High tracking of apolipoprotein B levels from the prepubertal age to adolescence in Spanish children.

AIM: To assess tracking of lipid and apolipoproteins from the prepubertal age (baseline, 6-8 years old) to adolescence (follow-up, 13-16 years old) in Spanish children. METHODS: The sample population included 385 healthy children (179 boys and 206 girls). Tracking was estimated by correlations between baseline and follow-up levels, multiple regression models in which the follow-up lipid was the dependent variable and analysing the percentage of individuals who remained in the same lipid levels status from prepubertal age to adolescence. RESULTS: Correlations between baseline and follow-up levels for low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apo B) were stronger in boys and for high density lipoprotein-cholesterol and apo A-I stronger in girls. Regression analyses showed that, after adjusting by body mass index (BMI), baseline LDL-cholesterol and apo B levels explain 23% and 39% of the variation of follow-up LDL-cholesterol and apo B levels, respectively, in boys and 13% and 22%, respectively, in girls. The strength of tracking for LDL-cholesterol and apo B was 79% and 89%, respectively, in boys and 72% and 82%, respectively, in girls. CONCLUSION: Apolipoprotein B showed the strongest tracking in both sexes, stronger than for LDL-cholesterol, which supports the importance of determining apo B levels as a marker of dyslipidaemia in children.

Association of the Q223R polymorphism with age at menarche in the leptin receptor gene in humans.

Although genetics clearly influences the onset of menarche, the association of age at menarche (AAM) with variants in genes related to energy homeostasis remains unexplored. Our aim was to analyze the relationship of the Q223R polymorphism in the leptin receptor gene (LEPR(Q223R)) with AAM in a population-based sample of healthy pubertal girls. The study included 338 Spanish girls aged between 11 and 17 yr. Data were collected on AAM. The Q223R polymorphism in LEPR was detected by TaqMan allelic discrimination assays. Girls carrying the RR genotype had a significantly younger AAM (11.5 yr) than those carrying the QR (11.9 yr) or QQ (12.0 yr) genotype (P < 0.05). Furthermore, we found a significantly higher frequency of the RR genotype in girls with an AAM of 11 yr or younger than in girls with an AAM older than 12 yr (23.9% vs. 7.8%, χ(2) = 11.17, P = 0.0008). Also, the RR genotype frequency in girls with an AAM between 11 and 12 yr was significantly higher than in girls with an AAM older than 12 yr (16.8% vs. 7.8%, χ(2) = 3.97, P = 0.0046). The Q223R polymorphism in the LEPR gene is associated with variations in AAM among Spanish girls, with the RR genotype being related to earlier onset.

Sex-specific association between leptin receptor polymorphisms and leptin levels and BMI in healthy adolescents.

AIM: To examine the relationship of three common polymorphisms in the leptin receptor (LEPR) gene, implicated in the regulation of body weight, with leptin levels and obesity-related phenotypes in a population-based sample of healthy pubertal children in Spain. METHODS: The study included 806 boys and girls aged 12-16 whose anthropometrical data and body composition were recorded. Serum leptin levels were determined by ELISA. The LEPR Q223R, K109R and K656N polymorphisms were determined by TaqMan® allelic discrimination assays. RESULTS: When analysing the Q223R polymorphism, we observed that female carriers of the RR genotype had significantly higher plasma leptin levels (18.2 vs. 15.1 ng/mL p = 0.016) and significantly higher mean BMI values (22.5 vs. 21.3 Kg/m² p = 0.032) than QR carriers. Furthermore, the frequency of the RR genotype in overweight-obese girls was significantly higher than that found in normal-weight girls. No significant differences were observed in boys. Neither boys nor girls showed significant differences when comparing leptin levels, anthropometric variables or body composition by K109R or K656N genotype. CONCLUSION: The fact, that the Q223R polymorphism in the LEPR gene is significantly associated with leptin levels and BMI only in girls, suggests a sex-specific influence of this polymorphism on these variables.

