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Creatine kinase monitoring in sport medicine
Paola Brancaccio*
†
, Nicola Maffulli
‡
, and Francesco Mario Limongelli
†
†
Department of Experimental Medicine—Sport Medicine, Centre of Excellence of Cardiovascular
Disease, Seconda Universita
`
di Napoli, Napoli, Italy, and
‡
Department of Trauma and Orthopaedic
Surgery, Keele University School of Medicine, Thornburrow Drive, Hartshill, Stoke on Trent ST4
7QB Staffs, UK
Areas of general agreement: Total creatine kinase (CK) levels depend on age,
gender, race, muscle mass, physical activity and climatic condition. High levels of
serum CK in apparently healthy subjects may be correlated with physical training
status, as they depend on sarcomeric damage: strenuous exercise that damages
skeletal muscle cells results in increased total serum CK. The highest post-
exercise serum enzyme activities are found after prolonged exercise such as
ultradistance marathon running or weight-bearing exercises and downhill
running, which include eccentric muscular contractions. Total serum CK activity
is markedly elevated for 24 h after the exercise bout and, when patients rest, it
gradually returns to basal levels. Persistently increased serum CK levels are
occasionally encountered in healthy individuals and are also markedly increased
in the pre-clinical stages of muscle diseases.
Areas that are controversial: Some authors, studying subjects with high levels of
CK at rest, observed that, years later, subjects developed muscle weakness and
suggested that early myopathy may be asymptomatic. Others demonstrated that,
in most of these patients, hyperCKemia probably does not imply disease.
In many instances, the diagnosis is not formulated following routine
examination with the patients at rest, as symptoms become manifest only after
exercise. Some authors think that strength training seems to be safe for patients
with myopathy, even though the evidence for routine exercise prescription is still
insufficient. Others believe that, in these conditions, intense prolonged exercise
may produce negative effects, as it does not induce the physiological muscle
adaptations to physical training given the continuous loss of muscle proteins.
Growing points: High CK serum levels in athletes following absolute rest and
without any further predisposing factors should prompt a full diagnostic
workup with special regards to signs of muscle weakness or other simple signs
that, in both athletes and sedentary subjects, are not always promptly evident.
These signs may indicate subclinical muscle disease, which training loads may
evidence through the onset of profound fatigue. It is probably safe to counsel
athletes with suspected myopathy to continue to undertake physical activity at
a lower intensity, so as to prevent muscle damage from high intensity exercise
and allow ample recovery to favour adequate recovery.
British Medical Bulletin 2007; 81 and 82: 209–230 & The Author 2007. Published by Oxford University Press.
DOI: 10.1093/bmb/ldm014 All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted: April 18, 2007
*Correspondence to:
Paola Brancaccio,
Department of
Experimental Medicine—
Sport Medicine,
Centre of Excellence of
Cardiovascular Disease,
Seconda Universita
`
di
Napoli, Napoli, Italy.
E-mail:
pabranca@libero.it
Published Online June 14, 2007
Areas timely for developing research: CK values show great variability among
individuals. Some athletes are low responders to physical training, with
chronically low CK serum levels. Some athletes are high responders, with higher
values of enzyme: the relationship among level of training, muscle size, fibre
type and CK release after exercise should be investigated further. In addition,
more details about hyperCKemia could come from the evaluation of the kinetics
of CK after stress in healthy athletes with high levels of CK due to exercise,
comparing the results with the ones obtained from athletes with persistent
hyperCKemia at rest. Finally, it would be important to quantify the type of
exercise more suited to athletes with myopathy and the intensity of exercise not
dangerous for the progression of the pathology.
Keywords: creatine kinase/muscular enzymes/myopathy/stress test
Introduction
The serum level of skeletal muscle enzymes is a marker of the func-
tional status of muscle tissue and varies widely in both pathological
and physiological conditions. An increase in these enzymes may rep-
resent an index of cellular necrosis and tissue damage following acute
and chronic muscle injuries.
1,2
Changes in serum levels of muscular
enzymes and isoenzymes are also found in normal subjects and in ath-
letes after strenuous exercise
3–6
: the amount of enzyme from muscle
tissue to blood can be influenced by physical exercise.
