Adverse effects associated with peribulbar injection of triamcinolone for the treatment of thyroid eye disease: a retrospective case series.

PURPOSE: Peribulbar injection of triamcinolone is an alternative treatment for thyroid eye disease; however the safety profile of this therapeutic option remains controversial. The aim of this study was to describe the occurrence of local and systemic adverse effects after peribulbar injection of triamcinolone in patients with thyroid eye disease. METHODS: This was a retrospective case series. Medical records of patients with thyroid eye disease treated with peribulbar injections of triamcinolone at a single academic institution between 2007 and 2019 were analyzed. Local and systemic complications were documented. RESULTS: A total of 123 patients were treated. Only 11 patients (8.9%) developed local complications. The most frequent complication was the presence of superficial eyelid ecchymosis (nine patients; 7.3%). Notably, systemic complications (hyperglycemic and suprarenal inhibition after stop treatment) occurred in two patients (1.6%). All complications were transient, and the patients did not have any long-term sequelae. CONCLUSIONS: Peribulbar injection of triamcinolone for the treatment of thyroid eye disease is linked to a very low rate of local or systemic complications. Prospective studies are warranted to delve into this topic.

Adverse effects associated with peribulbar injection of triamcinolone for the treatment of thyroid eye disease: a retrospective case series / Efeitos adversos de injeções peribulbares de triancinolona na doença ocular da tireoide: estudo retrospectivo de uma série de casos

ABSTRACT Purpose: Peribulbar injection of triamcinolone is an alternative treatment for thyroid eye disease; however the safety profile of this therapeutic option remains controversial. The aim of this study was to describe the occurrence of local and systemic adverse effects after peribulbar injection of triamcinolone in patients with thyroid eye disease. Methods: This was a retrospective case series. Medical records of patients with thyroid eye disease treated with peribulbar injections of triamcinolone at a single academic institution between 2007 and 2019 were analyzed. Local and systemic complications were documented. Results: A total of 123 patients were treated. Only 11 patients (8.9%) developed local complications. The most frequent complication was the presence of superficial eyelid ecchymosis (nine patients; 7.3%). Notably, systemic complications (hyperglycemic and suprarenal inhibition after stop treatment) occurred in two patients (1.6%). All complications were transient, and the patients did not have any long-term sequelae. Conclusions: Peribulbar injection of triamcinolone for the treatment of thyroid eye disease is linked to a very low rate of local or systemic complications. Prospective studies are warranted to delve into this topic.

RESUMO Objetivo: A injeção peribulbar de triancinolona é um tratamento alternativo para doenças oculares da tireoide; no entanto, a segurança desse procedimento continua controversa. O objetivo deste artigo é descrever os efeitos adversos locais e sistêmicos de injeções peribulbares de triancinolona em pacientes com doença ocular da tireoide. Métodos: Estudo retrospectivo de uma série de casos. Foram analisados os prontuários médicos dos pacientes com doença ocular da tireoide tratados com injeções de triancinolona peribulbar em uma única instituição acadêmica entre 2007 e 2019. Foram documentadas as complicações locais e sistêmicas. Resultados: Um total de 123 pacientes foram tratados. Apenas 11 (8,9%) pacientes apresentaram complicações locais, sendo a mais frequente a presença de equimoses palpebrais superficiais (7,3%), enquanto 2 (1,6%) pacientes apresentaram complicações sistêmicas (hiperglicemia e inibição da suprarrenal após a interrupção do tratamento). Todas estas complicações foram transitórias e nenhum paciente apresentou sequelas de longo prazo. Conclusões: As injeções peribulbares de triancinolona nas doenças oculares da tireoide têm uma taxa muito baixa de complicações, tanto locais quanto sistêmicas. São necessários estudos prospectivos para aprofundar este tópico.

Genetic determinants of plasma HDL-cholesterol levels in prepubertal children.

