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Juan F Ascaso

Publications and source records attributed to Juan F Ascaso.

13 recordsLinked to original sources
PubMed2006

[Role of atherogenic dyslipidemia in the development of metabolic syndrome].

BACKGROUND AND OBJECTIVE: Our goal was to know if the diagnosis of metabolic syndrome (MS) as defined by International Diabetes Federation (IDF) criteria 2005 identifies more subjects with atherogenic dyslipidemia and high cardiovascular risk than the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP-III) criteria. PATIENTS AND METHOD: Cross-sectional study in an adult population (20-70 years) of 344 subjects (158 males and 186 females), who visited an out-patient clinic in the metropolitan area of Valencia over a period of one year. Opportunistic search method was used. We studied: anthropometrics parameters, blood pressure, plasma lipids -non-high-density lipoprotein cholesterol (no-HDL-c), and total cholesterol:high-density lipoprotein cholesterol index (TC-HDL-c)-, glucose and insulin, and HOMA (Homeostasis Model Assessment) index. RESULTS: We have separated the subjects on the basis to the IDF or ATP-III criteria to define the MS. The MS define a group of subjects with important plasma lipids alterations and cardiovascular risk: increase of no-HDL-c, of TC:HDL-c index and of apolipoprotein B. The TC:HDL-c index was > or = 6 in 28.6% of the subjects with MS and only in 9.4% of the subjects without MS (p < 0.0001) by IDF criteria and in 34.6% of the subjects with MS-ATP-III, and in 8.6% without MS-ATP-III (p < 0.0001). The apolipoprotein B > or = 1.2 g/l was observed in 44% of the subjects with MS and only in 26% without MS IDF criteria (p < 0.0001), and only in 47.6% and 28.6%, respectively, by ATP-III criteria (p < 0.0001). CONCLUSIONS: The MS defined by the IDF or ATP-III criteria equally identifies subjects with atherogenic dyslipidemia, with increase of no-HDL-c, of the TC: HDL-c index and of the apolipoprotein B and, for this reason, with high cardiovascular risk.

Adult↗
PubMed2006

Semiquantitative multiplex PCR: a useful tool for large rearrangement screening and characterization.

Methods presently employed for detection of large rearrangements have several drawbacks, such as the amount of sample and time required, technical difficulty, or the probability of false-negative carriers. Using the low-density-lipoprotein receptor (LDLR) gene, whose mutations are responsible for familial hypercholesterolemia (FH), we have developed a procedure to detect large rearrangements in this gene based on semiquantitative PCR, with important improvements as compared to previous methods. Our method covers the complete LDLR gene and introduces an internal control in the reaction. The procedure discriminates the four different large rearrangements (two deletions and two insertions) that we have used as positive mutation controls (Valencia-1 to -5). All altered exons from each rearrangement are identified. Furthermore, when families from probands carrying these large rearrangements (34 members) were analyzed, our results agreed with those obtained previously with Southern blot. We have also analyzed a sample of 110 unrelated FH probands and the method has correctly identified the two different large rearrangements present and insertions or deletions as small as 1 bp. In conclusion, the method we present allows the identification of large rearrangements affecting exons of the gene, including small insertions or deletions or complete gene deletion. In addition, it constitutes a first characterization step of rearrangements, and is easy to carry out fast, and can be applied to the analysis of any gene.

Apolipoproteins B↗
PubMed2006

Effects of a controlled program of moderate physical exercise on insulin sensitivity in nonobese, nondiabetic subjects.

OBJECTIVE: To study the effect of a moderate, aerobic physical exercise program on insulin resistance and its accompanying metabolic changes in a group of healthy, middle-age, nonobese subjects, without modifying oxygen consumption and body weight. DESIGN: The inclusion of subjects was carried out among volunteers from the health personnel of our center, who complied with the inclusion criteria. PARTICIPANTS: Twelve subjects (age 30-60 years, 5 females), nonsmokers, body mass index (BMI) <27 kg/m2 and fasting plasma glucose <6.1 mmol/L. INTERVENTIONS: Insulin resistance was assessed using the Bergmann minimal model modified with insulin, and basal and maximum metabolic rate were measured with standard methods. All subjects completed a 2-month program of aerobic exercise using the American College of Sports Medicine guidelines, consisting of aerobic exercise of moderate, regular, and continual intensity (3 times per week), with a duration of 45 to 50 minutes per session. RESULTS: Following controlled exercise, no significant differences in BMI, waist-hip ratio, blood pressure, lipids, free fatty acids, and leptin plasma values were observed. Plasma glucose and insulin values decreased significantly (-0.37 mmol/L and -16.5 pmol/L, respectively). Insulin sensitivity showed an increase of 2.1 x 10(-4) mU L(-1) min(-1) (P = 0.001). Basal and maximum metabolic rate showed no significant differences after the exercise program. CONCLUSIONS: Moderate aerobic exercise increases insulin sensitivity in nonobese, nondiabetic subjects in the absence of significant changes in weight, BMI, waist-hip ratio, lipid profile, and oxygen consumption.

