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The Effect of Physical Fitness on Mortality is Overestimated
Many observational studies have shown that people who exercise more and have good cardiorespiratory fitness early in life are at lower risk of premature death from causes such as cancer and cardiovascular disease. However, a new study published in the European Journal of Preventive Cardiology suggests that the association between physical fitness and a reduced risk of mortality may be misleading.
"We found that people with high fitness levels in late adolescence had a lower risk of dying prematurely, for example from cardiovascular disease, compared to those with low fitness levels. But when we looked at their risk of dying in random accidents, we found an almost similarly strong association. This suggests that people with high and low fitness levels may differ in other important ways, which is something that previous studies have not fully taken into account," says Marcel Ballin, associated researcher in epidemiology and lead author of the study.
[...] The researchers started with a traditional analysis of mortality from cardiovascular disease, cancer and from all causes, as in previous observational studies. They adjusted their statistical models for factors such as BMI, age at conscription, year of conscription, and parents' income and education level. The results showed that the group with the highest fitness level had a 58 per cent lower risk of dying from cardiovascular disease, a 31 per cent lower risk of dying from cancer, and a 53 per cent lower risk of dying from all causes, compared with the group with the lowest fitness level.
Next, the researchers examined how fitness was associated with the risk of dying in random accidents such as car accidents, drownings and homicides. They chose random accidents because they assumed that there ought to be no association between the men's fitness in late adolescence and the risk of dying in random accidents. This method is called negative control outcome analysis and involves testing the validity of your results for a primary outcome by comparing them with an outcome where no association ought to be found. If, however, an association is found, it may indicate that the groups studied are not actually comparable, and that the study suffers from what is typically referred to as confounding. The researchers found that men with the highest fitness levels had a 53 per cent lower risk of dying in random accidents. Yet, it is unlikely that the men's fitness would have such a big effect on their risk of dying in random accidents.
These results were also confirmed when the researchers used the sibling comparison design. Using this method, the researchers compared the risk of premature death between siblings with different fitness levels to control for all the factors that the siblings share such as behaviours, environmental factors, and some genetic factors.
"It surprised us that the association with accidental mortality reflected the other associations, even after we controlled for all the factors that siblings share. This underlines how strong the assumptions are that you make in observational studies, since it appears to be very difficult to create comparable groups. The consequences may be that you overestimate the magnitudes of the effects you find," says Marcel Ballin.
Journal Reference: Ballin M, Nordström A, Nordström P, Ahlqvist VH. Cardiorespiratory fitness in adolescence and premature mortality: widespread bias identified using negative control outcomes and sibling comparisons. European Journal of Preventive Cardiology DOI:10.1093/eurjpc/zwaf267 [doi.org]. Published online 15 May 2025.
