Effect of statins on LDL particle size in patients with familial combined hyperlipidemia: a comparison between atorvastatin and pravastatin.

Background And Aim: Elevation of plasma cholesterol and/or triglycerides, and the prevalence of small dense low density lipoproteins (LDL) particles remarkably increase the risk in patients with familial combined hyperlipidemia (FCHL). There are, at present, inconsistent data on the effects of different treatments on size and density of LDL particles in FCHL patients.

Methods And Results: A multicenter, randomized, double-blind, double-dummy, parallel group study was designed to evaluate the effect of 3 months' treatment with atorvastatin (10mg/day) or pravastatin (20mg/day) on the lipid/lipoprotein profile and LDL size in a total of 86 FCHL patients.

Recurrent mutations of the apolipoprotein A-I gene in three kindreds with severe HDL deficiency.

Two siblings with high density lipoprotein (HDL) deficiency and no plasma apolipoprotein A-I (Apo A-I) were found to be homozygous for a cytosine deletion in exon 3 of Apo A-I gene (c.85 del C, Q5FsX11). This mutation causes a frameshift leading to a premature stop codon and abolishes the synthesis of Apo A-I.

Hypertriglyceridemia is associated with increased insulin resistance in subjects with normal glucose tolerance: evaluation in a large cohort of subjects assessed with the 1999 World Health Organization criteria for the classification of diabetes.

The current study retrospectively examined the association between insulin resistance and plasma triglycerides (TG) in a group of subjects with normal glucose tolerance. Among 1,434 subjects consecutively undergoing a standard oral glucose tolerance test (OGTT) between 1993 and 1998, 567 (age, 15 to 78 years) were classified as having a normal glucose tolerance according to the 1999 World Health Organization (WHO) criteria and were selected for the study. Serum insulin was measured by radioimmunoassay (INSI-CTK, Dia Sorin, Saluggia, Italy).

Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL(-).

A subpopulation of low-density lipoproteins (LDL) is present in human plasma that contains lipid hydroperoxides and is more negatively charged (LDL(-)) than normal native LDL. By circular dichroism and tryptophan lifetime measurements we found that apoB-100 secondary structure is markedly decreased and its conformation is severely altered in LDL(-). The low tryptophan fluorescence intensity confirms the oxidative degradation of the lipoprotein, and the very long lifetime value of one of its decay components indicates a low polarity environment for the remaining unbleached residues.

Effects of gemfibrozil on insulin sensitivity and on haemostatic variables in hypertriglyceridemic patients.

In order to assess the efficacy of gemfibrozil on lipid and haemostatic parameters in patients with plurimetabolic syndrome, a multicenter double-blind placebo controlled, parallel study was carried out in 56 patients with primary hypertriglyceridemia and glucose intolerance. These patients had elevated PAI activity and antigen and t-PA antigen levels at rest and after venous occlusion. Gemfibrozil reduced plasma triglyceride levels (P<0.

Fish intake, independent of apo(a) size, accounts for lower plasma lipoprotein(a) levels in Bantu fishermen of Tanzania: The Lugalawa Study.

Plasma lipoprotein(a) [Lp(a)] levels are largely genetically determined by sequences linked to the gene encoding apolipoprotein(a) [apo(a)], the distinct protein component of Lp(a). Apo(a) is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. In 2 racially homogeneous Bantu populations from Tanzania differing in their dietary habits, we found that median plasma levels of Lp(a) were 48% lower in those living on a fish diet than in those living on a vegetarian diet.

Analytical capillary isotachophoresis of total plasma lipoproteins: a new tool to identify atherogenic low density lipoproteins.

Plasma low density lipoproteins from 20 patients were separated by capillary isotachophoresis (ITP). In each patient the apparent diameter of the predominant LDL peak on whole plasma was also determined by nondenaturing gradient gel electrophoresis. Furthermore the concentration of the more electronegatively charged in vivo oxidized LDL- was accomplished using anion exchange high pressure liquid chromatography.

