Running and Your Heart, Part V: Coronary Calcifications

So I thought I was done with the Running and Your Heart series, but some questions came up that made me realize I needed to clarify a couple of points.  And I don't know, maybe we're not done with the series; I could see doing some more in-depth posts in the future about some specific issues.  A detailed post on atrial fibrillation might be in order.  For now, though, we're going to delve a bit deeper into coronary calcifications, their significance, and what the research means for us as distance runners.

image: the Heart Research Institute

As such, think of this post less as the fifth installment in the series and more as part IIIb, as we'll be addressing basically what we talked about in part III (and touched on briefly in part IV).  Let's recap some of the main points from that post.  The coronary arteries are blood vessels that carry blood to the heart muscle, supplying that muscle with the oxygen needed to carry out its function--namely, pumping blood throughout the body.  Blood flow through these blood vessels can be compromised by a disease process called arteriosclerosis--literally, a hardening of the arteries.  Generally, arteriosclerosis is caused by the accumulation of plaques within the walls of the arteries, resulting in a narrowing/hardening of the arteries (stenosis) that can impede the flow of blood to the heart muscle.  In times of increased stress on the heart (i.e., exercise), the demands of the heart muscle for oxygen are increased; if not enough blood is able to flow through these narrow, stenotic arteries to meet this demand, the heart muscle suffers from ischemia (lack of oxygen).  Prolonged ischemia, or complete occlusion of the artery, can lead to infarction, or death of a part of the heart muscle--which, if significant enough, can be debilitating or fatal.

Remember that in part III, we discussed the use of CT scans in detecting underlying coronary artery disease--namely, looking for calcium deposition in the coronary arteries.  Calcium is a component of many arterial plaques and is easily visible on high-resolution CT scans.  This test is especially useful in folks who don't have any symptoms of coronary disease but may have risk factors.  A growing body of research indicates that long-term endurance athletes--those who have been training at high levels or volumes for a decade or more--paradoxically have higher rates of coronary calcification than those of their age-matched peers in the general population, despite having much lower rates of many risk factors, like diabetes, hypertension, or obesity.  Remember that these studies have demonstrated correlation, not causation--we can't say that sustained exercise is the cause of this finding, only note that the relationship exists.  And recall also that we've yet to demonstrate what the real-world implications of these findings are--which is the point of this more involved discussion. To wit, the question: does having more coronary calcification lead to a higher risk of having a cardiac event?  The short answer is, yes--but for marathon runners, maybe not.

Numerous studies of the general population (that is to say, not specifically among marathon/ultramarathon runners) have correlated coronary artery calcification (CAC) scores to a higher risk of suffering a cardiac event, such as heart attack, death, or the need for revascularization (a re-opening of a blocked artery).  The exact degree of risk varies by study, but ranges from a four-fold risk increase to a twenty-fold increase have been reported in studies of varying size and quality.  Higher CAC scores are associated with a higher degree of risk, with significant risk increases generally seen with scores above 100 or 300 (zero is "normal").

OK, so that's bad.  Higher scores are associated with higher risk, and we've demonstrated that "obsessive" runners have higher scores, on average, than the general population.  That means our risk of suffering a significant cardiac event must be much higher, right?  Well, not necessarily.  First off, as I mentioned in the earlier post, there is research suggesting that long-term aerobic exercise leads to coronary arteries that have larger diameter, and have a greater ability to dilate.  (The autopsy of seven-time Boston Marathon champion Clarence DeMar famously revealed that his coronary arteries were two to three times wider than average.)  Secondly, to better understand our level of risk, we need to understand the nature of arterial plaque and the reasons one might suffer from a cardiac event.

Generally, narrowing of the coronary arteries, in and of itself, is unlikely to cause a cardiac event.  The precipitating factor in a cardiac event is often the rupture of an arterial plaque.  A piece of the plaque can break off and get carried "downstream" to a narrower part of the artery.  If it gets lodged there, it can cause a complete occlusion of blood flow to an area of the heart muscle, resulting in a heart attack.  So if we can identify which plaques are more susceptible to rupture, this will allow for a better stratification of risk.

Simply put, not all plaque is created equal.  Arterial plaque is generally composed of various substances: fat, cholesterol, calcium, and fibrin, to name a few.  One way of thinking of plaques is to classify them as either "hard" or "soft".  Hard plaque, made up of predominantly calcium, is generally considered more stable and less prone to rupture than softer (mostly cholesterol) or "mixed" plaque.  The good news is that while high-volume exercisers have higher CAC scores, they are much more likely to have hard, calcific plaques (read: stable) and much less likely to have mixed plaques than subjects who exercised the least.

