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Technical Briefs |
Departments of
1
Neurology and
2
Clinical Chemistry, Academic Medical Centre, 1100 DE Amsterdam, The Netherlands
aaddress correspondence to this author at: Department of Neurology, Academic Medical Centre, PO Box 22700, 1100 DE Amsterdam, The Netherlands; fax 31-20-6971438, e-mail E.Hoogerwaard{at}amc.uva.nl
Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are standard markers for the detection of ischemic myocardial damage (1)(2)(3). Both cTnI and cTnT can also be detected in the blood of patients with chronic heart failure (4)(5)(6)(7), which enables the identification of patients with latent or progressive myocardial damage.
Carriers of Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) are at risk for cardiac disease. In a cross-sectional study among 129 definite DMD/BMD carriers, 5.4% had dilated cardiomyopathy and 18% had left ventricle dilation (8). In the present study, we analyzed both cTnT and cTnI, together with creatine kinase (CK) and CK-MB mass, to establish the value of these markers in DMD and BMD carriers and their possible association with the presence of nonischemic myocardial damage.
We studied 129 definite carriers of DMD (n = 85) and BMD (n = 44) enrolled in a cross-sectional study (8)(9) to assess the presence of muscle weakness and cardiac involvement. All carriers underwent extensive cardiological examinations, including medical history, physical examination, electrocardiogram, and transthoracic M-mode and two-dimensional echocardiography (8)(9). This study was approved by the Medical Ethical Committee of the Academic Medical Centre in Amsterdam. All carriers participated only after giving informed consent.
We collected 10 mL of heparin blood by venipuncture. Plasma was prepared, aliquoted, and frozen at -80 °C until the measurement of total CK activity, CK-MB mass, and cTnI and cTnT concentrations.
Total CK activity (upper reference limit, 193 U/L) was measured (10) at 37 °C with an Hitachi 747 analyzer (Boehringer Mannheim).
CK-MB mass (upper reference limit, 7 µg/L) was measured by an immunoenzymometric assay (Immuno I analyzer). The total imprecision (CV) was <2.5%, and the detection limit in human serum was 0.06 µg/L. No interference from CK-MM or CK-BB could be detected. CK-MB mass (µg/L) was expressed as a ratio to total CK activity (µg/L over U/L). A ratio >3% was considered suggestive of cardiac involvement.
We measured cTnI (detection limit and upper reference limit, 0.4 µg/L) on a Stratus II analyzer (Dade International) by use of two monoclonal antibodies specific for cTnI (10). The immunoassay shows no cross-reactivity with human skeletal-muscle troponin I (3).
We measured cTnT (detection limit, 0.002 µg/L; upper reference limit, 0.1 µg/L) with an immunoassay on an ES600 analyzer (Boehringer Mannheim). The assay uses a myocardium-specific biotinylated antibody as the conjugate and a cardiac-specific antibody as the biotinylated component (11).
2 tests were used to analyze the relationship
between the different laboratory measurements and age and cardiac
abnormalities, respectively. To compare the means of serum CK
measurements, we used t-tests or the Mann–Whitney test as
appropriate.
The mean age of 129 carriers was 36.9 years (range, 18–58 years). None had symptoms or signs of ischemic heart disease. Seven carriers (5.4%, all DMD) had echocardiographic evidence of dilated cardiomyopathy, of whom five had signs or symptoms of congestive heart failure [four women had New York Heart Association (NYHA) class I; one woman had NYHA class II]. Furthermore, 23 DMD/BMD carriers (18%) had left ventricle dilation. In 17 cases (13%), borderline echocardiographic abnormalities were found, such as wall motion abnormalities or unilateral atrial dilation. Electrocardiographic abnormalities were seen in 61 carriers (47%). Only 38% had results that indicated a completely healthy heart.
Total CK activity was increased in 45% of the patients (58 cases):
53% of DMD carriers (45 cases) and 30% of BMD carriers (13 cases).
The mean CK was 306 U/L (48–1860 U/L). Five of seven carriers with
dilated cardiomyopathy had increased CK. In 22 (17%) of the DMD/BMD
carriers, CK-MB mass was increased. The CK-MB/CK total ratio was >3%
in three carriers (Table 1
), none of whom had dilated cardiomyopathy. No carriers had
detectable cTnI. Two carriers had detectable cTnT (Table 1
). In one
carrier with borderline echocardiographic abnormalities, cTnT was
slightly increased (0.16 µg/L).
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No significant difference was found in mean CK activity between carriers with and without muscle weakness. We found no clear correlation between CK and age, but mean CK activity showed a decreasing linear trend with increasing age groups (P = 0.044). There was no relationship between CK-MB and age.
In this study, we measured total CK, CK-MB mass, and cTnI and cTnT in a large group of DMD/BMD carriers. Measurements of cTnI and cTnT are superior to conventional measurements of CK-MB mass in detecting acute myocardial infarction (1)(2)(3) and minor myocardial injury (12). Both proteins are used as markers of cardiac cell injury (13). In patients with severe chronic heart failure (NYHA III and NYHA IV), cTnI (4)(6) and cTnT (5)(7) are often increased. In our study, none of three carriers with an increased CK-MB/CK-total ratio had dilated cardiomyopathy and none had detectable troponins. Thus a CK-MB/CK-total ratio >3% did not appear to be indicative of severe cardiac abnormalities in our study population. Two carriers had detectable cTnT; in one carrier with borderline echocardiographic abnormalities, it was slightly increased. In all other carriers, cTnT was not detectable. None of the carriers had detectable cTnI. Although 30 women (23%) among the DMD/BMD carriers showed left ventricle dilation or dilated cardiomyopathy on echocardiography, these abnormalities probably reflected cardiac dysfunction rather than cardiac cell necrosis. In our study group, no carrier had severe heart failure that was associated with increased troponins. cTnI and cTnT can be used, however, for carriers suspected of cardiac ischemia. Measurement of CK-MB alone could give a false-positive result because of high total CK.
Some authors have found a negative correlation between CK activity and age in DMD (14) and BMD carriers (15), whereas others have not (16). We found no such correlation, but we were able to demonstrate a linearly decreasing trend of total CK with increasing age groups of carriers. Surprisingly, only 53% of DMD carriers and 30% of BMD carriers had increased total CK. Only one earlier study found similar percentages (17), whereas most other studies found raised CK activity in 60–80% in DMD (16)(18)(19)(20)(21)(22) and 42–62% of BMD carriers (15)(20)(22). These relatively high percentages prompted clinicians in the predystrophin era to calculate the risk of being a carrier. Perhaps the difference between our study and those carried out before the 1990s is that in most of these investigations, repeat measurements of total CK were done, whereas we performed only one measurement.
In conclusion, detectable cTnI and cTnT are rare in DMB and BMD carriers and bear no relationship with disease-specific cardiac abnormalities. We cannot exclude the possibility that cTnI and cTnT will be increased in carriers with severe heart failure because no severe heart failure was present in our study group.
References
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