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.     

High density lipoprotein (HDL) subfractions in cardiovascular patients with low levels of HDL-cholesterol. Influence of hypertriglyceridaemia on subfraction concentration and composition

The major high density lipoprotein (HDL) subfractions were examined in angiographically defined cardiovascular patients with low HDL-cholesterol (HDL-C) levels. The aims were to study subfraction concentration and composition, and the extent to which hypertriglyceridaemia (HTG) modified these variables. Normotriglyceridaemic (NTG)-low HDL-C patients showed similar subfraction composition to age-matched healthy controls. However, these groups showed notable differences in subfraction composition compared to HTG-low HDL-C patients, particularly with regard to the HDL2 subfraction. HDL subfraction mass was significantly reduced in both cardiovascular groups; the HTG group showed a greater reduction in HDL2, whilst the NTG group showed a greater reduction in HDL3. The major HDL apoprotein (apo A-I) was lower in both subfractions of the cardiovascular patients. Apo A-II showed significant reductions only in the HTG patients.     

Metabolic effects of a biphasic oral contraceptive preparation containing ethinyloestradiol and desogestrel on serum lipoproteins and apolipoproteins

The effect of the administration of a biphasic oral contraceptive containing ethinyloestradiol and desogestrel on the distribution and composition of serum lipoproteins was studied in a group of 17 healthy female volunteers. The women were treated for a period of 6 months and compared with a control group of ten untreated volunteers. The serum lipoproteins were fractionated by density gradient ultracentrifugation into very low density lipoproteins (VLDL), low density lipoproteins (LDL), and into the high density lipoprotein (HDL) subfractions 2 and 3 (HDL2, HDL3). Lipids and apolipoproteins were assayed in the various fractions. No modification of either the lipid or apolipoprotein concentrations was observed in the control group. In the treated group, sex hormone-binding globulin (SHBG) and cortisol-binding globulin (CBG), and the serum content of cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) increased significantly after 3 and 6 months. The cholesterol and apolipoprotein B (apo B) content of VLDL increased significantly after 3 and 6 months, but remained unchanged in LDL. High density lipoprotein subfraction 2 (HDL2)-cholesterol was significantly increased after 3 and 6 months but apo A-I only after 6 months. Since apo A-II did not change, the apo A-I/A-II ratio increased significantly after 6 months of treatment. In the HDL3 fraction, the apo A-I increase was significant after 3 and 6 months, while the increase of apo A-II was significant after 6 months. The apo A-I/A-II ratio remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Separation of high density lipoprotein (HDL) using anti-apo A-I, apo A-II immuno-affinity chromatography to evaluate the effects of probucol]

An assessment has been made regarding the changes of the particles of lipoprotein A-I without A-II (Lp A-I) and lipoprotein A-I with A-II (LpA-I/A-II) which correspond to HDL subfraction isolated by the use of anti-apo A-I and A-II antibody affinity columns in order to quantitatively and qualitatively investigate the change of HDL caused by administration of probucol and pravastatin which are therapeutic drugs for hypercholesterolemia. Probucol caused significant decreases of HDL-cholesterol, plasma apo A-I/apo A-II ratio and particles larger in diameter than 10.4 nm. Comparing Lp A-I and A-I/A-II ratios with those in normolipidemic controls and the ratios before and after administration of probucol, the decrease of LpA-I ratio was found to be remarkable after prolonged administration of probucol, and it was presumed that the decrease of HDL cholesterol by prolonged administration reflects the decrease of LpA-I particles more than the decrease of LpA-I/A-II. On the other hand, no significant change was seen in HDL cholesterol, plasma apo A-I/apo A-II ratio or HDL particle size in the pravastatin group. It is considered essential to observe HDL from the aspect of apoprotein, which plays an important role in the metabolism of lipoprotein, in the assessment of the anti-atherogenic activity of HDL cholesterol in future. In other words, it is necessary to analyze the change of HDL from the aspect of Lp A-I and Lp A-I/AII and investigate their respective metabolisms and roles.     

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.     

