- Email: [email protected]
Serum cholesterol and triglycerides in patients suffering from ischemic heart disease and in healthy subjects
197
Atherosclerosis, 28 (1977) 197-204 Scientific @ Elsevier/North-Holland
Publishers,
Ltd.
SERUM CHOLESTEROL AND TRIGLYCERIDES IN PATIENTS SUFFERING FROM ISCHEMIC HEART DISEASE AND IN HEALTHY SUBJECTS *
D. BRUNNER,
S. ALTMAN,
K. LOEBL,
Medical Department A, Government Hygiene, Tel Aviv University (Israel) (Received (Revised, (Accepted
S. SCHWARTZ
Hospital
Jaffa,
and S. LEVIN
and Donolo
Institute
of Physiological
12 August, 1976) received 10 June, 1977) 11 June, 1977)
Summary Serum cholesterol (CH) and triglyceride (TG) values were determined in 142 male and 58 female patients 35-74 years old, who suffered from angina pectoris (AP) or had a myocardial infarction (MI) (in the following referred to as ischemic heart disease (IHD) patients), as well as in 2219 male and 1469 female healthy normotensive subjects. Blood samples were taken in the fasting state. Blood from patients who had suffered from MI was examined three months after the acute event. In age subgroups 35-44, 45-54 and 55-64 years, no significant differences in serum CH was found between IHD patients and healthy subjects, except in males 35-44 years old. However, TG values were significantly elevated in coronary patients of all age groups. In all subgroups with equal CH values, significantly higher TG values were found in IHD patients than in healthy controls. In all subgroups with equal TG levels, no difference in average CH values was found between IHD patients and healthy subjects, except in females with TG below 150 mg%. The results suggest that in the population from which the two groups were recruited, elevated TG values were equal or superior to elevated CH values as indicators of coronary risk. Key words
* This ment,
study
Cholesterol Serum lipids
was supported
Bethesda.
Correspondence
MD. should
Triglycerides
in part
by
grant
- Myocardial
HE
04520
from
infarction
the National
- Ischemic
Institutes
heart disease
of Health,
US Govern-
U.S.A. bc sent
to Dr.
Daniel
Bnmncr,
GovcmmrnL
Hospital,
P.O.
Box
93,
Jaffa,
Israel.
-
198
Introduction Epidemiological and clinical studies bear witness to a correlation between serum cholesterol (CH) levels and myocardial infarction (MI) and other clinical manifestations of ischemic heart disease (IHD) [l-4]. Since 1960, there has been growing interest in the bearing of serum triglyceride (TG) levels on IHD [5--S]. A significantly greater number of lipid abnormalities was demonstrated in patients with angiographically documented coronary artery disease as compared with healthy controls [9]. However, it has been suggested that serum CH is the most powerful risk factor for IHD, and that other lipids or lipoprotein fractions, and especially serum TG are only accompanying components which have no independent relationship and which confer no increased risk to the incidence of IHD [2,6,10,11]. This assumption is not supported by other studies [ 7,121. The purpose of the present investigation is to examine the relationship of serum TG and CH in patients with IHD and in healthy subjects. Material and methods This study comprises 142 male and 58 female patients, subsequently admitted to our ward with a diagnosis of IHD; 102 of the male and 42 of the female patients were hospitalized for acute MI. The diagnostic criteria of MI were: (a) typical chest pains; (b) serial ECG changes consistent with acute MI; (c) transient elevations of serum glutamic oxaloacetic transaminase. The remaining 40 male and 16 female patients were hospitalized for coronary insufficiency or for angina pectoris (AP). Coronary insufficiency was diagnosed in patients with typical chest pains without increased myocardial enzymes and associated with ST segment depression (Minnesota Code IV 1 and 2) and/or negative T-waves (Minnesota Code V 1 and 2), which lasted for one till six days. The AP-patients underwent a multistaged symptom-or-signs-limited workload test on a bicycle ergometer. 2 mm downsloping or horizontal ST-segment depression, and upsloping ST segments with 2 mm ST depression measured 0.08 set from the I-point (Minnesota Code for post-exercise records IX l-5) were considered indicative of AP. Only such patients were included in this study. Since the relationship of serum lipids does not vary with the type of coronary heart disease, AP-patients and post MI-patients were considered a uniform group. The control group consists of subjects who were examined in the course of the Tel Aviv-Donolo Prospective Ischemic Heart Disease Study [ 131. Initially, 4669 subjects were examined. After exclusion of all those with a systolic blood pressure higher than 160 mm Hg, and those with specific or non-specific ECGfindings of possible clinical significance, 3688 subjects remained, and these (2219 males and 1469 females) comprise the control group. Serum TG were determined in the last 452 subjects examined in the Prospective IHD Study. These subjects were in no way different from the remainder of the control group. 62 persons were excluded for increased blood pressure and/or pathological ECG-findings. Thus, the control group for the TG studies consists of 302 males and 88 females. Table 1 shows body weight and body height in age-specific groups. There
199 TABLE BODY
1 WEIGHT
AND
HEIGHT
Males Age
(years)
35-44 HC
IHD
HC
IHD
HC
IHD
15
834
40
871
57
514
30
(kg)
76.0
74.4
(10.8) Height
(cm)
a
170.7
(11.1) 169.4
(5.8)
Age
(6.7)
Height
HC
17 (kg)
(cm)
1163
74.6
(8.9)
(9.5)
(8.3)
168.9 (5.4)
168.4 (6.4)
IHD
HC
41
306
66.9
65.2
66.0
65.6
(10.4)
(11.1)
(10.1)
(10.8)
155.8
155.6
155.6
156.6
(6.3) a Standard
73.1
deviation
168.4 (6.0)
72.7 (10.3) 167.9 (6.6)
72.2 (9.5) 166.9 (7.6)
55-74
IHD
NO.
