Nutritional Treatment in a Cohort of Pediatric Patients with Familial Hypercholesterolaemia: Effect on Lipid Profile.

Background and aims: Familial Hypercholesterolaemia (FH) is characterised by a genetic alteration in the transport and metabolism of cholesterol that leads to elevated levels of total cholesterol (CT) and low-density lipoprotein cholesterol (LDL-C) and early onset of atherosclerosis. According to the current guidelines, diet and promotion of healthy habits are first-line treatments. Little is known about the effectiveness of cholesterol-lowering diet and healthy lifestyle habits on plasma cholesterol and lipid profile in children and adolescents with FH. The aim of the study is to investigate the effect of the nutritional counseling on plasma lipid profile in FH children at the first step of treatment. Methods: 115 FH children (2−17 years) were included in the study; dietary habits were evaluated through a Food Frequency Questionnaire (FFQ) and blood samples for lipid profile were collected at the enrollment (T0) and six months later (T1). Results: the lipid profile at T0 and T1, expressed as mean ± standard deviation in mg/dL, was, respectively: total cholesterol 285.9 ± 51.1 and 276.6 ± 46.8 (paired test difference p value < 0.01), LDL-cholesterol 214.9 ± 47.7 and 206.4 ± 46.6 (p value < 0.01), HDL-cholesterol 52.9 ± 13 and 54.4 ± 11.5 (p value 0.07), triglycerides 87 ± 46.7 and 82.2 ± 38.4 (p value 0.4), non-HDL cholesterol 233 ± 51.4 and 222.2 ± 47.4 (p < 0.01). In the dietary habits (weekly portions) we observed an improvement (p ≤ 001) for fruit and vegetables, fish, pulses, whole foods, and a reduction (p < 0.01) for meat, sausages, cheese, junk foods consumption. Conclusions: In FH children we have highlighted an improvement of the plasma lipid profile and in healthy dietary habits after nutritional counseling.

Mediterranean Dietary Treatment in Hyperlipidemic Children: Should It Be an Option?

BACKGROUND: Diet is considered the cornerstone of lipid management in hyperlipidemic children but evidence to demonstrate the effects of nutrient benefits on the lipid profile is limited. AIM: The aim of this study is to evaluate the impact of the Mediterranean diet on low-density lipoprotein (LDL-C) and non-high density lipoprotein (HDL-C) decrease in primary hyperlipidemia affected children and in the achievement of therapeutical target levels. METHODS: A retrospective cohort study was used, recruiting n = 223 children (10.05 ± 3.26 mean age years) with familial hypercholesterolemia (FH) (n = 61, 27%) and polygenic hypercholesterolemia (PH) (n =162, 73%). Secondary hyperlipidemias were excluded. Based on LDL-C and non-HDL-C decrease, participants were divided into two groups, named the Responder Group and Non-Responder Group. Participants and their families underwent dietary education by an expert nutritionist and were asked to fill in a weekly diary to be delivered at visits. Dietary indications were in line with daily caloric requirement, daily food quality and quantity intakes typical of the Mediterranean diet. These include carbohydrates, extra virgin olive oil, yoghurt and milk derivatives, fish and vegetable proteins, fresh seasonal vegetables and fresh fruits. Nuts or almonds were also recommended. The advice to limit intakes of meat, in particular red meat, and caution against junk food and sugar added food and beverages was provided. At medical visits, carried out at baseline (T0) and 6 months later (T1), children underwent anthropometric measurements and blood collection. Standard kits and methods were applied for lipid analysis. Statistical methods were performed by SAS version 9.4 (SAS Institute, Cary, NC, USA). Signed informed consent was given by parents according to the Declaration of Helsinki and the study was approved by the Local Committee. RESULTS: The Responder Group (n = 156/223, 70%) included 45 FH and 111 PH children, while the Non-Responder Group (n = 67/223, 30%) included 16 FH and 51 PH children. The Responder Group showed total cholesterol (TC), LDL-C and non-HDL-C median percentage decreases of 9.45, 13.51 and 10.90, respectively. These statistically significant changes (p ≤ 0.0001) were similar in the FH and PH subgroups but just PH subjects reached the LDL-C and non-HDL-C target, which fell below 130 mg/dL and 145 mg/dL, respectively. Saturated fatty acids (SFAs) were the main dietary parameter that distinguished between the Responder Group and the Non-Responder Group (p = 0.014). Positive correlations were found at T1 between dietary total lipids, SFAs and cholesterol with serum LDL-C, non-HDL-C and TC variations. These latter serum parameters had an inverse correlation with dietary carbohydrate at T1. Among macronutrients, SFAs were finally demonstrated to be the predictor of serum lipids variation at T1. CONCLUSIONS: The dietary intervention with a Mediterranean diet in children with primary hyperlipidemia significantly improves the lipid profile both in FH and PH subgroups and allows target levels of LDL-C and non-HDL-C in PH subjects to be reached. Responsiveness benefits should be primarily attributed to the reduction in SFAs, but changes in dietary lipids, cholesterol and carbohydrate intake may also play a role. In contrast, the Non-Responder Group showed a worsening of lipid profile regarding the unchanged diet.

