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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by high levels of cholesterol, triglycerides, or both. The basic metabolic abnormality is overproduction of apolipoprotein B-100. High atherogenicity has been attributed to all forms of FCHL. We evaluated combined bezafibrate-lovastatin therapy in 10 patients (9 men and 1 woman) with FCHL and markedly high cholesterol and triglyceride levels who were at high risk of coronary artery disease and who had not responded to diet and bezafibrate treatment alone. Eight patients had coronary artery disease, 6 had hypertension, and 3 had noninsulin-dependent diabetes mellitus. Lovastatin 20 mg/day was added to the bezafibrate 600 mg/day regimen for 6 weeks; the lovastatin dosage was then doubled to 40 mg/day for an additional 6 weeks. The addition of 20 mg of lovastatin resulted in decreases of 15%, 20%, and 13% in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, respectively. Increasing the dose of lovastatin to 40 mg resulted in further moderate decreases of 4%, 3%, and 8% in total cholesterol, LDL cholesterol, and triglycerides, respectively, compared with the 20 mg/day dosage. Although previous reports have emphasized the potential side effects of combination treatment with lovastatin and fibric acid derivatives, our patients tolerated the regimen well, with no significant subjective complaints or laboratory abnormalities. The bezafibrate-lovastatin combination is a possible therapeutic option for severe, resistant FCHL, but close medical supervision is needed because of potential side effects.
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PMID:Treatment of severe, resistant familial combined hyperlipidemia with a bezafibrate-lovastatin combination. 851 43

Secondary hyperlipoproteinemias are found in connection with other primary organic diseases. Typical examples are those seen with diabetes mellitus, liver and kidney diseases. In addition there are changes induced by hormonal dysfunctions such as hypothyroidism, by the use of oral contraceptives or in postmenopausal women. During pregnancy there is a physiological transient increase in lipoproteins. In addition to primary organic diseases there are a number of exogenous factors such as obesity, malnutrition and alcohol abuse causing hyperlipidemia. The relation between hypertension and hyperlipidemia described as familial dyslipidemic hypertension is less well known. Obesity, hypertension, dyslipidemia, hyperuricemia and impaired glucose tolerance are the basic conditions of the metabolic syndrome. Familial combined hyperlipidemia is a genetically determined, dyslipidemic syndrome with a high prevalence among patients with coronary artery disease and stroke. As there are some links between familial combined hyperlipidemia and secondary hyperlipoproteinemias, this disease entity is discussed together in this paper. Familial combined hyperlipidemia is metabolically, genetically and by this on a molecular level closely linked to familial dyslipidemic hypertension as well as the metabolic syndrome. The exact mechanism of this disease is currently unknown.
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PMID:[Secondary disorders of lipid metabolism, metabolic syndrome and familial combined hyperlipidemia]. 865 Sep 33

Mixed hyperlipidemia is characterized by both elevated total cholesterol and triglycerides. It is estimated to account for 10% to 20% of patients with dyslipidemia. This study assessed the lipid-altering efficacy and tolerability of simvastatin 40 and 80 mg/day as monotherapy. One hundred thirty patients (62 women [48%], 24 [16%] with type 2 diabetes mellitus, mean age 53 years) with mixed hyperlipidemia (baseline low-density lipoprotein [LDL] cholesterol 156 mg/dl [mean], and triglycerides 391 mg/dl [median) were randomized in a multicenter, double-masked, placebo-controlled, 3-period, 22-week, balanced crossover study, and received placebo, and simvastatin 40 and 80 mg/day each for 6 weeks. Compared with placebo, simvastatin produced significant (p <0.01) and dose-dependent changes in all lipid and lipoprotein parameters (LDL cholesterol 2.1%, -28.9%, and -35.5%; triglycerides -3.5%, -27.8%, and -33.0%; high-density lipoprotein cholesterol 3.3%, 13.1%, and 15. 7%; apolipoprotein B 3.8%, -23.1%, and -30.6%; and apolipoprotein A-I 4.0%, 8.2%, and 10.5% with placebo, and simvastatin 40 and 80 mg/day, respectively). The changes were consistent in patients with diabetes mellitus. One patient taking simvastatin 80 mg/day had an asymptomatic and reversible increase in hepatic transaminases 3 times above the upper limit of normal. Simvastatin 40 and 80 mg/day is effective in patients with mixed hyperlipidemia across the entire lipid and lipoprotein profile. The reductions in LDL cholesterol and triglycerides are large, significant, and dose dependent. The increase in high-density lipoprotein cholesterol was greater than that observed in patients with hypercholesterolemia, and appears dose dependent.
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PMID:Effects of simvastatin (40 and 80 mg/day) in patients with mixed hyperlipidemia. 1094 33