INTRODUCTION: Genetic determinants have been related to variation of high-density lipoprotein cholesterol (HDL-C) levels, but the extension of this association remains controversial. In our study, we analyzed the contribution of several polymorphisms on HDL-C-related genes to variation of plasma HDL-C in prepubertal children. METHODS: We studied 1269 (641 males and 628 females) 6-8 years old healthy children, who participated in a cross-sectional study examining cardiovascular risk factors in Spain. Common genetic variants in the apolipoprotein AI, apolipoprotein AII, cholesteryl ester transfer protein (CETP), hepatic lipase, ATP-binding cassette transporter A1, and paraoxonase genes were determined by PCR. RESULTS: CETP TaqI B2 carrier girls had significantly higher HDL-C levels than B1B1 girls. B2B2 boys had significantly higher (p<0.001) HDL-C than B1B1and B1B2 boys. In linear regression analysis, CETP TaqIB appears as the main predictor of HDL-C plasma levels, accounting for 4.5% and 1.8% of HDL-C variation in girls and boys respectively. CONCLUSIONS: Our data showed that among the studied polymorphisms only the CETP TaqIB polymorphism contributes to the variation in HDL-C levels in prepubertal children, particularly in girls, but overall these polymorphisms explain a small part of the variation of HDL-C plasma levels at this age.

High-density lipoprotein cholesterol and paraoxonase 1 (PON1) genetics and serum PON1 activity in prepubertal children in Spain.

BACKGROUND: Oxidative stress plays an important role in atherosclerosis. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that inhibits low-density lipoprotein (LDL) oxidation and may play a protective role against coronary heart disease. The aim of this study was to analyze the relationship between HDL-cholesterol (HDL-C) and PON1 in a Spanish prepubertal population with high plasma HDL-C levels. METHODS: The study population included 1,266 children between the ages of 6 and 8 years. Serum PON1 activity was measured by the hydrolysis of paraoxon. PON1 192Q/R and PON1 55L/M polymorphisms were analyzed by PCR and restriction analysis. RESULTS: The prevalence of the less common PON1 192R and PON 55M alleles in this population was 30% and 38%, respectively. No significant correlations between serum PON1 activity and lipid profile were observed. Multiple linear regression analysis showed that the PON1 192Q/R polymorphism accounts for 69% of PON1 activity in the children in the study, with the PON1 55L/M polymorphism accounting for an additional 5% of this variation in boys, and for an additional 3% together with HDL-C concentration in girls. CONCLUSIONS: PON1 192Q/R polymorphism is the main determinant of PON1 activity in the prepubertal population in this study, accounting for around 70% of serum PON1 activity. HDL-C concentration has a small contribution to serum PON1 activity in girls.

Análisis de la actividad paraoxonasa (PON1) y de los polimorfismos PON1 192 y PON1 55 en la población prepuberal del Estudio Cuatro Provincias / Serum paraoxonase activity and PON1 192 and PON1 55 polymorphisms in prepuberal children. The Four Provinces S

Introducción. La paraoxonasa 1 (PON1) es una éster hidrolasa presente en las lipoproteínas de alta densidad (HDL), relacionada con la eliminación de componentes oxidados de las lipoproteínas de baja densidad (LDL) y por ello con el riesgo cardiovascular. Nuestro estudio analiza la actividad PON1 y los polimorfismos 192 y 55 del gen PON1 en los niños de edad prepuberal integrantes del Estudio Cuatro Provincias. Métodos. La población de estudio la constituyen 1.275 niños de 6 a 8 años. La actividad PON1 en suero se determinó mediante la hidrólisis de paraoxon. Los polimorfismos genéticos PON1 192Q/R y PON1 55M/L se analizaron mediante amplificación por reacción en cadena de la polimerasa (PCR) y posterior análisis de restricción. Resultados. En nuestra población la frecuencia de los alelos PON192R y PON55M es del 30 y el 38%, respectivamente, sin diferencias significativas entre provincias. La actividad PON1 es más elevada en Orense y más baja en Murcia, tanto en la población total como para cada uno de los genotipos. En la provincia de Orense se observaron correlaciones significativas entre la actividad PON1 y los valores plasmáticos de colesterol total (CT), colesterol unido a HDL (cHDL) y apolipoproteína AI (apo AI). El análisis de regresión muestra que el polimorfismo PON1 192Q/R es el principal determinante de la actividad PON1 en nuestra población. Conclusiones. La frecuencia de los polimorfismos PON192 y PON55 no difiere significativamente entre provincias. Sin embargo, a pesar de que el polimorfismo PON192 es el principal determinante de la actividad PON1, Orense presenta la actividad PON1 más alta y Murcia la más baja, lo que sugiere que ya a esta edad existen factores que regulan esa actividad dentro de cada genotipo (AU)