Adherence to a Mediterranean diet, dyslipidemia and inflammation in familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP). METHODS AND RESULTS: In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p < 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p < 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies. CONCLUSIONS: Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH.

Dietary intake and lipid levels in Norwegian and Spanish children with familial hypercholesterolemia.

BACKGROUND AND AIMS: Both the Nordic and Mediterranean diets claim to have a beneficial effect on lipid metabolism and cardiovascular prevention. The objective of this study was to compare diets consumed by children with FH at the time of diagnosis in Norway and Spain and to study their relationship with the lipid profile. METHODS AND RESULTS: In this cross-sectional study, we appraised the dietary intake in children (4-18 years old) with (n = 114) and without FH (n = 145) from Norway and Spain. We compared Nordic and Mediterranean diet composition differences and determined the association between food groups and lipid profiles. RESULTS: The Spanish FH group had a higher intake of total fats (mainly monounsaturated fatty acids (MUFAs)), cholesterol and fibre, but a lower intake of polyunsaturated fatty acids (PUFAs) compared to the Norwegian FH group. The Norwegian children consumed more rapeseed oil, low-fat margarine and whole grains and less olive oil, eggs, fatty fish, meat, legumes and nuts. In the Norwegian FH group, fat and MUFAs were directly correlated with total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B and inversely correlated with high-density lipoprotein (HDL-C). In Spanish children with FH, the intake of fats (mainly MUFAs) was directly associated with HDL-C and apolipoprotein A1. CONCLUSIONS: Despite a similar lipid phenotype, diets consumed by children with FH in Norway and Spain have significant differences at time of diagnosis. Nutrition advice should be more adapted to local intake patterns than on specific nutrient composition.

Evaluación del control metabólico, el perfil cardiovascular y la adherencia a la dieta mediterránea de una cohorte de hipercolesterolemia familiar en un programa de salud pública / Metabolic control, cardiovascular profile, and adherence to the Mediterranean diet in a familial hypercholesterolemia cohort in a Public Health Program

ANTECEDENTES Y OBJETIVO: la hipercolesterolemia familiar heterocigota (HFH) es el trastorno del metabolismo lipídico monogénico más común que se asocia a patología cardiovascular prematura. Nuestro objetivo fue describir el grado de control metabólico, el perfil cardiovascular y la adherencia a la dieta mediterránea de una cohorte de pacientes con HFH. MATERIAL Y MÉTODOS: estudio de cohortes retrospectivo de casos índices y familiares diagnosticados genéticamente de HFH desde 2009 a 2017. Se analizaron los datos antropométricos, clínicos, analíticos, del estudio genético y del tratamiento. RESULTADOS: se estudiaron 138 sujetos con una edad media de 48,8 (17,7) años, el 55,8 % mujeres. Se encontró la mutación positiva en el 55,8 %. La media de colesterol total al diagnóstico fue de 281,1 (68,4) mg/dl y la de LDL de 204 (65) mg/dl. El 10,1 % presentaban cardiopatía isquémica previa. Entre los casos familiares se observó una menor edad media [32,89 (19,2) años vs. 50,3 (17,6) años, p < 0,001], así como valores de LDL inferiores en el momento del diagnóstico [181,9 (64,3) mg/dl vs. 226,8 (52) mg/dl, p < 0,005] en comparación con los casos índice. Se evidenció una correlación positiva entre dosis de tratamiento hipolipemiante y reducción de los niveles de LDL (r = 0,254, p < 0,05), aunque solo el 30 % de los pacientes alcanzaron sus objetivos de LDL. Los pacientes con HFH presentaron una elevada adherencia a la dieta mediterránea, con una puntuación media de 9,5 (1,9) en el test Predimed. CONCLUSIONES: la detección precoz de la HFH es necesaria para prevenir eventos cardiovasculares prematuros. El diagnóstico de casos familiares anticipa el tratamiento de los pacientes con HFH. Los pacientes con HFH están más sensibilizados sobre la adherencia a las dietas cardiosaludables

