Cardiovascular biomarkers, long considered an ideal tool for diagnosing cardiovascular diseases and disorders with precision, speed, and high accuracy, have typically helped guide physicians toward the optimal therapeutic approach. Physical exercise, almost always recommended for the prevention and therapy of cardiovascular maladies, can itself modify blood concentrations of several laboratory variables. Naturally, the finding of elevated cardiac biomarker levels after an acute bout of strenuous exercise tends to cause concern. However, researchers now believe that levels of some biomarkers that fall outside the normal range in healthy, physically active subjects may indicate an adaptive response to exercise rather than an underlying disease. This means that interpreting laboratory results in such individuals requires a bit of caution and a careful eye. This article explains several of these biomarkers, how they emerge, and what values may truly indicate a heart-related event.
The Role of Biomarkers
The definition of the term biomarker, standardized in 2001, defines it as a characteristic that is objectively measured/evaluated to indicate normal biological processes, pathogenic processes, or responses to a specific therapeutic intervention. Scientists measure biomarkers in a variety of ways: a biological sample (urine, blood, biopsy), an EKG or blood pressure reading, or an imaging test such as a CT scan. Several types of biomarkers exist, each with distinct characteristics and uses. A new biomarker holds clinical value only if one deems it accurate, easily reproducible, simple to interpret by clinicians, boasts a high sensitivity/specificity for producing the outcome it identifies, and the existence of ample data to suggest that knowledge of the given biomarker will modify the physician’s management choices (medication, therapy, etc.).
How Exercise Affects Biomarkers
Extensive research has led to the use of certain biomarkers as a means of diagnosing myocardial infarction and other related yet equally life-threatening medical conditions. It has come to light that participation in strenuous sports may elicit alterations in cardiac biomarkers, rendering it difficult to make an accurate clinical assessment as to whether a true cardiovascular emergency has in fact occurred.
Specific biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) on which physicians focus in their clinical diagnosis of pulmonary embolism, heart failure, and acute coronary syndrome seem particularly prone to undergoing alterations as a result of extreme physical activity. Right ventricular end diastolic diameter typically increases, while right ventricular ejection fraction as well as the ratio of early to late trans-mitral flow velocities drop, immediately following exercise. As we can see, if a physician or EMT does not possess knowledge of an ailing individual’s recent exercise experience, he might very easily misdiagnose this scenario as a life-altering cardiac event.
One research study looked at the impact of acute exercise and the ensuing 24-hour recovery period on serum concentration of cardiac troponins T and I (cTnT and cTnI) and N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP). For this study, the scientists focused specifically on healthy children/adolescents.
All 3 biomarkers showed a significant increase immediately following a bout of exercise. Both cTnT and cTnI decreased over the next 24-hour period; however, the decrease in cTnI did not meet the criteria for a “statistically significant” rating. Post-exercise peak values of cTnT aligned directly with both duration and intensity of the exercise, while NT-proBNP peak values aligned only with the length of a workout.
The release of BNP during and after exercise may not result from myocardial damage, as previously thought, but may actually function in an opposite manner, conferring cytoprotective and growth-regulating benefits. The scope of future research trials will hopefully shed more light on the various aspects of exercise-induced increases in BNP and cardiac troponins.
The Effects of Athletic Status
A very interesting research project took a two-pronged approach to this subject, assaying not only the release of cTnI and BNP following a session of high-intensity rowing, but also attempting to establish whether individual changes in biomarker levels might in any way reflect a subject’s athletic status—amateur/novice or seasoned athlete.
The volunteer subjects, comprising 18 elite and 14 amateur rowing athletes, had their cTnI and NT-proBNP levels measured before a 30-minute maximal rowing exercise, and again at 5 minutes, 1 hour, and at the 3rd, 6th, 12th, and 24th hours post-workout. Compared with pre-exercise levels, researchers noted significant individual heterogeneity in peak cTnI values, with 50% of elite and 3 amateur rowers exceeding the upper reference limit. Elite rowers had higher baseline and peak post-exercise cTnI levels than their novice counterparts but showed similar changes with exercise. No significant differences existed in baseline and peak post-exercise NT-proBNP between groups. Athletic status did not appear to affect changes in cardiac biomarkers in response to high-intensity rowing exercise.
Another study investigated the effects of long-term endurance exercise on cardiac morphology and function, as well as injury indicators, among amateur marathon runners. 33 volunteers, all amateur runners, participated in a marathon. The experimental group included participants with a National Athletic Grade of 2 or higher, and the control group included participants without a National Athletic Grade. Researchers assessed cardiac morphology, function, and injury indicators both before and immediately after participants’ participation in the Changsha International Marathon. All cardiac morphology and function indicators returned to pre-race levels after 24 hours; left ventricular end-diastolic and end-systolic volumes also showed similar trends. Both stroke volume and percent fractional shortening showed similar trends in their changes before and after the race.
Upon completion of the study, scientists found that high-level amateur marathon runners had greater heart volumes and wall/septal thicknesses than low-level marathon runners, with the most pronounced differences in heart volume. Long-term high-intensity endurance exercise caused some damage to the hearts of amateur runners. High-level runners exhibited better myocardial repair capacity, with greater decreases in myocardial injury markers at 24 hours post-race, whereas low-level runners showed much less myocardial repair capacity.
Nutrition, Exercise and Heart Stress/Muscle Damage
As personal trainers and coaches, we often speak to our more serious athletes about the importance of adequate food intake prior to endurance running competitions. However, no investigations to date have been documented with regard to whether dietary intake could prevent exercise-induced muscle damage and/or cardiac stress. Thus, a recent study sought to determine the associations between muscle damage/cardiac stress and the diets of endurance athletes 7 days prior to participating in a marathon race. Sixty-nine male runners recorded their dietary intake during the week leading up to a race, as well as on the day of the marathon. At the finish line, runners gave blood samples to quantify levels of serum creatine kinase (CK) and myoglobin, and muscle-brain isoform creatine kinase (CK-MB), prohormone of brain natriuretic peptide (NT-proBNP), cardiac troponin I (TNI), and cardiac troponin T (TNT) concentration, since these typically serve as markers of exercise-induced muscle damage and cardiac stress.
Results showed a positive association between consumption of meat during the week leading up to race day and post-race CK and myoglobin. Vegetable and fish intake, on the other hand, showed a negative association. In terms of fat consumption, both butter and fatty meat aligned positively with NT-proBNP (β = 0.796; p < 0.001) and TNI (β = 0.396; p < 0.001) post-marathon values, but not olive oil. The scientists drew the conclusion that the consumption of meat, butter, and fatty meat might relate to higher levels of EIMD and EICS, while consumption of fish, vegetables and olive oil might offer a protective role against EIMD and EICS.
Predictors: Exercise Duration or Intensity?
Numerous investigators have sought to examine which specific factors of an athlete’s behavior contribute to the release of cardiac-specific biomarkers. Experts have considered age, training experience, blood pressure, environmental factors, exercise intensity, and exercise duration, as these are often accurate predictors of the magnitude of post-exercise cTn concentrations. The variance appears primarily driven by the intensity and duration of exercise.
Early studies suggested that the magnitude of cTn release was positively related only to the duration of exercise. However, a 2007 study looking at exercise durations ranging from 0.5 to 22 hours showed that post-exercise cTn was inversely associated with exercise duration. Specifically, more athletes registered a cTn concentration greater than the URL after marathon running than after substantially longer ultra-endurance events. These data suggest that exercise intensity, rather than duration, may be the more potent stimulus for cTn release, since most marathon runners typically achieve a higher intensity than ultra-endurance athletes. In a recent study that documented a direct relationship among exercise heart rate, a surrogate for exercise intensity, and the prevalence of cTn after exercise, the importance of exercise intensity likewise emerged.
Exercise Training Likely a Factor
The heart remodels itself to a certain degree in response to exercise training, prompting several studies to examine the relationship between fitness status and the release of post-exercise cTn. Researchers looked at both event completion times and years of training. In several studies, more experienced marathon runners seemed less likely to have cTn elevations after running events than less experienced runners.
Two recent studies have examined whether exercise training alters post-exercise cTn release. One assessed cTnT concentrations at rest and after a 60-minute maximal run, before and after a 14-week training program in the intervention and control group. Before training, the 60-minute maximal run produced a heterogeneous cTnT response in both groups, with 71% of subjects exceeding the URL. Baseline and post-exercise cTnT rose more after training in the intervention group than in the control group.
The second study randomly assigned 48 young, sedentary, obese women to 12 weeks of high-intensity interval training, moderate-intensity continuous training, or no training in the control group. Researchers measured cTnT levels after the same absolute and relative exercise stimulus (60% of Vo2max). Results collectively indicate that the magnitude of post-exercise cTn release appears to be influenced by a combination of training status and exercise intensity, perhaps because trained individuals require a greater absolute exercise stimulus to achieve the same relative stimulus. to be affected
How Physicians Can Differentiate a Cardiac Event from Exercise-Induced Stress
In order to determine, with any degree of accuracy, whether biomarker elevations indicate an acute, life-threatening event like a heart attack or simply exercise-induced stress, medical professionals can rely on the following:
- Pattern of Release: In a true heart attack, troponin levels spike, followed a dynamic rise and fall pattern over the course of several hours. Exercise-induced elevations typically peak immediately post-exercise and clear the bloodstream much faster.
- Symptomology: Exercise-induced biomarker elevations rarely elicit severe/prolonged chest pain, shortness of breath, or changes in a resting electrocardiogram (ECG).
While once characterized as a completely benign physiological response, evidence now indicates that the degree of post-exercise troponin elevation has some predictive value. Highly trained athletes typically exhibit lower biomarker spikes due to myocardial adaptations that have occurred over time, thereby conferring short-term cardio protection. However, excessive/abnormally high spikes in older adults, or in those individuals with cardiovascular risk factors, can serve as an early marker for subclinical cardiovascular pathology, or a predictor of future cardiac events.
Laboratory abnormalities observed in marathon runners and other endurance exercisers have appeared in the literature as early as 1903. Healthy individuals, and seasoned athletes in particular, often show alterations in several cardiovascular biomarkers. In some subjects, biomarker levels may be high or low enough to indicate a pathological condition. Some medical experts feel that levels of biochemical variables that fall decidedly outside the normal range should prompt further testing or, in some cases, discourage further training or competition. At the very least, athletes whose bloodwork reveals abnormal results should receive a warning and perhaps some education about the dangers associated with physical activity. Abnormal levels of hematological and cardiac biomarkers found in athletes at baseline or after an acute bout of strenuous exercise seem to cause both concern and discrepancy; to that end, some professionals have purported to attribute such discrepancies to differences in the sampling time, participant fitness, and/or environmental conditions at the time of the exercise.
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