Electronegative low density lipoprotein subform (LDL-) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation.

There is increasing evidence that diabetes mellitus is characterized by an enhanced lipoprotein oxidation. We have therefore investigated whether a relationship exists between LDL oxidation and microalbuminuria, which is considered an early marker of vascular involvement in type 2 diabetic patients. We selected 12 microalbuminuric and 12 normoalbuminuric type 2 diabetic patients, and 12 control subjects comparable for age, sex and blood pressure values.

Effect of thyroid function on LDL oxidation.

In this study, the effect of different levels of thyroid hormone and metabolic activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16 patients with hyperthyroidism, 16 with hypothyroidism, and 16 age- and sex-matched healthy normolipidemic control subjects, the native LDL content in lipid peroxides, vitamin E, beta-carotene, and lycopene, as well as the susceptibility of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism was associated with significantly higher lipid peroxidation, as characterized by a higher native LDL content in lipid peroxides, a lower lag phase, and a higher oxidation rate than in the other two groups.

Increased levels of soluble P-selectin in hypercholesterolemic patients.

Background: Hypercholesterolemia is considered a major risk factor for the development of atherosclerosis. Enhanced lipid peroxidation and persistent platelet activation can be observed in vivo in hypercholesterolemic patients and may have pathophysiological implications in the occurrence of cardiovascular events. P-selectin may play an important role in the pathogenesis of multicellular events, including atherosclerosis.

LDL- is a lipid hydroperoxide-enriched circulating lipoprotein.

A subclass of LDL described on the basis of its greater electronegativity and oxidative status is further characterized using a new, highly sensitive single photon counting technique to measure lipid hydroperoxides. We describe in this report that these particles, which we refer to as LDL-, are enriched in lipid peroxides and other peroxidation products as compared to the bulk of the unmodified, normal LDL (nLDL) recovered from human plasma. This chemiluminescence-based, single photon counting technique has unique advantages in that analyses are performed on whole LDL, thus avoiding artifactual lipid peroxidation during lipid extraction.

Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study.

Background: There is evidence that populations with a high intake of fish, and specifically fish oils, are at reduced risk of cardiovascular disease. To explore the effect of fish intake, we compared two groups of Bantu villagers in Tanzania; one group live on the shores of Lake Nyasa and their diet includes large amounts of freshwater fish; the other group live in the nearby hills and have a vegetarian diet.

Methods: We carried out a cross-sectional study of 622 fish-consuming villagers and 686 vegetarian villagers.

Contribution of an in vivo oxidized LDL to LDL oxidation and its association with dense LDL subpopulations.

Oxidative modification of LDL is thought to be a radical-mediated process involving lipid peroxides. The small dense LDL subpopulations are particularly susceptible to oxidation, and individuals with high proportions of dense LDL are at a greater risk for atherosclerosis. An oxidatively modified plasma LDL, referred to as LDL-, is found largely among the dense LDL fractions.

Blood pressure, serum lipids, and fatty acids in populations on a lake-fish diet or on a vegetarian diet in Tanzania.

Major risk factors for coronary heart disease were assessed in two populations of Tanzania, one on a fish diet (FD) living along the coast of Lake Nyasa, and the other, mainly on a vegetarian diet (VD), living in a farming area. Lower blood pressure values were found in the FD subjects (n = 618) vs. VD (n = 618) (systolic blood pressure, SBP, 120 +/- 15 vs.

[Lipid peroxidation and LDL modifications in nondiabetic patients with ischemic heart disease: the role of insulin action].

Background: Nondiabetic patients with advanced coronary artery disease (CAD) were assessed for lipid peroxidation, LDL modifications and insulin action. Twenty-four patients and 10 normal controls were studied.

Methods: Insulin tolerance test (Kitt), glucose, insulin lipoproteins, electronegatively charged, modified, low density lipoproteins (LDL-) and the thiobarbituric acid reactivity (TBARS), as an index of lipid peroxidation, were determined.

