Fitness trumps heart genes: 12 years and 69 thousand

69,447 people from UK Biobank, 12 years of follow-up, full data on both VO2max and genetic heart risk. The Mayo Clinic tested whether fitness saves those with the "bad" genes. The conclusion is that it does, and equally for everyone.

What have [they/you] done

The study by Collings et al. in Mayo Clinic Proceedings (January 2026, full issue in May) is a standard UK Biobank setup, but from three sides simultaneously:

• 69,447 people, average age 57.6, 541 women
• VO2max measured via an ergometer in a clinic (not a fitness tracker, not a treadmill test - a proper ergometer test), normalised for sex and age
• Genetic risk of ischaemic heart disease assessed via weighted polygenic risk score
• The participants were divided into three fitness groups (lower 20%, middle 60%, upper 20%) and three genetic risk groups using the same principle
• 12-year median follow-up, 5448 new cases of atherosclerotic events (infarction, ischaemia, stroke)

So the question is simply: can the effect of training be measured separately from genetics, does it always go hand in hand with a “good metabolism from birth”?

What did you find

Each 1 SD difference in VO2max was associated with approximately +5.6 ml O₂/kg/min an 81% reduction in the risk of ASCVD (hazard ratio 0.92, 95% CI 0.89–0.95).

Regardless of:

• gender, age, education
• Smoking, BMI, blood pressure
• sugar, lipid profile
• Genetic risk

Last but not least. Among people with high the genetic risk, the training effect persisted (HR 0.91). Among Medium — also (HR 0.94). Among low — even a little stronger (HR 0.87, P=.06 for interaction — a weak hint, not a strong difference).

The absolute 10-year risk between the most and least trained: a difference of 1.2–1.6 percentage points within each genetic stratum. This sounds small until you remind yourself that this is an absolute figure for of all populations – and for a person with a high baseline risk, this means a much lower chance.

What does this mean in practice

The “I have good genes” argument is the most common argument why No to train. Mayo Clinic tested it literally, on a population that allows testing.

The argument doesn't hold up.

Fitness acts as a risk modifier independently of genetics. If your genes are against you, fitness still reduces the risk. If your genes are in your favour, fitness reduces it even further. It’s not just “10% people for whom it works” – it applies to everyone.

The second practical: 5.6 ml/kg/min isn't an astronomical figure. It's approximately the difference between someone who doesn't train at all and someone who regularly walks + occasionally runs. Such a difference can be achieved with 3–6 months of consistent work.

VO2max is not an innate indicator. It has a genetic component, yes. But the trainable part is much larger than the innate part.

What remains

This is an observational study, not an RCT. That is, causality is inductive. Reverse logic is possible: people with good genes find it easier to stay in shape, rather than “being in shape reduces risk”.

The authors took this into account using a polygenic risk score – which measures genetic predisposition separately from the current condition. However, it is impossible to completely eliminate reverse causality in a population study.

Secondly, a polygenic score only picks up well-known variants. Rare mutations (familial hypercholesterolaemia, for example) are missed by it. For these, the conclusions may be different – a separate genetic analysis and a separate prevention plan are needed for them.

Third, VO2max is not a panacea. It doesn't cure type 2 diabetes, it doesn't treat anxiety, it doesn't replace sleep. But among the controllable cardio-risk variables, it is the strongest.

[OPTIONAL personal paragraph – insert 3-5 lines about your own experiences (how you maintain VO2max over 50, what works, what doesn't) or delete this block entirely before publishing]

Which of these is useful?

VO2max is the strongest controllable variable for cardiac risk of all that we have today. And it can be trained at any age.

If there have been early heart attacks in your family, it's a reason to start, not a reason to give up. Mayo Clinic research clearly shows: the benefits of training are preserved precisely where they are most needed.

How to systematically improve VO2max is a separate topic. Basic benchmarks are in the section For active people.

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Sources

1. Collings PJ, Wang M, Chen Z, et al. Cardiorespiratory Fitness, Genetic Risk, and Incident Atherosclerotic Cardiovascular Events: A Prospective Cohort Study. Mayo Clinic Proceedings. 2026;101(5):782-795. doi:10.1016/j.mayocp.2025.07.036

Vitaliy · Founder of life:)on