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Serum creatine kinase in obese subjects before and during weight reduction
Clinica Chimica Acta, 133 (1983) 285-288 Elsevier
285
CCA 02638
Serum creatine kinase in obese subjects before and during weight reduction Flemming Obesity Unit, Department
Larsen
and Stephan
ofInternal Medicine, (Received
January
Rossner
*
Karolrnska Hospital, S- 104 01 Stockholm
(Sweden)
24th; revision May 30th, 1983)
Summary Obese subjects are at increased risk for cardiovascular disease manifestations. The CK value is an important aid in the diagnosis of myocardial infarction, but may also be increased by factors such as muscle mass or breakdown of muscle tissue. We analysed CK values in 120 obese patients in our Obesity Unit and also monitored CK values during a weight reduction programme in 26 of these patients. CK values did not increase with body weight, and during weight loss in a diet programme no systematic CK changes were observed. We conclude that in the evaluation of an elevated CK value in a coronary care unit, such an increased value cannot be accounted for by the overweight per se.
Introduction Serum creatine kinase (CK) has been considered to be the most reliable single enzyme reflecting myocardial damage and has therefore been extensively used for the routine diagnosis of acute myocardial infarction during recent years. The CK values may be affected by several factors. Physiological factors include large muscle mass, sex (males have higher values than females), day variation (higher values during day than during night) and higher values in ambulant patients compared to patients in hospital beds [l-3]. These factors illustrate that the CK levels under normal circumstances reflect skeletal muscle activity. High physical activity, trauma of skeletal muscle such as intramuscular injections and surgical procedures may also lead to increased plasma concentrations of CK [ 1,2]. Furthermore conditions such as hypothyroidism, degenerative muscle diseases and alcohol overconsumption may increase CK levels (for review see Nevins et al 1973, [4]). Obese patients are at increased risk for atherosclerotic manifestations. It is a
* Correspondence
0009-8981/83/$03.00
and proofs:
Stephan
Riissner.
0 1983 Elsevier Science Publishers
B.V.
286
common clinical situation that overweight patients with chest pains are referred to the coronary care unit for subsequent evaluation of a possible myocardial infarction. Such a diagnosis of myocardial infarction will be based on the history, the ECG changes and the serum enzyme pattern. Since no reference data for upper CK values with increasing body weight are available, there is often an uncertainty regarding the interpretation of elevated CK values in obese patients. The recent introduction of CK-MB analysis has increased the diagnostic armamentarium, but this test and other iso-enzyme assays are not available in many hospitals and certainly not around the clock. Therefore total CK will often have to suffice as an enzymatic screening procedure, the repeated sampling of which in most cases is sufficient for establishing the diagnosis of acute myocardial infarction [5]. The increase in muscle mass, associated with overweight, could theoretically lead to higher CK values in obese subjects [6]. Experimental studies have shown the distribution space of CK to be almost equal to the plasma volume [7], but plasma volume in obesity is not simply related to body weight, because the proportions of fat and muscle may vary considerably [6]. Furthermore the degree of vascularisation of adipose tissue may differ [7]. We therefore decided to analyse the influence of overweight on CK values. Since some skeletal muscle tissue is lost during the catabolism associated with a weight reduction programme [8], we also determined CK-values repeatedly during such a programme. Patients, result and comments Creatine kinase concentrations were determined spectrophotometrically by the methods recommended by Scandinavian Committee on Enzymes [9]. The reference interval limits used in our laboratory were for women 0.6-2.4 pkat/l and for men 0.6-2.9 p kat/l. The grossly overweight patients had all been referred to the Obesity Unit at the Karolinska Hospital for screening. Clinical data are summarised in Table I. Factors which could affect CK values such as hypothyroidism, alcoholism or recent intramuscular injections, muscular damage and severe exercise were excluded by concomitant analyses of TSH, serum aminotransferases and by detailed interviews. The median CK value for women was 1.6 pkat/l with a range from 0.5 to 11 .O p kat/l. For men the corresponding figures were 1.9 (0.5-5.7) p kat/l. The individual values are shown in Fig. 1. There was no trend for increasing values with increasing body weight.