Background. Paraoxonase (PON1) is an ester hydrolase related to the elimination of oxidized compounds of low-density lipoprotein (LDL) particles and therefore to cardiovascular risk. The aim of the present study was to analyze the relationship between serum PON1 activity and PON1 192 and 55 polymorphisms in the prepuberal children included in the Four Provinces Study. Methods. The study population included 1,275 children aged 6 to 8 years old. Serum PON1 activity was measured by paraoxon hydrolysis. PON1 192Q/R and PON1 55M/L polymorphisms were analyzed by polymerase chain reaction and restriction analysis. Results. In the population as a whole, the prevalence of the less common PON192R allele was 30% and that of the PON55M allele was 38%, without significant differences in the frequencies between provinces. PON1 activity was highest in Orense and lowest in Murcia, both in the group as a whole and within each genotype. In Orense, significant correlations between PON1 activity and plasma total cholesterol, high-density lipoprotein cholesterol and apolipoprotein AI levels were found. Regression analysis showed that the PON1 192Q/R polymorphism is the main determinant of PON1 activity in our population. Conclusions. No significant differences between provinces in the frequencies of the PON192 and PON55 polymorphisms were found. However, although the PON192 polymorphism is the main determinant of PON1 activity, Orense showed the highest activity and Murcia the lowest for all the genotypes, suggesting that already at this age some factors are regulating PON1 activity for each genotype (AU)

Dehydroepiandrosterone sulfate and high-density lipoprotein-cholesterol levels in overweight children.

OBJECTIVE: The association of childhood overweight with cardiovascular risk factors seems to change by sex and age, which may indicate that hormonal status could be the cause of this different association. In this study, we analyzed the relationship of dehydroepiandrosterone sulfate (DHEA-S) with the alterations associated with overweight by analyzing the influence of this hormone in the differences found in biochemical variables between normal-weight and overweight prepubertal children. RESEARCH METHODS AND DESIGN: The study included 684 6- to 8-year-old children (350 boys and 334 girls) categorized by the presence or absence of overweight, according to the age- and sex-specific cut-off points proposed for children. Lipid levels were determined by standard methods. DHEA-S and insulin levels were measured by radioimmunoassay. Biochemical variables were compared between normal-weight and overweight children by tertiles of DHEA-S. RESULTS: We observed that plasma high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein (apo)-AI levels were significantly lower in overweight than in normal-weight boys only in the highest tertile of DHEA-S. No significant differences in plasma glucose levels, total cholesterol, low-density lipoprotein-cholesterol, or apo B were found between overweight and normal-weight children in any DHEA-S tertile. In a Spearman correlation analysis, we observed a significant and negative correlation for weight and BMI with HDL-C and for weight and apo-AI levels only in the highest tertile of DHEA-S. DISCUSSION: Our study showed that, in our prepubertal population, the association of overweight with decreased HDL-C and apo-AI levels was present only in boys within the highest levels of DHEA-S, supporting the importance of hormonal influences on the association of metabolic alterations with overweight.

Cholesterol and saturated fat intake determine the effect of polymorphisms at ABCG5/ABCG8 genes on lipid levels in children.

PURPOSE: Analysis of mutations in genes of the cholesterol metabolic pathway has not completely explained the interindividual variability of blood cholesterol concentrations attributed to gene-nutrient interactions. Thus, we analyzed polymorphisms in the ABCG5 and ABCG8 genes, involved in the regulation of intestinal cholesterol absorption, with special interest in a potential interaction with diet to determine lipid levels. METHODS: The polymorphisms ABCG5 C1950G (Gln604Glu) and ABCG8 C1895T (Ala640Val) were determined by polymerase chain reaction and restriction analysis in 1227 healthy school children, aged 6 to 8 years. RESULTS: No significant differences were found in blood lipid levels between subjects with different genotypes of the two analyzed polymorphisms. However, important differences appeared when separating subjects by their different lipid intake. The presence of the ABCG8 C1895T and ABCG5 C1950G polymorphisms was associated with different plasma total cholesterol, low-density lipoprotein cholesterol complex, and apolipoprotein B levels only in low-cholesterol consumers (significantly for the C1895T polymorphism), and among children within the lower tertile of saturated fat intake (significantly for the C1950G polymorphism). CONCLUSION: Polymorphisms at the half-transporter ABCG5 and ABCG8 genes affect blood cholesterol concentrations in prepubertal children by influencing dietary responsiveness. This highly significant gene-nutrient interaction could explain the great individual differences in the plasma lipid response to cholesterol and fat intake.

