Clin Biochem, Vol. 25, pp. 313-316, 1992

0009-9120/92 $5.00 + .00 Copyright © 1992 The Canadian Society of Clinical Chemists.

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Observed Relationship Between Ratios HDL-Cholesterol/Total Cholesterol and Apolipoprotein A1/Apolipoprotein B JOHAN Departments

of Chemical

M . K U Y L 1 a n d D. M E N D E L S O H N

Pathology, 1University of the Orange Witwatersrand, South Africa

Epidemiological evidence suggests that the ratio HDLcholesterol (HDL-C)/total cholesterol (TC) or apolipoprotein A1 (apo A1)/apolipoprotein B (apo B) are good indicators of coronary heart disease risk. In investigating the distribution of these ratios in the typical population served by our routine laboratory, we analysed the lipid results of 541 serum samples submitted over a 2-month period for TC, HDL-C, apo A1, and apo B. Good correlation was observed between HDL-C and apo A1 (r = 0.664), and between TC and apo B (r = 0.674). Surprisingly, the correlation between the ratios HDL-C/TC (range: 0.05--0.40) and apo A1/apo B (range: 0.27-3.71) was even higher (r = 0.822). Similar significant correlations were observed in 31 heterozygous and 20 homozygous familial hypercholesterolemic subjects, viz. the correlations between HDL-C/TC (ranges: 0.04-0.24 and 0.02-0.12, respectively) and apo Al/apo B (ranges: 0.471.84 and 0.15-1.12, respectively) were r = 0.951 and r = 0.972, respectively.

KEY WORDS: apolipoprotein A1; apolipoprotein B; total cholesterol; HDL-cholesterol; familial hypercholesterolemia. Introduction he association of deficiency or excess of certain

T lipoproteins and apolipoproteins in blood with the development of atherosclerosis has been sup-

ported by epidemiological and genetic studies (1-3). Recent reports (4-6) have indicated that apolipoprotein A1 (apo A1) alone or combined as a ratio with apolipoprotein B (apo B), is a better predictor of coronary heart disease (CHD) than total cholesterol (TC) and or HDL-cholesterol (HDL-C). Because of this we include apo A1 and apo B determinations in a lipid profile request. Therefore, as part of the determination of reference intervals for these apolipoproteins for the laboratory's target population, we analysed retrospectively the results of routine samples submitted for lipid analysis over a 2-month pe-

Correspondence: Prof. J.M. Kuyl, Department of Chemical Pathology, University of the Orange Free State, P.O. Box 339 (G3), Bloemfontein 9300, Republic of South Africa. Manuscript received March 20, 1992; revised May 22, 1992; accepted June 24, 1992. CLINICALBIOCHEMISTRY,VOLUME25, OCTOBER1992


Free State and 2University

of the

riod, excluding repeat samples. We also included a group of homozygous and heterozygous familial hypercholesterolemic (FH) individuals attending our hyperlipidemic clinic for interpretive interest. Patients and methods All serum "lipid profile" results over a 2-month period (excluding duplicate and repeat samples) from fasting subjects were included in the study (541 cases), and grouped as in Table 1. These were compared with similar data from 31 heterozygote and 20 homozygote FH subjects attending our hyperlipidemic clinic; all were under treatment. Sera were assayed for: TC using a commercial enzymatic kit (Monotest cholesterol; high performance CHOD-PAP method; Boehringer, Mannheim, Germany). Interassay coefficient of variation (CV) was 4.1% at a level of 6.2 mmol/L. HDL-C was determined after MgC12-phosphotungstate precipitation with the same Boehringer PAP kit. Interassay CV was 6.6% at a level of 1.12 mmol/L. Apo A1 and apo B were determined with kits from Orion Diagnostica (Epsoo, Finland) in a turbidometric assay. Interassay CVs for apo A1 and apo B at levels of 1.41 g/L and 1.05 g/L, respectively, were 8.9% and 9.5%. Results Table i summarises the lipid data in the different subgroups. Serum cholesterol in blacks was lower than in whites (p < 0.01), confirming previous observations (7-9). Interestingly, the TC levels were higher in females (whites p < 0.01) but in the blacks this was not statistically significant. The HDL-C of the control females (blacks and whites) were the highest and the FH (heterozygotes and homozygotes) the lowest. Black females showed the highest values for the ratio HDL-C/TC, with the lowest in homozygous FH. The mean of the heterozygous FH group was significantly different from all other subgroups. This was not so clearly shown by the values 313


