Clinical Chemistry / Analytes in Collapsed Marathon Runners
Cardiac Biomarkers, Electrolytes, and Other Analytes
in Collapsed Marathon Runners
Implications for the Evaluation of Runners Following Competition
Arthur J. Siegel, MD,1,4 James Januzzi, MD,2,4 Patrick Sluss, PhD,3,4 Elizabeth Lee-Lewandrowski, MPH, PhD,3,4
Malissa Wood, MD,2,4 Terry Shirey, PhD,5 and Kent B. Lewandrowski, MD3,4
Key Words: Cardiac troponin T; B-type natriuretic peptide; N-terminal pro-B-type natriuretic peptide; Lactic acidosis; Ionized magnesium;
Acute coronary syndrome; Sudden cardiac death; Marathon
DOI: 10.1309/4L0M60MGAQBCHMV7
Abstract
We measured analytes in collapsed Boston
Marathon runners to compare with changes in
asymptomatic runners. Of collapsed runners at the
2007 marathon, 18.2% had a measurable cardiac
troponin T (cTnT) value with a mean postrace level
of 0.017 ng/mL (0.017 µg/L; SD, 0.02 ng/mL [0.02
µg/L]). Three subjects had cTnT values above the
cutoff (0.10 ng/mL [0.10 µg/L]) typically used for the
diagnosis of acute myocardial infarction. The mean
and median N-terminal pro-B-type natriuretic peptide
levels were 73 ng/L (SD, 77.3 ng/L) and 54.3 ng/L
(interquartile range, 22.8-87.3 ng/L), respectively, in
collapsed runners. Only 4.9% had values more than
the age-specific normal value (<125 ng/L for subjects
younger than 75 years). In collapsed subjects at the
2006 marathon, 18.0% had an abnormal sodium value,
including 18 cases of hypernatremia and 7 cases of
hyponatremia. The ionized calcium level was low in
49% of subjects, and the ionized magnesium level was
low in 19.5% and elevated in 1 subject. The blood
lactate level was elevated in 95% of subjects.
The frequency of elevated postrace cTnT levels in
collapsed athletes after endurance exercise is similar
to that in asymptomatic runners. Other metabolic
abnormalities, including hypernatremia, hyponatremia,
low ionized calcium and magnesium levels, and lactic
acidosis may contribute to muscle fatigue and collapse.
Although regular physical activity reduces future coronary heart disease events, episodes of vigorous exercise
such as marathon running may precipitate acute coronary
syndrome (ACS) and sudden death in 1 per 50,000 marathon
participants.1-5 Prior studies of changes in cardiac troponin
T (TnT) and I and B-type natriuretic peptide (BNP and
N-terminal pro-B-type natriuretic peptide [NT-proBNP])
levels in asymptomatic runners who completed a marathon
have demonstrated that mild to moderate elevations in levels
of these markers are common without apparent ACS or heart
failure.2,6-10 The mechanism of cardiac injury and myocyte
stress reflected by elevation of troponin and B-type natriuretic
peptide concentrations, respectively, remains under debate;
however, presumably these elevations result from an incomplete myocardial adaptation to training in which vulnerable
myocytes are selectively eliminated, particularly in athletes
with lesser training.11 As well, the effects of endurance exercise on electrolyte and lactic acid concentrations as a function
of collapse following exercise remains unclear.
In this study, we evaluated the levels of TnT, NT-proBNP,
electrolytes, ionized calcium and magnesium, and lactate in
collapsed marathon runners in the medical tent at the finish
line of the 2006 and 2007 Boston marathons. Our hypothesis
was that more prevalent abnormalities in cardiac biomarker,
electrolyte, and lactic acid results would be noted in collapsed
runners compared with asymptomatic runners.
Materials and Methods
All study procedures were approved by the McLean
Hospital (Belmont, MA) Institutional Review Board.
Heparinized blood samples were obtained from collapsed
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DOI: 10.1309/4L0M60MGAQBCHMV7
© American Society for Clinical Pathology
Clinical Chemistry / Original Article
marathon runners admitted to the finish line medical tent
at the 2006 and 2007 Boston marathons. Samples from the
2006 marathon were analyzed by whole blood point-of-care
technologies for electrolytes, glucose, serum urea nitrogen,
lactate, ionized calcium, and ionized magnesium using an
acute care analyzer (Nova Biomedical, Waltham, MA).
After the 2007 marathon, discarded plasma samples
were frozen at –80°C for subsequent analysis of TnT and
NT-proBNP on the Roche Elecsys 2010 immunoassay analyzer (Roche Diagnostics, Indianapolis, IN) using a fourthgeneration TnT assay and the standard Roche NT-proBNP
assay. The cut point yielding the highest functional
sensitivity at a 10% coefficient of variation for the TnT
assay is 0.03 ng/mL (0.03 µg/L), and the appropriate agematched upper limit of normal for the NT-proBNP assay
for this population is less than 125 ng/L. The imprecision
of the Roche NT-proBNP assay varies from less than 2.7%
(within-run) to less than 3.2% (total imprecision) across the
analytic range. Hemolyzed samples were excluded from
the study.