Dehydroepiandrosterone sulfate (DHEA-S) distribution in Spanish prepuberal children: relationship with fasting plasma insulin concentrations and insulin resistance.

BACKGROUND: The aim of this study was to analyze dehydroepiandrosterone sulfate (DHEA-S) levels in a population-based sample of Spanish prepuberal children and to investigate the relationship between DHEA-S and insulin. METHODS: 854 (440 boys and 414 girls) randomly selected prepuberal children were included in our study after a sampling. Children were 6 to 8 years old and were classified for the analysis in half-year intervals. DHEA-S and insulin levels were measured. RESULTS: DHEA-S levels increase significantly with age during prepuberty reaching the maximum level of DHEA-S for this period at 7.5 years old in girls and 8 years old in boys. Girls have significantly higher log DHEA-S levels than boys, except at the age of 8, where the levels are similar (median: 41.7 nmol/l girls and 41.1 nmol/l boys). DHEA-S correlates positively and significantly with weight, height, and BMI in all age intervals but the correlation between DHEA-S and insulin and HOMA is present only at the age of 6.5 in boys and 8 in girls. CONCLUSIONS: We report data about the distribution of DHEA-S in the Spanish prepuberal population. The maximum level of DHEA-S in this prepuberal period was reached before in girls than in boys, with girls having higher DHEA-S levels than boys until the end of this period. We found an important association between DHEA-S levels and weight, height and BMI but an inconsistent association of DHEA-S with insulin and HOMA.

epsilon3epsilon4 genotype as risk factor of myocardial infarction in middle-aged people in Spain.

Apolipoprotein E (apoE) plays an important role in lipid metabolism. Its epsilon4 allele has been consistently associated with lipoprotein disorders but its connection to myocardial infarction (MI) is controversial. Because epsilon4 frequency decreases with age we thought that the contradictory results in different studies could be due to the wide age range of the subjects included. To test our hypothesis, ApoE genotyping was performed in 474 MI cases and an analysis was performed by percentiles of age. The frequencies of epsilon3epsilon4 genotype and epsilon4 allele in the MI group as a whole (subjects aged 31 to 92) were not significantly different from those in our area general population. However, significant differences were observed when comparing by group of age. The frequencies decreased as age increased. The epsilon3epsilon4 and epsilon4 frequencies were significantly higher in MI subjects aged 31 to 56 than in subjects over 74. The epsilon3epsilon4 genotype prevalence in an age and sex matched control group of subjects aged 31 to 56 was significantly lower than in the 31-56 year-old MI group. In conclusion, our data shows different epsilon3epsilon4 and epsilon4 frequencies depending on the age range of the subjects with MI, being significantly higher in the middle-aged group. This finding may help explain the discrepancies between studies analyzing association between apoE genotype and MI, and emphasizes the idea of considering apoE genotype for prevention at early age.

Insulin and HOMA in Spanish prepubertal children: relationship with lipid profile.

OBJECTIVE: The effects of insulin or insulin resistance on the lipid profile seem to change with age. The aim of this study was to analyze insulin levels and an insulin resistance index and to investigate the relationship between these and the lipid profile in a population-based sample of Spanish prepubertal children. METHODS: 1048 (524 boys and 524 girls) randomly selected prepubertal children were studied. Children were 6 to 8 years old with a mean age of 6.7. Plasma lipid, FFA and insulin levels were measured. The homeostatic model assessment (HOMA) was calculated as an indicator of insulin resistance. RESULTS: When analyzing percentile values of insulin, HOMA and FFA by sex, we observed that girls had significantly higher insulin concentrations than boys (except at the 10th percentile) and significantly higher FFA (except at the 90th percentile) with no significant differences between sexes for HOMA. Multivariate regression analyses showed that insulin was positively associated with glucose, triglycerides and apoB in boys but not in girls, and negatively associated with FFA in both genders. CONCLUSIONS: We report here data about the distribution of insulin in the Spanish prepubertal population. The higher levels of insulin in prepubertal girls could indicate that girls start to be more insulin resistant than boys at this age, although other manifestations of insulin resistance are not yet detectable.