73.7
HC
(years)
35-54
Weight
65-74
5544
IHD
NO. Weight
45-54 ~____
(6.7)
(5.9)
(6.6)
in parentheses.
were no significant differences between patients and healthy subjects. Blood samples were obtained in the morning following a 12-h overnight fast. In post MI-patients, blood samples were drawn in our post-MI hospital unit three months after the acute event. During their hospitalization and before leaving the hospital, MI-patients were advised to avoid weight gain. Specific dietary or lipid lowering drug therapy was prescribed three months after the infarction only when indicated by serum lipid determinations. Serum CH was determined by the method described by Anderson and Keys [ 141 ; serum TG according to the method of Van Handel-Zilversmith [ 151. Results Tables 2 and 3 present the biochemical findings and standard deviations of males 35-44, 45-54, 55-64 and 65-74 years old, and of females 35-54 and 55-74 years old. For the relatively small number of females only two age groups have been established. Except for males of the youngest age group, no significant differences in CH levels between coronary patients and healthy controls were found. On the other hand, in all subgroups, in males as well as in females, the differences in TG values were of significance, on the level of P < 0.01 or P < 0.05.
200
TABLE
2
SERUM
LIPIDS
-MALES
35-44
No.
of cases
Cholesterol mg%
(mean)
(S.D.)
Statisticdl No.
IHD
HC
15
834
243.2
of cases
IHD
HC
40
871
219.4
36.5
225.1
50.8
59.3 P <
57
91.4
30
230.4
231.8
40.1
54.3
HC -
n.s.
134.5
57
71
30
152.5
132.4
128.2
64.3
59.5
0.01
514
55.1
126
189.9
IHD
HC
221.4
40.3
40
126.3
65-74
IHD
n.s.
105
228.8 123.6
significance
5544
P < 0.05 15
(mean)
(S.D.)
Statistical
218.4
61.4 significance
Triglycerides mg%
45-54 ____~
P < 0.01
52.4 P <
54.2
0.05
Tables 4 and 5 show subgroups of males and females, listed according to CH levels, less than 200,200-224,225-249 and 250 mg% and more. In all groups the patients had significantly higher TG values than the healthy controls with same CH levels, except for the group of males with CH level of 250 mg% or more, where control subjects, too, had increased TG values. Tables 6 and 7 show subgroups according to TG values, above and below 250 mg%. No healthy female had TG values over 250 mg%. In males as well as in females no significant differences in CH values were found. It is conceivable that the figures of female subjects in some of the subgroups are rather small, because MI and coronary artery disease are less common in females under the age of 54 years, and most of the healthy females have TG values less than 150 mg%.
TABLE
3
SERUM
LIPIDS
-FEMALES Age
(years)
35-54
55-74 HC
IHD
No. of caz.es Cholesterol mg%
(S.D.)
Statistical No.
17 (mean)
significance
39.3
41
306
267.1
58
200.8
98.0 30.8 )’ <
251.3
60.7
43.5 n.s.
56.8 significance
HC
n.s. 17
(mean)
mgqb (S.D.) Statistical
224.4
33.5
of cases
higlycerides
1163
236.2
IHD
0.01
41
30
190.1
109.5
76.5
33.2 I’ < 0.01
201
TABLE
4
SERUM
CHOLESTEROL
Specific
subgroups.
-
MALES
Cholesterol Less
than
(mg%) 200
225-249
200-224
250
or more
IHD
No.
of cases
49
Triglycerides
(mg%)
116.7
87.4
TABLE
HC
HC
IHD
85
25
60
36
48
139.9
172.7
131.9
190.9
188.7
94.9
75.5
87.6
57.4
84.1
P < 0.05
P < 0.05
122.2
n.s.
5
SERUM
CHOLESTEROL
Specific
subgroups
-
FEMALES
Cholesterol Less
than
(mg%) 250
250
IHD
No. of cases (mg%)
S.D.
