- Email: [email protected]
Racial differences in serum creatine kinase levels
LETTERS TO THE EDITOR
RACIAL KINASE
DIFFERENCES LEVELS
IN SERUM
TABLE
CREATINE
To the Editor: In discussing their finding of statistically significant interracial differences in serum creatine kinase activity, Dr. Black and colleagues (Am J Med 1986; 81: 479-487) suggested that the higher levels in blacks compared with those in whites could be due to a differential effect of physical activity. We were intrigued by this suggestion, as we found the variable of physical activity to be the major factor responsible for the higher levels of creatine kinase activity in black compared with white South African men. (A detailed account of this work is shortly to be submitted for publication.) We measured creatine kinase activity in 54 black men, 111 black women, 88 white men, and 67 white women. All were healthy volunteers. Blood sampling was performed before 8:30 A.M., at which time subjects were also questioned whether they did (exercisers) or did not (non-exercisers) undertake regular recreational activity. The exercisers were further subdivided into those who had exercised within the previous 72 hours and those who had not. Statistical comparisons were performed using the Mann-Whitney U test or the Kruskal-Wallis test. Descriptive statistics of creatine kinase activity for each race-gender group are shown in Table 1. Levels for black men were significantly higher than for white men when comparing groups (p
I
Descriptive Statistics of Creatine Kinase Activity for Each Race-Gender Group CreatineKinase Activity (IUlliler)
Race-Gender Group
Mean Age (years)
Black men (n = 54) White men (n = 88) Black women (n = 111) White women (n = 67)
27
71-3,170
386 f
494
216
23
42-6,685
243 f
701
142
22
99
21
100
Range
Mean f SD
38 f 97 50 f
93
Median
111 67
this seems unlikely. Potentially more plausible as an underlying explanation is the influence of genetic factors [l], since there is evidence that interindlvidual variation in creatine kinase activity is under some degree of genetic control [lo]; and Meltzer and Holy [2] reported a consistent trend towards an increase in serum levels with increasing skin pigmentation. A study comparing creatine kinase activity in black men and white men in response to exercise of the same intensity and duration should resolve the question whether differences in physical activity per se, or the influence of genetic factors on its effects, was responsible for the interracial variation we observed. Our finding of no significant interracial difference in creatine kinase activity in women demands additional comment, as it contrasts with the higher levels in black women reported by Dr. Black and colleagues and investigators in previous studies [l-5]. Although no reason for this discrepancy readily suggests itself, we should stress that our study involved an African population, whereas other reports have originated from North America or North America and Europe. It is also of interest that only 23 percent of black women were exercisers compared with 76 percent of white women. The degree to which such a notable difference in recreational activity is pertinent to the matter in hand is a moot point, since reasoning that indeed it is necessitates assuming physical activity was responsible for the interracial variation in creatine kinase activity among women in the other studies, and this cannot be ascertained from the available data. It is therefore not possible to develop this argument further. RICHARD
F. GLEDHILL,
M.D.
MARIA M. VAN NIEKERK, M.Med. (Path.) University of Pretoria South Africa CAREL A. VAN DER MERWE, D. Comm. Institute for Biostatistics Medical Research Council South Africa 1.
August 1987
Meltzer HY: Factors affecting serum creatine phosphokinase levels in the general population; the role of race, activity and age. Clin Chim Acta 1971; 33: 165-172.
The American Journal of Medicine
Volume 83
385
LETTERS
2.
3.
4.
5. 6.
7. 8.
9.
10.
