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Serum high density lipoprotein cholesterol correlates with presence but not severity of coronary artery disease
Serum High Density Lipoprotein Cholesterol Correlates with Presence but not Severity of Coronary Artery Disease
JOHN
0.
SWANSON,
M.D.
GORDON
PIERPONT,
M.D.,
ARNOLD
ADICOFF,
Ph.D.
M.D.
Minneapolis, Minnesota
From the Departments of Cardiology and Laboratory Medicine, Metropolitan Medical Center, Minneapolis, Minnesota; and the Department of Cardiology, Veterans Administration Medical Center and University of Minnesota Hospitals, Minneapolis, Minnesota. Requests for reprints should be addressed to Dr. Gordon L. Pierpont, Veterans Administration Medical Center, Cardiovascular Section (11 lC), Minneapolis, MN 55417. Manuscript accepted February 10. 1991.
An elevated serum level of low density lipoprotein (LDL) is a risk factor for the development of coronary artery disease, whereas elevated levels of high density lipoprotein (HDL) appear to have a protective effect, and the total cholesterol to HDL ratio has been suggested as an improved method for assessing risk. We determined cholesterol, HDL and triglycerides in 189 patients undergoing diagnostic cardiac catheterization to determine if these variables correlate with the severity of coronary artery disease assessed as the number of major coronary vessels having 270 percent stenosis. HDL was higher in the group with zero vessel disease (54 f 2.3 mg/dl f SEM) than in those with one, two or three vessel disease (43 f 1.8,45 f 1.8 and 51 f 1.2, respectively), and the cholesterol to HDL ratio was lower in the group with zero vessel disease (4.1 f 0.2 compared to 8.1 f 0.3,5.7 f 0.2 and 8.4 f 0.3 In the groups with 1, 2 and 3 vessel disease). Using analysis of variance, patients with no coronary artery disease (zero vessel disease) differed from those wlth coronary artery disease in HDL (pO.Ol), cholesterol (p O.OOS), but no signlflcant dlfferences were found between patients with coronary artery disease and a dlfferent number of vessels Involved. There were no significant differences between the groups in age, and although the group with zero vessel disease had more females than the others, there were no differences in cholesterol, HDL, cholesterol to HDL ratio, or triglycerides between male and female patients with no coronary artery disease. We conclude that the cholesterol to HDL ratio correlates with the presence but not severity of coronary artery disease. Elevated serum cholesterol levels have long been recognized as a risk factor for the development of ischemic heart disease. More recently, fractionation of cholesterol into high density lipoproteins (HDL) and low density lipoproteins, has been believed .to provide additional predictive information. The HDL fraction appears to have an inverse relationship to the development of ischemic heart disease, that is, high levels of HDL have a “protective” effect against the development of atherosclerosis [l-l 11. This study was designed to determine if HDL cholesterol, or more specifically, total cholesterol to HDL ratio, might correlate with the severity of coronary artery disease as well as its presence.
METHODS Lipid studies were performed on serum from 189 consecutive patients undergoing diagnostic heart catheterization for evaluation of known or sus-
August 1981
The American Journal of Medlclne
Volume 71
235
SERUM HDL CHOLESTEROLAND CORONARY ARTERY DISEASE-SWANSON ET AL.
TABLE I
Demographic
Data
Patients
0
Number Mean age (yr) Male (%) With positive family history for coronary artery
32 52.3 50.0+ 63.2 25.0 10.7 41.4+
disease (%) With history of hypertension With diabetes mellitus (%) Smokers (%)
(%)
No. of Vessels 1
2
3
40 52.8 72.5’ 74.1
51 55.8 94.1 62.5
66 55.4 92.4 71.7
42.5 5.3 67.6
34.7 18.8 60.9
36.4 9.8 63.0
p <0.05 (see text). + p >O.OOl (see text). l
petted ischemic heart disease. The blood samples were drawn following a 12 hour overnight fast. Triglyceride levels were determined using enzymatic hydrolysis [ 121. Total cholesterol was determined using an enzymatic hydrolysis with cholesterol esterase, and subsequently oxidation of the cholesterol with cholesterol oxidase forming hydrogen peroxide [ 131. The hydrogen peroxide reacts with phenol and 4-amino-phenazone to form a red dye, which is measured spectrophotometrically [ 141. This procedure utilized a kit commercially available from the Bio-Dynamics Division of Boehringer Mannheim Co. HDL cholesterol was determined using the heparin manganese chloride precipitation method
[W. Patients were classified into groups with zero, one, two or three vessel disease depending on whether or not there was 70 percent or greater narrowing of the transluminal diameter in the left anterior descending coronary artery, the left circumflex artery and/or the right coronary artery. Clinical classification of the patients was based on both objective and subjective criteria. They were considered to have a “positive family history” when one or more blood relatives (parent, grandparent, sibling, aunt, uncle, first cousin or child) had clinical coronary artery disease prior to age 70. The patients were classified as having hypertension if they were previously told by a physician that they had hypertension, or if they had a documented resting blood pressure greater than 160 mm Hg systolic or 95 mm Hg diastolic. A 2 hour postprandial glucose level was determined in every patient, and diabetes mellitus was considered to be present if it was higher than 140 ml/dl, or if the patient was previously told by a physician that he/she had diabetes mellitus.