TABLE 1 S u m m a r y Lipoprotein P a r a m e t e r s of the Different Groups Black Females [127] Cholesterol (mmol/L) HCL-C (retool/L) Apo-A1 (g/L) Apo-B (g/L) HDL-C/TC Apo-A1/Apo-B

5.71 1.25 1.41 0.91 0.23 1.66

-+ 0.75 -+ 0.32 -+ 0.26 +- 0.24 +- 0.07 -+ 0.58

White Females [152] 6.74 1.26 1.46 1.14 0.19 1.40

+-- 1.58 +- 0.35 -+ 0.35 +- 0.36 -+ 0.06 -+ 0.54

Black Males [88] 5.54 1.07 1.31 0.98 0.20 1.43

White Males [174]

+- 1.32 - 0.33 + 0.31 -+ 0.27 - 0.05 -+ 0.51

6.32 1.04 1.33 1.17 0.17 1.23

FHHeterozygotes [31]

+- 1.47 ~ 0.26 ± 0.26 + 0.36 ± 0.05 ± 0.39

7.18 0.84 1.30 1.32 0.12 1.11

- 1.88 +- 0.285 +- 0.34 +- 0.69 - 0.04 b -+ 0.36

FHHomozygotes [20] 12.10 0.72 1.13 2.21 0.065 0.58

+- 2.98 ~ -+ 0.26 a -+ 0.45 -+ 0.86" -+ 0.03 ~ -+ 0.28"

Data are m e a n -+ SD. N u m b e r of subjects i n brackets. ~Significantly different from heterozygous group (p < 0.001). bSignificantly different from all groups (p < 0.01).

TABLE 2 Correlation Coefficients Between the Different Lipoprotein Components

Cholesterol vs Apo-B HDL-C vs Apo-A1 HDL-CfrC vs Apo-A1/Apo-B (slope)

Black Females [127]

White Females [152]

Black Males [88]

White Males [174]

FHHeterozygotes [31]

FHHomozygotes [20]

0.817 a 0.664 a 0.801 ~ (6.74)

0.754 a 0.660 ~ 0.836 a (7.38)

0.741 ~ 0.746 ~ 0.765 ~ (7.40)

0.747 ~ 0.556 ~ 0.801 ~ (6.16)

0.677 ~ 0.600 a 0.951 a (7.86)

0,477 b 0.681 a 0.972 ~ (8.78)

N u m b e r of subjects i n brackets. "Statistically significant (p < 0.001). bStatistically significant (p < 0.05).

:l O o


o o

~11 3 -





° °c~b o










O -r=0.822




I,,IDL - C / T C

Figure 1 S c a t t e r g r a m of the HDL-C/TC a g a i n s t the apo-A1/apo-B values of 541 s e r u m samples s u b m i t t e d to a r o u t i n e diagnostic laboratory. -







m ~7

,~ 1.5v




DIDo D D (3 0"








F i g u r e 2 - - S c a t t e r g r a m of the H D L - C f r C a g a i n s t t h e apo-A1/apo-B from f a m i l i a l h y p e r c h o l e s t e r o l a e m i c subjects. (A) FH-homozygotes, n = 20; ([3) FH-heterozygotes, n = 31.

