Hipercolesterolemia en los padres e historia dínica familiar como predictores de hipercolesterolemia en los hijos / Parental hypercholesterolemia and family medical history as predictors of hypercholesterolemia in their children

Introducción.La hipercolesterolemia en los padres sería mejor predictor de hipercolesterolemia en niños que la historia clínica familiar. Objetivos. Comparar las fuerzas de asociación y los valores de predicción de la hipercolesterolemia en padres y la historia clínica familiar positiva con la hipercolesterolemia en hijos. Material y métodos. Estudio analítico, transversal. Se dosó colesterolemia en niños ≥ 6 y < 12 años y sus padres biológicos. Se realizó una encuesta a los padres. Se evaluó la asociación mediante el cálculo de odds ratio. Se determinó su valor de predicción. Se estudió la relación entre la hipercolesterolemia en padres y en hijos usando la regresión multinivel. Resultados. Se evaluaron 332 niños, 304 madres y 206 padres. El análisis entre uno/ambos progenitores con colesterolemia ≥ 240 mg/dl y niños ≥ 200 mg/dl mostró OR= 6,40; IC95 % =2,85-14,48; p <0,0001; sensibilidad= 69 %; espedhcidad= 74 %; valor predictivo positivo (VPP)= 34 %; valor predictivo negativo (VPN)= 93 %; razones de verosimilitud positiva (RVP)= 2,69; negativa (RVN)= 0,42. La historia clínica familiar vs. niños con colesterolemia ≥ 200 arrojó OR= 1,86; IC95 %= 0,84-4,11; p= 0,1272; sensibilidad= 69 %; especificidad= 46 %; VPP= 19 %; VPN= 89 %; RVP= 1,27; RVN= 0,68. Los hijos tuvieron 2,9 y 2,5 más mg/dl de colesterol por cada 10 mg/dl de aumento en colesterol en madres y padres, respectivamente. Conclusiones: La hipercolesterolemia en padres se asoció significativamente con la hipercolesterolemia en hijos y mostró mayor poder de predicción que la historia clínica familiar positiva.

Introduction. Parental hypercholesterolemia would be a better predictor of hypercholesterolemia than family medical history in children. Objectives. To compare the strength of association and predictive values of parental hypercholesterolemia versus a positive family history in pediatric hypercholesterolemia. Material and methods. Cross-sectional, analytical study. Cholesterol levels were measured in children aged ≥ 6 and < 12 years and in their biological parents. A survey was administered to parents. The association was estimated using the odds ratio (OR), and its predictive value was determined. The relationship between hypercholesterolemia in parents and their children was studied with multilevel regression. Results. A total of 332 children, 304 mothers, and 206 fathers were assessed. A cholesterol level ≥ 240 mg/dL in one or both parents and ≥ 200 mg/dL in children showed: OR= 6.40; 95 % confidence interval (CI)= 2.85-14.48; p < 0.0001; sensitivity= 69 %; specihcity= 74 %; positive predictive value (PPV)= 34 %; negative predictive value (NPV)= 93 %; positive likelihood ratio (LR+)= 2.69; negative likelihood ratio (LR-)= 0.42. Family medical history versus children with cholesterol level ≥ 200 showed: OR= 1.86; 95 % CI= 0.84-4.11; p= 0.1272; sensitivity= 69 %; specihcity= 46 %; PPV= 19 %; NPV= 89 %; LR+= 1.27; LR-= 0.68. Cholesterol was 2.9 and 2.5 mg/dL higher per every 10 mg/dL of increased cholesterol in mothers and fathers, respectively. Conclusions: Parental hypercholesterolemia was significantly associated with hypercholesterolemia in children and showed a higher predictive power than a positive family medical history.

Statin Treatments And Dosages In Children With Familial Hypercholesterolemia: Meta-Analysis / Tratamentos e Dosagens de Estatinas em Crianças com Hipercolesterolemia Familiar: Uma Meta-Análise

Abstract Background: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. Objective: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. Methods: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO and LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. Results: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. Conclusion: Statin treatment is efficient in lowering lipids in children with FH. There is need of large, long-term and randomized controlled trials to establish the long-term safety of statins.