Data for the different patients grouped according to number of diseased vessels is presented as mean plus or minus standard error of the mean (SEM), and comparisons were made using analysis of variance. Student’s t test was used when patients within a group were separated according to the presence or absence of specific traits, and comparisons of proportions utilized the standard normal deviate. Differences were considered significant for p values less than 0.05. RESULTS Demographic data on the patients in our study are presented in Table I. The data include the number of patients in each group, their mean age, the percent male, the percent with a positive family history, the percent with a history of hypertension, the percent with diabetes mellitus and the percent smokers. The mean ages of the patients in each group were as follows: 52.3 f 1.8 years for those with zero vessel disease, 52.8 f 1.6 years for one vessel disease, 55.8 f 1.2 years for two vessel disease and 55.4 f 1.2 years for three vessel disease. Although the patients with two and three vessel disease tended to be slightly older than those with zero and one vessel disease, these differences were not significant. Males dominated the groups with two and three vessel disease, whereas there were an equal number of males and females in the group with zero vessel disease, and approximately 75 percent of the group with one vessel disease were male. The percent males in the group with zero vessel disease
TABLE Ill TABLE II
Patients with No Stenosis 270 Percent
Patients with No Stenosis 170 Percent Smokers Male
HDL (mg/dl) Cholesterol (mg/dl) Cholesterol to HDL Triglycerides (mg/dl)
53.9 212.7 4.06 152.9
f 3.1 f 13.0 f 0.28 f 20.7
Female 54.9 210.5 4.04 127.9
f 3.4 f 8.7 f 0.30 f 12.4
NOTE: HDL = high density lipoproteins.
236
August 1961
The American Journal of Medicine
HDL (mg/dl) Cholesterol (mg/dl) Cholesterol to HDL Triglycerides (mgldl)
51.2 190.3 3.75 145.3
f 3.1 f 9.1 f 0.26 f 19.1
NOTE: HDL = high density lipoproteins. * p <0.05.
Volume 71
Nonsmokers 55.8 220.8 4.21 133.6
f 3.7 f 9.7’ f 0.32 f 17.8
SERUM HDL CHOLESTEROL AND CORONARY ARTERY DISEASE-SWANSON
differed significantly from that in the groups with one vessel disease for p <0.05 and from that in the groups with two and three vessel disease for p
0
1
ET AL.
and triglycerides for the patients in the group with zero vessel disease according to sex. There were no significant differences for any of these values between the males and females within this group. Table Ill presents the HDL, cholesterol, cholesterol to HDL ratio, and triglyceride values in the group of patients with no significant stenosis divided according to smokers and nonsmokers. The difference of 30 mg/dl in cholesterol between smokers and nonsmokers was significant for p <0.05, but none of the other values were significantly different when smokers were compared with nonsmokers. The data in Tables II and Ill thus suggest that any differences in the lipid values between groups is unlikely to be explained by sex or smoking biases, with the possible exception of total cholesterol. Figure 1 presents the mean data (fSEM) for cholesterol, HDL, cholesterol to HDL ratio and triglycerides for the patients according to the number of vessels in-
2-3
0
12
3
#VESSELS
SFVESSELS
240 i
70 G 2
60-
&
50.
g
40.
b
3 *
*
* 1
0
12
3 # VESSELS
* VESSELS
@we 1. Data (mean f SEM) for cholesterol, HDL, cholesterol to HDL ratio and triglycerides according to the number of coronary vessels with more than 70 percent stenosis.