Influence of probucol administration on lipoprotein cholesterol and apolipoproteins in normolipemic males

In order to interpret the known lipoprotein changes in probucol-treated patients, serum concentrations of apolipoproteins (A-I, A-II, B, C-II, C-III, E) were measured before, during and after probucol administration (2 X 500 mg p.d.), in 16 healthy males (30.3 +/- 5.6 years old). Cholesterol concentrations were determined in LDL and VLDL fractions as well as in HDL subfractions which were isolated by preparative ultracentrifugation. In addition, apolipoprotein A-I and A-II concentrations were measured in the HDL subfractions. Compared with the baseline values, significant apolipoprotein changes were found in the serum apolipoprotein A-I (151 +/- 18 to 115 +/- 31 mg/dl; P less than 0.001) and C-II levels during administration. The HDL subfraction analysis showed that the decrease of HDL-cholesterol and apolipoprotein A-I (59.9 +/- 23.5 to 34.4 +/- 16.4 mg/dl, P less than 0.001, and 65.7 +/- 49.0 to 37.5 +/- 23.5 mg/dl, P less than 0.05, respectively) was predominantly related to the HDL2b subfraction (d = 1.063-1.100 g/ml).     

Changes in the distribution and composition of high-density lipoproteins in primary hypothyroidism

The distribution and composition of high-density lipoprotein (HDL) subclasses were investigated in 14 women with severe hypothyroidism who were studied before and during treatment. The plasma concentrations of triglycerides, total cholesterol, HDL cholesterol, and of the apoproteins (apo) A-I, B, and E were increased in the hypothyroid state, while the apo A-II levels did not change significantly. After normalization of the thyroid function tests, the lipid and apoprotein levels were similar to those of normal individuals. Isopycnic ultracentrifugation in the density range 1.020 to 1.210 g/mL showed increases of both cholesterol and apo B in very-low-density lipoprotein (VLDL) and in low-density lipoprotein (LDL). The distribution of the HDL subclasses was modified in the hypothyroid subjects; both the less dense HDL fraction (d 1.063 to 1.100 g/mL; HDL2b), and the denser subclass (d 1.150 to 1.210 g/mL; HDL3b+3c) were increased, while the intermediate density subfraction (d 1.100 to 1.150 g/mL; HDL2a+3a) did not vary significantly. This redistribution of the HDL subfractions was associated with increased concentrations of cholesterol, phospholipid, and apo A-I in HDL2b, and of phospholipid and apo A-I in HDL3b+3c. Treatment of hypothyroidism decreased the concentrations of these fractions, and HDL2a+3a became the major HDL subclass in the euthyroid state. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were identical in the untreated and treated patients. The increased mass of protein and lipid within HDL2b and HDL3b+3c could therefore be attributed to an accumulation of identical-sized particles. The overall lipid and protein composition of the HDL lipoproteins was similar before and during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Lipoprotein distribution and composition in the human nephrotic syndrome

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.     

A study of the lipid transport system in the cat, Felix domesticus

Feline serum lipoproteins were fractionated into four distinct classes by density gradient ultracentrifugation and characterized with respect to physical and chemical properties. The distribution of serum lipids, lipoproteins and apolipoproteins was quite unlike that in man, the cat having five times as much high density lipoproteins (HDL) as low density lipoproteins (LDL). The lipoproteins in the d less than 1.019 g/ml fraction of cats were larger and were richer in triglycerides than their human counterparts and contained a considerable amount of beta-migrating particles. The low density lipoproteins of cats and man had similar chemical composition, but cat LDL had a higher negative charge, were smaller and contained apoprotein A-I. Cat HDL consisted of two distinct subfractions HDL2 and HDL3 with similar density boundaries and particle size as in man. In cat serum and HDL fraction apoprotein A-II was a minor component. Like human serum, fasting cat serum contained only the larger species of apoprotein B, apo B-100, whereas intestinal lymph contained exclusively the smaller apo B-48. Post heparin feline and human plasma possessed both lipoprotein lipase and hepatic lipase. Chylomicrons formed after a fat load in cats were removed from the circulation as rapidly as in man. It is concluded, that the cat is another animal model of potential interest for the study of lipoprotein metabolism.     

