The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.     

Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics

Plasma triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoproteins (apo) A-I, A-II, C-II, and C-III were determined and analyzed in 170 diabetic patients and 46 age-matched healthy normal subjects. The diabetics were separated into two groups: insulin-dependent diabetes mellitus (IDDM, n = 78) and noninsulin-dependent diabetes mellitus (NIDDM, n = 92). Significantly increased triglycerides, low HDL cholesterol, and normal cholesterol levels were found in the diabetics. The lipid profiles were similar in the IDDM and NIDDM groups. Plasma apo A-I, but not apo A-II, was low in both groups of diabetics. However, only in the IDDM subjects was there a statistically significant decrease in apo A-I when compared to normal subjects. The decreased apo A-I level negatively correlated with plasma triglycerides. Apo C-II and apo C-III were slightly increased in the diabetics compared to normal subjects. Apo C-II and apo C-III levels significantly correlated with plasma triglycerides (apo C-II, r = 0.70, P less than 0.0001; apo C-III, r = 0.71, P less than 0.0001). Only apo C-II correlated with total cholesterol. Thirty-eight to forty-two percent of the IDDM and NIDDM subjects had a clinical diagnosis of coronary artery disease (CAD) and/or peripheral arteriovascular disease (PAD). In the IDDM subjects, but not in the NIDDM subjects the incidence of CAD and/or PAD was associated with the decreased apo A-I levels as evaluated by a univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of apo B-100, C-II, and C-III were higher, whereas those of HDL cholesterol were lower, for subjects in the highest tertile of apo C-III levels group, which presented a typical hypertriglyceridemic lipid profile. Subjects in the middle and highest tertile of apo C-III levels groups had increased preβ₁-HDL, HDL_3c, HDL_3b (only in the highest tertile of apo C-III group), and HDL_3a, but decreased HDL_2a and HDL_2b contents compared with subjects in the lowest tertile of apo C-III levels group. With the elevation of apo C-III together with apo C-II levels, contents of small-sized preβ₁-HDL increased successively and significantly; but those of large-sized HDL_2b reduced successively and significantly. With a rise in apo C-III and apo A-I levels, those of preβ₁-HDL increased significantly. Moreover, subjects with high apo A-I levels showed a substantial increase in HDL_2b; on the contrary, HDL_2b declined progressively and obviously for subjects in the low apo A-I levels with the elevation of apo C-III levels. Correlation analysis illustrated that apo C-III levels were positively associated with preβ₁-HDL, preβ₂-HDL, and HDL_3a. The particle size of HDL shifted toward smaller sizes with the increase of plasma apo C-III levels, and the shift was more remarkable when the elevation of apo C-III and apo C-II was simultaneous; and besides, higher apo A-I concentrations could modify the effect of apo C-III on HDL subclass distribution profile. Large-sized HDL_2b particles decreased greatly for hypertriglyceridemic subjects who were characterized by elevated apo C-III and C-II accompanied with significantly lower apo A-I, which, in turn, blocked the maturation of HDL.     

Plasma lipids, lipoproteins and apolipoproteins in two kindreds of hypobetalipoproteinemia

Plasma lipids and apolipoproteins were quantified in two kindreds of hypobetalipoproteinemia. All affected members were asymptomatic but showed a decrease of 75% in apolipoprotein B and of 69% in LDL-cholesterol. There were no major changes in apo A-I and A-II but all affected family members had reduced levels of apo C-II (by 58%) and C-III (by 59%) without significant decrease in apo C-I and no specific decrease of apo C-III1. Apolipoprotein E is decreased in SDS-PAGE. The plasma level and phenotype of Lp(a) are not affected by HBL, suggesting that a catabolic rather than a synthetic mechanism is responsible for the disease. As shown by density gradient ultracentrifugation, HDL2 particles that contain essentially apolipoprotein A-I, cholesterol and phospholipids represent in affected subjects the major part of HDL. Due to the net reduction of apolipoprotein B-containing particles (VLDL and LDL) as acceptors of lipids in HBL, there is an accumulation of large particles rich in cholesteryl esters.     

