Roeters Van Lennep J.,Erasmus Medical Center |
Averna M.,University of Palermo |
Alonso R.,Lipid Clinic |
Alonso R.,Lipid Unit
Journal of Clinical Lipidology | Year: 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 management of HoFH cases. Four HoFH cases were selected for analysis and discussion: a 20-year-old female compound heterozygote; a 62-year old female homozygote; a 42-year-old female compound heterozygote; and a 36-year-old male homozygote. Each patient was commenced on lomitapide according to the prescribed protocol and subjected to routine follow-up. All four patients experienced clinically meaningful reductions in LDL-C levels of 35-73%. Three of the patients had evidence of steatosis or mildly elevated liver function tests) before lomitapide was started, but effects of lomitapide on hepatic function were not universal. Three of the patients experienced gastrointestinal adverse events, but were managed with appropriate dietary control. Lomitapide is an effective adjunct LLT in the management of patients with HoFH, with or without LA. Real-world use of lomitapide has a side-effect profile consistent with clinical trials and one that can be managed by adherence to recommendations on dose escalation, dietary modification and dietary supplements. © 2015 National Lipid Association. All rights reserved.
Heier I.,University of Oslo |
Soyland E.,Section for Climate Therapy |
Krogstad A.-L.,Section for Climate Therapy |
Rodriguez-Gallego C.,Lipid Clinic |
And 4 more authors.
British Journal of Dermatology | Year: 2011
Background Interferon (IFN)-α-producing plasmacytoid dendritic cells (pDCs), inflammatory CD11c+CD1c- myeloid dendritic cells (mDCs) and macrophages have been found to contribute to the pathogenesis of psoriasis. Heliotherapy is a well-established treatment modality of this disease, although the details of how the effects are mediated are unknown. Objectives To test the hypothesis that exposure to natural sun affects pathogenic DC subsets in lesional skin. Methods Skin biopsies were obtained from lesional and nonlesional skin in 10 patients with moderate to severe psoriasis subjected to controlled sun exposure on Gran Canaria. Biopsies were obtained at baseline, day 2 and day 16 and examined by immunohistochemistry. Results Sixteen days of heliotherapy had excellent clinical effect on patients with psoriasis, with significant reductions in Psoriasis Area and Severity Index (PASI) scores. In lesional skin pDC numbers and expression of MxA, a surrogate marker for IFN-α, were rapidly reduced. Inflammatory CD11c+CD1c- mDCs were significantly reduced whereas resident dermal CD11c+CD1c+ mDCs were unaffected. Expression levels of the maturation marker DC-LAMP (CD208) on mDCs were significantly reduced after sun exposure, as were the numbers of lesional dermal macrophages. A decrease of dermal DC subsets and macrophages was already observed after 1 day of sun exposure. An additional finding was that DC-SIGN (CD209) is primarily expressed on CD163+ macrophages and not DCs. Conclusions The clinical improvement in psoriasis following sun exposure is associated with rapid changes in dermal DC populations and macrophages in lesional skin, preceding the clinical effect. These findings support the concept that these DC subsets are involved in the pathogenesis of psoriasis and suggest that sun-induced clinical benefit may partly be explained by its effect on dermal DCs. © 2011 British Association of Dermatologists.
Toleikyte I.,University of Oslo |
Retterstol K.,Lipid Clinic |
Leren T.P.,University of Oslo |
Iversen P.O.,University of Oslo
Circulation | Year: 2011
Background-: Women with familial hypercholesterolemia (FH) are prone to early cardiovascular disease and death. It is unknown whether FH adversely affects pregnant women and birth outcomes. We determined whether heterozygous FH women are at higher risk of premature birth (<37 gestational weeks), delivering children with low birth weight (<2500 g) and/or with congenital malformations compared to women in general. Methods and Results-: We linked information from the Medical Genetics Laboratory with that of the Medical Birth Registry of Norway. We included 1869 FH women (≥14 years) from the Medical Genetics Laboratory and about 2 million (general population) from the Medical Birth Registry of Norway during the period 1967 to 2006. The registry match resulted in analysis of 2319 births of 1093 women with heterozygous FH. The mean (SD) prepregnancy total cholesterol concentration was 9.59 (2.06) mmol/L (370 [80 mg/dL]), whereas the concentration of total cholesterol was not available during pregnancy. The frequencies of prematurity, low birth weight, and congenital malformations for the 40-year period in the FH population were 6.8, 5.0, and 3.3, respectively. The corresponding values for the general population were 6.2, 5.2, and 3.2. The corresponding odds ratios were 1.11 (95 confidence interval 0.94-1.31; P=0.23), 0.96 (0.79-1.15; P=0.64), and 1.09 (0.87-1.37; P=0.45). Conclusions-: Women with FH do not appear to have a higher risk of preterm delivery or of having infants with low birth weight or congenital malformations than women in general, but, although this is unlikely, some undetected bias may obscure the real differences. © 2011 American Heart Association, Inc.
Sala-Vila A.,Institute Salud Carlos III ISCIII |
Ros E.,Lipid Clinic
Clinical Lipidology | Year: 2011
The polyunsaturated fatty acid of the n-3 series α-linolenic (ALA) is an essential fatty acid for humans, meaning that it cannot be synthesized and must be obtained from food sources. In addition, the inefficient synthesis of eicosapentaenoic (EPA) and docosahexaenoic (DHA), the more polyunsaturated n-3 fatty acids found in seafood, from ALA makes both EPA and DHA 'semi-essential. There is a growing body of scientific evidence from epidemiological studies and some clinical trials indicating that intake of marine n-3 fatty acids (EPA and DHA), either as fish oil concentrates or fatty (so-called blue) fish, has a cardioprotective effect. The association of dietary ALA, which is the vegetable n-3 fatty acid, with cardiovascular health has been less widely investigated than that of fish-derived n-3 fatty acids and is unclear. Thus, a new study relating ALA intake to cardiovascular outcomes in a sizable cohort is welcome. Such is the present report of 10-year findings in the MORGEN study, a large Dutch population-based cohort, part of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The contribution of this study to the growing body of knowledge relating ALA intake to health outcomes will be discussed here. © 2011 Future Medicine Ltd.
Farnier M.,Lipid Clinic
Expert Review of Cardiovascular Therapy | Year: 2015
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in lipoprotein metabolism, mainly by modulating LDL receptor activity. Alirocumab is a fully human IgG1 monoclonal antibody that binds PCSK9, increases the number of LDL receptors and decreases the levels of LDL cholesterol. The efficacy of alirocumab has been evaluated in more than 6000 subjects with primary hypercholesterolemia; in Phase III trials, alirocumab consistently reduced LDL-cholesterol up to 62% with every 2 weeks dosing compared with placebo and up to 36% compared with ezetimibe. Two doses, 75 and 150 mg, have been developed to propose a tailored approach in the treatment of hypercholesterolemic patients not controlled by maximally tolerated lipid-lowering therapy. Alirocumab was generally well-tolerated, with an acceptable safety profile. The ongoing ODYSSEY OUTCOMES trial will provide definitive evidence on the effect of alirocumab on cardiovascular morbidity and mortality and complementary data on the long-term safety and tolerability. Moreover, a cost-effectiveness analysis would be useful to determine the appropriate price of alirocumab. © 2015 Taylor & Francis.