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High density lipoproteins and apolipoprotein A in cerebrovascular disease
Atherosclerosis, 54 (1985)
Elsevier Scientific
343
343-346
Publishers
Ireland,
Ltd.
ATH 03582
Letter to the Editors
High Density Lipoproteins and Apolipoprotein Cerebrovascular Disease
A in
Dear Editors,
Animal and human experimental studies are bringing increasing evidence that atherosclerosis of cerebral arteries differs from coronary and peripheral atherosclerosis both in age at onset and in severity of the lesions [l-4]. Primates fed an atherogenic diet for several months showed little or no atherosclerosis in vertebral, basilar and middle cerebral arteries. In contrast, the carotid, coronary and peripheral arteries presented severe atherosclerotic lesions, as evidenced by light, scanning and electron microscopy [4]. It has been suggested that the explanation of this difference might reside in some structural [5] and functional [6] characteristics of the middle cerebral artery wall which constitute a barrier to atherogenic substances. On the other hand, the importance of decreased levels of high density lipoproteins (HDL) and particularly of apolipoprotein A (apo A) in the development of coronary and peripheral atherosclerosis has been repeatedly stressed [7-121. In previous investigations we observed that cholesterol and triglyceride concentrations were not increased in patients with cerebrovascular disease (CVD) contrary to what was found in patients with ischemic heart disease [13], in accordance with the results of the Framingham Study indicating that hyperlipoproteinemia (triglyceride and cholesterol increase) plays a minor role in the development of ischemic cerebrovascular disease [14]. These results were confirmed by other investigators (15,191. Using the laser-nephelometric method with a specific antibody against apo A (Apolipoprotein A and Apolipoprotein standard, Behring Institute) and the method of [16] for HDL cholesterol we determined the values of apo-A and HDL in a group of patients with CVD. The diagnosis of CVD was made by neurological-clinical examination, cerebral TC and Doppler sonography: the group included patients with stabilized ischemic lesions. A group of patients with ischemic heart disease and two groups of age- and sex-matched normal subjects (mainly blood donors), who on repeated clinical examinations were considered healthy, were studied as controls. Patients with CVD showed levels of HDL and apo A within the limits observed in the group of normal individuals. At the same time, in the group with ischemic heart disease the levels of HDL and apo A were decreased with statistically significant differences (see Table 1). The scarcity of alterations in the HDL and apo A levels observed in our patients 0021-9150/85/$03.30
0 1985 Elsevier Scientific
Publishers
Ireland,
Ltd
1
Normal
Ischemic
control
subjects
heart disease
58
66
76
subjects
Normal
control
71
disease
Cerebrovascular
group
Patient number
f SEM.
Patient
Values are mean
HDL CHOLESTEROL AND APO A VALUES CONTROL SUBJECTS (NCS)
TABLE
36+
8.1
9.2
54+
52+
47+
48k
8.5
8.2
9.2
44*12
61+12
62k11.3
(mg/lW
HDL ml)
DISEASE
Age (yr)
IN CEREBROVASCULAR
(CVD),
193 + 28
149 rt 32
191 k27
180+28
(mg/l@J
Apo A
I
ml)
IN ISCHEMIC
HEART
(IHD)
AND
IHD vs NCS P < 0.001 for both HDL and apo A
CVD vs NCS difference non-significant for both HDL and apo A
Statistical significance(P)
DISEASE
NORMAL
345
with cerebrovascular disease, together with the reported failure of inducing atherosclerotic lesions in cerebral arteries by atherogenic diet, may indicate that lipoprotein variations play a minor role as risk factors in atherosclerosis of intracranial arteries. Othei investigators have reported conflicting results about the role played by HDL in cerebrovascular disease [15,17,19], but the apo A level was not determined in those studies. Terrence et al. [21] have recently reported increased triglyceride levels in CVD patients with atherosclerosis of extracranial (carotid) arteries. The attention of investigators is now directed also towards alterations in coagulation factor levels. Increased levels of /3-thromboglobulin and platelet factor 4, as well as the presence of fibrinopeptide A, are frequently observed both in cerebral transient ischemic attacks [22] and in coronary artery disease [23]. Further investigations are needed in order to evaluate the role played by all these risk factors in the development of cerebrovascular disease taking into special account the presence or absence of atherosclerosis of extracranial (carotid) arteries. References 1 Suzuki, M., Atherosclerotic lesions of the cerebral arteries in young persons. In: Schettler and Weizel @is.), Atherosclerosis III, Springer Verlag, Berlin, 1974, p. 492. 