The complications (thromboembolism and jaundice), averse effects (metabolic disorders, hypertension and bleeding) and the risks (cancer and teratologic effects) of oral contraceptives are summarized and compared to those of other methods. Venous thrombosis is more frequent than arterial thrombosis; both are rare but can be severe; risk is decreased with minidose pills. Cholostatic jaundice is likely only in those with history of such jaundice in pregnancy. Decreased oral glucose tolerance similar to diabetes of pregnancy, similarly, is more common with high dose pills. Triglycerides, pre-beta lipoproteins and t otal cholesterol levels are increased to the upper limit of normal, but stabilize after 3 months of pill intake in normal women. Mixed hyperlipidemia in some women can be detected by the cholesterol to triglycerides ratio after 8 and 12 hours of fasting. Other possible side effects are hypertension, elevated thyroid hormone, depression due to abnormal tryptophan metabolism, acne, cholasma, varices, spotting, amenorrhea. The risk of cancer is still unknown, but that of chromosomal defects in unfounded. To avoid these complications, the physician must observe the contraindications of history of thromboembolism, heart disease, jaundice, hypertension and cancer, and follow patients regularly by gynecologic exam, glucose tolerance and blood lipid tests and take blood pressure. In comparison, diaphragms give 15% failure rates, and copper IUDs less than 1%, but about 10% expulsions and 10% removals for bleeding.
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PMID:[Complications of contraception]. 1225 11

The cellular retinoic acid binding protein-II (CRABP-II) is an intracellular protein involved in the transmission of the vitamin A-derived signal which regulates genes responsible for lipid metabolism and adipocyte differentiation. Cellular Retinoic Acid Binding Protein-II gene (CRABP-II) (GDB 134819) is located on chromosome 1q21-23 and this region has been linked with related disorders such as Familial Combined Hyperlipidemia (FCHL), type 2 Diabetes Mellitus, and Lipodystrophy. In this context we hypothesized that CRABP-II is an interesting protein and aimed to provide genetic markers for future studies. In order to do that, we screened the promoter and the entire coding regions for mutations in 53 patients diagnosed with FCHL and 89 normolipidemic controls. Two new single nucleotide polymorphisms (SNPs) were identified in the promoter region a C to A change at position -515 and a T to C substitution at position -394, the latter creating a binding site for SP1. The change -515C > A was identified in a FCHL patient whereas the -394T > C was found in 3 FCHL patients and 4 normolipidemic subjects. This report provides two new polymorphisms in CRABP-II, which can be used as genetic markers for future studies of association or linkage with diseases, particularly those associated with the metabolic syndrome.
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PMID:Two novel single nucleotide polymorphisms in the promoter of the cellular retinoic acid binding protein II gene (CRABP-II). 1262 90

