Endogenous Hypertriglyceridemia Research Articles

Relationship between GSTM1 and GSTT1 gene polymorphisms and plasma lipid and apolipoprotein levels in Chinese normalipidemic and endogenous hypertriglyceridemic subjects

To investigate effects of GSTM1 and GSTT1 gene polymorphisms on serum lipid and apopoprotein levels in healthy normolipidemic and endogenous hypertriglyceridemic subjects. Two hundred and thirty-seven healthy normolipidemic and 102 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using the multiplex polymerase chain reaction (PCR). Serum lipids were measured by enzymatic kits and apolipoproteins AⅠ, AⅡ, B100, CⅡ, CⅢ and E were measured by the RID kits. The non-null and null genotype frequencies for GSTM1 site were 39.2% and 60.8% in the control group, respectively, and 47.6% and 52.4% in the HTG group, respectively. The non-null and null genotype frequencies for GSTT1 site were 51.5% and 48.5% in the control group, respectively, and 57.3% and 42.7% in the HTG group, respectively. The GSTM1 and GSTT1 genotype frequencies in HTG subjects were not different from those in the controls, respectively (P>0.05). However, in control group subjects with both null genotypes (GSTT1- and GSTM1-) showed the lowest plasma HDL-C levels (1.29±0.30 mmol/L), whereas those with each of the other three genotype combinations showed relatively higher HDL-C levels. There was significant difference of HDL-C levels between subjects with GSTT1-/GSTM1-and those with GSTT1+/GSTM1-(P<0.05). Similar result was not observed in HTG group. No significant changes of lipid and lipoprotein levels were observed in either GSTM1 or GSTT1 polymorphism alone in control or HTG group. The present study provides an evidence that the presence of double deletion genotypes is associated with low HDL-cholesterol levels in normal Chinese subjects. However, these polymorphisms are not associated with lipid levels in endogenous hypertriglyceridemia in Chinese population of Chengdu area.

Genetic Variation in theOX40L/OX40System and Plasma Lipid and Lipoprotein Levels in a Chinese Hypertriglyceridemic Population

To investigate the variations of OX40 (tumor necrosis factor receptor superfamily, member 4) and its ligand OX40L genes and their relationships with serum lipids and apolipoproteins (apo) levels in Chinese healthy individuals and patients with endogenous hypertriglyceridemia (HTG) in the Chengdu area. The genotypes and allele frequencies of the rs3850641 and rs17568 polymorphisms in the OX40L and OX40 genes were assayed by polymerase chain reaction and restriction fragment length polymorphism. In the case-control study, which included 126 HTG subjects and 206 normal control subjects, the frequencies of the G allele at the rs3850641 site and the G allele at the rs17568 site in the patients were similar to those observed in the controls. In the HTG group, subjects with G allele carriers of the rs3850641 site had lower serum high-density lipoprotein cholesterol and apo AI levels as compared to those of genotype AA. In the case group, subjects with G allele carriers of the rs17568 site had higher serum low-density lipoprotein cholesterol (LDL-C) levels, while controls had lower serum total serum cholesterol and LDL-C levels. These results suggest that the rs3850641 and rs17568 polymorphisms in the OX40L and OX40 genes are associated with some of the lipid and lipoprotein variations in subjects with endogenous HTG and/or in the general population of Han Chinese.

Impaired Hepatic Ketogenesis in Moderately Obese Men With Hypertriglyceridemia

BackgroundSeveral studies suggest that increased nonesterified fatty acid flux and increased de novo lipogenesis may contribute to hypertriglyceridemia, but few studies have examined fatty acid oxidation as a factor.RationaleEndogenous hypertriglyceridemia...