of the apo A1/apo B ratio; although this ratio in the heterozygous FH group was significantly different from that in the homozygous FH group, it did not differ from the value in the white male group. Table 2 gives the correlations among the different lipid fractions. Significant linear correlations were found in all subgroups between TC and apo B, and between HDL-C and apo A1. The ratios HDL-C/TC and apo A1/apo B were consistently highly correlated in all the groups. Figures 1 and 2 are scattergrams of HDL-C/TC versus apo A1/apo B in the two main groups and demonstrate this linear relationship. Using the ratio HDL-C/(TC - HDL-C) instead of the ratio HDL-C/TC did not significantly alter the correlation values. Discussion We believe that the ratio HDL-CfrC is very useful in identifying individuals at risk for future CHD as well as monitoring the response of patients to therapy (10). Other investigators believe that apo A1 and apo B are better risk indicators of CHD (5). In this study we were mainly concerned with the distributions of lipid parameters in a heterogeneous population. Our results show high correlation between the ratios HDL-CfrC and apo A1/apo B for the two main groups studied (Figures 1 and 2). When these two major groups are subdivided into logical subgroups, the correlation between the two ratios is still high (Table 2), with similar slopes. We could find only one mention of a highly signifCLINICAL BIOCHEMISTRY, VOLUME 25, OCTOBER 1992

icant correlation between the ratios HDL/TC and apo A1/apo B in the literature (11). These workers mentioned only the correlation coefficient (r = 0.950) obtained from 45 subjects without showing the relevant ranges of HDL-C/TC and apo A1/apo B. If their result and ours is a consistent finding, which is not method-dependent, there must be a logical explanation for this. An explanation could be the highly significant correlations between HDL-C and apo A1, and between TC and apo B, respectively, suggesting that the separate ratios, i.e., HDL-CfrC and apo A1/apo B, are a measure of the dynamic equilibrium that exists in the fasting state in the blood between cholesterol transport to (apo B concentration) and from (apo A1 concentration) the peripheral cells. In conclusion, if HDL-C/TC is a good indicator of CHD risk, so is apo A1/apo B; thus it would not be cost-effective to routinely determine apo A1 and apo B together with TC and HDL-C unless abnormalities of apo A1 and apo B are specifically suspected. References 1. Stamler J, Wentworth D, Neaton JD. Is the relationship between serum cholesteroland risk of premature death from coronary heart disease continuous and graded? Findings in 356 222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). J A M A 1986; 256: 2823-8. 2. Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham study. J A M A 1986; 256: 2835-8. 315

KUYL AND MENDELSOHN 3. Abbott RD, Wilson PWF, Kannel WB, Castelli WP. High density lipoprotein cholesterol, total cholesterol screening, and myocardial infarction. The Framingham study. Arteriosclerosis 1988; 8: 207-11. 4. Aro A, Soimakallio S, Voutilainen E, Ehnholm C, Wiljasalo M. Serum lipoprotein lipid and apoprotein levels as indicators of the severity of angiographically assessed coronary a r t e r y disease. Atherosclerosis 1986; 62: 219-25. 5. Van Stiphout WAHJ, Hofman A, Kruijssen HACM, Vermeeren R, Groot PHE. Is the ratio ofapo B/apo A-I an early predictor of coronary atherosclerosis? Atherosclerosis 1989; 62: 179-82. 6. Pan QX, Liu P, Wang SC, et al. The study of serum apoprotein levels as indicators for the severity of angiographically assessed coronary artery disease. A m J Clin Pathol 1991; 95: 597-600. 7. Walker ARP, Walker BF. High-density-lipoprotein


8. 9.

10. 11.

cholesterol in African children and adults in a population free of coronary heart disease. B r Med J 1978; 2: 1336-8. Gomo ZAR. Concentrations of lipids, lipoproteins, and apolipoproteins in serum of Zimbabwean Africans. Clin Chem 1985; 31: 1390-2. Ngogang 7_J, Titanji VPK. The concentration of apolipoproteins and lipoprotein cholesterol in sera of normal and hypertensive African subjects from Yaounde, Cameroon. East Afr Med J 1985; 62: 446-51. Castelli WP, Abbott RC, McNamara PM. Summary of estimates of cholesterol used to predict coronary heart disease. Circulation 1983; 67: 730-4. Maciejko JJ, Levinson SS, Markyveck L, Smith MP, Blevins RD. New assay of apolipoproteins A-1 and B by rate nephelometry evaluated. Clin Chem 1987; 33: 2065-9.


apolipoprotein B.

Epidemiological evidence suggests that the ratio HDL-cholesterol (HDL-C)/total cholesterol (TC) or apolipoprotein A1 (apo A1)/apolipoprotein B (apo B)...
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