7
Muscle creatine
kinase (CK) activity measured from needle muscle biopsies shows
different behaviour before and after training,
8,9
and the serum level of
CK changes according to different protocols and to the intensity and
level of training.
10 – 12
The serum CK level can be raised from the damage of the muscle
tissue as a consequence of intense prolonged training. This may be a
consequence of both metabolic and mechanical causes. Indeed, meta-
bolically exhausted muscle fibres exhibit a decrease in the membrane
resistance following an increase in the internal free calcium ions, which
promotes the activation of the potassium channel.
13,14
Another mecha-
nism could be the local tissue damage with sarcomeric degeneration
from Z-disk fragmentation. CK is an indicator of muscle necrosis,
increasing with its extent.
15 – 17
The study of CK in sport medicine allows to obtain information on
the state of the muscle. High levels of serum CK in apparently healthy
subjects may be correlated with physical training status. However, if
these levels persist at rest, it may be a sign of subclinical muscle
disease, which training loads may evidence through the onset of symp-
toms such as profound fatigue.
18
P. Brancaccio et al.
210 British Medical Bulletin 2007;81 and 82
Background
CK is a dimeric globular protein consisting of two subunits with a mol-
ecular mass of 43 kDa. It buffers cellular ATP and ADP concentrations
by catalysing the reversible exchange of high-energy phosphate bonds
between phosphocreatine and ADP produced during contraction. At
least five isoforms of CK exist: three isoenzymes in cytoplasm
(CK-MM, CK-MB and CK-BB) and two isoenzymes (non-sarcomeric
and sarcomeric) in mitocondria. These are octameric proteins known
as macro-CK because of their large molecular size
19
from polymeriz-
ation of isoenzymes CK-MM and CK-BB with IgG in type I and with
mitocondrial CK in type II.
20
The presence of macro-CK isoenzymes
has a prognostic value: macro-CK type I is present in patients who
developed cardiovascular or autoimmune process, whereas macro-CK
type II isoenzymes are found in patients with malignant prolifera-
tion.
21 – 23
CK isoenzymes give specific information on injured tissue
because of their tissue distribution. In fact, CK-MM is found in several
domains of the myofibre where ATP consumption is high and is a
marker of muscle disease.
24
CK-MB increases in acute myocardial
infarction,
25
and CK-BB increases in brain damage.
26
Mitocondrial CK
is raised in mitochondrial myopathies.
27
MM-CK is specifically bound to the myofibrillar M-Line structure
located in the sarcomere, a complex structure containing at least 28
different proteins. A sarcomere is bordered at each end by a dark
narrow line known as the Z-line. Each Z-line bisects a lighter I-band,
which is shared between adjacent sarcomeres. At the centre of the sar-
comere is the dark A-band bisected by a less dense H-zone. In the
middle of the H-zone lies a narrow band of higher density, the M-line.
This site accounts for 5–10% of the total CK-MM: there are two pairs
of highly conserved lysine residues, which are necessary and sufficient
to mediate the isoenzyme-specific binding of CK into the M-line struc-
ture and which probably depend on the energy state of the muscle as
the binding properties change according to pH.
28
The M-line region
appears to be the only myofibrillar structure which connects thick fila-
ments (myosin) directly with each other, providing physical stability
between thick filaments during contraction.
Furthermore, the presence of MM-CK suggests that the M-line has a
structural and enzymatic role to regenerate ATP at sites of high-energy
consumption, thus providing myosin with sufficient ATP to work even
under strenuous conditions.
29
The Z-line is located at the end of the sarcomere, forming the junc-
tion between one sarcomere and the next. It contains numerous com-
ponents, which contribute to anchoring the thin filaments (mainly
CK monitoring in sport medicine
British Medical Bulletin 2007;81 and 82 211
composed of actin) in Z-line. It contains several other proteins, includ-
ing Myotilin, which have been implicated in limb-girdle muscular dys-
trophy type 1A. Moreover, there are transverse filaments connecting
myofibrils with each other at neighbouring Z- and M-lines, respecti-
vely, and with the sarcolemma, possibly contributing to transmission
of force along the fibril, even though sarcomeres have been damaged
or overstretched. The major constituent of the intermediate filaments is
desmin (and the associated synemine, paranemin and nestin), vinmen-
tin (which is not expressed in mature muscle), syncolin, Skelemin and
Plectin, whose absence is associated with muscular dystrophy. A third
set of filaments in muscle, constituted by titin, plays two crucial roles
in the sarcomere: it provides a template for the precise organization of
the myofibrillar proteins during development and determines the
mechanical behaviour of the muscle. Titin extends to the entire length
of a half-sarcomere, from Z-line to M-line, and interacts with teletho-
nin (or titin-cap) (Fig. 1), implicated in limb-girdle muscular dystrophy
type 2G.