Adult↗
PubMed2006

[Familial combined hyperlipidemia, metabolic syndrome and cardiovascular disease].

Our aim was to investigate the relationship between metabolic syndrome and cardiovascular disease (i.e., survivors of myocardial infarction) in patients with familial combined hyperlipidemia (FCH). We compared a group of 20 male patients with FCH who had survived a myocardial infarction with two other groups matched for age and body mass index, comprising 20 individuals with FCH who had not had a myocardial infraction and 20 control subjects. Plasma lipid, glucose, and insulin levels were determined. Metabolic syndrome was judged to present on the basis of World Health Organization (WHO) and National Cholesterol Education Program-Adult treatment panel (NCEP-ATPIII) criteria. Differences between the groups were evaluated using non-parametric tests and the association between ischemic coronary disease and other parameters was assessed by logistic regression analysis. According to WHO criteria, the metabolic syndrome was present in 19 FCH patients who had survived a myocardial infarction, in 11 individuals with FCH who had not had a myocardial infraction, and in six control subject (P<.001); the difference between FCH patients with and without myocardial infarction was significant (P<.01). Presence of the metabolic syndrome, as defined by WHO criteria, is a marker of cardiovascular risk in individuals with FCH.

Case-Control Studies↗
PubMed2005

[Determinants of postprandial lipemia measured as diurnal triglyceride profile in non diabetic normolipidemic subjects].

BACKGROUND AND OBJECTIVE: We decided to evaluate the clinical and biochemical predictors of postprandial lipemia, measured as daylong capillarly triglycerides (TGc) profiles, in normolipidemic non diabetic subjects. PATIENTS AND METHOD: We studied 76 normolipidemic non diabetic subjects (45 premenopausal females). Accutrend was used to measure daylong TGc profiles during 3 days in 6 previously standardized points: fasting, pre and 3 h after dinner and lunch and at bedtime. The area under the curve of TGc (AUC-TGc) was determined as expression of postprandial lipemia. RESULTS: Males showed significantly higher AUC-TGc (26.20 [11.00] vs 19.12 [6.57] in females; p < 0.001). Obese showed significantly higher values of AUC-TGc (27.87 [12.47] vs 20.05 [7.04]; p < 0.01). The AUC-TGc correlated with: age (r = 0.242; p < 0.05), body mass index (r = 0.312; p < 0.01), waist circumference (r = 0.394; p < 0.01), fasting plasma triglyceride (r = 0.634; p < 0.001), fasting insulinemia (r = 0.485; p < 0.001) and fasting HOMA (r = 0.484; p < 0.001). The multivariate analysis showed that HOMA (regression coefficient: 0.352; p = 0.02) and waist circumference (regression coefficient: 0.4; p = 0.05) were independent predictors of the AUC-TGc. CONCLUSIONS: Independent determinants of postprandial lipemia were waist circumference and HOMA.

Adult↗
PubMed2005

Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant disease characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C). Phenotypic expression is highly variable, being influenced by diet, age, gender, body mass index, apolipoprotein E genotype and type of LDL-receptor gene mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate lipid levels in several populations. To analyse the effect of this polymorphism in the lipid phenotype expression of FH and treatment response, we studied a sample of 222 Spanish FH patients, of whom 147 were studied before and after treatment with 20 mg of atorvastatin daily during 6 weeks. The variant was analysed by polymerase chain reaction amplification and single-strand confirmation polymorphism. Treatment reduced LDL-C, total cholesterol and TGs. Baseline fasting TGs and very-low-density lipoprotein cholesterol levels were lower in female T allele carriers (TG: 111+/-51 mg/dl GG, 89+/-35 mg/dl GT, 83+/-26 mg/dl TT, P=0.022; very-low-density lipoprotein cholesterol: 24+/-13 mg/dl GG, 16+/-5 mg/dl GT, 17+/-5 mg/dl TT, P=0.018). Triglyceride response to atorvastatin was modulated by this polymorphism in men (P=0.009), but not in women, although differences between genotypes were maintained after treatment. In conclusion, the MTP -493 GT polymorphism modulates pre- and post-treatment plasma TG values of FH in Spanish subjects in a gender-specific way. Other environmental and genetic factors likely also modulate this response.