57.1
Statistical
HC
32
16
91.6
236.7
132.8
38.3
111.0
72
149.1
or more
IHD
HC
26
Triglycerides
TABLE
IHD
32
57.2
P < 0.01
significance
HC
177.9
109
146.8
S.D. Statistical
IHD
HC
68.9
P < 0.01
significance
P < 0.01
6
TRIGLYCERIDES-MALES Specific
subgroups Triglycerides Less
than
(mg%) 150
IHD
No.
of cases
Cholesterol
HC
61 (mg%)
44.2
Statistical
TABLE
significance
TRIGLYCERIDES
HC
IHD
HC
62
86
19
22
228.9
216.9
251.8
246.1
35.3
56.8
n.s.
32.7
59.7
n.s.
52.0 n.s.
-
FEMALES
subgroups Triglycerides Less
than
IHD of cases
Cholesterol
(mg%)
S.D. Statistical
IHD
or more
7
Specific
No.
250
210.1
194
216.6
S.D.
150-249
150-249
150 HC
250
IHD
HC
IHD
28
76
19
12
11
248.2
221.8
158.5
260.3
279.2
54.7 significance
(mg%)
31.7 n.s.
50.0
50.0 Il.%
69.3
or more HC
202
Discussion
Serum lipid determinations of post-MI-patients were performed three months after the acute event. It has been reported that CH levels fall significantly following acute MI, and return to the pre-disease level after 12 weeks. The variations in TG were small and insignificant [ 161. Thus, it can be assumed that CH and TG levels determined three months after the acute event are similar to the pre-infarction values. Our results revealed that fasting TG levels were significantly elevated in patients with IHD when compared with sex- and age-matched healthy subjects. On the other hand, there was no significant difference in CH values between the two groups, with the exception of males between 35-44 years old. In subgroups with equal CH, TG levels were significantly higher in IHD patients of both sexes than in healthy controls. As opposed to this, in subgroups with equal TG, there was no significant difference in CH levels between the two groups. Carlson and Ericson [17] recently reported lipoprotein findings in Swedish men. As in our study, they found significantly higher TG levels in coronary patients than in healthy controls. However, contrary to our results, their patients also had significantly higher serum’ CH levels. Almost all TG in chylomicron-free serum are concentrated in the very low density lipoproteins or pre-beta-lipoproteins, coded by Fredericksen et al. as dislipoproteinemia type IV [ 181. Retrospective studies in European populations demonstrated that the TG rich pre-beta-lipoproteins are the commonest disorder in IHD [ 191. Our observations point to the same conclusions. Serum lipids may be influenced by various factors: overweight, diet or seasonal fluctuations. It was shown that overweight persons have higher serum TG values, whereas serum CH is not influenced by or associated with overweight [ 171. However, in our study the age-specific subgroups of patients and healthy persons did not differ in their relative body weight (Table 1). No individual diet information was obtained in our population study of 3668 healthy persons, nor from the 188 coronary patients. However, there is no reason to assume that their diet was different from the average diet habits in Israel. According to publications of the Central Bureau of Statistics of the Israel Government, the available nutrients per capita per day in 1973 were 96 g protein: 45 g were animal protein, 111 g fats and 380 g carbohydrates [ 201. Since blood samples of both, the healthy persons and the coronary patients, were collected over a period of two years, any possible influence of seasonal fluctuation would be balanced [ 21,221. Since our survey is not a prospective study, we can only surmise that in healthy subjects elevated serum TG levels, not associated with increased CH, represent an independent risk factor for future coronary disease. This assumption is at variance with the conclusions drawn from the Framingham Study, where it was found that CH and TG levels are closely correlated, and that TGrich-low-density-lipoprotein fractions alone have a limited independent relationship with the incidence of coronary artery disease. Similarly, Brown et al. [7] reported that marked hypertriglyceridemia combined with normal CH values is uncommon, and that the relationship of pure hypertriglyceridemia to
203
IDH is difficult to assess. But in contrast to this, Carlson and Boettinger [8], in analyzing the results of the Prospective Stockholm Study, noted considerable increase in risk of future IHD in subjects with elevated serum TG. They concluded that both, TG and CH are risk factors for IHD, independent of each other. In this context it is interesting to mention a three-year follow-up study of patients after coronary bypass surgery, in which hypertriglyceridemia predisposed to an increased risk of occlusion or stenosis of the aorta-coronary vein graft. Serum CH, however, did not affect the fate of the graft [23]. It seems that genetic and geographic differences, diversities in life style and nutritional habits are correlated with varieties of dislipoproteinemia and lipid levels which in their turn represent IHD risk factors. Our findings do not challenge the assumption that the risk of IHD increases with rising CH levels, and that subjects with CH higher than 350 mg% face