[Serum vitamin B12 levels in an adolescent population in Madrid]. / Concentración de vitamina B12 en suero en población puberal de la Comunidad de Madrid.

INTRODUCTION: Serum vitamin B12 concentration levels in children are essential to establish values in order to compare different regions or countries, and for considering e the possibility of supplementing diets with group B vitamins as a secondary prevention against cardiovascular diseases. MATERIAL AND METHODS: A cross-sectional epidemiological study was carried out to asses serum vitamin B12 levels in school children, 13-15 years of age, in Madrid. Folate and vitamin B12 vitamin determinations were performed on fasting blood samples. Genotype C677T of methylentetrahydrofolate reductase (MTHFR) enzyme was determined by PCR. RESULTS: The mean vitamin B12 level obtained in our study was 503 pmol/l; CI 95 % CI (478-528 pmol/l). The median was 471 pmol/l; interquartile range (IR) (337-632 pmol/l). No statistically significant differences were found by age or C677T genotype for MTHFR. Serum vitamin B12 concentrations were significantly higher in females. Prevalence of vitamin B12 deficiency (< 224 pmol/l) was 6 % in males and 4 % in females. CONCLUSIONS: Reference values for serum vitamin B12 concentrations in an adolescent population are presented. Prevalence of vitamin B12 deficiencies is higher in males.

Effects of long-term monounsaturated- vs polyunsaturated-enriched diets on lipoproteins in healthy men and women.

The effect of dietary-fat saturation on plasma lipoprotein concentrations was assessed in 46 men and 32 women placed on a diet enriched in polyunsaturated fatty acids (sunflower oil) for 12 wk and, under isocaloric conditions, on a diet enriched in monounsaturated fatty acids (olive oil) for the next 16 wk in men and 28 wk in women. Fat comprised 37% of the total energy intake in men and 36% in women. At the end of the monounsaturated fatty acid diet no change occurred in total cholesterol (TC) in men but it increased by 9% in women. High-density-lipoprotein (HDL) cholesterol increased by 17% in men and by 30% in women. The atherogenic index (TC:HDL cholesterol) fell significantly in both sexes. No significant changes occurred in plasma low-density-lipoprotein cholesterol or in total triglycerides values. These data show that when compared with polyunsaturates, monounsaturates increased HDL cholesterol and reduced the atherogenic risk profile in both sexes.

Effect of dietary monounsaturated fatty acids on plasma lipoproteins and apolipoproteins in women.

To determine the effects of dietary fat saturation on plasma lipoproteins, we studied 21 free-living normolipidemic women (13 pre- and 8 postmenopausal) on three consecutive diet periods. During the first 4 wk they consumed a saturated diet rich in palm oil and butter [19% saturated fatty acids (S), 14% monounsaturated fatty acids (M), and 3.5% polyunsaturated fatty acids (P)], followed by 6 wk of a monounsaturated diet rich in olive oil (11% S, 22% M, and 3.6% P), and 6 wk of a polyunsaturated diet rich in sunflower oil (10.7% S, 12.5% M, and 12.8% P). Compared with the diet rich in saturated fatty acids, both diets rich in unsaturated fatty acids had similar lowering effects on total and low-density-lipoprotein cholesterol. High-density lipoprotein cholesterol and apolipoprotein A-I were higher in the monounsaturated-rich period than in the polyunsaturated-rich (10.5% and 12.7% respectively, P less than 0.001) and the saturated-rich period (5.3%, and 7.9%, respectively, P less than 0.05). These effects were independent of menopause status. Our data show that at this level of fat intake (36% as calories), a monounsaturated-rich diet results in a less atherogenic lipid profile than either polyunsaturated- or saturated-rich diets.

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Pirifibrate in the treatment of hyperlipoproteinemias: a multicenter study.