2 Wissler, R.W. and Vesselinovitch, D., Atherosclerosis in nonhuman primates, Adv. Vet. Sci. Comp. Med., 21 (1977) 351. 3 Velican, C. and Velican, D., Discrepancies among data on atherosclerotic involvement furnished by gross inspection and by light microscopy, Atherosclerosis, 43 (1982) 39. 4 Weber, G., Fabbrini, P., Resi, L., Sforza, V., Tanganelli, P., Vesselinovitch, D. and Wissler, R.W., An ultrastructural comparison of diet induced atherosclerosis of arteries supplying the central nervous system in cynomolgus and rhesus monkeys, Appl. Path., 1 (1983) 121. 5 Dahl. E., Electron microscopic observation on cerebral arteries. In: Cervos-Navarro, Betz, Matakas, Wullenweber @is.), The Cerebral Vessel Wall, Raven Press, New York, 1976, p. 61. 6 Weber, G., Fabbrini, P. and Resi, L., Lack of endothelial Concanavalin A reactivity in the cerebral arteries of rabbits and monkeys, Atherosclerosis, 42 (1982) 125. 7 Caste& W.P., Doyle, J.Y., Gordon, T.G., Hjertland, M.C., Hulley, S.B., Kaga, A. and Zukel, W.J., HDL-Cholesterol and other lipids in coronary heart disease - The Cooperative Lipoprotein Phenotyping Study, Circulation, 55 (1977) 767. 8 Bradby, G.V.H., Valente, A.J. and Wilton, K.J., Serum high-density lipoproteins in peripheral vascular disease, Lancet, ii (1978) 1271. 9 Avogaro, P., Cazzolato, G., Bittolo-Bon, G. and Belussi, F., High density lipoproteins - Methods of analysis and role in human atherosclerosis, Ric. Clin. Lab., 12 (1982) 87. 10 Dioguardi, N. and Vergani, C., Lipoproteine e malattia cardiovascolare, Ospedale Maggiore, 73 (1978) 3. 11 Miller, N.E., Fsrde, O.H., ThelIe, D.S. and Mjos, O.D., HDL and coronary heart disease - A prospective case-control study, Lancet, i (1977) 965. 12 Fruchart, J.C., Parra, H., Cachera, S., Clavevy, M. and Bertrand, M., Lipoproteins and coronary artery disease - Comparison with the results of coronary angiography, Ric. Clin. Lab., 12 (1982) 101. 13 Airb, R., Pranzo, A. and Piantoni, S., Lipidi serici e malattia cerebrovasculare, Sett. Osped., 16 (1974) 4. 14 Kannel, W.B., Gordon, T. and Dawber, T.R., Role of lipids in the development of brain infarction The Framingham Study, Stroke, 5 (1974) 679. 15 RBssner, R., Kjellin, K.G., Mettinger, K.L. and S&ierstr6m, C.E., Normal serum cholesterol concentration in young patients with ischaemic cerebrovascular disease, Lancet, i (1978) 577.
346
16, Lopes-Virella, M.F., Stone, P. and Colwell, J.A., Cholesterol determination in high-density lipoproteins separated by three different methods, Clin. Chem., 23 (1977) 5. 17 Bihari-Varga, M., S&keIy, J. and Gruber, E., Plasma high density lipoproteins in coronary, cerebral and peripheral vascular disease - The influence of various risk factors, Atherosclerosis, 40 (1981) 337. 18 Bruck, J., Fisher, M. and Tschabitscher, H., ijber Veranderungen der Serum Lipoproteine bei zerebrovaskul’aren Erkrankungen, Wien. Klin. Wschr., 93 (1981) 604. 19 Avogaro, P., Cazzolato, G., Taroni, G.C. and Belussi, F., Chemical composition of ultracentrifugal fractions in different patterns of human atherosclerosis, Atherosclerosis, 26 (1977) 163. 20 Taggart, H. and Storet, R.W., Reduced high density lipoprotein in stroke - Relationship with elevated triglyceride and hypertension, Europ. J. Clin. Invest., 9 (1979) 219. 21 Terrence, CF. and Rao, G.R., Triglycerides as a risk factor in extracranial atherosclerotic cerebrovascular disease, Angiology, 34 (1983) 452. 22 Fabris, F., Randi, M.L., Crociani, M.E., Manzoni, S., Tonin, P., De Zanche, L.. Cella, G. and Girolami, A., Platelet-specific proteins with transient ischemic attacks, Ric. Chn. Lab., 13 (1983) 437. 23 Levine, S.P., Lindenfeld, J., Ellis, J.B., Raymond, N.M. and Krentz, L.S., Increased plasma concentration of platelet factor 4 in coronary artery disease, Circulation, 64 (1981) 626. Clinical Pathology Laboratory General Hospital Chiari - Rovato, 25032 Chiari (Bs) (Italy) (Received 1 June, 1984) (Revised, received 20 September, (Accepted 20 September, 1984)
R. Airb C.M. Ferrari 1984)
Elsevier Scientific
343
343-346
Publishers
Ireland,
Ltd.