Familial combined hyperlipidemia (FCH) is closely related with metabolic syndrome (MetSyn), and coronary artery disease (CAD) is positively associated to MetSyn and FCH. In this study, we evaluated the prevalence of MetSyn and its components between patients with FCH and a control group. We also investigated the role of MetSyn and diabetes mellitus (DM) on the incidence of CAD within the FCH group. Our study population consisted of 463 male and 243 female patients with FCH who were not receiving any hypolipidemic treatment, and 1128 men and 1154 women who came from the same geographical region. The prevalence of MetSyn was 42% and 19.8% among FCH subjects and controls, respectively, whereas MetSyn increased with age in both groups. The prevalence of CAD was 15.3% in the FCH group. Moreover, after dividing FCH patients into 3 subgroups, with and without MetSyn and with DM, CAD prevailed at a percentage of 15.2%, 11.1%, and 26.5%, respectively. However, statistically significant differences in the prevalence of CAD were observed only between FCH subjects with DM compared with the other 2 subgroups, even when an adjustment for age, sex, and smoking was conducted. People with FCH and MetSyn differed in several anthropometric, biochemical, and clinical characteristics, compared with the non-MetSyn subgroup of FCH. MetSyn is more prevalent in the FCH than in the control group. Among subjects with FCH, only DM was significantly associated with an increase in the prevalence of CAD in this subgroup compared with FCH individuals with or without MetSyn.
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PMID:Metabolic syndrome prevalence and characteristics in Greek adults with familial combined hyperlipidemia. 1716 Dec 36

Familial combined hyperlipidaemia (FCH) was identified in early genetic studies of populations as a dominant condition associated with mixed hyperlipidaemia and early onset coronary heart disease. Later studies extended the phenotype and noted that this genetic hyperlipidaemia was sensitive to environmental effects. This article reviews the definitions, animal models and genetics of FCH. In contrast to familial hypercholesterolaemia, which is caused by mutations in a limited number of affected genes, the genetics of FCH have remained obscure and very few definite candidate genes have been identified. A strong role for the apoA-I, A-IV, A-V, C-III cluster on chromosome 11 was identified early on and multiple associations have been found to hyperlipidaemia in this region and more strongly to adjacent sections of the chromosome. More recently quantitative trait mapping has identified a number of candidate genes including upstream transcription factor -1 (USF-1) on 1 q21 and CD-36 on chromosome 4. Of these the strongest evidence, based on 4 analyses, links the lipid components of FCH to intronic variants in the USF-1 gene on chromosome 1q21-23. Unfortunately USF-1 yet fails to show clear associations with diabetes and the metabolic syndrome which co-map to this region and are also associated with mixed hyperlipidaemia. Large scale validation of USF-1 variants in other populations is still awaited. It is likely that FCH is a heterogeneous condition, that is subject to wide-scale environmental confounding from common traits such as obesity and the metabolic syndrome, and that the resolution of its genetics is going to prove a severe challenge.
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PMID:Familial combined hyperlipidaemia: under - defined and under - diagnosed? 1822 Sep 35

Apolipoprotein B-100 (apo B-100) and small, dense LDL-C (sdLDL-C) are beneficial risk markers for CHD. Apo B-100 indicates the number of LDL particles that reflect the risk of CHD better than the LDL-C concentration. SdLDL is a lipoprotein subclass that causes arteriosclerosis with a much higher risk than large LDL. Apo B-100 is measured by a fully automated turbidimetric immunoassay, while small-dense LDL-C is measured by an enzymatic homogeneous assay with an automated analyzer. Elevated apo B-100 and sdLDL-C are observed among people with familial hypercholesterolemia, familial combined hyperlipidemia, diabetes mellitus, or metabolic syndrome, all of which lead to CHD with high probability. Although both apo B-100 and sdLDL-C are high in all of these cases, the two markers show noticeably different tendencies for each case. Familial hypercholesterolemia patients have higher apo B-100 than sdLDL-C; in contrast, people with diabetes mellitus or metabolic syndrome have higher sdLDL-C than apo B-100. Familial combined hyperlipidemia cases do not show much difference between the two values. The results of both apo B-100 or sdLDL-C can be good risk markers of CHD when tested individually, whereas the cause of CHD may be further clarified by assessing them in combination. By identifying the cause, patients can receive appropriate medical treatments. In conclusion, measuring both apo B-100 and sd LDL-C potentially implies further additional information on clinical utility.
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PMID:[Apolipoprotein B and small, dense LDL-C]. 2268 43

Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL-cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners.
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PMID:[Familial combined hyperlipidemia: consensus document]. 2503 22

Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL-cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners.
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PMID:[Familial combined hyperlipidemia: consensus document]. 2513 Nov 81


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