Effect of alcohol intake on human apolipoprotein A-I-containing lipoprotein subfractions

High-density lipoprotein comprises two main types of lipoprotein particles: (1) those that contain apolipoproteins A-I and A-II, designated LpA-I:A-II, and (2) those that contain apolipoprotein A-I but not apolipoprotein A-II, designated LpA-I. Both have been extensively studied and are believed to represent distinct metabolic entities that may confer differing protection against coronary artery disease risk. We have previously suggested that LpA-I might represent the antiatherogenic effect, which has been ascribed mainly to its effect on high-density lipoprotein cholesterol; we set out to investigate, in 344 men, the relation between LpA-I:A-II and LpA-I levels and alcohol consumption. As the alcohol intake rose, LpA-I:A-II levels increased, while LpA-I levels fell. On the assumption that LpA-I is the antiatherogenic fraction of high-density lipoprotein, the putative protective action of alcohol consumption against coronary artery disease should be reconsidered.     

Effect of weight reduction on the distribution of apolipoprotein A-I in high-density lipoprotein subfractions in obese non-insulin-dependent diabetic subjects

High-density lipoprotein (HDL) plays an important role in the process of reverse cholesterol transport, which may become suboptimal with increasing body fatness. HDL cholesterol that is reduced in obese subjects paradoxically decreases during weight reduction. To determine how weight reduction affects HDL subclasses that are involved in reverse cholesterol transport, we studied HDL from obese diabetic subjects before and after energy restriction within background diets high in either carbohydrate or monounsaturated fatty acids (MUFAs). Body weight, blood glucose, total cholesterol, and LDL cholesterol decreased after 8 and 12 weeks of weight reduction. With the very-low-fat diet, HDL cholesterol decreased significantly at 8 weeks, but recovered to initial levels after 12 weeks as body weight began to stabilize. Plasma apolipoprotein A-I (apo A-I) decreased substantially and significantly at 8 and 12 weeks with both diets, and was reflected in the reduction of apo A-I in HDL subclasses alpha1, alpha2, pre-beta1, and pre-beta2 + pre-beta3. The calculation of the percentage distribution of apo A-I among HDL species showed that only the proportion of pre-beta1-HDL decreased, whereas alpha2-HDL increased. This led to a significant increase in the alpha1 + alpha2/pre-beta ratio, ie, the ratio of the large cholesterol "storage" or "sink" HDL to the HDL "shuttle" fraction considered to be the initial acceptor of cell cholesterol. These data suggest that despite the reduction in HDL cholesterol and apo A-I, the redistribution of apo A-I in pre-beta1-HDL and alpha-HDL observed with weight reduction appears to revert to the pattern that we have previously reported in lean as opposed to overweight subjects.     

Effect of exercise training on plasma high-density lipoprotein cholesterol in coronary disease patients

The effects of chronic exercise training on plasma high-density lipoprotein cholesterol (HDL-C) were studied in 18 male coronary patients. Exercise consisted of aerobic activities utilizing approximately 70% of maximal oxygen uptake (V?O₂ max) for 20 to 40 minutes, three times weekly for 3 months. Significant increases in V?O₂ max, HDL-C, HDL-C/total cholesterol, and a decrease in percent body fat were documented after training. No significant changes were foundin total cholesterol, triglyceride, body weight, or low-density lipoprotein cholesterol. Vigorous physical training can contribute to increases in HDL-C in patients with coronary disease without changes in total cholesterol or body weight.     

