Cardiac troponin T in female athletes during a two-day mountain marathon.

SMJ 2003: 48(2): 41-42

¹Shave, E. Robert. ²Dawson, Ellen. ¹Whyte, P. Greg. ²George, Keith. ²Ball, Derek. ³Gaze, C. David. ³Collinson, O. Paul.

¹British Olympic Medical Centre, Northwick Park Hospital, Harrow, Middlesex, HA1 3UJ, UK.

²Dept. of Exercise and Sports Science, Manchester Metropolitan University, Hassall Road, Alsager, UK

³Dept. of Chemical Pathology, St.George’s Hospital Medical School, UK.

Address for correspondence and requests for reprints:

Robert Shave , British Olympic Medical Centre, Northwick Park Hospital, Watford Road , Harrow , Middlesex , HA1 3UJ, UK

e-mail: robert.shave@boa.org.uk

Running Title: cTnT following prolonged exercise.

Abstract:

Background: Equivocal studies exist on the potential of cardiac damage following prolonged endurance exercise.  Aims: The aim of the study was to examine humoral markers of cardiac damage in female athletes during a 2-day mountain endurance race. Methods: Venous blood samples were drawn from seven female competitors prior to, and immediately following day-1 and day-2 of the event.  The serum was analysed for total creatine kinase (CK), creatine kinase isoenzyme MB (CKMB), and cardiac troponin T (cTnT). Results: Elevations in CK and CKMB were apparent following day-1 of the event (mean ± SD; CK 84.1±54.6 mg/L vs. 387±276.7 mg/L, CKMB 2±1.7 mg/L vs. 5.9±1.7 mg/L) and subsequently rose further following race completion (CK 743±500 mg/L, CKMB 11.9±4.9 mg/L). Elevations in cTnT were noted in three competitors following day-1 cTnT (range 0.013-0.044 mg/L) and remained elevated in two competitors following day-2 (range 0.014-0.017 mg/L).  Conclusions: The elevations in cTnT likely represent release from the cytosolic fraction.  The mechanism responsible for such release is yet to be elucidated.

KEY WORDS:   endurance exercise, troponin, cardiac damage

Introduction

It is well documented that extreme exercise is associated with an acute decrease in cardiac function^1,2,3,4,5,6. However the aetiology of such dysfuntion has yet to be elucidated. Previous studies examining male athletes have implicated cardiomyocyte degradation as a mechanism underpinning the observed dysfunction ^7,8.  It must be recognised that much of the supporting evidence for this hypothesis is based upon positive results gained from assays and markers known to demonstrate considerable cross-reactivity with markers of skeletal muscle damage⁹; thus these results need to be viewed cautiously.  A new third generation cardio-specific troponin T assay (Roche Diagnostics, Lewes, Sussex) has recently been developed and validated within both clinical¹⁰ and athletic populations¹¹. Therefore cTnT represents the current marker of choice when examining cardiomyocyte degradation in the presence of skeletal muscle damage, further the presence of cTnT is now deemed pathognomonic of myocardial damage¹². Subsequently, the new third generation cardio-specific troponin T assay has been utilised to demonstrate an acute sub-clinical elevation of cTnT in male athletes during prolonged exercise¹³. Presently, however, there is a dearth of information regarding the potential for cardiomyocyte degradation following extreme exercise in female athletes.  Thus, the aim of the present study was to examine the effect of a two-day mountain endurance race upon cTnT concentrations in female athletes, as assessed by the new third generation assay.

Methods

Seven female competitors in the Lowe Alpine Mountain Marathon 2000 held in Glen Shiel (LAMM 2000) volunteered to take part in the study (mean ± SD; age: 44.1 ± 6.8 years; height: 159.1 ± 0.58 m; body mass: 57.4 ± 4.3 kg). Following ethics committee approval and prior to commencing the study each subject provided written informed consent. The event consisted of two days “arduous” exercise over mountainous terrain (completion time day-1: 374±14 min; completion time day-2: 298±9min; total completion time 672±19). Whole blood was collected prior to and immediately following exercise on day-1, and immediately following race completion on day-2. On each occasion 5 ml of blood was drawn from an ante-cubital vein, were allowed to clot, centrifuged and the serum separated and frozen for later analysis.  Serum samples were assayed for total CK (activity), CK-MB_mass and cTnT.  Total CK activity was determined using a Beckman LX-20 chemistry analyser according to the manufacturers guidelines (Beckman Coulter, CA, USA) with an upper reference limit of 269 U/L. CK-MB_mass and cTnT were analysed utilising electrochemiluminesence (ECL) technology employed within the Elecsys 1010 automated batch analyser (Roche Diagnostics, Mannheim, Germany).