TO THE EDITOR
Meltzer HY, Holy PA: Black-white differences in serum creatine phosphokinase (CPK) activity. Clin Chim Acta 1974; 54: 215224. Van Steirteghem AC, Robertson EA, Zweig MH: Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay. Clin Chim Acta 1979; 93: 25-28. Wong ET, Cobb C, Umehara MK, et al: Heterogeneity of serum creatine kinase activity among racial and gender groups of the population. Am J Clin Pathol 1983; 79: 582-586. Miller WG, Gruemer HD, Chinchilli VM: Upper reference limit for creatine kinase. Clin Chem 1985; 31: 158. Newham DJ, Jones DA, Edwards RHT: Large plasma creatine kinase changes after stepping exercise. Muscle Nerve 1983; 6: 380-385. Hunter JB, Critz JB: Effect of training on plasma enzyme levels in man. J Appl Physiol 1971; 31: 20-23. Berg A, Haralambie G: Changes in serum kinase and hexose phosphate isomerase activity with exercise duration. Eur J Appl Physiol 1978; 39: 191-201. Roti S, lori E, Guiducci U, et al: Serum concentrations of myoglobin, creatine phosphokinase and lactic dyhydrogenase after exercise in trained and untrained athletes. J Sports Med 1981; 21: 113-118. Meltzer HY, Dorus E, Grunhaus L, Davis JM, Belmaker R: Genetic control of human plasma creatine phosphokinase activity. Clin Genet 1978; 13: 321-326. Submitted
February
17, 1987, and accepted
May 7, 1987
The Reply: Gledhill et al’s findings are very interesting, and I cannot quarrel with their conclusion that exercise, even 72 hours prior to measurement as described, may have explained the changes noted. We, too, think that is a possibility, and as mentioned, we excluded those who had undergone strenuous exercise in the preceding 12 hours. I agree with Dr. Gledhill and colleagues that a more formal study of the influence of exercise is required, and I welcome the results of such an investigation. HENRY
R. BLACK,
JOEL
1.
2.
2.
366
August
1987
The American
Journal
of Medicine
Volume
23, 1987, and accepted
the quest 1971; 127: hospital: a J Psychia-
May 7, 1987
BUSH,
M.D.
Beth Israel Hospital 330 Brookline Avenue Boston, Massachusetts 022 15
THE
To the Editor: In their study on the CAGE questionnaire, Bush et al (Am J Med 1987; 82: 23 l-235) utilized the score achieved on the Michigan Alcoholism Screening Test (MAST) [ 11 as part of their “gold standard” of diagnosis for alcohol dependence and abuse. The MAST is itself a 25item screening test that includes in a more explicit fashion the four questions on the CAGE. Therefore, it would not be surprising that patients responding affirmatively on the CAGE questionnaire would also score two or more points on the MAST. The MAST, like the CAGE questionnaire, has not been extensively re-validated in a wide spectrum of patients [2], and so it too may be insensitive for the detection of patients in the early stages of alcoholism.
March
BOOKER
M.D.
I.
USING
M.D.
The Reply: Dr. Freiman correctly notes that the CAGE questionnaire consists of the four most sensitive questions in the Michigan Alcoholism Screening Test [ 11. In our diagnostic criteria, a person had to have a MAST score of 6 or more to be considered alcoholic. Each CAGE question counts for only one point. The designation of alcohol abuse required a MAST score of 3 or more plus a consumption of four to five drinks a day (for a 70 kg man). A MAST score of 2 was only positive for alcohol abuse if the person also drank in excess of nine drinks per day. However, I agree with Dr. Freiman’s comment on the fact that the MAST questionnaire has not been re-validated in many populations. We have found a very different test behavior for the CAGE questionnaire in young women seeking gynecologic care [2]. We agree that more validation studies are in order. The CAGE questionnaire, however, still appears to be more sensitive than the alcohol consumption history or laboratory screening tests, and therefore should find a place in the health care provider’s screening examination of patients.
School of Medicine 333 Cedar Street New Haven, Connecticut 065 lo-6056
ABUSE
Seizer ML: The Michigan Alcoholism Screening Test: for a new diagnostic instrument. Am J Psychiatry 1659-1663. Moore RA: The diagnosis of alcoholism in a psychiatric trial of the Michigan Alcoholism Screening Test. Am try 1972; 128: 1566-1569. Submitted
Yale University
SCREENING FOR ALCOHOL CAGE QUESTIONNAIRE
FREIMAN,
Ben Taub General Hospital 1502TaubLoop Houston, Texas 77030
Mayfield D, McLeod G, Hall P: The CAGE questionnaire: validation of a new alcoholism instrument. Am J Psychiatry 1974; 131: 1121-l 123. Halliday A, Bush B, et al: Alcohol abuse in women seeking gynecologic care. Obstet Gynecol 1983; 68: 322-326.