August 1981
The American Journal of Medlcine
Volume 71
237
SERUM HDL CHOLESTEROL AND CORONARY
ARTERY DISEASE-SWANSON
volved with disease. It can readily be seen that the pattern of values for each of these variables is similar in each graph. The values for the group with zero vessel disease are significantly different from the values for the groups with one, two and three vessel disease for p <0.005 for cholesterol, HDL and cholesterol to HDL ratio, and p
238
August 1981
The American Journal of Medicine
ET AL.
of severity as delineated by coronary artery score systems. It is not clear whether the data in the previously reported studies are basically different from our data, or rather that the major differences are in analysis and interpretation. It would be most interesting to examine the data of Barboriak et al. [ 181 and of Jenkins et al. [ 171 with those patients having minimal or no disease being excluded. If this produces a significant decrease in the correlation coefficient, it would suggest that the correlation is strongly dependent on differences in the cholesterol to HDL ratio between those with and those without CAD, with little effect due to severity of disease. Unfortunately, the best way to see if all the data are comparable would be to reanalyze all angiograms according to a uniform method and to apply the same statistical method in each case; this is unlikely to be accomplished. Since the prognoses in patients with stenosis of the left main coronary artery is much worse than that in patients with one, two or three vessel disease not involving the left main artery, it is unfortunate that we did not have enough patients with disease of the left main coronary artery to analyze separately. Four of our patients with three vessel disease also had left main coronary artery disease, and they were included in the group with three vessel disease. If they are omitted from the analysis completely, the results are unchanged. None of the other patients had significant disease of the left main coronary artery of greater than or equal to 70 percent stenosis. It is interesting to note that the average value of HDL in our male patients with no significant coronary artery stenosis (53.9 mg/dl) is higher than the values for white males in several populations as reported by Castelli et al. [23] in which the mean HDL ranged from 44.4 to 48.7 mg/dl. This discrepancy is most likely due to the fact that our group with zero vessel disease was highly selected in that there is documented catheterization evidence of no significant coronary artery disease. On the other hand, many of the subjects in the population studies will have coronary artery disease, even when not evident by gross screening methods. Thus the mean HDL from a general population likely is skewed downward by those who indeed have coronary artery disease. It is possible that this reasoning may also explain why we did not have a significant difference between males and females, in our group with zero vessel disease, whereas in most general populations the HDL is higher in females than males. In summary, we have shown that the cholesterol to HDL ratio correlates well with the presence of coronary artery disease but not with the severity of the disease. We, thus, believe that the cholesterol to HDL ratio is a
Volume 71
SERUM HDL CHOLESTEROLAND CORONARY ARTERY DISEASE-SWANSON
worthwhile test, when used in conjunction with other noninvasive data, to evaluate a patient for the likelihood of having coronary artery disease. However it will provide little additional clinical information in assessing a patient who is already known to have coronary artery disease.
ET AL.
ACKNOWLEDGMENT We gratefully acknowledge Gary Hemphill Ph.D., since he was instrumental in setting up the HDL Cholesterol Assay, and the technical assistance of Samuel D. Adicoff.
REFERENCES
2.
3. 4.
5.
6.
7.
a. 9.
10.
11.
12.
Medalie JH, Kahn HA, Neufeld HN, Riss E, Goldbourt U: Fiveyear myocardial infarction incidence-k. Association of single variables to age and birth place. J Chronic Dis 1973; 26: 329. Albers JJ, Wahl PW, Cabana VG, Hazard WR, Hoover JJ: Quantitation of apolipoprotein A-l of human plasma high density lipoprotein. Metabolism 1976; 25: 633. Berg K, Borresen A, Dahlen G: Serum-high-density-lipoprotein and atherosclerotic heart-disease. Lancet 1977; 1: 449. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease. N Engl J Med 1976; 294: 293. Castelli WP. Doyle JT, Gordon T, et al.: HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation 1977; 55: 767. Gordon T, Castelli WP, Hjortland MC. Kannel WB, Dawber TR: High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62: 707. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR: Diabetes, blood lipids and the role of obesity in coronary heart disease risk for women. Ann Intern Med 1977; 87: 393. Miller NE, Forde OH, Thelle DS, Mjos OD: The Tromso heart study. High-density lipoprotein and coronary heartdisease: a prospective case-control study. Lancet 1977; 1: 965. Albers JJ, Chenno MC, Hazard WR: High density lipoproteins in myocardial infarction survivors. Metabolism 1978; 27: 479. Goldbourt U, Medalie JH: High density lipoprotein cholesterol and incidence of coronary heart disease-the Israeli ischemic heart disease study. Am J Epidemiol 1979: 109: 296. Streja D, Steiner G, Kwitervoich PO: Plasma high-density Iipoproteins and ischemic heart disease. Studies in a large kindred with familial hypercholesterolemia. Ann Intern Med 1978; 89: 871. Bucolo G, David H: Quantitative determination of serum
13.