Resumo Fundamentos: Crianças com hipercolesterolemia familiar podem desenvolver dano endotelial precoce, aumentando o risco de desenvolver doenças cardiovasculares. As estatinas tiveram sua eficácia em diminuir níveis de colesterol LDL e eventos cardiovasculares em adultos comprovada. O efeito das estatinas na população pediátrica não está claramente demonstrado. Objetivo: Revisar sistematicamente a literatura para avaliar os efeitos e a segurança de diferentes estatinas e suas dosagens nos níveis de colesterol total em crianças e adolescentes com hipercolesterolêmica familiar. Métodos: Artigos publicados desde o início até fevereiro de 2016 foram pesquisados nas bases PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO e LILACS. Dois revisores independentes avaliaram a qualidade dos estudos incluídos. Realizamos meta-análise com efeitos aleatórios e variância inversa. Análises de subgrupos foram realizadas. Resultados: Dez ensaios envolvendo 1.543 pacientes preencheram os critérios de inclusão. Em nosso estudo, as análises demostraram reduções nos níveis de colesterol, de acordo com a intensidade das doses de estatina (alta, intermediária e baixa): (-104,61 mg/dl, -67,60 mg/dl, -56,96 mg/dl) e no nível de lipoproteínas de baixa densidade: [-105,03 mg/dl (IC95% -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (IC95% -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (IC95% -67.83, -50.11), I2 93,8%. A duração da terapia com estatina variou de 8 a 104 semanas, impedindo conclusões sobre os efeitos a longo prazo. Conclusão: O tratamento com estatinas é eficiente na redução de lipídios em crianças com hipercolesterolemia familiar. É necessário realizar ensaios controlados randomizados de longo prazo para estabelecer a segurança do uso de estatinas a longo prazo.

Two novel mutations in exon 3 and 4 of low density lipoprotein [LDL] receptor gene in patients with heterozygous familial hypercholesterolemia

To determine the common mutation of low density lipoprotein receptor in hypercholesterolemja patients requiring screening for heterozygous familial hypercholesterolemia [HeFH] in Karachi. Case-series. Dr. Ziauddin Hospital Laboratory and Dr. Rubina Ghani's Pathological and Molecular Laboratories, Karachi, for the PCR bench work from June 2008 to October 2009. All the patients selected for this study were from Dr. Ziauddin Hospital and National Institute of Cardiovascular Diseases. All the patients having high total cholesterol and LDL-cholesterol were included in this study with premature coronary artery diseases or a family history of hypercholesterolemia. Exclusion criteria included Diabetes mellitus, hypertension, renal disease, hypothyroidism and steroid therapy. After lipid profile with overnight fasting, DMA was extracted from whole blood collected in EDTA [ethylenediamine tetra acetic acid] tube and multiplex PCR [polymerase chain reaction] using forward and reverse primers of exons 3, 4, 9 and 14 of base pairs 162, 431, 550 and 496 respectively. Out of total of 120 hypercholesterolemia cases, 42 patients were classical cases of HeFH [heterozygous familial hypercholesterolemia] with xanthomas, xanthelasmas and LDL-C > 160 mg/dl. The total cholesterol [260 +/- 57 mg/dL] and LDL-C [192 +/- 39 mg/dL] of cases was significantly high as compared to, controls having total cholesterol [184 +/- 27 mg/dL] and LDL-C [105 +/- 22 mg/dL], p > 0.001. Two novel point mutations were noted in exon 3 and exon 4. The other 78 cases were probable with raised LDL-C [low density lipoprotein cholesterol] and family history of premature coronary heart diseases. The frequency of HeFH was 35% classical and 65% probable cases out of total 120 hypercholesterolemia patients from two tertiary care hospitals in Karachi. The point mutation on exon 3 and exon 4 of LDLR gene was the most common. PCR is useful for the detection of large re-arrangements in the LDL-receptor gene and is a rapid and reliable method for diagnosis of familial hypercholesterolemia

Evoluçäo clínica de pacientes com hipercolesterolemia familiar e doença coronaria submetidas a derivaçäo ileal parcial (bypass ileal) / Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery

Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy), or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years) showed a mean 30 percent reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease

Effects of a vegetarian diet vs. a vegetarian diet enriched with avocado in hypercholesterolemic patients

To determine the effects of a vegetarian diet with avocado as a source of monounsaturated fat on serum lipids, thirteen patients with phenotype II (twelve with IIa and one with IIb) dyslidipidemia were included in a prospective, transversal and comparative study in chich three four-week diets randomly assigned were assessed. One vegetarian diet (ALVD) was composed of 70 percent carbohydrates, 10 percent proteins and 20 percent lipids. another was composed of 60 percent carbohydrates, 10 percent proteins and 30 percent lipids, 75 percent of which was supplied by avocado (AVD). A third diet was an avocado-added free diet (FDWA). Body wight, body mass index (BMI), and serum lipids (total cholesterol (TC), high (HDL) and low density lipoprotein (LDL) cholesterol and triglycerides (TG) were evaluated. AVD produced a significant decrease in LDL. ALVD did not change TC and LDL, while FDWA increased them slightly. The three diets reduced TG levels, but only ALVD did so significantly. All three diets reduced HDL levels, particularly ALDV, which produced the greatest reduction. Low-fat carbohydrate-rich vegetarian diets may be harmful to hypercholesterolemic patients. The avocado addition to a vegetarian diet does not correct these undesirable effects. To obtain beneficial effects on lipid profiel with avocado, lower amounts of carbohydrates and polyunsaturated fatty acids are probably needed