TABLE
I
Clinical
characteristics
of the obese subjects, Sex
Outpatients at screening
F M
n
78 42
mean values and ranges
Age (years)
Body weight (kg)
Height (cm)
(range)
(range)
(range)
42 (16-67) 43 (18-67)
109 (73-160) 129 (67- 185)
167 (154-182) 181 (156-201)
287 CK pkat/l
po
A
7.0. 6.0. 5.04.0-
+
*
+
+
+
+
0
+
3.0.____*_______“__,___----__f__0-,-__. __________--_____+__+~,______--_-. 00 +0 +8 + OF ++ 1.0. +%, ““+z 0 ““s 0 00
2.0-
1:r
112 113 114
1:5
UPPer value
*
_--_____L______________-;-____z.s ________~____~_~_____________*,‘
00
(1
00
+
0”
+ “4 +_” L , o Cloe~o
1:6
117
1:s
00 0 +t: +
00
o” :
1:9
2:cl
2:1
212 2.3
BROCA INDEX kg/(cm-100)
Fig. 1. Creatine kinase concentrations in subjects with a wide range of obesity, kg/(cm - 100). Upper reference values for females and men are shown.
expressed
as Broca index,
Patient no CK change during weight loss +1.0
ACK
0
5
10
15
20
0.0 pkat/l
E -1.0
25
Weight loss
Fig. 2. Individual Obesity Unit.
weekly CK changes
in 26 patients
during
weight loss in a day-care
programme
of the
288
The reference interval limits used by the Karolinska Hospital laboratory are continuously updated and based on data from several hundreds of healthy subjects, but may be low, since 12 out of 42 obese males were found above the upper limit. In the report by Gerhardt and Waldenstrom, who used the same ‘Scandinavian CK method’, the upper limit given was 4.5 pkat/l for men (based on data from 109 males) and 2.5 pkat/l for women (127 females studied) [ 111. However, irrespective of the values used to define the upper limit, there was no trend for increasing CK values with increase in body weight in our study. We further analysed the effects of weight loss in 26 patients (8 males) out of the 120 who were subsequently referred to a day-care ward for a weight reduction programme (600 kcal for 6 weeks). CK values were determined weekly during a period when the mean weekly weight loss was about 2 kg. The mean weight reduction was 11 kg (range 5-35 kg). In this group the median value in females was 1.8 (0.7-4.6) pkat/l and in males 2.0 (0.4-5.8) pkat/l. No systematic CK changes were found with time during the weight reduction (Fig. 2). We conclude that obese subjects have CK-values which do not systematically differ from values obtained from reference groups. In the evaluation of an elevated CK value in the coronary care unit this cannot be accounted for by the overweight per se. References Garcia W. Elevated creatine phosphokinase levels associated with large muscle mass. J Am Med Assoc 1974; 228: 1395-1396. 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. Scott BB, Simmons AV, Newton KE, Payne RB. Interpretation of serum creatine kinase in suspected myocardial infarction. Br Med J 1974; 4: 691-693. Nevins M et al. Pitfalls in interpreting serum creatine phosphokinase activity. J Am Med Assoc 1973; 224: 1382- 1387. Ryan W, Karliner JS, Gilpin EA, Cove11 JW, DeLuca M, Ross Jr J. The creatine kinase curve area and peak creatine kinase after acute myocardial infarction: usefulness and limitations. Am Heart J 1981; 101: 1622168. Bray GA. Body composition in obesity. In: The obese patient. WB Saunders Comp.: Philadelphia. London, Toronto, 1976: 26-27. Grande P, Hansen BF, Christiansen C, Naestoft J. Estimation of acute myocardial infarct size in man by serum CK-MB measurements. Circulation 1982; 65: 756-764. Marliss EB. Protein diets for obesity: metabolic and clinical aspects. Can Med Assoc J 1978; 119: 1413-1421. The Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology. Recommended method for the determination of creatine kinase in blood modified by the inclusion of EDTA. Stand J Clin Lab Invest 1979; 39: 1-5. IO Cederquist DC, Brewer WD, Beegle RM, Wagoner AN, Dunsing D, Ohlson MA. Weight reduction on low-fat and low-carbohydrate diets. 1. Clinical results and energy metabolism. J Am Diet Assoc 1952; 28: 113-l 16. I I Gerhardt W, Waldenstrom J. Creatine kinase B-subunit activity in serum after immunoinhibition of M-subunit activity. Clin Chem 1979; 25/7: 1274-1280.