INTRODUCTION AND OBJECTIVE: familial heterozygous hypercholesterolemia (HFH) is the most common monogenic lipid metabolism disorder that associates premature cardiovascular disease. Our aim was to describe the degree of metabolic control, cardiovascular profile, and adherence to the Mediterranean diet in a cohort of HFH patients. Subjects and methods: a retrospective cohort study of the index cases and their relatives genetically diagnosed with HFH by the Endocrinology and Nutrition Service in the HCUV from 2009 to 2017. Anthropometric, clinical, laboratory, genetic, and treatment data were analyzed. RESULTS: a total of 138 subjects were studied, with a mean age of 48.8 (17.7) years, 55.8 % of them women. A gene mutation was found in 55.8 %, and 10.1 % had previous ischemic heart disease. At diagnosis mean total cholesterol was 281.1 (68.4) mg/dL, and LDL-C was 204 (65) mg/dL. Among family cases, at diagnosis, a lower mean age was observed [32.89 (19.2) years vs 50.3 (17.6) years, p < 0.001] as well as lower LDL values [181.9 (64.3) mg/dL vs 226.8 (52) mg/dL, p < 0.005] as compared to index cases. A positive correlation was observed between lipid-lowering treatment dose and LDL level reduction (r = 0.254, p < 0.05), although only 30 % of patients reached their LDL target. Patients with HFH were highly adherent to Mediterranean diet, with an average score of 9.5 (1.9) in the Predimed test. CONCLUSIONS: early HFH detection is necessary to prevent premature cardiovascular events. A diagnosis of cases among family members anticipates the treatment of patients with HFH. Patients with HFH are more sensitive to heart-healthy diets

Effects of a low-fat dietary regimen enriched with soy in children affected with heterozygous familial hypercholesterolemia.

INTRODUCTION: Familial hypercholesterolemia (FH) is an inheritable, autosomal dominant disorder leading to pathologically increased levels of low-density-lipoprotein cholesterol (LDL-C). Dietary treatment remains an important tool in the management of affected children even after the decision for the initiation of pharmacotherapy is made. However, little evidence is available regarding the optimal dietary regimen for the treatment of children affected with FH. METHODS: We present results from a randomized controlled trial in paediatric patients affected with heterozygous FH, assessing the effect of a soy-enriched fat modified diet (soy group) compared to fat modified diet (Control group) alone on LDL-C over a period of 13 weeks. Furthermore, we monitored isoflavone levels in plasma and urine as markers of adherence to the dietary treatments. RESULTS: LDL-C decrease was statistically significantly greater in the soy group compared to the control group at week 7 (Control group 176.3 ± 27.8 mg/dl, soy group 154.7 ± 29.2 mg/dl, p = 0.038), and showed a trend towards significant at week 13 (Control group 179.9 ± 41.8 mg/dl, soy group 155.0 ± 30.2 mg/dl, p = 0.089). Relative LDL-C decrease correlated significantly with the following plasma isoflavone concentrations measured in week 7: daidzein (p < 0.004, r = 0.576) and genistein (p < 0.017, r = 0.490). CONCLUSIONS: We provide evidence from a small randomized-controlled trial for the effectiveness and safety of a dietary treatment with soy in paediatric patients affected with heterozygous FH. The decrease in LDL-C was highly correlated with isoflavone levels, further highlighting a direct effect of soy ingestion. This study was registered under ClinicalTrials.gov Identifier No. NCT03563547.

Effect of quantitative and qualitative diet prescription on children behavior after diagnosis of heterozygous familial hypercholesterolemia.