Changes of HDL subfraction concentration and particle size by intralipid in vivo

The effects of the artificial triglyceride-phospholipid emulsion (10% intralipid) on HDL subfraction were studied in vivo. After a 14-h fast, subjects received intralipid via a 4-h infusion. Serum lipoproteins were analyzed before and at 4 and 6 h after the start of the infusion. At 4-h the following acute changes by infusion were observed. Triglyceride, phospholipid, free cholesterol, and esterified cholesterol in chylomicrons and VLDL increased. HDL2 as well as triglyceride, phospholipid, free cholesterol and protein within the HDL2 increased, while HDL3 decreased. An increase in HDL3 triglyceride was observed. The masses of apo A-I and A-II in the HDL2 density interval rose while these parameters fell in HDL3. There were decreases of apo C-II and C-III in the HDL subfractions and elevations in chylomicrons and VLDL. The particle size of the HDL subfractions increased. However, most of these acute changes at 4 h tended to disappear by 6 h. These results suggest that there is exchange of lipids and reversible transfer of apo C-II and C-III between HDL subfractions and intralipid, and conversion of HDL3 to HDL2 followed by the reverse conversion of HDL2 to HDL3 as the synthetic emulsion is cleared from the plasma.     

Lipids, lipoproteins, apolipoproteins, and other risk factors in Chinese men and women with and without myocardial infarction

One hundred and fifty-four male and 69 female Chinese patients, aged between 40 and 60 years, who had suffered myocardial infarction (MI) were investigated and compared with 216 men and 219 women who had no history or ECG evidence of coronary heart disease. The male MI patients had significantly raised levels of triglycerides (160 mg/dl), cholesterol (194 mg/dl), VLDL-CH (31 mg/dl), apolipoprotein B (122 mg/dl) and apolipoprotein E (4.7 mg/dl) and a lower apolipoprotein A-I level (126 mg/dl) than the control group (triglycerides 131, cholesterol 179, VLDL-CH 26, apo B 102, apo E4.2, and apo A-I 138 mg/dl). The women with MI also had higher values for the atherogenic lipids than the control group (triglycerides 175 vs. 134 mg/dl, cholesterol 218 vs. 186 mg/dl, LDL-CH 128 vs. 104 mg/dl, VLDL-CH 32 vs. 26 mg/dl, apo B 121 vs. 103 mg/dl and apo E 5.4 vs. 4.3 mg/dl), as well as lowered apolipoprotein A-I (128 vs. 144 mg/dl). The Lp(a) levels (men and women considered together) were significantly higher for the MI patients (34.3 mg/dl vs. 26.2 mg/dl). Anti-atherogenic lipoproteins such as HDL-cholesterol, HDL2-CH, HDL3-CH, phospholipids and apolipoprotein A-II, C-II and C-III showed no difference between the groups.     

Lipid and apoprotein behaviour after oral fat load in hypertriglyceridaemia.

Post-prandial profiles of plasma lipids and apoproteins have been studied in 13 hypertriglyceridaemic patients and in 24 normolipidaemic subjects who acted as controls. Triglyceride curves were different in the two groups: type IV patients reached the peak later than the controls (7-h vs 4 1/2-h) and cleared plasma triglycerides more slowly. The magnitude of post-prandial response was found to be higher in hypertriglyceridaemic patients. Positive correlations were also found between triglycerides response and fasting levels of triglycerides, apo B, apo C-II, apo C-III and apo E levels and negative correlations (not significant) with HDL-C levels in both hypertriglyceridemics and controls. In normolipidaemic subjects the triglyceride increase area was also correlated with age, BMI and total cholesterol, while in type IV patients with apo A-I and apo A-II levels. These data confirm that the magnitude of post-prandial phase is influenced by fasting levels of triglycerides-rich lipoproteins and that HDL are important determinants in the control of the post-prandial response. The most relevant finding in this study was the difference of the post-prandial profile of apoproteins C-II, C-III and E. These apoproteins significantly decreased nine hours after meal in the controls, while in hypertriglyceridaemics these apoproteins showed a rise over time. On the contrary apo A-I, apo A-II and apo B curves presented a similar profile in both groups. Possible mechanisms have been discussed, but further studies are necessary to understand the metabolic defects responsible for this behaviour in hypertriglyceridaemia.     