14.
15.
16.
17.
18. 19.
20.
21.
22.
23.
August 1981
triglycerides by the use of enzymes. Clin Chem 1973; 19: 476. Allain CC, Poon LS, Chan CSG, et al.: The enzymatic determination of total serum cholesterol. Clin Chem 1974; 20: 470. Trinder P: Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969; 6: 24. Lopes-Virella MF, Stone P, Ellis S, Colwell JA: Cholesterol determination in highdensity lipoprotein reported by three different methods. Clin Chem 1977; 23: 882. Pearson TA, Bulkley BH, Achuff SC, Kwiterovich PO, Gordis L: The association of low levels of HDL cholesterol and arteriographically determined coronary artery disease. Am J Epidemiol 1979; 109: 285. Jenkins PJ, Harper RW, Nestel PD: Severity of coronary atherosclerosis related to lipoprotein concentration. Br Med J 1978; 2: 388. Barboriak JJ, Anderson AJ, Rimm AA, King JF: High density lipoprotein cholesterol and coronary artery occlusion. Metabolism 1979; 28: 735. Oberman A, Jones WB, Riley CP, Reeves TJ, Sheffield LT, Trirner ME: Natural history of coronary artery disease. Bull NY Acad Med 1972; 48: 1109. Bruschke AVG, Proudfit WL, Sones FM: Progress study of 590 consecutive non-surgical cases of coronary artery disease followed 5 to 9 years. I. Arteriographic correlations. Circulation 1973; 47: 1147. Burggraf GW, Parker JO: Prognosis in coronary artery disease, angiographic hemodynamic and clinical factors. Circulation 1975; 51: 146. Detre K, Murphy ML, Hultgren H: Effect of coronary bypass surgery on longevity in high and low risk patients. Lancet 1977; 2: 1243. Castelli WP, Cooper GR, Doyle JT, et al.: Distribution of triglyceride and total, LDL and HDL cholesterol in several populations: a cooperative lipoprotein phenotyping study. J Chronic Dis 1977; 30: 147.
The American Journal of Medicine
Volume 71
239
JOHN
0.
SWANSON,
M.D.
GORDON
PIERPONT,
M.D.,
ARNOLD
ADICOFF,
Ph.D.
M.D.
Minneapolis, Minnesota
From the Departments of Cardiology and Laboratory Medicine, Metropolitan Medical Center, Minneapolis, Minnesota; and the Department of Cardiology, Veterans Administration Medical Center and University of Minnesota Hospitals, Minneapolis, Minnesota. Requests for reprints should be addressed to Dr. Gordon L. Pierpont, Veterans Administration Medical Center, Cardiovascular Section (11 lC), Minneapolis, MN 55417. Manuscript accepted February 10. 1991.
An elevated serum level of low density lipoprotein (LDL) is a risk factor for the development of coronary artery disease, whereas elevated levels of high density lipoprotein (HDL) appear to have a protective effect, and the total cholesterol to HDL ratio has been suggested as an improved method for assessing risk. We determined cholesterol, HDL and triglycerides in 189 patients undergoing diagnostic cardiac catheterization to determine if these variables correlate with the severity of coronary artery disease assessed as the number of major coronary vessels having 270 percent stenosis. HDL was higher in the group with zero vessel disease (54 f 2.3 mg/dl f SEM) than in those with one, two or three vessel disease (43 f 1.8,45 f 1.8 and 51 f 1.2, respectively), and the cholesterol to HDL ratio was lower in the group with zero vessel disease (4.1 f 0.2 compared to 8.1 f 0.3,5.7 f 0.2 and 8.4 f 0.3 In the groups with 1, 2 and 3 vessel disease). Using analysis of variance, patients with no coronary artery disease (zero vessel disease) differed from those wlth coronary artery disease in HDL (p
METHODS Lipid studies were performed on serum from 189 consecutive patients undergoing diagnostic heart catheterization for evaluation of known or sus-
August 1981
The American Journal of Medlclne
Volume 71
235
SERUM HDL CHOLESTEROLAND CORONARY ARTERY DISEASE-SWANSON ET AL.
