Commentary

The upper limit of cardiorespiratory fitness associated with longevity: an update

  • In 2013, mortality reductions with improving cardiorespiratory fitness (CRF) have been suggested to persist until 13 METs. More recently, accumulating evidence from large-scale studies suggests that mortality from all causes decreases with increasing CRF levels, apparently without upper limit of CRF. However, when baseline CRF is assessed in later life, upper limits of CRF decrease depending on the individual fitness level at baseline and the volume and intensity of physical activity performed during follow up. Consequently, both a CRF level as high as possible during early adulthood, achieved by appropriate exercise interventions, and a small CRF decline during later life, by continuation of regular physical activity, will help to optimize longevity.

    Citation: Johannes Burtscher, Gerhard Ruedl, Markus Posch, Klaus Greier, Martin Burtscher. The upper limit of cardiorespiratory fitness associated with longevity: an update[J]. AIMS Public Health, 2019, 6(3): 225-228. doi: 10.3934/publichealth.2019.3.225

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  • In 2013, mortality reductions with improving cardiorespiratory fitness (CRF) have been suggested to persist until 13 METs. More recently, accumulating evidence from large-scale studies suggests that mortality from all causes decreases with increasing CRF levels, apparently without upper limit of CRF. However, when baseline CRF is assessed in later life, upper limits of CRF decrease depending on the individual fitness level at baseline and the volume and intensity of physical activity performed during follow up. Consequently, both a CRF level as high as possible during early adulthood, achieved by appropriate exercise interventions, and a small CRF decline during later life, by continuation of regular physical activity, will help to optimize longevity.


    1. Introduction

    The risk of cerebral palsy (CP) is inversely correlated with gestational age at birth [1]. CP is accompanied with life-long consequences for the child, its family and society as a whole.Meta-analyses haveindicated that magnesium sulphate may be neuroprotective for the preterm infant, when the drug is given to women at high risk of preterm birth [2,3]. However, this was recently questioned by a trial sequential analysis (TSA), a statistical method which adjusts for risk of random errors [4]. The TSA demonstrated that additional data are needed before accepting magnesium sulphateas evidence-based therapy for women in preterm labour.

    Our aim is toinvestigate if antenatal magnesium sulphate administrated to women at risk of preterm birth can protect their children against CP.

    2. Materials and methodology:

    This trial is ongoing and is performed as a double-blinded, randomized, controlled, multicenter clinical trial. A study population consisting of 500 women, who are at risk of preterm birth at 24 to 32 weeks of gestation, are randomized to receive either intravenous magnesium sulphate or placebo with saline. The women are recruited from 14 obstetrics departments in Denmark. The children are followed up after 18 months of age by a questionnaire (The Ages & Stages Questionnaire), which is a standardized, validated questionnaire containing questions that can reveal signs of CP [5]. The trial is approved by the Scientific Ethics Committee of the Capital Region of Denmark (H-4-2011-024), the Danish Data Protection Agency (HVH-2011-41-6007) and is registered at ClinicalTrials.gov (no. NCT01492608).

    Inclusion criteria are: maternal age ≥ 18 years, gestational age 24+0 to 31+6 weeks, singleton or twin pregnancy, preterm rupture of membranes at 24+0 to 31+6 weeks with contractions and expected birth within 2-24 hours, or preterm contractions and expected birth within 2-24 hours and finally anticipated delivery within 2-24 hours of other reasons (for example fetal growth restriction).

    Exclusion criteria are major fetal abnormalities, maternal contraindication to magnesium sulphate (e.g. allergy, myasthenia gravis, kidney failure and heart disease), magnesium sulphate administrated for other reasons (e.g. for prevention of eclampsia) and lack of the ability to understand and speak Danish.

    2.1. Administration of magnesium sulphate:

    Magnesium sulphate is administrated as a loading dose of five grams infused for 20-30 minutes, followed by a maintenance dose of one gram per hour. Placebo is given in identical appearing doses. The maintenance infusion will be continued until delivery appears, or for 24 hours if delivery does not occur or no longer is considered imminent. The doses that are used in this project are similar to those used in Denmark for prevention of eclampsia. Blood pressure, pulse rate, respiration rate and reflexes are being controlled throughout the period. Also the fetal heart is monitored closely.