So while we know that elevated CAC scores in the general population put people at risk for cardiac events, the risk for runners who have elevated CAC scores may not be the same, because of the composition of their plaques, and possibly the dilation of their coronary arteries.  Perhaps this is why, despite the fact that runners appear to have paradoxically higher-than-expected rates of calcification, cardiac events among habitual marathoners seem to remain relatively infrequent occurrences.

Running and Your Heart, Part IV: Running and Mortality

photo: mpora.com

At long last, here is the final post in the "Running and Your Heart" series.  When we started I thought I'd finish this series in about 4-6 weeks.  Now it looks like we're pushing past 6 months.  Hopefully it will have been worth the wait.

So over the past several months we've (rather infrequently) investigated the relationship between long-term endurance exercise and the heart.  We've discussed normal heart function, cardiac adaptations to exercise, abnormalities that can arise from these adaptations, and the impact of marathon and ultramarathon running on coronary artery disease.  (As a brief aside, one of the theories that I discussed in the last post--that the increased coronary calcification seen in marathon runners is quite possibly hard, stable plaque that is less likely to rupture and cause actual problems--has since been supported by some recent studies.  Alex Hutchinson, whose work is generally spot-on, has a good summary of these articles in Runners' World.)  What I've tried to stress is that we should not be alarmist about these issues, but that we should not be naive either in thinking that our running makes us immune from heart disease.  Rather, we need to be aware of the potential problems that can arise from long-term training and be able to address these possibilities with our physicians in a responsible way.

OK, that's all well and good.  But when we start seeing articles with titles like "Fast Running is as Deadly as Sitting on the Couch, Scientists Find" and "Excessive Running Could Kill You", it's natural to feel a bit concerned.  We know running, on the whole, is good for us.  Since Jim Fixx gave us his seminal work The Complete Book of Running in 1977, detailing how running saved him from what seemed to be his genetically destined early cardiac death, we've taken it on faith that diligent training leads to longer lifespans.  But with all the studies in the past decade that have been hinting at correlations between long-term marathon running and paradoxical heart disease, is it possible that we're taking things too far?  Have we reached the point where all this running is actually shortening our lifespans?  (And wait a second, didn't Jim Fixx die pretty young after all?)

Much of the recent concern over the possibility that too much running might actually be bad for you centers on a couple of ideas.  One is the relationship between long-term marathon running and coronary artery disease, which we discussed in detail last time.  Just to sum up where I stand on this: I think it's pretty unambiguous that people who train vigorously for marathon-and-longer distance events for many years do have a higher incidence of coronary artery calcification than those who do not, and that the cardio-protective benefits of regular aerobic exercise require much less mileage and less intensity than many of us (including myself) are actually doing.  However, as I pointed out in the links above, not all coronary calcification is created equal; while you'd certainly prefer less calcification than more, and no calcification to any, the calcific plaques demonstrated in asymptomatic long-term runners are not the same in terms of composition (and possibly long-term risk) as those we'd associate with smoking, uncontrolled hypertension, diabetes, or other native disease states.  Even if we assumed that we may be at higher risk of suffering a serious cardiac-related event as a result of strenuous running (by no means a reliable assumption), I don't think the data support the conclusion that this risk outweighs the mortality benefit of the decreased incidence of high blood pressure, diabetes, and cancer that runners consistently demonstrate over their more sedentary peers.

The other idea that has received a lot of publicity in recent years is the so-called "U-shaped mortality distribution."  This concept is based largely on the work of James O'Keefe and other researchers involved in the Copenhagen City Heart Study, as well as Duck-chul Lee, who in 2012 presented a rather controversial abstract at the American College of Sports Medicine conference.  According to their research, when plotting mortality (the dependent variable) on the y-axis against mileage (the independent variable) on the x-axis, the data shows the highest mortality values at the lowest and highest ends of the exercise spectrum (i.e., a "U-shaped" distribution):

The "U-shaped" mortality curve.
figure: American College of Cardiology 

In other words, those runners logging much less mileage--as little as a mile a day in some cases, and certainly less than 20 miles a week--saw the greatest benefit in mortality, while those running more mileage saw little to no mortality benefit at all!

These are the studies that have prompted most of the terrifying headlines you've read in recent years, and these are the studies I want to talk about today.  Not to argue with their data, but to try to help us understand why some of the authors'--and the media's--conclusions are not necessarily as dire as we've been led to believe.