Platelet aggregation and lipoprotein leves in a patient with familial hypercholesterolemia after sective LDL-apheresis

Platelet aggregation was studied in a patient with familial hypercholesterolemia immediately after aphereis selective for low-density lipoprotein (LDL), a lipid-lowering procedure. This treatment reduced plasmatic levels of total and LDL-cholesterol, apo B, and triglyceride. Increased platelet aggregation was reduced immediately after the apheresis in whole blood as well as in platelet-rich plasma. However, aggregation in washed platelets remained unchanged after LDL-apheresis. In conclusion, in this patient reduction of LDL-cholesterol improved platelet function in the very short term.

Pérfil lipídico en sangre de cordón de recién nacidos normales y con alguna patología fetal y/o materna / Lipid profile in cord blood of normal newborns with some fetal and/or maternal pathology

Se realizaron determinaciones lipídicas en sangre de cordón de recién nacidos (RN) de ambos sexos, normales (n = 30) y con morbilidad neonatal o materna (n = 67), obtenida inmediatamente después del parto. Se consideró como RN sano una edad gestacional entre 38 y 41 semanas, peso > 2.500 g, Apgar > 7, así como ausencia de morbilidad perinatal, malformaciones congénitas y patología materna, como hipertensión arterial o diabetes. Las patologías consideradas fueron: grandes para edad gestacional, pretérmino, hipertensión materna, Apgar < 7, gemelos de pretérmino y otras. Al comparar los promedios de CT en los RN de pretérmino,Apgar < 7 con los RN normales (73 ñ 29; 73 ñ 24; 59 ñ 14 mg/dl) se encontró una diferencia significativa (p < 0.05). Para los promedios de los RN con HTA materna más pretérmino y gemelos de pretérmino (100 ñ 7; 104 ñ 26 mg/dl) la diferencia estadística fue mayor (p < 0,001). En estos dos últimos grupos, también se encontró diferencia significativa para el C-LDL (p < 0.001) (52 ñ 14; 64 ñ 24 mg/dl) comparado con RN normales (27 ñ 10 mg/dl). En los TG, fueron significativamente diferentes los promedios de los RN con HTA materna más pretérmino (58 ñ 51 mg/dl) y los con Apgar < 7 (45 ñ 47 mg/dl) comparados con RN normales (25 ñ 13 mg/dl) (p < 0,001 y p < 0,05 respectivamente). Siendo la hipercolesterolemia familiar el trastorno de las lipoproteínas más frecuente reconocido en la niñez,es importante su detección a edad temprana, así como saber diferenciarla de los niveles altos de colesterol, producto de alguna patología fetal o materna

Expression of low density lipoprotein receptors in lymphoblasts induced by anti-CD3 antibody in patients with hypercholesterolemia

Familial hypercholesterolemia(FH) is a disease based on defects of low-density lipoprotein receptors(LDL-R). To interrupt and control the natural course of this disease, early identification of these patients is important. The routine lipid profile tests for hypercholesterolemia can not differentiate objectively FH from secondary hypercholesterolemia. The exact diagnosis of FH heterozygotes is especially essential because it is easier to develop premature coronary heart diseases compared with secondary hyper-cholesterolemia. A simplified rapid and precise method for the mass screening of FH patients and the differentiation between FH heterozygote and secondary hyperlipidemia was needed. For the test, lymphocytes were used as target cells in LDL-R assay. After a 5 day culture with anti-CD3 Ab as a mitogen, indirect immunofluorescence stain and flow cytometric analysis were applied. The results were as follows; 74 +/- 9% of the stimulated lymphoblasts from normal controls expressed LDL-R activity. Cultured, but unstimulated, lymphocytes of normal controls showed 27 +/- 8% positivity and total cultured lymphocytes showed positivity of 46 +/- 11% positivity. Lymphoblasts, unstimulated lymphocytes, and total cultured lymphocytes from hyper-cholesterolemia without FH showed 74 +/- 10%, 25 +/- 10% and 50 +/- 17%, respectively, which showed no significant differences from normal control groups. FH Heterozygotes showed LDL-R positivity, 21 +/- 11% in lymphoblasts, 11 +/- 6% in unstimulated lymphocytes and 18 +/- 7% in total cultured lymphocytes. These data imply that adequately stimulated lymphocytes might be used for detecting defects in LDL-R and used to differentiate FH from secondary hypercholesterolemia.