much greater risk of developing IHD than those with CH levels, below 200 mg%. However, it is remarkable that even in the National Cooperative Pooling Project of American Surveys 53% of all patients had serum CH levels less than 250 mg%, and only 14.5% more than 300 mg% [24]. Thus, less than half of all patients with manifest IHD had elevated CH, most of them only to a moderate degree. Therefore the serum CH determinations of the majority of the patients did not label them as high risk cases. In our survey only 26% of all patients had CH levels higher than 250 mg%, and 36% below 200 mg%. In populations where many coronary patients have no elevated serum CH, the TG level may be useful as a predictor for future IHD. Particularly great differences in TG values between IHD patients and healthy subjects were found in the youngest age group, 35-44 years old. In the control group we found TG values over 150 mg% in 36% of males and in 12% of females. This, in the light of our findings, indicates that these subjects are high risk cases. The question whether reduction of increased serum TG in healthy subjects will result in a decreasing risk of future IHD can be answered only by a prospective study. References 1 Stamler, J., in: Lectures in Preventive Cardiology. Grune and Stratton Inc.. New York-London, 1967. 2 Kannel, W.B., Castelli, W.P.. Gordon, T. and McNamara, P.M., Serum cholesterol, lipid proteins and the risk of coronary artery disease, Ann. Intern. Med., 74 (1971) l-12. 3 Brunner, D. and Loebl. K.. Serum cholesterol. electrophorctic lipid pattern, diet and coronary artery disease. A study in coronary patients and in healthy men of different origin and occupations in Israel, Ann. Intern. Med.. 49 (1958) 732-750. 4 Keys. A., Coronary heart disease in seven countries, Circulation, 41 (1970) (suppl. 1.1) I-l. 5 Carlson, L.A.. Serum lipids in men with myocardial infarction. Acta Med. Stand., 167 (1960) 399. 6 Albrink. N., Triglycerides, lipoproteins and coronary artery disease, Arch. Int. Med.. 109 (1962) 345359. 7 Brown, D.F., Kinch. S.H. and Doyle, J.T.. Serum triglycerides in health and ischemic heart disease, New Engl. J. Med., 273 (1965) 947-952. 8 Carlson. L.A. and Boettinger. L.E.. Ischemic heart disease in relation to fasting values of plasma triglyceride and cholesterol. Lancct, 1 (1972) 865-868. 9 Heinle. R.A.. Levy, R.I., Fredericksen. D.S. and Corlin. R.. Lipid and carbohydrate abnormalities in patients with angiographically documented coronary artery disease. Am. J. Cardiol.. 24 (1969) 178186. 10 Wilhelmson, L., Wedel. H. and Tibblin, G.. Multivariate analysis of risk factors for coronary heart disease, Circulation, 48 (1973) 950-958.
204 11 Blackbum, 12 13 14 15 16 17 18 19
20 21 22
23 24
H., Progress in the epidemiology and prevention of coronary heart disease, In: Progress in Cardiology, Yu. P.N. and Goodwin, J.F. (eds.), Lea and Febiger, 1974. Rosenman, R.H.. Friedman, M.. Strauss, R., Jenkins, C.D.. Zyansky. S.J. and Wurm. M., Coronary heart disease in the western collaborate group study, J. Chron. Dis., 23 (1970) 173. Brunner, D., Altman, S.. Loebl. K. and Schwartz, S.. Donolo-Tel Aviv prospective study of ischemic heart disease, to be published. Anderson, J.T.. and Keys, A., Cholesterol in serum and lipoprotein fraction, its measurements and stability, Clln. Chem., 2 (1956) 145-159. Van Handel-Zilversmith, E.. Method for direct determination of serum triglycerides, J. Lab. Clin. Med., 50 (1957) 152-157. Fyfe. T., Baxter, R.H. and Cochran, K.M., Plasma lipid changes after myocardial infarction, Lancet, II (1971) 997-1001. Carlson. L.A. and Ericson, M., Quantitative and qualitative serum lipoprotein analysis, Atherosclerosis, 21 (1975) 435-450. Fredericksen, D.S., Levy, R.I. and Lees, R.S.. Fat transport in lipoproteins: An integrated approach to mechanism and disorder, New Engl. J. Med., 276 (1967) 34-44,94-103.148-156. D.. Lewis, R.. Chait, A., Oakley, C., Krikler, D., Mancini. M.. Micheli, H.. Weisswange. A., Pometta, Oriente. P., Paggi, E.. Carlson. L.A.. Ericson, M. and Boberg, J., Plasma lipids and lipoproteins in normal subjects and in atherosclerosis. A multicentre study, Eur. J. Clin. Invest.. 3 (1973) 255. Central Bureau of Statistics, Israel Government. Statistical abstract No. 25. Jerusalem. 1974. Unterschiede zwischen Infarktpatienten und KontrollVilllger. U. and Heyden. S., Das Infarktprofil. personen in der Ostschweiz, Schweiz. Med. Wschr., 96 (1966) 748. The interrelationship of serum cholesterol, hypertension, body Chapman, J.M. and Massey, F.J., weight and risk of coronary disease; results of the first ten years follow-up in the Los Angeles Heart Study, J. Chron. Dis.. 17 (1964) 933. Allard, C.. Goulet. C. and Grondin, C.K.. Patency of aortocoronary vein grafts and serum triglycerides (three-year follow-up), Am. J. Cardiol.. 33 (1974) 679-680 (Progress Rep. May 1974). Stamler, J.. The national cooperative pooling project in the United States, In: Preventive Cardiology, G. Tibblin. A. Keys and L. Werko (eds.), Almquist and Wiksell Forlag AG, Stockholm, 1972.
