NT-proBNP in Athletes: Heart Failure Marker or Training Adaptation?
Table of Contents
Introduction
In clinical practice, NT-proBNP is often included in the evaluation of patients presenting with exertional breathlessness, including athletic individuals. In some cases, athletes may show mildly elevated values, which can understandably raise concern—particularly when the result is interpreted using standard reference ranges designed for the general population.
NT-proBNP is a widely used biomarker in the evaluation of cardiac stress and heart failure in the general population, but it behaves in ways that are profoundly different in heavily trained athletes. Misinterpretation leads to unnecessary testing, training interruptions, and genuine anxiety for athletes who are, by most measures, physiologically exceptional.
For athletes, a mildly elevated NT-proBNP does not automatically indicate pathology and should not be a cause for immediate alarm. However, any elevation—particularly when measured at rest—should be interpreted in clinical context and, where appropriate, discussed with a cardiologist.
My aim with this article is to provide a clearer understanding of how NT-proBNP behaves in athletic populations, so that athletes can approach these results with more confidence and less unnecessary anxiety. At the same time, it is important to emphasize that this discussion is not a substitute for clinical evaluation. In my view, an elevated NT-proBNP should always be assessed in conjunction with a qualified clinician, ideally a cardiologist.
What NT-proBNP Actually Measures in Athletes
BNP (B-type natriuretic peptide) is released from ventricular cardiomyocytes in response to increased ventricular wall stress, such as that caused by volume overload or pressure overload. When proBNP is cleaved, it produces two fragments: the biologically active BNP and the inactive N-terminal fragment, NT-proBNP. Both are released in equimolar amounts from the cardiomyocyte—however, because NT-proBNP has a much longer half-life than BNP (approximately 120 minutes vs. 20 minutes), NT-proBNP serum values are approximately six times higher than BNP values in circulation [1].
In clinical medicine, NT-proBNP has become widely adopted because its longer half-life makes it more stable and consistently measurable. The physiological effects of BNP—vasodilation, natriuresis, inhibition of the renin-angiotensin-aldosterone system—represent the heart’s attempt to reduce its own workload when under stress[1].
In patients with heart failure, chronically elevated NT-proBNP reflects sustained ventricular overload: the heart is being stretched beyond its adaptive capacity. According to the 2021 ESC guidelines for the diagnosis and treatment of heart failure, NT-proBNP below 125 pg/mL in the non-acute outpatient setting makes a diagnosis of heart failure unlikely—it functions as a rule-out threshold, not a rule-in criterion [3]. In the acute setting, values below 300 pg/mL similarly reduce the likelihood of acute heart failure [3].
In clinical practice, the diagnosis of heart failure is rarely based on a single test. It typically requires a combination of findings, including clinical assessment, electrocardiography (ECG), imaging, and laboratory markers. In patients presenting with symptoms such as breathlessness, clinicians evaluate the overall clinical picture—looking for signs such as fluid retention, peripheral oedema, and reduced exercise tolerance. Imaging studies, including chest X-ray and, most importantly, echocardiography, play a central role in confirming the diagnosis.
In most cases, echocardiography is performed and interpreted by a cardiologist, and the final diagnosis is made in conjunction with specialist assessment. In my experience, cardiology input is often required already at the stage of clinical suspicion, particularly when biomarkers or symptoms raise concern.
Natriuretic peptides—most commonly NT-proBNP (often reported as “proBNP” in routine laboratory testing)—are used as part of this diagnostic process. An elevated value supports the suspicion of heart failure but does not establish the diagnosis on its own. Conversely, low values are particularly useful for ruling out clinically significant heart failure, especially in the non-acute setting.
The final diagnosis is typically made by a cardiologist, supported by echocardiographic findings and the overall clinical context.
NT-proBNP in Athletes After Endurance Exercise: What the Research Shows
The short answer: it rises, often substantially, in healthy athletes with perfectly normal hearts.
A systematic review of 53 reports encompassing 1,034 participants examined the pattern of BNP and NT-proBNP release after running [4]. In studies that compared post-running values to a pre-specified upper reference limit, values exceeding that limit were seen in 22.9% of runners for BNP and in 35.9% of runners for NT-proBNP [4]. In the reviewed studies, approximately one in three runners had post-race NT-proBNP above the upper reference limit—despite having no cardiac pathology.
The magnitude of elevation is positively associated with exercise duration. In a study of 105 healthy endurance athletes across three events—a marathon, a 100-km ultramarathon, and a mountain bike marathon—81 of 105 athletes exceeded the upper reference limit for NT-proBNP after exercise[5]. The highest increases were seen in 100-km runners, and NT-proBNP correlated significantly with exercise time (r = 0.55, p < 0.001)[5]. NT-proBNP was not related to exercise-induced increases in cardiac troponin I or T, suggesting a mechanism distinct from myocardial cell injury[5].
The kinetics are also instructive. A study measuring NT-proBNP in athletes before, immediately after, and at 3, 6, and 24 hours post-half-marathon in 17 trained, middle-aged males found that while NT-proBNP increased significantly at the end of the race and remained elevated at 24 hours, no athlete displayed values exceeding the clinical cut-off of 125 pg/mL[6]. This kinetic pattern mirrors what is seen with other cardiac markers in post-marathon blood work: transient elevation without structural damage. Notably, the change in NT-proBNP from pre-run values did not significantly correlate with plasma volume changes—indicating the elevation reflects a genuine physiological response rather than simply a hemoconcentration artifact[6].
Current reviews suggest that exercise-induced NT-proBNP elevations may reflect transient myocardial wall stress, cardiomyocyte metabolic changes, and neuroendocrinological responses, and may serve cytoprotective and growth-regulating functions as part of the cardiac adaptive response to exercise [2].
From a physiological perspective, natriuretic peptides primarily reflect myocardial wall stress rather than a specific disease process. They are released in response to increased ventricular stretch, which can occur in a variety of situations—not only in heart failure, but also during prolonged endurance exercise. In this sense, the biomarker reflects a shared underlying mechanism rather than a single pathological condition.
In clinical practice, NT-proBNP is typically measured in patients where there is a suspicion of cardiac pathology, particularly heart failure. It is not routinely used as a screening tool in otherwise healthy athletic populations. For this reason, elevated values in athletes are often encountered in the context of symptom evaluation rather than routine testing.
Importantly, the presence of elevated NT-proBNP in an athlete should not be attributed to training without appropriate evaluation. If cardiac symptoms are present, or if biomarker levels are clearly elevated at rest, the same diagnostic principles apply as in any other patient. Potential cardiac causes must be considered and, where appropriate, excluded through clinical assessment and imaging before attributing the finding to physiological adaptation.
In some cases, repeat measurement can provide additional context. In my clinical practice, I may re-check NT-proBNP after a period of rest to assess whether the elevation is transient. A decreasing value over time may be more consistent with a reversible or exercise-related response. However, this approach has clear limitations: transient cardiac events, such as arrhythmias, may also produce short-lived elevations. For this reason, biomarker kinetics alone cannot reliably distinguish between physiological and pathological causes, and should always be interpreted alongside the full clinical picture.
Resting NT-proBNP in Athletes: Why Athlete’s Heart Does Not Chronically Elevate It
This is one of the most clinically useful findings in the literature: despite having significantly enlarged ventricles, increased wall thickness, and substantially elevated cardiac output—including the well-documented blood volume expansion that characterises endurance adaptation—compared to sedentary controls, endurance athletes do not have elevated resting NT-proBNP.
A study comparing 20 well-trained male endurance athletes (triathletes, road cyclists, long-distance runners) with 20 healthy untrained controls, using cardiac magnetic resonance imaging to confirm athlete’s heart morphology, found no difference in resting NT-proBNP between groups [7]. The athletes’ median resting NT-proBNP was 24.7 pg/mL vs. 28.9 pg/mL in controls—a non-significant difference (p = 0.56) [7]. These findings are consistent with physiological hypertrophy rather than resting pathological ventricular overload [7].
The physiological logic is straightforward. NT-proBNP reflects myocardial wall stress. In the athlete’s heart, the ventricle has structurally adapted to accommodate higher stroke volumes—supported in part by the plasma-driven increases in RBC count that accompany endurance training—without generating the resting wall stress that would drive NT-proBNP secretion. This is consistent with physiological remodeling rather than chronic pathological overload.
At rest, there is no expectation that NT-proBNP would be chronically elevated in endurance athletes compared to the general population, provided that recent strenuous exercise is excluded. In fact, available evidence suggests that resting values are typically similar between trained and untrained individuals.
Elevations are more commonly observed in the period following prolonged or intense exercise, reflecting transient physiological stress rather than underlying pathology.
In my clinical practice, when I encounter an elevated NT-proBNP in an athletic individual at rest, I do not assume it to be a benign training-related finding. Instead, I approach it in the same way as in any other patient—with a structured evaluation aimed at identifying or excluding potential cardiac causes. Only once clinically significant pathology has been reasonably ruled out do I consider whether the finding may relate to recent training or physiological variation.
Conclusion
NT-proBNP tells a fundamentally different story in athletes than in sedentary patients. After prolonged endurance exercise, elevations are common, often substantial, and in most cases reflect transient physiological stress rather than underlying pathology. At rest, however, well-trained endurance athletes do not appear to have chronically elevated NT-proBNP, despite significant cardiac remodeling—highlighting the distinction between physiological adaptation and pathological overload.
For clinicians, the key is context. An elevated NT-proBNP in an athlete should not be dismissed as a training effect without appropriate evaluation, but neither should it be interpreted in isolation as evidence of disease. The same diagnostic principles apply as in any patient: symptoms, clinical findings, ECG, and imaging—particularly echocardiography—remain central to interpretation.
For athletes, the takeaway is reassurance with responsibility. A mildly elevated value, particularly after recent exercise, is often a normal physiological response. However, a clearly elevated NT-proBNP at rest, or in the presence of cardiac symptoms, warrants proper clinical assessment. Only once pathological causes have been reasonably excluded should training-related explanations be considered.
Ultimately, NT-proBNP is not a diagnosis—it is a signal. Understanding when that signal reflects adaptation and when it indicates potential disease is what separates informed interpretation from unnecessary alarm.
References
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC1860679/
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC5968914/
[3] https://pubmed.ncbi.nlm.nih.gov/35083827/
[4] https://pubmed.ncbi.nlm.nih.gov/26567808/
[5] https://pubmed.ncbi.nlm.nih.gov/16338248/