Pirifibrate, a new hypolipemic substance, was studied in a multicenter trial for three months in 151 patients diagnosed as having type IIa, IIb or IV hyperlipoproteinemia (HLP). The patients admitted into the study had not received any hypolipemic medication for four weeks immediately before the study. We observed falls of between 24.3% and 20.0% in the average levels of plasma cholesterol in types IIa and IIb HLP. The triglycerides showed a decrease in average values, which varied between 31.0% and 38.6% in types IIb and IV HLP. The alpha-lipoproteins always increased in three types of HLP studied, while the pre-beta-lipoproteins showed a fall in averages in types IIb and IV HLP. The beta-lipoprotein levels were reduced in type IIa HLP and reached statistical significance.

Spanish children's diet: compliance with nutrient and food intake guidelines.

OBJECTIVE: To compare the diet of Spanish children against the nutrient and food intake guidelines. To calculate an index of overall diet quality and check its validity against nutrient intake. DESIGN AND SETTING: Cross-sectional study in four cities in Spain, where information on food and nutrient intake was obtained from schoolchildren through a food frequency questionnaire. PARTICIPANTS: The sample included 1112 children (overall response rate of 85%) attending public and private schools and aged 6-7 y. Children were selected through random cluster sampling in schools, and stratified by sex and socioeconomic level. MAIN OUTCOME MEASURES: Mean nutrient intake, number of food servings, and the percentage of children who meet recommended nutrient and food-serving intake levels. The overall dietary quality was assessed using the Healthy Eating Index (HEI). RESULTS: Mean micronutrient intake exceeded 100% of the recommended dietary allowances, except for vitamin B6, which registered a mean intake of 77.1%. For almost all children, intake of saturated fat was above, and that of carbohydrate below, the recommended level, in contrast to the relatively high compliance with the recommendations for poly- and monounsaturated fatty acid, salt and fiber intake (69.7, 43.7, 40.7, and 30.1%, respectively). Consumption of food servings for each of the five American pyramid food groups came close to or exceeded USDA guidelines, with the exception of cereals, with 5.4 servings per day. The mean score obtained in the HEI was 64.6. Children who complied with all the food guide pyramid recommendations registered a higher dietary variety and a healthier nutritional profile. CONCLUSIONS: Children aged 6-7 y show scant compliance with the macronutrient goals for healthy eating. Micronutrient intake is adequate in general, yet there are small groups of children with risk of deficient intake of vitamins B6 and D. While Spanish children's eating habits are reasonably in line with American food guide pyramid guidelines, consumptions of cereals and fruit should be improved.

Dietary patterns among children aged 6-7 y in four Spanish cities with widely differing cardiovascular mortality.