Lee et. al. demonstrated a 20% reduced risk of mortality for runners vs. non-runners over a 15-year follow-up period--great news!  However, the study appeared to show that runners averaging more than 20 miles per week had not only higher rates of mortality than those running less, but that their mortality rates approached those of sedentary, non-running peers.  However, these findings were based on the researchers' adjustments for various conditions, including body mass index (BMI), smoking, diabetes, and hypertension.  What does this mean?  When comparing different groups of people, researchers can run into a problem with what are called confounding variables.  These are differences between groups that might affect what you're trying to measure.  In this case, the researchers were trying to determine the relationship between running mileage and mortality.  Of course, there are many different variables that contribute to one's mortality risk, and without accounting for these variables, it's difficult to ascertain whether differences between groups of data is due to what you're actually trying to measure (running mileage) or to something else that you're not measuring.  So the researchers performed what's called statistical correction to take these variables into account.  Simply put, they eliminated the effect of as many of these confounding variables as possible, trying to answer the question: "If all other things are equal--if all of these groups are made to be the same in terms of their rates of obesity, diabetes, blood pressure, etc.--then what effect does mileage run have on their mortality risk?"

Let's be clear: there's nothing underhanded about this.  Statistical correction is a perfectly legitimate (and in most cases necessary) part of scientific research; it's how we attempt to discern cause and effect in situations with many different variables in play.  In this particular case, however, we run into a problem.  The reason that running might have a benefit on mortality is that it makes you healthier overall.  That is to say, vigorous runners are less likely to be obese, to have high blood pressure, or to suffer from diabetes.  If you eliminate these benefits as "confounding variables," it only stands to reason that the mortality benefits of running disappear from the data as well.  The problem with this study wasn't that the authors tried to correct for confounders; it was their classification of the benefits of exercise as confounding variables in the first place.  Alex Hutchinson was all over this pretty much right away, and in 2013, cardiologist Thomas Weber pointed out the problem in the journal Heart:

"One possible explanation for the U-shaped curve...is that the authors adjust for body mass index, hypertension and hypercholesterolaemia. Running has been shown to lower those risk factors in a dose-dependent fashion with no sign of negative returns until at least 50 miles/week. Arguably, adjusting for all these factors is akin to adjusting for low-density lipoprotein (LDL) values in a study analysing the survival benefit of taking statins to treat hypercholesterolaemia. Put simply, this editorial represents a selective interpretation of the available data, at the best."

What Weber is saying is, if you were studying the impact of a drug for cholesterol on mortality, and you had two groups (one which took the drug and one which didn't), it wouldn't make any sense not to look at the differences in the cholesterol levels between these two groups--how else would you expect the drug to improve mortality if not by impacting cholesterol levels?  Similarly, if we grant that running makes us healthier because it protects against hypertension, diabetes, and obesity, then those are very likely the reasons it would have a mortality benefit; removing those effects from the analysis doesn't make sense.

Indeed, when the final paper of this study was published in 2014, the researchers eliminated the statistical correction--and the U-shaped mortality curve seemed to vanish!  Instead, the authors, now concluded,

"[R]unners across all 5 quintiles of weekly running time, even the lowest quintile of <51 minutes per week had lower risks of all-cause and CVD (ed: cardiovascular disease) mortality compared with non-runners. However, these mortality benefits were similar between lower and higher doses of weekly running time. In fact, among runners (after excluding non-runners in the analyses), there were no significant differences in hazard ratios of all-cause and CVD mortality across quintiles of weekly running time (all p-values >0.10)."

That is to say, running even a little bit lowered mortality risk, and this lower risk appeared constant regardless of the time or distance run per week. Perhaps not surprisingly, this received significantly less media attention than the earlier version of the results.

Similarly, the researchers in the Copenhagen City Heart Study reported findings that seemed to support the U-shaped mortality curve, concluding:

"We found a U-shaped association between jogging and mortality. The lowest mortality was among light joggers in relation to pace, quantity, and frequency of jogging. Moderate joggers had a significantly higher mortality rate compared with light joggers, but it was still lower than that of sedentary nonjoggers, whereas strenuous joggers had a mortality rate that was not statistically different from that of sedentary non joggers." 

and cited Lee's paper in their discussion of the results.  Again, however, these conclusions don't tell the whole story.  While this study followed nearly 1100 runners over a 12-year period, only 40 of these runners qualified as "strenuous joggers" according to the rubric of the study (running at a pace of 9:00/mile or less for at least 2.5 hours/week), and there were only two deaths among this group during the course of the follow-up period--not nearly enough of a rate to draw any meaningful conclusions.  As researcher Steve Farrell pointed out,

"Say that 2 blindfolded men ran across a busy highway and were not struck by a car. Would anyone conclude based on those two events, that it is perfectly safe for everyone to run blindfolded across a busy highway?"