TABLE I
Demographic
Data
Patients
0
Number Mean age (yr) Male (%) With positive family history for coronary artery
32 52.3 50.0+ 63.2 25.0 10.7 41.4+
disease (%) With history of hypertension With diabetes mellitus (%) Smokers (%)
(%)
No. of Vessels 1
2
3
40 52.8 72.5’ 74.1
51 55.8 94.1 62.5
66 55.4 92.4 71.7
42.5 5.3 67.6
34.7 18.8 60.9
36.4 9.8 63.0
p <0.05 (see text). + p >O.OOl (see text). l
petted ischemic heart disease. The blood samples were drawn following a 12 hour overnight fast. Triglyceride levels were determined using enzymatic hydrolysis [ 121. Total cholesterol was determined using an enzymatic hydrolysis with cholesterol esterase, and subsequently oxidation of the cholesterol with cholesterol oxidase forming hydrogen peroxide [ 131. The hydrogen peroxide reacts with phenol and 4-amino-phenazone to form a red dye, which is measured spectrophotometrically [ 141. This procedure utilized a kit commercially available from the Bio-Dynamics Division of Boehringer Mannheim Co. HDL cholesterol was determined using the heparin manganese chloride precipitation method
[W. Patients were classified into groups with zero, one, two or three vessel disease depending on whether or not there was 70 percent or greater narrowing of the transluminal diameter in the left anterior descending coronary artery, the left circumflex artery and/or the right coronary artery. Clinical classification of the patients was based on both objective and subjective criteria. They were considered to have a “positive family history” when one or more blood relatives (parent, grandparent, sibling, aunt, uncle, first cousin or child) had clinical coronary artery disease prior to age 70. The patients were classified as having hypertension if they were previously told by a physician that they had hypertension, or if they had a documented resting blood pressure greater than 160 mm Hg systolic or 95 mm Hg diastolic. A 2 hour postprandial glucose level was determined in every patient, and diabetes mellitus was considered to be present if it was higher than 140 ml/dl, or if the patient was previously told by a physician that he/she had diabetes mellitus.
Data for the different patients grouped according to number of diseased vessels is presented as mean plus or minus standard error of the mean (SEM), and comparisons were made using analysis of variance. Student’s t test was used when patients within a group were separated according to the presence or absence of specific traits, and comparisons of proportions utilized the standard normal deviate. Differences were considered significant for p values less than 0.05. RESULTS Demographic data on the patients in our study are presented in Table I. The data include the number of patients in each group, their mean age, the percent male, the percent with a positive family history, the percent with a history of hypertension, the percent with diabetes mellitus and the percent smokers. The mean ages of the patients in each group were as follows: 52.3 f 1.8 years for those with zero vessel disease, 52.8 f 1.6 years for one vessel disease, 55.8 f 1.2 years for two vessel disease and 55.4 f 1.2 years for three vessel disease. Although the patients with two and three vessel disease tended to be slightly older than those with zero and one vessel disease, these differences were not significant. Males dominated the groups with two and three vessel disease, whereas there were an equal number of males and females in the group with zero vessel disease, and approximately 75 percent of the group with one vessel disease were male. The percent males in the group with zero vessel disease
TABLE Ill TABLE II
Patients with No Stenosis 270 Percent
Patients with No Stenosis 170 Percent Smokers Male
HDL (mg/dl) Cholesterol (mg/dl) Cholesterol to HDL Triglycerides (mg/dl)
53.9 212.7 4.06 152.9
f 3.1 f 13.0 f 0.28 f 20.7
Female 54.9 210.5 4.04 127.9
f 3.4 f 8.7 f 0.30 f 12.4
NOTE: HDL = high density lipoproteins.
236
August 1961
The American Journal of Medicine
HDL (mg/dl) Cholesterol (mg/dl) Cholesterol to HDL Triglycerides (mgldl)
51.2 190.3 3.75 145.3
f 3.1 f 9.1 f 0.26 f 19.1
NOTE: HDL = high density lipoproteins. * p <0.05.
