Search results for "Hyperlipoproteinemia"
showing 10 items of 98 documents
Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach
2015
Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Ill…
Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with fam…
2009
Eur J Clin Invest 2010; 40 (2): 89–94 Abstract Background Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. Materials and methods Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear c…
Association between the TaqIB polymorphism in the cholesteryl ester transfer protein gene locus and plasma lipoprotein levels in familial hypercholes…
2001
Abstract Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides (TG) and cholesteryl ester between lipoprotein particles. Subjects with familial hypercholesterolemia (FH) have been reported to have higher CETP activities, which could contribute to the lower high-density lipoprotein-cholesterol (HDL-C) levels and increased cardiovascular risk observed in some of these patients. Several polymorphisms have been reported in the CETP locus; the common TaqlB polymorphism is associated, in normolipidemic subjects, with decreased CETP activity and levels and with increased HDL-C levels. No data is available on the influence of this polymorphism in FH subjects. We have e…
Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterole…
2010
Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched b…
Effectiveness of cascade filtration plasmapheresis in two patients affected by familial hypercholesterolemia
1995
Hypercholesterolemia has been recognised as a primary risk factor for coronary heart disease. Reduction of plasma levels of total and LDL cholesterol has been shown to decrease coronary atherosclerosis. Plasmapheresis represents an useful non-pharmacological tool to treat severe hypercholesterolemias. We have evaluated the effectiveness of a system of plasmapheresis using a cascade filtration method in two young male subjects (aged 16 and 26 years) with homozygous familial hypercholesterolemia. Both showed severe coronary atherosclerosis as determined by angiography. Procedures were performed at intervals of 7 days in each case. We observed a mean reduction of plasma levels of total cholest…
Treating homozygous familial hypercholesterolemia in a real-world setting: Experiences with lomitapide
2015
Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by markedly elevated plasma levels of low-density lipoprotein-cholesterol (LDL-C). Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor approved as an adjunct to other lipid-lowering therapies (LLTs), with or without lipoprotein apheresis (LA), for the treatment of adult HoFH. Diet with <20% calories from fat is required. Due to a varying genetic and phenotypic profile of patients with HoFH, individual patients may respond to therapy differently; therefore examining individual cases in a 'real-world' setting provides valuable information on the effective day-to-day manag…
Enhanced reduction in oxidative stress and altered glutathione and thioredoxin system response to unsaturated fatty acid load in familial hypercholes…
2014
Abstract Objectives Familial hypercholesterolemia (FH) is characterized by increased oxidative stress (OS) levels. In the postprandial state, lipids and lipoproteins modulate OS status through their impact on pro-oxidant and antioxidant mechanisms. The objective of this study was to evaluate in patients with FH the response to an unsaturated oral fat load test (OFLT) by analyzing the mRNA levels of genes involved in the glutathione and thioredoxin antioxidant systems. Design and Methods We analyzed 14 FH patients and 20 normolipidemic and normoglycemic controls. In both groups, mRNA values of antioxidant enzyme genes (glutathione and thioredoxin systems) were determined at baseline and at 2…
Oxidative stress and antioxidant enzyme values in lymphomonocytes after an oral unsaturated fat load test in familial hypercholesterolemic subjects
2012
Oxidative stress (OS) has been observed in conditions affecting the cardiovascular system. Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. In the postprandial state, circulating lipids and lipoproteins can modulate OS status. Our aim was to study the response of lymphomonocyte OS status and reactive oxygen species by-products after an oral unsaturated fat load test (OFLT) in those with FH and to compare this response with that obtained in normolipidemic, normoglycemic subjects. We studied 12 patients with FH and 20 healthy controls. In both groups, lymphomonocyte, oxidized/reduced glutathione ratio, and malondialdehyde were determ…
Fibrinolysis in hypertriglyceridaemic subjects in response to venous occlusion.
1993
We have measured various fibrinolytic and coagulation parameters (t-PA antigen, PAI, fibrinogen, plasminogen and factor VII) before and after 10 min of venous occlusion in 20 hypertryglyceridaemic subjects (twelve males and eight females, age 38 +/- 4 years, body mass index 23 +/- 1.5) and 20 healthy normal subjects, matched for sex (twelve males and eight females), age (37 +/- 3.5 years) and body mass index (22.8 +/- 1.4). At rest, t-PA:Ag, PAI, fibrinogen, plasminogen and factor VII were significantly (P < 0.005) higher in hypertriglyceridaemic subjects than in normal controls. After venous occlusion, the increase in all parameters except t-PA:Ag was more marked in the patient group than …
Long-Term Efficacy and Safety of the Microsomal Triglyceride Transfer Protein Inhibitor Lomitapide in Patients With Homozygous Familial Hypercholeste…
2017
Homozygous familial hypercholesterolemia is a genetic disorder characterized by low-density lipoprotein (LDL)-receptor dysfunction, markedly elevated levels of LDL-cholesterol (LDL-C) and premature atherosclerosis. Patients are often poorly responsive to conventional lipid-lowering therapies that upregulate LDL-receptor expression.1 Lomitapide inhibits microsomal triglyceride transfer protein, which lipidates nascent apolipoprotein (apo)B-containing lipoproteins. In a pivotal 78-week open-label trial, lomitapide, titrated to the maximal tolerable dose, decreased LDL-C by 50% at the end of the efficacy phase (week 26) in patients with homozygous familial hypercholesterolemia.2 The principal …