BACKGROUND: Diet and healthy modifications in lifestyle represent the first therapeutic approach for early intervention in hypercholesterolemia. We aimed to evaluate the impact of a qualitative dietetic program rather than a quantitative one on metabolic parameters and anxiety level of children affected by heterozygous familial hypercholesterolemia [heFH] and their mothers. METHODS: In a sample of 42 heFH normal weight children (11.4 ±â€¯2.9 years old), we investigated the factors which were associated with children perceived quality of life and with their mothers' anxiety levels after qualitative dietary changes rather than after quantitative ones. RESULTS: The administered diets had similar metabolic effects. However, higher Child Behavior Checklist (Behavior Problems subscale) [CBCL] scores were significantly associated with the permanence in quantitative diet, as well as children's higher age, higher Children's Depression Inventory 2 [CDI2] and State-Trait Anxiety Inventory for Children [STAI-CH] score, and with mothers' anxiety at the baseline. CONCLUSION: In heFH children, an intervention in the diet to improve food choice seems to be associated with a more healthy children behavior rather than a quantitative diet.

Special Commentary: Is diet management helpful in familial hypercholesterolemia?

PURPOSE OF REVIEW: Familial hypercholesterolemia is a genetic condition where low-density lipoprotein (LDL) receptor defects cause severe elevations of LDL cholesterol. As significant LDL-lowering effects are needed, medication is considered the cornerstone of therapy, and dietary therapy has received less emphasis. This review will re-visit older studies of diet intervention and new insights from genetic and mechanistic studies to determine the value of diet management for familial hypercholesterolemia patients. RECENT FINDINGS: Saturated fat reduction improves cardiovascular outcomes, particularly in those with genetic predisposition to risk. Secular trends in saturated fat intake may have improved familial hypercholesterolemia outcomes. Dietary mechanisms of LDL cholesterol-lowering complement pharmacologic approaches. SUMMARY: Diet treatment adds incremental health benefit to pharmacologic treatment in familial hypercholesterolemia.

Decreasing the Cholesterol Burden in Heterozygous Familial Hypercholesterolemia Children by Dietary Plant Stanol Esters.

This review covers the current knowledge about plant stanol esters as a dietary treatment option for heterozygous familial hypercholesterolemia (he-FH) children. The current estimation of the prevalence of he-FH is about one out of 200⁻250 persons. In this autosomal dominant disease, the concentration of plasma low-density lipoprotein cholesterol (LDL-C) is strongly elevated since birth. Quantitative coronary angiography among he-FH patients has revealed that stenosing atherosclerotic plaques start to develop in he-FH males in their twenties and in he-FH females in their thirties, and that the magnitude of the plaque burden predicts future coronary events. The cumulative exposure of coronary arteries to the lifelong LDL-C elevation can be estimated by calculating the LDL-C burden (LDL-C level × years), and it can also be used to demonstrate the usefulness of dietary stanol ester treatment. Thus, when compared with untreated he-FH patients, the LDL-C burden of using statin from the age of 10 is 15% less, and if he-FH patients starts to use dietary stanol from six years onwards and a combination of statin and dietary stanol from 10 years onwards, the LDL-C burden is 21% less compared to non-treated he-FH patients. We consider dietary stanol treatment of he-FH children as a part of the LDL-C-lowering treatment package as safe and cost-effective, and particularly applicable for the family-centered care of the entire he-FH families.

Effect of Caloric Restriction on Metabolic Dysfunction of Young Rapacz Familial Hypercholesterolemic Swine (Sus scrofa).

The Rapacz familial hypercholesterolemic (FH) swine model is well-characterized and used for studies of both spontaneous and inducible atherosclerosis but has not been used for studies of metabolic dysfunction to date. We examined whether parameters of metabolic syndrome including weight and adiposity, serum cholesterol, and glucoregulatory function could be modulated by restriction of caloric intake in the FH swine. Three groups of FH swine (n = 6 per group) were fed without restriction (AL), 80% of AL caloric intake, or 60% of AL caloric intake for 8.8 ± 0.5 mo beginning 2 wk after weaning. Caloric intake influenced the rate and magnitude of body weight gain and change in adiposity, as determined by dual-emission X-ray absorptiometry. At the conclusion of the study, pigs in the AL group reached a total least-square mean body weight of 94.2 kg and fat mass of 31.1%, whereas those fed 80% AL were 71.6 kg and 24.3% fat, and swine fed 60% AL were 46.1 kg and 14.1% fat. Serum cholesterol was greater in AL than 60% AL pigs at the end of the study. At 10 mo of age, intravenous glucose tolerance testing, performed to assess glucoregulatory function, indicated significant differences in serum glucose clearance profiles and insulin sensitivity between the AL- and 60% AL-fed swine. The AL-fed animals showed almost 5-fold lower insulin sensitivity when compared with animals fed 60% AL caloric intake. These results highlight the value of the FH swine model to study metabolic dysfunction due to changes in caloric intake.