Cigarette smoking,high-density lipoprotein cholesterol subfractions,and lecithin: cholesterol acyltransferase in young women

Much of the published data on the relationship of cigarette smoking (CS) with serum lipids and lipoproteins is based on studies of middle-aged individuals. Data on young women are scarce. This study examined the relationship of CS with high-density lipoprotein cholesterol (HDL-C) subfractions and lecithin:cholesterol acyltransferase (LCAT) activity in Japanese collegiate women. Twenty-three current smokers were individually matched for physical activity scores, age, and body mass index (BMI) with 23 nonsmokers. There were no significant differences between smokers and nonsmokers in the mean nutrient intakes. Smokers had significantly lower mean HDL-C, HDL2-C, total cholesterol, and LCAT activity than nonsmokers. In univariate analyses, BMI significantly negatively correlated with HDL-C and HDL2-C. LCAT activity significantly positively correlated with HDL3-C, LDL-C, total cholesterol (TC) and triglycerides (TG). In multiple regression analyses, the number of CS was positively related to TG. BMI was negatively related to TC. LCAT activity was positively related to LDL-C, TC, and TG. These results suggest that the known associations in older adults of CS with HDL-C subfractions and LCAT activity are already apparent in young women.     

High apolipoprotein B with low high-density lipoprotein cholesterol and normal plasma triglycerides and cholesterol

Increased numbers of small, dense low-density lipoprotein particles may be present in patients with low high-density lipoprotein cholesterol and normal plasma triglycerides and cholesterol. Measurment of apolipoprotein B is the key to diagnosis and such patients should be considered for statin therapy.     

The relationship of exercise and diet on high-density lipoprotein cholesterol levels in women

The relationship of exercise and diet on high-density lipoprotein (HDL) cholesterol was investigated in 45 long-distance runners (LD), 49 joggers (J), and 47 inactive (I) women. Fasting plasma triglycerides (TG), HDL cholesterol, total cholesterol (TC), and percent body fat (%BF) were measured in women ages 24-58 yr. TG levels were significantly lower in LD compared to I (p less than 0.02). Although TC was not significantly different among groups, HDL-cholesterol was higher in LD (78 mg/dl) compared to J (70 mg/dl) or I (62 mg/dl) (p less than 0.001). Multiple regression analyses indicated that alterations of plasma lipids and lipoprotein levels could not be attributed to intake differences of nutrients. Distance run and %BF were the strongest predictors of HDL-cholesterol in women. LD (23 %BF) were leaner than J (26 %BF) or I (30 %BF); however, when results were adjusted for %BF, significant differences between exercise groups remained for HDL cholesterol.     

Effect of 17 alpha-ethinylestradiol on the catabolism of high-density lipoprotein apolipoprotein A-I in the rat

The in vivo metabolism and tissue sites of catabolism of high-density lipoproteins (HDL), labelled specifically in the apolipoprotein (apo) A-I moiety, were studied in rats treated with 17 alpha-ethinylestradiol (EE) for 5 days. Apo A-I was labelled either with O-(4-diazo-3-[125I]iodobenzoyl)sucrose, a non-degradable labelling compound, or with 131ICl. It was found that EE treatment decreases the serum cholesterol concentration to 10 mg/dl and stimulates the serum decay of apo A-I labelled HDL. The latter effect could be attributed to an increased catabolism of apo A-I labelled HDL in the liver. The increased rates of the serum decay and tissue uptake of apo A-I labelled HDL in EE-treated rats were not affected by a bolus injection of unlabelled human low-density lipoprotein (LDL), administered at the time of the injection of the labelled HDL. When the serum cholesterol concentration was raised to physiological levels by a bolus injection of unlabelled rat HDL, both the serum decay and the tissue uptake of apo A-I labelled HDL were almost completely restored to conditions encountered in control animals. In vitro binding experiments showed that liver membranes obtained from EE-treated rats demonstrated a 6-fold increased specific binding of human 125I-LDL, but virtually unchanged specific binding of rat 125I-HDL, as compared with liver membranes obtained from control rats. It is concluded that rat HDL apo A-I catabolism is hardly mediated by the apo B/E receptor induced by EE treatment.     

