Carmen Saiz

Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population

Genetic variants at the cholesteryl ester transfer protein (CETP) locus have been associated with CETP activity and mass, as well as plasma high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels. We have examined allele frequencies and lipid associations for the common CETP TaqIB polymorphism in a sample of 514 healthy subjects (231 men, mean age 37.4 years, and 283 women, mean age 35.7 years) residing in Valencia (Spain). The frequency of the less common TaqIB2 allele (0.351; 95% CI: 0.322-0. 380) was significantly lower than those reported for Northern European populations. Consistent with previous studies, we found a significant association of the TaqIB polymorphism with HDL-C levels. Homozygotes for the B1 allele had lower HDL-C levels than subjects carrying the B2 allele (P trend<0.001 and 0.002, for men and women, respectively). No statistically significant genotype effects were observed for any of the other lipid measures. Multivariate models including TaqIB genotype, body mass index, smoking, alcohol, physical activity, marital status and education were fitted to predict HDL-C levels. The TaqIB polymorphism was consistently an independent predictor of HDL-C levels (P<0.001), and explained 5.8% of its variance. To evaluate gene-environmental interactions, first order interaction terms were tested into the multivariate model. No statistically significant interactions between the TaqIB genotypes and smoking, alcohol, physical activity or education were detected. In conclusion, we observed a significant association of the TaqIB polymorphism with HDL-C levels, which remained consistent across different levels of behavioral factors. Moreover, we found that the TaqIB2 allele frequency was lower in our sample than in other European populations, which could be a contributing factor to the unexpectedly high prevalence of coronary heart disease observed in the region of Valencia.

Gender specific associations of the Trp64Arg mutation in the β3‐adrenergic receptor gene with obesity‐related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation

Abstract. Corella D, Guillén M, Portolés O, Sorlí JV, Alonso V, Folch J, Sáiz C (School of Medicine, University of Valencia, Valencia, Spain). Gender specific associations of the Trp64Arg mutation in the β3‐adrenergic receptor gene with obesity‐related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. J Intern Med 2001; 250: 348–360.

Incidence of post-thrombotic syndrome and its association with various risk factors in a cohort of Spanish patients after one year of follow-up following acute deep venous thrombosis

Post-thrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). However, neither the incidence nor the moment of PTS appearance are known. The main reason are the criteria used to define PTS, the characteristics of the patients, the study design and the time of follow-up. Our aims were to estimate the early incidence of PTS and its associated factors in a cohort of carefully defined DVT patients. 135 patients with a previous episode of acute idiopathic, phlebographically confirmed DVT, in the lower limbs, were followed up over 12 months. Phlebography was then repeated to determine the appearance of PTS. In addition, we used a validated clinical scale in order to assess the correlation between the clinical and phlebographical diagnosis of the PTS. This scale was applied at 6 and 12 months. The incidence of phlebographically confirmed PTS within the first year was 56.3% for the isolated PTS and 5.9% for PTS plus recurrent DVT, regardless of age, sex, platelet count, INR, or anticoagulation. None of these patients could be diagnosed as having PTS using the clinical validated scale. However, those patients with phlebographically diagnosed PTS had a higher clinical score than those without (P=0.012). The only factor related to a higher risk of developing a PTS was the localization of the DVT, subjects with both proximal and distal DVT having the highest incidence (P=0.001). In conclusion, although patients had appropriate anticoagulation, early incidence of PTS was very high, thus making it necessary to develop better diagnostic methods in order to evaluate the PTS impact.

Prevalence of the methylenetetrahydrofolate reductase 677C > T mutation in the Mediterranean Spanish population. Association with cardiovascular risk factors

Methylenetetrahydrofolate reductase (MT-HFR) is a key enzyme involved in folate metabolism. A common cytosine (C) to a thymine (T) mutation at nucleotide 677 (677C > T) in the MTHFR gene which converts an alanine residue to a valine, has been related with several biochemical phenotypes and with cardiovascular risk, depending on the population studied. Our objective was to estimate the prevalence of the 677C > T mutation in a large and randomly selected sample (289 men and 427 women) from the Mediterranean Spanish population, and to test the association between this genetic variant and some cardiovascular risk factors. For both genders, the prevalence of CC, CT and TT subjects was 32.0, 52.2 and 15.8%, respectively. The frequency (95% confidence interval) of the 677T allele was 0.44 (0.40–0.48) in men and 0.40 (0.37–0.44) in women. This prevalence was significantly different from other European countries, and among the highest reported in the world for any healthy population. We found no association between the 677C > T gene variants and age, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or diastolic blood pressure in men and women. However, in men, a statistically significant increase of systolic blood pressure with the number of mutant alleles was found (122.2 mmHg in CC, 125.1 mmHg in CT and 128.5 mmHg in TT subjects; p for trend = 0.030). This association remained significant (p = 0.047) even after adjustment for age, BMI, alcohol consumption, tobacco smoking, education and physical activity.

