Mayo Clinic Proceedings Home

Prediction of Cardiovascular Mortality by Estimated Cardiorespiratory Fitness Independent of Traditional Risk Factors: The HUNT Study

Published:November 17, 2016DOI:



      To assess the predictive value of estimated cardiorespiratory fitness (eCRF) and evaluate the additional contribution of traditional risk factors in cardiovascular disease (CVD) mortality prediction.

      Participants and Methods

      The study included healthy men (n=18,721) and women (n=19,759) aged 30 to 74 years. A nonexercise algorithm estimated cardiorespiratory fitness. Cox proportional hazards models evaluated the primary (CVD mortality) and secondary (all-cause, ischemic heart disease, and stroke mortality) end points. The added predictive value of traditional CVD risk factors was evaluated using the Harrell C statistic and net reclassification improvement.


      After a median follow-up of 16.3 years (range, 0.04-17.4 years), there were 3863 deaths, including 1133 deaths from CVD (734 men and 399 women). Low eCRF was a strong predictor of CVD and all-cause mortality after adjusting for established risk factors. The C statistics for eCRF and CVD mortality were 0.848 (95% CI, 0.836-0.861) and 0.878 (95% CI, 0.862-0.894) for men and women, respectively, increasing to 0.851 (95% CI, 0.839-0.863) and 0.881 (95% CI, 0.865-0.897), respectively, when adding clinical variables. By adding clinical variables to eCRF, the net reclassification improvement of CVD mortality was 0.014 (95% CI, −0.023 to 0.051) and 0.052 (95% CI, −0.023 to 0.127) in men and women, respectively.


      Low eCRF is independently associated with CVD and all-cause mortality. The inclusion of traditional clinical CVD risk factors added little to risk discrimination and did not improve the classification of risk beyond this simple eCRF measurement, which may be proposed as a practical and cost-effective first-line approach in primary prevention settings.

      Abbreviations and Acronyms:

      BP (blood pressure), CRF (cardiorespiratory fitness), CV (cardiovascular), CVD (CV disease), eCRF (estimated CRF), HDL-C (high-density lipoprotein cholesterol), HUNT (Nord-Trøndelag Health Study), IDI (integrated discrimination improvement), IHD (ischemic heart disease), MET (metabolic equivalent), NRI (net reclassification improvement), PA (physical activity), rHR (resting heart rate), WC (waist circumference)
      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 to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Gulati M.
        • Pandey D.K.
        • Arnsdorf M.F.
        • et al.
        Exercise capacity and the risk of death in women: the St James Women Take Heart Project.
        Circulation. 2003; 108: 1554-1559
        • 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
        • Kokkinos P.
        • Myers J.
        • Kokkinos J.P.
        • et al.
        Exercise capacity and mortality in black and white men.
        Circulation. 2008; 117: 614-622
        • Myers J.
        • Prakash M.
        • Froelicher V.
        • Do D.
        • Partington S.
        • Atwood J.E.
        Exercise capacity and mortality among men referred for exercise testing.
        N Engl J Med. 2002; 346: 793-801
        • Kaminsky L.A.
        • Arena R.
        • Beckie T.M.
        • et al.
        • American Heart Association Advocacy Coordinating Committee, Council on Clinical Cardiology, and Council on Nutrition, Physical Activity and Metabolism
        The importance of cardiorespiratory fitness in the United States: the need for a national registry; a policy statement from the American Heart Association.
        Circulation. 2013; 127: 652-662
        • Artero E.G.
        • Jackson A.S.
        • Sui X.
        • et al.
        Longitudinal algorithms to estimate cardiorespiratory fitness: associations with nonfatal cardiovascular disease and disease-specific mortality.
        J Am Coll Cardiol. 2014; 63: 2289-2296
        • Myers J.
        • Kaykha A.
        • George S.
        • et al.
        Fitness versus physical activity patterns in predicting mortality in men.
        Am J Med. 2004; 117: 912-918
        • Gupta S.
        • Rohatgi A.
        • Ayers C.R.
        • et al.
        Cardiorespiratory fitness and classification of risk of cardiovascular disease mortality.
        Circulation. 2011; 123: 1377-1383
        • Jackson A.S.
        • Sui X.
        • O'Connor D.P.
        • et al.
        Longitudinal cardiorespiratory fitness algorithms for clinical settings.
        Am J Prev Med. 2012; 43: 512-519
        • Jurca R.
        • Jackson A.S.
        • LaMonte M.J.
        • et al.
        Assessing cardiorespiratory fitness without performing exercise testing.
        Am J Prev Med. 2005; 29: 185-193
        • Nes B.M.
        • Janszky I.
        • Vatten L.J.
        • Nilsen T.I.
        • Aspenes S.T.
        • Wisløff U.
        Estimating V˙O2peak from a non-exercise prediction model: the HUNT Study.
        Norway Med Sci Sports Exerc. 2011; 43: 2024-2030
        • Martinez-Gomez D.
        • Guallar-Castillón P.
        • Hallal P.C.
        • Lopez-Garcia E.
        • Rodríguez-Artalejo F.
        Nonexercise cardiorespiratory fitness and mortality in older adults.
        Med Sci Sports Exerc. 2015; 47: 568-574
        • Nes B.M.
        • Vatten L.J.
        • Nauman J.
        • Janszky I.
        • Wisløff U.
        A simple nonexercise model of cardiorespiratory fitness predicts long-term mortality.
        Med Sci Sports Exerc. 2014; 46: 1159-1165
        • Stamatakis E.
        • Hamer M.
        • O'Donovan G.
        • Batty G.D.
        • Kivimaki M.
        A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts.
        Eur Heart J. 2013; 34: 750-758
        • Paynter N.P.
        • LaMonte M.J.
        • Manson J.E.
        • et al.
        Comparison of lifestyle-based and traditional cardiovascular disease prediction in a multiethnic cohort of nonsmoking women.
        Circulation. 2014; 130: 1466-1473
        • Balady G.J.
        • Larson M.G.
        • Vasan R.S.
        • Leip E.P.
        • O'Donnell C.J.
        • Levy D.
        Usefulness of exercise testing in the prediction of coronary disease risk among asymptomatic persons as a function of the Framingham risk score.
        Circulation. 2004; 110: 1920-1925
        • Barlow C.E.
        • Defina L.F.
        • Radford N.B.
        • et al.
        Cardiorespiratory fitness and long-term survival in “low-risk” adults.
        J Am Heart Assoc. 2012; 1: e001354
        • Laukkanen J.A.
        • Rauramaa R.
        • Salonen J.T.
        • Kurl S.
        The predictive value of cardiorespiratory fitness combined with coronary risk evaluation and the risk of cardiovascular and all-cause death.
        J Intern Med. 2007; 262: 263-272
        • Krokstad S.
        • Langhammer A.
        • Hveem K.
        • et al.
        Cohort profile: the HUNT Study.
        Norway Int J Epidemiol. 2013; 42: 968-977
        • Garber C.E.
        • Blissmer B.
        • Deschenes M.R.
        • et al.
        • American College of Sports Medicine
        American College of Sports Medicine Position Stand: quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults; guidance for prescribing exercise.
        Med Sci Sports Exerc. 2011; 43: 1334-1359
        • Jackson A.S.
        • Blair S.N.
        • Mahar M.T.
        • Wier L.T.
        • Ross R.M.
        • Stuteville J.E.
        Prediction of functional aerobic capacity without exercise testing.
        Med Sci Sports Exerc. 1990; 22: 863-870
        • Rustad P.
        • Felding P.
        • Franzson L.
        • et al.
        The Nordic Reference Interval Project 2000: recommended reference intervals for 25 common biochemical properties.
        Scand J Clin Lab Invest. 2004; 64: 271-284
        • Newson R.B.
        Comparing the predictive powers of survival models using Harrell's C or Somers' D.
        Stata J. 2010; 10: 339-358
        • Cook N.R.
        • Ridker P.M.
        Advances in measuring the effect of individual predictors of cardiovascular risk: the role of reclassification measures.
        Ann Intern Med. 2009; 150: 795-802
        • Kerr K.F.
        • McClelland R.L.
        • Brown E.R.
        • Lumley T.
        Evaluating the incremental value of new biomarkers with integrated discrimination improvement.
        Am J Epidemiol. 2011; 174: 364-374
        • Pencina M.J.
        • D'Agostino Sr, R.B.
        • D'Agostino Jr., R.B.
        • Vasan R.S.
        Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.
        Stat Med. 2008; 27: 157-172
        • Pencina M.J.
        • D'Agostino R.B.
        • Pencina K.M.
        • Janssens A.C.
        • Greenland P.
        Interpreting incremental value of markers added to risk prediction models.
        Am J Epidemiol. 2012; 176: 473-481
        • Kerr K.F.
        • Wang Z.
        • Janes H.
        • McClelland R.L.
        • Psaty B.M.
        • Pepe M.S.
        Net reclassification indices for evaluating risk prediction instruments: a critical review.
        Epidemiology. 2014; 25: 114-121
        • Sundström J.
        • Byberg L.
        • Gedeborg R.
        • Michaëlsson K.
        • Berglund L.
        Useful tests of usefulness of new risk factors: tools for assessing reclassification and discrimination.
        Scand J Public Health. 2011; 39: 439-441
        • Goff Jr., D.C.
        • Lloyd-Jones D.M.
        • Bennett G.
        • et al.
        2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        Circulation. 2014; 129 ([published correction appears in Circulation. 2014;129(25, suppl 2):S74-S75]): S49-S73
        • Myers J.
        • Nead K.T.
        • Chang P.
        • Abella J.
        • Kokkinos P.
        • Leeper N.J.
        Improved reclassification of mortality risk by assessment of physical activity in patients referred for exercise testing.
        Am J Med. 2015; 128: 396-402
        • Greenland P.
        • Knoll M.D.
        • Stamler J.
        • et al.
        Major risk factors as antecedents of fatal and nonfatal coronary heart disease events.
        JAMA. 2003; 290: 891-897
        • McGill Jr., H.C.
        • McMahan C.A.
        • Gidding S.S.
        Preventing heart disease in the 21st century: implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.
        Circulation. 2008; 117: 1216-1227
        • Lloyd-Jones D.M.
        • Hong Y.
        • Labarthe D.
        • et al.
        • American Heart Association Strategic Planning Task Force and Statistics Committee
        Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond.
        Circulation. 2010; 121: 586-613
        • Conroy R.M.
        • Pyörälä K.
        • Fitzgerald A.P.
        • et al.
        • SCORE Project Group
        Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.
        Eur Heart J. 2003; 24: 987-1003
        • D'Agostino Sr, R.B.
        • Vasan R.S.
        • Pencina M.J.
        • et al.
        General cardiovascular risk profile for use in primary care: the Framingham Heart Study.
        Circulation. 2008; 117: 743-753