Effect of captopril on high-density lipoprotein subfractions in patients with mild to moderate essential hypertension

Changes in serum lipids, apolipoproteins, and lipoproteins including high-density lipoprotein (HDL) subfractions following administration of captopril in patients with hypertension were studied. Captopril (25 mg twice daily) was administered over a 12-week period to 17 patients with mild to moderate essential hypertension. Captopril was observed to significantly reduce both systolic and diastolic blood pressure, as well as to increase HDL2- cholesterol (HDL2-C) and to decrease HDL3-cholesterol (HDL3-C); however, no significant changes in total HDL-C were recognized. Total cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E did not change significantly. It is suggested that captopril monotherapy produces a favorable effect on HDL subfractions.     

Concentrations of apolipoproteins B, C-I, C-II, C-III and E in sera from normal men and their relation to serum lipoprotein levels

The concentrations of apolipoproteins B, C-I, C-II, C-III and E (by enzyme immunoassay), and cholesterol, triglycerides and phospholipids both in while serum and in serum very low (VLDL), low (LDL) and high (HDL) density lipoproteins, HDL2 and HDL3, were determined in sera from 29 randomly selected normolipidemic men, age 40-60 years, in Stockholm, Mean values, +/- SD, were for, apolipoprotein B, 720 +/- 162; C-I, 63 +/- 14; C-II, 27 +/- 11; C-III, 125 +/- 57; and for E, 25 +/- 6 mg/l. A skewness to the right of the distributions was found for apolipoproteins B and C-II and for serum triglycerides and VLDL lipids. The relations between the different variables were studied by linear correlation analysis. Several significant correlations existed between the lipoprotein levels. Apolipoprotein C-I, C-II and C-III were significantly correlated with each other, whereas neither apolipoprotein B nor apolipoprotein E was correlated with any other apolipoprotein. The following significant, positive correlations existed between the apolipoproteins and total serum lipids and/or lipids of lipoprotein density classes: apolipoprotein B with serum cholesterol and LDL lipids, apolipoprotein C-I with HDL3 cholesterol, apolipoprotein C-II with serum triglycerides and VLDL lipids, apolipoprotein C-III with serum cholesterol and phospholipids. Apolipoprotein E showed no correlation with either serum lipids or lipoproteins.     

Lipoproteins and apolipoproteins in young nonobese Arab women with NIDDM treated with insulin

The effects of insulin on the lipid values of nonobese non-insulin-dependent diabetic (NIDDM) Arab women requiring insulin was investigated to find whether these patients have the same coronary artery risk factor related to lipid levels. In this study, 55 NIDDM women on insulin therapy (mean age 28 +/- 8.1 yr and duration of disease 5 +/- 1.2 yr) and 70 control subjects (matched for sex, age, and body mass index) were studied for their plasma levels of lipids, lipoproteins, and apolipoproteins. Concentrations of total cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride (TG), LDL TG, high-density lipoprotein triglyceride (HDL TG), phospholipid, glucose, glycosylated hemoglobin (HbAtc), apolipoprotein B (apoB), LDL-apoB, and apoB/apoAl were significantly elevated in diabetic women compared with control subjects. There was no significant change in the levels of apoAll in plasma and lipoprotein fractions. Concentrations of HDL cholesterol (chol), HDL2-chol, HDL3-chol, plasma apoAl, HDL2-apoAl, HDL3-apoAl, and HDL-apoAl were significantly lower in diabetic women than in control subjects. There was no significant correlation between glucose or HbAtc and most of the lipids, lipoprotein lipids, and apolipoproteins measured. Despite normal body weight and insulin therapy, abnormalities in lipids, lipoprotein lipids, and apoB persisted in NIDDM patients compared with control subjects. Our data may favor an enhanced affinity toward atherosclerosis in these patients.     

HDL cholesterol subfractions and risk of developing type 2 diabetes among Pima Indians.

