Severe hypertriglyceridaemia in a Greek infant: a clinical, biochemical and genetic study.

UNLABELLED: A 32-day-old girl with massive hypertriglyceridaemia and clinical signs of chylomicronaemia syndrome is described. Genetic study of the patient revealed compound heterozygosity for a common lipoprotein lipase gene mutation (G188E) and a novel missense mutation (M301R), consistent with reduced post-heparin plasma lipoprotein lipase immunoreactive mass observed. CONCLUSION: to the best of our knowledge, this is the first description of a patient with a M301R mutation in the lipoprotein lipase gene. In addition, dietary therapy with medium-chain triglycerides was successful supporting the effectiveness of this therapeutic approach in familial chylomicronaemia syndrome.

A successful dietary treatment fails to normalize plasma triglyceride postprandial response in type IV patients.

The role of plasma triglycerides as a risk factor for cardiovascular disease is still under scrutiny. While recent studies have shown that postprandial triglyceridemia is an independent risk factor, normalization of fasting plasma triglycerides through modification of nutritional habits remains the primary approach in the treatment of hypertriglyceridemia. To address the issue of whether a satisfactory dietary regimen results in the control of postprandial lipemia, 53 type IV hypertriglyceridemic patients underwent an hypolipidemic diet for 3 months. All patients had a reduction of fasting lipid parameters (average TG: from 516+/-208 to 229+/-99 mg/dl; total cholesterol (Chol): from 261+/-42 to 213+/-40 mg/dl and HDL Chol: from 33+/-9 to 38+/-8 mg/dl). Taking plasma TG < or =200 mg/dl as the target for dietary intervention 26 patients were classified as 'responders' while the remaining 27 were 'non responders'. Even if fasting total TG, total Chol, HDL and LDL Chol were normal, both responders and non responders (P<0.0001) showed an exaggerated postprandial response to an oral fat load as compared to controls (20 normolipidemic subjects). Also when 10 responders and 10 controls, all male, were matched for plasma TG (129+/-43 versus 121+/-41 mg/dl) and other lipid parameters, a statistically significant difference between the two groups was observed at the time of each of the postprandial tests (P<0.0001) and for the area under the curve. The fact that the post prandial response is poorly modified by a dietary regimen, that effectively reduces plasma fasting TG, suggests that commonly used dietary regimens fail to restore a normal postprandial metabolism. Whether the cardiovascular risk for these patients is reduced after diet remains, therefore, to be addressed.

Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins.

Serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations are inversely correlated and mechanistically linked by means of lipid transfer activities. Phospholipid transfer activity (PLTA) moves phospholipids among serum lipoproteins; cholesteryl ester transfer activity (CETA), which exchanges cholesteryl esters (CE) and TG among lipoproteins, is stimulated by nonesterified fatty acids (NEFA). The aims of this study were (a) to develop a quantitative model that correlates the neutral lipid (NL = CE + TG) compositions of HDL and LDL with serum TG concentration; (b) identify the serum lipid determinants of CETA and PLTA, and; (c) identify the effects of serum TG reductions on the neutral lipid compositions of HDL and LDL, serum NEFA concentrations, and on PLTA and CETA. These aims were addressed in 40 hypertriglyceridemic subjects before and after treatment with an 85% concentrate of omega-3 fatty acids (Omacor) and in 16 untreated normolipidemic subjects. In vivo, the NL compositions of LDL and HDL were described by a mathematical model having the form of adsorption isotherms: HDL - (TG/NL) = (0.90 +/- 0.07) serum TG/(7.0 +/- 1.2 mmol/l + serum TG) and LDL - (TG/NL) = (0.65 +/- 0.08) serum TG/(4.9 +/- 1.5 mmol/l + serum TG). Reduction of serum TG was associated with reductions in HDL - (TG/NL), serum NEFA concentration, and serum CETA but not PLTA. These data suggest that both hypertriglyceridemia and the attendant elevated serum CETA but not PLTA are determinants of HDL and LDL composition and structure and that serum TG concentrations are good predictors of the NL compositions of HDL and LDL.

[Study of metabolic and clinical effects of polyunsaturated fatty acids omega-3 from "Eicovit" in patients with ischemic heart disease and familial hyperlipoproteinemia]. / Izuchenie kliniko-metabolicheskikh éffektov PNZhK omega-3, soderzhashchikhsia v "Eikovite", u bol'nikh ishemicheskoi bolezn'iu serdtsa i semeinymi giperlipoproteidemiiami.

