The strongest predictor of mortality that your doctor doesn't measure

Why you should know your VO2 max

In medicine, one of our core responsibilities is to assess your risk for disease, so we can take steps to prevent it. Measuring your blood pressure, checking blood glucose, and asking about smoking are familiar examples. We know that high blood pressure, high blood glucose and smoking significantly increase your risk of disease and death.

But there’s an even stronger predictor of mortality than all of them: VO₂ max.

VO2 max is a measure of your aerobic fitness. It tells you how efficiently your body can use oxygen during exercise - a process that depends on the coordinated function of your lungs, heart, red blood cells, and muscles (especially their mitochondria). It’s a window into how well your body can deliver life-giving oxygen. When I ask a patient if they are physically active, they might tell me the walk 10,000 steps per day, swim a few times a week, or play tennis with a friend regularly. However, we all have a tendency to exaggerate healthy behaviors (for example, I haven’t eaten sugar in years). VO₂ max cuts through the noise. It gives an objective answer: Are your activities actually building aerobic fitness?

What is a VO₂ Max Test?

The VO2 max test does not require a doctor’s prescription and costs about $200 (similar price as a coronary calcium scan). But it is not a pleasant test. You wear a heart monitor and tight-fitting mask that measures your oxygen consumption and carbon dioxide production. Then you get on a treadmill or bike and go until you cannot go anymore. Resistance is progressively increased during the test, so most people do not last more than 10-12 minutes. If you are gasping for air at the end, you did it right. You are then given a number—your VO2 max—which can be compared to averages for your age and gender. How well does that number predictor your mortality?

In 2022, Kokkinos et al. published a landmark observational study in the Journal of the American College of Cardiology that evaluated cardiorespiratory fitness and all-cause mortality in over 750,000 U.S. veterans. The study included adults aged 30 to 95 with a median follow-up of 10 years. It was also notable for its diversity, including large numbers of women, African Americans, and Hispanics. Participants completed a treadmill test to determine fitness levels and were then tracked over time. The results were stunning.

The first thing I see here is that the least fit subjects in this group had four-fold higher risk of death compared to the extremely fit subjects.

Second, there was a dose-response relationship between fitness and mortality: at every level of increased fitness there was a reduction in death. Even going from moderately fit to fit resulted in a 20% reduction in mortality.

Third, fitness outperformed traditional risk factors, such as hypertension, diabetes, and even smoking. Smoking increased the risk of death by about 40% whereas being unfit resulted in 400% increased risk of death (when comparing the two extremes of fitness levels).

Not just one study

The study by Kokkinos et al is not the first to report such results.

• Kodoma et al found similar results in their meta-analysis of 33 studies including 102,000 patients published in 2009 in JAMA.

• Mandsagar et al found very similar results in their observational study of 122,000 subjects at the Cleveland Clinic published in JAMA in 2018.

• Ekblom-Bak et al also found similar results in their observational study of 266,000 subjects in Sweden published in 2019.

These are observational studies and therefore can only show correlation, not causation. There is some selection bias—people who can complete a treadmill test may already be healthier. Those with high VO₂ max scores might also engage in other health-promoting behaviors, such as eating well or sleeping better. But the consistency across different populations, the strong dose-response, and the sheer magnitude of effect make this association hard to ignore.

In the editorial comment that accompanied the Kokkinos study, Lavie et al write:

“This study demonstrates that cardiorespiratory fitness may be a good and independent predictor of CVD-related mortality for men and women, across the spectrum of age and race, even superior to accepted CVD risk scores and risk factors. U.S. and European guidelines should include cardiorespiratory fitness as a CVD predictor and health marker at all ages, independently of both sex and race. Improving cardiorespiratory fitness should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight.”

This was written in 2022. Yet doctors still do not measure it.