184
JOURNAL OF ATHEROSCLEROSIS RESEARCH
S E R U M G L U C O P R O T E I N S IN MEN W I T H M Y O C A R D I A L I N F A R C T I O N L A R S - E R I K B O T T I G E R ANO L A R S A. CARLSON
Departments of 3led~cine, Karoli*~ska Instttz#et, at Serafimerlasarettet (Director" G. BIORCK, M.D.) and at Karolznska Siukhuset (Director. H. LAGERLOF, M.D.) and K i n g Gustaf V's Research I*~stztute (Director: G. BIRKE, M.D.), Stockholm (Sweden) (Received March 9th, 1961)
INTRODUCTION
The hypothesis t h a t changes of the ground substance of the intima might contribute to the development of atherosclerosis has led to studies of the mucopolysaccharide content of the arterial wall (for a recent review see ref. 1). This has also led to studies of the serum glucoproteins and their relationship to vascular disease, mainly atherosclerosis and diabetic angiopathy. In atherosclerosis several authors have found increased levels of the serum glucoproteins, including hexoses2, ~, hexosamines 2-4, and mucoprotein 4. In patients with diabetes mellitus an elevation of the glucoproteins has repeatedly been demonstrated, especially in the presence of vascular disease 5-8. In most of these studies, however, especially those related to atherosclerosis, the definition of the type and extent of the atherosclerotic processes has been inadequate. F u r t h e r m o r e the presence or absence of complicating diseases has not been dealt with in detail. In the present study the serum concentrations of hexoses, hexosamines and sialic acids have been determined in 47 men with previous myocardial infarction and without clinical signs of complicating disease. The d a t a have been compared with those of normal men. In addition the same determinations were carried out in 13 men with previous myocardial infarction and a significantly elevated erythrocyte sedimentation rate (E.S.R.). MATERIAL AND METHODS
The material was taken from the D e p a r t m e n t s of Medicine, Karolinska Sjukhuset and the Central Hospital, Danderyd. All men under the age of 65, registered under the diagnosis of coronary heart disease and without a n y other m a j o r disease, were personally examined b y the authors. Only men with definite evidence of a previous myocardial infarction (typical clinical history and characteristic ECG-findings) were included. No patient was included earlier t h a n at least 6 m o n t h s after the last infarction. Persons with heart decompensation, arterial hypertension, diabetes mellitus and/or signs of other m a j o r diseases were excluded. The upper limit for normal E.S.R. (WESTERGREN method) was fixed at 10 m m / h for subjects below 50 and at J. ,4theroscler. Res., 1 (1961) 184-188
185
SERUM GLUCOPROTEINS AFTER INFARCT
20 m m / h f o r t h o s e a b o v e 50. A c c o r d i n g t o t h e s e c r i t e r i a 60 m e n w e r e s e l e c t e d , 4 6 q 3 5 y e a r s old, o f w h o m 47 h a d a n o r m a l E . S . R . a n d 13 h a d e l e v a t e d v a l u e s . T h e m a t e r i a l h a s b e e n d e s c r i b e d i n d e t a i l p r e v i o u s l y 9. Blood samples were drawn
in t h e m o r n i n g a f t e r a n o v e r n i g h t fast. A n a l y s e s of
p r o t e i n - b o u n d c a r b o h y d r a t e s w e r e c a r r i e d o u t as d e s c r i b e d p r e v i o u s l y 1°. P r o t e i n w a s determined by a micro-biuret procedure, hexoses with anthrone reagent, hexosamines b y t h e ELSON-MORGAN p r o c e d u r e ~ m d sialic a c i d s b y t h e r e s o r c i n o l - C u r e a g e n t o f SVENNERHOLM. RESULTS
The results of the analyses of the various protein-bound carbohydrates are given in Table I. The patients with normal E.S.R. had normal values for hexoses, hexosamines TABLE I SERUM PROTEIN-BOUND CARBOHYDRATES IN MEN WITH PREVIOUS MYOCARDIALINFARCTION mg/100 ml. Mean value ± standard error of the mean. n
Normal men, 46-65 years lo 43 Men with previous myocardial infarction with normal E . S . R . , 46-65 years 47 p* Men with previous myocardial infarction with elevated E.S.R., 41-65 years 13 p*
Total prolezn
Hexoses
Hexosamines
Szahc acids
7.17 ± 0.06
113 ± 1.8
97 ~ 1.3
69 ± 1.0
6.95 ± 0.06 0.05 > P > 0 . 0 1
109 ~ 2.2 >0.05
96 4- 1.3 >0.05
70 q- 1.0 >0.05
7.17 :k 0.11 >0.05
136 4- 3.6 <0.001
112 4- 2.8 <0.001
75 ± 2.1 0.001 < P < 0.01
* Significance of the difference from the normal values (t-test).