Alleles↗
PubMed2004

[Clinical and biochemical characteristics of familial ligand-defective apo B-100 in a South European population].

BACKGROUND AND OBJECTIVE: To compare the lipoprotein phenotype between FDB and heterozygous familial hypercholesterolemia (FH); to study the prevalence and possible founder effect of familial ligand-defective apo B100 (FDB) in a Mediterranean population, and to analyze the clinical and biochemical characteristics of FDB patients. SUBJECTS AND METHOD: We studied 19 heterozygous FDB subjects (8 males) from 12 related families, carriers of the R3500Q mutation on the apo B gene, and 57 heterozygous FH (24 males) genetically characterized, randomly selected from a total of 213 FH. The genetic diagnosis was established with Southern blot analysis, PCR-SSCP analysis and automatic sequencing. In all subjects, plasma lipids and apolipoprotein levels were determined with standard procedures. RESULTS: We demonstrated a founder effect for the R3500Q mutation in a geographically isolated rural area from our community. The prevalence of FDB in this area is high: 4/350. Heterozygous FDB subjects showed a statistical significantly lower prevalence of xanthomas and coronary heart disease, plasma concentrations of total and LDL cholesterol, HDL cholesterol, apo B and apo A-I values than heterozygous FH subjects. CONCLUSIONS: A founder effect for the R3500Q mutation was found in a rural population with a high prevalence of FDB. In our population, FDB patients showed a mild clinical expression and lipoprotein phenotype compared with FH patients.

Adult↗
PubMed2004

Significance of high density lipoprotein-cholesterol in cardiovascular risk prevention: recommendations of the HDL Forum.

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.

Bezafibrate↗
PubMed2003

Abdominal obesity, insulin resistance, and metabolic syndrome in a southern European population.

BACKGROUND: Our objective was to investigate the relationship between abdominal obesity (AO), as measured by waist circumference (WC), insulin resistance (IR), and components of the metabolic syndrome (MS). METHODS: A cross-sectional study was carried out with 283 subjects (130 males and 153 females aged 25-65 years) from a primary care outpatient clinic in Valencia (Spain) over a period of 1 year. Body mass index (BMI), waist circumference (WC), blood pressure (BP), total cholesterol, triglycerides, HDL-C, glucose, and insulin were measured by standard methods. IR was defined as HOMA-IR equal to or greater than 3.8. RESULTS: The prevalence of IR was 39.6%. Subjects were divided into groups according to WC. A 'normal' WC was defined as below 88 cm in women and below 102 cm in men; 'AO' was defined as a WC equal to or above 88 cm in women and equal to or above 102 cm in men. The prevalence of IR was 31.7% in the group with normal WC and 54.6% in the AO group (P<0.001). The percentage of subjects with the MS (high BP, dyslipemia or abnormal glucose tolerance) significantly increased (P<0.001) in subjects with AO (48.4 vs. 18.8% in normal WC subjects). AO is an indicator of IR with an odds ratio of 2.59 (95% CI 1.55-4.29). CONCLUSIONS: AO, expressed as WC, appears to be a good indicator of risk for IR and the MS, particularly in non-obese subjects (BMI<30). The main independent parameters of risk for IR are WC and TG, whereas those for the MS are IR, WC, and age.

Journal Article↗
PubMed2003

Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population.