So what to make of all this?  It seems pretty clear that the substantial mortality benefits of aerobic exercise are conferred even after relatively small amounts of running--which is great news for the sedentary population and light exercisers in general--and I'd agree that at some point we reach a rate of diminishing returns, where further increases in mileage or intensity don't offer any additional mortality benefit.  But where that point lies has not been clearly defined, and I think that based on what we currently know, fears of increased mortality as a result of exceeding that threshold appear unfounded.  And generally, most of us who are interested in exploring our physical limits are doing so for reasons that go beyond "living longer."  As Amby Burfoot points out,

"Many aspects of exercise and running also follow a U-curve. This is why many people believe the moderate approach is the smartest path to follow. Of course, you’ll never qualify for the Boston Marathon that way. We all have to make our choices."

Certainly we don't need to run ultramarathons experience all the health benefits of regular exercise.  But it doesn't seem like we need to fear them either.

Running and Your Heart, Part III: Coronary Artery Disease

Coronary arteries, as seen via cardiac catheterization.
photo: pinterest.com

Before we get into it, let's just reiterate that this post (or anything else you read on the blog) is NOT to be construed as medical advice.  This is for informational and general-knowledge purposes only.  Furthermore, while I have a pretty good grasp on this stuff, I'm NOT a cardiologist, and anything you might read here is subject to my own interpretations (or mis-interpretations).  As such, this blog should not be taken as a substitute for medical care by a qualified professional.  I'm happy to provide information and try to answer people's questions.  But I AM NOT YOUR DOCTOR.

That being said...this blog is getting awful science-y.

In my continuing effort to either confuse the shit out of you, or freak you out (no, no, JK), I thought we'd delve a bit more into the relationship between distance running and heart health/disease by focusing on the coronary arteries.  Last time I talked about the normal adaptations the heart makes to endurance exercise ("the athlete's heart") and how these adaptations can be both beneficial and, in some cases, harmful.  In that post we quickly glossed over the coronary arteries, but today we're going to examine that aspect of the cardiovascular system in greater detail, because it's extremely important and because a lot of recent research has examined this relationship closely.

photo: pinterest.com

Recall from last time that the arteries carry oxygen-rich blood from the heart to the various muscles, tissues, and organs of the body, supplying them with the oxygen necessary to perform their particular functions.  The coronary arteries run directly over the heart muscle itself, bringing oxygen to the heart tissue and allowing the heart muscle to fulfill its ceaseless task of pumping blood throughout the body.  Given the heart's position of primacy in the body, you can see how the entire system relies to large extent on the uninterrupted flow of blood to its muscle.

As discussed previously, the term "heart disease" can encompass a wide variety of problems with the various physiologic systems at play in the heart: anatomic, structural, electrical, etc.  But most commonly, when someone refers to "heart disease," they mean an abnormality within the coronary arteries that compromises the flow of blood and the delivery of oxygen to the heart muscle.  This can take the form of stenosis, a hardening and narrowing of the artery that can disrupt blood flow.  Such narrowing occurs when various junk, usually cholesterol, builds up within the lumen of the artery.  (Picture a pipe or a hose that gets clogged with dirt and how that affects the flow of water through it.)  Over time, these plaques can harden and calcify, causing the artery to narrow and stiffen.  These stiff, narrow arteries thus lose their ability to dilate (expand) in response to an increased demand for oxygen--for example, during exercise.  So when a heart with narrow, inelastic coronary arteries is placed under the stress of exertion, the arteries cannot expand to meet that increased demand, and the heart muscle suffers from a lack of the necessary oxygen, called ischemia.  (This is the most common reason someone would have chest pain with exertion, also termed angina.)  Sometimes, a piece of these plaques can break off and become dislodged from the inner wall of the artery, travel downstream, and get stuck in a narrower part of the artery, causing a near-complete or complete cessation of blood flow to a particular part of the heart.  If prolonged, this can lead to infarction, or death of this part of the heart muscle: what is commonly known as a "heart attack."

So why do people get coronary artery disease?  Well, part of it is genetic; if your parents or siblings have coronary artery disease, you're more likely to suffer from it as well, and obviously you can't do anything about that.  But there are many modifiable risk factors for coronary stenosis, such as high blood pressure, diabetes, and smoking, that you can do something about.  And running helps with these factors: regular aerobic exercisers have lower rates of high blood pressure and diabetes, and are less likely to smoke.  But here's the kicker: despite the fact that distance running unquestionably reduces your risk factors for coronary disease, it may not actually reduce the chances of developing coronary disease.

CT scan reveals calcification of the coronary arteries.
photo: umm.edu

One of the problems with standard screening tests for coronary artery disease--namely, EKGs and stress tests--is that they are not particularly sensitive in detecting underlying coronary disease among fit individuals.  A routine exercise stress test aims to induce strain on the heart by gradually increasing the heart rate via exertion in a laboratory setting; patients are then assessed for symptoms of heart disease, or changes in blood pressure or heart monitor patterns.  For regular endurance exercisers, the limitations of this test are obvious.  If an athlete is increasing their heart rate via exercise on a daily basis without adverse symptoms, why would any abnormalities appear when she does it on a treadmill, in front of a physician?  However, in the past decade advances in technology have made high-resolution CT scanning widely available for the detection of underlying coronary artery disease.  A CT scan is not without downside--it does involve exposure to ionizing radiation, which is carcinogenic in high doses--but this modality can help identify at-risk individuals who might otherwise be missed by more traditional assessments of cardiovascular health.

