Clausen · Journal of the American College of Cardiology 2018 · Prospective cohort study · n=5107

Midlife Cardiorespiratory Fitness and the Long-Term Risk of Mortality: 46 Years of Follow-Up.

Cited 155 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective non-randomized cohort follow-up study

PubMed 30139444 · doi:10.1016/j.jacc.2018.06.045 · record verified 2026-08-26

What was done

Researchers analyzed 5,107 employed Danish men (mean age 48.8 ± 5.4 years) free of cardiovascular disease from the Copenhagen Male Study (1970–1971). Baseline cardiorespiratory fitness (Vo2 max estimated via bicycle ergometer) was grouped into 4 age-adjusted categories: below the lower limit of normal (lowest 5%), low normal (45%), high normal (45%), and above the upper limit of normal (top 5%). All-cause and cardiovascular mortality were tracked over 46 years through Danish national registers using multivariable restricted mean survival time models. Reverse causation was evaluated by excluding deaths in the first 10 years of follow-up.

What was found

Over 46 years of follow-up, 4,700 men (92%) died, including 2,149 (42.1%) from cardiovascular causes. Compared to men below the lower limit of normal fitness, life expectancy was longer by 2.1 years (95% CI: 0.7 to 3.4; p = 0.002) in the low normal group, 2.9 years (95% CI: 1.5 to 4.2; p < 0.001) in the high normal group, and 4.9 years (95% CI: 3.1 to 6.7; p < 0.001) in the above upper limit of normal group. Each unit increase in Vo2 max was associated with a 45-day increase in longevity (95% CI: 30 to 61; p < 0.001). Results were similar for cardiovascular mortality and remained essentially unchanged after excluding deaths in the first 10 years.

Why it matters

This study shows that midlife cardiorespiratory fitness has an enduring, dose-dependent relationship with survival over nearly five decades. It demonstrates that fitness-associated longevity gains are sustained into late life and are not merely artifacts of short-term reverse causation.

Limits

The study included only employed Danish men enrolled in the early 1970s, limiting applicability to women, unemployed individuals, and other ethnic populations. Vo2 max was estimated using an ergometer rather than directly measured with respiratory gas analysis, and fitness was assessed only at baseline without accounting for changes during follow-up.

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