Another pearl debunked?

Liberation from the bane of cardiovascular exercise
Time to hit the weights

Myocardial late gadolinium enhancement: prevalence, pattern, and prognostic relevance in marathon runners. (Breuckmann et al., 2009 Radiology)

In brief, this study showed that marathons kill.  Seriously.  And this applies to a lot of people; almost a half a million Americans participate in marathons annually.

MRI with late gadolinium enhancement (“LGE,” for short) a sensitive and powerful indicator of heart disease.  It gives few false positives and negatives.  Compared to other tests (EKG, stress tests, angiograms, etc.), if you have LGE you have a very high chance of cardiac mortality.

In this study, they recruited 102 recreational (nonprofessional) marathoners and 102 age-matched controls (~57 years of age).  All of the subjects were apparently healthy at baseline; anyone with pre-existing heart disease or diabetes was excluded.  The marathoners were hard-core: they ran in at least 5 marathons in the past 3 years and averaged 20 marathons in their life.  Furthermore, they ran ~35 miles per week.

12% of marathon runners had heart damage (as per LGE) compared to 4% of controls.  That is a pretty big difference: marathoners were 3 times more likely to have heart damage.

Does LGE affect cardiac events?

Here is a graph depicting the gravitas of LGE for marathoners:

“LE-” is the group of people with normal heart function.  Their line is almost completely straight indicating that almost 100% experienced no cardiac events.  “LE+” indicates people with LGE.  This figure basically confirms that LGE is a potent cardiac events predictor.  Over the course of the 2+ years of follow-up, 3 marathoners with LGE experienced a cardiac event compared to 1 marathoner who had normal heart function.

The numbers aren’t huge: 12 marathoners and 4 controls exhibited LGE.  4 marathoners experienced a cardiac event; 3 of them had LGE.  So marathoners were 3 times more likely to have an abnormal LGE than controls, and marathoners with LGE were 3 times more likely to experience a cardiac event than marathoners with a good heart.  IOW, a marathoner with LGE may be 9 times more likely to experience a cardiac event than a healthy control who has normal heart function.  If I were a marathoner I’d get this test done asap.  And more importantly, all of these people thought they were healthy (just like you and me); they exhibited no signs or symptoms of heart problems.

Conclusions, alternative explanations, and my take on Breuckmann’s study:

  1. Marathons are the antithesis of moderation.  They are an extremist activity.  As is running 35 miles a week.   Aerobic fitness will exhibit, like most things, an inverted U-shaped curve in relationship with mortality and quality of life.  IOW, a totally sedentary lifestyle is probably just as bad as running marathons, but running 1 mile a day or a few per week is probably beneficial.  A poor diet and sedentary lifestyle may be associated with obesity, atherosclerosis, thrombosis, whereas marathons are more like a cardiovascular-beatdown.
  2. How does marathon running kill?  Perhaps the overall stress of marathons or blood flow-induced shear stress damages the endothelial lining of vessels, which may contribute to an atherosclerotic or otherwise pathological process.  This would be exacerbated by the systemic inflammatory response associated with a prolonged high level of exertion.
  3. Then again maybe it’s all about diet:  running 35 miles per week requires a LOT of extra calories; there is bound to be some processed crap in there.  (sorry, my assumption here is that a healthy person might be able to eat a healthy 2,000 kcal diet, but if they were suddenly eating 4,000 kcal it probably wouldn’t be all the same foods as before just twice as much).  So maybe it’s the excessive caloric burden in general, or perhaps the added foods that are contributing to the problem.
  4. On the other hand, maybe they were juiced up!  I wouldn’t be surprised if running a marathon at 57 years of age required a little pharmaceutical-grade ergogenic enhancement.
  5. Last but not least, maybe their age-matched control population was not the best control group.  IOW, maybe the controls were very healthy, so anyone (including a marathoner) would appear less healthy than control.  That’s a good one.
  6. The opposite of #5.  Maybe the marathoner’s were a particularly unhealthy bunch (they were big smoker’s and drinker’s for most of their life, then gave it all up and started running… a lot of permanent damage was done prior to exercise training).


Fortunately for us, more data on these subjects were published a year earlier.