Obesity in Spanish schoolchildren: relationship with lipid profile and insulin resistance.

This article reports cross-sectional data from a total of 1048 children, 6 to 8 years of age, categorized by presence or absence of obesity, who participated in a voluntary survey of cardiovascular risk factors in Spain over the period of 1998 to 2000, to establish the relationship between obesity and its metabolic consequences at this age. The prevalence of obesity and overweight were 9.4% and 15.7%, respectively, in boys and 10.5% and 18.0%, respectively, in girls. We observed that, in both sexes, obese children had higher triglycerides and lower high-density lipoprotein-cholesterol levels than non-obese children. No differences were found in plasma glucose or low-density lipoprotein-cholesterol levels between normal and obese children. However, we observed that insulin levels and the homeostasis model assessment for insulin resistance were significantly (p<0.001) higher in obese children of both sexes but that free fatty acid levels were lower in obese children than in nonobese children, with a statistical significance in girls (0.72+/-0.30 vs. 0.61+/-0.16 mEq/liter). In summary, our survey found some metabolic consequences of obesity similar to those found in adults (elevated triglycerides, insulin, and the homeostasis model assessment for insulin resistance, and lower high-density lipoprotein-cholesterol). However, other features (glucose, total cholesterol, low-density lipoprotein-cholesterol, and free fatty acid levels) were found to behave differently, indicating that the association of obesity with risk factors seems to change as the children age and may depend on the chronology of sexual maturation.

Influence of apolipoprotein E genotype on fat-soluble plasma antioxidants in Spanish children.

BACKGROUND: Apolipoprotein (apo) E is a major determinant of plasma lipid concentrations, which in turn influence the plasma concentrations of various fat-soluble vitamins. OBJECTIVE: We aimed to analyze the effect of APOE genotype on fat-soluble antioxidant concentrations in children. DESIGN: A total of 926 healthy boys and girls aged 6-8 y were selected from 4 cities in Spain. APOE genotyping was carried out, and plasma concentrations of lipids, apolipoproteins, and lipid-soluble antioxidants were measured. RESULTS: Plasma lipid concentrations were strongly influenced by APOE genotype. The mean plasma concentration of alpha-tocopherol was 21.3 micromol/L, which is one of the highest values ever reported for a population of children. Although plasma concentrations of alpha-tocopherol, gamma-tocopherol, lycopene, and alpha-carotene varied significantly between subjects with different APOE genotypes, most of these differences disappeared after adjustment for lipoprotein-related covariates. Nevertheless, tocopherol concentrations remained elevated in individuals with the E2/2 genotype. Multivariate regression analysis showed interactions of APOE genotype with triacylglycerol and apo B in determining alpha-tocopherol concentrations. When subjects were stratified according to major apo E groups, apo B appeared to be the most important predictor of alpha-tocopherol concentrations in all groups, whereas triacylglycerol was identified only in carriers of the E2 allele. CONCLUSIONS: The association between APOE genotype and lipophilic antioxidant concentrations is dependent mainly on the effect of the polymorphism on lipoprotein concentrations. However, triacylglycerol plays a role in determining the variability of alpha-tocopherol concentrations in E2 carriers only. This suggests that the alpha-tocopherol content in each lipoprotein class varies according to APOE genotype.

Consistently high plasma high-density lipoprotein-cholesterol levels in children in Spain, a country with low cardiovascular mortality.

Coronary heart disease (CHD) mortality is relatively low in Spain compared with other developed countries and has remained low despite an apparent increase in mean plasma cholesterol concentration in adults over the last several years. It is accepted that pathologic processes related to arteriosclerosis development begin in childhood and seem to be related to the presence of cardiovascular risk factors at this age. High-density lipoprotein-cholesterol (HDL-C) levels in children have been inversely correlated with the incidence of coronary heart disease in the different countries studied. Childhood plasma lipoprotein profile might contribute to the low coronary heart disease mortality in Spain. Thus, we analyzed data on lipid levels over time in schoolchildren in Spain in the last decade. Plasma lipid levels were analyzed in prepuberal children (6 to 8 years) in 3 school-based surveys performed by our group in Madrid in 1987, 1993, and 1999. A significant increase in plasma total cholesterol (P < .05) and low-density lipoprotein-cholesterol (LDL-C) (P < .01) levels in prepuberal children was observed over the last decade. However, the mean concentration of plasma HDL-C remained stable and very high. These high levels of plasma HDL-C in Spanish school children may help to explain why the coronary heart disease mortality rate in Spain is low compared with that in other developed countries.