Therefore, the high serum levels of CK depend on sarcomeric
damage arising either from strenuous exercise or from muscular pathol-
ogy. Accurate history and a correct diagnostic approach help the physi-
cian to formulate the correct diagnosis.
Serum CK in healthy subjects
In normal serum, total CK is provided mainly by the skeletal muscle
and is almost only of the MM fraction. Total CK levels depend on age,
gender, race, muscle mass, physical activity and climatic condition. The
2.5 and 97.5 percentile reference limits have recently been revisited.
30
During foetal life, CK activity is provided mainly by the BB iso-
enzyme, changing to MM predominance during foetal development.
31
In the newborn, CK serum levels are higher than those in adults and
are dependent on gestational age, with values that reach adult levels
within the first 10 days of life.
32
In women, CK activity decreases
during pregnancy, but increases in late gestation with high values of
CK-MB.
33,34
Young adult males have high serum levels of CK,
35
which
decline slightly with age during the geriatric period.
36
There are marked sex differences in CK serum levels at rest,
37
with
lower values in females than in males. After muscular exercise,
sex-linked differences are still present,
38
and oestrogen may be an
important factor in maintaining post-exercise membrane stability, thus
limiting CK leakage from the damaged muscle.
39,40
Black men usually have higher values than Caucasians,
41
and,
although black men usually have an higher body weight and a denser
P. Brancaccio et al.
212 British Medical Bulletin 2007;81 and 82
lean body mass,
42
this does not correlate with CK levels
43
; but some
studies do not report any differences in the CK serum values between
black and white athletes.
44
Anyway, CK activity is related to body
mass
45
and physical activity, with resting levels higher in athletes than
in sedentary subjects, given the regular training that athletes
undergo.
46,47
Fig. 1 Proteins related to muscular dystrophies and localization in the sarcomere.
CK monitoring in sport medicine
British Medical Bulletin 2007;81 and 82 213
Cold weather induces higher serum CK increases following a stan-
dard exercise bout when compared with the same exercise bout at
warmer temperatures.
48
CK elevation in pathology
Monitoring of CK and characterization of its isoenzymes are widely
used in the diagnosis of myopathies, cardiomyopathies and encephalo-
pathies.
49 – 51
CK, and especially its MB isoenzyme, is a reliable marker
of myocardial necrosis, offering great sensitivity to detect infarct exten-
sion to predict worse prognosis.
52,53
Patients with neurological conditions such as acute cerebrovascular
accidents,
54
proximal spinal muscular atrophy
55
and amyotrophic
lateral sclerosis
56
show marked elevation of CK-BB. Elevated CK has
also been described in various neuromuscular conditions as a result of
muscle damage and necrosis
57
and in many muscular dystrophies such
as fa cioscapulohumeral dystrophy (FSHD) and myotonic dys trophy.
58,59
Primary skeletal muscle disorder manifests with pain, fatigue, weak-
ness, and serum CK elevation.
60
The levels of serum CK are different
in various myopathies according to the type of disease and the stage of
pathology (Table 1). Muscular dystrophy shows the highest CK
levels.
61,62
The low CK levels occur in the late stages of the condition
because muscle tissue has almost totally undergone fibrotic changes.
63
Other muscular pathologies, such as selenium deficiency
64
or nemaline
myopathy,
65
often present only slightly elevated serum enzyme levels.
Pain and weakness with mild elevation of enzymes can be due even to
the myocardial involvement in other pathology as dilated cardiomyo-
pathy in desmin-related myopathy
66,67
or polymyositis,
68
which have
levels of CK similar to the ones seen in myocardial infarction.