Association of endothelial lipase gene (LIPG) haplotypes with high-density lipoprotein cholesterol subfractions and apolipoprotein AI plasma levels in Japanese Americans

The LIPG gene on chromosome 18 encodes for endothelial lipase, a member of the triglyceride lipase family. Mouse models suggest that variation in LIPG influences high-density lipoprotein (HDL) metabolism, but only limited data are available in humans. This study examined associations of LIPG haplotypes, comprising a single nucleotide polymorphism (SNP) in the promoter region (-384A>C), and a nonsynonymous SNP in exon 3 (Thr111Ile or 584C>T), with lipoprotein risk factors in 541 adult Japanese Americans. A marginal association was found between LIPG diplotypes and HDL cholesterol (p=0.045). Stronger associations were seen for HDL3 cholesterol (p=0.005) and Apolipoprotein AI plasma levels (p=0.002). After adjustment for age, gender, smoking and medications, individuals homozygous for the minor allele at both SNPs (*4 haplotype) had a more favorable risk factor profile, compared to other haplotype combinations. No relationship was seen for plasma triglyceride levels or low-density lipoprotein (LDL) size, but the homozygous *4 diplotype was also associated with lower Apolipoprotein B and LDL cholesterol levels (p=0.001 and 0.015, respectively). In conclusion, this community-based family study of Japanese Americans demonstrates that LIPG variants are associated with HDL related risk factors, and may play a role in susceptibility to cardiovascular disease in this population.     

Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance

We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.     

Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio

Niacin significantly alters blood lipid concentrations but its use has been limited because of clinically disturbing side effects. In an attempt to circumvent these drawbacks, 55 patients with cardiovascular disease were given low-dose long-acting niacin, 1 g/d. Treatment was continued for a mean of 6.7 months and lipid values were compared with a non-treated group of 17 patients followed for a mean of 6.3 months. Lipid values did not change in the nontreated group. In the niacin-treated group total cholesterol and triglyceride levels also did not significantly change. High-density lipoprotein (HDL) cholesterol level rose 31% from 1.01 +/- 0.31 mmol/L to 1.32 +/- 0.31 mmol/L and total cholesterol/HDL cholesterol ratio was reduced 27% from 6.4 +/- 1.9 to 4.7 +/- 1.3. Despite these results, 40% of the patients left the study mainly because of side effects. Apart from one patient who developed overt diabetes, of questionable relationship to niacin, no patient developed serious side effects such as jaundice or peptic ulcer as seen with much higher doses of the drug. Although often difficult to administer to patients, niacin, particularly in low dose, deserves consideration as an inexpensive agent especially useful for elevating HDL cholesterol level and altering the total cholesterol/HDL cholesterol ratio.     

Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic patient subgroups

BACKGROUND: In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C). HYPOTHESIS: Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20-80 mg) and atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40 mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160 mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl). RESULTS: Both drugs produced similar increases in HDL-C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A-I in atorvastatin-treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL-C and triglycerides in a dose-dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL-C and apo A-I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment-by-subgroup interactions were observed. CONCLUSION: The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL-C and apo A-I with atorvastatin, but not simvastatin.     

Effect of exercise training on plasma levels and functional properties of high-density lipoprotein cholesterol in the metabolic syndrome

Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions' antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels.     

Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women

Lipid responses to a dietary intervention are highly variable between individuals. Part of this variation may be accounted for by individual differences in lipid-regulating genes that interact with diet to induce changes in lipoprotein metabolism. This study determined whether apolipoprotein E (APOE) genotype affects lipid responses to a low-fat, low-cholesterol diet in obese, postmenopausal women. Body weight and lipoprotein lipid responses to a 10-week, dietary intervention (American Heart Association [AHA] Step I) were compared in 61 women with the APOE 2/3 and APOE 3/3 genotype (APOE4-) and 18 women with the APOE 3/4 genotype (APOE4+) of a similar age, body composition, and maximal aerobic capacity. Body weight decreased by 2% in both groups, but changes in body weight correlated only with changes in low-density lipoprotein-cholesterol (LDL-C) (r =.27, P <.05). The dietary intervention decreased total cholesterol and LDL-C to a similar degree in both genotype groups. However, APOE4- women decreased high-density lipoprotein-cholesterol (HDL-C) by 17% +/- 11% and increased triglycerides by 20% +/- 41% in response to the diet, while APOE4+ women had a smaller decrease in HDL-C (-8% +/- 12%) and no change in plasma triglyceride. These group differences were significant for HDL-C (P <.01) and approached significance for triglycerides (P =.08). Moreover, APOE4- women decreased HDL(2)-C by 32% +/- 45%, while APOE4+ women increased HDL(2)-C by 12% +/- 62% (P <.01 between groups). It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the APOE4 allele benefit the most, while the lipid profile could worsen in women without the APOE4 allele.     

High-density lipoprotein cholesterol efflux, nitration of apolipoprotein A-I, and endothelial function in obese women

Subjects at risk of atherosclerosis might have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in the plasma. We considered whether the efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. A total of 54 overweight (body mass index [BMI] 25 to 29.9 kg/m(2)) or obese (BMI ≥30 kg/m(2)) women, aged 46 ± 11 years, were enrolled in a worksite wellness program. The HDL cholesterol averaged 57 ± 17 mg/dl and was inversely associated with the BMI (r = -0.419, p = 0.002). Endothelial function was assessed using brachial artery flow-mediated dilation. Cholesterol efflux from (3)H-cholesterol-labeled baby hamster kidney cells transfected with the adenosine triphosphate-binding cassette transporter 1 showed 8.2% to 22.5% cholesterol efflux within 18 hours when incubated with 1% serum and was positively correlated with brachial artery flow-mediated dilation (p <0.05), especially in the 34 subjects with BMI ≥30 kg/m(2) (r = 0.482, p = 0.004). This relation was independent of age, HDL or low-density lipoprotein cholesterol concentrations in plasma, blood pressure, or insulin resistance on stepwise multiple regression analysis (β = 0.31, R(2) = 0.21, p = 0.007). Nitration of apolipoprotein A-I tyrosine residues (using sandwich enzyme-linked immunosorbent assay) was significantly greater in women with a BMI ≥30 kg/m(2) and the lowest cholesterol efflux than in women with a BMI of 25 to 29.9 kg/m(2) and the greatest cholesterol efflux (p = 0.01). In conclusion, we have shown that decreased cholesterol efflux by way of the adenosine triphosphate-binding cassette transporter 1 is associated with increased nitration of apolipoprotein A-I in HDL and is an independent predictor of impaired endothelial function in women with a BMI of ≥30 kg/m(2). This finding suggests that the functional measures of HDL might be better markers for cardiovascular risk than the HDL cholesterol levels in this population.     

Influence of cholesteryl ester transfer protein, peroxisome proliferator-activated receptor α, apolipoprotein E, and apolipoprotein A-I polymorphisms on high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I:A-II concentrations: the Prospective Epidemiological Study of Myocardial Infarction study

The plasma level of high-density lipoprotein cholesterol (HDL-C) is known to be inversely associated with cardiovascular risk. However, besides lifestyle, gene polymorphism may influence the HDL-C concentration. The aim of this study was to investigate the possibility of interactions between CETP, PPARA, APOE, and APOAI polymorphisms and HDL-C, apolipoprotein (apo) A-I, lipoprotein (Lp) A-I, and Lp A-I:A-II in a sample selected from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study population who remained free of cardiovascular events over 5 years of follow-up. Healthy individuals (857) were randomly selected for genotyping the PRIME study subjects. The population was selected so as to provide 25% of subjects in the lowest tertile of HDL-C (≤28 mg/dL) in the whole PRIME study sample, 25% of subjects in the highest tertile of HDL-C (≥73 mg/dL), and 50% of subjects in the medium tertile of HDL-C (28-73 mg/dL). Genotyping was performed by using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assay. The CETP A373P rare allele c was less frequent in the group of subjects with high HDL-C, apo A-I, Lp A-I, and Lp A-I:A-II concentrations. Apolipoprotein A-I and Lp A-I were also found to be higher in the presence of the ?2 allele coding for APOE. The effect of the CETP A373P rare allele c on HDL-C was independent of all tested parameters except triglycerides. The respective effect of these polymorphisms and triglycerides on cardiovascular risk should be evaluated prospectively.     

Effects of omega-3 fatty acid supplementation and exercise on low-density lipoprotein and high-density lipoprotein subfractions

The purpose of this study was to examine the effect of combining exercise with omega-3 fatty acids (n-3fa) supplementation on lipoprotein subfractions and associated enzymes. Subjects were 10 recreationally active males, aged 25 +/- 1.5 years (mean +/- SE), who supplemented n-3fa (60% eicosapentaenoic acid [EPA] and 40% docosahexaenoic [DHA]) at 4 g/d for 4 weeks. Before and after supplementation, subjects completed a 60-minute session of treadmill exercise at 60% Vo(2)max. Following a 24-hour diet and activity control period, blood was collected immediately before and after the exercise session to assess lipid variables: high-density lipoprotein cholesterol (HDL-C) and subfractions, low-density lipoprotein cholesterol (LDL-C) and subfractions and particle size, lecithin:cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity. Supplementation with n-3fa alone increased total HDL-C and HDL(2)-C, while exercise alone increased total HDL-C, HDL(3)-C, and total LDL-C. LDL subfractions, particle size, and LCAT and CETP activities were not affected by supplementation. Combination treatment resulted in an additive effect for HDL(3)-C only and also increased LDL(1)-C versus baseline. LCAT and CETP activities were not affected by treatments. These results suggest that n-3fa supplementation or an exercise session each affect total HDL-C and subfractions but not LDL-C or subfractions. In addition, the combination of n-3fa and exercise may have additional effects on total HDL-C and LDL-C subfractions as compared to either treatment alone in active young men.     

Plasma apolipoprotein C-III transport in centrally obese men: associations with very low-density lipoprotein apolipoprotein B and high-density lipoprotein apolipoprotein A-I metabolism

CONTEXT: Apolipoprotein (apo) C-III is associated with hypertriglyceridemia and progression of cardiovascular disease. Plasma apoC-III is elevated in centrally obese men, and we hypothesized that the kinetics of apoC-III are disturbed in these subjects. OBJECTIVE: We developed a compartmental model to determine very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) apoC-III metabolic parameters in centrally obese men and investigated the associations with VLDL-apoB and HDL-apoA-I kinetics. STUDY DESIGN: Apolipoprotein kinetics was determined using stable isotope techniques and compartmental modelling in 39 centrally obese and 12 nonobese men. RESULTS: Compared with nonobese subjects, centrally obese subjects had increased plasma apoC-III concentration (160 +/- 5 mg/liter vs. 103 +/- 9 mg/liter, P < 0.001), reflecting increased concentrations of both VLDL-apoC-III and HDL-apoC-III. These related to increased production rate (PR) of VLDL-apoC-III (2.12 +/- 0.14 vs. 1.56 +/- 0.29 mg/kg x d, P < 0.05) and reduced fractional catabolic rate (FCR) of both VLDL- and HDL-apoC-III (0.70 +/- 0.02 pools/d vs. 0.82 +/- 0.05 pools/d, P < 0.05). In centrally obese men, VLDL-apoC-III concentration was significantly (P < 0.05) associated with VLDL-apoB concentration and PR as well as HDL-apoA-I FCR and PR and inversely with VLDL-apoB FCR. HDL-apoC-III concentration was significantly (P < 0.05) associated with the concentrations of both VLDL-apoB and HDL-apoA-I, the FCR, and the PR of HDL-apoA-I and inversely with the VLDL-apoB FCR. In multiple regression analysis, both VLDL-apoC-III and HDL-apoC-III concentrations were significantly associated with HDL-apoA-I FCR. CONCLUSIONS: In centrally obese men, elevated VLDL-apoC-III and HDL-apoC-III concentrations are a consequence of elevated production and decreased catabolism of VLDL-apoC-III and reduced catabolism of HDL-apoC-III, respectively. These defects are associated with disturbances in VLDL-apoB and HDL-apoA-I metabolism.