Utility of non-high-density lipoprotein cholesterol versus other lipoprotein measures in detecting subclinical atherosclerosis in young adults (The Bogalusa Heart Study)

Direct comparative data on the utility of non-high-density lipoprotein (HDL) cholesterol versus low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, apolipoprotein (apo) B, apo A-I, ratio to total cholesterol to HDL cholesterol, and ratio of apo B to apo A-I in detecting increased carotid intima-media thickness (IMT), a validated measurement of subclinical atherosclerosis, in asymptomatic younger adults are scant. This aspect was examined in 1,203 black and white subjects (71% white, 43% men) 24 to 43 years of age. In multivariate logistic regression analysis of each lipoprotein measurement (top quartile vs lower 3 quartiles specific for age, race, and gender) for detecting increased carotid IMT (top decile vs lower 9 deciles specific for age, race, and gender), only non-HDL cholesterol, total cholesterol/HDL cholesterol, and apo B emerged as significant correlates with respective odds ratios of 1.75 (95% confidence interval [CI] 1.10 to 2.78), 2.02 (95% CI 1.27 to 3.19), and 2.13 (95% CI 1.38 3.29), after adjusting for body mass index, systolic blood pressure, and other lipoprotein measurements. Regarding discriminating values of different lipoprotein measurements in detecting increased carotid IMT, area (c-value) under the receiver operating characteristic curve analysis for each lipoprotein measurement adjusted for age, race, gender, body mass index, and systolic blood pressure indicated that the c-value for non-HDL cholesterol (0.73) was similar to those for low-density lipoprotein cholesterol (0.76), total cholesterol/HDL cholesterol (0.72), apo B/apo A-I (0.71), and HDL cholesterol (0.70), but significantly (p <0.001) higher than that for apo A-I (0.69), triglycerides (0.64), and apo B (0.64). In conclusion, non-HDL cholesterol is as good as or better than other widely recommended lipoprotein measurements in the identification of subclinical atherosclerosis in young adults.     

Lipid and apoprotein modifications in body builders during and after self-administration of anabolic steroids

To determine the effects of anabolic steroids on serum lipid and apoprotein levels, 14 white male body builders who self-administered steroids for 2 to 3 months (steroid users) were studied; 10 agreed to screening while they were taking the drugs (ON treatment) and also at about 3 months following their suspension (OFF treatment). Controls consisted of 17 body builders who had never taken steroids (nonusers), and a group of 18 healthy sedentary subjects (controls). During the period of steroid administration, there was a slight reduction in total serum cholesterol, with a marked cholesterol decrease in the high-density lipoprotein (HDL) subfractions HDL2 and HDL3, and a significant reduction in the HDL2 cholesterol/HDL3 cholesterol ratio; the percentage of serum cholesterol transported by low-density lipoproteins (LDL) increased significantly. In addition, a marked apoprotein (apo) A-I reduction in the HDL2 and HDL3 subfractions was observed, as well as an apo A-II decrease that was significant only in the HDL3 subfraction, with an A-I/A-II ratio significantly reduced in both subfractions. Serum apo B was only slightly increased, with a very high B/A-I ratio. Apolipoprotein C-II and E levels showed no modifications, while apo C-III reduced significantly. Lipid and apoprotein values returned to almost normal levels in the OFF treatment period. Findings in the group of nonusers were similar to those in sedentary subjects. These results indicate that anabolic steroids profoundly alter the serum lipid-protein profile, and the changes may be caused in part by the significant differences observed in apoprotein levels.     

Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease

Lipoprotein (Lp) cholesterol and apolipoproteins (apo) A-I and B levels have been shown to be better markers for the presence of coronary artery disease than total cholesterol. In this study, we determined the plasma levels of lipoprotein particles containing apo A-I only (LpA-1), apo A-I and A-IL (LpA-I:A-1I), apo B and C-III (LpB:C-III) and apo B and E (LpB:E) in 145 patients with coronary artery disease (mean age ± SD, 51 ± 7 years) and 135 healthy control men (mean age 49 ± 11 years). Patients with CAD had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo B levels than controls. In patients with CAD, LpA-I (0.341 ± 0.093 vs. 0.461 ± 148 g/1) and LpA-1:A-II (0.694 ± 0.171 vs. 0.899 ± 0.148 g/1) were lower, whereas LpB:E (0.372 ± 0.204 vs. 0.235 ± 0.184 g/1) were higher than in controls (cases vs. controls, all P < 0.005). No significant differences were observed for LpB:C-III (0.098 ± 0.057 vs. 0.107 ± 0.061 g/1, p = 0.235) particles. Discriminant analysis indicates that LpA-II:A-I, LpE:B, LpA-I, and triglycerides best differentiate between cases and controls. Plasma apo C-III (0.027 ± 0.008 vs. 0.036 ± 0.020 g/1) and E (0.040 ± 0.015 vs. 0. 055 ± 0.029 g/1) were lower in the CAD group (P < 0.001). The finding that apo C-III and E levels are lower in the CAD patients relate to the fact that in our patients, HDL particles are the main carriers of apo E and C-III and that in addition to HDL-cholesterol, the protein component of HDL particles are reduced in CAD. We conclude that apo B, LpB:E but not LpB:C-III containing particles are increased in patients with CAD and that apo A-I containing particles, with or without apo A-II are reduced in patients with CAD. In addition, HDL-cholesterol and associated apolipoproteins (A-I, A-11, C-III and E) are reduced in CAD.     

Possible Link Between a Low Prevalence of Cardiovascular Disease and Mild Dyslipidaemia: a Study in Japanese Patients with Type 2 Diabetes

In 98 Japanese patients with Type 2 diabetes mellitus, serum total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), and apolipoproteins (apo) A-I, A-II, B, C-II, C-III, and E were determined. The data were compared with those in 47 normolipidaemic normal controls. The total cholesterol value of the diabetic patients was also compared to that of a general population (n = 2227). The diabetic patients were separated into those with cardiovascular disease (n = 20) and without it (n = 78) and a comparison of clinical characteristics and dyslipidaemia was also performed. The diabetic patients had slightly but significantly higher FFA, LDL-C, apo B, C-II, C-III, E, and B/A-I, and lower apo A-I and A-II compared to the normal controls. The total cholesterol level of the diabetic patients (5.17 ± 0.96 mmol^?1) was not significantly higher than that of the general population (5.12 ± 0.91 mmol^?1). By multivariate stepwise discriminant analyses, only total cholesterol significantly discriminated the patients with and without cardiovascular disease. In Japanese patients with Type 2 diabetes, a diabetic population with a very low prevalence of cardiovascular disease, high total cholesterol ís a risk factor for developing cardiovascular disease. Nevertheless, a markedly low prevalence of cardiovascular disease in Japanese with Type 2 diabetes compared to Caucasian counterparts may partly be due to the mildness of dyslipidaemia.     

Hyperthyroidism influences the distribution and apolipoprotein A composition of the high density lipoproteins in man

Hyperthyroidism has a different influence on the major high density lipoprotein (HDL) components cholesterol, apoprotein (apo) A-I, and apo A-II. To characterize in greater detail the alterations induced by hyperthyroidism within the HDL subclasses, we investigated HDL distribution and composition in 11 hyperthyroid women before and during treatment. The plasma concentrations of total cholesterol, HDL cholesterol, phospholipids, apo A-I, and apo B were decreased when the patients were hyperthyroid compared with the values during treatment. Apo A-II and apo C-III levels were only slightly lower in the hyperthyroid state. Triglyceride and apo E concentrations did not change significantly during therapy. Analysis of lipoprotein subclasses separated by isopycnic ultracentrifugation revealed 1) marked decreases in low density lipoprotein (LDL) cholesterol, phospholipids, and apo B; 2) less pronounced reductions in the very low density lipoprotein (VLDL) lipid and apo B concentrations; and 3) a consistent decrease in the HDL2b (density, 1.063-1.100 g/ml) fraction in the hyperthyroid patients. The reduction in HDL2b mass was associated with lower concentrations of HDL2b cholesterol, phospholipids, and apo A-I. The HDL2b apo A-II levels remained constant during treatment. Hyperthyroidism, therefore, modified the apo A composition of the HDL2b particles and resulted in a decreased molar apo A-I to apo A-II ratio within HDL2b. Further analysis of HDL particles differing in their apo A composition; i.e. HDL particles containing apo A-I only [(A-I)HDL] or containing both apo A-I and A-II [(A-I + A-II)HDL], by immunological procedures suggested that hyperthyroidism influenced the apo A content of HDL2b mainly by changing the proportions of (A-I)HDL and (A-I + A-II)HDL and the amount of apo A-I associated with (A-I)HDL. Treatment reversed the preferential decrease in (A-I)HDL within the HDL2b subclass. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were similar in the untreated and treated patients. Consequently, the decreased mass of apo A-I and lipids within HDL2b in the hyperthyroid patients could be attributed to a reduced number of identically sized particles within this fraction. These data demonstrate that the thyroid hormones are important regulators of HDL metabolism through their influence on the concentration and distribution of apo A-I.     