Table 1 CK values usually found in some muscular pathology
Muscular pathology CK value increases
Duchenne and Becker dystrophies 25–200-fold
Limb-girdle muscular dystrophy 10–100-fold
FSHD 2–7-fold
Distal myopathy 3-fold
Endocrine myopathy Up to 10-fold
Congenital myopathies Slight increase
Metabolic myopathy Slight increase
Mitochondrial myopathy Slight increase
Drug-induced myopathies Slight or no increase
P. Brancaccio et al.
214 British Medical Bulletin 2007;81 and 82
Hypothyr oidism is a common cause of endocrine myopathy and should
be consider ed in pa tients with unexplained persis tent elevation of serum
muscle enzymes, which ar e higher in patients with o v ert hypothyroidism
and low er in subclinical hypothyroidism.
69
Many authors suggest to
assessthyroidfunctioninpatientswithmuscleweaknessorelevationof
CK, although clinical signs of hypothyr oidism may be absent.
70,71
Infective rhabdomyolysis can be another cause of unexplained serum
CK increase, most frequently seen in patients with respiratory tract
infections
72
and cytomegalovirus infections.
73
Moreover, in paediatric
patients, an increase in serum mitochondrial CK can be associated with
rotavirus gastroenteritis, probably reflecting the diffusive intestinal epi-
thelial cell damage.
74
In crush syndrome,
75
CK serum levels have been used as a prognostic
tool.
76
In prolonged exposure to cold, as in the victims of avalanche,
crush injury to the muscles combines with hypoxia and hypercapnia
(secondary to rebreathing and hypothermia) to produce high serum
levels of CK.
77,78
A common cause of exercise-induced rhabdomyolysis
is carnitine palmitoyltransferase deficiency, which impairs mitochon-
drial oxidation of long-chain fatty acids, often detected by a chance
finding of elevated CK levels.
79
The risk of exertional rhabdomyolysis
is higher in anabolic androgenic steroids users.
80,81
Other causes of serum CK elevation can be intramuscular injections,
with the magnitude of serum CK elevation proportional to the injec-
tion volume
82
and the drug injected.
83
In compartment syndrome,
84
CK levels are useful to formulate the diagnosis. At surgery, local
muscle tissue damage occurs, with CK levels significantly higher in
major surgery than in minor procedures.
85
Increased CK levels have
been observed following convulsive seizures,
86,87
heat stroke,
88
admini-
stration of statins, which can lead to rhabdomyolysis when used
alone,
89
or following interaction with other drugs.
90
Rhabdomyolysis
has been observed following the ingestion of herbal medicine.
91
Physiological CK elevation
Strenuous exercise that damages skeletal muscle cell structure at the
level of sarcolemma and Z-disks
92
results in an increase in total
CK.
93,94
When exercise intensity is mild to moderate, the muscle tissue
is exercised without marked changes in the membrane permeability:
when the exercise intensity exceeds this range, membrane permeability
changes and enzymes are released. The boundary of the range of exer-
cise intensity which the muscle tissue can withstand is its break point:
when loading exceeds a certain limit of muscle ability, CK leaks into
CK monitoring in sport medicine
British Medical Bulletin 2007;81 and 82 215
the interstitial fluid, is taken up by the lymphatic system and returned
into the circulation.
95
Many factors determine the degree to which serum enzyme activities
increase during and after exercise. The highest post-exercise serum
enzyme activities are found after very prolonged competitive exercise
such as ultradistance marathon running
96
or triathlon events.
97
Weight-bearing exercises, which include eccentric muscular contrac-
tions such as downhill running, induce the greatest increases in serum
enzyme activities.
98
There is a breakpoint at 300–500 IU/l of CK
serum release after exercise, and the levels of enzyme are associated
with distinctive individual musclar properties. Subjects can be classified
into high and low responders. In high responders, the cross-sectional
area and volume of the quadriceps femoris muscle were significantly
lower than those in low responders.
99
Daily training may result in
persistent serum elevation of CK,
100
and resting CK levels are higher in
athletes,
101,102
but the significant increases of CK occurred after
exercise are usually lower in trained subjects when compared with
untrained subjects.
103 – 105
In fact, if athletes and sedentary
subjects undertake the same physical exercise test, the CK levels of
athletes are lower than those recorded in matched healthy control
subjects.
106,107
The time of CK release into and clearance from plasma depends on
the level of training, type, intensity and duration of exercise. Peak
serum CK levels of about 2-fold above baseline occur 8 h after strength
training.