OBJECTIVE: To examine the relationships between HDL cholesterol subfractions and the incidence of type 2 diabetes and to evaluate potential sex differences in these relationships. RESEARCH DESIGN AND METHODS: Proportional hazards analyses were performed to examine the relationships between HDL subfractions and the development of type 2 diabetes in Pima Indian women and men. Results were controlled for age, BMI, systolic blood pressure, and 2-h glucose. RESULTS: Some 54 of 123 women and 25 of 50 men developed type 2 diabetes during a mean follow-up of 10 (2-19) years. For women, in separate models, high levels of total HDL, HDL2a, and HDL3 were negatively associated with incidence of type 2 diabetes; results were unchanged in models further controlled for fasting insulin level or alcohol consumption. For men, the results were inconsistent and associated with wide confidence intervals; high total HDL and HDL3 were positively associated with incidence of type 2 diabetes in models further controlled for fasting insulin level, but the risk estimates were attenuated in models further controlled for alcohol consumption. CONCLUSIONS: High levels of total HDL, HDL2a, and HDL3 were potential protective factors against type 2 diabetes in women after accounting for alcohol consumption and insulin resistance. High levels of total HDL and HDL3 were predictive of type 2 diabetes in men; the relationship in men appeared to be due to an association with alcohol consumption. The sex differences in the effects of HDL cholesterol may be related to the effects of sex hormones or lipoproteins.     

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.      

Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men

So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p<0.001) with those of cholesterol, phospholipids, and ApoA1 in HDL2, respectively. Age correlated positively with sdLDL while increasing BMI correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2 constituents. Physical activity and alcohol intake correlated negatively with sdLDL constituents and positively with HDL2 components. Consumption of monounsaturated fatty acids (MUFA) correlated with a lower ratio of sdLDL to HDL2 cholesterol. A favorable lipoprotein subfraction profile linked to a reduced risk of cardiovascular disease in men was associated with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions.     

High-density lipoprotein cholesterol, monthly variation and association with cardiovascular risk factors in 1000 forty-year-old Dutch citizens.

High density lipoprotein cholesterol (HDL chol) levels were measured in about 1000 forty-year-old residents of the town of Leiden, The Netherlands. Mean levels (+/- S.D.) in women were 48.0 +/- 11.0 mg/dl; in men 42.5 +/- 10.7 mg/dl. In March mean levels in women were about 5 mg/dl lower than in June (P less than 0.001); in men there was a similar difference between mean levels in April and June (P less than 0.002). HDL chol levels were negatively related to smoking habits, relative body weight, and in women to use of oral contraceptives. Weak positive and negative correlations between HDL chol and serum cholesterol, respectively, were found in subgroups with high and low HDL chol levels, respectively.     

Direct quantitation of serum high density lipoprotein subfractions separated by gradient gel electrophoresis

This report describes the densitometric quantitation of the two main HDL subfractions separated by electrophoresis in a polyacrylamide gradient gel, HDLS (mean apparent diameter 9.3 nm) and HDLL (mean apparent diameter 10.6 nm). The electrophoresis was carried out in a linear gradient of polyacrylamide ranging from 23 to 180 g/l on total sera prestained for lipid components by Sudan black B in ethylene glycol. HDL subfractions were quantified by scanning the gels at 633 nm with a laser densitometer. The precision was checked by intra-assay and between-assay studies (coefficient of variation 1.2 and 2.9%, respectively). The results were compared with the cholesterol content of HDL subfractions (r = 0.99) and with the HDL2:HDL3 distribution (r = 0.95). Reference values were obtained from a population of 214 normolipidemic subjects. They were in good agreement with those already published for HDL2 and HDL3. The method which needs only 4 microliter of serum, can be set up with currently available apparatus and is compatible with large series of samples, should allow large scale explorations of the variation of HDL subfraction distribution in normal and pathological populations.     

Selective determination of cholesterol in high density lipoprotein subfractions (HDL2 and HDL3) in patients with cerebral and peripheral arteriosclerosis

Cholesterol levels in high density lipoprotein subfractions (HDL2 and HDL3) were evaluated in 69 patients (55 males, average age +/- SD 58.3 +/- 8.8, and 14 females, average age +/- SD 63.1 +/- 10.3) with extra-coronary arteriosclerosis (lower limbs, supraaortic trunks and both sites), and in 79 healthy age-matched control subjects. HDL cholesterol was significantly reduced in male and female patients. The HDL cholesterol decrease was due to a fall in both HDL2 and HDL3 cholesterols; nonetheless, an analysis of the HDL2-cholesterol/HDL3-cholesterol ratio disclosed that HDL2 cholesterol was the most reduced. Slightly higher plasma cholesterol and triglyceride levels were found in the patients as well as a higher plasma cholesterol/HDL-cholesterol ratio. On the contrary, the HDL2-cholesterol/HDL3-cholesterol ratio was significantly reduced in the patients. These preliminary findings suggest that, as in ischemic heart disease, the HDL cholesterol reduction in cerebral and peripheral arteriosclerosis is also mainly due to a reduction in the HDL2 subfraction. These results also lend further support to the proposal that determination of the HDL subfractions is useful for a better assessment of the risk profile for arteriosclerosis.     

Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys.

Mechanisms that might be responsible for the low levels of high density lipoprotein (HDL) associated with hypertriglyceridemia were studied in an animal model. Specific monoclonal antibodies were infused into female cynomolgus monkeys to inhibit lipoprotein lipase (LPL), the rate-limiting enzyme for triglyceride catabolism. LPL inhibition produced marked and sustained hypertriglyceridemia, with plasma triglyceride levels of 633-1240 mg/dl. HDL protein and cholesterol and plasma apolipoprotein (apo) AI levels decreased; HDL triglyceride (TG) levels increased. The fractional catabolic rate of homologous monkey HDL apolipoproteins injected into LPL-inhibited animals (n = 7) was more than double that of normal animals (0.094 +/- 0.010 vs. 0.037 +/- 0.001 pools of HDL protein removed per hour, average +/- SEM). The fractional catabolic rate of low density lipoprotein apolipoprotein did not differ between the two groups of animals. Using HDL apolipoproteins labeled with tyramine-cellobiose, the tissues responsible for this increased HDL apolipoprotein catabolism were explored. A greater proportion of HDL apolipoprotein degradation occurred in the kidneys of hypertriglyceridemic than normal animals; the proportions in liver were the same in normal and LPL-inhibited monkeys. Hypertriglyceridemia due to LPL deficiency is associated with low levels of circulating HDL cholesterol and apo AI. This is due, in part, to increased fractional catabolism of apo AI. Our studies suggest that variations in the rate of LPL-mediated lipolysis of TG-rich lipoproteins may lead to differences in HDL apolipoprotein fractional catabolic rate.     

Cholesterol distribution between HDL subfractions. A study of 498 subjects

Summary In 498 subjects (205 normolipidemics and 293 hyperlipidemics) of both sexes, the cholesterol content of high density lipoprotein (HDL) subfractions has been determined. The serum concentration of total HDL-cholesterol appears to be more strictly related to the cholesterol content of HDL₂ than to that of HDL₃. This latter one, however, gives a contribution to the variability of HDL-cholesterol so that the value of HDL-cholesterol cannot be assumed as a reliable estimate of the serum level of the more anti-atherogenic HDL₂ subfraction. The cholesterol content of HDL and its subfractions is higher in women than in men and decreases with increasing serum VLDL-cholesterol level and body weight. Both HDL₂- and HDL₃-cholesterol appear to largely depend from the metabolism of triglyceride-rich lipoproteins in accordance with the data of experimental studies.     

A dual-precipitation method evaluated for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 in human plasma

The dual-precipitation method for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 (Warnick et al., Clin Chem 1982;28:1574) was compared with quantification of cholesterol in HDL2 and HDL3 by zonal ultracentrifugation (Patsch et al., J Lipid Res 1974;15:356-66). For 39 plasma specimens differing widely in their HDL subfraction cholesterol concentration, the coefficient of correlation between the two methods was 0.94 for HDL2-cholesterol, 0.82 for HDL3-cholesterol. Storage of plasma specimens at -70 degrees C decreased the apparent content of HDL3-cholesterol by 5%; no significant changes in HDL2-cholesterol were observed. In frozen plasma, interference by apoB-containing lipoproteins and by lipoprotein(a) was negligible. Mean weight ratios of apoA-I to cholesterol were twice as high for HDL3 as for HDL2, reflecting the increased cholesterol content of HDL2. The study suggests that quantification of HDL2 and HDL3 cholesterol by precipitation is appropriate for use in epidemiological studies.     