Distribution and effect of apoL-I genotype on plasma lipid and apolipoprotein levels in Chinese normalipidemic and endogenous hypertriglyceridemic subjects

Background ApoL-I is a newly found component of HDL, and has a potential role in the lipid metabolism. This study was mainly to examine the possible association of the ApoL-I gene polymorphism with endogenous hypertriglyceridemia (HTG) in Chinese population. Methods Three hundred and thirty five Han Chinese (102 HTG and 233 healthy control subjects) in Chengdu area were studied using PCR-RFLP analysis. Results The Lys and Glu allele frequencies of apoL-I gene at Lys166Glu site in HTG and normal control groups were 0.857, 0.143 and 0.801, 0.199, respectively; The Ile and Met allele frequencies of the gene at Ile244Met site in HTG and the control groups were 0.868, 0.132 and 0.812, 0.188 respectively. The 166Glu and 244Met allele frequencies of the 2 polymorphisms in HTG subjects were not different from those in the normal controls, respectively ( P > 0.05). In HTG group, subjects with genotype Lys/lys of Lys166Glu site had a higher serum mean concentration of TG as compared to those of Glu allele carriers (3.64 ± 1.55 mmol/l vs 2.86 ± 0.51 mmol/l, P < 0.05). Subjects with genotype Ile/Ile of Ile244Met site had a higher serum mean concentration of TG as compared to those of Met allele carriers (3.59 ± 1.56 mmol/l vs 2.94 ± 0.88 mmol/l, P < 0.05). Conclusions The Lys166Glu and Ile244Met polymorphisms in apoL-I gene are associated with TG levels in subjects with endogenous hypertriglyceridemia in Chinese. However, these polymorphisms were not associated with the risk of HTG in the population.

Endogenous Hypertriglyceridemia Intensifies the Course of Cerulein-Induced Pancreatitis in Rat: Relation with Changes in the VLDL Composition

Aims: To study if the course of cerulein-induced pancreatitis in rats changes in a state of triglyceride-rich lipoprotein metabolism alteration. Methods: Two groups of rats received control diet during a 90-day period (A) and sucrose-rich diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received i.p. 45 µg cerulein/kg body weight (to induce acute pancreatitis). Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein profile and VLDL chemical composition were assessed. Then, pancreatic lipase hydrolytic activity on VLDL-triglycerides was evaluated in vitro. Results: Cellular vacuolization was observed in all of the cerulean-injected rats, but only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in subgroup B1 than in subgroup A1 (mean ± SEM, mg/dl 123,77 ± 25.7 vs. 65.8 ± 7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after cerulein-induced pancreatitis (80.38 ± 11.3 vs. 123,77 ± 25.7, p < 0.02). Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL triglyceride content, which decreased when rats were injected with cerulein. A negative correlation was found between VLDL-triglyceride content and serum pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a decrease in VLDL-triglyceride content post incubation with pancreatic lipase enriched serum (mean ± SD: 59.2 ± 27.7%, p < 0.01). Conclusions: The endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis and it could be related to the decrease in VLDL-triglycerides as a consequence of pancreatic lipase hydrolytic activity.

W16-P-081 The direct antiatherosclerotic therapy with drugs preventing intracellular cholesterol deposition

The accelerated atherosclerosis in diseases associatedwith elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin—a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor—was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, ortriglyceride:VLDL-B ratios. Further, there was no correlation between baseline triglycende levels and percent changes in remnant parameters. In conclusion, the HMG-CoA reductase inhibitor fluvastatin induced major reductions in indices of remnant lipoprotein concentrations, including intermediate density lipoprotein cholesterol and apo E. The total plasma apo E levels fell despite the increased HDL-C level, where more than half of the total apo E resides. The marked reduction in remnant lipoprotein, in addition to LDL-C with fluvastatin, may contribute to the antiatherosclerotic effect associated with this class of agents.

Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo

Thiazolidinediones have been shown to activate AMP-activated protein kinase activity in cultured cells. Whether they have a similar effect in vivo and if so whether it is physiologically relevant is not known. To assess these questions, we examined the effects of pioglitazone, administered orally to intact rats, on AMPK phosphorylation (AMPK-P) (a measure of its activation) and acetyl CoA carboxylase (ACC) activity and malonyl CoA concentration in rat liver and adipose tissue. In the first study, measurements were made in the Dahl-salt-sensitive rat (Dahl-S), a strain of Sprague–Dawley rat with endogenous hypertriglyceridemia and high levels of malonyl CoA that are restored to control values by pioglitazone. Treatment with pioglitazone (20 mg/kg bw/day for 3 weeks) did not significantly increase either P-AMPK or P-ACC (which varies inversely with ACC activity) in control rats. However, in the Dahl-S rats values for AMPK-P and ACC-P were 50% lower than in control rats and were doubled by pioglitazone treatment. In a second study, the effects of two weeks treatment with pioglitazone (3 mg/kg bw/day administered orally) were evaluated in Wistar rats. Under basal conditions (no manipulation of the animals), pioglitazone increased AMPK phosphorylation by twofold and decreased ACC activity and the concentration of malonyl CoA by 50% in liver. Following a euglycemic–hyperinsulinemic clamp (6 h), 50% decreases in AMPK and ACC phosphorylation (indicating an increase in its activity) and comparable increases in malonyl CoA concentration were observed in liver and adipose tissue. In both tissues, pre-treatment with pioglitazone prevented these changes. Where studied (in Wistar rats under basal conditions) treatment with pioglitazone decreased the concentration of ATP by 1/3 and increased the concentration of ADP and AMP in liver. The results indicate that treatment with pioglitazone can increase AMPK activity in rat liver and adipose tissue in a variety of circumstances. They also suggest that this activation of AMPK may be mediated by a change in cellular energy state. Whether these effects of pioglitazone contribute to its insulin-sensitizing and other actions in vivo remains to be determined.

Effect of the Australian National Heart Foundation recommended lipid-lowering diet in dialysis patients

The accelerated atherosclerosis in diseases associatedwith elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin—a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor—was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, ortriglyceride:VLDL-B ratios. Further, there was no correlation between baseline triglycende levels and percent changes in remnant parameters. In conclusion, the HMG-CoA reductase inhibitor fluvastatin induced major reductions in indices of remnant lipoprotein concentrations, including intermediate density lipoprotein cholesterol and apo E. The total plasma apo E levels fell despite the increased HDL-C level, where more than half of the total apo E resides. The marked reduction in remnant lipoprotein, in addition to LDL-C with fluvastatin, may contribute to the antiatherosclerotic effect associated with this class of agents.

Plasma apolipoprotein L concentrations correlate with plasma triglycerides and cholesterol levels in normolipidemic, hyperlipidemic, and diabetic subjects

Apolipoprotein L is a newly recognized component of human plasma lipoproteins. Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct HDL subpopulations. In an effort to gain inference as to its as yet unknown function, we studied biological determinants of apoL levels in human plasma. The distribution of apoL in normal subjects is asymmetric, with marked skewing toward higher values. No difference was found in apoL concentrations between males and females, but we observed an elevation of apoL in primary hypercholesterolemia (10.1 vs. 8.5 microgram/mL in control), in endogenous hypertriglyceridemia (13.8 microgram/mL, P < 0.001), combined hyperlipidemia phenotype (18.7 g/mL, P < 0.0001), and in patients with type II diabetes (16.2 microgram/mL, P < 0.02) who were hyperlipidemic. Significant positive correlations were observed between apoL and the log of plasma triglycerides in normolipidemia (0.446, P < 0.0001), endogenous hypertriglyceridemia (0.435, P < 0.01), primary hypercholesterolemia (0.66, P < 0.02), combined hyperlipidemia (0.396, P < 0.04), hypo-alphalipoproteinemia (0.701, P < 0.005), and type II diabetes with hyperlipidemia (0.602, P < 0. 01). Apolipoprotein L levels were also correlated with total cholesterol in normolipidemia (0.257, P < 0.004), endogenous hypertriglyceridemia (0.446, P = 0.001), and non-insulin-dependent diabetes mellitus (NIDDM) (0.548, P < 0.02). No significant correlation was found between apoL and body mass index, age, sex, HDL-cholesterol or fasting glucose and glycohemoglobin levels. ApoL levels in plasma of patients with primary cholesteryl ester transfer protein deficiency significantly increased (7.1 +/- 0.5 vs. 5.47 +/- 0.27, P < 0.006).