A 10-year experience using combined lipid-lowering pharmacotherapy in children and adolescents.

BACKGROUND: Current pediatric guidelines for heterozygous familial hypercholesterolemia (HeFH) propose pharmacotherapy (PT) with statins from age 8 to 10 years; however, schemes with absorption inhibitors combined with statins, could be started earlier. The aim of the study was to show the 10-year results of a combined treatment protocol. METHODS: Prospective, descriptive and analytical study. Pediatric patients (n=70; mean age at PT initiation 9.3 years [range, 2-17.5]) with HeFH who required PT between 2005 and 2015 were included. All patients ≥10 years, with LDL >190 mg/dL or >160 mg/dL with one cardiovascular risk factor (CVRF) or >130 mg/dL with two or more CVRF; and those patients 5-10 years and with LDL-C >240 mg/dL or a family history of a cardiovascular event before 40 years, were medicated. After a period on a lipid-lowering diet (LLD), all patients were started on ezetimibe. Patients who did not achieve the treatment goal were given statins. The variables were: age, age at PT initiation, duration of PT, initial LDL-C, mean LDL-C during ezetimibe monodrug therapy, mean LDL-C during combined PT, and percentage of LDL decrease. RESULTS: LDL-C levels were: Baseline: 235 mg/dL±55; after 3 months on ezetimibe: 167 mg/dL±47 (decrease: -27.62%). In 18 patients who did not reach the treatment goal atorvastatin was added and their LDL-C decreased -41.5% (p: 0.02). Overall, mean final LDL-C was 155 mg/dL±30.4 (range, 98-257) and treatment goals were reached in 74% of the patients. No severe side effects were reported. CONCLUSIONS: Combined and sequential treatment starting at early ages was shown to be safe and effective over this follow-up period.

Dietary counseling is associated with an improved lipid profile in children with familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Guidelines recommend cholesterol-lowering medication from 8 to 10 years of age and dietary recommendations. Little is known about the diet of FH children and the effect of dietary counseling. The aim of the study was to describe the diet of FH children with respect to fat quality, and to investigate if dietary counseling improved lipid profile. METHODS: Fifty-four FH children (5-18 years) were included in the study and dietary intake was recorded with a pre-coded food diary for four days. Information about plasma lipid levels was obtained. RESULTS: Median intake of total fat, monounsaturated fat, polyunsaturated fat (PUFA) and saturated fat (SFA) was 30.8, 10.4, 5.9 and 12.0 E %, respectively. Among non-statin treated FH children, SFA intake was significantly correlated with TC, LDL-C and apolipoprotein (apo) B (rsp = 0.55; p = 0.004, rsp = 0.46; p = 0.02, and rsp = 0.45; p = 0.02, respectively), and PUFA/SFA ratio significantly inversely correlated with TC (rsp = -0.42; p = 0.03). Compared to the first visit, non-statin and non-plant sterol treated FH children (n = 10) had significantly reduced levels of TC (p < 0.01), LDL-C (p = 0.01), high-density lipoprotein cholesterol (p = 0.02), apo B (p = 0.05) and apo A-1 (p = 0.02) levels at a later visit. CONCLUSIONS: FH children had a higher intake of SFA than recommended and the SFA intake was positively correlated with plasma TC, LDL-C and apo B levels in FH children not using statins. Importantly, the plasma lipid profile was improved in FH children after dietary counseling where focus was on reducing intake of SFA and dietary cholesterol.