High-density lipoprotein subfractions and influence of endothelial lipase in a healthy Turkish population: A study in a land of low high-density lipoprotein cholesterol

Abstract

Purpose. Low concentration of high-density lipoprotein (HDL) is prevalent in Turkey. Endothelial lipase (EL) regulates lipoprotein metabolism. Small, lipid-poor HDL particles represent more-efficient cholesterol acceptors than their large, lipid-rich counterparts. The aim of this study was to investigate HDL subfractions and the effect of EL on HDL concentrations in healthy Turkish population. Methods. 102 healthy subjects were included in the study (mean age 33.6 ± 10.3 years, 42 female). HDL subfractions were assayed by single precipitation method and EL concentrations were measured by competitive enzyme immunoassay. Results. Mean HDL concentrations were 1.45 ± 0.37 mmol/L in women, 1.10 ± 0.30 mmol/L in men. Small HDL subfraction levels did not differ statistically between < 1 mmol/L and ≥ 1.6 mmol/L total HDL groups. Small HDL was not correlated with EL, low density lipoprotein cholesterol (LDL), triglyceride (TG) and age but positively correlated with total cholesterol and HDL (r = 0.2, p = 0.017; r = 0.2, p = 0.028, respectively). Large HDL was not correlated with age, EL and total cholesterol, and negatively correlated with HDL, LDL, TG (r = ? 0.7, p < 0.001; r = ? 0.2, p = 0.045; r = ? 0.3, p < 0.001, respectively). If subjects were divided into two groups as HDL< 1 mmol/L and HDL > 1.6 mmol/L, mean EL concentrations were 475.83 ± 521.77 nmol/L and 529.71 ± 276.92 nmol/L, respectively (p = 0.086). Conclusion. There were no differences between small HDL concentrations in the HDL low and high groups. Our data did not support EL to be the reason for low HDL in a healthy Turkish population. Our results in a healthy population may serve as a reference for clinical studies on HDL subfractions.     

Evaluation of long-term frozen storage of plasma for measurement of high-density lipoprotein and its subfractions by precipitation

The concentration of high-density lipoprotein cholesterol (HDL-C) in plasma is now established as an independent risk factor for coronary heart disease, but more data are needed on the relative risk-predictive powers of different HDL subclasses. For epidemiologic and clinical purposes, isolation of HDL from other lipoproteins and separation of its two major subclasses, HDL2 and HDL3, are performed most conveniently by precipitation. Although storage of plasma is commonly necessary, little information is available on the long-term stability of HDL subclasses at different temperatures. Therefore, we quantified HDL-C, HDL2-C, and HDL3-C by dual precipitation with heparin-MnCl2/15-kDa dextran sulfate (H-M/DS) in samples of EDTA-plasma from 93 healthy subjects, after storage for one to 433 days at -20 degrees C, at -70 degrees C, or in liquid nitrogen (-196 degrees C). Fourteen samples (15%) were stored for a year or longer. At -20 degrees C, HDL-C decreased by 4.8% per year and HDL3-C decreased by 6.9% per year (P = 0.002 for both variables) relative to results obtained with samples stored in liquid nitrogen; total cholesterol, HDL2-C, and triglyceride did not change significantly at this temperature. When stored at -70 degrees C, none of the lipids showed any change relative to results obtained with liquid nitrogen. Thus, long-term storage of EDTA-plasma at -20 degrees C is unsuitable for subsequent quantification of HDL-C and its subclasses by H-M/DS dual precipitation. Storage at -70 degrees C is preferable, and is as reliable as storage in liquid nitrogen.     

Sexual differences in lipoprotein composition in a family with dyslipidemic hypertension with premature atheroschlerosis: deficiency of high-density lipoprotein-L and high-density lipoprotein-M "apolipoprotein-I alone" particle.

This article describes a family with a high incidence of premature atherosclerosis and primary hypertriglyceridemia in the women. The lipoprotein composition of this family was investigated with a new methodology that combines gradient ultracentrifugation to isolate lipoprotein subfractions with high-performance liquid chromatography to quantitate apolipoproteins. The major lipoprotein abnormalities that were identified in the hyperlipidemic women in this family were (1) an increased mass of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) with triglyceriderich VLDL but normal IDL composition; (2) triglyceride-rich low-density lipoprotein (LDL) with normal cholesterol and apolipoprotein B concentrations; (3) a relatively normal total mass of high-density lipoprotein (HDL)-L and HDL-M but with a reduction in the apolipoprotein A-I/A-II ratio and a decrease in the cholesterol to triglyceride ratio; (4) an elevation of HDL-D apolipoprotein A-I. The reduction in the apolipoprotein A-I/A-II ratio was also seen in the hyperlipidemic men and in most of nonhyperlipidemic family members and was the most common lipoprotein abnormality that was identified in this family (9 of 11 family members who were not on lipid-lowering medications were affected). The hypertriglyceridemic women appeared to have an increase in the "A-I + A-II" HDL particles in all subfractions and an increase in the "A-I alone" particles in HDL-D. These increases provided the apparently normal total mass of HDL that was observed in these women. These increases in HDL were not seen in the hypertriglyceridemic men. We conclude that a deficiency of the "A-I alone" particle in HDL-L and HDL-M may contribute to the premature atherosclerosis that was seen in this family and that it appears to precede the appearance of hypertriglyceridemia. The increase in the "A-I + A-II" HDL particles did not appear to provide the same protection as would be expected from "A-I alone" HDL.     