Effects of dehydroepiandrosterone-sulfate on the Apo E genotype influence on plasma lipid levels in prepubertal children.

Gender differences in the apolipoprotein (apo) E genotype effect on plasma lipid levels reported in adults have also been found in pre-pubertal children. In adults, the difference seems to be due to the influence of sexual hormones. The reason why this difference exits between pre-pubertal girls and boys, for whom those sexual hormones are not different, is unclear. However, there is an important difference in Dehydroepiandrosterone-sulfate (DHEA-S) levels between pre-pubertal boys and girls. To evaluate the influence of DHEA-S on apo E genetic determinants of plasma lipids levels in pre-pubertal children we measured plasma DHEA-S in 1045 healthy children (534 males and 511 females) 6 to 8 years old in which a different apoE influence on lipid levels had been reported between girls and boys. Our observations demonstrate that the extent of the lipid increasing or decreasing effects associated with each allele were modulated by DHEA-S. DHEA-S increases the hypolipemic effect of the epsilon2 allele and decreases the hyperlipemic effect of the epsilon4 allele. In conclusion, the interaction of apo E genotype and DHEA-S may represent a critical determinant of TC, LDL-C and apo B levels in children at the prepuberal age.

Consumption of bakery products, sweetened soft drinks and yogurt among children aged 6-7 years: association with nutrient intake and overall diet quality.

The present study tests the hypothesis that higher consumption of bakery products, sweetened soft drinks and yogurt is associated with higher intake of energy, saturated fats, sugars and worse overall diet quality among Spanish children. This is a cross-sectional study covering 1112 children aged 6.0-7.0 years in four Spanish cities. Nutrient and food intake were obtained through a food-frequency questionnaire, and overall diet quality calculated using the healthy-eating index (HEI) developed by Kennedy et al. (1995). Standardized methods were used to measure anthropometric variables. Associations of interest were summarized as the difference in nutrient and food consumption between the value of the fifth and the first quintile of consumption (dq) of bakery products, sweetened soft drinks or yogurt, adjusted for energy intake and BMI. Bakery products, sweetened soft drinks and yogurt supplied 15.5, 1.0 and 5.6 % energy intake respectively. Higher consumption of these three foods was associated with greater energy intake (P<0.001), but not with higher BMI. Consumption of bakery products was associated with the proportion of energy derived from intake of total carbohydrates (dq 4.5 %, P<0.001) and sugars (dq 2 %, P<0.001), but did not show association with the HEI. Consumption of sweetened soft drinks was associated with a lower consumption of milk (dq -88 ml, P<0.001) and Ca (dq -175 mg/d, P<0.001), and worse HEI (dq -2, P<0.01). Consumption of yogurt, while associated with higher energy intake from saturated fats (dq 1.77 %, P<0.001) and sugars (dq 2.02 %, P<0.001), showed no association with the HEI. Differences in the intake of nutrients and foods across quintiles of consumption of bakery products, sweetened soft drinks and yogurt were usually very small. We conclude that the impact of the consumption of bakery products, sweetened soft drinks and yogurt on the quality of the diet of Spanish children is only modest, although it may contribute to aggravating certain unhealthy characteristics of their diet, particularly excess energy, saturated fats and sugars. Therefore, consumption of bakery products and sweetened soft drinks should be moderated, and priority given to consumption of low-fat, low-sugar yogurt.

Influence of birth weight on the apo E genetic determinants of plasma lipid levels in children.