and sialic acids, whereas those with elevated E.S.R. showed significant increases above the normal levels of these compounds. The individual values for total protein-bound carbohydrate content in serum (hexoses plus hexosamines plus sialic acids) are given in Fig. 1. In one patient with normal E.S.R. this value fell above the upper normal limit (~ + 2s) of values for normal men of corresponding age 10. In the other group, six of the thirteen patients were found to have values a b o v e this limit. I t should be mentioned t h a t in normal men neither hexoses nor hexosamines varied with age 10. Sialic acids on the other hand increased slightly with age (approx. 1 mg/ 100 ml in 10 years), but the increase was so small that no corrections were considered necessary in this investigation. The myocardial-infarction patients did not show a n y significant changes of the protein-bound carbohydrates with age. DISCUSSION
In contrast to previous studies of the protein-bound carbohydrate content of serum J. Atheroscler. Res., 1 (1961) 184-188
186
L.-E. BOTTIGER, L. A. CARLSON
in patients with arteriosclerosis and in patients with diabetes mellitus with vascular complications we have not been able to d e m o n s t r a t e a n y increase of the hexoses, hexosamines and sialic acids in patients with coronary heart disease without elevated E.S.R. The previous findings in patients with diabetes mellitus and vascular disease are difficult to compare with our investigation, p a r t l y because the vascular disease in diabetes comprises not only atherosclerosis but also the perhaps more specific diabetic angiopathy, partly because of the influence of the frequently encountered complicating conditions with effect on serum-protein p a t t e r n and E.S.R. I t has been shown 5 mg/100
z,O0~
35O
mt
Normal
E(evoted
E S.R.
E S.R.
x
X+2s x x x
300-
×
o
×
o
xX x x x
o
x x
x
x
250.
x x
x
x
x
£-2s x 200"
Fig. 1. I n d i v i d u a l v a l u e s for t o t a l p r o t e i n - b o u n d c a r b o h y d r a t e c o n t e n t of s e r u m ( h e x o s e s + h e x o s a m i n e s + sialic acids) in p a t i e n t s w i t h p r e v i o u s m y o c a r d i a l i n f a r c t i o n a n d n o r m a l E . S . R . ( x ) a n d w i t h e l e v a t e d E . S . R . ((2)). T h e m e a n v a l u e (5) a n d t h e n o r m a l l i m i t s (~-±2 s) for n o r m a l m e n 10 of c o r r e s p o n d i n g a g e a r e i n d i c a t e d in t h e figure.
t h a t diabetics with hyaline vascular changes h a d higher protein-bound hexoses than diabetics without such changes. W i t h regard to previous studies in patients with arteriosclerosis, two things need comment. Firstly, the patients studied b y us h a d all suffered from a definite myocardial infarction, an occurrence which in more t h a n 90 % of cases is due to coronary atherosclerosis. This type of arterial disease differs from other types of arteriosclerosis as e.g. the calcification of-the media of the large arteries (MoNCKEBERG'Sdisease). In some previous studies, the arteriosclerotic process has not been a d e q u a t e l y described and it is difficult to judge if only cases with atherosclerosis were included in the materials studied. Secondly, in previous materials no clinical descriptions were given of the general condition of the patients with regard to complications a n d other diseases present, which in themselves might give rise to an increase of the proteinbound carbohydrates. This point is illustrated in our s t u d y b y the finding of signifiJ. Atheroscler. Res., 1 (1961) 184-188
SERUM GLUCOPROTEINS AFTER INFARCT
187
cantly elevated serum-glucoprotein values in the special group of thirteen p a t i e n t s which had an elevated E.S.R. It should be stressed that this group had suffered from a previous myocardial infarction, but had no other findings in the e x a m i n a t i o n pointing to a n y complicating disease except the elevated E.S.R. I t seems reasonable to ascribe the increase of the protein-bound carbohydrates in this group of p a t i e n t s to the condition which had caused the elevation of the E.S.R. and not to the arterial disease, the atherosclerosis, per se. In this connection it is also worth while to consider the occurrence of silent minor thrombosis in patients with arteriosclerosis. In a s t u d y 11 of elevated E.S.R. a n u m b e r of patients were found in whom the only diagnosis was arteriosclerosis. ACKNOWLEDGEMENT