Few data are available on genotype-phenotype interactions among familial hypercholesterolemia (FH) patients in South European populations and there are no data about the influence of R3500Q mutation on lipoprotein phenotype compared to low-density lipoprotein receptor (LDLR) mutations. The objective of the study is to analyze the influence of mutations in the LDLR and apolipoprotein B (apoB) genes on lipoprotein phenotype among subjects clinically diagnosed of FH living in East Spain. In all, 113 FH index patients and 100 affected relatives were studied. Genetic diagnosis was carried out following a protocol based on Southern blot and PCR-SSCP analysis. A total of 118 FH subjects could be classified into three groups according to the type of LDLR mutations (null mutations, missense mutations affecting the ligand binding 3-5 repeat, and missense mutations outside this domain). In addition, the lipoprotein phenotype of these FH groups was compared with 19 heterozygous subjects with familial ligand-defective apoB (FDB), due to R3500Q mutation. FH patients carrying missense mutations affecting the ligand binding repeat 3-5 showed total and LDL cholesterol levels significantly higher than FH patients with missense mutations in other LDLR domains or FDB patients. FH subjects carrying null mutations showed lower high-density lipoprotein cholesterol plasma values compared to FH carrying missense mutations. FDB subjects showed the lowest total and LDL cholesterol plasma values. In conclusion, the type of LDLR gene mutation and R3500Q mutation influences the lipoprotein phenotype of FH population from East Spain.

Adolescent↗
PubMed2003

Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism.

OBJECTIVE: To identify a reliable yet simple indirect method for detection of insulin resistance (IR). RESEARCH DESIGN AND METHODS: A total of 65 subjects (44 men and 21 women aged 30-60 years) were selected by a simple random sampling method. Inclusion criteria were voluntary participation from staff and hospital personnel, absence of abnormal glucose tolerance, and normal results of lipid profile and basic blood chemistry. A blood sample was taken after a 12-h overnight fast to determine plasma lipid, glucose, and insulin levels. An intravenous glucose tolerance test with administration of insulin after 20 min and extraction of multiple blood samples for glucose and insulin measurements and calculation of the minimal model approximation of the metabolism of glucose (MMAMG) S(i) value were performed. Three indirect indexes used to predict insulin sensitivity or IR were calculated, and metabolic syndrome was diagnosed using the Adult Treatment Panel III (ATP III) criteria. All results were correlated with those of the MMAMG. RESULTS: The 75th percentile value as the cutoff point to define IR corresponded with a fasting plasma glucose level of 12 mU/l, a homeostasis model assessment of 2.6, a 25th percentile for S(i) value of 21, and QUICKI (quantitative insulin sensitivity check index) and McAuley indexes of 0.33 and 5.8, respectively. The S(i) index correlated (P < 0.001) with all the indirect indexes and parameters of the metabolic syndrome. CONCLUSIONS: When compared with the S(i) index, the most sensitive and specific indirect method was the score proposed by McAuley et al. (specificity 0.91, sensitivity 0.75, 9.2 probability ratio of a positive test), followed by the existence of metabolic syndrome (specificity 0.91, sensitivity 0.66, 7.8 probability ratio of a positive test).

Adult↗
PubMed2002

[Influence of plasma lipids, APOE genotype and type of LDL receptor gene mutations on myocardial infarction in subjects with familial hypercholesterolemia].

BACKGROUND: Our goal was to analyze the relationship of lipids and lipoproteins, APOE genotype and mutations of the LDL receptor gene with the prevalence of myocardial infarction (MI) in patients with familial hypercholesterolemia (FH) from a Southern European FH population. PATIENTS AND METHOD: We studied 108 heterozygous FH subjects aged > 35 years (41 males). It was a cross-sectional study comparing individuals with FH and MI with individuals with FH without MI. In 88 FH subjects, a mutation of the LDL receptor gene was detected. These FH subjects were divided in carriers of null mutation or no null mutations. We compared lipids and lipoproteins and prevalences of LDL receptor type mutation and APOE genotype. RESULTS: Parameters associated with MI were: age, presence of xanthomas and arcus cornealis, plasma concentrations of total cholesterol (TC), LDLc, TC/HDLc ratio > 5.3 and *4 genotype of the APOE gene. Odds ratio for MI were as follows: presence of xanthomas and arcus cornealis, 1.36 (CI 95%, 1.08-1.71; P = 0.01), age > 54 years (50 th of FH group), 1.56 (CI 95%, 1.19-2.04; P = 0.001) and plasma TC values > 332 mg/dl (50 th of FH group), 1.34 (CI 95%, 1.05-1.71; P = 0.019). In the logistic regression model, only age and TC were significantly associated with MI. CONCLUSIONS: In FH subjects aged over 35 years from a Southern European population, MI is associated with age, plasma TC and LDLc values, TC/HDLc ratio and the *4 genotype. In addition, MI is related with age and TC plasma levels on an independent basis.

Adult↗