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Discriminative value of lipids and apoproteins in coronary heart disease
197
Atherosclerosis, 42 ( 1982) 197-203
Elsevier/North-Holland
Scientific
Publishers,
Ltd
Discriminative Value of Lipids and Apoproteins in Coronary Heart Disease G. De Backer ‘, M. Rosseneu 3 and J.P. Deslypere * National
Fund for Scientific Research, Academisch Ziekenhuis,
’Department
of Curdiology and ’ Department of Endocrinology,
Gent; und’ Algemeen Ziekenhuis St. Jun, Brugge (Belgium)
(Received 7 August. 1981) (Accepted 14 September, 1981)
Serum cholesterol, HDL cholesterol (HDL-C), and apoproteins, Al, A2 and B were determined in 70 male survivors of myocardial infarction and in an equal number of healthy controls, matched for age, sex and body mass index. In univariate analyses, the Apo B/APO Al ratio discriminated the best between cases and controls, giving a 72% exact classification. In a multivariate analysis, the Apo B/APO Al ratio, HDL-C and the Apo A2/Apo Al ratio contributed independently to the discrimination of cases from controls while the overall exact classification was 82%. These promising results were comparable in younger and older subgroups. Thus, the determination of apoproteins yielded complementary information in this cross-sectional survey and warrants further study in a prospective setting. Key words: Apoproteins function
- Atherosclerosis - Coronary heart disease - Discriminant - Lipids - Myocardial infarction
Introduction
Epidemiological studies have shown that within and between populations, the total serum cholesterol (TC) and HDL cholesterol (HDL-C) levels contribute independently to the prediction of coronary risk [l-5]. These results are of great importance to public health but do not apply to a similar extent to the prediction of individual risk. The atherogenic risk in a given patient is only partially characterized by his TC and HDL-C levels. Clinical and experimental studies do suggest that other lipid measurements and the apoprotein composition of the lipoproteins could be important for atherogenicity [6- 131. The purpose of the present study was to investigate the discriminative value of 0021-9150/82/0000-0000/$02.75
0 1982 Elsevier/North-Holland
Scientific
Publishers,
Ltd
198
different lipid and apoprotein measurements in survivors of myocardial infarction and in normal controls.
Patients and Methods The patients included in this report were 70 male subjects who had survived myocardial infarction, not less than 3 months before the present study. The diagno‘sis was based on WHO recommended criteria [14]. For these patients an equal number of controls was selected, matched for age and body mass index (W/H*). Controls were asymptomatic, free of electrocardiographic abnormalities and selected from a continuing population survey. None of the cases or the controls was on lidid-lowering drugs. The apoprotein measurements were made by immunonephelometry [ 151. TC and HDL-C were determined by Auto-Analyser according to Boy et al. [ 161and Steele et al. [17]. Cases were compared with controls by the Student t- and &i-square tests. The independent discriminant value of each variable was evaluated by a stepwise multiple discriminant function analysis’[ 181.
Results In Table 1 the patients are compared with the controls in age and body mass index. These results illustrate the comparability of both groups in age structure and degree of obesity. In Table2 mean values and standard deviations are presented for TC, HDL-C, Apo Al, Apo A2 and Apo B as well as for the ratios derived from these measurements as HDL-C/TC, Apo B/APO Al and Apo AZ/APO Al. The differences between cases and controls are not statistically significant for TC and Apo A2. For
TABLE I COMPARABILITY OF CASES AND CONTROLS IN AGE AND BODY MASS INDEX Cases (n = 70)
Controls (n = 70)
t
50.6 10.1 34-71
50.1 9.2 35-70
0.3 B
25.4 2.9 19-32
26.2 3.6 20-38
l.5a
Age W Mean SD Range Body mass index (wt, kg/l% m2) Mean SD Range a P not significant.
199
TABLE 2 COMPARISON
OF CASES AND CONTROLS cases
Total chol. (mg/ 100 ml) Mean SD HDL chol (mg/lOO ml) Mean SD Apo Al (mg/lOO ml) Mean SD Apo A2 (mg/ 100 ml) Mean SD Apo B (mg/lOO ml) Mean SD HDL-C/TC (S) Mean SD Apo B/APO Al (RI) Mean SD Apo AZ/APO Al (W) Mean SD
IN LIPIDS
(n = 70)
AND APOPROTEINS Controls
t
(n= 70)
1.7 =
253.6 30.7
242.4 46.3
45.7 7.6
56.9 13.2
6.2 ***
111.1 24.5
124.7 21.4
3.5 ***
46.3 12.6
43.0 6.9
143.2 31.9
113.4
18.2 3.7
24.3 7.2
6.3 ***
134.7 41.3
93.2 23.9
7.4 ***
42.0 8.2
34.9 4.9
6.2 **+
1.9=
6.3 ***
23.3
’ P not significant. *** P
3
DISCRIMINATIVE VALUE THE MEAN VALUES Variable
Mean value
OF THE LIPID
Cases (a n
TC (mg/ 100 ml) HDL-C (mg/ 100 ml) Apo Al (mg/lOO ml) Apo A2 (mg/ 100 ml) Apo B (mg/lOO ml) HDL-C/TC (W) Apo B/APO Al (S) Apo AZ/APO A (W) a * ** ***
P not significant. P
248 51 118 45 128 21 114 38
42 22 25 33 49 18 43 41
AND APOPROTEIN
Controls
mean value) % n 60 31 36 47 70 26 61 59
29 46 43 23 18 46 12 17
MEASUREMENTS
Total % correctly classified
Chisquare
60 68 63 57 72 70 72 68
4.1 15.1 8.3 2.4 25.4 21.0 26.9 15.6
% 41 66 61 33 26 66 17 24
* *** ** a *** *** *** ***
BASED
ON
200 TABLE 4 RESULTS OF THE STEPWISE DISCRIMINANT FUNCTION ANALYSIS BETWEEN CASES AND CONTROLS Variables
Coefficient
Total I correctly classified
F
Apo B/APO Al HDL-C Apo AZ/APO Al TC HDL-C/TC Constant
0.013 0.040 0.069 -0.021 -0.200 3.2
12 77 80 80 82
18.8 *** 6.3 * 4.9 * 0.3 2.1
* P-=0.05. ***
P
HDL-C, Apo Al, Apo B and the ratios the differences are highly significant (P
TABLE 5 DISCRIMINATIVE VALUE OF THE COMBINATION OF LIPID AND APOPROTEIN MEASUREMENTS ACCORDING TO AGE Age (yr)
Stepwise multiple discriminant function n and % exact classification Controls
Cases
G50 >50
Total
n
I%
n
%
n
x
27 g
75 82
M 40 26 30
85 87
6, 64 ::
80 84
201
strongest discriminator and was selected first. HDL-C and the Apo A2/Apo Al ratio added significantly to the discrimination of cases from controls. The overall percentage of exact classification was 82%. Finally the value of the discriminative function was studied separately in the 76 subjects aged 50 or below and in the 64 aged more than 50 years. The results are presented in Table 5. An equal discriminant value is found in younger and older age groups.
Discussion The increasing interest in detailed measurements of the lipoproteins and their protein and lipid moieties is based on experimental evidence linking the different fractions to specific functions, which may be important in the understanding and management of atherosclerosis. The high density lipoproteins in particular have received great attention over the last years because of their possible role in removing cholesterol from cells and their eventual “protective” effect against atherosclerosis. Epidemiological studies have clearly revealed the importance of total serum cholesterol as a risk indicator for CHD [l-3]; this links with the public health need for preventive efforts and allows the subclassification of the population in groups at different risk levels. However, the prediction of the risk for CHD on an individual basis derived from the traditional CHD risk factors is still unsatisfactory. Recent studies indicate that apoprotein quantification might prove useful in that respect [6- 131. In a previous study of the discriminative value of apoproteins and lipids in young patients with myocardial infarction we have applied a similar case control design [19]. In that study we were able to correctly classify 85% of the total population. Encouraged by these results we decided to replicate the study in a larger group with a broader age range. The matching procedure provided a good comparability of cases and controls in age and body mass index. TC was only a poor discriminator, but the mean levels of HDL-C, Apo Al and Apo B were significantly different between cases and controls. The discriminant value of these single measurements was less compared to the differences between cases and controls in ratios of lipids or apoproteins. The absolute values of the apoproteins Al and A2 were not so relevant, while their ratio was clearly of great discriminative value. The difference in ratio of Apo B/APO Al showed the greatest t-value. When the discriminant value of the Apo B/APO Al ratio was studied by calculating the percentage of exactly classified subjects using the overall mean as a cut-off point, 72% accuracy was observed. By the use of a stepwise discriminant function analysis the percentage of correctly classified subjects could be increased to 82%. The HDL-C quantification seems to contain a discriminative value independent from the Apo B/APO Al ratio. Moreover the internal proportional structure of a given lipoprotein seems to be important, as reflected by the Apo AZ/APO Al ratio. The latter may provide a more accurate reflection of the HDL-distribution.
202
When the results are separately analysed in the groups aged above or below 50 years, no major differences in results are observed. This suggests an equal discriminative value of the variables within the age range 35-70 years. Despite these promising results one should be cautious in implementing these results for the prediction of CHD risk in the general population. Indeed, case control studies have the disadvantage that observed differences may be influenced or introduced by the sickness itself and therefore be irrelevant in the prediction of risk. On the contrary, case control studies may be falsely negative by omitting the fatal cases in whom more pronounced differences from normal controls may have existed. In addition the differences in lipids and apoproteins between cases and controls may be mediated through other traditional risk factors or behavioural habits such as smoking, eating or exercise regimes. HDL and apoproteins seem to be related to alcohol consumption [20,24] smoking [ 11,21,22,24] and exercise practices [22,23,25]. These factors have not been investigated in a standardized way on our study. More than two thirds of the cases had ceased smoking after the infarct. Therefore, if at all, the differences in smoking habits between cases and controls should have reduced the difference in their lipid and apoprotein levels. The results as observed by us indicate the need for prospective studies of the predictive value of apoproteins in the identification of individuals with increased risk for atherosclerotic cardiovascular diseases.
References I Keys, A. (Ed.), Coronary heart disease in seven countries, Circulation, 41 (1970) Suppl. 1. 2 Wilhelmsen, L., Wedel, H. and Tibblin, G., Multivariate analysis of risk factors for coronary heart disease, Circulation, 48 ( 1973) 950. 3 Goldbourt, U., Medalie, J.H. and Neufeld, H.N., Clinical myocardial infarction over a five year period -A multivariate analysis of incidence, the Israel ischaemic heart disease study, J. Chron. Dis., 28 (1975) 217. 4 Gordon, T., Castelh, W.P., Hjdrtland, M.C., Kannel, W.B. and Dawber, T.R., High density lipoprotein as a protective factor against coronary heart disease -The Framingham Study, Amer. J. Med., 62 (1977) 707. ‘5 Miller, N.E., F&de, O.H., Thelle, D.S. and MjBs, O.D., The TromsS Heart Study-High density lipoprotein and coronary heart disease: A prospective case-control study, Lancet, i (1977) 965. 6 Avogaro, P., Bittolo Bon, G., Cazzolato, G. and Qunici, G.B., Are apohpoproteins better discriminators than lipids for atherosclerosis? Lancet, i (1979) 901. 7 Kostner, G.M., Avogaro, P., Carzolato, G., Marth, E., Bittolo Bon, G. and Qunici, G.B., Lipoprotein Lp(a) and the risk for myocardial infarction, Atherosclerosis, 38 (1981) 51. 8 Vergani, C., Trovato, G. and Dioguardi, N., Serum total lipids, lipoproteins cholesterol, apoproteins A and B in cardiovascular disease, Clin. Chim. Acta, 87 (1978) 127. 9 Berg, K., Borresen, A.C. and Dahlen, G., Serum-high-density-lipoprotein and atherosclerotic heart disease, Lance& i (1976) 499. IO Miller, G.J., High density lipoproteins and atherosclerosis, Ann. Rev. Med., 3 1 (1980) 97. 1I Fager, G., Wiklund, O., Olofsson, SO., Wilhelmsson, C. and Bondjers, G.. Serum apolipoprotein levels in relation to acute myocardial infarction and its risk factors, Atherosclerosis, 36 (1980) 67. 12 Ishikawa, T., Fidge, N., Thelle, D.S., F&de, O.H. and Miller, N.E., The Tromso Heart Study-Serum apolipoprotein Al concentration in relation to future coronary heart disease, Europ. J. Clin. Invest., 8 (1978) 179.
203
I3 Tyroler, H.A., Heiss, G., Schonfeld, G., Cooper, G., Heyden, S. and Hames, C.G., Apolipoprotein A-I, A-II and C-II in black and white residents of Evans Country, Circulation, 62 (1980) 249. 14 Ischaemic Heart Disease Registers, Report of a Working Group WHO, Copenhagen, 1971, Euro 8201 (5). 15 Rosseneu, M., Vercaemst, R., Vinaimont, N., Van Torhout, P., Henderson, L.O. and Herbert, P.N., Quantitative determination of human plasma apolipoprotein Al by laser immunonephelometry, Clin. Chem., 27 (1981) 856. 16 Boy, J., Bonnafe, M. and Mazer, J.B., Determination du cholesterol total par une modification de la methode de Pearson, Ann. Biol. Clin., I8 (1960) 669. 17 Steele, B.W., Koehler, D.F., Azar, M.M., Blaszkowski. T.P., Kula, K. and Dempsey, M.E., Enzymatic determination of cholesterol in HDL fractions prepared by a precipitation technique, Clin. Chem., 22 (1976) 98. 18 Lachenbruch, P.A., Discriminant Analysis, Hafner Press, New York, 1975. 19 Deslypere, J.P., De Backer, G., Rosseneu, M. and Vermeulen, A., Lipid and apoprotein levels in myocardial infarction survivors-A case control study, Acta Cardiol., In press. 20 Dedonder-Decoopman, E., Fievet-Desreumaux, C., Campos, E., Mouhn, S., Dewailly, P., Sezille, G. and Jaillard, J.. Plasma levels of VLDL- + LDL-cholesterol, HDL-cholesterol, triglycerides and apoproteins B and A-l in a healthy population-Influence of several risk factors, Atherosclerosis, 37 (1980) 559. 21 Berg, K, Borresen, A.L. and Dahlen, G., Effect of smoking on serum levels of HDL apoproteins, Atherosclerosis, 34 (I 979) 339. 22 Euger, SC., Herbjomsen, K., Erickssen, J. and Fretland, A., High density lipoproteins and physical activity-The influence of physical exercise, age and smoking on HDL cholesterol and the HDL/ total cholesterol ratio, Stand. J. Chn. Lab. Invest., 37 (1977) 251. 23 Christie, R.J., Bloore, H.G. and Logan, R.L., High density lipoproteins (HDL) cholesterol in middle-aged joggers, New Zealand Med. J., 652 (I 980) 39. 24 Garrison, R.J., Kannel, W.B., Feinleib, M., Castelli, W.P., McNamara, P.M. and Padgett, S.J., Cigarette smoking and HDL cholesterol-The Framingham Offspring Study, Atherosclerosis, 30 (1978) 17. 25 Huttunen, J.K., L&nsimies, E., Voutilainen, E., Ehnholm, C., Hietanen, E., Penn%, I., Siitonen, 0. and Rauramaa, R., Effect of moderate physical exercise on serum lipoproteins, Circulation, 60 (I 979) 1220.
Atherosclerosis, 42 ( 1982) 197-203
Elsevier/North-Holland
Scientific
Publishers,
Ltd
Discriminative Value of Lipids and Apoproteins in Coronary Heart Disease G. De Backer ‘, M. Rosseneu 3 and J.P. Deslypere * National
Fund for Scientific Research, Academisch Ziekenhuis,
’Department
of Curdiology and ’ Department of Endocrinology,
Gent; und’ Algemeen Ziekenhuis St. Jun, Brugge (Belgium)
(Received 7 August. 1981) (Accepted 14 September, 1981)
Serum cholesterol, HDL cholesterol (HDL-C), and apoproteins, Al, A2 and B were determined in 70 male survivors of myocardial infarction and in an equal number of healthy controls, matched for age, sex and body mass index. In univariate analyses, the Apo B/APO Al ratio discriminated the best between cases and controls, giving a 72% exact classification. In a multivariate analysis, the Apo B/APO Al ratio, HDL-C and the Apo A2/Apo Al ratio contributed independently to the discrimination of cases from controls while the overall exact classification was 82%. These promising results were comparable in younger and older subgroups. Thus, the determination of apoproteins yielded complementary information in this cross-sectional survey and warrants further study in a prospective setting. Key words: Apoproteins function
- Atherosclerosis - Coronary heart disease - Discriminant - Lipids - Myocardial infarction
Introduction
Epidemiological studies have shown that within and between populations, the total serum cholesterol (TC) and HDL cholesterol (HDL-C) levels contribute independently to the prediction of coronary risk [l-5]. These results are of great importance to public health but do not apply to a similar extent to the prediction of individual risk. The atherogenic risk in a given patient is only partially characterized by his TC and HDL-C levels. Clinical and experimental studies do suggest that other lipid measurements and the apoprotein composition of the lipoproteins could be important for atherogenicity [6- 131. The purpose of the present study was to investigate the discriminative value of 0021-9150/82/0000-0000/$02.75
0 1982 Elsevier/North-Holland
Scientific
Publishers,
Ltd
198
different lipid and apoprotein measurements in survivors of myocardial infarction and in normal controls.
Patients and Methods The patients included in this report were 70 male subjects who had survived myocardial infarction, not less than 3 months before the present study. The diagno‘sis was based on WHO recommended criteria [14]. For these patients an equal number of controls was selected, matched for age and body mass index (W/H*). Controls were asymptomatic, free of electrocardiographic abnormalities and selected from a continuing population survey. None of the cases or the controls was on lidid-lowering drugs. The apoprotein measurements were made by immunonephelometry [ 151. TC and HDL-C were determined by Auto-Analyser according to Boy et al. [ 161and Steele et al. [17]. Cases were compared with controls by the Student t- and &i-square tests. The independent discriminant value of each variable was evaluated by a stepwise multiple discriminant function analysis’[ 181.
Results In Table 1 the patients are compared with the controls in age and body mass index. These results illustrate the comparability of both groups in age structure and degree of obesity. In Table2 mean values and standard deviations are presented for TC, HDL-C, Apo Al, Apo A2 and Apo B as well as for the ratios derived from these measurements as HDL-C/TC, Apo B/APO Al and Apo AZ/APO Al. The differences between cases and controls are not statistically significant for TC and Apo A2. For
TABLE I COMPARABILITY OF CASES AND CONTROLS IN AGE AND BODY MASS INDEX Cases (n = 70)
Controls (n = 70)
t
50.6 10.1 34-71
50.1 9.2 35-70
0.3 B
25.4 2.9 19-32
26.2 3.6 20-38
l.5a
Age W Mean SD Range Body mass index (wt, kg/l% m2) Mean SD Range a P not significant.
199
TABLE 2 COMPARISON
OF CASES AND CONTROLS cases
Total chol. (mg/ 100 ml) Mean SD HDL chol (mg/lOO ml) Mean SD Apo Al (mg/lOO ml) Mean SD Apo A2 (mg/ 100 ml) Mean SD Apo B (mg/lOO ml) Mean SD HDL-C/TC (S) Mean SD Apo B/APO Al (RI) Mean SD Apo AZ/APO Al (W) Mean SD
IN LIPIDS
(n = 70)
AND APOPROTEINS Controls
t
(n= 70)
1.7 =
253.6 30.7
242.4 46.3
45.7 7.6
56.9 13.2
6.2 ***
111.1 24.5
124.7 21.4
3.5 ***
46.3 12.6
43.0 6.9
143.2 31.9
113.4
18.2 3.7
24.3 7.2
6.3 ***
134.7 41.3
93.2 23.9
7.4 ***
42.0 8.2
34.9 4.9
6.2 **+
1.9=
6.3 ***
23.3
’ P not significant. *** P
3
DISCRIMINATIVE VALUE THE MEAN VALUES Variable
Mean value
OF THE LIPID
Cases (a n
TC (mg/ 100 ml) HDL-C (mg/ 100 ml) Apo Al (mg/lOO ml) Apo A2 (mg/ 100 ml) Apo B (mg/lOO ml) HDL-C/TC (W) Apo B/APO Al (S) Apo AZ/APO A (W) a * ** ***
P not significant. P
248 51 118 45 128 21 114 38
42 22 25 33 49 18 43 41
AND APOPROTEIN
Controls
mean value) % n 60 31 36 47 70 26 61 59
29 46 43 23 18 46 12 17
MEASUREMENTS
Total % correctly classified
Chisquare
60 68 63 57 72 70 72 68
4.1 15.1 8.3 2.4 25.4 21.0 26.9 15.6
% 41 66 61 33 26 66 17 24
* *** ** a *** *** *** ***
BASED
ON
200 TABLE 4 RESULTS OF THE STEPWISE DISCRIMINANT FUNCTION ANALYSIS BETWEEN CASES AND CONTROLS Variables
Coefficient
Total I correctly classified
F
Apo B/APO Al HDL-C Apo AZ/APO Al TC HDL-C/TC Constant
0.013 0.040 0.069 -0.021 -0.200 3.2
12 77 80 80 82
18.8 *** 6.3 * 4.9 * 0.3 2.1
* P-=0.05. ***
P
HDL-C, Apo Al, Apo B and the ratios the differences are highly significant (P
TABLE 5 DISCRIMINATIVE VALUE OF THE COMBINATION OF LIPID AND APOPROTEIN MEASUREMENTS ACCORDING TO AGE Age (yr)
Stepwise multiple discriminant function n and % exact classification Controls
Cases
G50 >50
Total
n
I%
n
%
n
x
27 g
75 82
M 40 26 30
85 87
6, 64 ::
80 84
201
strongest discriminator and was selected first. HDL-C and the Apo A2/Apo Al ratio added significantly to the discrimination of cases from controls. The overall percentage of exact classification was 82%. Finally the value of the discriminative function was studied separately in the 76 subjects aged 50 or below and in the 64 aged more than 50 years. The results are presented in Table 5. An equal discriminant value is found in younger and older age groups.
Discussion The increasing interest in detailed measurements of the lipoproteins and their protein and lipid moieties is based on experimental evidence linking the different fractions to specific functions, which may be important in the understanding and management of atherosclerosis. The high density lipoproteins in particular have received great attention over the last years because of their possible role in removing cholesterol from cells and their eventual “protective” effect against atherosclerosis. Epidemiological studies have clearly revealed the importance of total serum cholesterol as a risk indicator for CHD [l-3]; this links with the public health need for preventive efforts and allows the subclassification of the population in groups at different risk levels. However, the prediction of the risk for CHD on an individual basis derived from the traditional CHD risk factors is still unsatisfactory. Recent studies indicate that apoprotein quantification might prove useful in that respect [6- 131. In a previous study of the discriminative value of apoproteins and lipids in young patients with myocardial infarction we have applied a similar case control design [19]. In that study we were able to correctly classify 85% of the total population. Encouraged by these results we decided to replicate the study in a larger group with a broader age range. The matching procedure provided a good comparability of cases and controls in age and body mass index. TC was only a poor discriminator, but the mean levels of HDL-C, Apo Al and Apo B were significantly different between cases and controls. The discriminant value of these single measurements was less compared to the differences between cases and controls in ratios of lipids or apoproteins. The absolute values of the apoproteins Al and A2 were not so relevant, while their ratio was clearly of great discriminative value. The difference in ratio of Apo B/APO Al showed the greatest t-value. When the discriminant value of the Apo B/APO Al ratio was studied by calculating the percentage of exactly classified subjects using the overall mean as a cut-off point, 72% accuracy was observed. By the use of a stepwise discriminant function analysis the percentage of correctly classified subjects could be increased to 82%. The HDL-C quantification seems to contain a discriminative value independent from the Apo B/APO Al ratio. Moreover the internal proportional structure of a given lipoprotein seems to be important, as reflected by the Apo AZ/APO Al ratio. The latter may provide a more accurate reflection of the HDL-distribution.