To evaluate the influence of birth weight on apolipoprotein (apo) E genetic determinants of plasma lipids levels in prepubertal children we studied 933 healthy children (491 males and 442 females) 6 to 8 years old (mean age of 6.7 y), whose weight was recorded at birth. Plasma lipid and apolipoprotein concentrations and apo E genotypes were determined. We observed a greater effect of the apo E polymorphism on total cholesterol (TC), LDL-cholesterol (LDL-C) and especially apo B levels in children with birth weight in the lower tertile compared with those with birth weights in higher tertiles. Taking the epsilon3 allele homozygosity as reference, in boys with birth weights in the low tertile the overall lowering effect of the epsilon2 allele on TC, LDL-C and apo B was greater (10.5% (p < 0.01), 20.2% (p < 0.01) and 18.8% (p < 0.01), respectively) than in those in the highest tertile (5.6% on TC, 10.3% on LDL-C and 12.6% (p < 0.01) on apo B). A similar trend in this effect between tertiles of birth weight was also observed in girls. For both sexes, linear regression analysis demonstrates a positive and significant interaction between birth weight and epsilon2, which may explain the fact that the decrease in TC, LDL-C and apo B associated with the epsilon2 allele is more marked the lower the birth weight. Taking into account the prevalence of apo E polymorphism, and that appears to be the main genetic factor affecting plasma lipids, the interaction of apo E genotype and birth weight could be an important determinant of TC, LDL-C and apo B levels, and, as a consequence, of atherosclerosis.

[Metabolic factors in school children population associated with adult cardiovascular mortality. Four provinces' study]. / Factores metabólicos en la población escolar asociados a mortalidad cardiovascular en los adultos. Estudio Cuatro Provincias.

BACKGROUND: Environmental factors in early stages of life may contribute to adult cardiovascular disease. We have examined certain anthropometric and biochemical variables in children aged 6-7 years from four Spanish provinces with high differences in mortality due to ischemic heart disease (IHD). PATIENTS AND METHOD: We performed a cross-sectional survey of 1,255 children (50.3% males) attending schools in Cádiz and Murcia provinces with a relatively high IHD mortality and Madrid and Orense provinces with a relatively low IHD mortality. Weight, body mass index (BMI) and prevalence of obesity were analyzed, and plasma glucose and lipid levels were measured by standardized methods. RESULTS: Compared with children in the two low-IHD-mortality provinces, those in the two high-IHD-mortality provinces had greater weight (p < 0.05) and BMI (p < 0.01) and higher prevalence of obesity (p < 0.01). Moreover, they had significantly higher (p < 0.01) plasma glucose, triglyceride and apo A-I levels. CONCLUSIONS: The higher prevalence of overweight and obesity, along with higher plasma glucose and triglyceride levels, in provinces with high coronary artery disease mortality indicates that children from these provinces are metabolically different from those in provinces with low coronary artery disease mortality. These alterations may thus contribute to the different IHD mortality in adulthood.

Factores metabólicos en la población escolar asociados a mortalidad cardiovascular en los adultos. Estudio Cuatro Provincias / Metabolic factors in school children population associated with adult cardiovascular mortality. Four Provinces Study

FUNDAMENTO: Existen evidencias sobre la contribución de factores ambientales en etapas tempranas de la vida a la aparición de la enfermedad cardiovascular en la edad adulta. Por ello, en el presente trabajo hemos examinado variables antropométricas y bioquímicas en niños de 6-7 años de cuatro provincias españolas con una gran variación en la mortalidad por cardiopatía isquémica (CI). PACIENTES Y MÉTODO: Estudio transversal en 1.255 niños en edad escolar (50,3 por ciento varones) de Cádiz y Murcia, provincias con alta mortalidad por CI, y de Madrid y Orense, provincias con baja mortalidad por CI, en los que se han analizado peso, índice de masa corporal (IMC) y prevalencia de obesidad, y se han determinado los valores plasmáticos de glucosa y el perfil lipídico mediante métodos estandarizados. RESULTADOS: Los niños de las provincias con mayor mortalidad tienen mayor peso (p < 0,05), IMC (p < 0,01) y prevalencia de obesidad (p < 0,01). Además, presentan valores plasmáticos significativamente más altos (p < 0,01) de glucosa, triglicéridos y apo A-I. CONCLUSIONES: La mayor prevalencia de sobrepeso y obesidad, junto con los elevados valores de glucosa y triglicéridos asociados a las provincias de alta mortalidad, indica que los niños de estas provincias son metabólicamente distintos de los de provincias de baja mortalidad. Estas alteraciones podrían contribuir a la distinta mortalidad cardiovascular en la edad adulta. (AU)