The mean age of the subjects was 39.1 years (SD, 10.4
years). Of the subjects, 62% were men and 38% were women.
Results
Mean values for whole blood point-of-care chemistry
analytes in collapsed marathon runners from the 2006 Boston
Marathon are shown in zTable 1z. Not all analytes were measured for each subject owing to the availability of analyzers
and samples for testing. Of 139 subjects, 25 (18.0%) had an
abnormal sodium value; 18 cases showed hypernatremia and
7 showed hyponatremia. The serum urea nitrogen level was
elevated in 20 (49%) of 41. Of the subjects, 45 (51%) of 89
had a low ionized calcium level and 9 (22%) of 41 an abnormal ionized magnesium level that was low in 8 and elevated
in 1 sample. Blood lactate levels were elevated in 75 (95%) of
79 cases and whole blood glucose levels in 43 (31%) of 139
cases, with no hypoglycemia noted.
The mean TnT value was 0.017 ng/mL (0.017 µg/L; SD,
0.02 ng/mL [0.02 µg/L]) in 99 collapsed marathon runners
at the 2007 Boston Marathon zTable 2z. Of the 99 collapsed
runners, 18 (18%) exhibited measurable levels of TnT and 8
(8%) had values of more than the threshold of 0.03 ng/mL
(0.03 µg/L) indicative of myocardial necrosis2 by a fourthgeneration TnT assay. Three subjects had TnT values of more
than the traditional cutoff point of 0.1 ng/mL (0.1 µg/L) used
for the diagnosis of acute myocardial infarction (0.106, 0.172,
and 0.108 ng/mL [0.106, 0.172, and 0.108 µg/L]).
The median NT-proBNP value was 54 ng/L (interquartile
range, 22.8-87.3 ng/L). Only 5 runners had NT-proBNP values of more than the age-adjusted cutoff value. These 5 values
showed modest elevations of NT-proBNP (186, 188, 224, 221,
and 331 ng/L). Of the 5 runners with an elevated NT-proBNP
level, 3 (60%) also had measurable levels of TnT.
Discussion
Multiple studies reporting elevations in cardiac TnT and
B-type natriuretic peptide (BNP or NT-proBNP) levels following marathon running clearly establish a myocardial source, further supported by recent data demonstrating strong associations
between elevated cardiac biomarkers and the postrace develop-
zTable 2z
Distribution of Troponin T Values in 99 Collapsed Marathon
Runners
Troponin T Range, ng/mL (µg/L)
<0.01 (<0.01)
>0.01 to <0.03 (>0.01 to <0.03)
0.03 to <0.10 (0.03 to <0.10)
>0.10 (>0.10)
No. (%) of Cases
81 (82)
10 (10)
5 (5)
3 (3)
zTable 1z
Summary of Whole Blood Routine Chemistry Testing Results in Collapsed Marathon Runners*
Analyte
No. of Samples
Sodium (mmol/L)
Potassium (mmol/L)
Ionized calcium (mmol/L)
Hematocrit (%)
Glucose (mg/dL)
Lactate (mmol/L)
Urea nitrogen (mg/dL)
Ionized magnesium (mmol/L)
*
139
139
89
134
139
79
41
41
Mean
142.3
4.31
1.09
45
117
3.45
19.76
0.47
SD
4.1
0.62
0.07
3.4
37
1.61
4.2
0.07
Minimum
129.6
3.41
0.9
37
58
1.1
3
0.23
Maximum
152.2
8.22
1.22
55
294
11.2
27
0.62
Reference ranges are as follows: sodium, 135-147 mmol/L; potassium, 3.5-5 mmol/L; ionized calcium, 1.14-1.30 mmol/L; hematocrit: male, 41%-53%; female, 36%-46%;
glucose, 70-110 mg/dL; lactate, <2 mmol/L; urea nitrogen, 8-25 mg/dL; and ionized magnesium, 0.47-0.65 mmol/L. Values for sodium, potassium, ionized calcium, lactate, and
ionized magnesium are given in Système International (SI) units; conversions to conventional units are as follows: sodium (mEq/L), divide by 1.0; potassium (mEq/L), divide
by 1.0; ionized calcium (mg/dL), divide by 0.25; lactate (mg/dL), divide by 0.111; ionized magnesium (mEq/L), divide by 0.50. Other values are given in conventional units;
conversions to SI units are as follows: hematocrit (proportion of 1.0), multiply by 0.01; glucose (mmol/L), multiply by 0.0555; urea nitrogen (mmol/L), multiply by 0.357.