Atherosclerosis, 28 (1977) 197-204 Scientific @ Elsevier/North-Holland
Publishers,
Ltd.
SERUM CHOLESTEROL AND TRIGLYCERIDES IN PATIENTS SUFFERING FROM ISCHEMIC HEART DISEASE AND IN HEALTHY SUBJECTS *
D. BRUNNER,
S. ALTMAN,
K. LOEBL,
Medical Department A, Government Hygiene, Tel Aviv University (Israel) (Received (Revised, (Accepted
S. SCHWARTZ
Hospital
Jaffa,
and S. LEVIN
and Donolo
Institute
of Physiological
12 August, 1976) received 10 June, 1977) 11 June, 1977)
Summary Serum cholesterol (CH) and triglyceride (TG) values were determined in 142 male and 58 female patients 35-74 years old, who suffered from angina pectoris (AP) or had a myocardial infarction (MI) (in the following referred to as ischemic heart disease (IHD) patients), as well as in 2219 male and 1469 female healthy normotensive subjects. Blood samples were taken in the fasting state. Blood from patients who had suffered from MI was examined three months after the acute event. In age subgroups 35-44, 45-54 and 55-64 years, no significant differences in serum CH was found between IHD patients and healthy subjects, except in males 35-44 years old. However, TG values were significantly elevated in coronary patients of all age groups. In all subgroups with equal CH values, significantly higher TG values were found in IHD patients than in healthy controls. In all subgroups with equal TG levels, no difference in average CH values was found between IHD patients and healthy subjects, except in females with TG below 150 mg%. The results suggest that in the population from which the two groups were recruited, elevated TG values were equal or superior to elevated CH values as indicators of coronary risk. Key words
* This ment,
study
Cholesterol Serum lipids
was supported
Bethesda.
Correspondence
MD. should
Triglycerides
in part
by
grant
- Myocardial
HE
04520
from
infarction
the National
- Ischemic
Institutes
heart disease
of Health,
US Govern-
U.S.A. bc sent
to Dr.
Daniel
Bnmncr,
GovcmmrnL
Hospital,
P.O.
Box
93,
Jaffa,
Israel.
-
198
Introduction Epidemiological and clinical studies bear witness to a correlation between serum cholesterol (CH) levels and myocardial infarction (MI) and other clinical manifestations of ischemic heart disease (IHD) [l-4]. Since 1960, there has been growing interest in the bearing of serum triglyceride (TG) levels on IHD [5--S]. A significantly greater number of lipid abnormalities was demonstrated in patients with angiographically documented coronary artery disease as compared with healthy controls [9]. However, it has been suggested that serum CH is the most powerful risk factor for IHD, and that other lipids or lipoprotein fractions, and especially serum TG are only accompanying components which have no independent relationship and which confer no increased risk to the incidence of IHD [2,6,10,11]. This assumption is not supported by other studies [ 7,121. The purpose of the present investigation is to examine the relationship of serum TG and CH in patients with IHD and in healthy subjects. Material and methods This study comprises 142 male and 58 female patients, subsequently admitted to our ward with a diagnosis of IHD; 102 of the male and 42 of the female patients were hospitalized for acute MI. The diagnostic criteria of MI were: (a) typical chest pains; (b) serial ECG changes consistent with acute MI; (c) transient elevations of serum glutamic oxaloacetic transaminase. The remaining 40 male and 16 female patients were hospitalized for coronary insufficiency or for angina pectoris (AP). Coronary insufficiency was diagnosed in patients with typical chest pains without increased myocardial enzymes and associated with ST segment depression (Minnesota Code IV 1 and 2) and/or negative T-waves (Minnesota Code V 1 and 2), which lasted for one till six days. The AP-patients underwent a multistaged symptom-or-signs-limited workload test on a bicycle ergometer. 2 mm downsloping or horizontal ST-segment depression, and upsloping ST segments with 2 mm ST depression measured 0.08 set from the I-point (Minnesota Code for post-exercise records IX l-5) were considered indicative of AP. Only such patients were included in this study. Since the relationship of serum lipids does not vary with the type of coronary heart disease, AP-patients and post MI-patients were considered a uniform group. The control group consists of subjects who were examined in the course of the Tel Aviv-Donolo Prospective Ischemic Heart Disease Study [ 131. Initially, 4669 subjects were examined. After exclusion of all those with a systolic blood pressure higher than 160 mm Hg, and those with specific or non-specific ECGfindings of possible clinical significance, 3688 subjects remained, and these (2219 males and 1469 females) comprise the control group. Serum TG were determined in the last 452 subjects examined in the Prospective IHD Study. These subjects were in no way different from the remainder of the control group. 62 persons were excluded for increased blood pressure and/or pathological ECG-findings. Thus, the control group for the TG studies consists of 302 males and 88 females. Table 1 shows body weight and body height in age-specific groups. There
199 TABLE BODY
1 WEIGHT
AND
HEIGHT
Males Age
(years)
35-44 HC
IHD
HC
IHD
HC
IHD
15
834
40
871
57
514
30
(kg)
76.0
74.4
(10.8) Height
(cm)
a
170.7
(11.1) 169.4
(5.8)
Age
(6.7)
Height
HC
17 (kg)
(cm)
1163
74.6
(8.9)
(9.5)
(8.3)
168.9 (5.4)
168.4 (6.4)
IHD
HC
41
306
66.9
65.2
66.0
65.6
(10.4)
(11.1)
(10.1)
(10.8)
155.8
155.6
155.6
156.6
(6.3) a Standard
73.1
deviation
168.4 (6.0)
72.7 (10.3) 167.9 (6.6)
72.2 (9.5) 166.9 (7.6)
55-74
IHD
NO.