Applying this test to an athletic population, researchers have discovered some surprising findings.  Despite having a lower incidence of hypertension, diabetes, and obesity, long-term marathon and ultramarathon runners actually have a higher incidence of coronary artery calcification than non-exercisers in the general population.  (Interestingly, runners who regularly train and compete at shorter distances do not demonstrate this finding.)  This paradoxical relationship has been reported as early as 2008, and has been validated several times since (including by yours truly and colleagues earlier this year).

Why does this happen?  We're not really sure, though several theories have been advanced that might account for this process.  One idea is that repeated high-intensity aerobic efforts subject the coronary vessels to more turbulent blood flow, which over time can lead to chronic inflammation and calcification.  Free radical formation, causing chronic oxidative stress, may also play a role. 

So, does this mean we should all stop running ultras?  Not necessarily.  No one has demonstrated as yet that this increase in coronary calcification leads to an increase in clinical signs of heart disease, or to an increase in mortality (we'll address this further in a subsequent post).  There is some thinking that the calcifications commonly seen in long-term distance runners are firmer and more stable than the softer plaque often seen in the general population, and therefore less likely to break apart and cause the downstream problems I talked about earlier.  Also, research demonstrates that long-term training leads to larger coronary arteries, with more ability to dilate (open up) than those in untrained subjects.  This might serve to counteract the narrowing effect of coronary calcification.  (If your hose is getting clogged, make the hose bigger, and water will be able to flow through more easily.)

OK, this isn't the most reassuring post of all time.  But let's sum up with what we actually know:

• long-term endurance exercise reduces your risk of high blood pressure, diabetes, high cholesterol, and obesity.  Since heart disease is only one of the issues that can arise in people who suffer from these ailments, this fact alone is probably reason enough to keep training.
• despite this, people who regularly train for and participate in marathons and ultramarathons appear to have a higher rate of coronary calcification than those who don't.  
• this higher incidence of calcification may or may not be clinically relevant.  But all things being equal, you'd rather it wasn't there.
• even runners with higher levels of coronary calcifications may not show signs or symptoms of disease, and standard screening tests may not pick up underlying disease in these people.

Therefore, my take-home point is not that we should all freak out and stop running.  But we should realize that we're not immune to coronary artery disease, even though we are invariably "healthier," on average, than non-runners.  For those of us entering our masters running careers, and who have been at this for several years or more, we should be cognizant of this risk.  Talk to your physician about the pluses and minuses of a CT scan of the coronary arteries, particularly if you have a family history of coronary artery disease in a close relative.  And check back next week when I'll tackle the "running versus mortality" question and try to debunk some of the negative press coverage you may have seen recently.

Lab Rat

As I've previously mentioned, I've recently started working with the Heart Center in their new sports cardiology practice, performing exercise physiology testing on athletes and assisting on a research project examining the relationship between distance running and heart disease.  However, though I've become quite familiar with performance testing over the past several months, I'd never undergone any physiologic tests myself.  That changed recently when my friend Beth Glace, a sports nutritionist and exercise scientist at NISMAT, recruited me to take part in a study on the mechanisms of fatigue in endurance athletes.

Ultrasound looking at muscle glycogen stores.
All photos: Charlotte Freer

I took the train into Manhattan and walked uptown to NISMAT, which is an extension of Lenox Hill Hospital that specializes in sports medicine and athletic performance.  I met Beth and her co-investigator, Ian, who showed me around and took me through the various elements of the research protocol.  First, I had my height and weight taken, and I underwent an ultrasound of my quadriceps, as a means of measuring my baseline glycogen stores in the muscle.  (Though I'm still on a low-carb/ketogenic diet, my levels were pretty normal.)  Then, I hopped onto the treadmill for a VO₂max test, the first arm of the protocol.  In this case, it didn't really matter what my max was, as this was just being used to determine the intensity at which I'd need to run during the latter stages of the project.  But surprisingly enough, we ultrarunners can get a bit competitive about some fairly mundane things, so I was pretty fired up to see what kind of numbers I could hit.

The dreadmill, with all kinds of fancy equipment.

