Vitamin D and Ischaemic Heart Disease
Rosengren, E.: Histamine metabolism in the pregnant and non-pregnant hamster. Proc. Soc. Exp. Biol. Med. 118: 884-888 (1965) Scatchard, G.: The attraction of proteins far small molecules
553
and ions. Ann. N. Y. Acad. Sd. 51: 660 665 (! 949) Verma. u.. K.R. Laumas: In vitro binding 01' progestcronc to receptars in the human endometrium and myometrium. Biochem. Biophys. Acta 317: 403 41 q (1973)
Requests for reprints should be addressed to: Professor Dr. F. Stutinsky, Laboratoire de Physiologie generale, 21 Rue Descartes, F 67000 Strasbourg (France) Horm. Metab. Res. 10 (1978) 553-556
Vitamin D and Ischaemic Heart Disease B. Lund, J. Badskjaer, Bj. Lund, O.H. Soerensen
Summary Vitamin 0 has been proposed as a risk factor of ischaemic heart disease. In 12 patients with acute myocardial infarction the major circulating vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), did not show any fluctuations during the first 4 days after onset of symptoms. The serum 25-HCC level was then measured in 128 patients consecutively admitted because of chest pain, 53 of whom had myocardial infarction and 75 had angina pectoris. The values found did not differ from those measured in 409 normal persons. The seasonal variations of serum 25-HCC were less pronounced in heart patients than in normals, probably due to less sun exposure in the summer months. The lcvcl~ of serum 25-HCC did not correlate with the concentrations of serlUJl cholesterol, glycerides, calcium or magnesium. Low serum calcium and magnesium were observed in all patients. Serum calcium was further reduced in the course of acu te myocardial infarctions while serum parathyroid hormone rose significantly. We conclude that patients with ischaemic heart disease are not ingesting or producing in their skin elevated amount of vitamin D. Key-Words: 25-Hydroxycholecalci[erol - Seasonal Variations
- Myocardialln[arction Angina Pectoris - Calcium Magnesium - Parathyroid Hormone - Cholesterol
Introduction During the last years much interest has focused on vitamin D as a possible risk factor of coronary heart disease. Knox (1973) found that both fat and vitamin D intake showed a positive association with ischaemic heart disease in England and Wales. Linden (1974) registered increasing prob ability of myocardial infarction with increasing daily intake of vitamin D in a population from northern Norway. Seelig (1975) suggested that the com bination of a high intake of vit· amin D and low intake of magnesium might contribute to the development of ischaemic he art disease. Recently, however, Schmidt-Gayk, Goossen, Lendle and Seidel (1977) reported normal levels of 25-hydroxy. cholecalciferol (25-HCC), the major circulating vitamin D metabolite, in 15 patients with myocardial infarction. Reeeived: 25 Aug. 1977
0018-5043/78
1132-0553
Aeeepted: 30 Dec. 1977 805.00
The present investigation was undertaken to study the levels of circulating 25-HCC in patients with ischaemic heart disease. Since serum cholesterol decreases in the course of the acute myocardial infarction, serial blood sampies were taken to investigate whether similar fluctuations occured in the 25-HCC level. The concentrations of serum calcium, magnesium, phosphate, parathyroid hormone (PTH), alkaline phosphatase, cholesterol and glycerides were measured simultaneously. Seasonal variations in serum 25-HCC were also studied in the patients.
Patients and Methods Serum levels of 25-HCC, PTH, calcium, magnesium, alkaline phosphatase, cholesterol and glycerides were followed during the acute myocardial infarction in 12 patients. The first sampIe was obtained within 4 hours after the onset of symptoms, further 3 sampIes were taken fastening on the following 3 days. The diagnosis was verified by ECG changes and enzyme elevations. When it was ascertained that the serum 25HCC level was unaffected in the course of the acute myocardial infarction, further measuremcnts were done in 128 patients consecutively admitted because 01' chest pain. Fiftythree of these had acute myocardial infarction and 75 had angina pectaris. A blood sampie was taken fastening on the first morning and the eoncentrations of 25-HCC, calcium, magnesium, phosphate, cholesterol and glycerides were measured. The correlations between serum 25-HCC and the other parameters were studied. Seasonal variations in the serum 25-HCC were compared with those obscrved in 409 normal persons. Serum 25-HCC was mcasured by a competitive protein-binding assay (Haddad and Chyu 1971) and PTH by a commercial double antibody radioimmunoassay using an antiserum against the COOH-terminal region (normal range 0.11·0.35 ng/ml). PTH No. 71/324 from the Medical Research Council, England, was used as standard. Statistical significance of differences in group means was determined by Wilcoxon test for two sampIes and correlation eocffieients by Spearman's rank correlation.