SUCCESSFUL THERAPY OF PSEUDOMONAS AERUGINOSA ENDOCARDllIS WITH CEFTAZIDIME AND TOBRAMYCIN To the Editor: Endocarditis due to Pseudomonas aeruginosa is a difficult therapeutic problem [i-3]. Combined medical and surgical therapy often is required to improve chances for cure, especially when left-sided valves are involved [ 1,4]. Ceftazidime is a new cephalosporin with excellent in vitro activity against P. aeruginosa, with 4 pg/ml typically inhibiting more than 90 percent of strains [5,6]. We report a medical cure of combined left- and right-sided P. aerugin-
83
RACIAL KINASE
DIFFERENCES LEVELS
IN SERUM
TABLE
CREATINE
To the Editor: In discussing their finding of statistically significant interracial differences in serum creatine kinase activity, Dr. Black and colleagues (Am J Med 1986; 81: 479-487) suggested that the higher levels in blacks compared with those in whites could be due to a differential effect of physical activity. We were intrigued by this suggestion, as we found the variable of physical activity to be the major factor responsible for the higher levels of creatine kinase activity in black compared with white South African men. (A detailed account of this work is shortly to be submitted for publication.) We measured creatine kinase activity in 54 black men, 111 black women, 88 white men, and 67 white women. All were healthy volunteers. Blood sampling was performed before 8:30 A.M., at which time subjects were also questioned whether they did (exercisers) or did not (non-exercisers) undertake regular recreational activity. The exercisers were further subdivided into those who had exercised within the previous 72 hours and those who had not. Statistical comparisons were performed using the Mann-Whitney U test or the Kruskal-Wallis test. Descriptive statistics of creatine kinase activity for each race-gender group are shown in Table 1. Levels for black men were significantly higher than for white men when comparing groups (p
I
Descriptive Statistics of Creatine Kinase Activity for Each Race-Gender Group CreatineKinase Activity (IUlliler)
Race-Gender Group
Mean Age (years)
Black men (n = 54) White men (n = 88) Black women (n = 111) White women (n = 67)
27
71-3,170
386 f
494
216
23
42-6,685
243 f
701
142
22
99
21
100
Range
Mean f SD
38 f 97 50 f
93
Median
111 67
this seems unlikely. Potentially more plausible as an underlying explanation is the influence of genetic factors [l], since there is evidence that interindlvidual variation in creatine kinase activity is under some degree of genetic control [lo]; and Meltzer and Holy [2] reported a consistent trend towards an increase in serum levels with increasing skin pigmentation. A study comparing creatine kinase activity in black men and white men in response to exercise of the same intensity and duration should resolve the question whether differences in physical activity per se, or the influence of genetic factors on its effects, was responsible for the interracial variation we observed. Our finding of no significant interracial difference in creatine kinase activity in women demands additional comment, as it contrasts with the higher levels in black women reported by Dr. Black and colleagues and investigators in previous studies [l-5]. Although no reason for this discrepancy readily suggests itself, we should stress that our study involved an African population, whereas other reports have originated from North America or North America and Europe. It is also of interest that only 23 percent of black women were exercisers compared with 76 percent of white women. The degree to which such a notable difference in recreational activity is pertinent to the matter in hand is a moot point, since reasoning that indeed it is necessitates assuming physical activity was responsible for the interracial variation in creatine kinase activity among women in the other studies, and this cannot be ascertained from the available data. It is therefore not possible to develop this argument further. RICHARD
F. GLEDHILL,
M.D.
MARIA M. VAN NIEKERK, M.Med. (Path.) University of Pretoria South Africa CAREL A. VAN DER MERWE, D. Comm. Institute for Biostatistics Medical Research Council South Africa 1.
August 1987
Meltzer HY: Factors affecting serum creatine phosphokinase levels in the general population; the role of race, activity and age. Clin Chim Acta 1971; 33: 165-172.
The American Journal of Medicine
Volume 83
385
LETTERS
2.
3.
4.
5. 6.
7. 8.
9.
10.
TO THE EDITOR
Meltzer HY, Holy PA: Black-white differences in serum creatine phosphokinase (CPK) activity. Clin Chim Acta 1974; 54: 215224. Van Steirteghem AC, Robertson EA, Zweig MH: Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay. Clin Chim Acta 1979; 93: 25-28. Wong ET, Cobb C, Umehara MK, et al: Heterogeneity of serum creatine kinase activity among racial and gender groups of the population. Am J Clin Pathol 1983; 79: 582-586. Miller WG, Gruemer HD, Chinchilli VM: Upper reference limit for creatine kinase. Clin Chem 1985; 31: 158. Newham DJ, Jones DA, Edwards RHT: Large plasma creatine kinase changes after stepping exercise. Muscle Nerve 1983; 6: 380-385. Hunter JB, Critz JB: Effect of training on plasma enzyme levels in man. J Appl Physiol 1971; 31: 20-23. Berg A, Haralambie G: Changes in serum kinase and hexose phosphate isomerase activity with exercise duration. Eur J Appl Physiol 1978; 39: 191-201. Roti S, lori E, Guiducci U, et al: Serum concentrations of myoglobin, creatine phosphokinase and lactic dyhydrogenase after exercise in trained and untrained athletes. J Sports Med 1981; 21: 113-118. Meltzer HY, Dorus E, Grunhaus L, Davis JM, Belmaker R: Genetic control of human plasma creatine phosphokinase activity. Clin Genet 1978; 13: 321-326. Submitted
February
17, 1987, and accepted
May 7, 1987
The Reply: Gledhill et al’s findings are very interesting, and I cannot quarrel with their conclusion that exercise, even 72 hours prior to measurement as described, may have explained the changes noted. We, too, think that is a possibility, and as mentioned, we excluded those who had undergone strenuous exercise in the preceding 12 hours. I agree with Dr. Gledhill and colleagues that a more formal study of the influence of exercise is required, and I welcome the results of such an investigation. HENRY
R. BLACK,
JOEL
1.