108
Increased CK levels after eccentric exercise are associated
with muscle injury, with a pronounced increase between 2 and 7 days
after exercise.
109
After prolonged exercise, total serum CK activity is markedly eleva-
ted for 24 h after the exercise bout when subjects rest and remains elev-
ated for 48 h when subjects train in the first week post-exercise.
110
The
release of CK following eccentric exercise peaked 96 h after the exer-
cise bout, and an additional bout of exercise produces only small
increases, probably from accelerated enzymatic clearance.
111
More
intense activity, such as a twice daily football training, leads to signifi-
cant increase of CK during the fourth day of training. CK levels
decrease between days 4 and 10, probably an adaptation to training.
112
A bout of exercise performed 48 h after an initial bout does not change
the time course of the CK leakage.
113
Normally, only CK-MM is present in the serum, but prolonged and
strenuous exercise increases the serum activity of all three
CK-isoenzymes in the absence of myocardial damage.
114
Probably, the
BB-fraction found in boxers
115
is a sign of cerebral damage.
CK serum levels reach their highest values only 5 min after a cycloerg-
ometer test, demonstrating that exercise duration rather than fitness
P. Brancaccio et al.
216 British Medical Bulletin 2007;81 and 82
levels seems to be related to serum CK, aspartate aminotransferase
(AST) and alanin aminotransferase (ALT) activities.
116
The decrease in the serum enzyme levels depends on the period of
rest after exercise, as short-term physical inactivity may reduce both
the lymphatic transport of CK and the release of the enzyme from the
muscle fibres.
117
Manual lymph drainage after treadmill exercise is
associated with faster decrease in the serum levels of muscle
enzymes.
118
Another factor that may reduce muscle damage and serum
concentrations of CK following prolonged exercise is supplementation
with branched-chain amino acids, often used in sports.
119
Persistent HyperCKemia
Persistently increased serum CK levels are occasionally encountered in
healthy individuals. Subjects often do not present any clinical manifes-
tation of a neuromuscular disorder or any condition known to be
associated with increased serum CK levels. Galassi et al.,
120
studying
subjects with high levels of CK at rest, observed that, years later, sub-
jects developed weakness. They suggest that early myopathy may be
asymptomatic.
121
Other authors demonstrated that, in most of these
patients, hyperCKemia probably does not imply disease,
122
and
patients without skeletal muscle abnormalities on muscle biopsy may
have idiopathic hyperCKemia (IH).
123
Familial IH is a benign geneti-
cally heterogeneous (although normally autosomal dominant) con-
dition often ascribed to caveolin-3 gene mutations, with a higher
penetrance in men.
124
In a long-term study of IH patients, there was no
clinical deterioration on electromyography (EMG), and muscle biopsy
demonstrated only minor, non-diagnostic abnormalities.
125
Recently,
40 subjects with persistent asymptomatic IH underwent clinical and
laboratory investigations, electromyography and muscle biopsy:
pathological findings were found in 55% of them, and a diagnosis of
muscular dystrophy was made in three subjects.
126
However, as the
diagnosis of muscular dystrophy does not depend on the level of CK, a
full workup may well be indicated in patients with unexplained high
enzymatic serum levels of CK.
127
Serum CK activity is also markedly increased in the pre-clinical
stages of some muscle diseases.
128
In the group of mitochondrial myo-
pathies, carnitine palmitoyltransferase deficiency has been detected
from elevated CK levels in routine blood tests, especially after exercise.
This myopathy is one of the most common causes of rhabdomyolysis
and severe exercise induced myalgia.
129,130
In the same group, the
defects of mitocondrial transport,
131
of beta-oxidation,
132
of Krebs
cycle,
133
and of respiratory chain
134
are other disorders that can
CK monitoring in sport medicine
British Medical Bulletin 2007;81 and 82 217
manifest by increased CK. Even mild or recurrent hyperCKemia may
indicate a metabolic disease, as is the case in patients with mitochon-
drial myopathy
135
and myoadenilate deaminase deficiency, who can
have serum CK levels only slightly elevated and can slowly develop
myalgia and progressive weakness.
136
The defects of glycogen storage
affect the glycolytic or the glycogenolytic pathway, causing myopathy
with hyperCKemia.