Alterations in high-density lipoprotein subfractions during postprandial lipidaemia induced by fat with and without ethanol

1. Serum lipid and apolipoprotein levels, distribution and composition of high-density lipoprotein (HDL) subfractions and lecithin:cholesterol acryltransferase activity were analysed in nine normolipidaemic subjects, in whom a hypertriglyceridaemic state was induced by the acute administration of ethanol (40 g) plus fat (70 g) or of fat only. 2. Triglyceride (TG) levels increased by 180% 4-6 h after fat plus ethanol intake, the hypertriglyceridaemic response being inversely correlated with the basal HDL2 mass (r = -0.82). Serum apolipoprotein (apo) B levels rose by 8%, HDL-cholesterol decreased by 10% and HDL-TG increased by 57% at 6-8 h. 3. When ethanol was omitted, serum cholesterol and TG rose by 6% and 70%, respectively; both apo AI and apo B levels went up by 8%, whereas HDL-cholesterol rose progressively (15%) at 12 h. 4. The flotation rates of both HDL2 and HDL3 increased, reaching a maximum 6-8 h after ethanol plus fat intake. These changes were due to an increase in TG and phospholipid contents, whereas cholesteryl esters and proteins decreased. 5. The alterations in HDL are attributable to the increase in TG-rich lipoproteins, to the stimulated cholesterol esterification (+15%) and to an enhanced transfer of newly formed cholesteryl esters to apo-B-containing lipoproteins in exchange for TG. 6. Changes in HDL properties were evident only when ethanol was given concomitantly with fat. 7. These findings suggest that in the postprandial phase lipoprotein changes may occur, which facilitate an improved removal of cholesterol from tissues.     

Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: an exploratory analysis of archived samples using two commercially available techniques

BACKGROUND: Cholesterol-rich lipoproteins, including low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), are known to promote atherosclerosis. Ezetimibe/simvastatin (E/S) is an efficacious lipid-lowering treatment that inhibits both the intestinal absorption and biosynthesis of cholesterol. OBJECTIVE: The aim of the current analysis was to compare the effects of ezetimibe and simvastatin monotherapy and E/S treatment on lipoprotein subfractions and LDL particle size in patients with primary hypercholesterolemia. METHODS: This was an exploratory (hypothesis generating) analysis of archived plasma samples drawn from patients in a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study. After a washout and diet/placebo run-in, patients with hypercholesterolemia (LDL-C, > or =145- < or =250 mg/dL; triglycerides, < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: E/S (10/10, 10/20, 10/40, or 10/80 mg), simvastatin monotherapy (10, 20, 40, or 80 mg), ezetimibe monotherapy (10 mg), or placebo. A subset of patients had lipid subfraction measurements taken at baseline (week 0) and postrandomization (week 12). Plasma samples were used to quantify cholesterol associated with VLDL subfractions (VLDLI+2 and VLDL3), IDL, and 4 LDL subfractions (LDL1-4) via the Vertical Auto Profile II method. LDL-C particle size was determined using segmented gradient gel electrophoresis. The primary end point was median percent change in subfraction cholesterol for E/S versus ezetimibe or simvastatin monotherapy, pooled across doses. RESULTS: Of the 1528 patients randomized in the original study, 1397 (91%) had lipid subfraction measurements taken. E/S was associated with significant reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe, simvastatin, and placebo. E/S resulted in near-additive reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe and simvastatin monotherapy. Of the subfractions examined, with regard to E/S, the greatest reductions were observed in IDL-C and LDL-C1, LDL-C2, and LDL-C3. When compared with placebo, ezetimibe, simvastatin, and E/S did not shift the distribution of LDL particles toward a larger, more buoyant LDL subclass pattern. CONCLUSION: E/S was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subfractions in these patients with primary hypercholesterolemia.     

Distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and HDL subfractions of untrained and trained normolipemic men.

The distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and within HDL subfractions (HDL2b, HDL2a, HDL3) was examined in 26 sedentary and 19 endurance trained normolipemic male individuals. The concentrations of lipids and apolipoproteins in serum and HDL subfractions and the concentrations of LpA-I and LpA-I:A-II were determined. Significant differences (Mann-Whitney-U-test) were found in serum concentrations of apoB (P < 0.05), apoA-II (P < 0.01) and LpA-I:A-II (P < 0.001). In HDL3 apoA-II concentration was significantly lower in the trained group (P < 0.05) but in HDL2 subclasses the concentrations of apoA-I and apoA-II did not differ between the groups. Despite similar concentrations of the two apolipoproteins, there were difference in the distribution of lipoprotein species within HDL2 subfractions. The concentrations of LpA-I did not differ, but the concentrations of LpA-I:A-II particles were higher in the trained group. Untrained and trained had similar concentrations of apoA-II (in HDL2b) but obviously more apoA-II containing particles and this leads to the assumption that within HDL2 of endurance trained individuals LpA-I:A-II particles have a lower apoA-II content compared with particles of untrained individuals. The data emphasize, that normolipemic individuals of different maximum oxygen uptake have a different distribution and composition of lipoprotein species (LpA-I, LpA-I:A-II).     

Variation in concentration of lipids, lipoprotein lipids, and apolipoproteins A-I and B in plasma from healthy women

The components of total variation--biological, inter- and intra-individual, and analytical--of plasma lipids, lipoprotein lipids, and apolipoproteins A-I and B have been determined in a population of 44 healthy women, ages 18-35 years. Blood was sampled three separate times at three-month intervals, with no restrictions on diet or physical activity during these periods. The greatest inter-individual variances were observed for high-density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, and total plasma cholesterol. Triglycerides had the highest intra-individual variance (CV 22%). The percentage of inter- and intra-individual variances of apolipoprotein A-I concentrations were more reflective of total HDL- and HDL2-cholesterol content than of HDL3-cholesterol. Concentrations of calculated low-density-lipoprotein cholesterol showed a greater inter-individual variation (18.6%) than did apolipoprotein B (10.7%). The laboratory CVs for these analytes were similar to other reported values. From these data, we computed the expected variation for subjects in our study for single and repeated measurements. Such considerations can influence decision-making in the clinical setting or in designing epidemiological studies.     

Smoking and plasma lipoproteins in man: effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution

Abstract. In a survey of a healthy population (n = 197), LDL cholesterol, plasma triglycerides and VLDL triglycerides were found to be substantially increased and plasma HDL cholesterol decreased in smokers. The lipid-associated atherogenic risk in smokers as assessed by the LDL/HDL ratio was significantly higher [2.89 (SD 1.18, n= 63)] than in non-smokers [2.38 (SD 0.98, n= 86) P < 0.01]. The lower HDL level found in smokers was explained by a lower HDL-2 subfraction as determined by analytical ultracentrifugation. HDL 2b, 2a and 3a, measured by gradient gel electrophoresis, were all lower in the smokers but this was only significant for HDL 2a. Smoking had no effect on Lp(a) levels. HDL cholesterol and HDL-2 were strongly negatively correlated whereas LDL cholesterol and LDL/HDL ratio were strongly positively correlated with the plasma triglyceride concentration. There was a small but significant reduction in plasma CETP activity [non-smokers 49%t/μl (SD 17, n= 90), smokers 43%t/μl (SD 17, n= 66) P < 0.05] but CETP activity was not correlated with any measure of HDL in this population. Smoking was found to be an important independent contributor to the variation in plasma triglyceride, HDL, HDL-2 and LDL/HDL ratio. After correcting for sex, age, BMI, alcohol consumption, oral contraceptive use and plasma triglycerides smoking was still found to be significantly associated with HDL and the LDL/HDL ratio. Upon adjustment for covariant factors the mean differences between smokers and non-smokers for HDL cholesterol, HDL-2 and LDL/HDL were 0.15 mM, 16 mg dl-¹ and 0.39 respectively. There appeared to be important sex differences in the influence of smoking on plasma lipoproteins. In women the main impact of smoking was on triglyceride levels and they in turn affected LDL and HDL. In contrast, in men, smoking had little impact on triglycerides and affected HDL more directly. We conclude that smoking cigarettes has an important effect on plasma lipoprotein metabolism through multiple mechanisms.