    2.2. Follow-up of the children:

    The children are followed up after 18 months of age. A questionnaire will be sent to the parents. If signs of CP are revealed from the questionnaire, the children will be examined neurologically by a pediatrician. The effect will be assessed blinded to the treatment.

    3. Power calculation:

    A total sample size of 500 patients would allow us to detect or reject a difference in CP of 25% or more with a 5% type 1 error risk. The present trial will with a power of only 13%, not in itself have the power to detect a significant difference between magnesium and placebo treatment. Instead, when the trial is completed, the results will be added to the existing data in a cumulative meta-analysis, in order to ‘close the gap of evidence’ in a TSA, and determine whether magnesium sulphate has an effect. The power of the new meta-analysis will be 63%. We used a one-sided test as a harmful effect of magnesium sulphate on CP seems unlikely according to previous data.

    4. Current status and future perspectives:

    To date more than 380 women have been included in the trial. We expect the inclusion period to end in December 2016. Positive results of this trial will support a change of the clinical guidelines concerning the treatment of women with threatening preterm birth.

    Conflict of Interest

    No conflict of interests.



    Conflict of interest



    All authors declare no conflict of interest in this paper

    [1] Mandsager K, Harb S, Cremer P, et al. (2018) Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing. JAMA Netw Open 1: e183605. doi: 10.1001/jamanetworkopen.2018.3605
    [2] Laukkanen JA, Kurl S, Salonen JT (2002) Cardiorespiratory fitness and physical activity as risk predictors of future atherosclerotic cardiovascular diseases. Curr Atheroscler Rep 4: 468–476. doi: 10.1007/s11883-002-0052-0
    [3] Kodama S, Saito K, Tanaka S, et al. (2009) Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA 301: 2024–2035. doi: 10.1001/jama.2009.681
    [4] O'Keefe JH, Lavie CJ (2013) Run for your life … at a comfortable speed and not too far. Heart 99: 516–519. doi: 10.1136/heartjnl-2012-302886
    [5] Feldman DI, Al-Mallah MH, Keteyian SJ, et al. (2015) No evidence of an upper threshold for mortality benefit at high levels of cardiorespiratory fitness. J Am Coll Cardiol 65: 629–630. doi: 10.1016/j.jacc.2014.11.030
    [6] Clausen JSR, Marott JL, Holtermann A, et al. (2018) Midlife Cardiorespiratory Fitness and the Long-Term Risk of Mortality: 46 Years of Follow-Up. J Am Coll Cardiol 72: 987–995. doi: 10.1016/j.jacc.2018.06.045
    [7] Imboden MT, Harber MP, Whaley MH, et al. (2018) Cardiorespiratory Fitness and Mortality in Healthy Men and Women. J Am Coll Cardiol 72: 2283–2292. doi: 10.1016/j.jacc.2018.08.2166
    [8] Burtscher M, Förster H, Burtscher J (2008) Superior endurance performance in aging mountain runners. Gerontology 54: 268–271. doi: 10.1159/000148649
    [9] Laukkanen JA, Zaccardi F, Khan H, et al. (2016) Long-term Change in Cardiorespiratory Fitness and All-Cause Mortality: A Population-Based Follow-up Study. Mayo Clin Proc 91: 1183–1188. doi: 10.1016/j.mayocp.2016.05.014
  • This article has been cited by:

    1. Lene Drasbek Huusom, Hanne Trap Wolf, Antenatal magnesium sulfate treatment for women at risk of preterm birth is safe and might decrease the risk of cerebral palsy, 2018, 23, 2515-446X, 195, 10.1136/bmjebm-2018-110897
    2. Caroline A. Crowther, Philippa F. Middleton, Merryn Voysey, Lisa Askie, Lelia Duley, Peter G. Pryde, Stéphane Marret, Lex W. Doyle, Jenny E Myers, Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis, 2017, 14, 1549-1676, e1002398, 10.1371/journal.pmed.1002398
    3. Clément Chollat, Loïc Sentilhes, Stéphane Marret, Fetal Neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application, 2018, 9, 1664-2295, 10.3389/fneur.2018.00247
    4. H T Wolf, L Huusom, T Weber, A Piedvache, S Schmidt, M Norman, J Zeitlin, Use of magnesium sulfate before 32 weeks of gestation: a European population-based cohort study, 2017, 7, 2044-6055, e013952, 10.1136/bmjopen-2016-013952
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