137
A form of persistent asymptomatic
hyperCKemia can be due to desmin abnormalities and has been
reported in patients with only mild neuromuscular abnormalities.
138
In
many instances, the diagnosis is not formulated following routine
examination with the patients at rest, as the symptoms become mani-
fest only after exercise. For example, in two case reports, the patients
were athletes in whom muscle symptoms such as pain and cramping
developed insidiously after severe exercise: the diagnosis of myoto-
nia
139
and paramyotonia congenita
140
was made following an exercise
test. Becker muscular dystrophy,
141,142
FSHD,
143
and limb-girdle mus-
cular dystrophy
144
exhibit persistent hyperCKemia and exertional
muscle pain. In some instances, the elevated serum CK levels are
associated with myocardial pathology because the myopathy manifests
with dilated cardiomyopathy, as in lamin A/C gene defects
145
or limb-
girdle muscular dystrophy.
146
Furthermore, malignant hyperthermia
may sometimes cause unexplained, persistently increased serum CK
levels in otherwise healthy subjects, with no significant correlation
between the magnitude of CK increase and the severity of malignant
hyperthermia.
147
Some studies focused on the quality of life in patients with IH or
mild symptoms because of myopathies. Reijneveld et al.
148
studied the
response to exercise in subjects with IH: exercise does not result in
more extensive damage when compared with healthy subjects, even
though long-term data were not available. Other authors studied the
effect of exercise in FSHD.
149
Strength training seems to be safe for
patients with FSHD, even though the evidence for routine exercise pre-
scription is still insufficient.
150,151
Monitoring of serum CK in sport
In athletes, the study of CK at rest and after exercise could be an
important tool for coaches and clinicians.
152
Athletes have higher
resting CK when compared with untrained subjects,
153
probably
because of the greater muscle mass and the daily training performed.
However, after exercise, CK serum activity depends on the level of
training: although athletes experience greater muscle soreness when
compared with untrained subjects, their peak serum activity is lower.
154
P. Brancaccio et al.
218 British Medical Bulletin 2007;81 and 82
Also, the most marked increase in CK occurs in the less-trained
subjects.
155
Other authors attribute this behaviour to training adap-
tation and identified a relationship between peak power and release of
CK with the athletes achieving the lowest peak power showing the
greatest increase in CK.
112
However, marked CK increase is reported
after exertional rhabdomyolysis following marathon running
156
and is
often even greater when the exercise is strenuous in cold weather.
157
The risk of skeletal muscle injuries is increased when athletes use andro-
genic steroids or creatine supplements.
158,159
In addition a large
increase in serum CK levels combined with reduced exercise tolerance
could be a marker of overtraining.
160
However, muscle recovery cannot
be evaluated by changes in serum CK levels, as there is no correlation
between serum enzyme leakage and muscular performance impairment
after exercise.
161
In addition, CK values show great variability, and ath-
letes with chronically low CK serum levels (low responders) have low
variability when compared with those who have higher values (high
responders). Therefore, the diagnosis of overtraining becomes possible
only if a large increase is observed in combination with reduced exercise
tolerance.
162
Noakes,
163
in 1987, hypothesized that subjects with abnormally
large increase in serum CK activity after exercise may have unrecog-
nized subclinical myopathy.
163
This is indeed the case in some meta-
bolic myopathies such as McArdles, disease,
164
or mutation in some
sarcolemmal protein such as caveolin-3
165,166
and alpha-dystroglycan,
with a correlation between the reduction of protein expression and the
clinical phenotype,
167
or cytoskeleton
168
and components of nuclear
envelope as lamins.
169,170
In conclusion, persistent CK elevation must
be carefully investigated
171
and could be important to evaluate CK
serum activity at rest and after exercise to identify silent myopathies.
In fact, if a genetic trait predisposes to exertional rhabdomyolysis, the
myopathy could be symptomatic only after exercise, as seen in the
early stage of Becker’s syndrome.
172
Unexplained exertional limitation
including myalgia, fatigue or dyspnoea could be a sign of
myopathy.
173
Patients misdiagnosed with fibromyalgia may rarely have a myopa-
thy.
174
In these patients, before performing a muscle biopsy, measure-
ments of CK serum levels can be the first laboratory sign of muscle
disease.