Results As it is shown in Fig. 1 no changes were seen in circulating 25-HCC in the course of 12 cases of acute
© 1978 Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Department 01 Medicine E. Frederiksberg Hospital, Copenhagen Division of Cardiology, Hvidovre Hospital, University of Copenhagen and Department of Orthopaedic Surgery, Frederiksborg County Hospital, Denmark
554
B. Lund, J. Badskjaer, Bj. Lund, O.H. Soerensen
40
25-HCC ng/",l
35 30 25 20 15 10 5 4 Oay.
2
Chol.. terol "'"'01/1
Glyceride. "'ft\Ol/l
5.0 10
~
4.0
------..-----
1.0
6
5
3.0
7~
Fig. I Serum concentrations of 25-hydroxycholecalciferol (25-HCO, cholesterol and gly cerides d uring the firs t 4 days of acute myocardial infarction (12 ca-
2.0
4 Oay.
4 Da,.
2
so:s).
Table 1 Serum values of parathyroid hormone (PTH), calcium, magnesium, phosphate and a1kaline phosphatase from 12 patients during the first 4 days of acute myocardial infarction Day PTH
3.
2.
1.
4.
0.45
± 0.08
0.47
± 0.10
0.52
± 0.13
0.54
± 0.17
Calcium (mmol/l)
2.42
± 0.10
2.33
± 0.19
2.28
± 0.10
2.33
± 0.09
Magnesium (mmol/l)
0.87
± 0.12
0.86
± 0.10
0.85
± 0.11
0.86
± 0.07
Phosphate (mmol/l)
0.98
± 0.31
1.03
± 0.27
0.94
± 0.22
1.01
± 0.28
Alkaline Phosphatase (i.u.!!)
155
± 87
143
± 73
141
± 66
146
± 72
(/lg!1)
myocardial infarction, while significant reductions occured in the concentrations of serum cholesterol (P < 0.02). The serum glycerides also decreased, but not significantly. In Table I it is seen that there was a significant decrease in serum calcium (P < 0.0 I) from the first to the third day whereas PTH increased significantly (P < 0.01). Serum magnesium, phosphate and alkaline phosphatase remained unchanged. The results found in the 128 patients admitted consecutively because of chest pain are given in Fig. 2 and Table 2. The 25-HCC levels were lower in these patients than in norm als in the months of May-June (P < 0.01) and July-August (P < 0.05), whiJe no differences were seen in the other months studied. Serum calcium and magnesium were significantly lower in
both groups of heart diseases (P < 0.0 I), whiJe serum cholesterol was significantly higher (P < 0.01) than in normals. Serum glycerides did not differ significantly from normal values. No correlation was found between the serum levels of 25-HCC and serum cholesterol neither in the infarction group (r = 0.21) nor in the patients with angina pectoris (r = 0.02). Serum 25-HCC did not correlate with th;: concentrations of calcium (r =0.15) or magnesium (r = 0_09). Discussion The present results do not support the theory that patients with ischaemic heart disease have a higher vitamin 0 intake than the rest of the population. On the contrary we registered significantly reduccd 25-
Downloaded by: Universite Laval. Copyrighted material.
9
555
Vitamin 0 and Ischaemic Heart Oisease
ngl ml
60
May-June Ju ly-Aug.
Sept.-Oct.
Nov.-Oec.
·
0
50
r----- -----
40
0
· ·
~
..·· ··
I
f-------o- 30
20
· · c-----"--..·· · · t-----:·· · I
10
-~--
..· ··· o •
I
I I
~
r---.,.---
~...