Volume 71
Nonsmokers 55.8 220.8 4.21 133.6
f 3.7 f 9.7’ f 0.32 f 17.8
SERUM HDL CHOLESTEROL AND CORONARY ARTERY DISEASE-SWANSON
differed significantly from that in the groups with one vessel disease for p <0.05 and from that in the groups with two and three vessel disease for p
0
1
ET AL.
and triglycerides for the patients in the group with zero vessel disease according to sex. There were no significant differences for any of these values between the males and females within this group. Table Ill presents the HDL, cholesterol, cholesterol to HDL ratio, and triglyceride values in the group of patients with no significant stenosis divided according to smokers and nonsmokers. The difference of 30 mg/dl in cholesterol between smokers and nonsmokers was significant for p <0.05, but none of the other values were significantly different when smokers were compared with nonsmokers. The data in Tables II and Ill thus suggest that any differences in the lipid values between groups is unlikely to be explained by sex or smoking biases, with the possible exception of total cholesterol. Figure 1 presents the mean data (fSEM) for cholesterol, HDL, cholesterol to HDL ratio and triglycerides for the patients according to the number of vessels in-
2-3
0
12
3
#VESSELS
SFVESSELS
240 i
70 G 2
60-
&
50.
g
40.
b
3 *
*
* 1
0
12
3 # VESSELS
* VESSELS
@we 1. Data (mean f SEM) for cholesterol, HDL, cholesterol to HDL ratio and triglycerides according to the number of coronary vessels with more than 70 percent stenosis.
August 1981
The American Journal of Medlcine
Volume 71
237
SERUM HDL CHOLESTEROL AND CORONARY
ARTERY DISEASE-SWANSON
volved with disease. It can readily be seen that the pattern of values for each of these variables is similar in each graph. The values for the group with zero vessel disease are significantly different from the values for the groups with one, two and three vessel disease for p <0.005 for cholesterol, HDL and cholesterol to HDL ratio, and p
238
August 1981
The American Journal of Medicine
ET AL.
of severity as delineated by coronary artery score systems. It is not clear whether the data in the previously reported studies are basically different from our data, or rather that the major differences are in analysis and interpretation. It would be most interesting to examine the data of Barboriak et al. [ 181 and of Jenkins et al. [ 171 with those patients having minimal or no disease being excluded. If this produces a significant decrease in the correlation coefficient, it would suggest that the correlation is strongly dependent on differences in the cholesterol to HDL ratio between those with and those without CAD, with little effect due to severity of disease. Unfortunately, the best way to see if all the data are comparable would be to reanalyze all angiograms according to a uniform method and to apply the same statistical method in each case; this is unlikely to be accomplished. Since the prognoses in patients with stenosis of the left main coronary artery is much worse than that in patients with one, two or three vessel disease not involving the left main artery, it is unfortunate that we did not have enough patients with disease of the left main coronary artery to analyze separately. Four of our patients with three vessel disease also had left main coronary artery disease, and they were included in the group with three vessel disease. If they are omitted from the analysis completely, the results are unchanged. None of the other patients had significant disease of the left main coronary artery of greater than or equal to 70 percent stenosis. It is interesting to note that the average value of HDL in our male patients with no significant coronary artery stenosis (53.9 mg/dl) is higher than the values for white males in several populations as reported by Castelli et al. [23] in which the mean HDL ranged from 44.4 to 48.7 mg/dl. This discrepancy is most likely due to the fact that our group with zero vessel disease was highly selected in that there is documented catheterization evidence of no significant coronary artery disease. On the other hand, many of the subjects in the population studies will have coronary artery disease, even when not evident by gross screening methods. Thus the mean HDL from a general population likely is skewed downward by those who indeed have coronary artery disease. It is possible that this reasoning may also explain why we did not have a significant difference between males and females, in our group with zero vessel disease, whereas in most general populations the HDL is higher in females than males. In summary, we have shown that the cholesterol to HDL ratio correlates well with the presence of coronary artery disease but not with the severity of the disease. We, thus, believe that the cholesterol to HDL ratio is a
Volume 71
SERUM HDL CHOLESTEROLAND CORONARY ARTERY DISEASE-SWANSON
worthwhile test, when used in conjunction with other noninvasive data, to evaluate a patient for the likelihood of having coronary artery disease. However it will provide little additional clinical information in assessing a patient who is already known to have coronary artery disease.