Mild exercise therapy increases serum high density lipoprotein2 cholesterol levels in patients with essential hypertension

In ten patients with essential hypertension who were on a prescribed regimen of supervised mild exercise, we examined serum lipids, HDL cholesterol subfractions (HDL2 and HDL3), and apolipoproteins. The findings were compared with data on age- and sex-matched hypertensives not on this regimen of exercise. Blood samples were obtained from the auricle during the multistage exercise test, and changes in levels of lactate were measured. The exercise was done for 30 minutes three times weekly for 10 weeks. A significant reduction of both systolic and diastolic blood pressure was evident at 10 weeks. Serum concentrations of HDL2 cholesterol increased significantly at 10 weeks, but there were no changes in total and HDL3 cholesterol. No significant changes were observed in serum concentrations of total cholesterol, triglyceride, and apolipoproteins, (apo) A-I, apo A-II, apo B, apo C-II, apo C-III and apo E following 10 weeks of exercise therapy. In the hypertensive controls who were not on exercise therapy, blood pressure as well as all parameters related to lipoproteins remained unchanged. Thus, mild exercise lowers blood pressure and improves the lipoprotein profile.     

Relationship of the phenotypic expression of the A-IMilano apoprotein with plasma lipid and lipoprotein patterns

The plasma lipoprotein and apolipoprotein profile of 29 adult A-IMilano (A-IM) carriers and 29 age- and sex-matched non-affected subjects of the same kindred was examined, in order to investigate linkages between the lipid and apoprotein abnormalities and the phenotypic expression of the biochemical disorder. Carriers (A-IM+) showed a higher prevalence of hypertriglyceridemia (12 out of 29); they also had lower plasma total cholesterol, esterified cholesterol and phospholipids, compared to non-carriers. Lipoproteins were characterized by a significant enrichment of triglycerides in low and high density fractions (LDL and HDL), and by the expected striking reduction of HDL mass and cholesterolemia. Conversely, no significant alterations of the major circulating apolipoprotein levels, except for apo A-I and apo A-II, were noted in the A-IM+. The increased free cholesterol/esterified cholesterol ratio in plasma (most marked in HDL), was accompanied by a significant reduction of the lecithin cholesterol acyl transferase molar activity. Several correlations pertaining to lipids, lipoproteins and apoproteins were examined: cholesterol and triglycerides in HDL and, more remarkably, apoprotein A-I and C-III levels in plasma were significantly correlated in the A-IM+. While there was no significant prevalence of specific apo E phenotypes, plasma triglycerides and apo C-II levels were highly correlated in the carriers. The A-IM subjects, while in the presence of severe lipoprotein risk factors, may have alternative mechanisms of cholesterol disposal, potentially responsible for the apparently low prevalence of atherosclerosis.     

Apo B-containing lipoprotein particles in poorly controlled insulin-dependent diabetes