285
CCA 02638
Serum creatine kinase in obese subjects before and during weight reduction Flemming Obesity Unit, Department
Larsen
and Stephan
ofInternal Medicine, (Received
January
Rossner
*
Karolrnska Hospital, S- 104 01 Stockholm
(Sweden)
24th; revision May 30th, 1983)
Summary Obese subjects are at increased risk for cardiovascular disease manifestations. The CK value is an important aid in the diagnosis of myocardial infarction, but may also be increased by factors such as muscle mass or breakdown of muscle tissue. We analysed CK values in 120 obese patients in our Obesity Unit and also monitored CK values during a weight reduction programme in 26 of these patients. CK values did not increase with body weight, and during weight loss in a diet programme no systematic CK changes were observed. We conclude that in the evaluation of an elevated CK value in a coronary care unit, such an increased value cannot be accounted for by the overweight per se.
Introduction Serum creatine kinase (CK) has been considered to be the most reliable single enzyme reflecting myocardial damage and has therefore been extensively used for the routine diagnosis of acute myocardial infarction during recent years. The CK values may be affected by several factors. Physiological factors include large muscle mass, sex (males have higher values than females), day variation (higher values during day than during night) and higher values in ambulant patients compared to patients in hospital beds [l-3]. These factors illustrate that the CK levels under normal circumstances reflect skeletal muscle activity. High physical activity, trauma of skeletal muscle such as intramuscular injections and surgical procedures may also lead to increased plasma concentrations of CK [ 1,2]. Furthermore conditions such as hypothyroidism, degenerative muscle diseases and alcohol overconsumption may increase CK levels (for review see Nevins et al 1973, [4]). Obese patients are at increased risk for atherosclerotic manifestations. It is a
* Correspondence
0009-8981/83/$03.00
and proofs:
Stephan
Riissner.
0 1983 Elsevier Science Publishers
B.V.
286
common clinical situation that overweight patients with chest pains are referred to the coronary care unit for subsequent evaluation of a possible myocardial infarction. Such a diagnosis of myocardial infarction will be based on the history, the ECG changes and the serum enzyme pattern. Since no reference data for upper CK values with increasing body weight are available, there is often an uncertainty regarding the interpretation of elevated CK values in obese patients. The recent introduction of CK-MB analysis has increased the diagnostic armamentarium, but this test and other iso-enzyme assays are not available in many hospitals and certainly not around the clock. Therefore total CK will often have to suffice as an enzymatic screening procedure, the repeated sampling of which in most cases is sufficient for establishing the diagnosis of acute myocardial infarction [5]. The increase in muscle mass, associated with overweight, could theoretically lead to higher CK values in obese subjects [6]. Experimental studies have shown the distribution space of CK to be almost equal to the plasma volume [7], but plasma volume in obesity is not simply related to body weight, because the proportions of fat and muscle may vary considerably [6]. Furthermore the degree of vascularisation of adipose tissue may differ [7]. We therefore decided to analyse the influence of overweight on CK values. Since some skeletal muscle tissue is lost during the catabolism associated with a weight reduction programme [8], we also determined CK-values repeatedly during such a programme. Patients, result and comments Creatine kinase concentrations were determined spectrophotometrically by the methods recommended by Scandinavian Committee on Enzymes [9]. The reference interval limits used in our laboratory were for women 0.6-2.4 pkat/l and for men 0.6-2.9 p kat/l. The grossly overweight patients had all been referred to the Obesity Unit at the Karolinska Hospital for screening. Clinical data are summarised in Table I. Factors which could affect CK values such as hypothyroidism, alcoholism or recent intramuscular injections, muscular damage and severe exercise were excluded by concomitant analyses of TSH, serum aminotransferases and by detailed interviews. The median CK value for women was 1.6 pkat/l with a range from 0.5 to 11 .O p kat/l. For men the corresponding figures were 1.9 (0.5-5.7) p kat/l. The individual values are shown in Fig. 1. There was no trend for increasing values with increasing body weight.