Colesterol-IDL y/o colesterol-ß-VLDL: un nuevo parámetro en diferentes fenotipos lipoprotéicos / IDL- an/or ß-VLDL cholesterol: a new parameter in different lipoproteic phenotypes

IDL y/o ß-VLDL son consideradas una lipoproteína aterogénica. Nuestro objetivo es evaluar su concentración plasmática en diferentes fenotipos primarios y secundarios de dislipemia (según OMS). Se definió normolipemia de acuerdo a colesterol (C) total *200 mg/dl, triglicéridos *170 mg/dl, C-LDL *160 mg/dl, C-HDL *40 mg/dl y ausencia de "ß-ancha" en el lipodograma electroforético. El percentilo 90 de la concentración de C-IDL previamente hallado en 30 controles sanos fue 12 mg/dl. Los datos obtenidos no reflejan necesariamente la distribución de fenotipos y patologías en la población general, debido a que se obtuvieron en un laboratorio de referencia. Entre 99 pacientes normolipénicos (NL), cuya Xñ DS fue de 8,8 ñ 6,5 mg/dl, se encontró un subgrupo de 22 con C-IDL > 12 mg/dl cuya Xñ DS fue 18,7 ñ 5,3 mg/dl. En el fenotipo IIa la Xñ fue 12,3 ñ 8,3 mg/dl (n=40). En el fenotipo IIb la Xñ DS fue 16,4 ñ 7,9 mg/dl (n=20). Los fenotipos III y V presentaron en todos los casos C-IDL elevado (Xñ DS = 64,6 ñ 28,6 y 19,2 ñ 3,2 mg/dl respectivamente). En el fenotipo IV la Xñ DS fue 22,6 ñ 11,6 mg/dl (n=10). Todos los fenotipos presentaron C-IDL mayor que los NL (p<0.05 o menor, test U-Mann Whitney). El 22%de los pacientes "aparentemente" NL tenían C-IDL > 12 mg/dl, siendo éstos postmenopáusicas, diabéticos u obesos. De estos datos surge la conveniencia de incluir la medida de C-IDL en el seguimiento de estas patologías y de los fenotipos IIb, III, IV y V

Electroforesis de lipoproteínas en gel de agarosa / Lipoproteins in agar gel electrophoresis

Los perfiles de los tipos clásicos mencionados pueden encontrarse en forma aislada o en diversas combinaciones. Muchas veces el perfil resulta limítrofe entre dos clasificaciones, siendo difícil incluirlo en uno de los dos tipos. Este problema se presenta en el 10%de las muestras

Homozygous familial hypercholesterolaemia. Report of three cases.

Homozygous familial hypercholesterolaemia is a rare disorder encountered in one in a million in the general population. Case reports of three patients from two families are presented. A 25 year male presented with extensive myocardial infarction and had a fatal outcome. His younger brother (14 years), as also a 12 year girl from another family with multiple planar xanthomata and tuberose xanthomata, are presented.

Familial hypercholesterolaemia--report of two cases.

Two young female patients aged 12 and 20 years with homozygous familial hypercholesterolaemia are presented with autopsy reports. Both had extensive coronary artery disease with myocardial infarction and tendon xanthomas. The first case had additional aortic stenosis.

Infarto del miocardio y tendinitis aquiliana como manifestaciones de hipercolesterolemia familiar / Myocardial infarction and Achilles tendinitis as manifestations of familial hypercholesterolemia

La hipercolesterolemia familiar (HF) es un trastorno genetico caracterizado por disminucion de los receptores para LDL colesterol que se manifiesta por aumento de los niveles plasmaticos de LDL, enfermedad coronaria (EC) prematura y manifestaciones osteoarticulares como xantomas tendinosos y artritis. Se informa el caso de un hombre de 30 anos, sin antecedentes reumatologicos ni cardiovasculares, quien concomitantemente presento infarto agudo del miocardio (IM) y tendinitis aguda del Aquiles. Las caracteristicas clinicas y el patron lipidico fueron compatibles con HF (hiperlipoproteinemia IIa). Se discuten las caracteristicas clinicas del paciente y las manifestaciones reumatologicas de las hiperlipoproteinemias

Familial hypercholesterolemia (FH) is a genetic disorder characterized by a decrease in LDL cholesterol receptors; patents exhibit increased plasmatic LDL levels, early coronary artery disease and osteoarticular manifestations such as tendinous xanthomata and arthritis. We report the case of a thirty year-old man wlth no cardiovascular or rheumatologic history who presented with concomitant acute myocardial Jnfarctlon and acute Achilles'' tendinitis. Clinical features and lipid work-up were consistent with FH (Hyperlipoproteinemia IIa).