The goal of this study was to compare the structural and biological characteristics of apolipoprotein (apo) B-100-containing particle subfractions isolated from poorly controlled diabetic patients with insulin-dependent diabetes (IDDM), and healthy controls matched for sex, age and body mass index (BMI). Different apo B-containing particles were isolated by sequential immunochromatography and were free of apo A-I, apo A-II, apo A-IV and apo(a). Particles lipoprotein (Lp) B/C-III contained apo B and apo C-III. They were free of apo E. Particles Lp B/E contained apo B and apo E. They were free of apo C-III. Particles Lp B were devoided of apo C-III and apo E. All these particles could contain other known apolipoproteins not cited here, as for example apo C-II and/or apo C-I. The plasma levels of cholesterol, triglycerides, phospholipids, apo A-I, B-100, C-III, E, total Lp B/C-III. total Lp B/E were not different between patients and controls. The physico-chemical properties of Lp B/C-III and Lp B/E were similar in both groups. Only Lp B from patients exhibited some changes, an increase in the size and a decrease in the cholesterol and cholesteryl ester levels. The conformational properties of the lipoproteins were studied through their immunoreactivity against four different anti-apo B-100 monoclonal antibodies (MAb) for which sequential epitopes have been located on the protein, and one MAb for which the epitope is conformationally expressed. Again, minor changes were observed between patients and controls, and only a slight decrease in the immunoreactivity of the epitope encompassing amino-acid residues 405 to 539 of Lp B and of the conformationally expressed epitope of Lp B/C-III were found in patients. Nevertheless, whatever these conformational and/or physico-chemical modifications may be, they were not sufficient to induce functional alterations in the binding of the particles from the patients to the LDL-receptor of HeLa cells. This study shows that IDDM is not associated with any significant abnormalities in the apo-containing lipoprotein particles. The excessive occurrence of coronary heart disease (CHD) and other atherosclerotic vascular disease in patients with IDDM must have other causes.     

Clinical studies on lipid metabolism in hyperthyroidism and hypothyroidism--evaluation of serum apolipoprotein levels before and after treatment

The present study was undertaken to assess lipid metabolism in patients with thyroid dysfunction with special reference to serum apolipoprotein levels. Serum lipid, lipoprotein and apolipoprotein levels were determined in 28 hyperthyroid and 16 hypothyroid female patients while untreated and euthyroid. Apolipoproteins were measured by the method of single radial immuno-diffusion (SRID). These results were compared with the values of 28 female controls. In the untreated hyperthyroid group, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were significantly decreased compared to the controls and increased after treatment. In hypothyroidism, these values before treatment were higher than those in the controls and decreased after treatment. Serum apo A-I, A-II, B and C-III levels were significantly decreased in the untreated hyperthyroid group compared to the control values. Apo C-II and E levels in hyperthyroidism were identical both before and after treatment compared with the control values, respectively. In the untreated hypothyroidism, apo B, C-II, C-III and E levels were significantly elevated compared to the controls, and these changes in apolipoproteins except apo C-II were restored after treatment. Apo A-I and A-II levels in the untreated hypothyroidism were not statistically different from the values after treatment or those in the control group. Serum thyroid hormone (T3, T4) levels inversely correlated apo B and C-III in all subjects. In hypothyroidism, serum TSH positively correlated with apo B, C-II and C-III. The increase in relative body weight (%RBW) in hyperthyroidism during treatment correlated with the changes of TC and LDL-C. In conclusion, these results indicate that thyroid hormones have a substantial influence on the serum apolipoprotein levels, and that measurement of apolipoproteins as well as lipids and lipoproteins in patients with thyroid dysfunction may be useful to evaluate the lipid metabolism and the effect of therapy.     

Levels of serum lipids, apolipoproteins A-I and B and pseudocholinesterase activity and their discriminative values in patients with coronary by-pass operation

Serum lipids and apoproteins A-I and B were measured in 115 male patients and serum pseudocholinesterase activity (PChE) was determined in 83 patients with 3 vessel coronary artery disease (CAD). The control subjects were matched according to sex, smoking, relative weight and age and were free from heart disease. The CAD patients had significantly higher serum VLDL cholesterol and triglyceride levels and lower HDL cholesterol and apo A-I levels and lower HDL to total cholesterol ratio than the controls. The concentrations of serum total cholesterol and LDL cholesterol were only slightly (6.4% and 8.8%, on an average) higher in CAD patients than in controls. The apo B levels of CAD patients were also slightly lower in patients than in controls. The CAD patients had slightly higher PChE activities than controls. The ratios of apo A-I to PChE and HDL cholesterol to PChE were significantly (about 30%, P less than 0.001) lower in patients than in controls. In discriminant analysis between the groups HDL cholesterol and apo A-I showed the best (74% success in reclassifying the patients to correct groups), and total cholesterol, triglycerides, LDL cholesterol and apo B remarkably weak discriminating power among the single variables of serum lipids and lipoproteins. In discriminating analysis the apo A-I/PChE and HDL cholesterol/PChE ratios showed relatively high (77.1 and 71.1% success from the patients to correct groups) and serum PChE activity weak discriminating power. These results indicate that low levels of HDL cholesterol and apo A-I and the low ratio of HDL cholesterol to total cholesterol are the most potent metabolic risk factors for 3 vessel coronary artery disease in a population with relatively high serum total cholesterol level. The determinations of apo A-I/PChE and HDL cholesterol/PChE ratios may be an additional, valuable tool in discriminating the risk for CAD.     

