Middle-aged men with the highest cardiorespiratory fitness (CRF) levels live an average of five years longer than peers with age-adjusted CRF in the bottom 5 percent of the population, according to a study with 46 years of follow-up.
CRF is recognized as a predictor of all-cause and cardiovascular mortality, but most of that evidence was established in epidemiological studies with shorter follow-up periods. According to the researchers, shorter follow-up durations increase the odds of reverse causation bias, in which there might be an underlying, undiagnosed disease upon study inclusion that causes a lower level of CRF and leads to earlier death.
But in this study, published online Aug. 20 in the Journal of the American College of Cardiology, the survival benefit was noted even when excluding patients who died within 10 years of study enrollment, limiting the odds of reverse causation bias.
“The benefits of higher midlife CRF extend well into the later part of life,” concluded lead author Johan S.R. Clausen, MD, and colleagues.
The researchers studied 5,107 employed men who were an average of 48.8 years old when they were enrolled in the Copenhagen Male Study in 1970 or 1971. All of the men were free of cardiovascular disease at baseline and tested for maximal oxygen consumption (VO2 max) using a bicycle ergometer. Danish national registers allowed the authors to construct survival time models for both all-cause and cardiovascular mortality; 92 percent of participants died during follow-up, including 42 percent from cardiovascular disease.
Compared to participants with VO2 max in the bottom 5 percent for their age, those between the 5th and 50th percentiles lived an average of 2.1 years longer after multivariable adjustment. An additional 0.8 years of life expectancy (2.9 years overall) was added for individuals in the 50th to 95th percentiles, while the top 5 percent lived a full 4.9 years longer than the bottom 5 percent.
Similar associations were seen for cardiovascular mortality, and in another analysis excluding individuals who died in the first 10 years of follow-up, the results remained similar.
“Although the reassurance offered by this additional analysis was a notable strength of the study, the long follow-up also added some uncertainty to the interpretation of the data, which merits discussion,” three researchers wrote in an accompanying editorial. “Drawing potentially causal inferences between states and events that are far apart by nearly five decades is difficult, because of the likely plethora of changes that are bound to occur (e.g., changes in participant behavior, life circumstances and also broader societal changes).”
Specifically, the editorialists pointed out that physically active transportation has significantly increased in Copenhagen since the 1970s. About 60 percent of work commutes in 2016 were either walking or by bicycle, which may have led to an undetected increase in the physical activity of study participants because VO2 max was only measured at enrollment.
Emmanuel Stamatakis, PhD; Annemarie Koster, PhD; and Paul Jarle Mork, PhD, found it notable that the biggest gains in life expectancy could be achieved simply by improving from the bottom 5 percent of CRF.
“The preceding life expectancy estimates showed that there was relatively little variation (2.1 to 2.9 years) in the middle 90 percent of the age-adjusted CRF distribution, which corresponded to a wide range of average CRF levels,” they wrote. “Essentially, the results of the current study imply that the substantial longevity gains might be realized simply by moving away from the least-fit end of the CRF distribution. This is in line with previous observations in a predominately male U.S. sample in which more than half the reduction in all-cause mortality occurred between the low and moderate CRF groups.”
Clausen’s group pointed out CRF is based on both genetic factors and physical activity. They said higher levels of CRF may lower inflammation—which contributes to the development of atherosclerosis—and promote new vessel growth and the formation of cardiac collaterals.
Despite its demonstrated associations with all-cause and cardiovascular mortality, CRF is rarely used in predictive models, Clausen et al. said—even if studies have shown stronger prognostic abilities for CRF than accepted risk factors such as hypertension, obesity or hyperlipidemia.
“Previous studies have confirmed that the addition of CRF to conventional risk factors improved prediction of long-term cardiovascular events and mortality,” they wrote. “Using a bicycle ergometer … to assess CRF is a practical, quick, and cheap test with minimal adverse effects.”
The authors said additional studies are needed to determine the best physical activity regimens to improve CRF and long-term health, including whether the regimens work equally well for men and women.
“Regardless of whether the identified associations were causal or predictive, the current study supported the use of CRF as a clinical vital sign,” Stamatakis and colleagues wrote in the editorial. “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.”