Sometimes, the asymmetry of muscular involvement shows myopathic
features, and the pathology is evident at careful clinical examination.
175
In other instances, the myopathy could have a prevalent cardiac pheno-
type.
176
Athletes are at a higher risk of injuries during sport activities if
there is muscle weakness.
177
Therefore, even the less severe myopathies
could cause pain and muscle imbalance in athletes.
178
CK monitoring in sport medicine
British Medical Bulletin 2007;81 and 82 219
Persistent hyperCKemia in athletes
Stiffness, muscle soreness and pain are normal features of physical
training: often, both athletes and coaches pay little attention to these
symptoms. However, if they are resistant to rest and massage, or recur
too frequently, they should prompt a diagnostic workup. Sometimes,
these are the only signs of a silent myopathy. Kaar et al.
178
diagnosed
FSHD in a baseball player complaining of shoulder pain. In other
athletes, biopsy-proven myopathies were the cause of unexplained exer-
cise impairment.
179
In these instances, evaluation of CK at rest and
after exertion could be a simple and non-invasive method to guide
diagnosis.
High CK serum levels in athletes following absolute rest and without
any further predisposing factors should prompt a full diagnostic
workup with special regards to signs of muscle weakness or other
simple signs that, in both athletes and sedentary subjects, are not
always promptly evident. These include cranial asymmetry and evalua-
tion of the symmetric position of the inferior angle of the scapula and
the iliac spines.
180 – 182
Mutation in sarcomeric proteins is the prime
cause of a major class of disease that affects cardiac function, such as
familial hypertrophic cardiomyopathy, or leads to a variety of other
myopathies including limb-girdle muscular dystrophy type 2G (teletho-
nin),
183
limb-girdle muscular dystrophy type 1A (myotilin),
183
nema-
line myopathy (actin, tropomyosin and nebulin),
184
desmin-related
myopathy (desmin),
184
and other myopathies ( plectin).
185
In these sub-
jects, repeated intense prolonged exercise does not induce the physio-
logical muscle adaptations to physical training given the continuous
loss of muscle proteins.
186
In addition, although the increase in serum levels of CK is the most
useful screening laboratory test to identify myopathies, some cause no
increase in CK, and CK increase does not occur only in myopathies.
187
The determination of lactate during and after stress test is another
simple method to detect the impairment of oxidative metabolism of
mitocondrial myopathies
188,189
and McArdle’s disease,
190
as the sensi-
tivity of method seems to be higher than the resting values determi-
nation. Therefore, the approach to subjects with muscular symptoms
must be multidisciplinary,
191
and athletes with recurrent muscle disease
or persistently high CK at rest should be considered exactly as all other
subjects in the same condition and undergo clinical and instrumental
examination to achieve a diagnosis with (Fig. 2):
(i) accurate history taking to identify predisposing factor or familiarity of
the pathology;
(ii) assessment of serum CK levels after at least 1 week of rest;
P. Brancaccio et al.
220 British Medical Bulletin 2007;81 and 82
Fig. 2 Algorithm for detection of muscle pathology in subject with hyperCKemia.
CK monitoring in sport medicine
British Medical Bulletin 2007;81 and 82 221
(iii) physical examination to identify postural asymmetries;
(iv) assessment of serum CK levels after exercise, as in some myopathies,
post-exercise serum CK levels may be a better indicator of carrier status
than rest CK serum levels
192
;
(v) measurements of lactic acid after stress, which has a high sensitivity and
specificity in mitocondrial myopathies;
(vi) echocardiography to identify genetic muscular pathology phenotypically
expressed as a cardiomyopathy
193
;
(vii) electromyographic examination;
(viii) magnetic resonance imaging to study muscle involvement in myopathies,
which cannot be detected by manual muscle strength testing
194
;
(ix) muscle biopsy;
(x) protein analyses and genetic testing.
Concluding remarks
It is probably safe to counsel athletes with suspected myopathy to con-
tinue to undertake physical activity at a lower intensity, so as to
prevent muscle damage from high intensity exercise and allow ample
recovery to favour adequate recovery. Accurate history taking and clini-
cal examination should help to clarify whether more invasive investi-
gations, including muscle biopsies, should be considered.
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