Physicians' Academy for Cardiovascular Education

Cardiorespiratory fitness related to longevity in middle-aged men without CVD

Midlife cardiorespiratory fitness and the long-term risk of mortality

Literature - Clausen JSR, Marott JL, Holtermann A et al. - JACC 2018; 72(9) DOI: 10.1016/j.jacc.2018.06.045

Introduction and methods

Since the mid-20th century, research has shown that physical activity and cardiorespiratory fitness (CRF) are inversely associated with cardiovascular disease (CVD) and mortality, and even a small increase in CRF is associated with a significantly lower risk of mortality [1-3]. CRF is measured as maximum oxygen (V02max) uptake per minute per kilogram body weight, which can be estimated with non-exercise algorithms and exercise-based tests [4,5]. However, sparse evidence of the association between CRF and CV and all-cause mortality exists [4,6]. Therefore, this sub-analysis of the Copenhagen Male study assessed the relation between CRF and mortality in middle-aged, employed men without CVD.

This analysis of the prospective Copenhagen Male cohort study (1970-1971) included 5,107 men aged 40-59 years who were followed for 46 years. Initial measures included blood pressure, height and weight. CRF (VO2-max adjusted for age) was estimated with Åstrand’s nomogram, by using a standard bicycle ergometer test. Heart rate was measured by using a stethoscope and stopwatch in a working steady state, with 100, 150 and 200 W as workloads, based on the participant’s weight and height or the heart rate in the first minute of the examination. A physician interviewed all subjects at inclusion and a questionnaire was used to assess CV risk factors, and self-reported physical activity (high/moderate/low), smoking (never/former/present) and alcohol (high/moderate/low) consumption, and the occurrence of familial coronary heart disease, hypertension, and diabetes. General health status and previous CVDs were evaluated during the interview. Vital status was extracted from the Danish national Central Person Register and deaths from CVDs were extracted from the Danish Register of Causes of Death. For this analysis, all subjects with self-reported pre-existing CVD at inclusion were excluded.

Because VO2-max decreases with age, the authors developed an age-standardized VO2-max, to be able to categorize participants by CRF levels: below lower limit of normal (BLLN), low normal (LN), high normal (HN) and above upper limit of normal (AULN).The endpoints were all-cause mortality and CV mortality.

Main results

Baseline characteristics

All-cause mortality

CV mortality with competing risk

Sensitivity analysis


This prospective study on measured CRF, with the longest follow-up so far, showed a strong and dose-responsive association between increased levels of midlife CRF and longevity in healthy, middle-aged men. The effect on longevity was not specifically related to CV mortality. These findings show that the benefits of higher midlife CRF extend well to later in life, suggesting that health care professionals should recommend fitness-enhancing physical activity to improve public health and to promote healthy aging.

Editorial comment

In their editorial comment [7], Stamatakis et al. discuss the lack of repeated CRF measures in the Clausen et al. study, which might have led to overestimation of the independent associations between CRF and future mortality risk, and the lack of data on physical demands at work and CRF in terms of all-cause mortality risk. Next, they discuss the translation of the results into a public health and clinical practice message, including the positive effects of less vigorous intensity on all-cause and CVD mortality. They conclude: ‘The study by Clausen et al. made excellent use of a historical data resource and contributed important information on the question of whether CRF is associated with long-term mortality risk.’(…) ‘Regardless of whether the identified associations were causal or predictive, the current study supported the use of CRF as a clinical vital sign. Promoting incidental physical activity such as active transportation in the least fit and least physically active segments of the middle-aged adult population is a safe investment that will likely lead to improvements in CRF and will certainly save lives.’


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