Apolipoprotein A-I containing lipoproteins in coronary artery disease

At least 2 main types of lipoprotein particles are identified within HDL. Those which contain apo A-I and apo A-II (LpA-I:A-II) and those which contain apo A-I but not apo A-II (LpA-I). This study was designed to elucidate to what degree the HDL cholesterol decrease observed in coronary artery disease affects these 2 types of lipoprotein particles. Concentrations of LpA-I:A-II and LpA-I were measured in plasma from 100 normolipidemic male subjects with angiographically defined coronary artery disease (CAD(+)) or without CAD (CAD(-)) and from 50 control subjects, matched for age. CAD(+) subjects had significantly lower levels of HDL cholesterol, total apo A-I, and LpA-I than controls. When compared to CAD(-) subjects, only their levels of HDL cholesterol and LpA-I were found lower. In both cases (CAD(+) vs CAD(-) and CAD(+) vs controls), LpA-I levels were decreased while LpA-I:A-II levels were unchanged. Even, when the levels of their total plasma lipids and lipoproteins are normal, atherosclerotic patients are characterized by a different distribution of apo A-I between LpA-I and LpA-I:A-II. These data support the view that LpA-I might represent the "antiatherogenic" fraction of HDL.     

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.     

Correlation of high density lipoprotein (HDL)-associated sphingosine 1-phosphate with serum levels of HDL-cholesterol and apolipoproteins

BACKGROUND: Extracellular sphingosine 1-phosphate (S1P) has been shown to contribute to the action of high density lipoprotein (HDL) on endothelial and smooth muscle cells. We examined the relationship of lipoprotein-associated S1P concentrations with cholesterol (C) and apolipoprotein (apo) contents of lipoprotein and lipoprotein subfractions characterized by capillary isotachophoresis (cITP). METHODS: Blood samples were drawn from 16 volunteers. S1P concentrations were quantified by bioassay based on the ability of S1P to stimulate its receptor. cITP was performed using plasma that had been prestained with NBD-ceramide. RESULTS: In plasma, S1P was concentrated in HDL and associated with LDL at a much lower concentration. HDL-S1P was the major determinant of the plasma S1P concentration. HDL-S1P was strongly and positively (p<0.001) correlated with serum levels of HDL-C (r=0.82), apo A-I (r=0.91) and apo A-II (r=0.92). HDL-S1P was strongly and positively (p<0.01) correlated with the apo A-I- and apo A-I/apo A-II-containing cITP HDL subfractions [fast HDL-C (r=0.66) and intermediate HDL-C (r=0.80)], but was not significantly correlated with apo E-containing slow HDL, suggesting that S1P is associated with both apo A-I HDL and apo A-I/A-II HDL. LDL-S1P was positively correlated (p<0.01) with levels of LDL-C (r=0.65) and apo B (r=0.85). CONCLUSION: Lipoprotein-associated S1P was related to the lipoprotein composition of cholesterol and apolipoproteins, suggesting that extracellular S1P may play different roles depending on the particles with which it is associated.     

Preliminary report: kinetic studies on the modulation of high-density lipoprotein, apolipoprotein, and subfraction metabolism by sex steroids in a postmenopausal woman

To investigate the effects of estrogens and androgens on the metabolism of high density lipoproteins (HDL) and low density lipoproteins (LDL), a normolipidemic postmenopausal woman was studied under the following conditions: (1) during supplementation with ethinyl estradiol (0.06 mg/d); (2) without sex steroid therapy; (3) during treatment with stanozolol, an androgenic, anabolic steroid (6 mg/d). During these manipulations HDL and LDL cholesterol levels fluctuated widely but reciprocally: during estrogen supplementation HDL increased while LDL decreased; during stanozolol HDL-C decreased while LDL-C increased. Simultaneous changes in post-heparin plasma hepatic triglyceride lipase activity paralleled those of LDL (and opposed those of HDL), decreasing with estrogen and increasing with stanozolol. During all three phases, autologous 125I-HDL turnover studies disclosed similarities between HDL2 and apolipoprotein A-I metabolism and between HDL3 and apolipoprotein A-II metabolism. In the untreated state the residence times of HDL2 and apo A-I were only half those of HDL3 and apo A-II. During estrogen treatment HDL2 and apo A-I, residence times were selectively prolonged, coming to resemble those of HDL3 and apo A-II, which remained unchanged. By contrast, during stanozolol treatment HDL3 and apo A-II residence times were selectively reduced, coming to resemble those of HDL2 and apo A-I, which remained unchanged. Apo A-I levels increased on estrogen and decreased on stanozolol, while apo A-II remained stable. Hence, estrogen increased HDL primarily by retarding the catabolism of the HDL2 subfraction rich in apo A-I, whereas stanozolol decreased HDL by accelerating the catabolism of HDL3, relatively rich in apo A-II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between charge-based apolipoprotein B-containing lipoprotein subfractions and remnant-like particle cholesterol levels