The test followed a standard protocol, which includes a very brief warmup followed by progressive increases in intensity, until the subject/athlete can't go any further.  I was placed on a heart rate monitor and affixed a plastic headset that held in place the tube into which I'd have to breathe.  This tube ran into an analyzer that measured the relative volumes, rates, and percentages of the various gases I inhaled and exhaled.  From this, Beth and Ian could see not only my VO₂max, but also my lactate threshold (technically my ventilatory threshold, I'll probably bore you with some details about the difference in a future post), and, via a measurement called the respiratory exchange ratio (RER, or sometimes just R) could also determine whether I was burning carbohydrates, fats, or a mixture of the two, at various intensities.

I began by walking on the treadmill at 3mph (20:00/mile), which increased by 1 mph each minute, until reaching 6mph (10:00/mile) at the four-minute mark.  From that point on, with each passing minute, the incline increased by 2%.  Beth informed me that the treadmill had a max gradient of 20%, after which (if I was still running) the speed would then increase to 7mph (8:30 pace) for a minute.  If I could somehow keep going for that minute, the test would automatically stop.  And so I arrived at my arbitrary goal.

If you've never had a VO₂max test before, it is a very brief, very exquisite sort of torture.  The goal is to push the athlete to run to their maximum effort; thus, the test needs to be difficult enough to induce exhaustion, but short enough that the athlete doesn't end the test prior to reaching their max due to accumulated fatigue.  For the first eight minutes or so, then, the test is rather benign, but as the grade pushes past 12%, it begins to get unpleasant quite rapidly.  After eleven minutes, I reached 16% and was really starting to feel it.  At twelve minutes and 18%, I knew I could at least get to the 20% maximum grade, but I wasn't sure how long I could hold it there.  I fought my way through the entire minute at 20% and briefly entertained the possibility that I could finish an entire minute at 20% and 7mph, but after about 15 seconds I gave a desperate signal to stop.

The numbers were pretty cool; it's amazing how much data is generated from these tests and what it can be used for.  I was able to reach a VO₂max of 4.59 L/min, or 70.1 ml/kg/min, which is a pretty solid value for an old man.  My ventilatory/lactate threshold occurred at 88% of my VO₂max, which is near the upper end of normal.  (Higher is better: beyond the LT, lactate accumulation occurs faster than lactate clearance, and the steady accumulation of lactate will lead to fatigue; thus, being able to exercise as close to max effort as possible before reaching that point is obviously beneficial.)  Most interesting to me were the RER values.  I didn't start burning carbs at all until I was nearly halfway through the test, and I didn't hit an RER of 0.85 (metabolizing 50% carbs and 50% fat) until the ten-minute mark, running at at 14% grade with a heart rate of 171.  (My max HR came in at 184, slightly above predicted.)  Beth described this as very unusual, but consistent with the theory behind the ketogenic diet.  Nice to see that it's working.

Torture device.  I mean, the Biodex.

So that took care of the baseline testing.  I returned to the lab a week later for the main part of the protocol.  I began on a virtually empty stomach, having been instructed by Beth only to drink 13 oz. of Ensure about an hour prior to arrival.  After re-weighing and rechecking my ultrasound, I was seated on the Biodex, which was used to measure muscle contraction strength in my right quadricep.  Ian explained that first, they would measure a voluntary contraction, as I tried to extend my leg as forcefully as possible against resistance.  Then, they would provide stimulation with a magnetic field over my femoral nerve, which would induce an involuntary contraction.  Measuring the difference in the amount of force between these two, before and after exercise, would suggest whether fatigue was mediated by central (nervous) or peripheral (muscle) mechanisms.

Probably before I knew what was coming.

After strapping in to the seat, I pushed as hard as I could for about five seconds, and the force was measured.  Ian then positioned the magnet over the femoral nerve in my right thigh and induced a few isolated contractions.  It was forceful enough to make my body jump, but not painful.  Then came the payoff: I again gave a maximal voluntary contraction; after about three seconds, Ian introduced a continuous magnetic field, stimulating a sustained involuntary contraction as I continued to apply voluntary force.  As soon as he hit the button, I screamed; it wasn't painful exactly, but was one of the weirdest and most uncomfortable feelings I've ever experienced.  We did that twice more.  Then the real testing could start.

Waiting with dread...

The meat of the test was a two-hour continuous run on the treadmill, at 70% of my VO₂max.  Beth attached the breathing apparatus every fifteen minutes to ensure that I was maintaining the appropriate work rate.  My blood sugar and blood lactate levels were checked every hour.  When the two hours were up, the ultrasound measurements were repeated, and I was once again subjected to the Biodex, which remained just as unpleasant.  Then, back on the treadmill for a 2km time trial, as hard as I could push myself.  Then weighed again, ultrasounded again, and--you guessed it--the Biodex again.

Either really tired, or just anticipating getting back on the Biodex.