TABLE
I
Clinical
characteristics
of the obese subjects, Sex
Outpatients at screening
F M
n
78 42
mean values and ranges
Age (years)
Body weight (kg)
Height (cm)
(range)
(range)
(range)
42 (16-67) 43 (18-67)
109 (73-160) 129 (67- 185)
167 (154-182) 181 (156-201)
287 CK pkat/l
po
A
7.0. 6.0. 5.04.0-
+
*
+
+
+
+
0
+
3.0.____*_______“__,___----__f__0-,-__. __________--_____+__+~,______--_-. 00 +0 +8 + OF ++ 1.0. +%, ““+z 0 ““s 0 00
2.0-
1:r
112 113 114
1:5
UPPer value
*
_--_____L______________-;-____z.s ________~____~_~_____________*,‘
00
(1
00
+
0”
+ “4 +_” L , o Cloe~o
1:6
117
1:s
00 0 +t: +
00
o” :
1:9
2:cl
2:1
212 2.3
BROCA INDEX kg/(cm-100)
Fig. 1. Creatine kinase concentrations in subjects with a wide range of obesity, kg/(cm - 100). Upper reference values for females and men are shown.
expressed
as Broca index,
Patient no CK change during weight loss +1.0
ACK
0
5
10
15
20
0.0 pkat/l
E -1.0
25
Weight loss
Fig. 2. Individual Obesity Unit.
weekly CK changes
in 26 patients
during
weight loss in a day-care
programme
of the
288
The reference interval limits used by the Karolinska Hospital laboratory are continuously updated and based on data from several hundreds of healthy subjects, but may be low, since 12 out of 42 obese males were found above the upper limit. In the report by Gerhardt and Waldenstrom, who used the same ‘Scandinavian CK method’, the upper limit given was 4.5 pkat/l for men (based on data from 109 males) and 2.5 pkat/l for women (127 females studied) [ 111. However, irrespective of the values used to define the upper limit, there was no trend for increasing CK values with increase in body weight in our study. We further analysed the effects of weight loss in 26 patients (8 males) out of the 120 who were subsequently referred to a day-care ward for a weight reduction programme (600 kcal for 6 weeks). CK values were determined weekly during a period when the mean weekly weight loss was about 2 kg. The mean weight reduction was 11 kg (range 5-35 kg). In this group the median value in females was 1.8 (0.7-4.6) pkat/l and in males 2.0 (0.4-5.8) pkat/l. No systematic CK changes were found with time during the weight reduction (Fig. 2). We conclude that obese subjects have CK-values which do not systematically differ from values obtained from reference groups. In the evaluation of an elevated CK value in the coronary care unit this cannot be accounted for by the overweight per se. References Garcia W. Elevated creatine phosphokinase levels associated with large muscle mass. J Am Med Assoc 1974; 228: 1395-1396. 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. Scott BB, Simmons AV, Newton KE, Payne RB. Interpretation of serum creatine kinase in suspected myocardial infarction. Br Med J 1974; 4: 691-693. Nevins M et al. Pitfalls in interpreting serum creatine phosphokinase activity. J Am Med Assoc 1973; 224: 1382- 1387. Ryan W, Karliner JS, Gilpin EA, Cove11 JW, DeLuca M, Ross Jr J. The creatine kinase curve area and peak creatine kinase after acute myocardial infarction: usefulness and limitations. Am Heart J 1981; 101: 1622168. Bray GA. Body composition in obesity. In: The obese patient. WB Saunders Comp.: Philadelphia. London, Toronto, 1976: 26-27. Grande P, Hansen BF, Christiansen C, Naestoft J. Estimation of acute myocardial infarct size in man by serum CK-MB measurements. Circulation 1982; 65: 756-764. Marliss EB. Protein diets for obesity: metabolic and clinical aspects. Can Med Assoc J 1978; 119: 1413-1421. The Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology. Recommended method for the determination of creatine kinase in blood modified by the inclusion of EDTA. Stand J Clin Lab Invest 1979; 39: 1-5. IO Cederquist DC, Brewer WD, Beegle RM, Wagoner AN, Dunsing D, Ohlson MA. Weight reduction on low-fat and low-carbohydrate diets. 1. Clinical results and energy metabolism. J Am Diet Assoc 1952; 28: 113-l 16. I I Gerhardt W, Waldenstrom J. Creatine kinase B-subunit activity in serum after immunoinhibition of M-subunit activity. Clin Chem 1979; 25/7: 1274-1280.