Author + information
- David I. Feldman, BS,
- Mouaz H. Al-Mallah, MD,
- Steven J. Keteyian, PhD,
- Clinton A. Brawner, PhD,
- Theodore Feldman, MD,
- Roger S. Blumenthal, MD and
- Michael J. Blaha, MD, MPH∗ ()
- ↵∗Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Carnegie 565A, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21287
Although the importance of achieving a “healthy” level of cardiorespiratory fitness is well established (1), some experts have suggested that individuals achieving extreme levels of fitness are at an increased risk of death resulting from cardiovascular disease (CVD) (2). However, it may not be accurate to conclude that all such individuals achieving elite levels of fitness are at increased risk (3). To inform this debate, we sought to determine whether there is a threshold where higher levels of fitness were no longer associated with a lower risk for all-cause mortality.
Of 69,855 patients, we studied a subgroup of 37,855 patients free of known CVD, with high fitness levels of ≥10 metabolic equivalents (METs) from the Henry Ford Exercise Testing Project (The FIT Project) (4). Exercise capacity, expressed in METs, was estimated from the peak treadmill workload. All patients were followed for all-cause mortality by using linkage with the death master file.
Follow-up was 11.5 ± 4.5 years for all-cause mortality. First, we calculated crude mortality stratified by age and high-fitness groups (METs 10 to 11, 12 to 13, and ≥14). Kaplan-Meier curves were constructed using time-to-death data, with log rank testing for significant differences. We then performed hierarchical multivariable Cox regression analysis to calculate hazard ratios and 95% confidence intervals (CI) associated with increasing levels of high cardiorespiratory fitness: unadjusted; adjusted for age, sex, and race (Model 1); and further adjustment for traditional risk factors including smoking, diabetes, hypertension, antihypertensive medication, hyperlipidemia, and family history (Model 2). Finally, using standard post-estimation techniques from fully adjusted regression models, we plotted estimated mortality relative to the complete range of common METs values (1 to 16) and constructed a graphic assessment for a threshold effect.
The mean age was 49.6 ± 11 years of age, with 63.7% males. The mean cardiorespiratory fitness level for the high-fitness population was 11.2 ± 1.6 METs, with 62% of patients in the 10- to 11-METs group; 33% in the 12- to 13-METs group; and 5% in the group at ≥14 METs.
Figure 1A shows a graded decrease in mortality across increasing high cardiorespiratory fitness groups after the age of 30 years. Kaplan-Meier analysis demonstrated a statistically significant progressive improvement in survival across increasingly high-fitness groups (p < 0.001) that persisted for up to 20 years of follow-up.
In multivariate models, there was a significant reduction in mortality for the most highly fit groups, independent of all study covariates. Compared with individuals in the reference, 10- to 11-METs group, those in the 12- to 13- and >14-METs groups had a mortality reduction of 51% (95% CI: 0.44 to 0.54) and 79% (95% CI: 0.15 to 0.28), respectively, in an unadjusted model; 36% (95% CI: 0.57 to 0.71) and 65% (95% CI: 0.25 to 0.47) in Model 1; and 32% (95% CI: 0.61 to 0.75) and 61% (95% CI: 0.28 to 0.53) in Model 2, respectively. In a graphic analysis of predicted mortality across the range of commonly attained MET values, we observed a consistent decrease in mortality with higher fitness with no evidence of a threshold effect (Figure 1B).
In summary, in a large study of cardiorespiratory fitness testing, we observed no upper threshold for mortality benefit with increasing fitness, even in the most highly fit subjects. Our data appear to contrast with recent reports in the mainstream media signaling possible cardiovascular harm at the highest exercise levels (2,3) and support the public health message that all patients should engage in regular, moderate to vigorous exercise (3).
In 2013, O’Keefe et al. (3) argued that mortality reductions persist until 13 METs, at which point there may be no additional gains and possible harms in cardiovascular health and longevity. In fact, some experts have advanced the concept of “cardiotoxicity” due to the acute abnormalities associated with extreme endurance exercise (EEE) (2). However, there is also recognition that the changes associated with EEE may resolve in most people and may ultimately represent no major harm. For example, in 2012, Kim et al. (5) reported that the risk of sudden cardiac death in all U.S. marathoners from 2000 to 2010 was 0.0005%, suggesting that cardiotoxicity concerns may be overstated.
There are several limitations to our study. The FIT Project describes a measurement of cardiorespiratory fitness in everyday clinical practice with few extreme athletes and cannot be considered a study of cardiotoxicity attributable to EEE. Also, patients in The FIT Project might have been more likely to have other traditional cardiovascular risk factors than ultra-marathoners, which may have accentuated the benefits of increasing physical fitness. Finally, although the population was large, our study still lacked sufficient power to model patients with >16 METs, although exploratory analysis suggested a continued mortality decrease in this group.
In conclusion, our study suggests a continuous, graded reduction in mortality extending to individuals with an estimated exercise capacity of >14 METs. Although more research is needed on the cardiovascular effects of EEE, our data caution against any public health message that might dissuade patients from routine vigorous physical activity with the goal of reaching the highest levels of cardiorespiratory fitness.
- American College of Cardiology Foundation