The influence of antiatherosclerotic diet with including 15 g preparation "Eikovit" containing fat of freshwater fish on fat acid composition of erythrocytes membrane was studied in 399 patients with ishemic heart disease and hyperlipidemia. Against a background of positive influence on clinical symptoms of diseases, lipids of blood serum, homeostasis expressed influence of PUFA omega-3 in "Eikovit" on biomembrane fat acid composition was noted. It was shown sharp increasing a quota an eicosapentaenic acid by simultaneous reducing PUFA omega-6 level.

Efectos del aguacate sobre los niveles de lípidos séricos en pacientes con dislipidemias fenotipo II y IV / Effects of avocado plasma lipid concentrations in patients with hypercholesterolemia

Para examinar el efecto del aguacate sobre los niveles de lípidos séricos en pacientes dislipidémicos, se incluyeron a 8 sujetos con dislipidemia fenotipo IV y 8 del fenotipo II en un estudio dietético, en un modelo cruzado en el que se compararon dos dietas: una dieta rica en ácidos grasos monoinsaturados (DRCA), en la que el aguacate fue su principal fuente (30 por ciento de calorías totales como grasas y de ellas 75 por ciento del aguacate), con restricción de grasas saturadas y menos de 300 mg de colesterol por día. La otra fue una dieta baja en grasas saturadas y en grasa total, sin aguacate (DRSA). Ambas dietas duraron 4 semanas y su orden fue asignado aleatoriamente. Los pacientes realizaron sus tres alimentos en el comedor de nuestra unidad. Tanto la DRCA como la DRSA redujeron significativamente los niveles de colesterol total y colesterol-LDL sólo en el fenotipo II. En el fenotipo IV, la DRCA produjo un descenso moderado de los triglicéridos, mientras que la DRSA incrementó sus niveles. La DRCA produjo un importante incremento en los niveles de colesterol-HDL en ambos fenotipos, mientras que la DRSA sólo lo hizo en el fenotipo II. El aguacate es una excelente fuente de ácidos grasos monoinsaturados, y puede utilizarse dentro de los planes dietéticos de manejo de los pacientes con dislipidemias, con ventajas sobre las dietas más bajas en grasa total y con mayor cantidad de carbohidratos

[Effects of avocado on the level of blood lipids in patients with phenotype II and IV dyslipidemias]. / Efectos del aguacate sobre los niveles de lípidos séricos en pacientes con dislipidemias fenotipo II y IV.

To examine the effects of avocado on plasma lipid concentrations a two-diet trial involving 8 phenotype IV and 8 phenotype II dyslipidemia patients was carried out. A diet rich in monounsaturated fatty acids (DRCA) using the avocado as their major source (30% of the total calories were consumed as fat, 75% of the total fat from the avocado), with restriction of saturated fat and less of 300 mg of cholesterol per day was evaluated. Patients also were in a low-saturated fat diet without avocado (DRSA). The three daily meals were eaten at our clinical unit. Diets were four weeks in duration and they were assigned in a crossover design. In phenotype II both DRCA and DRSA significantly reduced total cholesterol and LDL-cholesterol levels. On phenotype IV DRCA produced a mild reduction on triglyceride levels while DRSA increased them. On HDL-cholesterol concentrations DRCA produced a significant increase in both phenotypes while DRSA did it only in phenotype IV. Avocado is an excellent source of monounsaturated fatty acids in diets designed to treat hypercholesterolemia with some advantages over low-fat diets with a greater amount of carbohydrates.

Short-term response to dietary counseling of hyperlipidemic outpatients of a lipid clinic.

OBJECTIVE: To evaluate the efficacy of a limited dietary intervention delivered by dietitians in a single counseling session on plasma lipid levels in free-living subjects with hyperlipidemia. DESIGN: A 2-month, nonrandomized comparative study of dietary counseling efficacy in subjects with hyperlipidemia. Dietary instruction was conducted in a lipid clinic by dietitians. Subjects were instructed to follow a diet low in saturated fat and cholesterol (National Education Cholesterol Program step 1 or 2 diets) for 2 months with concomitant energy restriction for weight reduction when necessary. Another group of patients who did not receive dietary counseling during the same period served as a control. SUBJECTS: Ambulatory patients were recruited from the Lipid Clinic of the Montreal Clinical Research Institute. INTERVENTION: Dietary counseling was provided to 104 subjects with hypercholesterolemia and 113 subjects with hypertriglyceridemia. They were compared with 72 subjects with hypercholesterolemia and 80 subjects with hypertriglyceridemia who did not receive dietary counseling. RESULTS: In the hypercholesterolemic group, significant reductions in plasma cholesterol (mean +/- standard deviation = -5.7 +/- 11.7%) and low-density lipoprotein cholesterol (LDL-C) (-7.3 +/- 14.2%) and no changes in plasma very-low-density lipoprotein cholesterol (VLDL-C) or high-density lipoprotein cholesterol (HDL-C) were observed after dietary counseling. The LDL-C response to diet was normally distributed, and 20% of the individuals with hypercholesterolemia reached LDL-C levels below 4.1 mmol/L. In patients with hypercholesterolemia and no clinical evidence of familial hypercholesterolemia, (n = 76) the reductions in plasma cholesterol (-6.6 +/- 10.8%) and LDL-C (-8.2 +/- 14%) were more pronounced. Among the latter patients, 27.6% reached LDL-C levels below 4.1 mmol/L. In subjects with hypertriglyceridemia, the reductions in plasma cholesterol (-4.8 +/- 12.8%), triglycerides (-20.7 +/- 33%), and VLDL-C (-19.5 +/- 29%) were associated with an increase in LDL-C (+8.5 +/- 25.7%) and HDL-C (+5.5 +/- 18%). Of the subjects with hypertriglyceridemia, 20% had triglyceride levels below 2.3 mmol/L after treatment. No significant changes were observed in the control groups during the same period. CONCLUSIONS: Dietary counseling of subjects with hypercholesterolemia or hypertriglyceridemia was associated with beneficial changes in plasma lipid levels after 2 months of dietary intervention. However, longer and more controlled dietary interventions are necessary for most patients to achieve lipid goals.

Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients.

The susceptibility of low-density lipoprotein (LDL) to oxidation was studied in hypertriglyceridemic men (5 with type III and 5 with type IV) at baseline on a low-saturated-fat, low-cholesterol diet, after 6 weeks of dietary supplementation with fish oil (Promega, 12 g/d), and after 6 weeks of fish oil combined with probucol (500 mg BID). The relative content of n-3 polyunsaturated fatty acids in plasma and LDL was increased during the two treatment periods, and a low alpha-tocopherol to n-3 polyunsaturated fatty acids ratio was observed. Plasma thiobarbituric acid-reactive substances (TBARS) levels were unchanged after 6 weeks of fish oil, but the ratio of lipid peroxides to the reduced triglyceride (TG) levels (MDA:TG) was significantly higher (P < .01). Addition of probucol lowered both absolute levels of TBARS (P < .01) and the MDA to TG ratio (P < .001). The susceptibility of LDL to Cu(2+)-catalyzed oxidation was evaluated over a 5-hour time course by determining TBARS formation, free amino group levels, and changes in LDL electrophoretic mobility. TBARS levels that were higher in native LDL (1.019 < d < 1.050 g/mL) after 6 weeks of fish oil than at baseline (P < .01) were reduced 52.3 +/- 11.3% by the addition of probucol (P < .001). With fish oil alone, TBARS production after exposure of LDL to Cu2+ for 5 hours was increased 17.0 +/- 5.8% compared with corresponding baseline values (P < .001), whereas a 64.1 +/- 14.3% reduction from the previous period was observed with fish oil + probucol (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertriglyceridemia and regulation of fibrinolytic activity.

A relation between elevated triglyceride (TG) levels and alterations of the fibrinolytic system has been recognized in studies of patients with coronary heart disease. In this investigation, the total fibrinolytic activity and the levels of specific components of the fibrinolytic system were evaluated in plasma samples from a highly selected group of patients with type IV hyperlipoproteinemia before and after a dietary treatment aimed at reducing TG levels. The fibrinolytic response of type IV patients was comparable to that of normolipidemic subjects, whereas tissue-type plasminogen activator antigen levels before and after venous occlusion (p less than 0.01) and resting plasminogen activator inhibitor-1 (PAI-1) antigen (p less than 0.01) and activity (p less than 0.01) were significantly higher in hypertriglyceridemic subjects compared with controls. After dietary treatment, a 22% reduction in TG levels was attained in type IV patients, with no appreciable modification of fibrinolytic parameters. The analysis of the single-patient data revealed a tendency toward normalization of PAI-1 levels only in those patients who showed a TG reduction greater than or equal to 20%. Very low density lipoproteins (VLDLs) from both normal and type IV patients concentration-dependently stimulated PAI-1 release by endothelial cells and HepG2 cells, with the effect of VLDL from type IV patients being more pronounced on HepG2 cells. The release of PAI-1 induced by VLDL in competent cells may thus account for the elevated levels of this antifibrinolytic protein that occur in hypertriglyceridemic patients.

Effect of dietary treatment on the lipid, lipoprotein and fatty acid compositions in type IV familial hypertriglyceridemia.

