Troponin Spikes After Exercise Not Linked to CAD in Middle-aged Athletes

Elevations in cardiac troponin (cTn) after long bouts of aerobic exercise are not associated with subclinical coronary artery disease in middle-aged athletes, a new study shows.

The release of cTn after exercise was relatively common in this study of 1,011 long-distance walkers, cyclists, and runners, but there was no difference in the prevalence and magnitude of coronary atherosclerosis among those with large elevations in cTn and those with little, report investigators.

“For the athletes, this is good news,” senior investigator Thijs Eijsvogels, PhD (Radboud University Medical Center, Nijmegen, the Netherlands), told TCTMD. “It’s a neutral study. There was no difference between the high and low [cTn] responders. It means that if you compete in an exercise event, and it happens that you have very high postexercise troponin, it’s unlikely attributable to underlying coronary disease.”

Acute bouts of exercise are well known to elevate concentrations of cTn, a biomarker typically used to identify myocardial injury or acute coronary syndromes. In one study of marathon runners, for example, nearly all had increases in cardiac troponin I (cTnI) after the event, with half exceeding the cutoff used to diagnose myocardial infarction. It’s not known why troponins increase after exercise, and there remains some debate around the significance of the finding in athletes.

“What we see in athletes reporting elevated troponins is that they are completely asymptomatic,” said Eijsvogels. “It’s an isolated increase in this cardiac biomarker. What is actually quite striking is if we look at the variation in the magnitude of those changes, it varies from one individual to another individual. In some athletes, it’s a 1%, 2%, or 5% increase, whereas in another athlete we might see a 1,000% increase.”  

Paul Thompson, MD (Hartford Hospital/University of Connecticut), who has investigated the relationship between exercise and troponin release, said that many people have elevations in cTn after an endurance event, meaning that there has likely been some stress on the heart.

“We don’t know what causes it, and some people have postulated that it’s really a marker of subclinical atherosclerosis,” Thompson told TCTMD. “If someone runs a marathon and they have a rise in troponin, it might mean their coronary arteries aren’t so good. This study is useful because it says that’s not true. There was no correlation between the extent of atherosclerosis and the extent of [troponin] elevation. It’s checking one box as to what might be the cause of it.”

Similarly, Aaron L. Baggish, MD (Université de Lausanne, Switzerland), said the study adds to an extensive body of research showing that cTn release after intense or prolonged exercise is common. The rise should not be considered a marker of underlying pathology in an athlete without ischemic symptoms, he said.  

“Postexercise troponin bumps often exceed conventional upper-limit-of-normal/acute MI cut points but have no relationship with clinical acute coronary syndromes,” Baggish told TCTMD. “While it has been interesting to study this phenomenon, the actionable clinical message is simple. Do not check a troponin level in an athlete after exercise unless there is a clear clinical picture of an acute coronary syndrome.”

If you do, he added, “you’ll be stuck with a meaningless result.”

High and Low Troponin Responders

The new analysis, which was published this week in JACC, includes male and female athletes 40 years and older (< 70 years) enrolled in the prospective TREAT cohort study. All participated in long-distance endurance events—walking ≥ 15 km, cycling ≥ 100 km, and running ≥ 15 km—and had baseline and postexercise high-sensitivity (hs) cTnT and cTnI measurements.

Baseline hs-cTnT was 5.8 ng/L, increasing to 14.3 ng/L after the event. More than 51% of athletes had hs-cTnT levels greater than the 99th percentile upper reference limit (URL). The concentration of hs-cTnI increased from 2.0 ng/L at baseline to 7.4 ng/L after the sporting event, with 15.9% of athletes reporting concentrations exceeding the 99th percentile URL.  

After the event, baseline and postexercise hs-cTnT and hs-cTnI concentrations were ranked highest to lowest and given a rank number. The numbers were added together and participants with the lowest sum score were labeled “high” troponin responders and those with the highest score were designated “low” troponin responders. Roughly 10% of the total cohort underwent CT scans within 3 months of the sporting event, and among them, there were 68 high and 34 low troponin responders.

For the athletes, this is good news. Thijs Eijsvogels

Overall, there was no difference in the coronary artery calcium (CAC) score between high and low troponin responders, nor was there any difference in the prevalence of those with a CAC score greater than zero. Atherosclerotic plaques on CT were evident in 62% of athletes, with 11% having obstructive disease, but there was no significant difference in the prevalence of coronary artery disease, obstructive disease, and hemodynamically significant stenosis assessed by CT-fractional flow reserve in the high versus low troponin responders.  

Postexercise hs-cTnT and hs-cTnI concentrations, and the pre- to postexercise changes, did not correlate with CAC scores. There were only weak associations between hs-cTnT measurements at baseline and after exercise, as well as the change from before to after exercise, and coronary atherosclerosis on CT. With hs-cTnI, only the change with exercise was weakly linked to atherosclerosis.  

Not CAD, But What Else?

In an editorial, Cian McCarthy, MBBCh, and Meagan Wasfy, MD (both Mass General Brigham/Harvard Medical School, Boston, MA), say the results suggest that epicardial coronary disease isn’t the main driver of postexercise troponin elevations. However, the reason for the spike after exercise is still not known.

They suggest several irreversible and reversible mechanisms, including the myocardial necrosis that may occur when prolonged ischemia leads to cell death and release of intracellular proteins, including cTn.

“Other mechanisms for postexercise cTn rise include those that may be benign, reflecting transient perturbations in physiology that return to normal without consequence,” they write. “Alternately, higher elevation in cTn in response to repetitive, large exercise doses may still help identify those susceptible to cumulative negative effects, such as arrhythmias and myocardial fibrosis that are also more common in male endurance athletes.”

Thompson noted that elevated resting cTn levels in the general population are considered a marker of risk, but said the increase in athletes is unlikely to be cause for concern. Still, the long-term impact of these postexercise bumps in troponin are uncertain. “It doesn’t mean they have coronary artery disease, but it may be something funny, like maybe their heart muscle cells leak. We can’t exclude other possibilities,” he pointed out.

While cTnT and cTnI both increase after exercise, Thompson said cTnI is more specific to the heart. With skeletal muscle injury and repair, cTnT increases more than cTnI. Also, cTnT can increase from other skeletal muscle diseases. “That’s why I say ‘T stands for trouble’ when I’m on the wards with trainees,” Thompson said. “It can often be from other things besides the heart injury.”   

Do not check a troponin level in an athlete after exercise unless there is a clear clinical picture of an acute coronary syndrome. Aaron L. Baggish

At this stage, Eijsvogels is fairly confident that a large release of cardiac troponin after exercise reveals something about the person’s cardiac health. 

“In general population studies, they have repetitively shown that if you have higher troponin concentrations, in the end this is associated with clinical outcomes during follow-up,” he said. “Of course, we know the cardiovascular health is much better in athletes compared to those in the general population, but I still think if you’re an athlete and you are a high responder to cardiac troponin, it tells something about your heart health. It’s not coronary atherosclerosis but maybe it’s something else.”

To TCTMD, Eijsvogels said exercise intensity and duration are two variables associated with the release of cardiac troponins, but they still don’t know what explains the interindividual differences or the clinical relevance of the high concentrations.

“In one of our previous studies in long-distance walkers—so a different population engaged in moderate-intensity exercise, average age was 60 years old—we found that if you had a high cardiac troponin concentration following exercise, that was associated with an increased risk for major adverse cardiovascular events and death during follow-up when compared with a low troponin concentration,” he said. “Whether we can extrapolate those findings to other exercise disciplines, such as cycling or running, we don’t know at this stage.”