2.
2.
366
August
1987
The American
Journal
of Medicine
Volume
23, 1987, and accepted
the quest 1971; 127: hospital: a J Psychia-
May 7, 1987
BUSH,
M.D.
Beth Israel Hospital 330 Brookline Avenue Boston, Massachusetts 022 15
THE
To the Editor: In their study on the CAGE questionnaire, Bush et al (Am J Med 1987; 82: 23 l-235) utilized the score achieved on the Michigan Alcoholism Screening Test (MAST) [ 11 as part of their “gold standard” of diagnosis for alcohol dependence and abuse. The MAST is itself a 25item screening test that includes in a more explicit fashion the four questions on the CAGE. Therefore, it would not be surprising that patients responding affirmatively on the CAGE questionnaire would also score two or more points on the MAST. The MAST, like the CAGE questionnaire, has not been extensively re-validated in a wide spectrum of patients [2], and so it too may be insensitive for the detection of patients in the early stages of alcoholism.
March
BOOKER
M.D.
I.
USING
M.D.
The Reply: Dr. Freiman correctly notes that the CAGE questionnaire consists of the four most sensitive questions in the Michigan Alcoholism Screening Test [ 11. In our diagnostic criteria, a person had to have a MAST score of 6 or more to be considered alcoholic. Each CAGE question counts for only one point. The designation of alcohol abuse required a MAST score of 3 or more plus a consumption of four to five drinks a day (for a 70 kg man). A MAST score of 2 was only positive for alcohol abuse if the person also drank in excess of nine drinks per day. However, I agree with Dr. Freiman’s comment on the fact that the MAST questionnaire has not been re-validated in many populations. We have found a very different test behavior for the CAGE questionnaire in young women seeking gynecologic care [2]. We agree that more validation studies are in order. The CAGE questionnaire, however, still appears to be more sensitive than the alcohol consumption history or laboratory screening tests, and therefore should find a place in the health care provider’s screening examination of patients.
School of Medicine 333 Cedar Street New Haven, Connecticut 065 lo-6056
ABUSE
Seizer ML: The Michigan Alcoholism Screening Test: for a new diagnostic instrument. Am J Psychiatry 1659-1663. Moore RA: The diagnosis of alcoholism in a psychiatric trial of the Michigan Alcoholism Screening Test. Am try 1972; 128: 1566-1569. Submitted
Yale University
SCREENING FOR ALCOHOL CAGE QUESTIONNAIRE
FREIMAN,
Ben Taub General Hospital 1502TaubLoop Houston, Texas 77030
Mayfield D, McLeod G, Hall P: The CAGE questionnaire: validation of a new alcoholism instrument. Am J Psychiatry 1974; 131: 1121-l 123. Halliday A, Bush B, et al: Alcohol abuse in women seeking gynecologic care. Obstet Gynecol 1983; 68: 322-326.
SUCCESSFUL THERAPY OF PSEUDOMONAS AERUGINOSA ENDOCARDllIS WITH CEFTAZIDIME AND TOBRAMYCIN To the Editor: Endocarditis due to Pseudomonas aeruginosa is a difficult therapeutic problem [i-3]. Combined medical and surgical therapy often is required to improve chances for cure, especially when left-sided valves are involved [ 1,4]. Ceftazidime is a new cephalosporin with excellent in vitro activity against P. aeruginosa, with 4 pg/ml typically inhibiting more than 90 percent of strains [5,6]. We report a medical cure of combined left- and right-sided P. aerugin-
83