Hyperlipoproteinemia affects cytokine production in whole blood samples ex vivo. The influence of lipid-lowering therapy

Low-density lipoprotein (LDL)-receptor deficient mice, thus hypercholesterolemic, combine protection against infection with an ex vivo two- to threefold higher pro-inflammatory cytokine production in macrophages. A pro-inflammatory cytokine profile ex-vivo is also associated with survival of gram-negative sepsis in man. We hypothesized that high lipoprotein levels would be associated with a pro-inflammatory cytokine production and could explain the resistance to fatal infection. We treated 10 patients with familial hypercholesterolemia (FH) with HMG-CoA reductase inhibitors, and 13 patients with endogenous hypertriglyceridemia (HTG) with fibrates. Blood samples were stimulated ex vivo with lipopolysaccharide (LPS), to assess the cytokine production capacity. FH patients had significantly lower tumor necrosis factor-alpha (TNF-α) production, compared to normolipidemic controls ( P=0.001). Lipid lowering treatment in FH patients did not affect TNF-α production. HTG patients showed significantly higher TNF-α production at baseline than matched normolipidemic controls ( P<0.001), while lowering of serum triglycerides in these patients resulted in a significant decrease in TNF-α production ( P=0.019). The IL-10 production was not affected. These data refute our hypothesis that high LDL-cholesterol levels are associated with a pro-inflammatory cytokine production capacity. In contrast, the study suggests that very-low-density lipoprotein (VLDL) in hypertriglyceridemic patients augments TNF-α production.

Dietary counselling effectively improves lipid levels in patients with endogenous hypertriglyceridemia: emphasis on weight reduction and alcohol limitation.

To evaluate the short-term effect of dietary counselling in patients with endogenous hypertriglyceridemia and evaluate the effects of advised nutrient changes. A prospective dietary intervention study in patients with endogenous hypertriglyceridemia from January I st 1988 to December 31 st 1996 according to the Dutch guidelines for a healthy diet. Before and after the dietary intervention period of 12 weeks, 24h food recalls were used to assess dietary intake and macronutrient composition. Effectiveness was evaluated by assessment of body weight, serum lipids, lipoproteins and insulin resistance parameters. Leiden outpatient Lipid Clinic. Forty-five newly diagnosed, untreated patients with endogenous hypertriglyceridemia. A significant reduction in energy intake and body weight as well as changes in macronutrient composition were observed. Total serum triacylglycerol and cholesterol levels decreased by 31% and 15%, respectively. No effects were observed on serum glucose and insulin levels. Weight reduction was significantly correlated with reduction of total plasma triacylglycerol levels and inversely correlated with changes in HDL cholesterol levels. Of all nutrients assessed, only reduction of alcohol intake correlated with improvement of total serum triacylglycerol. Short-term dietary counselling in patients with endogenous hypertriglyceridemia can effectively improve serum lipid and lipoprotein levels. With regard to the advised nutrient changes, weight loss and limitation of alcohol intake prove to be the best predictors of triacylglycerol reduction.

Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the SstI polymorphism.