202
When the results are separately analysed in the groups aged above or below 50 years, no major differences in results are observed. This suggests an equal discriminative value of the variables within the age range 35-70 years. Despite these promising results one should be cautious in implementing these results for the prediction of CHD risk in the general population. Indeed, case control studies have the disadvantage that observed differences may be influenced or introduced by the sickness itself and therefore be irrelevant in the prediction of risk. On the contrary, case control studies may be falsely negative by omitting the fatal cases in whom more pronounced differences from normal controls may have existed. In addition the differences in lipids and apoproteins between cases and controls may be mediated through other traditional risk factors or behavioural habits such as smoking, eating or exercise regimes. HDL and apoproteins seem to be related to alcohol consumption [20,24] smoking [ 11,21,22,24] and exercise practices [22,23,25]. These factors have not been investigated in a standardized way on our study. More than two thirds of the cases had ceased smoking after the infarct. Therefore, if at all, the differences in smoking habits between cases and controls should have reduced the difference in their lipid and apoprotein levels. The results as observed by us indicate the need for prospective studies of the predictive value of apoproteins in the identification of individuals with increased risk for atherosclerotic cardiovascular diseases.
References I Keys, A. (Ed.), Coronary heart disease in seven countries, Circulation, 41 (1970) Suppl. 1. 2 Wilhelmsen, L., Wedel, H. and Tibblin, G., Multivariate analysis of risk factors for coronary heart disease, Circulation, 48 ( 1973) 950. 3 Goldbourt, U., Medalie, J.H. and Neufeld, H.N., Clinical myocardial infarction over a five year period -A multivariate analysis of incidence, the Israel ischaemic heart disease study, J. Chron. Dis., 28 (1975) 217. 4 Gordon, T., Castelh, W.P., Hjdrtland, M.C., Kannel, W.B. and Dawber, T.R., High density lipoprotein as a protective factor against coronary heart disease -The Framingham Study, Amer. J. Med., 62 (1977) 707. ‘5 Miller, N.E., F&de, O.H., Thelle, D.S. and MjBs, O.D., The TromsS Heart Study-High density lipoprotein and coronary heart disease: A prospective case-control study, Lancet, i (1977) 965. 6 Avogaro, P., Bittolo Bon, G., Cazzolato, G. and Qunici, G.B., Are apohpoproteins better discriminators than lipids for atherosclerosis? Lancet, i (1979) 901. 7 Kostner, G.M., Avogaro, P., Carzolato, G., Marth, E., Bittolo Bon, G. and Qunici, G.B., Lipoprotein Lp(a) and the risk for myocardial infarction, Atherosclerosis, 38 (1981) 51. 8 Vergani, C., Trovato, G. and Dioguardi, N., Serum total lipids, lipoproteins cholesterol, apoproteins A and B in cardiovascular disease, Clin. Chim. Acta, 87 (1978) 127. 9 Berg, K., Borresen, A.C. and Dahlen, G., Serum-high-density-lipoprotein and atherosclerotic heart disease, Lance& i (1976) 499. IO Miller, G.J., High density lipoproteins and atherosclerosis, Ann. Rev. Med., 3 1 (1980) 97. 1I Fager, G., Wiklund, O., Olofsson, SO., Wilhelmsson, C. and Bondjers, G.. Serum apolipoprotein levels in relation to acute myocardial infarction and its risk factors, Atherosclerosis, 36 (1980) 67. 12 Ishikawa, T., Fidge, N., Thelle, D.S., F&de, O.H. and Miller, N.E., The Tromso Heart Study-Serum apolipoprotein Al concentration in relation to future coronary heart disease, Europ. J. Clin. Invest., 8 (1978) 179.
203
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