I'm not gonna lie, it was a pretty exhausting day.  But it was really interesting to see some of these processes in action, and I got a great feel for the different types of data that a treadmill test can generate.  I'll talk a little more about some of this stuff as the sports cardiology program starts to launch and I start seeing patients in the real world.

Running and Your Heart, Part II: The Athlete's Heart

Last week, inspired by some recent schoolwork and research, and mildly prompted by my collapse at Rocky Raccoon,  I started a series of posts on distance running and cardiac health.  The first post used my last twenty miles at Rocky as a jumping-off point to talk a little bit about pulmonary edema, and rather obliquely about cardiac illness.  I'd like to delve a little bit more into the relationship between endurance exercise, heart health, and heart disease.  In light of some of the recent media coverage of these issues, we're going to discuss some facts and address some common misconceptions and/or misinterpretations of some of the data out there, with the goal of all of us becoming better informed regarding this topic and better able to make rational decisions about our athletic future.

Before we can get into dysfunction, though, we have to talk about normal function, and about the physiologic adaptations that the heart makes to long-term endurance exercise.  Many of these adaptations are beneficial, but they're not without problems, either.

The normal heart

Chambers (and valves) of the heart

I don't think there's any need to get into a bunch of esoteric facts about the heart (It pumps six liters of blood per minute! It weighs 300 grams!) but we should first go through a few basics.  I'm sure you can remember from ninth grade biology that the heart is a muscle that pumps blood through the body.  You might also remember that the heart is split into two sides (left and right), each of which has two chambers (an atrium and a ventricle).  The right side of the heart pumps de-oxygenated blood to the lungs, where the red blood cells bind to oxygen.  Blood from the lungs then returns to the left side of the heart, from where (whence?) it is pumped out to the rest of the body so that the various tissues and organs can use that oxygen.  Having delivered oxygen to the tissues, the blood then returns to the right side of the heart to begin the cycle again.  Blood flows throughout the circulatory system in what is essentially a series of tubes; veins carry blood to the heart, while arteries carry blood from the heart.

OK, simple enough.  From a basic standpoint, that's all we need the heart to do: pump oxygen-poor blood to the lungs, deliver oxygen-rich blood to the rest of the body.  So when we talk about cardiac disease, we're most generally talking about a failure of the heart to fulfill that function.  But there are a bunch of different ways in which this basic function can be compromised.  For our purposes, there are three systems inherent to normal heart function that we want to be familiar with in order to understand possible dysfunction: the coronary arteries, the conduction system, and the heart muscle itself.

Coronary arteries

We spoke briefly about the heart muscle last week; simply put, the muscle squeezes, increasing the pressure within the chambers of the heart, and forces blood out into the circulation.  The muscle is the heart's engine.  The coronary arteries are responsible for delivering oxygen to the heart muscle.  Wait a minute, you're saying, didn't you just say that arteries carry blood AWAY from the heart?  Yes, I did!  Thanks for paying attention!  Arteries do indeed carry blood away from the ventricles, but in this case they don't have to go very far.  The coronary arteries arise from the aorta immediately after the blood leaves the left ventricle, and they surround the heart, supplying oxygen-rich blood to the muscle.  When you hear the term "heart attack," this is usually used to mean an interruption of blood flow to the heart muscle, usually due to a narrowing of, or blockage within, the coronary arteries. We're going to do an entire post about the coronary arteries next week, so for now, just think of them as the heart's plumbing system.

The conduction system, then, is the wiring.  This system is comprised of electrical fibers that coordinate the heartbeat.  The depolarization of these electrical cells causes the atria, and then the ventricles, to contract synchronously.  The contraction of the atria forces blood into the ventricles, and the contraction of the ventricles forces blood out into the circulation.  When you see that familiar tracing that we all know represents a beating heart:

what you're looking at is a graphic representation of the heart's electrical activity.  (I'm not going to go into what each of those little squiggles means, but if you're interested, read this.)  Without the orderly input of the electrical/conduction system, these contractions may lose their synchronicity, robbing the heart muscle of its ability to pump blood effectively--or contractions can cease altogether.

The athlete's heart

Note the enlarged (dilated) cardiac chambers
in the athlete's vs. non-athlete's heart.
Photo: cyclingtips.com

Like any other muscle, the heart responds to exercise by adapting to stress.  Weight lifting, for example, places the skeletal muscles under stress, ultimately causing the muscles to adapt by increasing muscle mass and size (hypertrophy).  Similarly, aerobic exercise means that the muscles requires more oxygen, necessitating increased cardiac output (the amount of blood the heart pumps).  Over time, the heart muscle adapts by increasing the mass and thickness of the muscular wall of the left ventricle.  Other adaptations include dilation (or enlargement) of the various heart chambers, and dilation of the coronary arteries (which I'll discuss more in next week's post).   In the absence of a history of vigorous exercise, many of these structural changes--hypertrophic ventricular walls, atrial dilation--would be considered pathologic.  That is to say, when we see these sorts of things in the population at large, they are usually the result of chronic high blood pressure or underlying cardiac disease, are usually associated with a loss of the heart's pump function, and can lead to congestive heart failure, pulmonary edema, and other general badness.  But in endurance athletes, who demonstrate these changes in the setting of preserved pump function, they are usually considered normal adaptations to long-term vigorous exercise that we term the athlete's heart.