Hypertriglyceridaemia is a common metabolic disorder frequently found in patients with coronary heart disease. Numerous studies have revealed an association between the SstI polymorphism in the APOC3 gene and increased plasma apoC3 and triglyceride levels. In addition, two different variants within the promoter region have been recently suggested to be the mutations of the APOC3 gene leading to hypertriglyceridaemia. In the present study, we have applied haplotype analysis to investigate whether these promoter polymorphisms are involved in the lipid disorders of patients with distinct types of hypertriglyceridaemia: combined hyperlipidaemia (CHL), familial dysbetalipoproteinaemia (FD) and endogenous hypertriglyceridaemia (HTG). The -482 and -455 polymorphisms were significantly more frequent in FD patients (P = 0. 017) and endogenous HTG patients (P < 0.0001) than in CHL patients and a control group. The SstI polymorphism was only significantly more frequent in HTG patients (P < 0.0001). However, we did not find differences in frequencies for these polymorphisms in the APOC3 gene between CHL patients and a control group. Haplotype analysis indicates that the SstI polymorphism arose on the allele containing both promoter polymorphisms. The haplotype containing the SstI polymorphism is found five times more frequently among HTG patients (OR 5.28, 95% CI 1.65-16.90), which strongly suggests it is associated with an increased risk for severe hypertriglyceridaemia.

Effect of two oral contraceptives containing ethinyl estradiol and gestodene or norgestimate on different lipid and lipoprotein parameters

The effect of a triphasic oral contraceptive containing ethinyl estradiol and gestodene (EE/GSD) on various lipid and lipoprotein parameters was compared with that of a monophasic formulation containing 35 μg ethinyl estradiol and 250 μg norgestimate (EE/NGM). Blood samples were collected from 46 women on days 2, 11, and 21 of the preceding control cycle and of the third, sixth, and twelfth treatment cycles. There was no significant difference between formulations with regard to the influence on any measured parameter. As compared with controls, a significant increase was observed in the plasma levels of total triglycerides (24–78%), total phospholipids (7–20%), very low density lipoprotein (VLDL) triglycerides (61–76%), VLDL-phospholipids (14–60%), low density lipoprotein (LDL) triglycerides (8–35%), LDL-phospholipids (28–30%), high density lipoprotein (HDL) cholesterol (8–16%), HDL 3-cholesterol (11–20%), HDL-triglycerides (17–66%), HDL-phospholipids, HDL 3-phospholipids (7–11%), apolipoprotein (apo) A-I (5–20%) and apo A-II (10–40%) during treatment with both formulations. In contrast, the LDL-cholesterol levels were significantly decreased. These changes in lipid metabolism appear to reflect a predominance of the effect of the estrogen component. The results indicate that both low dose oral contraceptives containing different progestins and different amounts of EE do not exert a deleterious effect on lipoprotein metabolism, as high HDL-cholesterol and low LDL-cholesterol levels are known as low risk factors of cardiovascular disease. In contrast to endogenous hypertriglyceridemia, an EE-induced rise in triglyceride levels does not appear to increase cardiovascular risk if LDL is not increased.

Abnormal metabolism of free fatty acids in hypertriglyceridaemic men: apparent insulin resistance of adipose tissue.

There is growing evidence that endogenous hypertriglyceridaemia is frequently accompanied by a state of insulin resistance. The present study was performed to determine whether patients with primary endogenous hypertriglyceridaemia commonly have abnormalities in plasma concentrations and turnover rates of free fatty acids (FFA), which could reflect a state of insulin resistance in adipose tissue and could account for raised plasma triglycerides. Hypertriglyceridaemic and normotriglyceridemic control patients underwent measurements of plasma concentrations and turnover rates of FFA. Fat weights in both groups were determined by hydrodensitometry, and fat distribution was assessed by skin-folds and measurement of waist and hip circumferences. Other measurements included plasma glucose, insulin, lipids, and lipoproteins. Fifteen men with normal plasma triglycerides and 21 men with primary endogenous hypertriglyceridaemia were studied. Men in both groups varied in body weights and total fat weights, but total fat weights were entirely overlapping for the two groups. Waist-to-hip ratios and waist circumferences also were similar for the two groups. For any total body fat content or waist circumference, most hypertriglyceridaemia patients had higher mean plasma concentrations of FFA and higher turnover rates (flux) for FFA than did normotriglyceridemic patients. Hypertriglyceridaemic patients also had higher fasting insulin concentrations for a given body fat content. In general, both FFA flux and plasma insulin levels were positively correlated with plasma concentrations of triglyceride and inversely with high density lipoprotein (HDL) cholesterol. These studies indicate that many patients with primary endogenous hypertriglyceridaemia have increased flux of FFA and hyperinsulinemia that cannot be explained either by increased total body fat content or by greater waist circumferences than observed in normotriglyceridemic patients.