Running: the risk of coronary events : Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. (Möhlenkamp et al, 2008 European Heart Journal)

The marathoners are group I.  Group II is an age-matched control group and group III is a control group that was matched for other risk factors including BMI, lipid profile, and smoker status.  As a side note, this type of control population is far better than statistically adjusting for risk factors.  When data are statistically adjusted, you are no longer comparing people, per se, but rather are comparing a person to a mathematically derived variable (or something like that).  IOW, I really like Möhlenkamp’s choices for the control populations.

The most interesting numbers IMO:

Indeed marathoners had 42% higher HDL and 18% lower LDL than age-matched controls (like the controls from Breuckmann’s study).  This suggests lipid profile is a poor indicator of LGE.  And there were more smokers in the age-matched control group.  This basically strikes down my alternative explanation #5 above; the controls were not a healthier group of people.

Coronary artery calfification scores:

From these data (look at the middle of the three numbers in each column), it looks like although marathoners were more likely to exhibit LGE, they had a similar degree of coronary artery calcification compared age-matched controls.  Furthermore, marathoners had significantly more coronary artery calcification than the controls that were matched for other risk factors, which more implies marathon running per se increases coronary artery calcification.

Furthermore, given the increased cardiac events in marathoners compared to age-matched controls (Breuckmann’s study), these results suggest that LGE is a more powerful indicator of risk than increased coronary artery calcification.

Coronary artery calcification is not a bad indicator, however:

The green line indicates event-free survival in runners with the least coronary artery calcification (they experienced zero cardiac events).  The blue dotted line is runners with intermediate coronary artery calcification, and the red dashed line is runners with the most coronary artery calcification.  This graph basically shows that the extent of coronary artery calcification is a pretty good predictor of cardiac events.


Interestingly, coronary artery calcification was not associated with years of running, miles per week, or number of marathons.  This is odd because coronary artery calcification was much worse in marathoners compared to risk-factor matched controls.   And number of marathons was significantly associated with LGE.  Does this mean that simply being a marathoner worsens coronary artery calcification, and the more you run worsens LGE?  I don’t know enough about these measurements to speculate on their pathological relationship, but in general, they are both pointing in the same direction.

But what about cardiac events in the risk-factor matched controls?  “data not shown”



More conclusions/alternative explanations:  going back to point #5 (above) regarding the possibility of an extra-healthy control group (which was subsequently de-bunked by comparing their lipid profiles and smoking history), it is also possible that this was a particularly unhealthy group of marathon runners (back to explanation #6) …  There were a LOT of former smokers; maybe it is people who started caring about their health, so they quit smoking and started running.  This could also possibly explain why coronary artery calcification was associated with marathons but not weekly running distance, number of marathons, etc.  IOW, former poor diet or lifestyle habits caused the coronary artery calcification and caused these subjects to start running (a bona fide confounding factor).  This may be supported by considering how these studies recruit their subjects.  Which marathoner is more likely to enter into this study, which entailed a labor-intensive comprehensive battery of cardiovascular and blood tests?  The recreational runner who has been healthy their whole life, to whom running is simply a hobby; or the runner who gave up their former poor diet and lifestyle to begin a health crusade and is now totally obsessed.  I think the latter has more motivation to sign-up.

But none of that explains the correlation with all measures of the marathoner (miles ran per week, number of marathons, etc) and LGE.  The LGE data suggest that marathons (training for and running in) are pathologically related to heart function.  And we still can’t rule out a role for diet!  Marathon training/running burns a LOT of calories.  Maybe it’s something their eating?  No food intake data were collected or reported in either study (but we know that unless these guys were losing weight, their food intake increased to match their expenditure; we just don’t know what they were eating).

Alternatively, maybe it’s not what they ate, but simply that they were eating so much more… the “rate of living” theory said that increased energy expenditure causes aging, disease, and death via free radicals.  Thus, caloric restriction, in which both food intake and metabolic rate are markedly reduced, improves longevity.

“Keep a quiet heart, sit like a tortoise, walk sprightly like a pigeon, and sleep like a dog.”  -Li Ching-Yuen (1677-1933)


Calories proper