'Normolipidemic' tendinous and tuberous xanthomatosis.

Background: Multiple tendinous and tuberous xanthomas are characteristically associated with hyperlipidemic states. However, normolipidemic tendinous and tuberous xanthomas have been reported in the literature, with normal levels of cholesterol, cholestanol and plant sterols.

Objective And Method: To delineate the disorder and to suggest its likely origin, a case of apparently normolipidemic severe tuberous and tendinous xanthomatosis was studied.

Naturally occurring modified low density lipoproteins are similar if not identical: more electronegative and desialylated lipoprotein subfractions.

Previous studies demonstrated that more electronegative low density lipoprotein (LDL) isolated from human blood by ion exchange chromatography has a chemical composition and physical properties similar to desialylated LDL obtained by lectin chromatography (Avogaro et al., 1988; Orekhov et al., 1989).

[Decrease of insulin resistance after splenectomy in a diabetic patient with liver cirrhosis and portal hypertension. Physiopathologic evaluation].

Liver cirrhosis is characterized by an increased incidence of glucose intolerance, diabetes and insulin resistance. We report a cirrhotic man (41 years old) who developed glucose intolerance and diabetes with insulin resistance over a period of six years. This patient suffered from severe portal hypertension with oesophageal varices and a enormously increased spleen volume.

Probucol protects low-density lipoproteins from in vitro and in vivo oxidation.

Twelve patients with primary hypercholesterolemia were treated for 12 weeks with probucol (500 mg b.i.d.

Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

Using ion exchange high pressure liquid chromatography, total plasma low density lipoprotein (LDL) from 30 hypercholesterolemic and 10 normocholesterolemic cynomolgus monkeys was subfractionated into unmodified LDL (n-LDL) and more negatively charged LDL (LDL-). In hypercholesterolemic monkeys, the absolute LDL-cholesterol level was 16.54 +/- 2.

Dynamic liver radionuclide scanning in the evaluation of liver failure and portal hypertension in cirrhotic patients.

Dynamic liver radionuclide scanning was performed in cirrhotic patients to correlate three parameters derived by this technique to the severity of liver function impairment and clinical-endoscopic signs of portal hypertension. We found a close association between the severity of liver failure (Child-Pugh criteria) and both the relative blood flow (p < 0.05) and the shape (shifting to the left) of the early flow curve (p < 0.

Relationship of triglycerides and HDL cholesterol in hypertriglyceridemia.

Hypoalphalipoproteinemia (plasma HDL-cholesterol concentration at or below 35 mg/dl as reported in the National Cholesterol Education Program Guidelines) is a well known risk factor for premature coronary artery disease (CAD). In hypertriglyceridemic patients, hypoalphalipoproteinemia is commonly believed to be linked to the derangement of triglyceride metabolism. In this study the occurrence of primary hypoalphalipoproteinemia has been investigated in a cohort of hypertriglyceridemic patients whose plasma triglyceride concentration had been normalized either through diet or diet plus drug treatment.

Some questions concerning a small, more electronegative LDL circulating in human plasma.

Atherosclerosis and its complications are prevalent worldwide with a high prevalence in western societies. The disease may sometimes be explained by a defect of low density lipoprotein (LDL) specific receptors. However, the prevalence of receptor defect is rather rare and a large body of evidence supports the possibility that an alternative pathway, the so-called "scavenger pathway", constitutes the gate through which cholesterol enters into the parietal wall and gives origin to the "foam cell".

Characterization of a more electronegatively charged LDL subfraction by ion exchange HPLC.

Low density lipoproteins (LDL), collected from 32 normal male subjects (aged 30-60), were subfractionated by high resolution ion exchange chromatography (IE-HPLC). By this procedure two LDL subfractions were eluted. The first corresponds to normal LDL (nLDL); while the second one corresponds to a more electronegative subfraction, called LDL-.

Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I.

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period.