ET AL.
ACKNOWLEDGMENT We gratefully acknowledge Gary Hemphill Ph.D., since he was instrumental in setting up the HDL Cholesterol Assay, and the technical assistance of Samuel D. Adicoff.
REFERENCES
2.
3. 4.
5.
6.
7.
a. 9.
10.
11.
12.
Medalie JH, Kahn HA, Neufeld HN, Riss E, Goldbourt U: Fiveyear myocardial infarction incidence-k. Association of single variables to age and birth place. J Chronic Dis 1973; 26: 329. Albers JJ, Wahl PW, Cabana VG, Hazard WR, Hoover JJ: Quantitation of apolipoprotein A-l of human plasma high density lipoprotein. Metabolism 1976; 25: 633. Berg K, Borresen A, Dahlen G: Serum-high-density-lipoprotein and atherosclerotic heart-disease. Lancet 1977; 1: 449. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease. N Engl J Med 1976; 294: 293. Castelli WP. Doyle JT, Gordon T, et al.: HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation 1977; 55: 767. Gordon T, Castelli WP, Hjortland MC. Kannel WB, Dawber TR: High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62: 707. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR: Diabetes, blood lipids and the role of obesity in coronary heart disease risk for women. Ann Intern Med 1977; 87: 393. Miller NE, Forde OH, Thelle DS, Mjos OD: The Tromso heart study. High-density lipoprotein and coronary heartdisease: a prospective case-control study. Lancet 1977; 1: 965. Albers JJ, Chenno MC, Hazard WR: High density lipoproteins in myocardial infarction survivors. Metabolism 1978; 27: 479. Goldbourt U, Medalie JH: High density lipoprotein cholesterol and incidence of coronary heart disease-the Israeli ischemic heart disease study. Am J Epidemiol 1979: 109: 296. Streja D, Steiner G, Kwitervoich PO: Plasma high-density Iipoproteins and ischemic heart disease. Studies in a large kindred with familial hypercholesterolemia. Ann Intern Med 1978; 89: 871. Bucolo G, David H: Quantitative determination of serum
13.
14.
15.
16.
17.
18. 19.
20.
21.
22.
23.
August 1981
triglycerides by the use of enzymes. Clin Chem 1973; 19: 476. Allain CC, Poon LS, Chan CSG, et al.: The enzymatic determination of total serum cholesterol. Clin Chem 1974; 20: 470. Trinder P: Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969; 6: 24. Lopes-Virella MF, Stone P, Ellis S, Colwell JA: Cholesterol determination in highdensity lipoprotein reported by three different methods. Clin Chem 1977; 23: 882. Pearson TA, Bulkley BH, Achuff SC, Kwiterovich PO, Gordis L: The association of low levels of HDL cholesterol and arteriographically determined coronary artery disease. Am J Epidemiol 1979; 109: 285. Jenkins PJ, Harper RW, Nestel PD: Severity of coronary atherosclerosis related to lipoprotein concentration. Br Med J 1978; 2: 388. Barboriak JJ, Anderson AJ, Rimm AA, King JF: High density lipoprotein cholesterol and coronary artery occlusion. Metabolism 1979; 28: 735. Oberman A, Jones WB, Riley CP, Reeves TJ, Sheffield LT, Trirner ME: Natural history of coronary artery disease. Bull NY Acad Med 1972; 48: 1109. Bruschke AVG, Proudfit WL, Sones FM: Progress study of 590 consecutive non-surgical cases of coronary artery disease followed 5 to 9 years. I. Arteriographic correlations. Circulation 1973; 47: 1147. Burggraf GW, Parker JO: Prognosis in coronary artery disease, angiographic hemodynamic and clinical factors. Circulation 1975; 51: 146. Detre K, Murphy ML, Hultgren H: Effect of coronary bypass surgery on longevity in high and low risk patients. Lancet 1977; 2: 1243. Castelli WP, Cooper GR, Doyle JT, et al.: Distribution of triglyceride and total, LDL and HDL cholesterol in several populations: a cooperative lipoprotein phenotyping study. J Chronic Dis 1977; 30: 147.
The American Journal of Medicine
Volume 71
239