ATH 03582
Letter to the Editors
High Density Lipoproteins and Apolipoprotein Cerebrovascular Disease
A in
Dear Editors,
Animal and human experimental studies are bringing increasing evidence that atherosclerosis of cerebral arteries differs from coronary and peripheral atherosclerosis both in age at onset and in severity of the lesions [l-4]. Primates fed an atherogenic diet for several months showed little or no atherosclerosis in vertebral, basilar and middle cerebral arteries. In contrast, the carotid, coronary and peripheral arteries presented severe atherosclerotic lesions, as evidenced by light, scanning and electron microscopy [4]. It has been suggested that the explanation of this difference might reside in some structural [5] and functional [6] characteristics of the middle cerebral artery wall which constitute a barrier to atherogenic substances. On the other hand, the importance of decreased levels of high density lipoproteins (HDL) and particularly of apolipoprotein A (apo A) in the development of coronary and peripheral atherosclerosis has been repeatedly stressed [7-121. In previous investigations we observed that cholesterol and triglyceride concentrations were not increased in patients with cerebrovascular disease (CVD) contrary to what was found in patients with ischemic heart disease [13], in accordance with the results of the Framingham Study indicating that hyperlipoproteinemia (triglyceride and cholesterol increase) plays a minor role in the development of ischemic cerebrovascular disease [14]. These results were confirmed by other investigators (15,191. Using the laser-nephelometric method with a specific antibody against apo A (Apolipoprotein A and Apolipoprotein standard, Behring Institute) and the method of [16] for HDL cholesterol we determined the values of apo-A and HDL in a group of patients with CVD. The diagnosis of CVD was made by neurological-clinical examination, cerebral TC and Doppler sonography: the group included patients with stabilized ischemic lesions. A group of patients with ischemic heart disease and two groups of age- and sex-matched normal subjects (mainly blood donors), who on repeated clinical examinations were considered healthy, were studied as controls. Patients with CVD showed levels of HDL and apo A within the limits observed in the group of normal individuals. At the same time, in the group with ischemic heart disease the levels of HDL and apo A were decreased with statistically significant differences (see Table 1). The scarcity of alterations in the HDL and apo A levels observed in our patients 0021-9150/85/$03.30
0 1985 Elsevier Scientific
Publishers
Ireland,
Ltd
1
Normal
Ischemic
control
subjects
heart disease
58
66
76
subjects
Normal
control
71
disease
Cerebrovascular
group
Patient number
f SEM.
Patient
Values are mean
HDL CHOLESTEROL AND APO A VALUES CONTROL SUBJECTS (NCS)
TABLE
36+
8.1
9.2
54+
52+
47+
48k
8.5
8.2
9.2
44*12
61+12
62k11.3
(mg/lW
HDL ml)
DISEASE
Age (yr)
IN CEREBROVASCULAR
(CVD),
193 + 28
149 rt 32
191 k27
180+28
(mg/l@J
Apo A
I
ml)
IN ISCHEMIC
HEART
(IHD)
AND
IHD vs NCS P < 0.001 for both HDL and apo A
CVD vs NCS difference non-significant for both HDL and apo A
Statistical significance(P)
DISEASE
NORMAL
345
with cerebrovascular disease, together with the reported failure of inducing atherosclerotic lesions in cerebral arteries by atherogenic diet, may indicate that lipoprotein variations play a minor role as risk factors in atherosclerosis of intracranial arteries. Othei investigators have reported conflicting results about the role played by HDL in cerebrovascular disease [15,17,19], but the apo A level was not determined in those studies. Terrence et al. [21] have recently reported increased triglyceride levels in CVD patients with atherosclerosis of extracranial (carotid) arteries. The attention of investigators is now directed also towards alterations in coagulation factor levels. Increased levels of /3-thromboglobulin and platelet factor 4, as well as the presence of fibrinopeptide A, are frequently observed both in cerebral transient ischemic attacks [22] and in coronary artery disease [23]. Further investigations are needed in order to evaluate the role played by all these risk factors in the development of cerebrovascular disease taking into special account the presence or absence of atherosclerosis of extracranial (carotid) arteries. References 1 Suzuki, M., Atherosclerotic lesions of the cerebral arteries in young persons. In: Schettler and Weizel @is.), Atherosclerosis III, Springer Verlag, Berlin, 1974, p. 492. 