The latest generation of high-sensitivity cardiac troponin assays are able to quantify very low concentrations of troponin in the majority of people. Indeed, international guidelines now recommend the use of low concentrations of troponin to risk-stratify patients with suspected acute coronary syndrome.¹ Furthermore, troponin is an independent predictor of cardiovascular events in apparently healthy populations, and therefore, concentrations within the reference range may have a wider role in guiding the use of preventative therapies.² However, troponin can become significantly elevated after physical exercise. Interpreting troponin concentrations in this context is challenging because the kinetics of troponin release after physical exercise are not well understood. Most previous research has used assays that are not able to quantify troponin within the reference range, or has involved endurance athletes and evaluated a single time point rather than serial sampling.³

In this study, we evaluated the effect of intensity and duration of physical exercise on troponin concentration in 10 physically active healthy volunteers (7 men and 3 women; age, mean±SD, 34±7 y). The study was approved by the Research Ethics Committee and was conducted with written informed consent. Eligibility was assessed using the Physical Activity Readiness Questionnaire, the American Heart Association Pre-Participation Screening Questionnaire, and a 12-lead electrocardiogram. All participants underwent an initial fitness test using a maximal graded exercise test on a cycle ergometer to exhaustion to quantify their lactate threshold. They subsequently attended 3 study visits, at least 7 days apart, during which they underwent exercise on a cycle ergometer. The first visit involved low-intensity cycling (50%–60% of the participant’s lactate threshold) for 60 minutes. During the second visit, participants cycled at high intensity (80%–90% lactate threshold) for 60 minutes, and during the third study visit, participants cycled at moderate intensity (60%–70% lactate threshold) for 4 hours. Troponin concentrations were measured at the start of exercise and then hourly for up to 6 hours during each study visit, followed by measurements at 1, 2, and 7 days thereafter using the ARCHITECT_STAT high-sensitive troponin I assay (Abbott Laboratories). This assay has a limit of detection of 1.2 ng/L and an upper reference limit (99th percentile) of 34 ng/L in men and 16 ng/L in women. Change in troponin concentration within each study visit was evaluated by a 1-way repeated-measures ANOVA and paired t tests. We compared troponin concentrations between visits by a 2-way repeated-measures ANOVA.

Study participants had a median troponin concentration of 1.8 ng/L (interquartile range, 0.8–5.7) at baseline. Troponin was elevated after moderate- and high-intensity exercise (1-way ANOVA, P<0.001 for both), but was unchanged after low-intensity exercise (P=0.055). Troponin concentrations were significantly higher after the shorter duration of high-intensity exercise (peak, 13.0 ng/L [6.5–27.1]) compared with the longer duration of moderate-intensity exercise (6.9 ng/L [2.9–7.9]; 2-way ANOVA, P=0.028). After moderate- and high-intensity exercise, troponin concentration returned to baseline within 48 hours (Figure). The median heart rate and peak power output were 112 bpm (interquartile range, 99–142) and 113 W (88–135), respectively, during low-intensity exercise, 151 bpm (135–162) and 139 W (127–159) during moderate-intensity exercise, and 155 bpm (139–165) and 178 W (161–205) during high-intensity exercise.

Figure. The effect of exercise intensity and duration on cardiac troponin release. A, Median high-sensitivity cardiac troponin I concentrations after low-, moderate-, and high-intensity exercise. Values are median (interquartile range) in ng/L; n = 10 participants. Statistical tests performed on log-transformed troponin ratio relative to baseline concentration at each time point. B, Individual participant time-activity curves illustrating fold-changes in cardiac troponin I concentration from baseline. *One-way repeated-measures ANOVA comparing troponin concentration across time points. †Significant difference from baseline concentration using paired t tests (P value <0.05). NA indicates not assessed.

Our findings suggest that the magnitude of troponin release is more significantly associated with intensity than duration of physical exercise. The underlying mechanisms of release after exercise are still incompletely understood. It is thought that a small pool of troponin exists unbound within the cytosol of cardiomyocytes. Mechanical shear stress as a result of the hemodynamic response to strenuous physical activity may transiently increase cell membrane permeability, leading to the release of troponin from this cytosolic pool. Differences in the cellular mechanisms of release are likely to explain why the duration of exercise-induced troponin release is significantly shorter than in acute myocardial infarction, where troponin concentrations remain elevated for >1 week.

