.L.
        Trends in obesity among adults in the United States, 2005 to 2014.
        JAMA. 2016; 315: 2284-2291
        • Lavie C.J.
        • De Schutter A.
        • Parto P.
        • et al.
        Obesity and prevalence of cardiovascular diseases and prognosis: the obesity paradox updated.
        Prog Cardiovasc Dis. 2016; 58: 537-547
        • Ortega F.B.
        • Lavie C.J.
        • Blair S.N.
        Obesity and cardiovascular disease.
        Circ Res. 2016; 118: 1752-1770
      2. Nyström CD, Henriksson P, Martínez-Vizcaíno V, et al. Does cardiorespiratory fitness attenuate the adverse effects of severe/morbid obesity on cardiometabolic risk and insulin resistance in children? a pooled analysis [published online ahead of print September 22, 2017]. Diabetes Care. https://doi.org/10.2337/dc17-1334.

        • Carlson S.A.
        • Fulton J.E.
        • Pratt M.
        • Yang Z.
        • Adams E.K.
        Inadequate physical activity and health care expenditures in the United States.
        Prog Cardiovasc Dis. 2015; 57: 315-323

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