73.7
HC
(years)
35-54
Weight
65-74
5544
IHD
NO. Weight
45-54 ~____
(6.7)
(5.9)
(6.6)
in parentheses.
were no significant differences between patients and healthy subjects. Blood samples were obtained in the morning following a 12-h overnight fast. In post MI-patients, blood samples were drawn in our post-MI hospital unit three months after the acute event. During their hospitalization and before leaving the hospital, MI-patients were advised to avoid weight gain. Specific dietary or lipid lowering drug therapy was prescribed three months after the infarction only when indicated by serum lipid determinations. Serum CH was determined by the method described by Anderson and Keys [ 141 ; serum TG according to the method of Van Handel-Zilversmith [ 151. Results Tables 2 and 3 present the biochemical findings and standard deviations of males 35-44, 45-54, 55-64 and 65-74 years old, and of females 35-54 and 55-74 years old. For the relatively small number of females only two age groups have been established. Except for males of the youngest age group, no significant differences in CH levels between coronary patients and healthy controls were found. On the other hand, in all subgroups, in males as well as in females, the differences in TG values were of significance, on the level of P < 0.01 or P < 0.05.
200
TABLE
2
SERUM
LIPIDS
-MALES
35-44
No.
of cases
Cholesterol mg%
(mean)
(S.D.)
Statisticdl No.
IHD
HC
15
834
243.2
of cases
IHD
HC
40
871
219.4
36.5
225.1
50.8
59.3 P <
57
91.4
30
230.4
231.8
40.1
54.3
HC -
n.s.
134.5
57
71
30
152.5
132.4
128.2
64.3
59.5
0.01
514
55.1
126
189.9
IHD
HC
221.4
40.3
40
126.3
65-74
IHD
n.s.
105
228.8 123.6
significance
5544
P < 0.05 15
(mean)
(S.D.)
Statistical
218.4
61.4 significance
Triglycerides mg%
45-54 ____~
P < 0.01
52.4 P <
54.2
0.05
Tables 4 and 5 show subgroups of males and females, listed according to CH levels, less than 200,200-224,225-249 and 250 mg% and more. In all groups the patients had significantly higher TG values than the healthy controls with same CH levels, except for the group of males with CH level of 250 mg% or more, where control subjects, too, had increased TG values. Tables 6 and 7 show subgroups according to TG values, above and below 250 mg%. No healthy female had TG values over 250 mg%. In males as well as in females no significant differences in CH values were found. It is conceivable that the figures of female subjects in some of the subgroups are rather small, because MI and coronary artery disease are less common in females under the age of 54 years, and most of the healthy females have TG values less than 150 mg%.
TABLE
3
SERUM
LIPIDS
-FEMALES Age
(years)
35-54
55-74 HC
IHD
No. of caz.es Cholesterol mg%
(S.D.)
Statistical No.
17 (mean)
significance
39.3
41
306
267.1
58
200.8
98.0 30.8 )’ <
251.3
60.7
43.5 n.s.
56.8 significance
HC
n.s. 17
(mean)
mgqb (S.D.) Statistical
224.4
33.5
of cases
higlycerides
1163
236.2
IHD
0.01
41
30
190.1
109.5
76.5
33.2 I’ < 0.01
201
TABLE
4
SERUM
CHOLESTEROL
Specific
subgroups.
-
MALES
Cholesterol Less
than
(mg%) 200
225-249
200-224
250
or more
IHD
No.
of cases
49
Triglycerides
(mg%)
116.7
87.4
TABLE
HC
HC
IHD
85
25
60
36
48
139.9
172.7
131.9
190.9
188.7
94.9
75.5
87.6
57.4
84.1
P < 0.05
P < 0.05
122.2
n.s.
5
SERUM
CHOLESTEROL
Specific
subgroups
-
FEMALES
Cholesterol Less
than
(mg%) 250
250
IHD
No. of cases (mg%)
S.D.
57.1
Statistical
HC
32
16
91.6
236.7
132.8
38.3
111.0
72
149.1
or more
IHD
HC
26
Triglycerides
TABLE
IHD
32
57.2
P < 0.01
significance
HC
177.9
109
146.8
S.D. Statistical
IHD
HC
68.9
P < 0.01
significance
P < 0.01
6
TRIGLYCERIDES-MALES Specific
subgroups Triglycerides Less
than
(mg%) 150
IHD
No.
of cases
Cholesterol
HC
61 (mg%)
44.2
Statistical
TABLE
significance
TRIGLYCERIDES
HC
IHD
HC
62
86
19
22
228.9
216.9
251.8
246.1
35.3
56.8
n.s.