OBJECTIVE: Classic cardiovascular risk factors, such as smoking, arterial hypertension and hypercholesterolaemia, cannot explain a substantial part of the geographic differences in cardiovascular mortality. Anthropometric and nutritional factors in early stages of life may contribute to adult cardiovascular disease. Therefore, this work examines certain anthropometric variables and diet among children aged 6-7 y, living in four Spanish cities with widely differing ischaemic heart disease (IHD) mortality. DESIGN AND SETTING: Cross-sectional anthropometric and dietary survey in four cities in Spain. SUBJECTS: A total of 1112 children (50.1% males, 49.9% females) attending public and private schools in Cadiz and Murcia, cities with a relatively high IHD mortality, and Madrid and Orense, cities with a relatively low IHD mortality. A standardized method was used to measure anthropometric variables, and a food-frequency questionnaire completed by subjects' mothers, to measure diet. OUTCOME MEASURES: Body mass index (BMI), overweight (BMI>17.6 kg/m(2)), obesity (BMI>20.1 kg/m(2)) and intake of food and nutrients. RESULTS: Children in the four cities showed a high prevalence of overweight (range across cities, 28.9-34.5%) and obesity (8.5-15.7%). They also had a moderately hypercaloric diet (range, 2078-2218 kcal/day), marked by an excessive intake of lipids (45.0-47.3% kcal), particularly saturated fats (16.6-16.9% kcal), proteins (17.0-17.3% kcal), sugars (20.0-21.9% kcal) and cholesterol (161.6-182.9 mg/1000 kcal/day), and a low intake of complex carbohydrates (17.5-18.1% kcal) and fibre (19.6-19.9 g/day). Compared with children in the two low-IHD-mortality cities, those in the two high-IHD-mortality cities had a greater BMI (mean difference, 0.61 kg/m(2); P=0.0001) and ponderal index (0.58 kg/m(3); P=0.0001) and a higher intake of energy (104 kcal/day; P=0.007), cholesterol (16.00 mg/1000 kcal/day; P=0.0001) and sodium (321 mg/day; P=0.0001). Inter-city differences in anthropometric variables remained after adjustment for birthweight. CONCLUSIONS: Intake of fats, especially saturated fats, and cholesterol should be reduced among Spanish children. It could contribute to a needed reduction of the high prevalence of overweight and obesity in children. If the differences in anthropometric variables and diet between children from the cities with high and low coronary mortality are maintained in future or continue into adulthood, this could contribute to consolidate or even increase the IHD mortality gradient across cities. The finding that differences in anthropometric variables are independent of birthweight suggests that the childhood, rather than intrauterine environment, is involved in the development of such differences. SPONSORSHIP: This study was partly funded by grants from the International Olive Oil Board (Consejo Oleícola Internacional), Comunidad Autónoma de Madrid, Fundación Pedro Barrié de la Maza, and Fundación Eugenio Rodríguez Pascual.

[Diet and atherosclerosis]. / Dieta y aterosclerosis.

The relationship between diet and atherosclerosis is due to the diet influence on lipoprotein composition. However, because of the multifactorial basis of the atherosclerosis, diet components have another potential intervention mechanisms in the atherosclerosis process, such as the influence on other cardiovascular risk factors (hypertension, obesity, diabetes) or the influence on the coagulation system and the relationship endothelium-platelets. We will review the effect of diet components on these factors, specially its effects on the haemostasia system, which alteration is responsible for provoking ischemic heart disease. We have to consider that the main objective when treating dyslipidaemias, besides of avoiding acute pancreatitis in cases of strong hypertrigliceridaemia, is to prevent arteriosclerosis development and its clinical manifestations such as ischemic heart disease. Besides, we know that genetic, in addition to provoke familial susceptibility to atherosclerosis, has an essential importance in the response to ambiental factors as diet is.

[The 4 Provinces Study: its principal objectives and design. The Researchers of the 4 Provinces Study]. / Estudio Cuatro Provincias: principales objectivos y diseño. Investigadores del Estudio Cuatro Provincias.

INTRODUCTION AND OBJECTIVES: Spain shows an important variation in the geographical distribution of ischaemic heart disease and cerebrovascular disease mortality. In this article, the primary objectives and design of the Four Provinces study are described. In this study we analyzed the contribution of environmental factors (diet, lipid profile and plasma antioxidants), acting in childhood, to explain differences in cardiovascular mortality rates between different provinces in Spain. METHODS: An ecological design was projected in which the units to study were four Spanish provinces with a wide variation in cardiovascular mortality in adulthood. The design compares diet, anthropometric variables and biological markers (particularly plasma lipids and antioxidant levels) in 6-7-year-old children, between the two provinces with the highest cardiovascular mortality rates and the two provinces with the lowest. The information for each province is collected in a cross-sectional manner in a representative sample of children from each province. DISCUSSION: Evidence from the literature concerning Northern European countries suggest the contribution of environmental factors during early age in the development of cardiovascular disease in adulthood. The "Four Provinces" study will provide, for the first time, information about the influence of factors in early childhood of cardiovascular risk in a Mediterranean country. The study will also offer interesting data about food intake during school age in four provinces and it will allow us to estimate values of population of the variables of interest in those provinces.