Una visión genética de la hipercolesterolemia familiar / A genetic view of familial hypercholesterolemia

Objetivo: mostrar información revisada de manera sistemática de estudios publicados relacionados con la hipercolesterolemia familiar (HF), la nutrición y los genes que intervienen en el desarrollo de esta patología. Resultados: el análisis de los resultados de investigación consultados pone de manifiesto que la hipercolesterolemia familiar es un trastorno que se produce debido a mutaciones en genes que codifican el receptor de LDL, que se puede transmitir de forma autosómica dominante o bien autosómica recesiva. La importancia de su diagnóstico radica en que las personas afectas presentan una elevada frecuencia de enfermedad coronaria prematura, reduciéndose de forma importante su expectativa de vida. Conclusiones: no existen criterios clínicos específicos con un valor predictivo absoluto para el diagnóstico de HF; el diagnóstico genético permite demostrar defectos funcionales en el gen del receptor LDL, constituyendo la confirmación definitiva del diagnóstico, de ahí la importancia de presentar una visión genética del desarrollo de esta patología, que puede ser tratada para generaciones futuras de manera adecuada a través de la dietoterapia en la familia afectada (AU)

Objective: to show reviewed information of published studies relating to Familial Hypercholesterolemia (FH), nutrition, and genes involved in the development of this pathology. Results: an analysis showing familial hypercholesterolemia as a disorder occuring due to mutations in gene encoding of the LDL receptor, which can be transmitted as an autosomal dominant or autosomal recessive. It’s diagnosis is important for those with a greater likelihood of premature coronary disease, and can significantly reduce life expectancy. Conclusions: there are no specific clinical criteria with absolute predictive value for the diagnosis of HF, Genetic diagnosis can prove functional defects in the LDL receptor gene, constituting definitive confirmation of the diagnosis, thus the importance of presenting a genetic vision of development of this disease, which can be treated adequately through diet therapy affecting future generations in the family concerned (AU)

Plasma cholesterol-lowering activity of dietary dihydrocholesterol in hypercholesterolemia hamsters.

OBJECTIVE: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of ß-sitosterol (SI) in hamsters fed a high cholesterol diet. METHODS AND RESULTS: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter. CONCLUSION: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Effect of a low-fat diet enriched either with rapeseed oil or sunflower oil on plasma lipoproteins in children and adolescents with familial hypercholesterolaemia. Results of a pilot study.

BACKGROUND/OBJECTIVES: There is convincing evidence that unsaturated fatty acids exert favourable effects on plasma cholesterol levels. However, it is not clear which type of oil has the most pronounced effect, especially not in paediatric patients. The aim was to compare two low-fat diet regimes enriched with either monounsaturated fatty acids by rapeseed oil (RO) or polyunsaturated fatty acids by sunflower oil (SO) in children affected with familial hypercholesterolaemia (FH). SUBJECTS/METHODS: Twenty-one children aged 6-18 years affected with FH were enrolled in this randomized and double-blind pilot trial. The subjects and their families were trained to adhere to a low-fat/low-cholesterol diet. All visible fats were to be replaced by either RO or SO (14-27 g/day) for 13 weeks. Dietary adherence was controlled by repeated 4-day dietary records; plasma lipids, lipoproteins and risk markers were assessed at baseline and post-intervention. Out of 21 subjects, 16 could be followed-up after 6 months. RESULTS: Both fat-modified diets resulted in significant reduction in total cholesterol concentrations of 9.4% (RO P<0.005 vs SO P<0.05) and low-density lipoprotein (LDL) cholesterol concentrations of 12.7% (P<0.005) for RO and 11.3% (P<0.05) for SO. The reduction of the LDL/high-density lipoprotein (HDL) cholesterol ratio (RO 9% vs SO 3.5%) and high-sensitivity C-reactive protein (RO 16.8% vs SO 1.7%) were not statistically significant, respectively. In most participating families, a change in eating habits could be observed. CONCLUSIONS: A fat-modified diet enriched with RO seems to have very similar effects on cholesterol levels as with SO. However, our study suggests that RO has possibly more favourable effects concerning cardiovascular risk profile. Both diets appear to be feasible and were well accepted among our subjects. Although these results are promising, larger trials will be required to validate our findings.

Liver transplantation for the treatment of homozygous familial hypercholesterolaemia in an era of emerging lipid-lowering therapies.

Homozygous familial hypercholesterolaemia (FH) causes severe premature coronary artery disease because of very high levels of low density lipoprotein (LDL)-cholesterol. Standard lipid-lowering drugs and LDL-apheresis may not be sufficiently effective. Liver transplantation replaces defective LDL receptors and vastly improves the lipid profile, and we present the first report of an Australian adult to receive this treatment. Emerging drug treatments for FH may be alternatives to LDL-apheresis and transplantation, but long-term safety and efficacy data are lacking for all of these options.

Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia.