32.7
59.7
n.s.
52.0 n.s.
-
FEMALES
subgroups Triglycerides Less
than
IHD of cases
Cholesterol
(mg%)
S.D. Statistical
IHD
or more
7
Specific
No.
250
210.1
194
216.6
S.D.
150-249
150-249
150 HC
250
IHD
HC
IHD
28
76
19
12
11
248.2
221.8
158.5
260.3
279.2
54.7 significance
(mg%)
31.7 n.s.
50.0
50.0 Il.%
69.3
or more HC
202
Discussion
Serum lipid determinations of post-MI-patients were performed three months after the acute event. It has been reported that CH levels fall significantly following acute MI, and return to the pre-disease level after 12 weeks. The variations in TG were small and insignificant [ 161. Thus, it can be assumed that CH and TG levels determined three months after the acute event are similar to the pre-infarction values. Our results revealed that fasting TG levels were significantly elevated in patients with IHD when compared with sex- and age-matched healthy subjects. On the other hand, there was no significant difference in CH values between the two groups, with the exception of males between 35-44 years old. In subgroups with equal CH, TG levels were significantly higher in IHD patients of both sexes than in healthy controls. As opposed to this, in subgroups with equal TG, there was no significant difference in CH levels between the two groups. Carlson and Ericson [17] recently reported lipoprotein findings in Swedish men. As in our study, they found significantly higher TG levels in coronary patients than in healthy controls. However, contrary to our results, their patients also had significantly higher serum’ CH levels. Almost all TG in chylomicron-free serum are concentrated in the very low density lipoproteins or pre-beta-lipoproteins, coded by Fredericksen et al. as dislipoproteinemia type IV [ 181. Retrospective studies in European populations demonstrated that the TG rich pre-beta-lipoproteins are the commonest disorder in IHD [ 191. Our observations point to the same conclusions. Serum lipids may be influenced by various factors: overweight, diet or seasonal fluctuations. It was shown that overweight persons have higher serum TG values, whereas serum CH is not influenced by or associated with overweight [ 171. However, in our study the age-specific subgroups of patients and healthy persons did not differ in their relative body weight (Table 1). No individual diet information was obtained in our population study of 3668 healthy persons, nor from the 188 coronary patients. However, there is no reason to assume that their diet was different from the average diet habits in Israel. According to publications of the Central Bureau of Statistics of the Israel Government, the available nutrients per capita per day in 1973 were 96 g protein: 45 g were animal protein, 111 g fats and 380 g carbohydrates [ 201. Since blood samples of both, the healthy persons and the coronary patients, were collected over a period of two years, any possible influence of seasonal fluctuation would be balanced [ 21,221. Since our survey is not a prospective study, we can only surmise that in healthy subjects elevated serum TG levels, not associated with increased CH, represent an independent risk factor for future coronary disease. This assumption is at variance with the conclusions drawn from the Framingham Study, where it was found that CH and TG levels are closely correlated, and that TGrich-low-density-lipoprotein fractions alone have a limited independent relationship with the incidence of coronary artery disease. Similarly, Brown et al. [7] reported that marked hypertriglyceridemia combined with normal CH values is uncommon, and that the relationship of pure hypertriglyceridemia to
203
IDH is difficult to assess. But in contrast to this, Carlson and Boettinger [8], in analyzing the results of the Prospective Stockholm Study, noted considerable increase in risk of future IHD in subjects with elevated serum TG. They concluded that both, TG and CH are risk factors for IHD, independent of each other. In this context it is interesting to mention a three-year follow-up study of patients after coronary bypass surgery, in which hypertriglyceridemia predisposed to an increased risk of occlusion or stenosis of the aorta-coronary vein graft. Serum CH, however, did not affect the fate of the graft [23]. It seems that genetic and geographic differences, diversities in life style and nutritional habits are correlated with varieties of dislipoproteinemia and lipid levels which in their turn represent IHD risk factors. Our findings do not challenge the assumption that the risk of IHD increases with rising CH levels, and that subjects with CH higher than 350 mg% face much greater risk of developing IHD than those with CH levels, below 200 mg%. However, it is remarkable that even in the National Cooperative Pooling Project of American Surveys 53% of all patients had serum CH levels less