Education modulates the association of the FTO rs9939609 polymorphism with body mass index and obesity risk in the Mediterranean population

OBJECTIVE To define whether the rs9939609 FTO (fat mass and obesity associated) single nucleotide polymorphism (SNP) is associated with anthropometric measurements and its modulation by educational level in a Mediterranean population. METHODS We studied 3 independent adult samples: a random sample (n = 1580) from the general population (GP), obese hospital patients (OHP) (n = 203) and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and height were directly measured. Education and physical activity (PA) were measured using questionnaires. RESULTS The rs9939609 presented heterogeneous associations with BMI. In the GP, the minor A-allele was significantly associated with greater BMI, following a co-dominant pattern (P = 0.009), whereas in the OHP this association was recessive (P = 0.004). Conversely, we did not find a significant association with BMI in the HCR group (P < 0.596). In the GP we found a significant interaction between the FTO SNP and education (P = 0.048). In the stratified analysis, no association of the FTO SNP with greater BMI in university subjects was detected (P = 0.786), whereas the association was observed in non-university subjects (P = 0.001). The FTO × education interaction (P = 0.020) was also observed in determining obesity risk in the GP. A-allele carriers had a greater risk of being obese only if they had no university education (OR: 1.56; 95%CI: 1.09-2.23 for TA and OR: 2.01; 95%CI: 1.27-3.26 for AA subjects). The interaction of the FTO with education remained significant even after adjustment for PA. CONCLUSIONS The association of the FTO SNP with greater BMI and obesity risk in the GP was strongly modulated by education.

Amino Acid Change in the Carbohydrate Response Element Binding Protein Is Associated With Lower Triglycerides and Myocardial Infarction Incidence Depending on Level of Adherence to the Mediterranean Diet in the PREDIMED Trial

Background—A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene–diet interactions modulating these traits are unknown. Methods and Results—We studied 7166 participants in the PREvención with DIeta MEDiterránea trial testing a Mediterranean diet (MedDiet) intervention versus a control diet for cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids, MLXIPL polymorphisms, and cardiovascular events were assessed. Data were analyzed at baseline and longitudinally. We used multivariable-adjusted Cox regression to estimate hazard ratios for cardiovascular outcomes. The MLXIPL-rs3812316 was associated with lower baseline triglycerides (P=5.5×10−5) and lower hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63–0.85; P=1.4×10−6 in G-carriers versus CC). This association was modulated by baseline adherence to MedDiet. When adherence to MedDiet was high, the protection was stronger (odds ratio, 0.63; 95% CI, 0.51–0.77; P=8.6×10−6) than when adherence to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70–1.09; P=0.219). Throughout the follow-up, both the MLXIPL-rs3812316 (P=3.8×10−6) and the MedDiet intervention (P=0.030) were significantly associated with decreased triglycerides. Likewise in G-carriers MedDiet intervention was associated with greater total cardiovascular risk reduction and specifically for myocardial infarction. In the MedDiet, but not in the control group, we observed lower myocardial infarction incidence in G-carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12–0.93; P=0.036 and 0.90; 95% CI, 0.35–2.33; P=0.830, respectively). Conclusions—Our novel results suggest that MedDiet enhances the triglyceride-lowering effect of the MLXIPL-rs3812316 variant and strengthens its protective effect on myocardial infarction incidence. Clinical Trial Registration—URL: www.controlled-trials.com. Unique Identifier: ISRCTN35739639.

High dietary protein intake is associated with an increased body weight and total death risk.

BACKGROUND & AIMS High dietary protein diets are widely used to manage overweight and obesity. However, there is a lack of consensus about their long-term efficacy and safety. Therefore, the aim of this study was to assess the effect of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk. METHODS A secondary analysis of the PREDIMED trial was conducted. Dietary protein was assessed using a food-frequency questionnaire during the follow-up. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of body weight and waist circumference changes, cardiovascular disease, cardiovascular death, cancer death and total death. RESULTS Higher total protein intake, expressed as percentage of energy, was significantly associated with a greater risk of weight gain when protein replaced carbohydrates (HR: 1.90; 95%CI: 1.05, 3.46) but not when replaced fat (HR: 1.69; 95%CI: 0.94, 3.03). However, no association was found between protein intake and waist circumference. Contrary, higher total protein intake was associated with a greater risk of all-cause death in both carbohydrate and fat substitution models (HR: 1.59; 95%CI: 1.08, 2.35; and HR: 1.66; 95%CI: 1.13, 2.43, respectively). A higher consumption of animal protein was associated with an increased risk of fatal and non-fatal outcomes when protein substituted carbohydrates or fat. CONCLUSIONS Higher dietary protein intake is associated with long-term increased risk of body weight gain and overall death in a Mediterranean population at high cardiovascular risk.

