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1.
Eur J Prev Cardiol ; 27(2): 157-165, 2020 01.
Article in English | MEDLINE | ID: mdl-31403880

ABSTRACT

AIMS: The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in patients with homozygous familial hypercholesterolaemia. METHODS AND RESULTS: In 12 homozygous familial hypercholesterolaemia patients treated with lipid-lowering drugs ± biweekly lipoprotein apheresis sessions (nine patients), daily lomitapide was added. The lipid profile (total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol) before and after lomitapide treatment was evaluated. The follow-up period with lomitapide treatment was 3-24 months (13.8 ± 7.9). The median baseline low-density lipoprotein cholesterol level was 900 mg/dl (348-1070), after lipid-lowering drugs therapy was 383.5 mg/dl (214-866) and after lipid-lowering drugs + time-averaged level was 288 mg/dl (183.7-716.6). The addition of lomitapide lowered low-density lipoprotein cholesterol levels further by 56.8% compared to lipid-lowering drugs alone (mean reduction 262, 95% confidence interval (105.5-418.7), p = 0.005) and by 54% (mean reduction 182.9, 95% confidence interval (-342 - -23), p = 0.031) comparing to lipid-lowering drugs + lipoprotein apheresis (time-averaged level). The time-averaged level of low-density lipoprotein cholesterol in lipid-lowering drugs + lipoprotein apheresis patients compared with lipid-lowering drugs + lomitapide was 54% in favour of lomitapide (p = 0.031). CONCLUSIONS: Treatment with lomitapide in homozygous familial hypercholesterolaemia patients has a beneficial effect with a constant decrease of low-density lipoprotein cholesterol by 57% compared with classical lipid-lowering therapy and by 54% compared with classical lipid-lowering therapy and time-averaged level of low-density lipoprotein cholesterol.


Subject(s)
Anticholesteremic Agents/therapeutic use , Benzimidazoles/therapeutic use , Carrier Proteins/antagonists & inhibitors , Cholesterol, LDL/blood , Homozygote , Hyperlipoproteinemia Type II/drug therapy , Adolescent , Adult , Anticholesteremic Agents/adverse effects , Benzimidazoles/adverse effects , Biomarkers/blood , Blood Component Removal , Child , Cholesterol, HDL/blood , Female , Genetic Predisposition to Disease , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Male , Middle Aged , Phenotype , Time Factors , Treatment Outcome , Triglycerides/blood , Young Adult
2.
Open Cardiovasc Med J ; 12: 59-70, 2018.
Article in English | MEDLINE | ID: mdl-30159092

ABSTRACT

BACKGROUND: The influence of biomarkers in human lifespan has been investigated but with no clear results yet. MATERIALS AND METHODS: Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died <75 years, comprised of 2 generations: middle-aged (FD1) and children (FD2). RESULTS: Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively). CONCLUSION: Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family's lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

3.
Genet Mol Biol ; 38(2): 129-37, 2015 May.
Article in English | MEDLINE | ID: mdl-26273214

ABSTRACT

In this work, we examined the impact of polymorphism in the cytochrome P450 (CYP) 3A5 gene, CYP3A5*1 (6986A > G, rs 776746), on the reduction in the lipid levels caused by simvastatin and atorvastatin. We studied 350 hyperlipidemic patients who received 10-40 mg of atorvastatin (n = 175) or simvastatin (n = 175) daily. Genotyping for CYP3A5 was done by PCR-RFLP analysis. Differences in the lipid profile before and after treatment were expressed as the % difference. The frequency of CYP3A5polymorphism was 13.4% for heterozygotes and 86.6% for homozygotes. Comparison of the responses to same dose of each drug showed that the highest % difference was associated with total cholesterol (TC) in subjects receiving atorvastatin 40 mg compared with simvastatin 40 mg (p = 0.048). However, comparison of the responses to equivalent doses of atorvastatin vs. simvastatin revealed no difference in the % change in any of the lipid parameters examined. In individuals with the same CYP3A5 genotype, a head to head comparison of the efficacy of the same dose of simvastatin vs. atorvastatin revealed an advantage for atorvastatin. For equivalent doses of atorvastatin vs. simvastatin there was no difference in the % change in any of the lipid parameters examined. Within the same genotype there was a significant difference in the % change related to the drug treatment.

4.
Angiology ; 66(2): 169-73, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24402318

ABSTRACT

Plasma lipids are major risk factors for coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) and apolipoprotein (apo) E genes are involved in lipoprotein metabolism, thus affecting plasma lipid and lipoproteins levels. Furthermore, such polymorphisms have been associated with susceptibility to CHD and obesity. We evaluated the influence of the gene polymorphisms of CETP TaqIB (B1, B2) and I405V (V, I) and apo E (∊2,∊3,∊4) on lipid levels, according to body mass index (BMI) in Greek men with CHD. The TaqIB (B1, B2) polymorphism affected plasma low-density lipoprotein cholesterol levels in overweight men with CHD, whereas the I405V (V, I) polymorphism affected triglyceride concentrations in normal weight men. No correlation was found between BMI and apo E polymorphisms. Large prospective studies are required to investigate the relationships of CETP and apo E polymorphisms with lipids, BMI, and CHD susceptibility.


Subject(s)
Apolipoproteins E/genetics , Body Mass Index , Cholesterol Ester Transfer Proteins/genetics , Coronary Disease/genetics , Genetic Variation , Aged , Apolipoprotein E2/genetics , Apolipoprotein E3/genetics , Apolipoprotein E4/genetics , Biomarkers/blood , Cholesterol, LDL/blood , Coronary Disease/blood , Coronary Disease/diagnosis , Genetic Predisposition to Disease , Greece , Humans , Male , Middle Aged , Phenotype , Risk Factors , Triglycerides/blood
5.
Cholesterol ; 2014: 109263, 2014.
Article in English | MEDLINE | ID: mdl-25580288

ABSTRACT

Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG), which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings.

6.
Open Cardiovasc Med J ; 4: 14-9, 2010 Jan 29.
Article in English | MEDLINE | ID: mdl-20200605

ABSTRACT

PURPOSE: High levels of high density lipoprotein (HDL) cholesterol are associated with a decreased risk of coronary heart disease (CHD). Subjects with high levels of HDL cholesterol (>70 mg/dl; 1.79 mmol/l) as well as high levels of low density lipoprotein (LDL) cholesterol, could represent a group with longevity syndrome (LS). Since HDL particles are influenced by cholesteryl ester transfer protein (CETP) activity, it is worth studying the CETP polymorphism. The aim of the study was to detect whether 2 genetic variants of the CETP are associated with the LS. SUBJECTS AND METHODS: The study population consisted of 136 unrelated men and women with no personal and family history of CHD; 69 met the criteria for LS and 67 did not meet these criteria and had "normal" HDL cholesterol (>40 and <70 mg/dl; >1.03 and <1.79 mmol/l). All patients were genotyped for the TaqIB and I405V polymorphisms. RESULTS: The B2 allele frequency of TaqIB polymorphism was higher in the LS in comparison with the non-LS group (p=0.03) whereas B1 allele frequency was higher in the non-LS group (p=0.03). CONCLUSIONS: Gene polymorphisms could help decide whether individuals who have increased levels of both LDL cholesterol and HDL cholesterol require treatment. Some of the prerequisites could include that subjects with LS should not only have very high levels of HDL cholesterol but also favorable gene polymorphisms. However, further investigations with a larger sample and including other gene polymorphisms, are needed.

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