© American Society for Clinical Pathology
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Siegel et al / Analytes in Collapsed Marathon Runners
ment of abnormalities shown on 2-dimensional echocardiography.9 In a recent study of asymptomatic marathon runners
following competition, more than 60% of participants had
measurable increases in TnT levels, with 40% at or above the
decision limit for acute myocardial necrosis (TnT ≥0.03 ng/
mL [0.03 µg/L]). These changes were inversely related to training experience.9 In another recent study, postrace cardiac TnT
levels were elevated (≥0.01 or ≥0.1 ng/mL [0.01 or 0.1 µg/L])
in 68% of 482 runners following the 2002 Boston Marathon,
including 11% with a TnT level of 0.075 ng/mL (0.075 µg/L)
or more or of 0.5 ng/mL (0.5 µg/L) or more.11
In contrast with these results in asymptomatic runners
who completed a marathon, in our study, only 18% of collapsed runners showed measurable TnT values, with 8%
greater than 0.03 ng/mL (0.03 µg/L); 3 had values of more
than 0.1 ng/mL (0.1 µg/L). These percentages are distinctly
lower than those observed by Neilan et al9 and Fortescue
et al11 in asymptomatic runners. Because the degree of TnT
release seems to somewhat parallel the degree of endurance
exercise, it may be that our collapsed runners did not achieve
the intensive myocardial stress achieved by runners who complete a full marathon. Lending further support to this concept
is that the values for NT-proBNP in collapsed runners in our
study were generally within the age-adjusted normal range
and lower than the median postrace NT-proBNP level of 131
pg/mL reported in asymptomatic runners who successfully
completed the race.9 Thus, in aggregate, our data suggest that
cardiovascular insufficiency does not underlie the mechanism
of collapse in the vast majority of collapsed runners.
Rapid whole blood point-of-care analyte results in 135
collapsed runners at the 2006 race demonstrated frequent
abnormalities of sodium, lactate, ionized calcium, and ionized
magnesium levels. Hypernatremia was observed in 13% and
hyponatremia in 5% of collapsed marathon runners (compared with 25% and 6%, respectively, during the 2004 race
at warmer temperatures12). Prevention of hypernatremia and
hyponatremia is the focus of recently revised recommendations for optimal hydration issued by the American College
of Sports Medicine and the International Marathon Medical
Directors Association.13,14 The former guidelines emphasize
preventing dehydration in higher performance athletes by
advice to drink “ahead of thirst,” and the latter stress drinking
to thirst only to minimize the risk of overhydration, especially
in slower marathon runners and walkers.15
Elevated levels of whole blood lactate were observed in
95% of collapsed runners. Of these, 32 (40.5%) had values
more than the range commonly regarded as a “critical value”
(31.5 mg/dL [3.5 mmol/L]).16 Of the subjects, 51% had a low
ionized calcium level and 23% an abnormal ionized magnesium level (8 of 9 had hypomagnesemia). The low ionized
calcium values are most likely a consequence of the elevations
in lactate because lactic acidosis is known to decrease the ion950
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ized calcium level.17 Metabolic acidosis also is a known cause
of hypomagnesemia, as was found in 8 cases. Low ionized
calcium and magnesium levels may contribute to impaired
skeletal muscle and, potentially, myocardial function18 in the
collapsed runners. The mean glucose value of 117 mg/dL (6.5
mmol/L) in collapsed runners reported herein is similar to the
mean of 110 mg/dL (6.1 mmol/L) reported in asymptomatic
finishers.6 No collapsed runners were hypoglycemic.
The mechanism underlying exertional triggering of acute
cardiac events remains unknown. Relative risks 2.38- and
16.9-fold greater in apparently healthy women and men,
respectively, have been reported for acute cardiac events,
including sudden death, during strenuous exercise compared
with baseline at rest.1,19 Marathon running is associated with
an abrupt but transient increase in relative risk for ACS in
persons who are otherwise at relatively low risk. Despite
improved emergency cardiac care along race courses in recent
years, the rate of sudden death predominantly in middle aged
men has remained at 1 per 50,000 marathoners during the last
2 decades.4,5 The Marine Corps and Los Angeles marathons
experienced multiple cases of cardiac arrest in 2007, perhaps
reflecting increasing participation of older runners. Boston
Marathon entrants between ages 40 and 59 years increased
from 4,000 in 1997 to 10,000 in 2007.20
Although we show comparable (if not lower) levels of
diagnostic and prognostically meaningful cardiac biomarkers
among endurance athletes compared with levels in athletes
who finished the marathon, we also found prevalent abnormalities in various electrolytes, which in conjunction with
lactic acidosis and a decrease in ionized calcium and magnesium levels may contribute to the enhanced risk for ventricular
fibrillation during acute exertional events. Furthermore, the
significance of these metabolic abnormalities as related to
exercise-induced collapse is not yet clear.
From the 1Department of Medicine, McLean Hospital, Belmont,
MA; Departments of 2Cardiology and 3Pathology, Massachusetts
General Hospital and 4Harvard Medical School, Boston; and
5Nova Biomedical, Waltham, MA.
Address reprint requests to Dr Lewandrowski: Clinical
Chemistry, Gray 5, Massachusetts General Hospital, Fruit St,
Boston, MA 02114.
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