Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolemia: an expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is well established since three decades, lowering serum LDL-C levels by more than 70% per session. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment targets and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia.

This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.

Lp(a) does not affect intima media thickness in hypercholesterolemic children -a retrospective cross sectional study.

Purpose: Combined hyperlipidaemia results in premature atherosclerosis and a high burden of cardiovascular morbidity and mortality. Early identification of highly affected subjects within this population is of utmost importance to enable informed treatment decisions. The measurement of intima media thickness (IMT) is a readily available, non-invasive method to investigate evidence of early atherosclerosis. To assess the usefulness of this method in pediatric subjects with hypercholesterolemia, we here examined a possible interaction of LDL-C and Lp(a) on IMT. Methods: Blood lipids (Lp(a), LDL-cholesterol, total cholesterol, triglycerides, high density lipoprotein (HDL) -cholesterol, apolipoprotein A1, apolipoprotein B), anthropometric parameters (age, height, weight, body mass index (BMI)) and possibly existing early evidence of atherosclerotic lesions measured by intima media thickness (IMT zscore).as a surrogate parameter was examined retrospectively in 113 children and adolescents (aged 1-18 years) with elevated Lp(a) and/or LDL-cholesterol (Lp(a) > 30 mg/dL, LDL>130 mg/dL). Furthermore, we compared hsCRP levels between groups. Results: There were no significant differences in IMT Zscore or hsCRP between groups. Regression analysis did not reveal a statistically significant interaction between Lp(a) and LDL-C. Conclusions: At the age of 6-18 years, we found no significant differences in early markers of atherosclerosis between subjects with high Lp(a)- and/or high LDL-cholesterol with no detectable synergistic effects between the two lipoproteins.

Long-Term Efficacy and Safety of Evinacumab in Patients with Homozygous Familial Hypercholesterolemia: Real-World Clinical Experience.

Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition characterized by markedly elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations from birth and increased risk of premature atherosclerotic cardiovascular disease. Evinacumab is an inhibitor of angiopoietin-like 3 protein that offers a new approach for correcting high LDL-C in HoFH. Evinacumab was administered intravenously (15 mg/kg Q4W) for 24 months in 7 patients with genetically confirmed HoFH, receiving background lipoprotein apheresis (LA) and/or lipid-lowering treatment (LLT). Assessment of efficacy and safety were carried out before and after 24 months of evinacumab treatment. The LDL-C lowering effect of evinacumab without LA were also investigated in the 7 HoFH patients after a subsequent compassionate extension period. Twenty-four months of treatment with evinacumab against background LA and LLT resulted in a significant reduction in LDL-C (−46.8%; p < 0.001). LDL-C reduction with evinacumab was maintained during the compassionate extensions period in the absence of treatment with LA (−43.4%; mean follow-up of 208 ± 90 days). Evinacumab was well-tolerated, with no major adverse event reported or significant changes in liver and muscle enzyme concentrations. Our findings suggest that evinacumab is a safe and effective treatment for patients with HoFH receiving best standard of care in a routine setting.

Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT.