··r·
~
·· .. :.a I
·r· ·0·
f r---re
·
0
o pe 0,01
pe 0,05
n. s.
n. s.
Fig. 2 The seasonal variations in serum 25-hydroxycholecalciferol (25-HCC) in 128 patients with ischaemic heart disease. Normal mean valucs ± SO of 409 persons are shown by horilontallines.
HCC values in the summer months among the he art patients which might be explained by discomfort of
direct sun exposure. 25-HCC represents the major metabolitc of vitamin D circulating in the blood and (1973) found a positive association between vitamin D intake and mortality rates from ischaemic heart disease, but since the vitamin D intake also correlated positively with cancer of the stornach, cerebrovascular diseases and bronchitis, the results were difficult to interpret. The normal 25-HCC level found in our patients does of course not exclude the possibility that intake of large doses of vitamin D might produce coronary atherosclerosis. In agreement with other studies we found significantly reduced serum concentrations of calcium (Jacobs 1974) and magnesium (Abraham, Eylath, Weinstein and Czaczkes 1977, Seelig and Heggtveit 1974) in patients with ischaemic heart disease. Serum calcium was further reduced during the first days of the acute myocardial infarction while the magnesium, phosphate and alkali ne phosphatase levels remained unchanged. The increase in serum PTH in the course of the acute period might be secondary to the progressive hypocalcaemia. lt is weil documented that serum cholesterol falls rapidly du ring the first days of the acute myocardial infarction while the changes in the serum glycerides are more inconstant (Doods and Mills 1959, Tibb/in and Cramer 1963). Similar results were observed in this study. The serum 25-HCC which circulates bound to an alpha-globulin, was not affected by the acute myocardia-l infarction.
Table 2 Serum values of 25-hydroxycholecalciferol (25-HCC), calcium, magnesium, cholesterol and glycerides from 75 patients with angina pcctoris and 53 patients with acute myocardial infarction and from normal persons (mean ± SO)
(ng/ml)
Calcium (mmol/l)
Magnesium (mmol/l)
Cholesterol (mmol/l)
Glycerides (mmol/l)
Angina Pectoris
23.5 ± 9.6
2.29 ±0.16++
0.87±0.10
6.50 ± 1.43++
\.53 ± 0.78
Myocardial infarction
24.0 ± 10.0
2.32 ±0.\3++
0.85 ± 0.11 ++
6.72 ± \.61++
\.59 ± 1.28
Normals
28.8 ± 12.3
2.39 ± 0.20
0.91 ± 0.15
5.50 ± 1.50
1.40 ± 0.80
25 ··HCC
++ P < 0.01
has a plasma half-life as long as 21 days in normal man (Mawer, Lumb, Schaefer and Stanbury 1971). Determination of this metabolite gives a good information of the state of vitamin D nutrition in the individual, a more exact information than a questionnaire completed retrospectively by the patients. Surprisingly Linden (1974) registered a low intake of vitamin D in the angina pectoris group and a high in take in the infarction group, We did not find any differences in the serum 25-HCC levels of these 2 groups. Knox
As shown in many other studies serum cholesterol was gene rally elevated in the patients with ischaemic heart disease. lt has been suggested that vitamin D administration increases serum cholesterol (Fleischman, Bierenbaum, Raichelson, Hayton and Watson 1970), but we were unable to demonstrate any correlation between serum 25-HCC and the concentrations of cholesterol or glycerides neither in the infarction group nor in the angina pectoris group.
Downloaded by: Universite Laval. Copyrighted material.
25 - H C C
556
F. Brion, H. Parvez, S. Parvez, C. Marnay-Gulat, Y. Raoul
Referenees
Abraham, S.A., U. Eylath, M. Weinstein, E. Czaczkes: Serum magnesium levels in patients with acute myocardial infarction. N. Eng. J. Med. 296: 862-863 (1977) Doods, c., G.L. Mills: Influence of myocardial infarction on plasmalipoprotein eoncentration. Laneet I: 1160-1163 (1959) Fleischman, A./., M.L. Bierenbaum, R. Raichelson, T. Hay· ton, P. Watson: Vitamin D and hypereholesterolemia in adult humans. In: Atherosclerosis, Proceedings of the second international symposium. Springer-Verlag, New York, p. 468-472,1970 Haddad, l. G., Kl. Chyu: Competitive protein-binding radioassay far 25-hydroxycholecalciferol. J. Clin. Endocrinol. Metab. 33: 992-995 (1971) lacobs, D.: Calcium and myocardial infarction. S. Afr. Med. J. 48: 523 527 (1974) Knox, E.G.: lschaemic-heart-disease mortality and dietary in take ofealcium. Lancet 1: 1465-1467 (1973)
Linden, v.: Vitamin D and myocardial infarction. Brit. Med. J.3:647-650(1974) Mawer, E.B., G.A. Lumb, K Schaefer, S. W. Stanbury: The metabolism of isotopically labe lied vitamin D 3 in man: the influence of the state of vitamin D nutrition. Clin. Science 40: 39-53 (1971) Schmidt-Gayk, H., l. Goossen, F. Lendle, D. Seidel: Serum 25-hydroxycholecalciferol in myocardial infarction. Atherosclerosis 26: 55-58 (1977) Seelig, M.S., H.A. Heggtveit: Magnesium interrelationships in ischemic heart disease: A review. Amer. J. Clin. Nutr. 27: 59-79 (1974) Seelig, M.S.: Ischaemic he art disease, vitamins D and A, and magnesium. Brit. Med. J. 3: 647-648 (1975) Tibblin, G., K Cramer: Serum lipids during the course of an acute myocardial infarction and one year afterwards. Acta Med. Scand. 174: 451 -455 (1963)
Horm. Metab. Res. 10 (1978) 556-560
Effects of Glucocorticoids Upon Adrenal and Urinary Epinephrine and Norepinephrine and the Activity of Enzyme PhenylethanolamineN-methyltransferase in Rats Made Partially Deficient in Vitamin 0: Role of Vitamin 0 Supplementation F. Brion, H. Parvez, S. Parvez, C. Marnay-Gulat, Y. Raoul Laboratoire de Physiologie, U.E.R. Mecanisme d'action des medicaments et des '')xiQues. Universite Paris V, et Unite de Neuropharmacologie, Universite Paris X I, Orsay, France
Summary lnfluence of individual and combined administration of hydroeortisone and vitamin D upon adrenal and urinary catecholamines in vitamin D deprived rats has been studied. One month ofvitamin D free diet resulted in 49% increase in adrenal norepinephrine and 22% decrease in Phenylethanolamine-NMethyltransferase (PNMT) aetivity whereas epinephrine remained unaffected from the value of normally fed rats. Daily administration of vitamin D for 11 days did not abolish adrenal norepinephrine increase but partially restored PNMT activity. Hydrocortisone treatment produced increases in adrenal epinephrine and PNMT activity. Combined treatment with hydrocortisone and vitamin D reversed the effects of individual treatment. One month of vitamin D free diet deereased urinary excreti on of both norepinephrine and epinephrine by 24% and 77% Received: 30 Apr. 1977 0018-5043/78
1132-0556
respectively compared to standard diet values. Daily administration of vitamin D restored to normal level the urinary exeretion of epinephrine and norepinephrine in one month vitamin D deprived rats. Four injections of hydrocortisone modified epinephrine and narepinephrine urinary excretion to normal value, but theses effects were totally reversed after 9 days of treatment. The combined administration of vitamin D and hydrocortisone for 11 days totally restored both urinary monoamines. From these results it can be gathered that presence of vitamin D is a permissive faetor for the glueoeortieoids to exert their effeets on adrenal monoamine storage and exeretion. Key-Words: Epinephrine - Norepinephrine - Adrenal Vitamin D - PNMT - Hydrocortisone - Monoamine Urinary Excretion -- Diet
Accepted: 5 June 1978 • 05.00
© 1978
Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Requests for reprints should be addressed to: Dr. B. Lund, Medical Department E, Frederiksberg Hospital, Ndt. Fasanvcj., DK2000 Copenhangen F (Denmark)
Rosengren, E.: Histamine metabolism in the pregnant and non-pregnant hamster. Proc. Soc. Exp. Biol. Med. 118: 884-888 (1965) Scatchard, G.: The attraction of proteins far small molecules
553
and ions. Ann. N. Y. Acad. Sd. 51: 660 665 (! 949) Verma. u.. K.R. Laumas: In vitro binding 01' progestcronc to receptars in the human endometrium and myometrium. Biochem. Biophys. Acta 317: 403 41 q (1973)
Requests for reprints should be addressed to: Professor Dr. F. Stutinsky, Laboratoire de Physiologie generale, 21 Rue Descartes, F 67000 Strasbourg (France) Horm. Metab. Res. 10 (1978) 553-556
Vitamin D and Ischaemic Heart Disease B. Lund, J. Badskjaer, Bj. Lund, O.H. Soerensen
Summary Vitamin 0 has been proposed as a risk factor of ischaemic heart disease. In 12 patients with acute myocardial infarction the major circulating vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), did not show any fluctuations during the first 4 days after onset of symptoms. The serum 25-HCC level was then measured in 128 patients consecutively admitted because of chest pain, 53 of whom had myocardial infarction and 75 had angina pectoris. The values found did not differ from those measured in 409 normal persons. The seasonal variations of serum 25-HCC were less pronounced in heart patients than in normals, probably due to less sun exposure in the summer months. The lcvcl~ of serum 25-HCC did not correlate with the concentrations of serlUJl cholesterol, glycerides, calcium or magnesium. Low serum calcium and magnesium were observed in all patients. Serum calcium was further reduced in the course of acu te myocardial infarctions while serum parathyroid hormone rose significantly. We conclude that patients with ischaemic heart disease are not ingesting or producing in their skin elevated amount of vitamin D. Key-Words: 25-Hydroxycholecalci[erol - Seasonal Variations
- Myocardialln[arction Angina Pectoris - Calcium Magnesium - Parathyroid Hormone - Cholesterol
Introduction During the last years much interest has focused on vitamin D as a possible risk factor of coronary heart disease. Knox (1973) found that both fat and vitamin D intake showed a positive association with ischaemic heart disease in England and Wales. Linden (1974) registered increasing prob ability of myocardial infarction with increasing daily intake of vitamin D in a population from northern Norway. Seelig (1975) suggested that the com bination of a high intake of vit· amin D and low intake of magnesium might contribute to the development of ischaemic he art disease. Recently, however, Schmidt-Gayk, Goossen, Lendle and Seidel (1977) reported normal levels of 25-hydroxy. cholecalciferol (25-HCC), the major circulating vitamin D metabolite, in 15 patients with myocardial infarction. Reeeived: 25 Aug. 1977
0018-5043/78
1132-0553
Aeeepted: 30 Dec. 1977 805.00
The present investigation was undertaken to study the levels of circulating 25-HCC in patients with ischaemic heart disease. Since serum cholesterol decreases in the course of the acute myocardial infarction, serial blood sampies were taken to investigate whether similar fluctuations occured in the 25-HCC level. The concentrations of serum calcium, magnesium, phosphate, parathyroid hormone (PTH), alkaline phosphatase, cholesterol and glycerides were measured simultaneously. Seasonal variations in serum 25-HCC were also studied in the patients.
Patients and Methods Serum levels of 25-HCC, PTH, calcium, magnesium, alkaline phosphatase, cholesterol and glycerides were followed during the acute myocardial infarction in 12 patients. The first sampIe was obtained within 4 hours after the onset of symptoms, further 3 sampIes were taken fastening on the following 3 days. The diagnosis was verified by ECG changes and enzyme elevations. When it was ascertained that the serum 25HCC level was unaffected in the course of the acute myocardial infarction, further measuremcnts were done in 128 patients consecutively admitted because 01' chest pain. Fiftythree of these had acute myocardial infarction and 75 had angina pectaris. A blood sampie was taken fastening on the first morning and the eoncentrations of 25-HCC, calcium, magnesium, phosphate, cholesterol and glycerides were measured. The correlations between serum 25-HCC and the other parameters were studied. Seasonal variations in the serum 25-HCC were compared with those obscrved in 409 normal persons. Serum 25-HCC was mcasured by a competitive protein-binding assay (Haddad and Chyu 1971) and PTH by a commercial double antibody radioimmunoassay using an antiserum against the COOH-terminal region (normal range 0.11·0.35 ng/ml). PTH No. 71/324 from the Medical Research Council, England, was used as standard. Statistical significance of differences in group means was determined by Wilcoxon test for two sampIes and correlation eocffieients by Spearman's rank correlation.
Results As it is shown in Fig. 1 no changes were seen in circulating 25-HCC in the course of 12 cases of acute
© 1978 Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Department 01 Medicine E. Frederiksberg Hospital, Copenhagen Division of Cardiology, Hvidovre Hospital, University of Copenhagen and Department of Orthopaedic Surgery, Frederiksborg County Hospital, Denmark
554
B. Lund, J. Badskjaer, Bj. Lund, O.H. Soerensen
40
25-HCC ng/",l
35 30 25 20 15 10 5 4 Oay.
2
Chol.. terol "'"'01/1
Glyceride. "'ft\Ol/l
5.0 10
~
4.0
------..-----
1.0
6
5
3.0
7~
Fig. I Serum concentrations of 25-hydroxycholecalciferol (25-HCO, cholesterol and gly cerides d uring the firs t 4 days of acute myocardial infarction (12 ca-
2.0
4 Oay.
4 Da,.
2
so:s).
Table 1 Serum values of parathyroid hormone (PTH), calcium, magnesium, phosphate and a1kaline phosphatase from 12 patients during the first 4 days of acute myocardial infarction Day PTH
3.
2.
1.
4.
0.45
± 0.08
0.47
± 0.10
0.52
± 0.13
0.54
± 0.17
Calcium (mmol/l)
2.42
± 0.10
2.33
± 0.19
2.28
± 0.10
2.33
± 0.09
Magnesium (mmol/l)
0.87
± 0.12
0.86
± 0.10
0.85
± 0.11
0.86
± 0.07
Phosphate (mmol/l)
0.98
± 0.31
1.03
± 0.27
0.94
± 0.22
1.01
± 0.28
Alkaline Phosphatase (i.u.!!)
155
± 87
143
± 73
141
± 66
146
± 72
(/lg!1)
myocardial infarction, while significant reductions occured in the concentrations of serum cholesterol (P < 0.02). The serum glycerides also decreased, but not significantly. In Table I it is seen that there was a significant decrease in serum calcium (P < 0.0 I) from the first to the third day whereas PTH increased significantly (P < 0.01). Serum magnesium, phosphate and alkaline phosphatase remained unchanged. The results found in the 128 patients admitted consecutively because of chest pain are given in Fig. 2 and Table 2. The 25-HCC levels were lower in these patients than in norm als in the months of May-June (P < 0.01) and July-August (P < 0.05), whiJe no differences were seen in the other months studied. Serum calcium and magnesium were significantly lower in
both groups of heart diseases (P < 0.0 I), whiJe serum cholesterol was significantly higher (P < 0.01) than in normals. Serum glycerides did not differ significantly from normal values. No correlation was found between the serum levels of 25-HCC and serum cholesterol neither in the infarction group (r = 0.21) nor in the patients with angina pectoris (r = 0.02). Serum 25-HCC did not correlate with th;: concentrations of calcium (r =0.15) or magnesium (r = 0_09). Discussion The present results do not support the theory that patients with ischaemic heart disease have a higher vitamin 0 intake than the rest of the population. On the contrary we registered significantly reduccd 25-
Downloaded by: Universite Laval. Copyrighted material.
9
555
Vitamin 0 and Ischaemic Heart Oisease
ngl ml
60
May-June Ju ly-Aug.
Sept.-Oct.
Nov.-Oec.
·
0
50
r----- -----
40
0
· ·
~
..·· ··
I
f-------o- 30
20
· · c-----"--..·· · · t-----:·· · I
10
-~--
..· ··· o •
I
I I
~
r---.,.---
~...
··r·
~
·· .. :.a I
·r· ·0·
f r---re
·
0
o pe 0,01
pe 0,05
n. s.
n. s.
Fig. 2 The seasonal variations in serum 25-hydroxycholecalciferol (25-HCC) in 128 patients with ischaemic heart disease. Normal mean valucs ± SO of 409 persons are shown by horilontallines.
HCC values in the summer months among the he art patients which might be explained by discomfort of
direct sun exposure. 25-HCC represents the major metabolitc of vitamin D circulating in the blood and (1973) found a positive association between vitamin D intake and mortality rates from ischaemic heart disease, but since the vitamin D intake also correlated positively with cancer of the stornach, cerebrovascular diseases and bronchitis, the results were difficult to interpret. The normal 25-HCC level found in our patients does of course not exclude the possibility that intake of large doses of vitamin D might produce coronary atherosclerosis. In agreement with other studies we found significantly reduced serum concentrations of calcium (Jacobs 1974) and magnesium (Abraham, Eylath, Weinstein and Czaczkes 1977, Seelig and Heggtveit 1974) in patients with ischaemic heart disease. Serum calcium was further reduced during the first days of the acute myocardial infarction while the magnesium, phosphate and alkali ne phosphatase levels remained unchanged. The increase in serum PTH in the course of the acute period might be secondary to the progressive hypocalcaemia. lt is weil documented that serum cholesterol falls rapidly du ring the first days of the acute myocardial infarction while the changes in the serum glycerides are more inconstant (Doods and Mills 1959, Tibb/in and Cramer 1963). Similar results were observed in this study. The serum 25-HCC which circulates bound to an alpha-globulin, was not affected by the acute myocardia-l infarction.
Table 2 Serum values of 25-hydroxycholecalciferol (25-HCC), calcium, magnesium, cholesterol and glycerides from 75 patients with angina pcctoris and 53 patients with acute myocardial infarction and from normal persons (mean ± SO)
(ng/ml)
Calcium (mmol/l)
Magnesium (mmol/l)
Cholesterol (mmol/l)
Glycerides (mmol/l)
Angina Pectoris
23.5 ± 9.6
2.29 ±0.16++
0.87±0.10
6.50 ± 1.43++
\.53 ± 0.78
Myocardial infarction
24.0 ± 10.0
2.32 ±0.\3++
0.85 ± 0.11 ++
6.72 ± \.61++
\.59 ± 1.28
Normals
28.8 ± 12.3
2.39 ± 0.20
0.91 ± 0.15
5.50 ± 1.50
1.40 ± 0.80
25 ··HCC
++ P < 0.01
has a plasma half-life as long as 21 days in normal man (Mawer, Lumb, Schaefer and Stanbury 1971). Determination of this metabolite gives a good information of the state of vitamin D nutrition in the individual, a more exact information than a questionnaire completed retrospectively by the patients. Surprisingly Linden (1974) registered a low intake of vitamin D in the angina pectoris group and a high in take in the infarction group, We did not find any differences in the serum 25-HCC levels of these 2 groups. Knox
As shown in many other studies serum cholesterol was gene rally elevated in the patients with ischaemic heart disease. lt has been suggested that vitamin D administration increases serum cholesterol (Fleischman, Bierenbaum, Raichelson, Hayton and Watson 1970), but we were unable to demonstrate any correlation between serum 25-HCC and the concentrations of cholesterol or glycerides neither in the infarction group nor in the angina pectoris group.
Downloaded by: Universite Laval. Copyrighted material.
25 - H C C
556
F. Brion, H. Parvez, S. Parvez, C. Marnay-Gulat, Y. Raoul
Referenees
Abraham, S.A., U. Eylath, M. Weinstein, E. Czaczkes: Serum magnesium levels in patients with acute myocardial infarction. N. Eng. J. Med. 296: 862-863 (1977) Doods, c., G.L. Mills: Influence of myocardial infarction on plasmalipoprotein eoncentration. Laneet I: 1160-1163 (1959) Fleischman, A./., M.L. Bierenbaum, R. Raichelson, T. Hay· ton, P. Watson: Vitamin D and hypereholesterolemia in adult humans. In: Atherosclerosis, Proceedings of the second international symposium. Springer-Verlag, New York, p. 468-472,1970 Haddad, l. G., Kl. Chyu: Competitive protein-binding radioassay far 25-hydroxycholecalciferol. J. Clin. Endocrinol. Metab. 33: 992-995 (1971) lacobs, D.: Calcium and myocardial infarction. S. Afr. Med. J. 48: 523 527 (1974) Knox, E.G.: lschaemic-heart-disease mortality and dietary in take ofealcium. Lancet 1: 1465-1467 (1973)
Linden, v.: Vitamin D and myocardial infarction. Brit. Med. J.3:647-650(1974) Mawer, E.B., G.A. Lumb, K Schaefer, S. W. Stanbury: The metabolism of isotopically labe lied vitamin D 3 in man: the influence of the state of vitamin D nutrition. Clin. Science 40: 39-53 (1971) Schmidt-Gayk, H., l. Goossen, F. Lendle, D. Seidel: Serum 25-hydroxycholecalciferol in myocardial infarction. Atherosclerosis 26: 55-58 (1977) Seelig, M.S., H.A. Heggtveit: Magnesium interrelationships in ischemic heart disease: A review. Amer. J. Clin. Nutr. 27: 59-79 (1974) Seelig, M.S.: Ischaemic he art disease, vitamins D and A, and magnesium. Brit. Med. J. 3: 647-648 (1975) Tibblin, G., K Cramer: Serum lipids during the course of an acute myocardial infarction and one year afterwards. Acta Med. Scand. 174: 451 -455 (1963)
Horm. Metab. Res. 10 (1978) 556-560
Effects of Glucocorticoids Upon Adrenal and Urinary Epinephrine and Norepinephrine and the Activity of Enzyme PhenylethanolamineN-methyltransferase in Rats Made Partially Deficient in Vitamin 0: Role of Vitamin 0 Supplementation F. Brion, H. Parvez, S. Parvez, C. Marnay-Gulat, Y. Raoul Laboratoire de Physiologie, U.E.R. Mecanisme d'action des medicaments et des '')xiQues. Universite Paris V, et Unite de Neuropharmacologie, Universite Paris X I, Orsay, France
Summary lnfluence of individual and combined administration of hydroeortisone and vitamin D upon adrenal and urinary catecholamines in vitamin D deprived rats has been studied. One month ofvitamin D free diet resulted in 49% increase in adrenal norepinephrine and 22% decrease in Phenylethanolamine-NMethyltransferase (PNMT) aetivity whereas epinephrine remained unaffected from the value of normally fed rats. Daily administration of vitamin D for 11 days did not abolish adrenal norepinephrine increase but partially restored PNMT activity. Hydrocortisone treatment produced increases in adrenal epinephrine and PNMT activity. Combined treatment with hydrocortisone and vitamin D reversed the effects of individual treatment. One month of vitamin D free diet deereased urinary excreti on of both norepinephrine and epinephrine by 24% and 77% Received: 30 Apr. 1977 0018-5043/78
1132-0556
respectively compared to standard diet values. Daily administration of vitamin D restored to normal level the urinary exeretion of epinephrine and norepinephrine in one month vitamin D deprived rats. Four injections of hydrocortisone modified epinephrine and narepinephrine urinary excretion to normal value, but theses effects were totally reversed after 9 days of treatment. The combined administration of vitamin D and hydrocortisone for 11 days totally restored both urinary monoamines. From these results it can be gathered that presence of vitamin D is a permissive faetor for the glueoeortieoids to exert their effeets on adrenal monoamine storage and exeretion. Key-Words: Epinephrine - Norepinephrine - Adrenal Vitamin D - PNMT - Hydrocortisone - Monoamine Urinary Excretion -- Diet
Accepted: 5 June 1978 • 05.00
© 1978
Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Requests for reprints should be addressed to: Dr. B. Lund, Medical Department E, Frederiksberg Hospital, Ndt. Fasanvcj., DK2000 Copenhangen F (Denmark)