Association of Lp(a) rather than integrally-bound apo(a) with triglyceride-rich lipoproteins of human subjects

The majority of apolipoprotein (a) [apo(a)] in plasma is characteristically associated with Lipoprotein (a) [Lp(a)], having a buoyant density (1.05–1.08 g/ml) intermediate between low density lipoproteins (LDL) and high density lipoproteins (HDL). In the fed (postprandial) state or in the presence of fasting (endogenous) hypertriglyceridemia, a small proportion of plasma apo(a) is found in the density <1.006 g/ml fraction of plasma, associated with larger and less dense triglyceride-rich lipoproteins (TRL). In order to further characterize the presence of apo(a) in ultracentrifugally-separated TRL (UTC-TRL), this lipoprotein fraction was isolated from plasma obtained in the fed state (three hours after an oral fat load) from healthy normolipidemic subjects (Lp(a): 38±8 mg/dl (mean±S.E.), n=4) and also from plasma obtained after an overnight fast from hypertriglyceridemic patients (plasma TG: 8.16±2.00 mmol/l, Lp(a): 41±3 mg/dl, n=18). Apo(a) in 3 h-postprandial UTC-TRL (5±2% of total plasma apo(a)) and in hypertriglyceridemic UTC-TRL (8±2% total apo(a)) was separable by electrophoresis and/or gel chromatography (FPLC) from the majority of UTC-TRL lipid. Apo(a) in UTC-TRL fractions had slow pre- β electrophoretic mobility and was isolated in a lipoprotein size-range smaller than VLDL and larger than LDL, consistent with it being Lp(a). Recentrifugation of UTC-TRL resulted in the majority of apo(a) being recovered in the density>1.006 g/ml fraction. Addition of proline to plasma samples before ultracentrifugation (final concentration: 0.1 M) substantially reduced the amount of Lp(a) in UTC-TRL. TRL separated from plasma by FPLC contained less apo(a) (2–5% of total plasma apo(a)), but this apo(a) was also readily dissociable from TRL lipid, had slow pre- β electrophoretic mobility, and was associated with a lipoprotein with the size of Lp(a). Our data suggest that apo(a) in the TRL fraction of subjects with postprandial triglyceridemia or endogenous hypertriglyceridemia is not an integral component of plasma VLDL or chylomicrons, but represents the presence of non-covalently bound Lp(a).

97 Short-term effects of dietary counselling in endogenous hypertriglyceridemia

97 Short-term effects of dietary counselling in endogenous hypertriglyceridemia

Intraaortic balloon pumping dilates coronary arterioles being mediated by endothelium-derived nitric oxide