Effect of gemfibrozil on lipids, apoproteins, and postheparin lipolytic activities in normolipidemic subjects

The lipid lowering agent Gemfibrozil was tested in 8 normolipidemic subjects during a three-month intake. Plasma triglycerides decreased by 41% and Very Low Density Lipoprotein (VLDL) triglycerides decreased by 54%. The reduction of plasma cholesterol, less marked (by 10%), was due to a decrease of Low Density Lipoprotein by 20% while High Density Lipoprotein (HDL) increased up to 30%. The separation of HDL demonstrated that only HDL3 were increased. The determination of the apoproteins in plasma and lipoprotein fractions showed similar results with a decrease of apo B (by 20%) and an increase of apo A-I and apo A-II, mainly in the HDL3 fraction. Plasma postheparin lipolytic activities (PHLA) were not influenced by the therapy and no correlation was found between these activities and any of the plasma or lipoprotein lipids. The apo C-III/apo C-II ratio in VLDL decreased by 30%; however, no correlation was found between this ratio in plasma as well as VLDL and triglycerides. In addition, the Intra Venous Fat Tolerance Test did not demonstrate any improvement of the clearance of exogenous fat. The lipid lowering efficacy of Gemfibrozil, its collateral effects, and the possible mechanisms of action are discussed.     

Changes in serum apolipoprotein concentrations after L-thyroxine therapy in infants with congenital hypothyroidism

To further characterize the impact of thyroid hormones on the serum lipid profile, we studied serum apolipoproteins in infants with congenital hypothyroidism before and after L-thyroxine (L-T4) replacement therapy. Serum high-density lipoprotein cholesterol (HDLC) decreased after L-T4 therapy. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels did not change significantly after therapy. Two months after L-T4 replacement therapy, serum apolipoprotein A-I (apo A-I), C-III, and E declined and apo B increased significantly. No significant changes were observed for serum concentrations of apo A-II and C-II after L-T4 substitution. We conclude that in infants, thyroid hormone reduces serum levels of apo A-I, the principal protein component of HDLC, and this may contribute to the decline of serum HDLC concentrations after L-T4 replacement therapy.     

Quantification of plasma lipids and apolipoproteins in British Halflop rabbits. A comparison between normocholesterolemic rabbits, hypercholesterolemic rabbits (modified WHHL rabbits) and rabbits fed an atherogenic diet

We have established isolation methods and developed electroimmunoassays for rabbit apolipoprotein A-I (apo A-I), apo B, apo C-III and apo E. The assays were used to characterize a hyperlipidemic strain of the British Halflop rabbits (BHL rabbits), obtained after cross-breeding with WHHL rabbits and referred to as modified WHHL rabbits, and to investigate the changes in the apolipoprotein levels induced by feeding normal BHL rabbits an atherogenic diet (0.25% cholesterol and 3% coconut oil). The modified WHHL rabbits were characterized by increased levels of apo B, apo C-III and apo E as well as cholesterol, phospholipids and triacylglycerol as compared to chow-fed BHL rabbits, while the apo A-I levels were only half of those found in the chow-fed animals. The modified WHHL rabbits had virtually no low density lipoprotein (LDL) receptor activity and a low fractional catabolic rate (FCR) of LDL. These results indicate that the modified WHHL rabbit has the homozygous form of the LDL receptor deficiency. The BHL rabbits fed the atherogenic diet showed increased levels of cholesterol, triacylglycerol, apo B, apo C-III and apo E, as compared to those of the chow-fed BHL rabbits. The apo E and apo C-III reached levels in the range of or even higher than those of the modified WHHL rabbits. The apo A-I levels on the other hand did not differ from those of the chow-fed rabbits. Feeding an atherogenic diet led to a decrease in the FCR of LDL to a level similar to that found in the modified WHHL rabbits.