OBJECTIVE: Both mildly modified LDL subfraction that carries a more-negative electric charge and remnant-like particles (RLP) are closely related to triglyceride (TG) levels. We examined the relation between the RLP-cholesterol (C) level and charge-based apolipoprotein (apo) B-containing lipoprotein subfractions as determined by capillary isotachophoresis (cITP) in patients with hypercholesterolemia. METHODS AND RESULTS: cITP apo B lipoprotein subfractions were identified by analyzing plasma depleted of the related lipoproteins. While fast-migrating triglyceride-rich lipoprotein (fTRL) subfraction contained both chylomicrons and VLDL fraction, slow TRL (sTRL) only contained VLDL. cITP fLDL also contained VLDL fraction, i.e., beta-VLDL. Levels of cITP fTRL and sTRL were significantly correlated with serum levels of TG, RLP-C, apo C-II, and C-III. Levels of cITP sTRL were also correlated with apo E. Levels of cITP fLDL were positively correlated with not only LDL-C levels but also levels of TG, RLP-C, apo C-II, C-III, and E. CONCLUSION: cITP fast LDL correlated with RLP-C levels and modified the relation between RLP-C and TG levels.     

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.     

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)     

Associations of resting heart rate with concentrations of lipoprotein subfractions in sedentary men

In major prospective studies it has been reported that high heart rate at rest predicts the development of coronary heart disease (CHD) or cardiovascular disease (CVD) in men, but the mechanisms producing these relationships are unknown. Since lipoprotein levels contribute strongly to the risk of CHD and CVD, we examined the relationship of resting heart rate to plasma concentrations of high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoproteins, apolipoprotein (apo) A-I and A-II, and serum concentrations of lipoprotein subfractions in 81 men to determine if atherogenic lipoproteins could potentially induce the reported association of heart rate with development of CHD or CVD. The significant (p less than or equal to .05) Spearman's correlations for resting heart rate vs HDL2 mass (rs = -.24), HDL3 mass (rs = -.40), HDL cholesterol (rs = -.36), apo A-I (rs = -.29), triglycerides (rs = .31), VLDL cholesterol (rs = .24), VLDL mass (rs = .27), and LDL mass of Sof 0-7 subfraction (rs = .30) lend support to our hypothesis of lipoprotein-induced relationships of CHD with heart rate. The correlations for resting heart rate vs triglycerides, HDL cholesterol, HDL3 mass, VLDL mass, and LDL mass of Sof 0-7 subfraction remain significant when adjusted for adiposity, age, smoking habits, diet, and physical fitness as measured by maximum aerobic power (VO2 max) or submaximal heart rate during a graded exercise test.     

The effects of cholestyramine on high density lipoprotein metabolism.

This study on 4 type II hyperlipoproteinaemic subjects examines the effects of pharmacologic doses (8 g twice daily) of the bile acid sequestrant cholestyramine on the plasma distribution and chemical composition of the high density lipoprotein subfractions, HDL2 and HDL3, and describes the influence of the drug on the metabolism of the major HDL aporoteins, apolipoprotein A-I and A-II. Cholestyramine lowered plasma low density lipoprotein cholesterol (32%; P less than 0.05) without affecting the level of that lipid in very low density or high density lipoproteins. However, the plasma HDL2/HDL3 ratio and apolipoprotein A-I concentration rose significantly on treatment, while apolipoprotein A-II remained unchanged. The rise in apolipoprotein A-I derived from an increase in its synthetic rate and produced a relative enrichment of the protein with respect to apolipoprotein A-II in both HDL subfractions. These results demonstrate the cholestyramine treatment affects HDL metabolism in a way which, according to current concepts, may prove beneficial to the recipient.