This investigation has been supported b y a grant from the Swedish National Association against H e a r t and Chest Diseases. SUMMARY
Serum protein-bound carbohydrates (hexoses, hexosamines and sialic acids) h a v e been analysed in 60 men with previous myocardial infarction. In the 47 patients with normal erythrocyte sedimentation rate (E.S.R.) the m e a n values did not differ from those of normal men and the total carbohydrate content was increased above the 95 % normal limit in only one case. In those with elevated E.S.R. the mean values of all three carbohydrates, and therefore also the total c a r b o h y d r a t e contents, were significantly elevated a b o v e the normal limit in 6 out of 13 patients. I t is concluded t h a t atherosclerosis per se is not accompanied b y any rise in serum protein-bound carbohydrates. The possibility t h a t complications of vascular disease as well as other t y p e s of arteriosclerosis might give rise to elevation of the proteinbound carbohydrates is discussed. R~SUM~ Les hydrates de carbone li6s aux prot~ines du s6rum sanguin (hexoses, hexosamines et acide sialique) ont 6t6 analys6s chez 60 hommes atteints d'infarctus myocardique. Chez les 47 patients qui avaient une vitesse de s6dimentation normale, les valeurs moyennes trouv6es ne sont pas diff~rentes de celles observ6es chez l'homme normal, et la quantit6 totale d ' h y d r a t e s de carbone n'6tait sup6rieure aux limites de la normale que dans un seul cas. Chez les 13 patients qui avaient une vitesse de s6dimentation augment6e, les valeurs moyennes trouv6es pour chacun des trois hydrates de carbone, et en cons6quence la valeur trouv6e pour la totalit6 des hydrates de carbone, 6talent significativement sup6rieures ~ la limite normale dans six cas. En conclusion, l'athdroscl6rose en elle-m~me ne s'accompagne pas d'une a u g m e n tation des hydrates de carbone li6s aux prot~ines. L'hypoth~se que des complications J. Atheroscler. Res., 1 (1961) 184-188
188
L.-E. BOTTIGER, L. A. CARLSON
de la maladie vasculaire ou des autres types d'art6rioscl6rose puissent d~terminer une 616vation des hydrates de carbone li6s aux prot6ines est discut6e. ZUSAMMENFASSUNG
Bei 60 M~innern, die einen Myocardinfarkt durchgemacht hatten, wurden die proteingebundenen Kohlenhydrate (Hexosen, Hexosamine, Sialins/iuren) des Serums untersucht. Bei den 47 Patienten, die eine normale Blutk6rperchensenkungsgeschwindigkeit hatten, unterschieden sich die Mittelwerte nicht gegentiber gesunden Kontrollpersonen. Der Gesamtkohlenhydratgehalt war tiber den 95 % Bereich der Normalen nur in einem einzigen Falle gesteigert. Bei den Patienten mit erh6hter Blutk6rperchensenkungsgeschwindigkeit waren die Mittelwerte aller drei Kohlenhydrate und dementsprechend auch der Gesamtkohlenhydratgehalt in 6 yon 13 F~illen signifikant tiber den Normalbereich erh6ht. Es wird der Schluss gezogen, dass eine Atherosklerose per se nicht yon einem Anstieg der proteingebundenen Kohlenhydrate begleitet ist, Die M6glichkeit, dass Komplikationen der Gef/isserkrankung oder auch andere Typen von Arteriosklerose Anlass zu der Erh6hung der proteingebundenen Kohlenhydrate geben k6nnen, wird er6rtert. REFERENCES 1 j . E. KIRK, in The Arterial Wall, A. I. LANSING, ed., W i l l i a m s a n d Wilkins Co., Baltimore, 1959, p. 161. 2 K. D. VOIGT AND E. GADERMANN, Chn. Chzm. Acta, 1 (1956) 364. 3 H. C. MOLLER-SPREER, U. WEI~BER AND K. D. VOIGT, K h n . Wschr., 38 (1960) 28. 4 C. J. SCHWARTZ AND H. R. GILMORE, Circulation, 18 (1958) 191. 5 N. T6RNBLOM AND K. NORDSTR6M, Acta Endocrinol., 17 (1954) 426. 6 p. EJARQUE, A. MARBLE AND E. F. TULLER, A m . J. Ned., 27 (1959) 221. 7 ]D. INTROZZI, C. BERNASSONI AND L. BUSCARINI, Acta N e d . Scan&, 160 (1958) 1. 8 H. BEGSTERMANN, Ergeb. inn. Ned. Kinderheilk., 7 (1957) 1. 9 L. A. CARLSON, Acta N e d . Scan&, 167 (1960) 399. 10 L.-E. B6TTIGER AND L. A. CARLSON, Clin. Ch,m. Acta, 5 (1960) 664. 11 ~k. LILJESTRAND AND B. OLHAGEN, Acta Ned. Scan&, 151 (1955) 425.
J. Atheroscler. Res., 1 (1960) 184-188