What's the big deal? Aren't adaptations good?

So, in general, we think of the chronic adaptations associated with the athlete's heart to be beneficial, or at the very least neutral.  They allow for us to increase our cardiac output to meet the demands of intense aerobic activity, and do not appear to be associated with the sort of pathology we would otherwise expect from these kinds of changes in heart morphology.  However, there is some evidence that suggests that there may be some downside to some of the adaptations of the athlete's heart.

For example, take the dilation seen in the heart's chambers, particularly the left atrium and right ventricle.  There is a hereditary disease called arrhythmogenic right ventricular cardiomyopathy, a rare condition that causes dilation of the right ventricle and fibrous deposition or "scarring" within the myocardium (the muscular layer of the heart wall).  This fibrous tissue can interrupt the electrical pathways of the heart (remember that conduction system stuff?), serving as an origination point for life-threatening ventricular arrhythmias (abnormal heart rhythms).  The dilated RV seen in long term athletes can be accompanied by similar fibrous deposition, leading to some speculation that there may be an "exercise-induced arrhythmogenic right ventricle" that may mimic the inherited condition.  (Some have posited this as the theoretical framework for the death of Ryan Shay at the US Olympic Trials marathon in 2007, though that--in fact, all of this--remains unproven.)  Dilation of the left atrium also seems to place athletes at increased risk of atrial fibrillation or atrial flutter, two abnormal heart rhythms that, while not as dangerous as ventricular arrhythmias, can still cause significant cardiovascular complications.

No bueno.

Another interesting cardiac finding associated with ultra-endurance exercise relates to cardiac enzymes.  Many of you are probably familiar with rhabdomyolysis, a fun little problem in which repeated skeletal muscle trauma (as seen in, say, a 100-mile run) causes breakdown of muscle tissue and the release of enzymes called myoglobin and creating phosphokinase into the bloodstream.  Just like skeletal muscles, heart muscle contains these enzymes; but there are also enzymes that are specific to cardiac muscle, notably troponin.  Troponin is generally only minimally detectable in the bloodstream; elevated troponin levels generally imply damage to the heart muscle, usually from ischemia (lack of blood flow)-- a "heart attack."  Now, several studies have detected significant elevations in troponin levels following prolonged exercise.  Does this mean that we're giving ourselves small heart attacks during every ultra we run?  Probably not; while troponin elevations following heart attacks tend to peak many hours after the event, and persist for several days to weeks, post-exercise troponin elevations typically appear, and resolve, very rapidly.  Furthermore, while there have been studies showing reduction in LV and RV function following ultra endurance events, in almost every case function has been demonstrated to return to normal within one week, unlike what we would see in a "heart attack."  It appears possible that the transient elevation in troponin following extreme exercise is related to increased permeability (leakiness) of the cardiac cell membranes rather than ischemia, cell death, or permanent heart damage.

What does all this mean?

I know, I hit you with a lot of information, and right now you might be freaking out a little bit.  Freaking you out is not the objective of this post.  We're going to talk big picture in a couple of weeks, and hopefully when we're done you'll feel pretty comfortable with the whole deal.  For now, here's the take-home points:

• there are several adaptations that the heart makes to accommodate long-term, vigorous aerobic exercise
• most of these adaptations are generally beneficial
• there are some morphologic changes (that is, the the size/shape of the heart) that may increase the risk of arrhythmias in athletes
• most of the evidence we have at this time shows correlation, not causation, and much of the framework surrounding this remains theoretical/speculative

Again, we'll go big picture in a couple of weeks, and I'll be able to draw things together a little bit more.  The point of all this is just to make you a little more aware and informed about some of the interesting stuff that's out there, and maybe to generate some fodder for a discussion with your doctor if you have questions or concerns.  

If you want some really detailed reading on this stuff, check our these highly scientific articles:

George K, Whyte GP, Green DJ, Oxborough D, Shave RE, Gaze D, and Somauroo J. (2012). The endurance athletes heart: acute stress and chronic adaptation. British Journal of Sports Medicine, 46(S1), i29-i36.

O'Keefe JH, Patil HR, Lavie CJ, Magalski A, Vogel RA, and McCullough PA. (2012). Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise. Mayo Clinic Proceedings, 87(6), 587-595.