Epidemiología del perfil lipídico de la población anciana española: el estudio EPICARDIAN

Fundamento y objetivo Estimar la prevalencia de dislipemia en sujetos mayores de 65 anos no institucionalizados de medios urbano y rural espanoles y describir el perfil lipidico: concentraciones de colesterol total (CT), colesterol ligado a lipoproteinas de baja densidad (cLDL), colesterol ligado a lipoproteinas de alta densidad (cHDL) y trigliceridos, por edad, sexo y zonas geograficas Pacientes y metodo Estudio epidemiologico, transversal y multicentrico de la poblacion anciana (edad mayor o igual a 65 anos) no institucionalizada en 3 areas geograficas: Arevalo (Avila), Begonte (Lugo) y area urbana de Lista (Madrid). Se obtuvo una muestra aleatoria estratificada por edad y sexo a partir de los padrones de cada zona. La tasa de participacion fue del 84,6%. En la fase I se realizo una entrevista domiciliaria (n = 4.522) con examen fisico y determinacion de CT en sangre capilar (Reflotron®). En la fase 2, a un tercio de la muestra elegido al azar (n = 1.907), se le realizo una determinacion centralizada de CT, cHDL, cLDL y trigliceridos Resultados La media (DE) de CT en el total de la poblacion fue 230,3 (46,8) mg/dl. Las cifras de CT descendieron significativamente con la edad (p Conclusiones La prevalencia de dislipemia es superior a las estimaciones realizadas por la Sociedad Espanola de Arteriosclerosis para la poblacion anciana europea (50%), mayor en mujeres y en grupos de menor edad (65–69 anos). El grado de conocimiento, tratamiento y control de la hipercolesterolemia es muy escaso entre la poblacion anciana espanola

Prevention and early detection of tuberculosis

Abstract1,570 subjects with known TB contacts (active TB, old TB and primary infection) and individuals with no known contacts but belonging to ‘efined TB risk groups’ were screened at the Department of Tuberculosis Prevention at the La Fe Hospital in Valencia. The total infection rate was 40.13% and active TBC was diagnosed in 2.23% of the population screened. Infection and disease rates were significant in all the groups examined, showing the need for correct screening not only for active TB contacts but also for child primary infection contacts, old TB cases not previously screened and subjects with no known contacts but belonging to a ‘TB risk group’.

Modulación de la expresión fenotípica del paciente con cistinuria: influencia de la intervención terapéutica y de la dieta

OBJETIVOS El fenotipo final del paciente con cistinuria depende, por una parte, de la ausencia o defecto molecular mas o menos grave en el transporte de cistina y aminoacidos dibasicos; y por otra parte tambien de factores ambientales. El objetivo del presente estudio es conocer el efecto de la modulacion de diversos factores ambientales (pH urinario, ingesta de liquido, tratamiento farmacologico y en especial la dieta) sobre el fenotipo final del paciente con cistinuria. METODOS Se estudiaron 45 sujetos diagnosticados como pacientes con cistinuria (25 hombres y 20 mujeres), 42 individuos pertenecientes al arbol genealogico de estos pacientes con cistinuria (15 hombres y 27 mujeres) y 90 controles. Se obtuvieron datos antropometricos, clinicos (antecedentes personales y familiares de infecciones urinarias, colicos, expulsion de calculos y problemas renales), bioquimicos (analisis microscopico de orina y cuantificacion de aminoacidos en orina) y estilo de vida (dieta y tratamiento recibido). El estudio estadistico incluyo, ademas de pruebas de comparacion de frecuencias y de medias, regresion logistica y analisis multivariante. RESULTADOS De los 45 pacientes con cistinuria, solo el 20% presentaban cristales de cistina en orina; el resto de manifestaciones fenotipicas de la enfermedad, se encontraron con la misma prevalencia que en el grupo de familiares y el grupo control. El 50% de los pacientes no estaban siguiendo ninguna pauta terapeutica, y de estos, solo en el 50% era efectivo. En pacientes con cistinuria, la presencia de cristales de cistina se asocio a una dieta rica en carnes y baja en productos lacteos (p<0,05). El consumo de carnes tambien tendia a asociarse a mayor riesgo de presentar infecciones urinarias, mientras que la expulsion de piedras mostro una tendencia negativa con una dieta rica en fitatos. El consumo elevado de naranjas y mandarinas fue la variable de la dieta que mas se asocio con las concentraciones de aminoacidos en orina, fundamentalmente con menores niveles de lisina y arginina (p<0,05). CONCLUSIONES Diversos componentes de la dieta, ademas del tratamiento estandar, modulan las manifestaciones fenotipicas de la enfermedad.