BACKGROUND: A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolaemia (FH). However, a consensus has yet to be reached on the most appropriate dietary treatment. Plant sterols are commonly used in FH although patients may know them by other names like phytosterols or stanols. OBJECTIVES: To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register, which is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated with each new issue of The Cochrane Library), quarterly searches of MEDLINE and the prospective handsearching of one journal - Journal of Inherited Metabolic Disease. Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 22 August 2013. We also searched PubMed to 05 February 2012. SELECTION CRITERIA: Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial eligibility and risk of bias and one extracted the data, with independent verification of data extraction by a colleague. MAIN RESULTS: In the 2014 update of the review, 15 trials have been included, with a total of 453 participants across seven comparison groups. The included trials had either a low or unclear risk of bias for most of the parameters used for risk assessment. Only short-term outcomes could be assessed due to the short duration of follow up in the included trials. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included trials. No significant differences were noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found for the following comparisons and outcomes: for the comparison between plant sterols and cholesterol-lowering diet (in favour of plant sterols), total cholesterol levels, mean difference 0.30 mmol/l (95% confidence interval 0.12 to 0.48); decreased serum LDL cholesterol, mean difference -0.60 mmol/l (95% CI -0.89 to -0.31). Fasting serum HDL cholesterol levels were elevated, mean difference -0.04 mmol/l (95% CI -0.11 to 0.03) and serum triglyceride concentration was reduced, mean difference -0.03 mmol/l (95% CI -0.15 to -0.09), although these changes were not statistically significant. Similarly, guar gum when given as an add on therapy to bezafibrate reduced total cholesterol and LDL levels as compared to bezafibrate alone. AUTHORS' CONCLUSIONS: No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, for the primary outcomes: evidence and incidence of ischaemic heart disease, number of deaths and age at death,due to the lack of data on these. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein, dietary fibers to a cholesterol-lowering diet.

Successful outcome in a rare case of pregnancy with familial hypercholesterolemia and dilated cardiomyopathy.

Familial hypercholesterolemia is a rare disorder characterized by high cholesterol levels and early cardiovascular disease. Early detection and treatment with statins and other hypolipidemic agents are effective in heterozygous patients. Low-density lipoprotein apheresis and liver transplantation are treatment options in homozygous familial hypercholesterolemia. We report a case of a 27-year-old pregnant woman with familial hypercholesterolemia who presented with breathlessness and swelling in the joints. She had been taking statins previously, which were stopped and she had been put on low-lipid and low-residue diet to reduce the risk of acute coronary event and sudden intrauterine death. She was found to have dilated cardiomyopathy with 25% ejection fraction. At 36 weeks of gestation, we carried out cesarean section in view of poor biophysical profile. Familial hypercholesterolemia is a very rare disorder with only a few cases reported in the published work during pregnancy. Statins are contraindicated during pregnancy and diet modification remains the mainstay of therapy.

Emerging low-density lipoprotein therapies: Microsomal triglyceride transfer protein inhibitors.

Microsomal triglyceride transfer protein, which is localized in the endoplasmic reticulum of enterocytes and hepatocytes, is necessary for the formation of chylomicron and very low-density lipoprotein particles. Lomitapide is a small molecule microsomal triglyceride transfer protein inhibitor that was recently approved by the Food and Drug Administration as an adjunct to a low-fat diet and other lipid-lowering therapies for reducing low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (FH). Results from clinical trials of lomitapide have demonstrated its ability to reduce atherogenic lipoprotein concentrations in this population. Most recently, in a phase 3 clinical trial of 29 men and women with homozygous FH (mean baseline LDL-C, 336 mg/dL) who were on stable doses of concomitant lipid therapies and a low-fat diet, lomitapide was gradually titrated over 26 weeks (from 5 to 60 mg/d), followed by 52 weeks at the maximum tolerated dose. LDL-C decreased from baseline by 50% at 26 weeks, and reductions were maintained through the end of the study. Gastrointestinal disorders were the most frequent side effects and the most common reason for failure to tolerate lomitapide dose escalation. Few patients had elevated aspartate or alanine aminotransferases; bilirubin and alkaline phosphatase levels were unaffected; and hepatic fat increased by ≈ 10 g/100 g. In conclusion, recent data support the LDL-C-lowering efficacy of low-dose titrated lomitapide in patients with homozygous FH; however, concerns regarding increased hepatic fat will need to be addressed in long-term safety studies.