[Secondary prevention of myocardial infarction in Spain. The PREVERSE study]. / La prevención secundaria del infarto de miocardio en España. Estudio PREVESE.

INTRODUCTION AND OBJECTIVES: We present the results from the PREVESE Study, conducted in two phases: the first to identify the secondary prevention measurements recommended in Spain in patients who were discharged after a myocardial infarction; the second, 6 months later, to determine their evolution. METHODS: Data was collected from 1,242 patients in 39 hospitals. An analysis was made of the patients background, risk factors, working status, diagnostic procedures used during hospitalization, laboratory findings and drug therapy prescribed at discharge. At the second control, the risk factors status, diagnostic or assessment tests performed during the 6-month period, working status, mortality and cardiac events were revised. RESULTS: The previous history and risk factors studied showed a high risk profile among patients after myocardial infarction. Among the drug therapies prescribed at discharge the small percentage (6.7%) of lipid lowering prescriptions should be highlighted. An improvement in the risk factor profile was found at the six month checkup with a substantial reduction in the number of smokers, a very low number of hypertensives and an improvement in physical activity. There was no improvement in total-cholesterol levels. CONCLUSIONS: The implementation of preventive measures is not similar in all risk factors. An improvement is reached in prevention of smoking habit and hypertension, but not in the treatment of abnormal levels of hyperlipidemia.

[Lipoprotein profile in children and adolescents of the Autonomous Community of Madrid]. / Perfil lipoproteico en niños y adolescentes de la Comunidad Autónoma de Madrid.

BACKGROUND: The aim of study was to know the lipoproteins distribution in children and adolescents from the Autonomous Community of Madrid, Spain, and to compare with other studies. MATERIAL AND METHODS: The sample included 3,635 children and adolescents (1,853 males and 1,782 females), 4 to 18 years of age. We measured total cholesterol and triglyceride levels with enzymatic methods, the HDL-cholesterol concentration in the supernatant after precipitation of the rest of the lipoproteins, and LDL-cholesterol concentrations were calculated by Friedewald formula. RESULTS: Total cholesterol levels were 174 +/- 25 mg/dl (4.50 +/- 0.64 mmol/l), triglycerides 60 +/- 24 mg/dl (0.67 +/- 0.28 mmol/l), LDL-cholesterol 100 +/- 22 mg/dl (2.59 +/- 0.58 mmol/l), HDL-cholesterol 61 +/- 13 mg/dl (1.6 +/- 0.34 mmol/l). 19.23% of the children studied had cholesterol levels above 200 mg/dl (> 5.18 mmol/l), and 41.5% of them had levels higher than 180 mg/dl (> 4.66 mmol/l). CONCLUSIONS: The cholesterol levels as well as the HDL-cholesterol levels in the student population of Madrid, Spain, were higher when compared to other studies. Less variation was found in the LDL-cholesterol concentrations.

[Clinical manifestations of heterozygote familial hypercholesterolemia in Spain. Study of 301 cases from the central and northern areas]. / Manifestaciones clínicas de la hipercolesterolemia familiar heterozigota en España. Estudio de 301 casos de la zona centro y norte.

RATIONALE: To characterize clinical manifestations of familial hypercholesterolemia (FH) in Spain. PATIENTS AND METHODS: A group of 301 cases of FH from central and north regions of Spain. RESULTS: With a mean (SD) cholesterol level of 346 (58) mg/dl, only 7.6% of the patients have xanthomas and 20% ischaemic heart disease. 51% have a familial history of ischaemic heart disease. CONCLUSIONS: Different from the results of literature, xanthomas are very infrequent in FH in Spain, so diagnosis should be suspected from other data. The high prevalence of familial history of ischaemic heart disease supports the usefulness of this feature as a marker for diagnosis and prevention.