BACKGROUND: The HAUSER-RCT study showed that 24 weeks of evolocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in paediatric patients with heterozygous familial hypercholesterolaemia was safe and improved lipid parameters compared to placebo. Here, we aimed to evaluate the safety and efficacy of evolocumab in this population for an additional 80 weeks. METHODS: HAUSER-OLE was an 80-week, single-arm, open-label extension of HAUSER-RCT, a randomised controlled trial, and was conducted at 46 centres in 23 countries. Paediatric patients aged 10-17 years with heterozygous familial hypercholesterolaemia who completed 24 weeks of monthly treatment with subcutaneously administered placebo or 420 mg evolocumab in HAUSER-RCT with no serious treatment-emergent adverse events were eligible to enrol in HAUSER-OLE. All patients received open-label subcutaneous evolocumab 420 mg monthly with background statins with or without ezetimibe for 80 additional weeks. The primary endpoint was treatment-emergent adverse events. Efficacy was evaluated by changes in lipids from the baseline of HAUSER-RCT to the end of HAUSER-OLE (104 weeks). This study is registered with ClinicalTrials.gov (NCT02624869) and is now completed. FINDINGS: Between Sept 10, 2016, and Nov 25, 2019, 157 patients were enrolled in HAUSER-RCT and received randomised treatment; 150 continued to HAUSER-OLE, received evolocumab treatment, and were included in the full analysis set, presented here. 146 (97%) of 150 patients completed the open-label extension. The incidence of treatment-emergent adverse events in HAUSER-OLE was 70% (105 of 150). Overall, the most common treatment-emergent adverse events were nasopharyngitis (22 [15%] of 150), headache (14 [9%]), and influenza-like illness (13 [9%]). Serious treatment-emergent adverse events occurred in four (3%) of 150 patients (perforated appendicitis and peritonitis, wrist fracture, anorexia nervosa, and headache); none was considered related to evolocumab. No treatment-emergent adverse events led to treatment discontinuation. At week 80, the mean percentage change from baseline in LDL cholesterol was -35·3% (SD 28·0). INTERPRETATION: After 80 weeks of treatment, evolocumab was safe, well tolerated, and led to sustained reductions in LDL cholesterol in paediatric patients with heterozygous familial hypercholesterolaemia. When lipid goals cannot be achieved with conventional treatments, evolocumab is an effective add-on therapy in paediatric patients. FUNDING: Amgen. TRANSLATIONS: For the French, Spanish, Spanish, Portuguese, Italian and Dutch translations of the abstract see Supplementary Materials section.

Efficacy and Safety of PCSK9 Monoclonal Antibodies in Patients With Diabetes.

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that have proven efficacy in improving cardiovascular outcomes. Roles for the PCSK9 molecule in metabolic pathways beyond LDL receptor processing and cholesterol homeostasis are well established. PCSK9 genetic variants associated with lower LDL-C levels correlate with a higher incidence of type 2 diabetes (T2DM), calling into question the appropriateness of these drugs in patients with T2DM and those at high risk of developing diabetes, and whether cardiovascular benefit seen with PCSK9 inhibitors might be offset by resultant dysglycemia. The purpose of this review was to examine the role of PCSK9 protein in glucose homeostasis, the impact of PCSK9 inhibition in relation to glucose homeostasis, and whether some of the cardiovascular benefit seen with PCSK9 inhibitors and statins might be offset by resultant dysglycemia. METHODS: Comprehensive literature searches of electronic databases of PubMed, EMBASE, and OVID were conducted by using the search terms hyperlipidaemia, PCSK9, diabetes, and glucose as well as other relevant papers of interest collected by the authors. The retrieved papers were reviewed and shortlisted most relevant ones. FINDINGS: Genetically determined lower circulating LDL-C and PCSK9 concentrations may have an incremental effect in increasing T2DM incidence, but any perceived harm is outweighed by the reduced risk of atherosclerotic cardiovascular disease achieved through lower lifetime exposure to LDL-C. PCSK9 monoclonal antibodies are effective and safe in patients with T2DM and those at high risk of developing it. The number-needed-to-treat to prevent one atherosclerotic cardiovascular disease event in the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study in the subgroup with diabetes is significantly lower than for those without. Therefore, T2DM or being at high risk to develop it should not be a reason to avoid these agents. The safety of PCSK9 inhibition in relation to glucose homeostasis may depend on the method of inhibition and whether it occurs in circulation or the cells. Data from experimental studies and randomized controlled trials suggest no detrimental effect of PCSK9 monoclonal antibodies on glucose homeostasis. More data and large randomized controlled studies are needed to assess the impact of other methods of PCSK9 inhibition on glucose homeostasis. IMPLICATIONS: PCSK9monoclonal antibodies markedly reduce LDL-C and consistently reduce cardiovascular mortality in patients with and without diabetes. Current evidence does not suggest an adverse effect of PCSK9 monoclonal antibodies on glycemic parameters.

Risk Assessment and Clinical Management of Children and Adolescents with Heterozygous Familial Hypercholesterolaemia. A Position Paper of the Associations of Preventive Pediatrics of Serbia, Mighty Medic and International Lipid Expert Panel.

Heterozygous familial hypercholesterolaemia (FH) is among the most common genetic metabolic lipid disorders characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a significantly higher risk of developing premature atherosclerotic cardiovascular disease. The majority of the current pediatric guidelines for clinical management of children and adolescents with FH does not consider the impact of genetic variations as well as characteristics of vascular phenotype as assessed by recently developed non-invasive imaging techniques. We propose a combined integrated approach of cardiovascular (CV) risk assessment and clinical management of children with FH incorporating current risk assessment profile (LDL-C levels, traditional CV risk factors and familial history) with genetic and non-invasive vascular phenotyping. Based on the existing data on vascular phenotype status, this panel recommends that all children with FH and cIMT ≥0.5 mm should receive lipid lowering therapy irrespective of the presence of CV risk factors, family history and/or LDL-C levels Those children with FH and cIMT ≥0.4 mm should be carefully monitored to initiate lipid lowering management in the most suitable time. Likewise, all genetically confirmed children with FH and LDL-C levels ≥4.1 mmol/L (160 mg/dL), should be treated with lifestyle changes and LLT irrespective of the cIMT, presence of additional RF or family history of CHD.

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents.

PURPOSE OF REVIEW: To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. RECENT FINDINGS: Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.

Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia.

BACKGROUND: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. RESULTS: A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. CONCLUSIONS: In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.).

Correction to: Lomitapide - a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia.

Due to errors during galley proofing, the original version of this article has been corrected.

Lipoprotein(a) concentration, genetic variants, apo(a) isoform size, and cellular cholesterol efflux in patients with elevated Lp(a) and coronary heart disease submitted or not to lipoprotein apheresis: An Italian case-control multicenter study on Lp(a).

BACKGROUND: Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. OBJECTIVE: The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). METHODS: We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. RESULTS: Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 µg/mg vs 16.01 ± 0.98 µg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 µg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).

Lomitapide-a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia.

PURPOSE OF REVIEW: Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition characterized by high levels of Low density lipoprotein cholesterol (LDL-C); overt, early-onset atherosclerotic cardiovascular disease (ASCVD); and premature cardiovascular events and mortality. Lomitapide is a first-in-class microsomal triglyceride transfer protein inhibitor for the treatment of HoFH. This review provides an update on data emerging from real-world studies of lomitapide following on from its pivotal phase 3 clinical trial in HoFH. RECENT FINDINGS: Recent registry data have confirmed that HoFH is characterized by delayed diagnosis, with many patients not receiving effective therapy until they are approaching the age when major adverse cardiovascular events may occur. Data from case series of varying sizes, and from a 163-patient registry of HoFH patients receiving lomitapide, have demonstrated that lomitapide doses are lower and adverse events less severe than in the phase 3 study. Lomitapide enables many patients to reach European Atherosclerosis Society LDL-C targets. Some patients are able to reduce frequency of lipoprotein apheresis or, in some cases, stop the procedure altogether-unless there is significant elevation of lipoprotein (a). Modelling analyses based on historical and clinical trial data indicate that lomitapide has the potential to improve cardiovascular outcomes and survival in HoFH. Real-world clinical experience with lomitapide has shown the drug to be effective with manageable, less marked adverse events than in formal clinical studies. Event modelling data suggest a survival benefit with lomitapide in HoFH.

Lipid profile and left ventricular geometry pattern in obese children.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children. PATIENTS AND METHODS: In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex. RESULTS: Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12-16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97). CONCLUSION: Increased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.

A complicated pregnancy in homozygous familial hypercholesterolaemia treated with lipoprotein apheresis: A case report.

BACKGROUND AND AIMS: During pregnancy total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels increase significantly and lipoprotein apheresis (LA) is considered the most effective therapy in homozygous familial hypercholesterolaemia (HoFH) for modulating lipid and lipoprotein levels and reducing maternal and foetal complications. CLINICAL CASE: A primigravida 28 years old Caucasian female patient, previously diagnosed as to be HoFH, was admitted at our outpatient service at the beginning of pregnancy. METHODS: The patient was continuously submitted to LA every two weeks without foetal complication. During pregnancy two methods have been utilised: selective apheresis, and later plasma exchange. At 33 weeks gestational age the patient developed progressively hypertension, associated to LDL-C levels increase. Weekly LA was favoured. RESULTS: At 34 weeks +5 days patient suddenly experienced acute chest pain and abnormal electrocardiogram heart tracing and cardiac enzymes increase. An emergency caesarean section was performed without complications and the foetus was healthy. The patient was immediately transferred to Coronary Intensive Care Unit, where she was diagnosed non-ST elevation myocardial infarction (NSTEMI). Notwithstanding the patient improved in few days and was quickly discharged in fair clinical condition. CONCLUSIONS: LA is a safe and effective tool in HoFH subjects even in pregnancy. Evidence based guidelines for the management of these patients during pregnancy are still lacking.

A successful term pregnancy with severe hypertriglyceridaemia and acute pancreatitis. Clinical management and review of the literature.

BACKGROUND AND AIMS: Acute hyperlipidaemic pancreatitis (HP) may develop in pregnancy in patients with genetic predisposition. There are no accepted guidelines for the management of this rare but life-threatening condition in pregnancy. Plasma exchange (PEX) was suggested as a suitable option to treat HP in pregnancy; however, further evidence from case reports/case series are needed. METHODS: Three PEX procedures (2000 ml of plasma replaced with 5% albumin) were performed in one week in a pregnant patient at 25 weeks of gestational age with severe HP. Triglyceride related genes (LPL, APOA5, APOE, GPIHBP1, GPD1, LMF1, CREB3L3) were screened by DNA sequencing. Medline and Embase databases were searched electronically in January 2018 using different combinations of the relevant medical subject headings for "pancreatitis in pregnancy" and "therapeutic apheresis". RESULTS: Gene profiling assessed a combined heterozygous state for the variants pSer19Trp of the APOA5 gene and pCys130Arg of the APOE (allele E4) gene. PEX led to significant and progressive reduction of triglyceride plasma levels along with cholesterol and C-reactive protein. Meanwhile a fast improvement of pregnant clinical condition was observed. This allowed the delivery at term of a healthy newborn without gestational complications. An outcome hardly achievable in patients managed exclusively by a pharmacological approach. CONCLUSIONS: PEX led to a positive maternal outcome in absence of foetal and gestational complications in a case of severe HP in pregnancy. As clinical trials are lacking, case reports still represent the best way to reasonably implement clinical management of this rare but life-threatening disease.

Homozygous familial hypercholesterolaemia in childhood - The first case report in Southeast Europe.

Homozygous familial hypercholesterolaemia (HoFH) is the rare, severe, but treatable disease characterised by exceedingly high levels of low-density lipoprotein cholesterol (LDL-C) and subsequent premature coronary heart disease. Of note, HoFH detection rate and patient access to healthcare and treatment modalities still differ considerably across EU countries. To our current knowledge, there are still no published reports describing HoFH in the paediatric population of Southeastern Europe. In this case report, a few important topics on obstacles in getting adequate health care service and management of HoFH children from Southeastern Europe are tackled.

Optical coherence tomography of retinal and choroidal layers in patients with familial hypercholesterolaemia treated with lipoprotein apheresis.

PURPOSE: Detect and quantify morpho-functional alterations of the retina and choroid in patients affected by familial hypercholesterolemia (FH) treated with lipoprotein apheresis (LA) using optic coherence tomography (OCT) and optic coherence tomography-angriography (OCTA). DESIGN: Observational study. SUBJECTS: To be diagnosed: A group of 20 patients (40 eyes) being clinically and genetically diagnosed as FH and under treatment (FH-Group)", for at least 2 years, was compared to a control group of 20 healthy subjects (40 eyes), with a normal lipid profile and no ocular disease (CT-Group). METHODS: Participants were studied with the slit lamp, binocular indirect fundoscopy, OCT and OCTA. MAIN OUTCOME MEASURES: Best corrected visual acuity (BVCA), spherical equivalent (SE), intraocular pressure (IOP), central macular thickness (CMT), choroidal thickness (CHT), retinal nerve fiber layer in four quadrants (RNFL (Superior = Sup; Inferior = Inf; Nasal = Nas Temporal = Temp), and the mean value across the four quadrants (RNFL G), foveal avascular zone (FAZ) and vascular density (VD). RESULTS: FH subjects had smaller RNFL superiorly (108 ±â€¯19,38 µm OD/111 ±â€¯16,56 µm OS FH-Group vs 127 ±â€¯7,42 µm OD/129 ±â€¯14,64 µm OS CT-Group; P < 0,001 for both OD and OS) and inferiorly (108 ±â€¯23,58 µm OD/115 ±â€¯17,33 µm OS FH-Group vs 128 ±â€¯18,15 µm OD/133 ±â€¯17,38 µm OS CT-Group; P = 0,002 OD; P = 0,001 OS). G RNFL was consequently smaller (93 ±â€¯12,94 µm OD/94 ±â€¯10,49 µm OS FH-Group vs 101 ±â€¯9,01 µm OD/101 ±â€¯10,20 µm OS CT-Group; P = 0,03 OD; P = 0,02 OS). FH subjects had a larger FAZ (0,31 ±â€¯0,08 mm2 OD/0,33 ±â€¯0,10 mm2 in OS FH-Group vs 0,21 ±â€¯0,05 mm2 OD/0,21 ±â€¯0,07 mm2 OS CT-Group; P < 0,001 OD; P = 0,002 OS). CONCLUSIONS: Early signs of retinal vessel damage in FH patients can be detected and quantified with OCT and OCTA.

Serum uric acid and left ventricular geometry pattern in obese children.

BACKGROUND: Relative importance of traditional and non-traditional components of metabolic syndrome (MetSy) as risk factors for subclinical target organ damage in obese children is still under investigation. Recent studies highlight the role of serum uric acid (SUA) as an emerging non-traditional independent risk factor which correlates with obesity, MetSy, type 2 diabetes, preclinical cardiac and extracardiac organ damage, as well as cardiovascular events. AIMS: To study the relationship between SUA and left ventricular geometry pattern in obese children with or without MetSy. PATIENTS AND METHODS: In this cross-sectional study, a total of 73 obese children, 64.4% male, and 35.6% female, with median age of 15 years (IQR = 12-16) were examined. Body mass index, glycaemia, standard lipid profile, fasting insulin level, HOMA index, serum uric acid level, 24-h average systolic blood pressure, left ventricular mass index (LVMI) and relative wall thickness (RWT) were evaluated in all children. RESULTS: LVMI in our study group was 46 g/m2.7 (IQR = 42-55) while the RWT was 37% (IQR = 31-41). Median SUA level was 341 µmol/L (IQR = 283-387). In the entire sample of children, SUA was independently associated with the RWT (coeff = 0.02, p < 0.01). In a sub-group of metabolically unhealthy children, we found no statistically significant association between SUA and LVMI nor between SUA and RWT (coeff. = 0.002, p = 0.92; coeff. = 0.01, p = 0.20, respectively). CONCLUSION: Serum uric acid is an important independent non-traditional risk factor for the development of concentric left ventricular geometry in obese children. These findings deserve further investigation to determine whether high SUA in obese children may be a therapeutic target.