We observed significant heterogeneity in the magnitude of troponin release across individual participants, with the ratio of peak troponin concentration compared with baseline ranging from 2 to 600 across individual participants. Although only 3 participants had troponin concentrations above the 99th percentile after moderate or high-intensity exercise, 9 of 10 had concentrations above the threshold of 5 ng/L used to risk-stratify patients with suspected acute coronary syndrome.⁴ This has important clinical implications given the increasing use of early rule-out pathways, which use low concentrations of troponin to make clinical decisions. Our data would suggest that the intensity, duration, and elapsed time since physical exercise should be considered when interpreting troponin concentrations. Furthermore, recent reports suggest that greater exercise-induced troponin release may be associated with higher risk of future adverse cardiovascular events.⁵ Further research is required to understand the determinants of heterogeneity in this response to exercise and the clinical significance of these exercise-induced troponin elevations, particularly in individuals with lower cardiorespiratory fitness.

We thank Marina Mocognie, Russell Wilson, and Neil Guthrie, laboratory technicians at Napier University, for their assistance in the study.

This study was funded by the British Heart Foundation through a Clinical Research Training Fellowship (FS/18/25/33454), a Senior Clinical Research Fellowship (FS/16/14/32023), and a Research Excellence Award (RE/18/5/34216).

Drs Lee, Chapman, Anand, and Shah have received honoraria from Abbott Diagnostics. Dr Mills reports research grants awarded to the University of Edinburgh from Abbott Diagnostics and Siemens Diagnostics outside the submitted work, and honoraria from Abbott Diagnostics, Siemens Diagnostics, Roche Diagnostics and Singulex. The other authors report no conflicts.

*L. Marshall and Dr Lee contributed equally.

Data sharing: The data that supports the findings of this study are available from the corresponding author upon reasonable request.

https://www.ahajournals.org/journal/circ

最新一代的高灵敏度心脏肌钙蛋白测定能够量化大多数人中非常低的肌钙蛋白浓度。实际上，国际准则现在建议使用低浓度的肌钙蛋白对疑似急性冠脉综合征的患者进行风险分层。¹此外，肌钙蛋白是看似健康的人群中心血管事件的独立预测因子，因此，参考范围内的浓度可能在指导预防性治疗的使用中具有更广泛的作用。^2个但是，体育锻炼后肌钙蛋白会明显升高。在这种情况下解释肌钙蛋白的浓度是具有挑战性的，因为体育锻炼后肌钙蛋白释放的动力学尚不清楚。以前的大多数研究都使用了无法在参考范围内定量肌钙蛋白的测定方法，或者让耐力运动员参与进来，并评估了单个时间点而不是连续采样。³

在这项研究中，我们评估了体育锻炼的强度和持续时间对10名身体健康的健康志愿者（7名男性和3名女性；年龄，均值±SD，34±7岁）中肌钙蛋白浓度的影响。这项研究已获得研究伦理委员会的批准，并在获得知情同意书的情况下进行。使用“体育活动准备情况调查表”，“美国心脏协会参与前筛查表”和12导联心电图对资格进行评估。所有参加者都进行了初步体能测试，使用最大功率的分级运动测试在自行车测功机上进行了筋疲力尽，以量化他们的乳酸阈值。随后，他们进行了3次研究访问，至少相隔7天，在此期间，他们在自行车测功机上进行了锻炼。第一次就诊涉及60分钟的低强度骑行（参与者乳酸盐阈值的50％–60％）。在第二次访问期间，参与者以高强度（80％–90％乳酸阈值）骑车60分钟，在第三次研究访问期间，参与者以中等强度（60％–70％乳酸阈值）骑车4小时。肌钙蛋白浓度在运动开始时进行测量，然后在每次研究访视期间每小时进行一次，长达6小时，然后使用ARCHITECT在第1、2和7天进行测量_STAT高敏感性肌钙蛋白I测定法（Abbott实验室）。此测定法的检测限为男性1.2 ng / L，参考上限（99％）为34 ng / L，女性为16 ng / L。每次研究访视中肌钙蛋白浓度的变化通过1次重复测量方差分析和配对t检验进行评估。我们通过两次重复测量方差分析比较两次访视之间的肌钙蛋白浓度。

研究参与者在基线时的肌钙蛋白中位数浓度为1.8 ng / L（四分位间距为0.8-5.7）。肌钙蛋白在中等强度和高强度运动后升高（单向方差分析，两者均P <0.001），而在低强度运动后则无变化（P = 0.055）。高强度运动持续时间较短（峰值，13.0 ng / L [6.5–27.1]）后，肌钙蛋白浓度显着高于中强度运动持续时间较长（6.9 ng / L [2.9–7.9]）； 2-方差分析，P= 0.028）。经过中等强度和高强度运动后，肌钙蛋白浓度在48小时内恢复到基线（图）。在低强度运动中，平均心率和峰值功率输出分别为112 bpm（四分位间距，99-142）和113 W（88-135），151 bpm（135-162）和139 W（127-159） ）在中等强度的运动中，以及155 bpm（139-165）和178 W（161-205）在高强度运动中。

数字。 运动强度和持续时间对心脏肌钙蛋白释放的影响。甲，后低，中度平均高灵敏度心肌肌钙蛋白I的浓度，和高强度的运动。值是中位数（四分位间距），单位为ng / L；n = 10名参与者。在每个时间点对相对于基线浓度的对数转换后的肌钙蛋白比率进行统计测试。B，个体参与者时间-活动曲线，示出了心肌肌钙蛋白I浓度相对于基线的倍数变化。*单次重复测量方差分析，比较各个时间点的肌钙蛋白浓度。†使用配对的t检验与基线浓度存在显着差异（P值<0.05）。NA表示未评估。

我们的研究结果表明，肌钙蛋白释放的强度与强度的关系比运动时间长得多。运动后释放的潜在机制仍不完全清楚。认为肌钙蛋白的一小部分不存在于心肌细胞的胞质溶胶中。由于对剧烈体育活动的血液动力学反应而产生的机械剪切应力可能会暂时增加细胞膜的通透性，从而导致肌钙蛋白从该胞质池中释放出来。细胞释放机制的差异可能可以解释为什么运动诱导的肌钙蛋白释放的持续时间明显短于急性心肌梗塞，在急性心肌梗死中肌钙蛋白浓度持续升高> 1周。

我们观察到个体参与者中肌钙蛋白释放量的显着异质性，个体参与者中肌钙蛋白峰值浓度与基线的比值在2到600之间。尽管只有3位参与者在中度或高强度运动后肌钙蛋白浓度高于99％，但10个人中有9个人的浓度高于5 ng / L阈值，用于对疑似急性冠脉综合征的患者进行风险分层。⁴考虑到越来越多地使用早期排除途径，这具有重要的临床意义，早期排除途径使用低浓度的肌钙蛋白来做出临床决定。我们的数据表明，解释肌钙蛋白浓度时应考虑自体育锻炼以来的强度，持续时间和经过的时间。此外，最近的报告表明，运动引起的肌钙蛋白释放增加可能与将来发生不良心血管事件的风险增加有关。⁵需要进一步的研究来理解运动反应中异质性的决定因素，以及这些运动引起的肌钙蛋白升高的临床意义，特别是对于心肺功能不佳的患者。

感谢纳皮尔大学实验室技术员Marina Mocognie，Russell Wilson和Neil Guthrie在研究中的协助。

这项研究由英国心脏基金会通过临床研究培训奖学金（FS / 18/25/33454），高级临床研究奖学金（FS / 16/14/32023）和研究卓越奖（RE / 18 / 5/34216）。

Lee，Chapman，Anand和Shah博士已从雅培诊断获得酬金。Mills博士报告了在提交的工作之外，由Abbott Diagnostics和Siemens Diagnostics授予爱丁堡大学的研究经费，以及由Abbott Diagnostics，Siemens Diagnostics，Roche Diagnostics和Singulex授予的酬金。其他作者报告没有冲突。

* L。马歇尔和李博士做出了同样的贡献。

数据共享：在合理的要求下，可以从通讯作者处获得支持本研究结果的数据。

https://www.ahajournals.org/journal/circ