CK-MB_mass assay coefficient of variation (CV) were 3.8% at 6.24 mg/L, 3.2 % at 15.9 mg/L, 3.6% at 40.5 mg/L. The analytical measuring range was 0.1 to 500 mg/L. There was no cross reactivity with CK-MM (0%) and minimal cross-reactivity with CK-BB (0.28%). The upper reference limit was 5 mg/L. The cTnT assay CV’s were 5.5% at 0.32 mg/L and 5.4% at 6.0mg/L, with a detection limit of 0.01 mg/L (which coincides with the 99^th percentile value) and an upper limit of 25 mg/L. Cross reactivity with human skeletal troponin T was 0.001%, human cardiac troponin I, 0.002%, skeletal tropomyosin 0.001%, cardiac tropomyosin 0.1% and cardiac myosin light chain 1, 0.003%.  0.1mg/L is the accepted criteria for acute myocardial infarction (AMI)¹², however values exceeding the 99^th percentile i.e. 0.01mg/L (Roche Diagnostics, Mannheim, Germany) but lower than 0.1mg/L represent minor myocardial injury¹².  Thus a cTnT value above the lower detection limit is pathognomonic of myocardial damage.

Results

Results are listed in Table I, compared to pre-exercise data CK activity and CKMB_mass were elevated following day one of the LAMM 2000 (mean ± SD; CK 84.1±54.6 mg/L vs. 387±276.7 mg/L, CKMB_mass 2±1.7 mg/L vs. 5.9±1.7 mg/L).  Further increases in CK activity and CKMB_mass were present following race completion (CK 743±500 mg/L, CKMB 11.9±4.9 mg/L).  cTnT was elevated following day-1 of the race in 3 athletes (cTnT range 0.013-0.044 mg/L), and remained elevated in 2 athletes following day-2 (cTnT range 0.014-0.017 mg/L), however, at no point within the study did cTnT values exceed the clinical threshold (0.1 mg/L) for acute myocardial infarction (AMI) ¹². 

Table I.  Humoral markers at Baseline, following day-1 and following day-2 of a two-day mountain marathon.

Discussion

The physiological stress of the LAMM 2000 was of significant magnitude to induce skeletal muscle damage, as evidenced by the increase in both CK activity and CKMB_mass. Within the present study cTnT concentrations exceeding the AMI cut-off value (>0.1mg/L) were not apparent. However, sub-AMI levels of cTnT were evident in three subjects. Although not above the AMI reference level, the cTnT within the present study represents a release from the myocardium, and was thus indicative of secondary cardiac damage likely brought about by extreme exertion. The minor values might represent a release from the cytosolic fraction, and not degradation of the sarcomere. The cytosolic component of the cardio-myocyte holds 2-8% of the total cTnT^7,14.  Previous studies have demonstrated cytosolic release of cTnT following cardiomyocyte membrane damage¹⁵. The aetiology of such membrane damage following extreme exercise is yet to be elucidated; however a host of mechanisms may be implicated, for example, oxidative stress, free fatty acid damage propagated by catecholamine induced lipolysis, magnesium deficiency and potassium deficiency, all of which are mediated by endurance exercise¹⁶. Thus the presence of cTnT in both the present and previous studies may be indicative of a cytosolic release and not sarcomeric degredation following cell necrosis. The impact of such an acute cytosolic release and the ramifications of repeated bouts of release from the cytosol need further investigation.  Until such work is completed it is unclear as to whether extreme exercise may impose a “real cardiac risk”.

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