The effects of a 2-month dietary treatment (1,625 +/- 177 kcal, 40 +/- 2.3% carbohydrate, 35 +/- 3.7% fat, 25 +/- 2% protein, polyunsaturated/saturated fat ratio = 1.02 +/- 0.06) on the overall composition of serum lipids, lipoproteins and the fatty acid composition of cholesterol esters and phospholipids in very low (VLDL), intermediate (IDL), low (LDL) and high (HDL) density lipoprotein in 5 patients with primary familial hypertriglyceridemia type IV were assessed. The data were compared with those for 9 normolipidemic subjects. Treatment decreased serum triglycerides (-52%) and total cholesterol (-12%) due to decrease in free cholesterol (-30%). It produced a significant decrease in all the constituents of VLDL (-58%), but the VLDL remained significantly higher after treatment than those of control subjects. The diet caused a decrease in triglycerides (-16%, -29% and -33%, respectively), and an increase in cholesterol in IDL, LDL and HDL. The IDL level in the treated patients remained significantly higher than in the controls. The LDL cholesterol/HDL cholesterol ratio was unchanged after treatment. The fatty acid compositions of the patients before treatment and the controls were not significantly different. The diet caused a decrease in palmitoleic and oleic acids in the cholesterol ester fraction and an increase in linoleic acid, but this was significant only in VLDL and HDL. The diet decreased the eicosapentaenoic acid but the drop was only significant in IDL and LDL. There was also a decrease in linolenic acid, only significant in IDL. The diet induced only minor changes in the phospholipid fractions. We concluded that a single nutritional regimen can effectively decrease the serum lipids and normalize the lipoprotein composition of type IV hypertriglyceridemic patients.

A possible contribution of decrease in free fatty acids to low serum triglyceride levels after diets supplemented with n-6 and n-3 polyunsaturated fatty acids.

Intraindividual comparisons of diets supplemented with sunflowerseed oil (rich in linoleic acid, LA, C18:2n-6), linseed oil (enriched with alpha-linolenic acid, LNA, C18:3n-3) and canned mackerel (rich in eicosapentaenoic acid, EPA, C20:5n-3 and docosahexaenoic acid, DHA, C22:6n-3) were made in 30 patients with primary hyperlipoproteinemia (HLP) of phenotypes IIa (n = 9), IIb (n = 7), IV (n = 7) and V (n = 7). The lipid- and blood pressure-lowering effects of polyunsaturated fatty acids (PUFA), particularly those of the EPA- and DHA-rich diet, were confirmed irrespective of the type of HLP. Apolipoproteins A-I and B remained unchanged. The most remarkable finding was a substantial depression of free fatty acids (FFA) within a standardized glucose tolerance test (GTT) associated with the fall of serum triglycerides after diets enriched with n-6 and especially after those supplemented with n-3 PUFA. It was suggested that the decrease of FFA indicates reduced peripheral lipolysis, which might be a hitherto ignored factor involved in the triglyceride-lowering action of n-6 and, more pronounced, of n-3 PUFA.

The effect of n-3 fatty acids on lipids and haemostasis in patients with type IIa and type IV hyperlipidaemia.

Plasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type IIa and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

Dietary n-3 fatty acids and children with hyperlipidaemia.

A review of the literature shows that no studies on children with primary genetic lipid disorders have been published. Case reports are presented indicating that hyperlipidaemias presenting in children--both familial hypercholestrolaemia and disorders with secondary hyperlipidaemia (triglycerides) may benefit of the intake of n-3 fatty acids.

Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects.

We studied the effects of dietary supplementation with an encapsulated fish oil concentrate (Maxepa) on platelet function, fibrinolysis, and plasma lipids and lipoproteins in 9 normal subjects, 10 patients with type IV hyperlipoproteinemia, and 6 with type IIB hyperlipoproteinemia. After a baseline period, the subjects crossed over randomly between treatment periods with Maxepa (providing 3.24 g eicosapentaenoic acid and 2.16 g docosahexaenoic acid per day) and safflower oil (used as a control), given for 6 weeks each. Administration of Maxepa led to a slight prolongation of the bleeding time in all groups and to modest inhibition of platelet aggregation in the type IV hyperlipoproteinemics and normal subjects, with partial (41%) inhibition of thromboxane synthesis from baseline levels noted in the normal group. Plasma total fibrinolytic actively did not change significantly in any group. Maxepa treatment resulted in a marked decrease in triglyceride and VLDL-cholesterol and a slight increase in HDL-cholesterol was noted after Maxepa in the type IV hyperlipoproteinemics (4.11 +/- 0.13 mmol/l vs. 3.10 +/- 0.16 mmol/l, Maxepa vs. safflower oil). We conclude that dietary supplementation with fish oil results in a relatively minor degree of inhibition of platelet function in normal and hyperlipoproteinemic subjects, and a potentially adverse increase in LDL-cholesterol in type IV hyperlipoproteinemics.