The prevalence and clinical characteristics of hyperapobetalipoproteinemia (hyperapoB) and other phenotypes of dyslipoproteinemia were examined in 99 men (aged ≤50 years) and 104 women (≤60 years) undergoing elective diagnostic coronary arteriography. HyperapoB was the most common phenotype (34%) associated with premature coronary artery disease (CAD). Only 20.2% of patients with CAD had a normal lipoprotein phenotype. The significant odds ratios for CAD were as follows: hypertriglyceridemic hyperapoB 17.45 (p < 0.0001), type IV 6.54 (p = 0.0001), type IIa 4.73 (p = 0.008), normotriglyceridemic hyperapoB 2.54 (p = 0.03) and type IIb 8.73 (p = 0.05). The strong association of hypertriglyceridemic hyperapoB with CAD reflected the multiplicative effect of increased low-density lipoprotein apolipoprotein B and endogenous hypertriglyceridemia, and was independent of the effects of age, sex, diabetes mellitus, systemic hypertension, body mass index and cigarette smoking. The ratio of apolipoprotein B to A-1 was better than those of low-density to high-density lipoprotein cholesterol and total to high-density lipoprotein cholesterol at discriminating dyslipidemic phenotypes from normal. Obesity was increased approximately 1.5- to two-fold in the hypertriglyceridemic phenotypes, diabetes was more prevalent in hypertriglyceridemic hyperapoB (6.8-fold; p < 0.001) and type IV (4.4-fold; p = 0.02), and hypertension was increased 1.5- to twofold in most dyslipidemic groups. The data indicate that hyperapoB and endogenous hypertriglyceridemia both contribute to the risk of premature CAD.

Coronary risk factor clustering due to microcirculation disturbance — “Perfusion metabolism theoery”

The prevalence and clinical characteristics of hyperapobetalipoproteinemia (hyperapoB) and other phenotypes of dyslipoproteinemia were examined in 99 men (aged ≤50 years) and 104 women (≤60 years) undergoing elective diagnostic coronary arteriography. HyperapoB was the most common phenotype (34%) associated with premature coronary artery disease (CAD). Only 20.2% of patients with CAD had a normal lipoprotein phenotype. The significant odds ratios for CAD were as follows: hypertriglyceridemic hyperapoB 17.45 (p < 0.0001), type IV 6.54 (p = 0.0001), type IIa 4.73 (p = 0.008), normotriglyceridemic hyperapoB 2.54 (p = 0.03) and type IIb 8.73 (p = 0.05). The strong association of hypertriglyceridemic hyperapoB with CAD reflected the multiplicative effect of increased low-density lipoprotein apolipoprotein B and endogenous hypertriglyceridemia, and was independent of the effects of age, sex, diabetes mellitus, systemic hypertension, body mass index and cigarette smoking. The ratio of apolipoprotein B to A-1 was better than those of low-density to high-density lipoprotein cholesterol and total to high-density lipoprotein cholesterol at discriminating dyslipidemic phenotypes from normal. Obesity was increased approximately 1.5- to two-fold in the hypertriglyceridemic phenotypes, diabetes was more prevalent in hypertriglyceridemic hyperapoB (6.8-fold; p < 0.001) and type IV (4.4-fold; p = 0.02), and hypertension was increased 1.5- to twofold in most dyslipidemic groups. The data indicate that hyperapoB and endogenous hypertriglyceridemia both contribute to the risk of premature CAD.

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations.

Gemfibrozil or placebo was administered for 3 months to 24 individuals with endogenous hypertriglyceridemia and normal glucose tolerance. Mean ( +/- SEM) fasting plasma triglyceride (TG) concentrations decreased (4.01 +/- 0.55 to 1.34 +/- 0.12 mmol/L; P < 0.001) and high density lipoprotein cholesterol concentrations increased (0.54 +/- 0.03 to 0.67 +/- 0.04 mmol/L; P < 0.001) in gemfibrozil-treated patients, associated with lower (P < 0.01-0.001) plasma free fatty acid and TG concentrations when measured at hourly intervals in response to breakfast (0800 h) and lunch (1200 h). However, day-long plasma glucose and insulin responses to meals in the 2 groups were similar before and after treatment, as were the steady state plasma glucose and insulin concentrations at the end of a 180-min infusion of somatostatin, insulin, and glucose. Thus, marked decreases in both plasma TG and free fatty acid concentrations seen in association with gemfibrozil neither enhanced insulin-mediated glucose disposal nor lowered ambient plasma insulin concentrations in patients with endogenous hypertriglyceridemia.

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations