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Removal of serum cholesterol in control and hyperlipidaemic subjects
480 cc.4 5034 Removal of serum cholesterol in control and hyperlipidaemic
subjects
Triglyceride metabolism of plasma very low density lipoproteins has been shown to be characterized by conventional enzyme kinetics in manl. Furthermore, more detailed analyses of plasma triglyceride kinetics have indicated that a normal healthy population is divided at least in two, possibly in three different subgroups with different maximal removal velocity (I’,,,) of triglycerides but with the same plasma triglyceride concentration at half maximal removal (Km)B. In the present study an attempt was made to reveal a similar heterogeneity with regard to cholesterol metabolism. For this purpose conventional enzyme plot of [S] VGYSW[S] jl’ was performed according to Fig. I for normolipidaemic healthy control subjects, hyperglyceridaemic patients with variable serum cholesterol and patients with familial hypercholesterolaemia of our earlier3-6 and unpublished studies. In this plot [S] ==:serum total cholesterol concentration (mg/roo ml) and V = sterol balance (mg/day/kg of body weight), i.e. the removal velocity at which serum cholesterol is removed into faeces as neutral sterols and bile acids. Because sterol balance studies were performed on a low-cholesterol diet (dietary intake about 1.5 mg/day/kg of body weight) in metabolic steady state the sterol balance value closely equals removal. It can be seen, as was reported for plasma triglycerides?, that the control group of 13 subjects appears to comprise two subgroups, the one of seven cases in which the correlation coefficient between [.S! and iS]jV was o.qo (group I) and the other of five
Fig. I. Correlation of serum cholesterol concentration/sterol balance (ordinate) with serum cholesterol level (abscissa). The two regression lines are for the two subgroups found in healthy normal controls. The I/,,, of the lower line is 26.5 mg/day/kg and the corresponding K, 152 mg/roo ml. For the upper line these values are 18.9 and 152, respectively. Vm,, is obtained by r/slope of the line. The intercepts of the lines at the x axis correspond the negative values of I<,. IKH = hvperCholesterola~Inia, HG = hJ~ergll”ceridaenIja.
BRIEF NOTES
481
subjects (group II) with Y = 0.88. One case is seen to fall above these two curves. The regression lines of the two groups intercept the x axis at about the same point so values appear to be identical : for group I, 152 mg/roo ml and for group II, 163 mg/roo ml. The corresponding V n,sx (r/slope of the lines) would be different, viz. 26.5 and 18.9 mgjdaylkg, respectively. It is thus possible that if cholesterol influx is increased, e.g. due to high absorption of dietary cholesterol or as a consequence of obesity-induced enhancement of cholesterol synthesis the latter group is more likely to develop hypercholesterolaemia than the former one. This may explain the poor correlation found between serum cholesterol and cholesterol production in obese subjects3. No significant correlations were obtained if, instead of the sterol balance data, either bile acid or neutral sterol values were used separately in the plot of the two groups, suggesting that normally, cholesterol removal may be determined by the cholesterol uptake from plasma lipoproteins to the liver. Though the number of normal subjects studied is quite small, the results suggest that a normal population is heterogeneous, comprising two, possibly three subgroups with different cholesterol
that the K,
elimination capacity. It remains to be shown whether these groups are related to those reported to have different triglyceride kineticP. Hyperglyceridaemic subjects are not specifically located on either of the lines defined for the controls in Fig. I. Some of the cases with normal serum cholesterol level are located below the lines, indicating enhanced synthesis and effective removal. On the other hand, most of the values at the elevated serum cholesterol levels are seen to fall above the lines. This suggests that overproduction of cholesterol is not the primary cause of hypercholesterolaemia in these patients, defective removal being the most likely initiating factor4-5. The / S]/V correlated positively (Y = 0.68) with [S], the regression equation being y = 0.11 x-8.12. A significant correlation (r = 0.54) was found between the [S] /V and ‘S ] also in patients with familial hypercholesterolaemia, the regression coefficient (y =- 0.10 ~-4.54) being identical with that of the hyperglyceridaemic patients but greater than in the two control groups. In addition, l;ig. I shows that most of the spots are located above the regression lines of the controls, indicating cholesterolaemia
that production of cholesterol may be even subnormal may be a result of impaired cholesterol elimination
and that hyperfrom the blood.
ACKNOWLEDGEMENT
The study has been performed Life Assurance
under a contract
with the iZssociation
of Finnish
T. A.
MIETTINEN
Companies.
Third Department of Medicine, Cniversity o_fHelsinki, Helsinki 29 (Finland) I 1 3 4
c;. E. ‘r. T.
M. A. A. A.
REAVEN, D. B. HILL, I<. C. GROSS A.UD J. W. FARQUAAR, J. Clin. 1nuest., 44 (1965) 1826. NIKKILA AND &I. KEKKI, Acta Mrd. Sand., 190 (1971) 49. I\IIIETTINEN, Ci+‘cUhtiO?%, 44 (1971) 842. XIETTINEX, Early diagnosis of coronary heart disease, in Advances in Cardiology, Vol. 5, liarger, Basel, 1972, in press. _=,T. A. MIETTINES, .4nn. Clzn. RES., 3 (1971) 264.
Received
February
15, 1972 Clin. Chim. Acta, 39 (1972) 480-481
subjects
Triglyceride metabolism of plasma very low density lipoproteins has been shown to be characterized by conventional enzyme kinetics in manl. Furthermore, more detailed analyses of plasma triglyceride kinetics have indicated that a normal healthy population is divided at least in two, possibly in three different subgroups with different maximal removal velocity (I’,,,) of triglycerides but with the same plasma triglyceride concentration at half maximal removal (Km)B. In the present study an attempt was made to reveal a similar heterogeneity with regard to cholesterol metabolism. For this purpose conventional enzyme plot of [S] VGYSW[S] jl’ was performed according to Fig. I for normolipidaemic healthy control subjects, hyperglyceridaemic patients with variable serum cholesterol and patients with familial hypercholesterolaemia of our earlier3-6 and unpublished studies. In this plot [S] ==:serum total cholesterol concentration (mg/roo ml) and V = sterol balance (mg/day/kg of body weight), i.e. the removal velocity at which serum cholesterol is removed into faeces as neutral sterols and bile acids. Because sterol balance studies were performed on a low-cholesterol diet (dietary intake about 1.5 mg/day/kg of body weight) in metabolic steady state the sterol balance value closely equals removal. It can be seen, as was reported for plasma triglycerides?, that the control group of 13 subjects appears to comprise two subgroups, the one of seven cases in which the correlation coefficient between [.S! and iS]jV was o.qo (group I) and the other of five
Fig. I. Correlation of serum cholesterol concentration/sterol balance (ordinate) with serum cholesterol level (abscissa). The two regression lines are for the two subgroups found in healthy normal controls. The I/,,, of the lower line is 26.5 mg/day/kg and the corresponding K, 152 mg/roo ml. For the upper line these values are 18.9 and 152, respectively. Vm,, is obtained by r/slope of the line. The intercepts of the lines at the x axis correspond the negative values of I<,. IKH = hvperCholesterola~Inia, HG = hJ~ergll”ceridaenIja.
BRIEF NOTES
481
subjects (group II) with Y = 0.88. One case is seen to fall above these two curves. The regression lines of the two groups intercept the x axis at about the same point so values appear to be identical : for group I, 152 mg/roo ml and for group II, 163 mg/roo ml. The corresponding V n,sx (r/slope of the lines) would be different, viz. 26.5 and 18.9 mgjdaylkg, respectively. It is thus possible that if cholesterol influx is increased, e.g. due to high absorption of dietary cholesterol or as a consequence of obesity-induced enhancement of cholesterol synthesis the latter group is more likely to develop hypercholesterolaemia than the former one. This may explain the poor correlation found between serum cholesterol and cholesterol production in obese subjects3. No significant correlations were obtained if, instead of the sterol balance data, either bile acid or neutral sterol values were used separately in the plot of the two groups, suggesting that normally, cholesterol removal may be determined by the cholesterol uptake from plasma lipoproteins to the liver. Though the number of normal subjects studied is quite small, the results suggest that a normal population is heterogeneous, comprising two, possibly three subgroups with different cholesterol
that the K,
elimination capacity. It remains to be shown whether these groups are related to those reported to have different triglyceride kineticP. Hyperglyceridaemic subjects are not specifically located on either of the lines defined for the controls in Fig. I. Some of the cases with normal serum cholesterol level are located below the lines, indicating enhanced synthesis and effective removal. On the other hand, most of the values at the elevated serum cholesterol levels are seen to fall above the lines. This suggests that overproduction of cholesterol is not the primary cause of hypercholesterolaemia in these patients, defective removal being the most likely initiating factor4-5. The / S]/V correlated positively (Y = 0.68) with [S], the regression equation being y = 0.11 x-8.12. A significant correlation (r = 0.54) was found between the [S] /V and ‘S ] also in patients with familial hypercholesterolaemia, the regression coefficient (y =- 0.10 ~-4.54) being identical with that of the hyperglyceridaemic patients but greater than in the two control groups. In addition, l;ig. I shows that most of the spots are located above the regression lines of the controls, indicating cholesterolaemia
that production of cholesterol may be even subnormal may be a result of impaired cholesterol elimination
and that hyperfrom the blood.
ACKNOWLEDGEMENT
The study has been performed Life Assurance
under a contract
with the iZssociation
of Finnish
T. A.
MIETTINEN
Companies.
Third Department of Medicine, Cniversity o_fHelsinki, Helsinki 29 (Finland) I 1 3 4
c;. E. ‘r. T.
M. A. A. A.
REAVEN, D. B. HILL, I<. C. GROSS A.UD J. W. FARQUAAR, J. Clin. 1nuest., 44 (1965) 1826. NIKKILA AND &I. KEKKI, Acta Mrd. Sand., 190 (1971) 49. I\IIIETTINEN, Ci+‘cUhtiO?%, 44 (1971) 842. XIETTINEX, Early diagnosis of coronary heart disease, in Advances in Cardiology, Vol. 5, liarger, Basel, 1972, in press. _=,T. A. MIETTINES, .4nn. Clzn. RES., 3 (1971) 264.
Received
February
15, 1972 Clin. Chim. Acta, 39 (1972) 480-481