than 250 mg%, and only 14.5% more than 300 mg% [24]. Thus, less than half of all patients with manifest IHD had elevated CH, most of them only to a moderate degree. Therefore the serum CH determinations of the majority of the patients did not label them as high risk cases. In our survey only 26% of all patients had CH levels higher than 250 mg%, and 36% below 200 mg%. In populations where many coronary patients have no elevated serum CH, the TG level may be useful as a predictor for future IHD. Particularly great differences in TG values between IHD patients and healthy subjects were found in the youngest age group, 35-44 years old. In the control group we found TG values over 150 mg% in 36% of males and in 12% of females. This, in the light of our findings, indicates that these subjects are high risk cases. The question whether reduction of increased serum TG in healthy subjects will result in a decreasing risk of future IHD can be answered only by a prospective study. References 1 Stamler, J., in: Lectures in Preventive Cardiology. Grune and Stratton Inc.. New York-London, 1967. 2 Kannel, W.B., Castelli, W.P.. Gordon, T. and McNamara, P.M., Serum cholesterol, lipid proteins and the risk of coronary artery disease, Ann. Intern. Med., 74 (1971) l-12. 3 Brunner, D. and Loebl. K.. Serum cholesterol. electrophorctic lipid pattern, diet and coronary artery disease. A study in coronary patients and in healthy men of different origin and occupations in Israel, Ann. Intern. Med.. 49 (1958) 732-750. 4 Keys. A., Coronary heart disease in seven countries, Circulation, 41 (1970) (suppl. 1.1) I-l. 5 Carlson, L.A.. Serum lipids in men with myocardial infarction. Acta Med. Stand., 167 (1960) 399. 6 Albrink. N., Triglycerides, lipoproteins and coronary artery disease, Arch. Int. Med.. 109 (1962) 345359. 7 Brown, D.F., Kinch. S.H. and Doyle, J.T.. Serum triglycerides in health and ischemic heart disease, New Engl. J. Med., 273 (1965) 947-952. 8 Carlson. L.A. and Boettinger. L.E.. Ischemic heart disease in relation to fasting values of plasma triglyceride and cholesterol. Lancct, 1 (1972) 865-868. 9 Heinle. R.A.. Levy, R.I., Fredericksen. D.S. and Corlin. R.. Lipid and carbohydrate abnormalities in patients with angiographically documented coronary artery disease. Am. J. Cardiol.. 24 (1969) 178186. 10 Wilhelmson, L., Wedel. H. and Tibblin, G.. Multivariate analysis of risk factors for coronary heart disease, Circulation, 48 (1973) 950-958.
204 11 Blackbum, 12 13 14 15 16 17 18 19
20 21 22
23 24
H., Progress in the epidemiology and prevention of coronary heart disease, In: Progress in Cardiology, Yu. P.N. and Goodwin, J.F. (eds.), Lea and Febiger, 1974. Rosenman, R.H.. Friedman, M.. Strauss, R., Jenkins, C.D.. Zyansky. S.J. and Wurm. M., Coronary heart disease in the western collaborate group study, J. Chron. Dis., 23 (1970) 173. Brunner, D., Altman, S.. Loebl. K. and Schwartz, S.. Donolo-Tel Aviv prospective study of ischemic heart disease, to be published. Anderson, J.T.. and Keys, A., Cholesterol in serum and lipoprotein fraction, its measurements and stability, Clln. Chem., 2 (1956) 145-159. Van Handel-Zilversmith, E.. Method for direct determination of serum triglycerides, J. Lab. Clin. Med., 50 (1957) 152-157. Fyfe. T., Baxter, R.H. and Cochran, K.M., Plasma lipid changes after myocardial infarction, Lancet, II (1971) 997-1001. Carlson. L.A. and Ericson, M., Quantitative and qualitative serum lipoprotein analysis, Atherosclerosis, 21 (1975) 435-450. Fredericksen, D.S., Levy, R.I. and Lees, R.S.. Fat transport in lipoproteins: An integrated approach to mechanism and disorder, New Engl. J. Med., 276 (1967) 34-44,94-103.148-156. D.. Lewis, R.. Chait, A., Oakley, C., Krikler, D., Mancini. M.. Micheli, H.. Weisswange. A., Pometta, Oriente. P., Paggi, E.. Carlson. L.A.. Ericson, M. and Boberg, J., Plasma lipids and lipoproteins in normal subjects and in atherosclerosis. A multicentre study, Eur. J. Clin. Invest.. 3 (1973) 255. Central Bureau of Statistics, Israel Government. Statistical abstract No. 25. Jerusalem. 1974. Unterschiede zwischen Infarktpatienten und KontrollVilllger. U. and Heyden. S., Das Infarktprofil. personen in der Ostschweiz, Schweiz. Med. Wschr., 96 (1966) 748. The interrelationship of serum cholesterol, hypertension, body Chapman, J.M. and Massey, F.J., weight and risk of coronary disease; results of the first ten years follow-up in the Los Angeles Heart Study, J. Chron. Dis.. 17 (1964) 933. Allard, C.. Goulet. C. and Grondin, C.K.. Patency of aortocoronary vein grafts and serum triglycerides (three-year follow-up), Am. J. Cardiol.. 33 (1974) 679-680 (Progress Rep. May 1974). Stamler, J.. The national cooperative pooling project in the United States, In: Preventive Cardiology, G. Tibblin. A. Keys and L. Werko (eds.), Almquist and Wiksell Forlag AG, Stockholm, 1972.