2 Wissler, R.W. and Vesselinovitch, D., Atherosclerosis in nonhuman primates, Adv. Vet. Sci. Comp. Med., 21 (1977) 351. 3 Velican, C. and Velican, D., Discrepancies among data on atherosclerotic involvement furnished by gross inspection and by light microscopy, Atherosclerosis, 43 (1982) 39. 4 Weber, G., Fabbrini, P., Resi, L., Sforza, V., Tanganelli, P., Vesselinovitch, D. and Wissler, R.W., An ultrastructural comparison of diet induced atherosclerosis of arteries supplying the central nervous system in cynomolgus and rhesus monkeys, Appl. Path., 1 (1983) 121. 5 Dahl. E., Electron microscopic observation on cerebral arteries. In: Cervos-Navarro, Betz, Matakas, Wullenweber @is.), The Cerebral Vessel Wall, Raven Press, New York, 1976, p. 61. 6 Weber, G., Fabbrini, P. and Resi, L., Lack of endothelial Concanavalin A reactivity in the cerebral arteries of rabbits and monkeys, Atherosclerosis, 42 (1982) 125. 7 Caste& W.P., Doyle, J.Y., Gordon, T.G., Hjertland, M.C., Hulley, S.B., Kaga, A. and Zukel, W.J., HDL-Cholesterol and other lipids in coronary heart disease - The Cooperative Lipoprotein Phenotyping Study, Circulation, 55 (1977) 767. 8 Bradby, G.V.H., Valente, A.J. and Wilton, K.J., Serum high-density lipoproteins in peripheral vascular disease, Lancet, ii (1978) 1271. 9 Avogaro, P., Cazzolato, G., Bittolo-Bon, G. and Belussi, F., High density lipoproteins - Methods of analysis and role in human atherosclerosis, Ric. Clin. Lab., 12 (1982) 87. 10 Dioguardi, N. and Vergani, C., Lipoproteine e malattia cardiovascolare, Ospedale Maggiore, 73 (1978) 3. 11 Miller, N.E., Fsrde, O.H., ThelIe, D.S. and Mjos, O.D., HDL and coronary heart disease - A prospective case-control study, Lancet, i (1977) 965. 12 Fruchart, J.C., Parra, H., Cachera, S., Clavevy, M. and Bertrand, M., Lipoproteins and coronary artery disease - Comparison with the results of coronary angiography, Ric. Clin. Lab., 12 (1982) 101. 13 Airb, R., Pranzo, A. and Piantoni, S., Lipidi serici e malattia cerebrovasculare, Sett. Osped., 16 (1974) 4. 14 Kannel, W.B., Gordon, T. and Dawber, T.R., Role of lipids in the development of brain infarction The Framingham Study, Stroke, 5 (1974) 679. 15 RBssner, R., Kjellin, K.G., Mettinger, K.L. and S&ierstr6m, C.E., Normal serum cholesterol concentration in young patients with ischaemic cerebrovascular disease, Lancet, i (1978) 577.
346
16, Lopes-Virella, M.F., Stone, P. and Colwell, J.A., Cholesterol determination in high-density lipoproteins separated by three different methods, Clin. Chem., 23 (1977) 5. 17 Bihari-Varga, M., S&keIy, J. and Gruber, E., Plasma high density lipoproteins in coronary, cerebral and peripheral vascular disease - The influence of various risk factors, Atherosclerosis, 40 (1981) 337. 18 Bruck, J., Fisher, M. and Tschabitscher, H., ijber Veranderungen der Serum Lipoproteine bei zerebrovaskul’aren Erkrankungen, Wien. Klin. Wschr., 93 (1981) 604. 19 Avogaro, P., Cazzolato, G., Taroni, G.C. and Belussi, F., Chemical composition of ultracentrifugal fractions in different patterns of human atherosclerosis, Atherosclerosis, 26 (1977) 163. 20 Taggart, H. and Storet, R.W., Reduced high density lipoprotein in stroke - Relationship with elevated triglyceride and hypertension, Europ. J. Clin. Invest., 9 (1979) 219. 21 Terrence, CF. and Rao, G.R., Triglycerides as a risk factor in extracranial atherosclerotic cerebrovascular disease, Angiology, 34 (1983) 452. 22 Fabris, F., Randi, M.L., Crociani, M.E., Manzoni, S., Tonin, P., De Zanche, L.. Cella, G. and Girolami, A., Platelet-specific proteins with transient ischemic attacks, Ric. Chn. Lab., 13 (1983) 437. 23 Levine, S.P., Lindenfeld, J., Ellis, J.B., Raymond, N.M. and Krentz, L.S., Increased plasma concentration of platelet factor 4 in coronary artery disease, Circulation, 64 (1981) 626. Clinical Pathology Laboratory General Hospital Chiari - Rovato, 25032 Chiari (Bs) (Italy) (Received 1 June, 1984) (Revised, received 20 September, (Accepted 20 September, 1984)
R. Airb C.M. Ferrari 1984)